An unusual case of a microscopic alveolar adenoma coexisting with lung carcinoma: a case report and review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Alveolar adenomas are extremely rare, benign, primary lung tumors of unknown histogenesis that are characterized by proliferative type II alveolar epithelium and septal mesenchyma. Mostly incidental, they are clinically important as they can imitate benign primary and secondary malignant tumors and at times are difficult to differentiate from early-stage lung cancer. We describe the case of a 59-year-old man with an incidental microscopic alveolar adenoma coexisting with poorly differentiated lung carcinoma.</p> <p>Case presentation</p> <p>A 59-year-old Caucasian man with a medical history of smoking and chronic obstructive pulmonary disease was incidentally found to have a right upper lobe mass while undergoing a computed tomographic chest scan as part of a chronic obstructive pulmonary disease clinical trial. Our patient underwent a right upper lobectomy after a bronchoscopic biopsy of the mass revealed the mass to be a carcinoma. A pathological examination revealed an incidental, small, 0.2 cm, well circumscribed lesion on the staple line margin of the lobectomy in addition to the carcinoma. Histopathological and immunohistochemical examinations revealed the lesion to be an alveolar adenoma.</p> <p>Conclusions</p> <p>We report the rare presentation of a microscopic alveolar adenoma coexisting with lung carcinoma. Alveolar adenoma is an entirely benign incidental neoplasm that can be precisely diagnosed using immunohistochemical analysis in addition to its unique histopathological characteristics.</p

Adipose segmentation in small animals at 7T: a preliminary study

<p>Abstract</p> <p>Background</p> <p>Small animal MRI at 7 Tesla (T) provides a useful tool for adiposity research. For adiposity researchers, separation of fat from surrounding tissues and its subsequent quantitative or semi- quantitative analysis is a key task. This is a relatively new field and a priori it cannot be known which specific biological questions related to fat deposition will be relevant in a specific study. Thus it is impossible to predict what accuracy and what spatial resolution will be required in all cases and even difficult what accuracy and resolution will be useful in most cases. However the pragmatic time constraints and the practical resolution ranges are known for small animal imaging at 7T. Thus we have used known practical constraints to develop a method for fat volume analysis based on an optimized image acquisition and image post processing pair.</p> <p>Methods</p> <p>We designed a fat segmentation method based on optimizing a variety of factors relevant to small animal imaging at 7T. In contrast to most previously described MRI methods based on signal intensity of T1 weighted image alone, we chose to use parametric images based on Multi-spin multi-echo (MSME) Bruker pulse sequence which has proven to be particularly robust in our laboratory over the last several years. The sequence was optimized on a T1 basis to emphasize the signal. T2 relaxation times can be calculated from the multi echo data and we have done so on a pixel by pixel basis for the initial step in the post processing methodology. The post processing consists of parallel paths. On one hand, the weighted image is precisely divided into different regions with optimized smoothing and segmentation methods; and on the other hand, a confidence image is deduced from the parametric image according to the distribution of relaxation time relationship of typical adipose. With the assistance of the confidence image, a useful software feature was implemented to which enhances the data and in the end results in a more reliable and flexible method for adipose evaluation.</p> <p>Results</p> <p>In this paper, we describe how we arrived at our recommended procedures and key aspects of the post-processing steps. The feasibility of the proposed method is tested on both simulated and real data in this preliminary research. A research tool was created to help researchers segment out fat even when the anatomical information is of low quality making it difficult to distinguish between fat and non-fat. In addition, tool is designed to allow the operator to make adjustments to many of the key steps for comparison purposes and to quantitatively assess the difference these changes make. Ultimately our flexible software lets the researcher define key aspects of the fat segmentation and quantification.</p> <p>Conclusions</p> <p>Combining the full T2 parametric information with the optimized first echo image information, the research tool enhances the reliability of the results while providing more flexible operations than previous methods. The innovation in the method is to pair an optimized and very specific image acquisition technique to a flexible but tuned image post processing method. The separation of the fat is aided by the confidence distribution of regions produced on a scale relevant to and dictated by practical aspects of MRI at 7T.</p

