Jin Young An

EGFR Mutation Status in Primary Lung Adenocarcinomas and Corresponding Metastatic Lesions: Discordance in Pleural Metastases

UNLABELLED We evaluated EGFR and KRAS mutations between 37 paired primary tumors and corresponding metastases in lung adenocarcinoma. A substantial discordance was found in EGFR mutation status between primary tumors and corresponding metastases including pleural metastases. Moreover, the responsiveness to EGFR tyrosine kinase inhibitors tend to be correlated with EGFR mutation status in metastatic lesions than in primary tumors. INTRODUCTION The aim of this study was to compare epidermal growth factor receptor (EGFR) and KRAS mutations between primary tumors and corresponding metastases including pleural metastases in lung adenocarcinoma. METHODS Thirty-seven paired primary lung adenocarcinomas and corresponding metastatic tumors were analyzed for EGFR and KRAS mutations. In addition, 21 pleural metastases including malignant pleural effusion or pleural biopsy were used in performing these mutation analyses. RESULTS EGFR mutations were detected in 18 primary lung adenocarcinomas (48.6%) and in 16 corresponding metastases (43.2%). EGFR mutations showed a discordance rate of 16.2% (6 of 37 patients) between primary lung adenocarcinomas and corresponding metastases. Among 21 pleural metastases, 3 patients (14.3%) showed that the EGFR mutation was discordant. KRAS mutations were detected in one primary tumor and in two metastatic tumors. Eighteen patients were treated with EGFR tyrosine kinase inhibitors. One of seven patients who experienced partial response had EGFR mutations only in the metastasis, and two of seven patients who experienced progressive disease carried wild-type EGFR only in the metastasis. CONCLUSIONS EGFR mutations were discordant between primary tumors and corresponding metastases in a significant portion of lung adenocarcinomas. Furthermore, these discordance was also observed in metastases to the pleura, the nearest metastatic site.

Detection of EGFR Mutation Status in Lung Adenocarcinoma Specimens with Different Proportions of Tumor Cells Using Two Methods of Differential Sensitivity

Introduction: To evaluate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma specimens with different proportions of tumor cells using two methods with different sensitivities. Methods: EGFR mutation status was determined by peptide nucleic acid (PNA) clamping and direct sequencing. The samples consisted of 41 cell blocks of malignant pleural effusions with various proportions of tumor cells, as well as 23 lung biopsy specimens containing more than 20% tumor cells and the corresponding surgically resected tumors. Results: In the analysis of malignant pleural effusions, EGFR mutations were detected only by PNA clamping in four of nine patients who exhibited partial response to EGFR tyrosine kinase inhibitors; all the cell blocks of these four patients contained less than 20% tumor cells. Direct sequencing revealed wild-type EGFR, whereas PNA clamping revealed mutant EGFR, in one of five patients who exhibited progressive disease in response to EGFR tyrosine kinase inhibitor; the cell block of this patient contained a high proportion of tumor cells. A comparison of biopsy specimens containing sufficient tumor cells and the corresponding surgically resected tumors revealed discordance in the EGFR mutation status in four patients based on PNA clamping, whereas no discrepancies were observed by direct sequencing. Conclusions: Highly sensitive methods, such as PNA clamping, may be superior to direct sequencing for the detection of EGFR mutations in diagnostic specimens with a low proportion of tumor cells. Direct sequencing may be more representative when diagnostic specimens with a high proportion of tumor cells are available.

Diagnostic Value of Circulating Extracellular miR-134, miR-185, and miR-22 Levels in Lung Adenocarcinoma-Associated Malignant Pleural Effusion

Purpose The accurate and timely diagnosis of malignant pleural effusion (MPE) in lung cancer patients is important because MPE has a poor prognosis and is classified as stage IV disease. Molecular biomarkers for pleural effusion, such as circulating extracellular microRNAs (miRNAs) isolated from pleural fluid, may help in the diagnosis of MPE. The present study examined whether miRNAs that are deregulated in lung cancer (miR-134, miR-185, and miR-22) can serve as diagnostic markers for lung adenocarcinoma-associated MPE (LA-MPE). Materials and Methods Real-time reverse transcription quantitative polymerase chain reaction was used to measure the expression of the three miRNAs in samples from 87 patients with pleural effusion comprising 45 LA-MPEs and 42 benign pleural effusions (BPEs). The area under the receiver operating characteristic curve (AUC) was then used to evaluate the diagnostic performance of each of the three miRNAs and compare it with that of the common tumor marker, carcinoembryonic antigen (CEA). Results The expression of all three miRNAs was significantly lower in LA-MPE than in BPE (p <0.001). The AUCs for miR-134, miR-185, miR-22, and CEA were 0.721, 0.882, 0.832, and 0.898, respectively. Combining CEA with the three miRNAs increased the diagnostic performance, yielding an AUC of 0.942 (95% confidence interval, 0.864 to 0.982), with a sensitivity of 91.9% and a specificity of 92.5%. Conclusion The present study suggests that the expression levels of circulating extracellular miR-134, miR-185, and miR-22 in patients with pleural effusion may have diagnostic value when differentiating between LA-MPE and BPE.

