Biomedical subjects

Claire Danel

Publications and source records attributed to Claire Danel.

At least 19 recordsLinked to original sources

PubMed2006

Intrapulmonary lymph node metastasis and renal cell carcinoma.

Intrapulmonary lymph node metastasis occuring after nephrectomy for renal cell carcinoma is a particular recurrence modality. Authors report two male patients presenting with this recurrence 2 and 4 years after treatment of the primary and who underwent surgery. Surgery confirmed the diagnosis and demonstrated station 7 minimal metastases and positive pleural lavage cytology in both patients. The first patient survived 2 years and the second was alive disease free at 33 months follow-up. Such metastases probably originate from the thoracic duct. Resection confirms the diagnosis and may be part of the treatment.

Adult↗

PubMed2006

A morphometric study of mucins and small airway plugging in cystic fibrosis.

RATIONALE: Little knowledge exists on structural changes and plugging in small airways in cystic fibrosis. OBJECTIVE: To characterise the extent of plugging and contribution of secreted mucins to the plugs. METHODS: Small airways in patients with cystic fibrosis at transplantation (n = 18) were compared with control non-smokers (n = 10). Tissue sections were stained with Alcian blue (AB)/periodic acid-Schiff (PAS), for mucins MUC5B and MUC5AC, and for neutrophils and its chemoattractant interleukin (IL) 8. Epidermal growth factor receptor (EGFR) and its ligand pro-transforming growth factor alpha were also identified using immunohistochemical staining. Epithelial and luminal contents were assessed morphometrically. RESULTS: Plugs occupying >50% of total luminal volume were found in 147 of 231 (63.6%) airways in patients with cystic fibrosis, but only in 1 of 39 (2.6%) airways in controls. In the epithelium of patients with cystic fibrosis, AB/PAS, MUC5B, and MUC5AC-stained volume densities were increased 10-fold (p < 0.01), indicating increased mucin production. In airway lumens, staining for mucins was also increased in cystic fibrosis, indicating increased mucin secretion. In the epithelium of patients with cystic fibrosis, neutrophil numbers were markedly increased and were inversely correlated with volume densities of mucous glycoconjugates (r = -0.66, p < 0.005). IL8 staining was increased in the epithelium of patients with cystic fibrosis and colocalised with mucins. Staining for EGFR and for pro-transforming growth factor alpha were increased in the epithelium of patients with cystic fibrosis; positive correlations were found between EGFR-stained volume density and both AB/PAS and IL8-stained volume densities. CONCLUSIONS: Most of the small airways are plugged in cystic fibrosis at the time of transplantation. Mucins contribute to airway plugging. Recruited neutrophils may be involved in mucin secretion in the plugs. Increased expression of EGFR and its ligand suggests roles in mucin synthesis and neutrophil recruitment.

Adult↗

PubMed2006

Cushing's syndrome secondary to bronchopulmonary carcinoid tumor: report of two cases and literature review.

Bronchopulmonary carcinoid tumors have been associated with a variety of endocrine disorders including Cushing's syndrome (CS), which is caused by ectopic adrenocorticotrophic hormone (ACTH) secretion. We report two cases of CS secondary to bronchopulmonary carcinoid tumors. The first patient, a 29-year-old woman, presented hypokalemia, high serum ACTH level and high free-urinary cortisol, raising suspicion of an ectopic ACTH syndrome. Chest computed tomography and Octreoscan showed a peripheral nodule in the left-superior lobe of the lung. After lobectomy, a typical bronchopulmonary carcinoid was diagnosed. The second patient, a 16-year-old boy, presented "moon face" and progressive asthenia, high serum ACTH level and high free-urinary cortisol, raising the same hypothesis. Chest computed tomography and Octreoscan showed a peripheral nodule in the middle lobe. After lobectomy, an atypical bronchopulmonary carcinoid was diagnosed. Both cases had IA stage (T1N0M0), positively immunostaining for chromogranin and ACTH. Neither of these patients had hypophysary microadenomas, adrenal adenomas or recurrence of CS after surgical treatment, demonstrating that CS was caused solely by the presence of the bronchopulmonary carcinoid tumors.

