Ho Joong Kim

Sixteen Cases of Sclerosing Hemangioma of the Lung Including Unusual Presentations

Sclerosing hemangiomas (SH) of the lung are uncommon tumors and are thought to be benign. However, the biologic behavior of this tumor has not yet been characterized adequately. The clinicopathologic features were reviewed and analyzed for 16 cases of SH. The age of the patients ranged from 37 to 73 yr (mean 50.6 yr). There were fifteen female and one male patient. The SH located at the intraparenchyme in 14 cases, the interlobar fissure in one case and the visceral pleura in one case. The size of SH ranged from 0.3 cm to 8 cm (mean 2.6 cm). There were five unusual presentations of SH including a case having two SH with multiple nodules of atypical adenomatous hyperplasia in the same lobe, a case showing adenocarcinoma-like area within the SH, a case showing one peribronchial lymph node metastasis (N1 nodal stage) with location of interlobar major fissure, a case showing alveolar adenoma-like area within the SH, and one case with a large visceral pleural-based pedunculated mass presenting as mediastinal mass. All patients were alive and well without recurrence at the last follow up. Here, we reviewed previously published literatures and discussed the histogenesis of SH.

Predictors for Benign Solitary Pulmonary Nodule in Tuberculosis - Endemic Area

Background Solitary pulmonary nodule (SPN) may show different presentation in tuberculosis (TB)-endemic countries. The aim of this study was to identify clinical and radiological predictors favoring benign or malignant SPN in TB-endemic region. Methods Two hundred one SPNs in 201 consecutive Korean patients were included (<3 cm in diameter, all confirmed by pathology or bacteriology, 93 benign and 108 malignant diseases). For clinical parameters, age, sex, smoking status and amount, and past history of pulmonary tuberculosis and diabetes mellitus were investigated retrospectively. For radiological parameters, size, location, margin characteristics, presence of calcification, pleural tag, surrounding satellite nodule, cavitation, internal low attenuation, open bronchus sign, surrounding ground-glass opacity, enhancement pattern of the SPNs and mediastinal lymph node (LN) enlargement were analyzed on chest CT scans. Results Patients with a older age (60.7±9.6 vs 56.2±13.1, p = 0.008) and more than 40-pack years smoking (27.8% vs 14.0%, p = 0.017) were more frequently related with malignant than benign SPN. On chest CT scans, spiculated margin, contrast enhancement more than 20 Hounsfield unit and presence of pleural tag and mediastinal LN enlargement were more frequently observed in malignant than benign SPNs. In contrast to previous studies, satellite lesions (21.5% vs 1.9%, p < 0.001) and cavitation (20.4% vs 5.6%, p = 0.001) were more frequently seen in benign than malignant SPN. Positive predictive values of benignity were 90.9% and 76.0%, respectively, when satellite lesions and cavitation were found in cases of SPN. Conclusion Satellite lesions and cavitation on chest CT scan could be useful predictors for benign SPN in TB-endemic areas.

Preoperative Concurrent Chemoradiotherapy for Stage IIIA Non-Small Cell Lung Cancer

