BRAF V600E Mutation of Non-Small Cell Lung Cancer in Korean Patients.

Background and Objectives: BRAF mutational status in resected non-small cell lung cancer (NSCLC) in the Korean population is poorly understood. We explored BRAF (particularly BRAF V600E) mutational status among Korean patients with NSCLC. Materials and Methods: This study included 378 patients with resected primary NSCLC who were enrolled from January 2015 to December 2017. The authors obtained formalin-fixed paraffin-embedded (FFPE) tissue blocks and performed peptide nucleic acid (PNA)-clamping polymerase chain reaction (PCR) for detecting BRAF V600, real-time PCR for detecting BRAF V600E, and immunohistochemical analyses using the mutation-specific Ventana VE1 monoclonal antibody. For positive cases in any methods mentioned above, direct Sanger sequencing was additionally performed. Results: The PNA-clamping method revealed the BRAF V600 mutation in 5 (1.3%) of the 378 patients. Among these five patients, real-time PCR, direct Sanger sequencing detected BRAF V600E mutations in three (0.8%) patients. Thus, two cases showed differences in their PNA-clamping and the others. Direct Sanger sequencing of PNA-clamping PCR product was performed for two cases showing negative results on direct Sanger sequencing; both contained BRAF mutations other than V600E. All patients harboring BRAF mutations had adenocarcinomas, and all patients with V600E mutation exhibited minor micropapillary components. Conclusions: Despite the low incidence of the BRAF mutation among Korean patients with NSCLC, lung adenocarcinoma patients with micropapillary components should be prioritized in terms of BRAF mutation testing. Immunohistochemical staining using Ventana VE1 antibody may serve as a screening examination for BRAF V600E.

Localization Technique Using Mixture of Indigo Carmine and Lipiodol of Pulmonary Nodule via Bronchoscopic Navigation.

Background and Objectives: As the number of minimally invasive surgeries, including video-assisted thoracoscopic surgery, increases, small, deeply located lung nodules are difficult to visualize or palpate; therefore, localization is important. We studied the use of a mixture of indigo-carmine and lipiodol, coupled with a transbronchial approach-to achieve accurate localization and minimize patient discomfort and complications. Materials and Methods: A total of 60 patients were enrolled from May 2019 to April 2022, and surgery was performed after the bronchoscopy procedure. Wedge resection or segmentectomy was performed, depending on the location and size of the lesion. Results: In 58/60 (96.7%) patients, the localization of the nodules was successful after localization, and 2/60 required c-arm assistance. None of the patients complained of discomfort during the procedure; in all cases, margins were found to be free from carcinoma, as determined by the final pathology results. Conclusions: We recommend this localization technique using mixture of indigo carmine and lipiodol, in concert with the transbronchial approach, because the procedure time is short, patient's discomfort is low, and success rate is high.

Applying Fibrin Glue under Pleurography for Intractable Secondary Spontaneous Pneumothorax.

BACKGROUND: Prolonged air leakage is a problem that can frequently develop in patients with a secondary spontaneous pneumothorax (SSP) or in those who undergo thoracic surgery. However, the management of an air leak is difficult and reoperation might be avoided due to several reasons including adhesions. Herein, we introduce a fibrin glue application under pleurography (FGAP) and short-term outcomes in patients who underwent this procedure. METHODS: FGAP was performed in 20 patients with an intractable persistent air leakage who had poor lung function, comorbidities to undergo general anesthesia and were expected severe adhesions due to previous surgery. All medical records were retrospectively reviewed. RESULTS: Eighteen cases sealed soon after dropping the glue. One patient had a prolonged air leak for 12 days and another patient required an operation to control air leakage 16 days after the procedure. The mean duration of postoperative drainage was 4.17 ± 2.11 days (range: 3-14 days). No postprocedural complications were recorded. The mean duration of follow-up was 12.01 ± 5.02 months (range: 4-22 months). CONCLUSION: FGAP could be a treatment option to seal air leaks, especially in cases with intractable air leakage.

Factors Affecting Postoperative Lung Expansion in Patients with Pyogenic Empyema.

