Purpose: The introduction of immune checkpoint inhibitors represents a major advance in the treatment of lung cancer, allowing sustained recovery in a significant proportion of patients. Nivolumab is a monoclonal anti–programmed death cell protein 1 antibody licensed for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy. In this study, we describe the demographic and clinical outcomes of patients with advanced NSCLC treated with nivolumab in the Korean expanded access program. Materials and Methods: Previously treated patients with advanced non-squamous and squamous NSCLC patients received nivolumab at 3 mg/kg every 2 weeks up to 36 months. Efficacy data including investigator-assessed tumor response, progression data, survival, and safety data were collected. Results: Two hundred ninety-nine patients were treated across 36 Korean centers. The objective response rate and disease control rate were 18% and 49%, respectively; the median progression-free survival was 2.1 months (95% confidence interval [CI], 1.87 to 3.45), and the overall survival (OS) was 13.2 months (95% CI, 10.6 to 18.9). Patients with smoking history and patients who experienced immune-related adverse events showed a prolonged OS. Cox regression analysis identified smoking history, presence of immune-related adverse events as positive factors associated with OS, while liver metastasis was a negative factor associated with OS. The safety profile was generally comparable to previously reported data. Conclusion This real-world analysis supports the use of nivolumab for pretreated NSCLC patients, including those with an older age.

Little is known about the long-term prognosis of or predictors for the different clinical types of atrial fibrillation (AF) in Korean populations. The aim of this study was to validate a risk stratification to assess the probability of AF progression from paroxysmal AF (PAF) to persistent AF (PeAF) or permanent AF. A total of 434 patients with PAF were consecutively enrolled (mean age; 71.7 +/- 10.7 yr, 60.6% male). PeAF was defined as episodes that are sustained > 7 days and not self-terminating, while permanent AF was defined as an ongoing long-term episode. Atrial arrhythmia during follow-up was defined as atrial premature complex, atrial tachycardia, and atrial flutter. During a mean follow-up of 72.7 +/- 58.3 months, 168 patients (38.7%) with PAF progressed to PeAF or permanent AF. The mean annual AF progression was 10.7% per year. In univariate analysis, age at diagnosis, body mass index, atrial arrhythmia during follow-up, left ventricular ejection fraction, concentric left ventricular hypertrophy, left atrial diameter (LAD), and severe mitral regurgitation (MR) were significantly associated with AF progression. In multivariate analysis, age at diagnosis (P = 0.009), atrial arrhythmia during follow-up (P = 0.015), LAD (P = 0.002) and MR grade (P = 0.026) were independent risk factors for AF progression. Patients with younger age at diagnosis, atrial arrhythmia during follow-up, larger left atrial chamber size, and severe MR grade are more likely to progress to PeAF or permanent AF, suggesting more intensive medical therapy with close clinical follow-up would be required in those patients.
Aged ; Atrial Fibrillation/epidemiology/mortality/*pathology ; Atrial Flutter/*epidemiology/mortality/pathology ; Atrial Premature Complexes/*epidemiology/mortality/pathology ; Disease Progression ; Echocardiography ; Female ; Heart Atria/pathology/ultrasonography ; Humans ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Retrospective Studies ; Tachycardia, Ectopic Atrial/*epidemiology/mortality/pathology ; Tachycardia, Paroxysmal/*epidemiology/mortality/pathology ; Thromboembolism/epidemiology/mortality ; Treatment Outcome

No abstract available.
Toll-Like Receptors*

BACKGROUND: Diagnosing a pulmonary embolism is difficult because its presenting symptoms are nonspecific and there are limitations with all of the objective tests. The D-dimer is known to be a marker of the lysis of intravascular cross-linked fibrin as a result of the activation of the endogenous fibrinolytic pathways, and the D-dimer assay is these an objective method for diagnosing a pulmonary embolism. This study assessed the benefits of the D-dimer test for diagnosing a pulmonary embolism using semiquantitative latex agglutination. METHODS: The latex agglutination results of 185 patients were retrospectively reviewed. The D-dimer test was performed at the time a pulmonary embolism was suspected. Ninety patients(group I) were diagnosis with PE through spiral chest CT or a chest CT angiogram, perfusion/ventilation scans, and/or pulmonary angiogram. Ninety-five patients (group II) were found not to have a pulmonary embolism through the above tests. RESULTS: The male to female ratio and mean age in groups I and II was 37:55, and 57 years old to 50:45 and 52 years old, respectively. When the cut off value for a positive D-dimer assay was set to 500 microgram, the sensitivity, positive predictive value, negative predictive value and specificity was 86.7%, 61.4%, 79.3%, and 48.4%, respectively. CONCLUSION: The semiquantitative latex agglutination method in the D-dimer test has a lower sensitivity and negative predictive value than the well known ELISA test particularly for small emboli. Therefore, this test is not a suitable screening test for excluding a pulmonary embolism.
Agglutination* ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Fibrin ; Humans ; Latex* ; Male ; Mass Screening ; Middle Aged ; Pulmonary Embolism* ; Retrospective Studies ; Tomography, X-Ray Computed

