Background/Aims: We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). Methods: We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. Results: The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. Conclusions Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

BACKGROUND: Recent findings in molecular pathology suggest that genetic translocation and/or overexpression of oncoproteins is important in salivary gland tumorigenesis and diagnosis. We investigated PLAG1, SOX10, and Myb protein expression in various salivary gland neoplasm tissues. METHODS: A total of 113 cases of surgically resected salivary gland neoplasms at the National Cancer Center from January 2007 to March 2017 were identified. Immunohistochemical staining of PLAG1, SOX10, and Myb in tissue samples was performed using tissue microarrays. RESULTS: Among the 113 cases, 82 (72.6%) were benign and 31 (27.4%) were malignant. PLAG1 showed nuclear staining and normal parotid gland was not stained. Among 48 cases of pleomorphic adenoma, 29 (60.4%) were positive for PLAG1. All other benign and malignant salivary gland neoplasms were PLAG1-negative. SOX10 showed nuclear staining. In normal salivary gland tissues SOX10 was expressed in cells of acinus and intercalated ducts. In benign tumors, SOX10 expression was observed in all pleomorphic adenoma (48/48), and basal cell adenoma (3/3), but not in other benign tumors. SOX10 positivity was observed in nine of 31 (29.0%) malignant tumors. Myb showed nuclear staining but was not detected in normal parotid glands. Four of 31 (12.9%) malignant tumors showed Myb positivity: three adenoid cystic carcinomas (AdCC) and one myoepithelial carcinoma with focal AdCC-like histology. CONCLUSIONS: PLAG1 expression is specific to pleomorphic adenoma. SOX10 expression is helpful to rule out excretory duct origin tumor, but its diagnostic value is relatively low. Myb is useful for diagnosing AdCC when histology is unclear in the surgical specimen.
Adenoma ; Adenoma, Pleomorphic ; Antibody-Dependent Cell Cytotoxicity ; Carcinogenesis ; Carcinoma, Adenoid Cystic ; Diagnosis ; Immunohistochemistry ; Oncogene Proteins ; Oncogene Proteins v-myb ; Parotid Gland ; Pathology, Molecular ; Salivary Gland Neoplasms ; Salivary Glands ; SOX Transcription Factors ; Translocation, Genetic

BACKGROUND: Soman, a potent irreversible acetylcholinesterase (AChE) inhibitor, induces delayed neuronal injury by reactive oxygen species (ROS). Midazolam is used in patients with pathologic effects of oxidative stresses such as infection, hemodynamic instability and hypoxia. We investigated whether midazolam protects the Central Nervous System (CNS) from soman intoxication. The present study was performed to determine whether midazolam protects B35 cells from ROS stress for the purpose of exploring an application of midazolam to soman intoxication. METHODS: Glucose oxidase (GOX) induced ROS stress was used in a B35 neuroblastoma cell model of ROS induced neuronal injury. To investigate the effect of midazolam on cell viability, LDH assays and fluorescence activated cell sorting (FACS) analysis was performed. Western blotting was used for evaluating whether Akt-phosphorylation is involved in cell-protective effects of midazolam. RESULTS: GOX derived ROS injury decreased cell viability about 1.6-2 times compared to control; midazolam treatment (5 and 10 microg/ml) dose-dependently increased cell viability during ROS injury. On western blots, Akt-phosphorylation was induced during pretreatment with midazolam; it was diminished during co-treatment with LY-294002, an inhibitor of Akt-phosphorylation. FACS analysis confirmed that the cell protective effect of midazolam is mediated by an anti-apoptotic effect. GOX-induced apoptosis was inhibited by midazolam and the finding was diminished by LY-294002. CONCLUSIONS: Midazolam protects neuronal cells from GOX-induced ROS injury; this effect is mediated by an anti-apoptotic effect through Akt-phosphorylation. This shows that midazolam may be useful in soman intoxication.
Acetylcholinesterase ; Anoxia ; Apoptosis ; Blotting, Western ; Cell Survival ; Central Nervous System ; Chromones ; Flow Cytometry ; Glucose Oxidase ; Hemodynamics ; Humans ; Midazolam ; Morpholines ; Neuroblastoma ; Neurons ; Oxidative Stress ; Reactive Oxygen Species ; Soman