BACKGROUND: In patients with parapneumonic empyema, decortication is usually preferred to ensure functional lung re-expansion. However, there could be patients exhibiting incomplete postoperative lung expansion and inadequate drainage despite decortication. Therefore, we evaluated factors affecting postoperative lung expansion in patients undergoing decortication. METHODS: A total of 221 patients with pyogenic empyema who underwent video-assisted thoracoscopic surgery (VATS) between January and October 2016 in our hospital were reviewed in terms of surgical success. The following factors were evaluated: age; the time between identification of a localized effusion and surgical referral; chest tube drainage durations; any underlying morbidity preoperative blood culture data; and the thickness of the visceral pleura. RESULTS: Several factors that significantly prolonged the postoperative time to lung expansion were evident in patients with diabetes mellitus (DM) and bacteremia; postoperative chest tube drainage was significantly longer in those with DM (p = 0.009) and bacteremia (p = 0.01); and postoperative hospitalization time was significantly longer in patients with bacteremia (p = 0.01). The thickness of the visceral pleura was strongly correlated with postoperative chest tube drainage duration and postoperative hospitalization time (Pearson correlation coefficient, r = 0.245, p = 0.00). CONCLUSIONS: In patients with DM, bacteremia, or thickened pleura, the time to lung expansion after operation was longer. Therefore, stricter pre- and post-operative control of blood-sugar levels and adequate antibiotics are required to facilitate postoperative lung re-expansion. In patients with thickened pleurae, prolonged chest tube placement is unavoidable.

Notch1 modulates oxidative stress induced cell death through suppression of apoptosis signal-regulating kinase 1.

Notch1 genes encode receptors for a signaling pathway that regulates various aspects of cell growth and differentiation; however, the role of Notch1 signaling in p38 mitogen-activated protein kinase (MAPK) signaling pathway is still not well defined. In this study, we found that Notch1 intracellular domain (Notch1-IC) prevents oxidative stress-induced cell death through the suppression of the Apoptosis signal-regulating kinase (ASK) 1 signaling pathway. Notch1-IC inhibited H2O2-induced activation of ASK1 and the activation of downstream kinases in the p38 MAPK signaling cascade. The results of both in vivo binding and kinase studies have revealed that ASK1 is the direct target of Notch1-IC, whereas it produced no effect on either MAP kinase kinase (MKK) 3 or p38 MAPK. Notch1-IC blocked both the homooligomerization of ASK1 and inhibited ASK1 activity. Furthermore, Notch1-IC facilitated the translocation of activated ASK1 toward the nucleus. Notch1 knockdown was determined to be highly susceptible to oxidative stress-induced activation of ASK1-MKK3/MKK6-p38 MAPK signaling cascade and cell death. Taken together, our findings suggest that Notch1-IC may act as a negative regulator in ASK1 signaling cascades.

Parasternal mass revealing as a postvaccinal Bacillus Calmette-Guérin (BCG)-elicited sternal osteomyelitis.

Although osteomyelitis is a very rare complication of Bacillus Calmette-Guérin (BCG) vaccination, sternal osteomyelitis as a late complication of BCG vaccination diagnosed by polymerase chain reaction (PCR) in a child is described.We might consider BCG osteomyelitis in the case of osteomyelitis without bacterial isolation within a year after BCG vaccination, the absence of pulmonary foci, and a contact to the patient with tuberculosis.

Prognostic impact of limited resection vs. inadequate adjuvant therapy in patients with pathologic stage II or III non-small cell lung cancer: results from the Korean Association of Lung Cancer Registry.

BACKGROUND: For patients with stage II and III non-small cell lung cancer (NSCLC), various multi-modality treatments are required. However, depending on the individual conditions of patients, there will be a significant difference in prognosis. Therefore, this study investigated the clinical impact of inadequate treatment (limited surgery and inadequate adjuvant therapy) in patients with NSCLC stage II or III using data from the Korean Association of Lung Cancer Registry (KALC-R) between 2014 and 2016. METHODS: Of the 8,110 new lung cancer cases registered at the Korea Central Cancer Registry in 2014-2016, 721 patients with stage II or III NSCLC were selected and divided into three groups according to differences in cancer treatment methods. In group A, patients underwent standard surgery and completed adjuvant therapy. In group B, patients underwent standard surgery without completing adjuvant therapy. In group C, patients received adjuvant therapy after limited surgery. After performing propensity score matching (PSM) for selected patients, overall survival (OS) and disease-free survival (DFS) rates of the three groups of patients with stage II and III NSCLC patients were then compared. RESULTS: Of the 721 patients with NSCLC, 239, 437, and 45 belonged to groups A, B, and C, respectively. After 1:3 PS matching for groups B and C, the 5-year survival rate of patients with stage II or III NSCLC were 68.0% and 26.7% for groups B and C, respectively and the DFS rate was 59.1% and 16.2% for groups B and C, respectively. CONCLUSIONS: The therapeutic effect of the standard surgery was the best. Although patients received adjuvant therapy, limited resection resulted in a poorer prognosis in compromised patients compared with omitting adjuvant therapy followed by standard surgery. Thus, surgical treatment should be considered in patients who are unable to complete surgical and adjuvant therapy.