No abstract available.

No abstract available.

BACKGROUND: New stent implantation during intracoronary brachytherapy is discouraged due to the high risk of late thrombosis. However, new stent implantation is inevitable in some cases due to the inadequate ballooning or major dissections. Long-term follow-up results of newly implanted stents during brachytherapy are not well-known. We performed this study to evaluate the long-term clinical outcomes of newly implanted stents during intracoronary brachytherapy. METHODS: In the Seoul national university Post-Angioplasty RhEnium irradiation (SPARE) trial, patients were treated with conventional catheter-based technique and then randomized to either beta- radiation (RG) or control group (CG). Radiation was performed with 188 -rhenium-filled conventional balloon catheter system. From 1999 to 2001, new stent implantation was performed in 58 and 56 patients in RG and CG, respectively. Clinical and angiographic follow up data were analyzed. RESULTS: In RG, short-term angiographic restenosis rate was lower than CG (28.6% vs 53%, p=0.03). In RG, late thrombosis was found in 3 patients. However, there was no late thrombosis in CG. Two year major cardiac event rates were not different between the 2 groups (RG: 25.9% vs CG: 28.3%). Independent predictors for major cardiac event in RG were major dissections (>or=type C) after stent implantation (beta=70, p=0.01) and longer administration of dual antiplatelets (aspirin+clopidogrel/ ticlopidine, >6 months, beta=0.07, p=0.04). CONCLUSION: Stenting during intracoronary brachytherapy seems to be ineffective in reducing long-term event rates. When new stent implantation is inevitable during brachytherapy, extreme attention is required not to make a dissection and long-term dual antiplatelet treatment should be followed after stent implantation.
Angioplasty ; Brachytherapy ; Catheters ; Follow-Up Studies ; Humans ; Rhenium ; Seoul ; Stents* ; Thrombosis ; Ticlopidine

PURPOSE: To determine the patterns of evaluation and treatment in the patient with early breast cancer treated with conservative surgery and radiotherapy and to improve the radiotherapy techiniques, nationwide survey was performed. MATERIALS AND METHODS: A web-based database system for Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Two hundreds sixty-one randomly selected records of eligible patients treated between 1998~999 from 15 hospitals were reviewed. RESULTS: The patients ages ranged from 24 to 85 years(median 45 years). Infiltrating ductal carcinoma was most common histologic type (88.9%) followed by medullary carcinoma (4.2%) and infiltrating lobular carcinoma (1.5%). Pathologic T stage by AJCC was T1 in 59.7% of the casses, T2 in 29.5% of the cases, Tis in 8.8% of the cases. Axillary lymph node dissection was performed in 91.2% of the cases and 69.7% were node negative. AJCC stage was 0 in 8.8% of the cases, stage I in 44.9% of the cases, stage IIa in 33.3% of the cases, and stage IIb in 8.4% of the cases. Estrogen and progesteron receptors were evaluated in 71.6%, and 70.9% of the patients, respectively. Surgical methods of breast-conserving surgery was excision/lumpectomy in 37.2%, wide excision in 11.5%, quadrantectomy in 23% and partial mastectomy in 27.5% of the cases. A pathologically confirmed negative margin was obtained in 90.8% of the cases. Pathological margin was involved with tumor in 10 patients and margin was close (less than 2 mm) in 10 patients. All the patients except one recieved more than 90% of the planned radiotherapy dose. Radiotherapy volume was breast only in 88% of the cases, breast+supraclavicular fossa (SCL) in 5% of the cases, and breast+SCL+posterior axillary boost in 4.2% of the cases. Only one patient received isolated internal mammary lymph node irradiation. Used radiation beam was Co-60 in 8 cases, 4 MV X-ray in 115 cases, 6 MV X-ray in 125 cases, and 10 MV X-ray in 11 cases. The radiation dose to the whole breast was 45~9.4 Gy (median 50.4) and boost dose was 8~20 Gy (median 10 Gy). The total radiation dose delivered was 50.4~70.4 Gy (median 60.4 Gy). CONCLUSION: There was no major deviation from current standard in the patterns of evaluation and treatment for the patients with early breast cancer treated with breast conservation method. Some varieties were identified in boost irradiation dose. Separate analysis for the datails of radiotherapy planning will be followed and the outcome of treatment is needed to evaluate the process.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal ; Carcinoma, Lobular ; Carcinoma, Medullary ; Estrogens ; Humans ; Korea* ; Lymph Node Excision ; Lymph Nodes ; Mastectomy, Segmental* ; Radiotherapy

