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.

No abstract available.
Astrocytoma* ; Encephalitis, Herpes Simplex* ; Herpes Simplex*

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

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

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

Malignant germ cell tumors occur in children and young women in reproductive age, of all the germ cell malignancies, only pure dysgerminomas had a high cure rate prior to 1970. This was due to the exquisite radiosensitivity of these tumors. Multiple-agent chemotherapy has dramatically improved the pmgnosis of patients with malignant ovarian germ cell tumors. Clinicopathological analysis was performed on 21 cases of malignant germ cell tumors of the ovary, 9 cases at the department of Obstetrics & Gynecology, Kyung-pook National University Hospital, 4 cases, at the department of Obstetrics and Gynecology, Dong-guk University Kyungju Hospital and 8 cases, at the department of Obstetrics and Gynecology, Dae-gu Fatima Hospital during the period 10 years from July. 19S8 to June. 1997 The results were summarized as follows: 1. The mean age of the patients was 21.8 years old, ranging from 10 to 61 years old. 2. Main initial symptoms were abdominal distension(33.3%), abdominal mass palpation(33.3%), abdominal pain(28.6%), amenorrhea(4.8%) in order. 3. Histologically, the tumors were classified as immature teratoma(57.1%), dysgerminoma(19%), mixed germ cell tumor(9.5%), endodermal sinus tumor(9.5%), embryonal cell carcinoma(4.8%). 4, According to FIGO classification Stage I was the most prevalent(57.1%) at the time of diagnosis while Stage III was forward in 48.6%, Stage II in 9.5%, and no Stage IV, 5. The 5-year survival rate was 80.4% and three patients have died of malignancy and the other 18 patients live without disease from 11 to 102 months, with a median follow-up of 34.2 months. 6. Prognostic factors of malignant germ cell tumors in this study were the clinical stage, the presence of ascites and the residual tumor mass.
Ascites ; Child ; Classification ; Daegu ; Diagnosis ; Drug Therapy ; Dysgerminoma ; Endoderm ; Female ; Follow-Up Studies ; Germ Cells* ; Gyeongsangbuk-do ; Gynecology ; Humans ; Middle Aged ; Neoplasm, Residual ; Neoplasms, Germ Cell and Embryonal* ; Obstetrics ; Ovary* ; Radiation Tolerance ; Survival Rate

In 1988, the International Federatioa of Gynecology and Obstetrics(FIGO) Cancer Committee changed the staging of endometrial carcinoma from a clinical one to a surgicopathologic one. The emphasis in the new FIGO system was changed to the pathologic findings in the uterus, cervix, adnexae, and pelvic and/or periaortic nodes, and peritoneal cytologic findings. The major changes in this staging system were the use of the depth of myometrial invasion and the identification of tumor cells in peritoneal cytologic examination and of invasion in the retroperitoneal lymph nodes, Preoperative endocervical curettage was no longer necessary. This is a reflection of the increase in the primary surgical approach to the treatment of this disease and has allowed the identification of a number of prognostic factors on which postoperative therapy can be based. This retrospective study was based on a clinical review of 45 patients with endometrial carcinoma from Jan, 1985 through Jan, 1996 who underwent primary surgical evaluation at the Department of Obstetrics and Gynecology, Kyungpook National University Medical College. The results obtained are as follows; l. Age distribution of endometrial cancer was concentrated on the age group of 50-59(55.6%) and mean age was 53.9 years. 2. The mean parity and mean BMI(Body Mass Index) of endometrial cancer were 3.8 and 25.0(cm/kg2). 3. The Menstrual status at the time of development of endometrial cancer showed that 24 cases (53.3%) were postmenopausal, 11 cases (24.4%) were premenopausal and 10 cases(22.2%) were menstruating. 4. According to the clinical stage adopted by FIGO classification, stage I was found in 71.1%, stage II in 17.8%, stage III in 2,2%, stage IV in 0.0%. 5. Surgical restaging according to new FIGO classification(1988), stage IA was found in 4.4%, stage IB in 37.8%, stage IC in 28.9%, stage IIA in 0.0%, stage IIB in 0.0%, stage IIIA in 6.7%, stage IIIB in 4.4%, stage IIIC in 8.9%, stage IVA in 2.2% and IVB in 6.7%. 6. According to WHO histopathological classification, the percentage of the adenocarcinoma was 86.7%, adenoacanthoma 4.4%, papillary serous adenocarcinoma 2.2%, and adenosquamous cell carcinoma 6.7%. 7, The relationship between histologic grade and depth of invasion was somewhat correlated but no staistical significance. 8. There was no correlation between BMI(Body Mass Index) and histologic grade, depth of invasion. 9. Surgery upstaged 15.6% of clinical stage I patients and 62,5% of clinical stage II, but 37.5% of clinical stage II patients was downstaged. 10. All cases were primarily treated by surgery. Regarding the types of operation, total abdominal hysterectomy with bilateral salpingoophorectomy was performed in 44.4%, radical hysterectomy with both pelvic lymphadnectomy in 42.2%, total abdominal hysterectomy with bilateral salpingoophorectomy with selective pelvic lymph node dissection in 8.9%, and laparoscopic assisted vaginal hysterectomy in 2.2%. 11. The mean follow up interval was 38.6 months. 28 cases were followed up and 10 cases of surgical stage I revealed over 5 year salvage. 5-year survivals for surgical stage IA, IB, IC, III, and IV were 100, 100, 92.3, 88.9, and 100%, respectively.
Adenocarcinoma ; Age Distribution ; Cervix Uteri ; Classification ; Curettage ; Endometrial Neoplasms* ; Female ; Follow-Up Studies ; Gyeongsangbuk-do ; Gynecology ; Humans ; Hysterectomy ; Hysterectomy, Vaginal ; Lymph Node Excision ; Lymph Nodes ; Neoplasm Staging ; Obstetrics ; Parity ; Retrospective Studies ; Uterus