Adolescent↗

PubMed2006

Pulmonary cystic disorder related to light chain deposition disease.

Light chain deposition disease (LCDD) is a rare disorder that very uncommonly affects the lung. We report three cases of severe cystic pulmonary LCDD leading to lung transplantation. Such a presentation has never been previously reported. The three patients present with a progressive obstructive pulmonary pattern associated with numerous cysts diffusely distributed in both lungs. The disease was histologically characterized by non-amyloid amorphous deposits in the alveolar walls, the small airways and the vessels. It was associated with emphysematous-like changes and small airway dilation. Monotypic kappa light chain fixation was demonstrated on the abnormal deposits and along the basement membranes. Electron microscopy revealed coarsely granular electron-dense deposits in the same localizations. Mild extrapulmonary deposits were found in salivary glands in one patient. No immunoproliferative disorder was identified. We conclude that LCDD may primarily affect the lung, present as a pulmonary cystic disorder, and lead to severe respiratory insufficiency.

Adult↗

PubMed2006

Prognostic value of histology in resected lung cancer with emphasis on the relevance of the adenocarcinoma subtyping.

BACKGROUND: Adenocarcinoma (AC) is the most common lung cancer, followed by squamous cell carcinoma (SCC). Controversy exists concerning both cell types. Our purpose was to compare their prognosis after resection and determine whether AC subtyping may have any significance. METHODS: From 1993 to 2002, 574 patients with SCC and 565 with AC underwent a curative resection and were compared according to sex, age, type of resection, TNM system classification, and survival. One hundred fifty-nine patients with ACs demonstrated a pure histologic pattern according to the 1999 World Health Organization classification, and 406 were of the mixed subtype including cell types with potentially different aggressiveness. Therefore, we compared subgroups according to presence or not of bronchioloalveolar carcinoma or solid adenocarcinoma with mucin component, or both. RESULTS: Compared with ACs, SCCs had a higher number of males and older patients, and incidences of endobronchial tumors, pneumonectomies, and stage II tumors were higher. Global survival rates were not different. The ACs with solid AC with mucin components (n = 239) were characterized by more males and stage IIB patients, and had poorer survival rates (38.6% vs 61.4%; p < 0.0014) than the ACs without solid AC with mucin component. When comparing these with SCCs, 5-year survival rates were: ACs without solid AC with mucin component (58.1%), SCCs (50.2%), and ACs with solid AC with mucin component (36.8%) (p < 0.000019). Multivariate analysis demonstrated these subgroups and SCCs to be independent factors of prognosis. CONCLUSIONS: Solid ACs with a mucin component demonstrated the poorest prognosis after resection. Further studies of this cell type, which should be looked for carefully, may help improve targetting adjuvant therapies.

Adenocarcinoma↗

PubMed2006

Typical bronchopulmonary carcinoid tumors: a ramifying bronchial presentation with metastatic behavior.

Bronchopulmonary typical carcinoid tumors (BTCT) are neuroendocrine neoplasms with histologic low grade characteristics considered benign. However, despite reassuring histologic classification, some of them demonstrate an aggressive nature and metastatic behavior. During a not yet concluded study aiming at establishing criteria to predict this metastatic behavior, three uncommon cases were observed. Metastasis occurred despite typical carcinoid microscopic features in 3 female patients of African origin presenting at macroscopic examination as ramifying bronchopulmonary typical carcinoid tumors following the bronchial tree. We suggest that clinical ramifying presentation may be related to metastatic behavior, even for bronchopulmonary typical carcinoid tumors not displaying histologic criteria for atypical carcinoid tumors.