The role of local ablative therapy in patients with advanced invasive mucinous adenocarcinoma of the lung.

PURPOSE: Invasive mucinous adenocarcinoma (IMA) of the lungs is a rare subtype of lung adenocarcinoma with a limited understanding of its prognosis, particularly in advanced stages. This study aimed to assess the prognosis of patients with advanced IMA by focusing on treatment modalities. METHODS: This single-center retrospective study evaluated 33 patients with IMAs diagnosed with advanced-stage disease or disease progression after curative treatment between 2011 and 2021. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). OS and PFS were calculated from the date of the diagnosis of advanced IMA. RESULTS: The study cohort included 13 patients at the initial advanced stage and 20 patients who progressed after curative treatment. Treatment modalities included conventional chemotherapy in 24 patients (72.7%), targeted therapy in seven (21.2%), immunotherapy in 13 (39.4%), and local ablative therapy (LAT) in 13 (39.4%). The median OS was 32 months (95% confidence interval [CI], 2.9-61.0), with LAT significantly associated with improved OS compared to non-LAT treatment (not reached vs. 11.3 months, p = 0.001). However, there was no significant difference in OS based on conventional chemotherapy (p = 0.396), targeted therapy (p = 0.655), or immunotherapy (p = 0.992). In multivariate analysis, LAT remained an independent prognostic factor for OS (hazard ratio, 0.125; 95% CI, 0.026-0.608; p = 0.01). PFS was 8.6 months (95% CI, 3.6-13.7), with no significant differences observed among the treatment modalities. CONCLUSION: Our findings suggest that LAT may provide favorable survival outcomes in patients with advanced IMA.

Effect of transpleural perfusion with oxygenated perfluorocarbon in a rat model of acute lung injury.

BACKGROUND: Despite advances in critical care, more effective methods of systemic oxygenation in patients with acute lung injury or acute respiratory distress syndrome are needed. The goal of this study was to determine if it is possible to increase systemic oxygenation by transpleural perfusion with oxygenated perfluorocarbon in animals with induced acute lung injury. METHODS: Eighteen Sprague-Dawley rats were intubated, and acute lung injury was induced by aspiration of 0.1N HCl (1 mL/kg) through the tracheal tube. Inflow and outflow tubes were placed in the thoracic cavity and connected to a perfusion circuit containing a roller pump, warmer, and oxygenator. Rats in group I were not treated after aspiration of HCl, those in group II were perfused with oxygenated saline, and those in group III were perfused with oxygenated perfluorocarbon. Arterial blood gases were collected every 30 minutes for 180 minutes. At the last step of the experiments, pathological examination of the lungs and parietal pleura was performed. RESULTS: PaO(2) in group III was significantly higher than that in group I or II. PaCO(2) in group III was significantly lower than that in the other two groups. Histological examination showed relatively well-delineated zones of inflammation-free coagulative necrosis of lung parenchyma in all groups. CONCLUSIONS: Transpleural perfusion with oxygenated perfluorocarbon in an animal model of induced acute lung injury resulted in a significant increase in systemic oxygenation and depletion of systemic carbon dioxide, and might be a useful method for improving systemic oxygenation in patients with acute lung injury.

Intrathoracic muscular transposition in chronic tuberculous empyema.

BACKGROUND: The effective management of chronic tuberculous empyema requires an evacuation of pus and a re-expansion of the lung or an obliteration of the empyema space such as closed thoracostomy, decortication, or open window thoracostomy (OWT) followed by intrathoracic muscular transposition (IMT). However, the most effective management of chronic tuberculous empyema is still debatable. METHODS: From June 1999 to July 2010, 18 patients with chronic tuberculous empyema who underwent OWT and/or IMT were enrolled in this study. The causes of empyema, and methods and outcomes of treatment were retrospectively reviewed. The success rate of IMT was investigated to evaluate the efficacy. RESULTS: Mean patient age was 54.3 ± 14.9 years and 16 patients were male. Depending on operative methods, three groups were divided: OWT only (n = 4); two-stage operation as OWT followed by IMT (n = 7); and one-stage operation as OWT with IMT simultaneously (n = 7). Of 14 patients who underwent IMT, 13 patients successfully recovered from empyema and bronchopleural fistula (BPF) (success rate, 92.86%), but one patient developed a secondary bacterial infection. There was no operative mortality. CONCLUSION: This study suggests that IMT may be an effective option to control infection or BPF in chronic tuberculous empyema.