OBJECTIVES AND BACKGROUND: In head and neck cancer including hypopharyngeal carcinoma, cisplatin and 5-fluorouracil usually have been used as neoadjuvant chemotherapeutic agents. We investigated the difference in the influences of cisplatin and 5-fluorouracil (5-FU) on the p53 protein expression and cell responses (cell cycle arrest and apoptosis) in the hypopharyngeal cell line (PHUH-12). METHOD: PNUH-12 with a mutant type p53 (one point mutation at the 78th base, C to G, in exon 7) was treated with cisplatin and 5-FU. Changes in the cell line were assessed by MTT assay, Western blotting (p53 and p21 protein), DNA fragmentation, PI stain, and DNA flow cytometry. RESULTS: The p53 protein expression was increased after the treatment with cisplatin and 5-FU. The expression of p21 protein was increased after the treatment with 5-FU, not cisplatin. With cisplatin, we observed apoptosis by DNA fragmentation and PI stain and the increased S phase on DNA flow cytometry. But, with 5-FU, we couldn't observe apoptosis by DNA fragmentation, PI, and flow cytometry and only the increased G1 phase on DNA flow cytometry. CONCLUSION: In hypopharyngeal cell line (PNUH-12), cisplatin induced p53 dependent apoptosis and 5-FU induced p53 and p21 dependent G0/G1 cell cycle arrest, but not apoptosis.
Apoptosis ; Blotting, Western ; Cell Cycle Checkpoints ; Cell Line ; Cisplatin* ; DNA ; DNA Fragmentation ; Exons ; Flow Cytometry ; Fluorouracil* ; G1 Phase ; Head and Neck Neoplasms ; Hypopharyngeal Neoplasms ; Point Mutation ; S Phase

The present study was undertaken to find out the role of NO on cataractogenesis in the experimenally-induced uveitis(EIU) model. Nitrite and nitrate, stable oxidative products of nitric oxide(NO), were measured in the aqueous humor and the progression of inflammations and lens opacities were evaluated with slit lamp biomicroscope. Immunoperoxidase staining and immunofluorescent staining for inducible NO synthase(iNOS) and peroxynitrite were performed to confirm the site of production of NO and peroxynitrite. The grades of inflammation were peaked at 24 hours inflammation was gradually decreased after 48 hours and lens opacity after 72 hours. These changes returned to the baseline level by one week after LPS injection. Similarly, NO concentration in aqueous humor was peaked at 24 hours. And it was then decreased after 48 hours and returned to the baseline level by one week. These inflammatory signs and lens opacities were significantly decreased in NG-nitro-L-arginine methyl ester(L-NAME) administrated group. Inflammatory cells in anterior chamber, iris, and ciliary body expressed highly iNOS which was coincide with peroxynitrite immunolocalization. Therefore, these results suggest that cataract formation in EIU is related to the NO production in aqueous humor. Furthermore, lipid peroxidation by peroxynitrite is possibly related with cataractogenesis in EIU. But, we need a further evaluation to seek the relationship between cataractogenesis and increased nitric oxide concentration, combined with studies of other biochemical changes in anterior chamber and lens.
Anterior Chamber ; Aqueous Humor ; Cataract* ; Ciliary Body ; Inflammation ; Iris ; Lipid Peroxidation ; Nitric Oxide ; Nitroarginine ; Peroxynitrous Acid ; Uveitis*