The diagnostic efficacy and safety of endobronchial ultrasound-guided transbronchial needle aspiration as an initial diagnostic tool

Background/Aims Real-time, convex probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used for the staging of malignant mediastinal lymph nodes. We evaluated the diagnostic efficacy and safety of EBUS-TBNA when used as an initial diagnostic tool. Methods We retrospectively studied 56 patients who underwent EBUS-TBNA as an initial diagnostic tool between August 2010 and December 2011. Procedure purpose were classified into four categories: 1) intrathoracic masses adjacent to the central airway; 2) enlarged lymph nodes for concurrent diagnosis and staging in suspected malignancy; 3) enlarged lymph nodes in suspected malignancy cases with inability to perform percutaneous core needle biopsy (PCNB); and 4) solely mediastinal masses/lymph nodes in lieu of mediastinoscopy. Results The diagnostic accuracy of EBUS-TBNA regardless of procedure purpose was calculated to be 83.9%. Furthermore, the diagnostic accuracy of malignant disease was significantly higher than benign disease (93.9% vs. 70.6%, p < 0.001). The diagnostic accuracy of EBUS-TBNA for each disease is as follows: tuberculosis, 50%; sarcoidosis, 60%; aspergillosis, 100%; lung abscess, 100%; lung cancer, 93%; and lymphoma, 100%. There were minor complications in seven patients during the EBUS-TBNA procedure. The complications included mild hypoxia and bleeding. Conclusions In conclusion, EBUS-TBNA is a useful initial diagnostic tool for both benign and malignant diseases. EBUS-TBAN is also a very safe procedure and less invasive compared to mediastinoscopy or PCNB.

Extranodal Interdigitating Dendritic Cell Sarcoma Presenting in the Pleura: A Case Report

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from the antigen-presenting cells of the immune system. This disease usually involves the lymph nodes, and rarely, extranodal sites may be affected. The authors report a case of extranodal IDCS presenting in the pleura. A 32-yr-old man presented with progressive chest pain. Imaging studies showed diffuse pleural thickening with pleural effusion. Morphological and immunohistochemical analysis of an incisional biopsy of the pleura were consistent with a diagnosis of IDCS; tumor cells were positive for S100 and CD45, but negative for CD1a, CD21, CD35, B cell and T cell markers. The patient was administered chemotherapy, but died of progressive disease. Although its incidence is extremely rare, this case suggests that extranodal IDCS should be considered in the differential diagnosis of undifferentiated neoplasms and that immunohistochemical staining be performed using appropriate markers.

Diagnostic performance of CD66c in lung adenocarcinoma-associated malignant pleural effusion: comparison with CEA, CA 19-9, and CYFRA 21-1.

Summary Various tumour markers have been evaluated in malignant pleural effusions, but not CD66c. This study evaluated the diagnostic ability of CD66c in lung adenocarcinoma-associated malignant pleural effusions (LA-MPEs) and compared it with other known tumour markers. Forty-seven cases of LA-MPE and 52 cases of benign pleural effusions were collected. The levels of CD66c, CEA, CA 19-9, and CYFRA 21-1 were measured by enzyme immunoassay. The expression of CD66c, CEA, and CA 19-9 in cell blocks was measured by immunocytochemistry. CEA had the best diagnostic values, with a sensitivity of 87.2% and specificity of 92.3%. Both CD66c and CA 19-9 showed the highest specificity of 98.1%, with sensitivities of 63.8% and 55.3%, respectively. CYFRA 21-1 had a sensitivity of 83.0% and specificity of 76.9%. CEA combined with CA 19-9 reached a sensitivity of 91.5% and a specificity of 98.1%. The sensitivities of immunocytochemical staining for CD66c, CEA, and CA 19-9 were 72.5%, 75%, and 40%, respectively. CD66c showed a diagnostic performance comparable to CYFRA 21-1 and CA 19-9 by enzyme immunoassay. Immunocytochemical study showed that CD66c and CEA were more sensitive than CA19-9. Both studies support CD66c as a potential tumour marker to differentiate LA-MPE from benign effusions.