Pulmonary mass diagnosed as extrauterine epithelioid trophoblastic tumor.

Pulmonary extrauterine epithelioid trophoblastic tumors (ETTs) are extremely rare. A 26-year-old nonsmoking woman with a history of a suspected subclinical miscarriage presented with a large mass in the right lower lobe that was confirmed to be a pulmonary extrauterine ETT using immunohistochemical stains. When a nonsmoking fertile woman presents with a pulmonary mass and an elevated serum ß-human chorionic gonadotrophin in the absence of gynecologic disease, pulmonary extrauterine ETT should be considered.

Periostin mediates human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth in a xenograft lung adenocarcinoma model.

Mesenchymal stem cells stimulate tumor growth in vivo through a lysophosphatidic acid (LPA)-dependent mechanism. However, the molecular mechanism by which mesenchymal stem cells stimulate tumorigenesis is largely elusive. In the present study, we demonstrate that conditioned medium from A549 human lung adenocarcinoma cells (A549 CM) induces expression of periostin, an extracellular matrix protein, in human adipose tissue-derived mesenchymal stem cells (hASCs). A549 CM-stimulated periostin expression was abrogated by pretreatment of hASCs with the LPA receptor 1 (LPA(1)) inhibitor Ki16425 or short hairpin RNA-mediated silencing of LPA(1), suggesting a key role of the LPA-LPA(1) signaling axis in A549 CM-stimulated periostin expression. Using a xenograft transplantation model of A549 cells, we demonstrated that co-injection of hASCs potentiated tumor growth of A549 cells in vivo and that co-transplanted hASCs expressed not only periostin but also α-smooth muscle actin (α-SMA), a marker of carcinoma-associated fibroblasts. Small interfering RNA- or short hairpin RNA-mediated silencing of periostin resulted in blockade of LPA-induced α-SMA expression in hASCs. In addition, silencing of periostin resulted in blockade of hASC-stimulated growth of A549 xenograft tumors and in vivo differentiation of transplanted hASCs to α-SMA-positive carcinoma-associated fibroblasts. Conditioned medium derived from LPA-treated hASCs (LPA CM) potentiated proliferation and adhesion of A549 cells and short interfering RNA-mediated silencing or immunodepletion of periostin from LPA CM abrogated proliferation and adhesion of A549 cells. These results suggest a pivotal role for hASC-secreted periostin in growth of A549 xenograft tumors within the tumor microenvironment.

Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: a pilot study.

BACKGROUND: Treatment of critical limb ischemia (CLI) by bypass operation or percutaneous vascular intervention is occasionally difficult. The safety and efficacy of multiple intramuscular adipose tissue-derived mesenchymal stem cells (ATMSC) injections in CLI patients was determined in the study. METHODS AND RESULTS: The study included 15 male CLI patients with ischemic resting pain in 1 limb with/without non-healing ulcers and necrotic foot. ATMSC were isolated from adipose tissue of thromboangiitis obliterans (TAO) patients (B-ATMSC), diabetes patients (D-ATMSC), and healthy donors (control ATMSC). In a colony-forming unit assay, the stromal vascular fraction of TAO and diabetic patients yielded lesser colonies than that of healthy donors. D-ATMSC showed lower proliferation abilitythan B-ATMSC and control ATMSC, but they showed similar angiogenic factor expression with control ATMSC and B-ATMSC. Multiple intramuscular ATMSC injections cause no complications during the follow-up period (mean follow-up time: 6 months). Clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during follow-up, and all amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography before and 6 months after ATMSC implantation showed formation of numerous vascular collateral networks across affected arteries. CONCLUSIONS: Multiple intramuscular ATMSC injections might be a safe alternative to achieve therapeutic angiogenesis in patients with CLI who are refractory to other treatment modalities.

Chronic destructive pulmonary tuberculosis: assessment of disease activity by computed tomography.