Since laparoscopic liver resection was first introduced in 2001, Korean surgeons have chosen a laparoscopic procedure as one of the treatment options for benign or malignant liver disease. We distributed and analyzed a nationwide questionnaire to members of the Korean Laparoscopic Liver Surgery Study Group (KLLSG) in order to evaluate the current status of laparoscopic liver resection in Korea. Questionnaires were sent to 24 centers of KLLSG. The questionnaire consisted of operative procedure, histological diagnosis of liver lesions, indications for resection, causes of conversion to open surgery, and postoperative outcomes. A laparoscopic liver resection was performed in 416 patients from 2001 to 2008. Of 416 patients, 59.6% had malignant tumors, and 40.4% had benign diseases. A total laparoscopic approach was performed in 88.7%. Anatomical laparoscopic liver resection was more commonly performed than non-anatomical resection (59.9% vs 40.1%). The anatomical laparoscopic liver resection procedures consisted of a left lateral sectionectomy (29.3%), left hemihepatectomy (19.2%), right hemihepatectomy (6%), right posterior sectionectomy (4.3%), central bisectionectomy (0.5%), and caudate lobectomy (0.5%). Laparoscopy-related serious complications occurred in 12 (2.8%) patients. The present study findings provide data in terms of indication, type and method of liver resection, and current status of laparoscopic liver resection in Korea.
*Hepatectomy/statistics & numerical data ; Humans ; *Laparoscopy/statistics & numerical data ; Liver/*surgery ; Liver Diseases/pathology/surgery ; Liver Neoplasms/pathology/surgery ; Postoperative Complications/epidemiology ; Questionnaires ; Republic of Korea

PURPOSE: To investigate the role of radiotherapy for squamous cell carcinomas of the external auditory canal and middle ear. MATERIALS AND METHODS: A series of 35 patients who were treated at a single institution from 1981 through 2007 were retrospectively analyzed. Thirteen patients were treated by radiotherapy alone; four by surgery only and 18 by a combination of surgery and radiotherapy. The total radiation dose ranged from 39~70 Gy (median, 66 Gy) in 13~35 fractions for radiotherapy alone and 44~70 Gy (median, 61.2 Gy) in 22~37 fractions for the combined therapy. Clinical end-points were the cause of specific survival (CSS) and local relapse-free survival (LRFS). The median follow-up time was 2.8 years (range, 0.2~14.6 years). RESULTS: The 3-year CSS and LRFS rate was 80% and 63%, respectively. Based on a univariate analysis, performance status and residual disease after treatment had a significant impact on CSS; performance status and histologic grade for LRFS. Patients treated by radiotherapy alone had more residual disease following the course of treatment compared to patients treated with the combined therapy; 69% vs. 28%, respectively. CONCLUSION: Our results suggest that radiation alone was not an inferior treatment modality for CSS compared to the combined therapy for squamous cell carcinoma of the external auditory canal and middle ear. However, local failure after radiotherapy is the main issue that will require further improvement to gain optimal local control.
Carcinoma, Squamous Cell ; Ear Canal ; Ear, Middle ; Follow-Up Studies ; Humans ; Retrospective Studies