Aged↗

PubMed2006

Prognostic factors and surgical indications of pulmonary epithelioid hemangioendothelioma: a review of the literature.

BACKGROUND: Pulmonary epithelioid hemangioendothelioma is a rare vascular tumor of low-grade malignancy, the prognosis of which remains unpredictable. The purpose of this analysis based on 80 patients was to determine prognostic factors and to evaluate results of surgery. METHODS: We recorded data of 75 patients from reports published in the English and French literature using the terms "intravascular bronchoalveolar tumor" or "pulmonary epithelioid hemangioendothelioma" or a combination of both. We added to this database 5 more cases of pulmonary epithelioid hemangioendothelioma operated on in our thoracic surgery department from 1989 to 2005. Univariate and multivariate analyses of prognostic factors were performed using the log rank test and the Cox model. The factors we tested were age, sex, clinical symptoms, biologic and radiologic findings, and surgical treatment. RESULTS: There were 49 women and 31 men with a mean age of 39.7 years (range, 7 to 72 years). The 5-year survival probability was 60% (range, 47% to 71%). Univariate analysis showed that loss of weight, anemia, pulmonary symptoms, and more particularly pleural hemorrhagic effusions were significant factors of poor prognosis, with a median survival of less than 1 year. Multivariate analysis showed a statistically worse survival in patients with hemorrhagic symptoms (hemoptysis, p < 0.0001; pleural effusion, p < 0.0001). CONCLUSIONS: Pulmonary epithelioid hemangioendothelioma typically occurs among young patients. Surgery can be proposed in cases of unilateral single or multiple nodules. There is no single effective treatment in cases of bilateral multiple nodules. Lung transplantation should be evaluated in patients with vascular aggressivity with pleural hemorrhagic effusion and anemia.

Adolescent↗

PubMed2006

Ileal Crohn's disease in a woman with Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction. A subset of patients also show ceroid deposition, which can result in pulmonary fibrosis or granulomatous colitis. Whether this colitis may be considered Crohn's disease is under debate. We report a case of a patient with HPS associated with inflammatory bowel disease which affected the distal small bowel but not the colon. Ileitis was severe, and recurred rapidly after surgery. Search for mutations in HPS1, ADTB3A, HPS3, HPS4 and for CARD15 were negative. Symptoms and ileal ulcerations which recurred after surgery were successfully treated with azathioprine and infliximab.

Adult↗

PubMed2006

Epidermal growth factor receptor mutation in lung cancer are linked to bronchioloalveolar differentiation.

In lung cancer, an association was made between drastic clinical response to epidermal growth factor receptor (EGFR) inhibitors and the presence of somatic mutations within the tyrosine kinase domain of the EGFR. In some cases, patients with partial response or disease stabilization do not always have EGFR-mutated tumors. To go further in the characterization of the EGF pathway, we screened EGFR, ERBB2, ERBB3, KRAS, BRAF, and PIK3CA for mutations in 2 groups of White patients with nonsmall cell lung cancer (45 cancers from women and 46 cancers from men). Associations between TP53 mutations, clinicopathologic parameters, and EGF pathway molecular alterations were analyzed. All mutations were exclusive and essentially found in EGFR and KRAS. We demonstrated that EGFR mutations were linked to female sex, absence of smoking, late age at diagnosis, and adenocarcinoma (ADC) with bronchioloalveolar (BAC) features. Moreover, in invasive ADC with BAC component, microdissection assays showed that mutations were retrieved in both tumor subtypes suggesting that EGFR mutations appear early in lung carcinogenesis. On the contrary, KRAS mutations correlated with smoking, younger age at diagnosis, and ADC subtype regardless of BAC differentiation. These results suggest the existence of distinct carcinogenesis pathways both leading to disruption of EGF regulation and targeted either by tobacco carcinogens or by unidentified toxic. The identification of BAC features in ADC helps clustering patients that are more likely to fit the EGFR-mutated group.