Thirty-one patients with stage IIIA non-small cell lung cancer (NSCLC) were treated with preoperative concurrent chemoradiotherapy (CCRT) followed by surgery. The treatment protocol could not be completed in eight patients. The acute hematologic toxicities of grade III or IV occurred in 48.4% (15/31) after the first chemotherapy cycle, and in 39.1% (9/23) after the second cycle. The most common non-hematologic toxicity was radiation esophagitis. Surgery was attempted in 23 patients and successful in 22 patients (resection rate = 71.0%). Pathologic complete response and down-staging were achieved in 13.6% (3/22) and 68.2% (15/22). The median survival period, 2-year overall survival, local control and disease-free survival rates of all 31 patients and of 22 patients who underwent surgery were 19 months, 37.2%, 49.1%, 35.5%, and 19 months, 43.2%, 51.8%, 25.6%, respectively. On the basis of our observations, preoperative CCRT followed by surgery for stage IIIA NSCLC has resulted in outcomes comparable with those in previous reports.Thirty-one patients with stage IIIA non-small cell lung cancer (NSCLC) were treated with preoperative concurrent chemoradiotherapy (CCRT) followed by surgery. The treatment protocol could not be completed in eight patients. The acute hematologic toxicities of grade III or IV occurred in 48.4% (15/31) after the first chemotherapy cycle, and in 39.1% (9/23) after the second cycle. The most common non-hematologic toxicity was radiation esophagitis. Surgery was attempted in 23 patients and successful in 22 patients (resection rate = 71.0%). Pathologic complete response and down-staging were achieved in 13.6% (3/22) and 68.2% (15/22). The median survival period, 2-year overall survival, local control and disease-free survival rates of all 31 patients and of 22 patients who underwent surgery were 19 months, 37.2%, 49.1%, 35.5%, and 19 months, 43.2%, 51.8%, 25.6%, respectively. On the basis of our observations, preoperative CCRT followed by surgery for stage IIIA NSCLC has resulted in outcomes comparable with th...

Possibility of skin epithelial cell transdifferentiation in tracheal reconstruction.

In tissue engineering, injured tissue is normally reconstructed with cells obtained from that tissue itself. However, it is difficult to obtain cells for reconstruction of the trachea because of its shape and limited accessibility. Therefore, other cell sources having similar form and function or stem cells are used for tracheal reconstruction. In a previous study, we used autologous skin epithelial cells and successfully reconstructed canine tracheas. We found that the tracheal epithelial layer was completely covered with ciliated cells, which is a remarkable finding because skin and tracheal epithelial cells originate from different germinal layers and have very different forms. In this study, to elucidate the origin of the ciliated cells, we identified the stem cell contents of skin epithelial cells on primary culture, marked the skin epithelial cells with PKH26 dye, and transplanted them onto canine tracheas. After 5 months, we identified PKH26 fluorescence on the tracheal epithelial layers, especially over the tracheal cartilages. Consequently, we demonstrated that transplanted autologous skin epithelial stem cells can remain viable on the trachea for a few months and can transdifferentiate into tracheal epithelial cells and chondrocytes.

Carinal resection and reconstruction in thoracic malignancies

The purpose of this study was to present clinical outcomes of malignant tumors involving the carina after surgery in order to establish the management guidelines.

Main Bronchial Reconstruction with Sparing of Pulmonary Parenchyma for Benign Diseases

Main bronchial reconstruction is anatomically suitable for benign main bronchial stenosis. But, it has been hardly recommended for operative mortality and morbidity. This study was aimed at providing validity and the proper clinical information of bronchoplasty for benign main bronchial stenosis by reviewing the results we obtained over the last ten years for main bronchial reconstruction operations. We retrospectively reviewed admission and office records. Twenty eight consecutive patients who underwent main bronchoplasty were included. Enrolled patients underwent main bronchial reconstruction for benign disease (tuberculosis in 21, trauma in 4, endobronchial mass in 3). Concomitant procedures with main stem bronchoplasty were performed in 19 patients. There were no incidences of postoperative mortality and significant morbidity. There were 2 cases of retained secretions, and these problems were resolved by bronchoscopy or intubation. All of the patients are still alive without obstructive airway problem. Bronchoplasty should be considered as one of the primary treatment modalities, if it is anatomically feasible.

SAT0346 Anti-Drug Antibodies as A Predictor for the Discontinuation of Anti-TNF Agents in Patients with Spondyloarthrtis