A total of 90 Acinetobacter isolates from freshwater and seawater in Gangjin Bay of Korea was investigated for the distribution of genomic species, antimicrobial resistance patterns and clonal relatedness. By amplified ribosomal DNA restriction analysis, eighty-nine Acinetobacter isolates were classified into 11 Acinetobacter genomic species. A. johnsonii (n=23) was the most prevalent, followed by A. baumannii (n=13), A. calcoaceticus (n=13), Acinetobacter genomic species 11 (n=10), A. phenon 6/ct13TU (n=9), A. junii (n=5), A. venetianus (n=5), Acinetobacter genomic species 17 (n=4), 14BJ (n=3), A. phenon 10/1271 (n=2), Acinetobacter genomic species 3 (n=1), and ungrouped (n=1). The majority of Acinetobacter genomic species were isolated from the site A and B, and some known nosocomial pathogens in the clinical environment were observed among them. Of the 11 antimicrobial drugs tested, several A. johnsonii isolates exhibited high-frequency resistance to a wide variety of antimicrobial agents, including ampicillin-sulbactam, piperacillin, ceftazidime, cefotaxime, and sulfamethoxazole (p < 0.001). Some Acinetobacter genomic species were resistant to currently used antibiotics but all isolates were susceptible to imipenem, amikacin, and tetracycline. Based on the results of antimicrobial resistance pattern and phylogenetic analysis, 23 A. johnsonii isolates were classified into 19 pulsotypes. In conclusion, there was a significant difference in the distribution of Acinetobacter species between freshwater and seawater. Predominance of A. johnsonii strains was probably due to their ability to proliferate in the contaminated aquatic environment originated from local geographic features. Therefore, the waste effluent from animals and humans plays an important role in the distribution of Acinetobacter species in aquatic environment.
Acinetobacter ; Amikacin ; Ampicillin ; Animals ; Anti-Bacterial Agents ; Anti-Infective Agents ; Bays ; Cefotaxime ; Ceftazidime ; DNA, Ribosomal ; Fresh Water ; Humans ; Imipenem ; Korea ; Piperacillin ; Seawater ; Sulbactam ; Sulfamethoxazole ; Tetracycline

BACKGROUND: Coronary artery disease (CAD) has recently become one of the major causes of mortality and morbidity in Korea. However, not much epidemiologic and demographic data has yet been reported. The purpose of this study was to investigate the clinical features as well as the prognostic factors of patients with CAD. METHODS: We prospectively enrolled 1,665 consecutive patients with CAD who had been admitted to the Catholic University Hospitals from December 1999 to April 2003. RESULTS: Acute myocardial infarction (AMI) was the most common cause of admission (n=715, 42.9%). Dyslipidemia, hypertension and smoking were the most common risk factors. More than 70% of the patients who underwent percutaneous coronary intervention (PCI) received stent implantation. A total of 965 (612 males) patients were followed at least for 6 months (the mean follow-up duration was 23.8+/-12.2 months). The incidence rates of major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, target vessel revascularization) and cardiac death were 15.1% (n=146) and 2.2% (n=21), respectively. There was no difference in overall survival between the patients treated with medical therapy and those treated with PCI. By Cox regression analysis, the independent prognostic factors for MACE were PCI (95% CI: 1.75-4.85; p<0.01) and multivessel disease (95% CI: 1.03-2.04; p<0.05), and the independent prognostic factors for cardiac death were medical therapy (95% CI: 1.08-14.41; p<0.05) and old age (95% CI: 1.13-16.13; p<0.05). CONCLUSIONS: There was no difference in overall survival between the patients treated with medical therapy and those treated with PCI. However, PCI was superior to medical therapy for preventing death of the patients with acute coronary syndrome.
Acute Coronary Syndrome ; Coronary Artery Disease* ; Coronary Disease ; Coronary Vessels* ; Death ; Dyslipidemias ; Follow-Up Studies ; Heart* ; Hospitals, University ; Humans ; Hypertension ; Incidence ; Korea ; Mortality ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Prognosis ; Prospective Studies ; Risk Factors ; Smoke ; Smoking ; Stents

