Sarcoidosis is a multisystem disorder that is characterized by noncaseous epithelioid cell granulomas, which may affect almost any organ. Thoracic involvement is common and accounts for most of the morbidity and mortality associated with the disease. Thoracic radiologic abnormalities are seen at some stage in approximately 90% of patients with sarcoidosis, and an estimated 20% develop chronic lung disease leading to pulmonary fibrosis. Although chest radiography is often the first diagnostic imaging study in patients with pulmonary involvement, computed tomography (CT) is more sensitive for the detection of adenopathy and subtle parenchymal disease. Pulmonary sarcoidosis may manifest with various radiologic patterns: Bilateral hilar lymph node enlargement is the most common finding, followed by interstitial lung disease. At high-resolution CT, the most typical findings of pulmonary involvement are micronodules with a perilymphatic distribution, fibrotic changes, and bilateral perihilar opacities. Atypical manifestations, such as masslike or alveolar opacities, honeycomb-like cysts, miliary opacities, mosaic attenuation, tracheobronchial involvement, and pleural disease, and complications such as aspergillomas, also may be seen. To achieve a timely diagnosis and help reduce associated morbidity and mortality, it is essential to recognize both the typical and the atypical radiologic manifestations of the disease, take note of features that may be suggestive of diseases other than sarcoidosis, and correlate imaging features with pathologic findings to help narrow the differential diagnosis.
A fusion gene, echinoderm microtubule associated protein like 4 -anaplastic lymphoma kinase (EML4-ALK), with transforming activity has recently been identified in a subset of non-small cell lung cancer (NSCLC), but its pathogenetic, diagnostic, and therapeutic roles remain unclear. Both frequency and type of EML4-ALK transcripts were investigated by reverse transcription PCR in 120 frozen NSCLC specimens from Italy and Spain; non-neoplastic lung tissues taken far from the tumor were used as controls. In cases carrying the fusion transcript, we determined EML4-ALK gene and protein levels using fluorescence in situ hybridization, Western blotting, and immunoprecipitation. We also analyzed ALK protein levels in paraffin samples from 662 NSCLC specimens, including the 120 cases investigated in the molecular studies. EML4-ALK transcripts (variants 1 and 3) were detected in 9 of 120 NSCLC samples but were not specific for NSCLC since they were also found in noncancerous lung tissues taken far from the tumor. Notably, no transcripts were detected in matching tumor samples from these patients. Fluorescence in situ hybridization analysis of cases expressing EML4-ALK transcripts showed that only a minority of cells harbored the EML4-ALK gene. None of these cases was found to express the EML4-ALK protein as examined by immunohistochemistry, Western blotting, and immunoprecipitation. The EML4-ALK transcript cannot be regarded as a specific diagnostic tool for NSCLC. Our results show therefore that the causal role and value of EML4-ALK as a therapeutic target remain to be defined.
Objective. Giant cell arteritis (GCA) may involve the aorta. Retrospective studies have demonstrated a higher prevalence of aortic aneurysm among patients with GCA compared with the general population. We investigated the prevalence of aortic aneurysm in a cohort of patients with biopsy-proven GCA using a defined protocol and assessed whether persisting low-grade disease activity is associated with higher risk of developing aortic aneurysm. Methods. Fifty-four patients with GCA (14 men and 40 women) were cross-sectionally evaluated after a median followup of 5.4 years (range 4.0 -10.5 years). The screening protocol included a chest radiograph, abdominal ultrasonography scan, and computed tomography scan when aortic aneurysm was suspected or changes with respect to the baseline chest radiograph were observed. Clinical and laboratory data, corticosteroid requirements, and relapses were prospectively recorded. Results. Twelve patients (22.2%) had significant aortic structural damage (aneurysm/dilatation), 5 of them candidates for surgical repair. Aortic aneurysm/dilatation was more frequent among men (50%) than women (12.5%; relative risk 3.5, 95% confidence interval 1.53-8.01, P ؍ 0.007). At the time of screening, patients with aneurysm/dilatation had lower serum acute-phase reactants, lower relapse rate, and needed shorter periods to withdraw prednisone than patients without aortic structural damage. Conclusion. There is a substantial risk of developing aortic aneurysm/dilatation among patients with GCA. Our data do not support that aneurysm formation mainly results from persistent detectable disease activity. Additional factors including characteristics of the initial injury or the target tissue may also determine susceptibility to aortic aneurysm/ dilatation.