Background Tumor necrosis factor (TNF) blocking agent has shown to be effective in patients with axial spondyloarthritis (SpA) including ankylosing spondylitis (AS) as up to 60-70%. However, the other 30-40% of patients fails to respond. This non-responsiveness to TNF blocking agent has been suggested as the result of the development of antibodies against it, anti-drug antibodies (ADA), which have been described well in patients with rheumatoid arthritis and Crohns disease. Objectives The aim is to assess whether ADA is related to the clinical efficacy in SpA patients on anti-TNF agents. Methods According to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA, consecutive patients were recruited at a single tertiary hospital who received treatment with adalimumab (Ada) or infliximab (Ifx): 86 AS, 11 inflammatory bowel disease associated SpA, 3 psoriatic SpA and 2 undifferentiated SpA. Serum samples were collected at the enrolment for the drug and ADA levels, which were measured by ELISA. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at baseline (at the beginning of the current anti-TNF agents), at 3 month and then every 6 months. The reactivation of tuberculosis infections, side-effects or infusion reactions, and the cause for discontinuation of therapy were assessed prospectively. Results A total of 102 patients were studied (89.2% male; mean age at sampling 35.2±18.0 years; mean disease duration 11.3±7.9 years). HLA-B27 was positive in 65 of 76 patients (85.5%). Among 102 patients, 74 were treated with Ada and 28 with Ifx. Eighteen patients (17.6%) had switched from other kinds of anti-TNF agents including Ada, Ifx and etanercept. Latent tuberculosis (TB) infection was detected in 22 patients (21.6%) before starting anti-TNF agents and the treatment regimen with isoniazid and rifampin was commenced by a TB expert. ADA was demonstrated in 8 patients (7.8%) (5 of Ada and 3 of Ifx) and all of them were anti-TNF naïve patients. Patients who developed ADA had lower levels of the corresponding drugs (Ada level: 0.45±0.68 vs 4.42±2.12, p<0.0001; Ifx level 0.91±1.36 vs 3.38±2.24, p=0.076). At baseline, no differences in BASDAI were found in patients with or without ADA, and neither ESR nor CRP was different. The median period under prospective observation was 15 months (range 0 – 17, mean 12.7±7.8). ADA-positive patients had a significantly higher cumulative drug discontinuation rate due to inefficacy and adverse events (37.5% vs 6.4%, p=0.022). There was no reactivation of tuberculosis during anti-TNF treatment. Conclusions Our result suggests that in SpA patients the presence of ADA to current Ada or Ifx can predict the drug discontinuation in future due to inefficacy or adverse events. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3465

FRI0511 Global metabolite profiling of synovial fluids from different forms of inflammatory arthritis for the identification of putative biomarker in rheumatoid arthritis

Background Metabolomics is the study of unique chemical fingerprints of specific cellular processes. Metabolite profiling is recently applied in identifying biomarkers in medical research including rheumatologic diseases. Objectives The aim is to assess the metabolite profiling of synovial fluid in patients with different forms of inflammatory arthritis and to identify putative biomarker for rheumatoid arthritis (RA) compared to the other inflammatory arthritis. Methods Synovial fluid samples were obtained from patients with RA (n = 13, mean age 44.2 ± 10.7 yr) and ankylosing spondylitis (AS) (n = 7, mean age 35.4 ± 10.7 yr), Behcet’s disease (BD) (n = 5, mean age 41.6 ± 12.5 yr) and gout (n = 13, mean age 45.9 ± 7.9 yr). To identify putative biomarkers for RA, the synovial fluid samples were divided into two groups; RA versus non-RA (NRA) which included AS, BD and gout. The metabolites of synovial fluid were analyzed using gas chromatography/time-of-flight mass spectrometry (GC/TOF MS). The multivariate statistical analyses by orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted for the comparison between two groups. The potential biomarkers in RA patients were identified and evaluated by variable importance for projection (VIP) values, non-parametric Wilcoxon-Mann-Whitney test and one-way ANOVA test. Chemometric model validation was finally carried out using receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Results A total of 119 metabolites were identified from 38 samples. The metabolite profiling between RA and NRA were clearly discriminated by OPLS-DA (Figure 1). Candidates of biomarkers in RA were determined by VIP values extracted from OPLS-DA and 41 metabolites were selected by VIP scores of greater than 1.0, of which 29 metabolites were elevated in RA and 12 metabolites in NRA. After eliminating variables with no significant difference using Wilcoxon-Mann-Whitney test and one-way ANOVA test, 23 of 41 metabolites were selected as putative biomarkers for RA compared to NRA. Fifteen metabolites were higher level in RA (succinic acid, octadecanol, asparagines, terephtalic acid, salicylaldehyde, glutamine, citrulline, tyrosine, uracil, lysine, phenylalanine, ribitol, tryptophan, xylose and pyrophosphate) and 8 metabolites in NRA (isopalmitic acid, glycerol, myristic acid, palmitoleic acid, hydroxylamine, ethanolamine, alanine and serine). These metabolites were validated by AUC, all of which had AUC > 0.8. ROC curve analysis for the power of discrimination of RA from NRA showed a sensitivity of 69.2% and a specificity of 92%. Image/graph Conclusions Our study suggests that the synovial fluid metabolomic profiling can be a novel approach in differentiating RA from AS, BD and gout. A set of validated metabolites could be a putative biomarker in synovial fluid of RA patients. Disclosure of Interest None Declared