BACKGROUND: Determination of disease activity of chronic destructive pulmonary tuberculosis (TB) on imaging studies can be difficult because several imaging findings due to disease chronicity such as a residual cavity can be misinterpreted as an active disease. PURPOSE: To evaluate computed tomography (CT) findings to predict active disease in patients with chronic destructive pulmonary TB. MATERIAL AND METHODS: CT findings of 36 patients with chronic active destructive pulmonary TB and 78 patients with chronic inactive destructive pulmonary TB were reviewed and their patterns of lung lesions were compared. Statistical comparisons were performed using chi-square and Student's T tests for univariate analyses, and a stepwise logistic regression method was used for multivariate analysis. RESULTS: Based on univariate analyses, cavitary destruction (P = 0.015), non-branching centrilobular nodules (P < 0.001), tree-in-bud pattern (P < 0.001), airspace nodules (P < 0.001), and cavities in other lobes (P = 0.001) were more frequently seen in chronic active destructive pulmonary TB. A stepwise logistic regression analysis demonstrated that tree-in-bud pattern (odds ratio, 52.3; 95% confidence interval, 6.2-437.2; P < 0.001) were significant CT findings associated with active disease. CONCLUSION: Tree-in-bud pattern were the most characteristic CT findings to predict active disease in patients with chronic destructive pulmonary TB.

Direct lipiodol injection used for a radio-opaque lung marker: stability and histopathologic effects.

The objective of this study was to evaluate the effects on the histopathologic findings of directly injected lipiodol into lung and to identify the existence of remaining lipiodol in the lung according to the follow-up time. Forty rats were randomly assigned to 1 of 4 groups: group I (n = 10) served as the control group and received 0.2 mL of normal saline; groups II (n = 10), III (n = 10), and IV (n = 10) served as experimental groups and received 0.1-0.2 mL of lipiodol under fluoroscopy. At 3 hours (groups I and II), 24 hours (group III), and 1 week (group IV) after injection, the radiographic presence of lipiodol and histopathologic findings of each group were evaluated. Minimal acute lung injuries developed and the radio-opaque lipiodol nodule remained in group II. In group III, acute lung injuries were the most serious. However, acute injuries disappeared and foamy macrophages accumulated within the alveolar space in group IV. In this group, remaining lipiodol was also identified on radiograph. Directly injected lipiodol caused acute lung injury, which disappeared at 1 week along with the resolving process. On radiographs, directly injected lipiodol remained after 1 week. Lipiodol could be used as a safe and stable biomaterial for marking pulmonary nodules.

Localization of pulmonary nodules with lipiodol prior to thoracoscopic surgery.

BACKGROUND: Preoperative localization with lipiodol for identifying small or deeply seated pulmonary nodules is simple and useful for thoracoscopic surgery. Although several studies about performance and complication rates of lipiodol localization have been reported, there has been no report about the performance and complication rates of lipiodol localization with regard to the CT appearance of pulmonary nodules. PURPOSE: To evaluate the performance and complication rates of localization of pulmonary nodules with lipiodol prior to video-assisted thoracoscopic surgery with regard to the CT appearance of nodules. MATERIAL AND METHODS: After institutional review board approval and informed consent were obtained, lipiodol marking was performed in 67 patients (33 men and 34 women; mean age 58 years) with 68 nodules. All nodules were marked with 0.4-0.5 mL lipiodol under CT guidance on the day of surgery. The size of the targeted nodule and the shortest distance to the accessible pleural surface were measured. Lipiodol accumulation of a targeted nodule was scored by use of a four-point scale (0: none, 1: within 1 cm around a nodule, 2: partial accumulation within a nodule, 3: total accumulation within a nodule). Any complications after localization of nodules were noted. We analyzed the score of lipiodol accumulation and the presence of complications for the CT appearance of pulmonary nodules using the Mann Whitney U test, Fisher's exact test and the Kruskall Walis test. RESULTS: The average nodule size was 11.4 mm (range 3.0-28.3 mm) and the average distance to the pleural surface was 13.7 mm (range 0-51.4 mm). Lipiodol accumulation scores of nodules were as follows: score 3 (n=19, 28%), score 2 (n=37, 54%), score 1 (n=11, 16%), and score 0 (n=1, 2%). Lipiodol accumulation scores of nodules were different according to the size of nodules (Kruskal Wallis test, p=0.023). Pneumothorax after localization occurred in 20 (29%) patients and the incidence was higher in nodules located in the subpleural area (Mann Whitney U test, p=0.048). Pulmonary hemorrhage along the needle tract occurred in five (7%) patients and was more frequent in patients with deep nodules as compared to shallow nodules (Mann Whitney U test, p < 0.001). CONCLUSION: Lipiodol marking under CT guidance is a useful and safe procedure for the intraoperative localization of pulmonary nodules. Of variable CT findings, lesion size is important to determine the degree of lipiodol accumulation and the lesion depth is the most important feature for the development of postprocedural complications.