Clinical demographics and outcomes in mechanically ventilated patients in Korean intensive care units

Knowledge of clinical demographics and outcomes of mechanically ventilated patients is important but there are few prospectively collected data in Korea. The objective of the present study was to describe the current status of mechanically ventilated patients in Korea as of 2010. We analyzed the data of Korean patients (275 patients in 12 Korean intensive care units [ICU]) participating in a multinational prospective cohort study on mechanical ventilation. The most common indication for mechanical ventilation was pneumonia (23%). Pressure-limited ventilation modes were preferred over volume-cycled ventilation modes. Non-invasive positive pressure ventilation was used in only seven (2%) patients as the initial ventilatory support. Median duration of mechanical ventilation was 7 days and ICU mortality was 36%. The multiple logistic regression model revealed that the Simplified Acute Physiology Score II (SAPS II) score at ICU admission (odds ratio [OR], 1.034; 95% confidence interval [CI], 1.001-1.036; P=0.033), peak pressure (OR, 1.054; 95% CI, 1.016-1.095; P=0.006), and the number of failed organs (OR, 2.132; 95% CI, 1.634-2.781; P<0.001) were independently associated with ICU mortality. This study provides a snapshot of current practice of mechanical ventilation in Korea. Graphical Abstract

Invasive aspergillosis involving the lungs and brain after short period of steroid injection: a case report.

Invasive pulmonary aspergillosis (IPA) has emerged as a severe infection in patients with immunocompromised hosts. However, recently, several IPA cases, without an apparent predisposition to immunodeficiency, has been reported. A 72-year-old woman was admitted for evaluation of general weakness and poor oral intake. She reported no medical history, except for intraarticular injection of a corticosteroid for joint pain for the duration of two months. A chest radiography revealed multiple cavitary nodules in both lungs. Examination of specimens, obtained by percutaneous needle biopsy, led to a diagnosis of invasive aspergillosis. Brain magnetic resonance imagining revealed numerous peripheral thin enhancing cystic nodules in both cerebral hemispheres. We initiated intravenous administration of amphotercin B. However, the patient died after nine days. Here, we report an invasive aspergillosis case, which involves the lungs and brain after a short period of steroid injection.

Transcultural adaptation and validation of the korean version of the brief illness perception questionnaire for patients with pulmonary tuberculosis

Background and Aim: The brief illness perception questionnaire (BIPQ) has been used in many populations for both adults and children, and it provides a rapid assessment of illness perception. This study was performed to create a translated version of the BIPQ to fit the Korean society and to test its validity through pulmonary tuberculosis (TB) patients. Methods: Translation and transcultural adaptation of BIPQ, applicable to the Korean society, was performed in accordance with the international guidelines. Internal consistency, test-retest reliability, concurrent validity, and discrimination validity were evaluated. To assess the discrimination validity, the BIPQ scores were compared between pulmonary TB and chronic obstructive pulmonary disease (COPD). Results: Sixty-eight patients with pulmonary TB participated in this study. Cronbachs α coefficient was 0.753, which indicated satisfactory internal consistency. The concurrent validity showed significant correlations (Pearsons correlation of 0.753). The test-retest reliability was confirmed with an intraclass correlation coefficient of 0.892. The total score of BIPQ in patients with COPD was significantly higher than that in those with pulmonary TB (37.67 vs. 30.85; P= 0.005), which supported the discrimination validity. Conclusions: The Korean version of BIPQ was found to be a reliable and valid questionnaire for patients with pulmonary TB.

Fistula Formation between Right Upper Bronchus and Bronchus Intermedius Caused by Endobronchial Tuberculosis: A Case Report

Endobronchial tuberculosis is defined as a tuberculous infection of the tracheobronchial tree and has a prevalence of up to 50% in active pulmonary tuberculosis cases. The most common complication of endobronchial tuberculosis is bronchial stenosis; benign fistula formation by endobronchial tuberculosis is rare, especially inter-bronchial fistula formation. We reported a rare case of a 73-year-old woman with a fistula between the right upper bronchus and bronchus intermedius. A diagnosis of inter-bronchial fistula caused by endobronchial tuberculosis was based on the results of chest computed tomography scans, bronchoscopy, and microbiological and pathological tests. The patient was treated with anti-tuberculous medication, and her symptoms gradually improved.