ACVR1 Gene Mutation in Sporadic Korean Patients with Fibrodysplasia Ossificans Progressiva

Fibrodysplasia ossificans progressiva (FOP; OMIM 135100) is a rare but extremely disabling genetic disorder of the skeletal system, and is characterized by the progressive development of ectopic ossification of skeletal muscles and subsequent joint ankylosis. The c.617G>A; p.R206H point mutation in the activin A type I receptor (ACVR1) gene has been reported to be a causative mutation of FOP. In the present study, mutation analysis of the ACVR1 gene was performed in 12 patients diagnosed or suspected to have FOP. All patients tested had a de novo heterozygous point mutation of c.617G>A; p.R206H in ACVR1. Mutation analysis confirmed a diagnosis of FOP in patients with ambiguous features, and thus, could be used for diagnostic purposes. Early confirmation through mutation analysis would allow medical professionals to advise on the avoidance of provoking events to delay catastrophic flare-ups of ectopic ossifications

Nodular Ground-Glass Opacities on Thin-section CT: Size Change during Follow-up and Pathological Results

OBJECTIVE: To evaluate the inter-group differences in growth and the pathological results of nodular ground-glass opacities (GGOs) according to their size and focal solid portions. MATERIALS AND METHODS: Ninety-six nodular GGOs in 55 individuals followed by CT for at least one month from an initial chest CT were included. Forty nodular GGOs in 30 individuals were pathologically confirmed to be: adenocarcinoma (n = 15), bronchioloalveolar carcinoma (BAC) (n = 11), atypical adenomatous hyperplasia (AAH) (n = 8), focal interstitial fibrosis (n = 5) and aspergillosis (n = 1). Lesions were categorized based on high-resolution CT findings: pure nodular GGO (PNGGO) 10 mm, mixed nodular GGO (MNGGO) 10 mm. In each group, the change in size during the follow-up period, the pathological results and the rate of malignancy were evaluated. RESULTS: Three MNGGO lesions, and none of the PNGGO, grew during the follow-up period. Resected PNGGOs 10 mm were focal interstitial fibrosis (n = 4), AAH (n = 2), BAC (n = 2), and adenocarcinoma (n = 2). Resected MNGGOs 10 mm were adenocarcinoma (n = 11), BAC (n = 3), and aspergillosis (n = 1). CONCLUSION: Mixed nodular GGOs (MNGGOs) had the potential for growth; most were pathologically adenocarcinoma or BAC. By contrast, PNGGOs were stable for several months to years; most were AAH, BAC, or focal interstitial fibrosis.This study is supported by Seoul National University Hospital Research Grant (04- 2006-044-0)

Endobronchial Ultrasound-guided Transbronchial Needle Biopsy for Diagnosis of Mediastinal Lymphadenopathy in Patients with Extrathoracic Malignancy

Mediastinal lymphadenopathy associated with extrathoracic malignancy or a metastasis of unknown origin (MUO) requires pathological verification. Surgical exploration or endoscopic ultrasound-guided fine needle aspiration is limited to application. We investigated the effectiveness of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) for evaluating mediastinal lymphadenopathy in patients with an extrathoracic malignancy. We retrospectively analyzed data from 59 patients who underwent EBUS-TBNA with a core biopsy because of a suspected mediastinal metastasis between September 2008 and August 2010. All patients had previously been diagnosed with an extrathoracic malignancy (n = 39, 66.1%) or a suspected MUO without a thoracic lesion (n = 20, 33.9%). A total of 88 lymph nodes was analyzed. EBUS-TBNA findings indicated malignancies in 34 patients (57.6%). The EBUS-TBNA sensitivity and specificity for the detection of mediastinal malignancy in patients with a previous extrathoracic malignancy were 96.3% and 100%, respectively. For MUO patients without a thoracic lesion, the sensitivity and specificity were 61.5% and 100%, respectively. The overall sensitivity and specificity were 81.0% and 100%, respectively (P = 0.053). EBUS-TBNA is a safe and effective modality for evaluating mediastinal lymphadenopathy in patients with a previous extrathoracic malignancy or a MUO without a thoracic lesion. The application of this diagnostic tool is likely to have significant clinical implications

Expression of CD99 in Pleomorphic Carcinomas of the Lung

Pleomorphic carcinoma of the lung (PCL) is characterized by a mixture of sarcomatoid and carcinoma components, and a poor prognosis. However, no immunophenotype of tumor markers has been characterized in PCL. To charaterize the immunophenotype for CD99 in PCL, we performed an immunohistochemical evaluation of PCLs for thyroid transcription factor-1 (TTF-1), cytokeratin (CK) 7 and 20, and for CD99. CD99 was found to be expressed in both carcinomatous (47%) and sarcomatous components such as spindle cells (92%) and giant cells (57%). In the case of spindle cells, CK7 was expressed in 6 cases (46%) and TTF-1 in 2 cases (15%), whereas for giant cells CK7 was expressed in 8 cases (57%) and TTF-1 in one case (7%). However, CK20 was not expressed in either the carcinomatous or sarcomatous components in any case. Thus, CD99 was found to be widely expressed in both sarcomatous and carcinoma component in PCL. A clinicopathological analysis showed no direct correlation between the expression of CD99 and the clinical indices (stage, survival rate, invasion) of PCL

The Effect of Simvastatin on the Proliferation and Differentiation of Human Bone Marrow Stromal Cells

Statins have been postulated to affect the bone metabolism. Recent experimental and epidemiologic studies have suggested that statins may also have bone protective effects. This study assessed the effects of simvastatin on the proliferation and differentiation of human bone marrow stromal cells (BMSCs) in an ex vivo culture. The bone marrow was obtained from healthy donors. Mononuclear cells were isolated and cultured to osteoblastic lineage. In the primary culture, 10-6 M simvastatin diminished the mean size of the colony forming units-fibroblastic (CFU-Fs) and enhanced matrix calcification. At near confluence, the cells were sub-cultured. Thereafter, the alkaline phosphatase (ALP) activities of each group were measured by the time course of the secondary culture. Simvastatin increased the ALP activity in a dose dependent manner, and this stimulatory effect was more evident during the early period of culture. A 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was performed during the secondary culture in order to estimate the effect of simvastatin on the proliferation of human BMSCs. When compared to the control group, simvastatin significantly decreased the proliferation of cells of each culture well. 10-6 M of simvastatin also significantly enhanced the osteocalcin mRNA expression level. This study shows that simvastatin has a stimulatory effect on bone formation through osteoblastic differentiation, and has an inhibitory effect on the proliferative potential of human BMSC

Role of Echocardiography in Atrial Fibrillation

Atrial fibrillation (AF) is most common arrhythmia and its prevalence appears to be increasing as the population ages. Echocardiography can play a key role in risk stratification and management of patients with AF. Transthoracic echocardiography allows rapid and comprehensive assessment of cardiac anatomical structure and function. Pulmonary vein flow monitoring using echocardiography has the potential to an increasing role in the evaluation of cardiac function and AF ablation procedures. Transesophageal echocardiography also provides accurate information about the presence of a thrombus in the atria and thromboembolic risk. The novel technique of intracardiac echocardiography has emerged as a popular and useful tool in the everyday practice of interventional electrophysiology. Other imaging modalities, such as computed tomography and magnetic resonance imaging have complementary roles in risk stratification and assessment of patients with AF. Echocardiography continues to be the foundation of clinical evaluation and management of AF

The IASLC Lung Cancer Staging Project: A Renewed Call to Participation

Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project