A Multicenter, Randomized, Open, Comparative Study for the Efficacy and Safety of Oral Moxifloxacin 400 mg Once a Day and Clarithromycin 500 mg Twice Daily in Korean Patients with Acute Exacerbations of Chronic Bronchitis

Background : Moxifloxacin is a newly developed drug which is more potent and safe compared to previous fluoroquinolones. This drug effectively eradicates organisms such as beta-lactamase-producing or other resistant bacteria. Moxifloxacin is known to be effective in treating respiratory infections such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniaeme, Legionella spp. and Mycoplasma pneumoniae. Methods : In a multicenter, randomized, open, comparative study, the efficacy and safety of oral moxifloxacin taken 400 mg once a day and clarithromycin taken 500 mg twice daily for 7 days were compared for the treatment of Korean patients with acute exacerbations of chronic bronchitis. Results : A total of 170 patients were enrolled, and they were divided into two groups: 87 in the moxifloxacin group and 83 in the clarithromycin group. Of those enrolled, 76 (35 for bacteriologic efficacy) in the moxifloxacin group and 77 (31 for bacteriologic efficacy) in the clarithromycin group were included in the efficacy analysis. All were included in the safety analysis. Clinical success was noted in 70 (92.1%) of 76 moxifloxacin-treated patients and 71 (92.2%) of 77 clarithromycin-treated patients. Bacteriologic success rate seemed to be higher in moxifloxacin group (73.5%) than in clarithromycin group (54.8%), but statistically insignificant (p=0.098). Drug susceptibility among organisms initially isolated was higher in moxifloxacin group on Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae (p

Comparison of PCR-Line Probe and PCR-SSCP Methods for the Detection of Rifampicin Resistant Mycobacterium Tuberculosis.

Background: Rifampicin (RFP) is a key component of the antituberculous short-course chemotherapy and the RFP resistance is a marker of multi-drug resistant (MDR) tuberculosis. RPoB gene encodes the -subunit of RNA polymerase of M. tuberculosis which is the target of RFP. And the mutations of rpoB gene have been found in about 96% of rifampicin resistant clinical isolates of M. tuberculosis. So in order to find a rapid and clinically useful diagnostic method in identifying the RFP resistance, we compared the PCR -line probe method with PCR-SSCP for the detection of the rpoB gene mutation in cultured M. tuberculosis. Methods: 45 clinical isolates were collected from patients who visited Sung Kyun Kwan University Hospital. The RFP susceptibility test was referred to the referral laboratory of the Korean Tuberculosis Institute. 33 were rifampicin resistant and 12 were rifampicin susceptible. The susceptibility results were compared with the results of the PCR-BSCP and PCR-line probe method. Results: We could find rpoB mutations in 27/33(81.8%) RFP-resistant strains by PCR-line probe method, and in 23/33 (69.7%) by PCR-SSCP and there was no significant difference between two methods. There was no mutation in rifampicinn susceptible strains by both methods. Conclusion: PCR-line probe method would be a rapid, sensitive and specific method for the detection of rifampicin resistant Mycobacterium tuberculosis.