Vasculitis is an inflammatory destructive process affecting blood vessels. Pulmonary vasculitis may be secondary to other conditions or constitute a primary, and in most cases idiopathic, disorder. Underlying conditions in the secondary vasculitides are infectious diseases, connective tissue diseases, malignancies, and hypersensitivity disorders. The most widely used approach to classifying the primary vasculitides is based on the size of the affected vessels (large, medium, small). Thoracic involvement is most commonly seen with primary idiopathic large-vessel vasculitides (Takayasu arteritis, giant cell arteritis, Behçet disease) and primary small-vessel antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome). The radiologic manifestations of primary pulmonary vasculitis are extremely variable and include vessel wall thickening, nodular or cavitary lesions, ground-glass opacities, and consolidations. Diffuse alveolar hemorrhage is a clinical syndrome that usually results from primary small-vessel vasculitis in the lungs. Although chest radiography is often the first imaging study performed in patients with pulmonary involvement by vasculitis, chest radiographs often fail to show the exact pattern and extent of thoracic involvement and CT is more useful in assessment of the thoracic findings. The pulmonary primary vasculitides are rare disorders, and their diagnoses are among the most demanding challenges in medicine because their signs and symptoms are nonspecific and overlap with those of infections, connective tissue diseases, and malignancies; thus, diagnosis of vasculitis relies on recognition of characteristic combinations of particular clinical, radiologic, laboratory, and histopathologic features.
The combined assessment of a panel of six serum TMs is a more accurate marker for LC presence than these same TMs considered individually. The potential of these TMs in the diagnostic and screening settings deserves further research.
Insufficient evidence exists on the risk of pleural mesothelioma from non-occupational exposure to asbestos. A population-based case–control study was carried out in six areas from Italy, Spain and Switzerland. Information was collected for 215 new histologically confirmed cases and 448 controls. A panel of industrial hygienists assessed asbestos exposure separately for occupational, domestic and environmental sources. Classification of domestic and environmental exposure was based on a complete residential history, presence and use of asbestos at home, asbestos industrial activities in the surrounding area, and their distance from the dwelling. In 53 cases and 232 controls without evidence of occupational exposure to asbestos, moderate or high probability of domestic exposure was associated with an increased risk adjusted by age and sex: odds ratio (OR) 4.81, 95% confidence interval (CI) 1.8–13.1. This corresponds to three situations: cleaning asbestos-contaminated clothes, handling asbestos material and presence of asbestos material susceptible to damage. The estimated OR for high probability of environmental exposure (living within 2000 m of asbestos mines, asbestos cement plants, asbestos textiles, shipyards, or brakes factories) was 11.5 (95% CI 3.5–38.2). Living between 2000 and 5000 m from asbestos industries or within 500 m of industries using asbestos could also be associated with an increased risk. A dose–response pattern appeared with intensity of both sources of exposure. It is suggested that low-dose exposure to asbestos at home or in the general environment carries a measurable risk of malignant pleural mesothelioma. © 2000 Cancer Research Campaign
Background: Tumor markers have been extensively studied in lung cancer, reporting some relationship to the histology, but their clinical utility is not clear. Methods: ProGRP, CEA, SCC, CA 125, CYFRA 21-1 and NSE were studied prospectively in 155 patients with unconfirmed suspicion of lung cancer and in 647 patients with lung cancer: 182 squamous, 205 adenocarcinomas, 19 large-cell lung cancer (LCLC), 175 small-cell lung cancer (SCLC) and 66 unspecific non-small-cell lung cancer (NSCLC). Results: Abnormal tumor marker serum levels were found in less than 5.3% of the patients with benign diseases, excluding CA 125 (21.3%). Tumor markers were related to histological type and tumor extension with significantly higher CEA (p <0.01) and CA 125 (p <0.007) serum levels in adenocarcinomas, SCC (p <0.0001) and CYFRA 21-1 (p <0.008) in squamous tumors and ProGRP (p <0.0001) and NSE (p <0.0001) in SCLC. Tumor markers may be useful in the histological differentiation of NSCLC and SCLC. Patients with SCC serum levels >2 ng/ml were always NSCLC, while those with SCC <2 ng/ml and ProGRP >100 pg/ml and NSE >35 ng/ml were all SCLC patients. The sensitivity was 76.7 and 79.5%, specificity was 97.2 and 99.6%, with a positive predictive value of 98.6 and 98.6% and a negative predictive value of 60.7 and 92.9% in the differentiation of NSCLC and SCLC, respectively. Conclusions: Tumor marker determination in patients with suspicious signs of lung cancer suggests, in a few hours, the histological diagnosis in the majority of lung cancer patients.
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