Adenocarcinoma, Bronchiolo-Alveolar↗

PubMed2005

beta2-Adrenoceptor agonist modulates endothelin-1 receptors in human isolated bronchi.

Chronic exposure of human isolated bronchi to beta(2)-adrenergic agonists, especially fenoterol, potentiates smooth muscle contraction in response to endothelin-1 (ET-1), a peptide implicated in chronic inflammatory airway diseases. Our objective was to determine whether ET-1 receptors ETA and ETB are involved in fenoterol enhancement. Twenty-two human bronchi were sensitized to ET-1 by prolonged incubation with 0.1 microM fenoterol (15 h, 21 degrees C). Removing the epithelium after fenoterol incubation limited the maximal contraction (0.10+/-0.36 g without epithelium versus 1.18+/-0.22 with, n=8, P=0.04). After 15 h incubation, 14 and 8 paired rings were fixed, respectively, for immunolabeling of bronchial ETA and ETB receptors, and to determine the mRNA expression levels using real-time quantitative reverse transcription polymerase chain reaction. ETA and ETB receptor mRNA expressions were 1.27- +/- 0.14-fold (not significant) and 2.24- +/- 0.28-fold (P<0.01) higher, respectively, in fenoterol-treated bronchi than in paired controls. Fenoterol incubation significantly increased epithelial ETA and ETB receptor labeling intensity scores (P=0.001 and P=0.002, respectively, versus controls), and enhanced the diffuse localization of ETA receptors on the epithelial cells (P=0.002 versus controls), but did not change the ETB-receptor immunolabeling intensity on airway smooth muscle. We conclude that fenoterol-induced sensitization of human isolated bronchi involves epithelial ETA and ETB receptors, which suggests perturbation of the epithelial regulation of airway smooth muscle contraction in response to ET-1.

Adrenergic beta-Agonists↗

PubMed2005

Real-time RT-PCR detection of CK19, CK7 and MUC1 mRNA for diagnosis of lymph node micrometastases in non small cell lung carcinoma.

Metastatic lymph nodes (LNs) are the major prognostic factor in resected non small cell lung carcinoma (NSCLC). However, almost 50% of pN0 patients relapse, suggesting metastatic cells undetected by current staging procedures. A combination of markers [cytokeratins 19 and 7 (CK19, CK7) and mucin type 1 (MUC1) mRNAs] was therefore evaluated by real-time RT-PCR in order to detect occult cancer cells. Forty-three NSCLC tumor samples, 4 micrometastatic, 6 metastatic and 84 histologically negative mediastinal LNs from 19 patients with NSCLC were evaluated as well as blood mononuclear cells from 29 healthy volunteers and 17 benign LNs. When tested on cell lines, RT-PCR was particularly efficient for evaluation of CK19, CK7 and MUC1 mRNA expression. All tumor samples were positive for at least 1 marker and 74% of samples were positive for all 3 markers. CK7 and CK19 mRNA were not detected in benign LN and blood cells from healthy donors in contrast with MUC1 mRNA. Only CK7 and CK19 mRNA were therefore used for evaluation of mediastinal LNs: the 6 histologically metastatic and the 4 micrometastatic LNs were positive for at least one marker. Among the 84 histologically negative LNs, 6 (7%) were positive for at least one marker, potentially changing the stage of 2 out of 19 patients. In conclusion, in our feasibility study, parallel molecular detection of CK19 and CK7 mRNA can be considered a specific diagnostic tool for the assessment of microscopic lymphatic spread. Its prognostic impact remains to be evaluated in a prospective study.

Aged↗

PubMed2005

Multidrug resistance-associated protein (MRP1) is overexpressed in DNA aneuploid carcinomatous cells in non-small cell lung cancer (NSCLC).