BACKGROUND AND OBJECTIVE: Eosinophil is a major inflammatory cell in allergic diseases and parasitic infestations. Various cytokines such as GM-CSF, IL-3 and IL-5 are known to activate eosinophils and prolong their survival. Among them, IL-5 is the most potent stimulator of eosinophil survival. Recently, it was reported that increased expression of Bcl-2 is related to prolonged survival of IL-5 stimulated eosinophil. Theophylline is a useful drug in bronchial asthma, due not only to bronchial dilation but also to its anti-inflammatory effects. It has been suggested that anti inflammatory action of theophylline derives from the reduction of inflammatory cells in the airways which is mechated by stimulat on of apoptosis of inflammatory cells. In this study, we investigated, by measuring Bcl-2 expression of IL-5 stimulated eosinophil, the effect of theophylline on apoptosis as one of the anti-inflammatory action. MATERIAL AND METHOD: Peripheral eosinophils were isolated from atopic patients by using Perco- 11 discontinuous gradient and purified by negative selection technique using MACS. Eosinophil viability and apoptosis were measured by FACscan. Expression of Bcl-2 protein in eosinophils was detected by Western blot and ELISA. RESULTS: IL-5 increased the percentage of viable eosinophils and reduced the apoptosis of eosinophils in a dose dependent manner. The increased survival of IL-5 stimulated eosinophils was reduced by theophylline via activation of apoptosis. Bcl-2 was increased when eosinophils were cultured with IL-5 only, but when theophylline was cocultured, reduced Bcl-2 was seen with Western blot and ELISA. CONCLUSION: IL-5 increases the survival of eosinophil through the enhanced expression of Bcl- 2. Theophylline has counter action against IL-5 via inhibition of Bcl-2 induced by IL-5. Inhibiting the prolongation of eosinophil survival caused by IL-5 might be one possible mechanism of antiinflammatory effects of theophylline.
Apoptosis ; Asthma ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Eosinophils* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Interleukin-3 ; Interleukin-5 ; Theophylline*

BACKGROUND: Interleukin-5 (IL-5), IL-3, and GM-CSF are known to prolong the survival of eosinophils, and IL-5 has the most potent effect on eosinophil survivaL It is also known that divergent signals induce apoptosis in different cells. But, There have been few reports on about the intracellular signals that trigger the effectors of apoptosis. Cyclic AMP (cAMP) can modulate apoptosis in many cells. But, the role of intracellular cAMP in the IL-5 induced eosinophil survival is still not completely understood. OBJECTIVES: This study was aimed to elucidate the role of intracellular cAMP in IL-5 induced eosinophil survival. MATERIAL AND METHOD: Eosinophils were isolated from peripheral blood of atopic patients. Eosinophil viability was measured by means of propidium iodine (PI) method and the number of viable cells was counted by FAC scan (Becton Dickinson, USA). Cells were cultured with or without IL-5, and also with various cAMP-elevating agents (dibutyryl cAMP, 8-bromo-cAMP, N6- benzoyl cAMP). The concentrations of cAMP were measured by cAMP enzyme immunoassay system(BiotrakTM, Amersham). Finally cAMP dependent protein kinase A inhibitor (H8) was added to eosinophils to examine the effect of decreased intracellular cAMP activity on the viability of eosinophils stimulated with IL-5. RESULTS: The percentage of viable eosinophils was reduced rapidly from 92.1+/-1.8% to 8.23+/- 3.41% without IL-5 (p<0.05; n=ll, 4-day incubation). Upon addition of IL-5, it was increased to 33.02+7.8% (p<0.05; n=ll). In the absence of IL-5, the addition of cAMP-elevating agent increased eosinophil viability in a dose-dependent manner. Upon addition of H8 (24 uM), the eosinophil viability increased by IL-5 (52.5+/-6.4%) was significantly reduced to 27.2+/-5.4% (p<0.05;n=7). Compared with tissue culture media (TCM) only, IL-5 produced persistent elevation of intracellular cAMP of eosinophils in a time and dose dependent manner.
8-Bromo Cyclic Adenosine Monophosphate ; Apoptosis* ; Culture Media ; Cyclic AMP ; Cyclic AMP-Dependent Protein Kinases ; Eosinophils* ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Immunoenzyme Techniques ; Interleukin-3 ; Interleukin-5 ; Iodine ; Propidium