Systemic Inhibition of NF-κB Activation Protects from Silicosis

Background: Silicosis is a complex lung disease for which no successful treatment is available and therefore lung transplantation is a potential alternative. Tumor necrosis factor alpha (TNFα) plays a central role in the pathogenesis of silicosis. TNFα signaling is mediated by the transcription factor, Nuclear Factor (NF)-κB, which regulates genes controlling several physiological processes including the innate immune responses, cell death, and inflammation. Therefore, inhibition of NF-κB activation represents a potential therapeutic strategy for silicosis. Methods/Findings: In the present work we evaluated the lung transplant database (May 1986-July 2007) at the University of Pittsburgh to study the efficacy of lung transplantation in patients with silicosis (n = 11). We contrasted the overall survival and rate of graft rejection in these patients to that of patients with idiopathic pulmonary fibrosis (IPF, n = 79) that was selected as a control group because survival benefit of lung transplantation has been identified for these patients. At the time of lung transplantation, we found the lungs of silica-exposed subjects to contain multiple foci of inflammatory cells and silicotic nodules with proximal TNFα expressing macrophage and NF-κB activation in epithelial cells. Patients with silicosis had poor survival (median survival 2.4 yr; confidence interval (CI): 0.16-7.88 yr) compared to IPF patients (5.3 yr; CI: 2.8-15 yr; p = 0.07), and experienced early rejection of their lung grafts (0.9 yr; CI: 0.22-0.9 yr) following lung transplantation (2.4 yr; CI:1.5-3.6 yr; p<0.05). Using a mouse experimental model in which the endotracheal instillation of silica reproduces the silica-induced lung injury observed in humans we found that systemic inhibition of NF-κB activation with a pharmacologic inhibitor (BAY 11-7085) of IκBα phosphorylation decreased silica-induced inflammation and collagen deposition. In contrast, transgenic mice expressing a dominant negative IκBα mutant protein under the control of epithelial cell specific promoters demonstrate enhanced apoptosis and collagen deposition in their lungs in response to silica. Conclusions: Although limited by its size, our data support that patients with silicosis appear to have poor outcome following lung transplantation. Experimental data indicate that while the systemic inhibition of NF-κB protects from silica-induced lung injury, epithelial cell specific NF-κB inhibition appears to aggravate the outcome of experimental silicosis. © 2009 Di Giuseppe et al

Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)

Diagnostic significance of Aspergillus species isolated from respiratory samples in an adult pneumology ward.

Although the diagnostic significance of isolating Aspergillus spp. from respiratory cultures has been studied in immunocompromised hosts with invasive pulmonary aspergillosis (IPA), little is known of such infections in immunocompetent patients with other forms of aspergillosis. In this study of adult pneumology ward patients, we examined the association between Aspergillus spp. and disease prevalence. Laboratory records from April 1998 to March 2009 were reviewed to identify patients with Aspergillus spp. in respiratory samples. Correlations between the isolated species and clinical characteristics of patients were evaluated. During the study period, 165 Aspergillus spp. isolates were detected in the respiratory cultures of 139 patients. Of these patients, 62 (45%) were colonized with Aspergillus spp. and displayed no clinical symptoms of aspergillosis, while 77 (55%) had a form of pulmonary aspergillosis, characterized as either chronic necrotizing pulmonary aspergillosis (CNPA) (48%), aspergilloma (29%), IPA (13%), or allergic bronchopulmonary aspergillosis (ABPA) (10%). The dominant species were Aspergillus fumigatus (41%), A. niger (32%), and A. versicolor (12%). A. fumigatus was most commonly isolated in patients with IPA, aspergilloma, and CNPA, whereas A. niger was the dominant species in colonized patients and those with ABPA. Isolation of an Aspergillus spp. from respiratory samples does not confirm it as the etiologic pathogen because airway colonization by Aspergillus spp. is a common feature in several chronic lung diseases. Repeated isolation of the identical Aspergillus species and detection of anti-Aspergillus antibodies and/or Aspergillus antigens in sera are needed to determine the isolate represents the etiologic agent of disease