Resistance to chemotherapy is intrinsically present in most nonsmall-cell lung carcinomas (NSCLC). No parameter has yet been determined to predict the response to chemotherapy. However, MRP1 (multidrug resistance-associated protein) is suspected to play an important role in resistance to treatment. The genetic basis for this resistance is not clearly understood, but it could result from chromosome reassortments catalyzed by aneuploidy. The aim of this study was to investigate MRP1 expression concurrently to DNA ploidy analysis in order to evaluate the link between MRP1 expression and chromosome 16 (MRP1 gene location) aberrations in NSCLC before treatment. Eighty-four surgical tumor specimens, 18 selected samples containing more than 80% of carcinomatous cells and 11 samples from normal bronchial epithelium were studied. Samples were stained by MRP1 FITC indirect staining and propidium iodide and analyzed by Flow Cytometry. Fifty tumors contained at least 1 DNA-aneuploid clone and the percentage of MRP1-positive cells was higher in DNA-aneuploid cells (p = 0.0003). All tumors expressed MRP1, but the level of expression was 3-fold higher in DNA-aneuploid cells than in DNA-diploid cells (normal bronchial cells as well as carcinomatous cells) (p < 0.0001). FISH analysis of 24 tumor imprints using a chromosome 16 alpha-satellite centromere probe demonstrated significantly more frequent gain of chromosome 16 in DNA-aneuploid tumors. These results suggest that MRP1 overexpression in NSCLC could be a consequence of chromosome 16 reassortments catalyzed by aneuploidy and that DNA-aneuploid tumors could require different treatment modalities from those applied to DNA-diploid tumors.

Aneuploidy↗

PubMed2005

A rare inferior middle mediastinal tumor resection under extra-corporeal circulation.

An inferior middle mediastinal mass was observed in a 51-year-old woman initially presenting as pericardial effusion and mimicking lymph node disease. Thoracotomy demonstrated a tumor invading the posterior atrial wall. Complete resection was possible under the extracorporeal circulation. The tumor proved to be a soft tissue myoepithelioma in an exceptional location. Despite the difficult surgical resection due to location, prognosis of this absolutely rare tumor without cytologic features of malignancy should be good.

Extracorporeal Circulation↗

PubMed2005

Skip mediastinal lymph node metastasis and lung cancer: a particular N2 subgroup with a better prognosis.

BACKGROUND: Lymph node (LN) metastases from lung cancer may skip the intrapulmonary nodes directly to the mediastinum ([N1-]N2 vs [N1+]N2). This phenomenon is frequent. Patients with such a metastatic pattern appear to have a better prognosis following surgery. Our purpose was to further study the clinical significance and prognostic value of this particular group of (N1-)N2 patients. METHODS: We retrospectively analyzed the data of 731 patients with a pN2 stage who underwent resection for non-small cell lung cancer. Patients with (N1-)N2 metastases (n = 209) were compared to patients with intrapulmonary (N1+)N2 (n = 522). RESULTS: In the (N1-)N2 group, lobectomies were more frequent (54% vs 33%, p = 0.00), metastases more frequently involved a single LN station (79.4% vs 56.3%, p < 0.000001), and primary tumor was more often located in the upper lobes (67.4% vs 55.6%, p = 0.0066). (N1-)N2 was a factor of better prognosis (5 year survival rates 34.4% vs 18.5%, p = 0.00006), which proved also significant when only a single station was involved (38.4% vs 24%, p = 0.0005). These results were confirmed by multivariate analysis. CONCLUSIONS: (N1-)N2 skip metastasis is a unique subgroup of pN2 disease. Lung lymph drainage anatomy may explain the occurrence of these metastases. They form an independent prognostic factor of survival suggesting the need for further study, the results of which may lead to better knowledge of lung cancer, improved classification, and adapted adjuvant therapy.

Adenocarcinoma↗

PubMed2005

Association of CK19 mRNA detection of occult cancer cells in mediastinal lymph nodes in non-small cell lung carcinoma and high risk of early recurrence.