Nerve Cable Graft Interposition in Patients with Brachial Plexus Schwannoma: Case Reports.

Schwannomas are rare benign tumors that develop in Schwann cells lining peripheral nerves. Schwannomas of the brachial plexus are especially rare, accounting for 5% of all cases. Although several treatments can be considered, the exact method of treatment is unclear owing to the scarcity and sporadic occurrence of schwannomas. Tumor resection is performed in most cases, and nerve damage is inevitable in cases of neuroinvasive schwannoma. In this case series, we present our successful use of transposition of cable-grafted nerves for the treatment of schwannomas. We performed cable-grafted nerve interposition in addition to tumor resection, leading to increased recovery of nerve damage. To relieve postoperative symptoms and minimize sequelae, precise surgical tumor resection followed by nerve interposition using a cable-grafted nerve may be recommended.

Extralobar Supradiaphragmatic Pulmonary Sequestration Arising from the Retroperitoneum Through a Congenital Diaphragmatic Defect

Here, we report the rare case of a 13-year-old girl with a congenital diaphragmatic hernia (also known as Bochdalek hernia), which was revealed to be an extralobar pulmonary sequestration that was treated using laparoscopic and video-assisted thoracic surgery sequestrectomy and repair of the diaphragm defect after detection of a supradiaphragmatic mass connected with the retroperitoneum. The patient showed no postoperative complications at a 1-month follow-up examination.

Cancer Testis Antigen, NOL4, Is an Immunogenic Antigen Specifically Expressed in Small-Cell Lung Cancer.

To identify cancer/testis (CT) antigens and immunogenic proteins, immunoscreening of testicular and small-cell lung cancer cell line NCI-H889 cDNA libraries was performed using serum obtained from a small-cell lung cancer (SCLC) patient. We obtained 113 positive cDNA clones comprised of 74 different genes, designated KP-SCLC-1 through KP-SCLC-74. Of these genes, 59 genes were found to be related to cancers by EMBASE analysis. Three of these antigens, including KP-SCLC-29 (NOL4), KP-SCLC-59 (CCDC83), and KP-SCLC-69 (KIF20B), were CT antigens. RT-PCR and western blot analysis showed that NOL4 was frequently present in small-cell lung cancer cell lines (8/9, 8/9). In addition, NOL4 mRNA was weakly, or at a low frequency, or not detected in various cancer cell lines. Our results reveal that NOL4 was expressed at protein levels in small-cell lung cancer tissues (10/10) but not detected in lung adenocarcinoma and squamous cell carcinoma by immunohistochemical analysis. Serological response to NOL4 was also evaluated by western blot assay using NOL4 recombinant protein. A humoral response against NOL4 proteins was detected in 75% (33/44) of small-cell lung cancer patients and in 65% (13/20) of healthy donors by a serological western blot assay. These data suggest that NOL4 is a specific target that may be useful for diagnosis and immunotherapy in SCLC.

IS6110-restriction fragment length polymorphism and spoligotyping analysis of Mycobacterium tuberculosis clinical isolates for investigating epidemiologic distribution in Korea.

The Beijing family of Mycobacterium tuberculosis has been emerging in the world. However, there are few nationwide data of genotypic distribution in Korea. This study aimed to identify the genotypic diversity of clinical isolates of M. tuberculosis and to demonstrate the population of Beijing family in Korea. We collected 96 clinical M. tuberculosis isolates from 11 university hospitals nationwide in Korea from 2008 to 2009. We observed 24 clusters in IS6110-RFLP analysis and 19 patterns in spoligotyping. Seventy-five isolates were confirmed to be Beijing family. Two isolates of the K strain and 12 isolates of the K family strain were also found. We found that drug resistance phenotypes were more strongly associated with Beijing family than non-Beijing family (P=0.003). This study gives an overview of the distribution of genotypes of M. tuberculosis in Korea. These findings indicate that we have to pay more attention to control of M. tuberculosis strains associated with the Beijing family.