This study was designed to screen occult cancer cells by CK19 mRNA detection using reverse transcriptase-polymerase chain reaction (RT-PCR) in mediastinal lymph nodes stations (MLNS) in non-small cell lung carcinoma (NSCLC). In 49 NSCLC patients free of mediastinal adenopathy on computed tomograph, 254 MLNS were evaluated by histopathology, immunohistochemistry (IHC) and RT-PCR. Of 225 non-tumoral MLNS on histopathology, 32 (14.2%) were positive by RT-PCR. IHC did not provide significant additional results. Seventeen patients were without mediastinal tumoral extension on histopathology and RT-PCR (Group 1), 16 were upgraded by RT-PCR (Group 2) and 16 pN2 on histopathology (Group 3). The two-year cancer-related death survival in Groups 1 (100%) and 2 (64.5%) was significantly different (P=0.04). The relative risk of recurrence in Group 2 compared with Group 1, evaluated by the Cox model multivariate analysis, was 5.61 (P=0.02). In conclusion, CK19 mRNA detected by RT-PCR in MLNS was significantly associated with an increased risk of rapid recurrence.

Adult↗

PubMed2005

Pulmonary sequestration and aspergillosis.

OBJECTIVE: Pulmonary sequestration (PS) is an uncommon congenital disease. Symptoms when present are usually secondary to pyogenic infection. Our objective was to draw attention on superimposed fungal infection. METHODS: During the last 20 years, we operated upon 19 intralobar PS. Four of six patients operated during the last decade proved to have intralobar PS containing Aspergillus. RESULTS: In one patient aspergillosis presented as an aspergilloma and communications between the sequestration and small bronchi were present. In another patient diagnosis was made before operation because of positive precipitins test. In two patients aspegillosis was discovered by the pathologist. CONCLUSIONS: Review of literature demonstrates PS fungal colonization to be a rare but recently reported entity (14 cases reported). The observation of four consecutive patients leads us to suggest that PS aspergillosis must be considered in order to evaluate its incidence.

Adult↗

PubMed2005

[Contribution of bronchoalveolar lavage to the management of interstitial lung disease].

Bronchoalveolar lavage (BAL) is a minimally invasive method for exploring the distal lung. It enables collection of free cellular and acellular material present in the alveoli. Over the last two decades BAL has become a fundamental tool for positive diagnosis of interstitial lung disease and even more for differential diagnosis. It has contributed greatly to the diagnosis of lung infections, particularly in immunosuppressed patients. In the context of non-infectious infiltrative disease, the diagnostic contribution of BAL is limited due to the lack of a specific cell profile. It remains a fundamental tool for the differential diagnosis of idiopathic interstitial pneumonia. With BAL, a number of infectious or tumoral diseases can be ruled out with precision. It is also an important element for the evaluation of possible iatrogenic disease. BAL has transformed the diagnosis of interstitial lung disease and considerably reduced the indications for surgical biopsy.

Bronchoalveolar Lavage↗

PubMed2005

[Usefulness of transbronchial and surgical biopsies for the management of interstitial lung disease].

Interpretation of lung material can be very difficult in patients with interstitial lung disease. The pathologist must be particularly familiar with this type of situation since, unlike tumor diseases, the diagnosis is not purely histological and must always be established in correlation with the clinical and radiological presentation. In patients with suspected interstitial lung disease, the first diagnostic step is to perform a transbronchial biopsy or bronchoalveolar lavage. In many cases the two minimally invasive techniques can be combined to guide the diagnosis or establish confirmation. The indications for surgical biopsy can thus be limited to very exceptional situations. We recall here the requirement for rigorous handling of the endoscopic or surgical specimens and discuss the specific difficulties in interpreting the pathological material, focusing on the contribution of the pathological study to clinical surveillance of the disease course and its complications, particularly in treated patients. A close collaboration between clinicians and pathologists is essential for optimal diagnosis and management of interstitial lung disease.

Biopsy↗