Endothelium, particularly pulmonary endothelium, is predisposed to injury by reactive oxygen species (ROS) and their derivatives. Heme oxygenase (HO) has been demonstrated to provide cytoprotective effects in models of oxidant-induced cellular and tissue injuries. In the present study, we investigated the effects of YS 49 against oxidant [tert-butylhydroperoxide (TBH) ]-induced injury using cultured sheep pulmonary artery endothelial cells (SPAECs). The viability of SPAECs was determined by quantifying reduction of a fluorogenic indicator Alamar blue. We found that TBH decreased cell viability in a time- and concentration-dependent manner. YS 49 concentration- and time-dependently increased HO-1 induction on SPAECs. As expected, YS 49 significantly decreased the TBH-induced cellular injury. In the presence of zinc protophorphyrin, HO-1 inhibitor, effect of YS 49 was significantly inhibited, indicating that HO-1 plays a protective role for YS 49. Furthermore, YS 49 showed free radical scavenging activity as evidenced by 1, 1-diphenyl-2-picrylhydrazyl (DPPH) and inhibition of lipid peroxidation. However, YS 49 did not inhibit apoptosis induced by lipopolysaccharide (LPS) in SPAECs. Taken together, HO-1 induction along with strong antioxidant action of YS 49 may be responsible for inhibition of TBH-induced injury in SPAECs.
Apoptosis ; Cell Survival ; Endothelial Cells* ; Endothelium ; Heme Oxygenase (Decyclizing) ; Lipid Peroxidation ; Pulmonary Artery* ; Reactive Oxygen Species ; Sheep* ; Zinc

BACKGROUND: With an increasing awareness of the limitations of both mechanical prostheses and bioprostheses, aortic valvuloplasty has gained attention as an alternative procedure for aortic valve disease. MATERIAL AND METHOD: Eight consecutive patients underwent aortic valvuloplasty caused by leaflet prolapse between June 1999 to June 2000. Mean age of the patients was 18.4+/- 12.6 year. Four paitents(50%) were male. Six patients had tricuspid valves and ventricular septal defect and two patients had bicuspid valves. The extent of aortic insufficiency was 3.5+/- 0.5 by preoperative Doppler echocardiography. The technique involved triangular resection of the free edge of the prolapsed leaflet, annular plication at the commissure, and resection of a raphe when present in bicuspid valves. RESULT: There was no in-hospital mortality or morbidity. Mean follow-up was complete at 11.9+/- 3.6months. There was no late mortality or morbidity. The amount of the severity of aortic insufficiency, as assessed by echocardiography preoperatively, postoperatively and at late follow-up was 3.5+/- 0.5, 0.6+/- 0.5 and 0.8+/- 0.6, respectively(p value = 0.01). There was one patient with grade 2/4 aortic insufficiency and in the other patients, grade 1/2 or trivial aortic insufficiency were detected with late echocardiograms. CONCLUSION: Triangular resection in the patients with aortic leaflet prolapse offers a good early clinical result, but long-term follow-up is necessary.
Aortic Valve ; Bioprosthesis ; Echocardiography ; Echocardiography, Doppler ; Follow-Up Studies ; Heart Septal Defects, Ventricular ; Hospital Mortality ; Humans ; Male ; Mitral Valve ; Mortality ; Prolapse ; Prostheses and Implants ; Tricuspid Valve

Patients with severe Ebstein's anomaly showing in the neonatal period, represent progressive cardiac enlargement with pulmonary hypoplasia and functional pulmonary atresia with patent ductus arteriosus-dependent pulmonary circulation. Biventricular repair in these patients had been mostly unsuccessful except for Starnes' procedure that converts the anatomy to single ventricle physiology for Fontan procedure. A 4-days old male was admitted with the diagnosis of severe Ebstein's anomaly with anatomic pulmonary atresia and severe cardiac enlargement. He successfully underwent biventricular repair with vertical plication method of atrialized right ventricle, tricupid annuloplasty, transannular right ventricular outflow tract reconstruction, atrial septal defect patch closure with fenestration, and right atrial reduction angioplasty. Postoperatively, cardiothoracic ratio was significantly reduced and mild tricuspid regurgitation was remnant in echocardiography. The patient is currently 10 months old and is fully active without restrictions.
Angioplasty ; Critical Illness* ; Diagnosis ; Ebstein Anomaly* ; Echocardiography ; Fontan Procedure ; Heart Septal Defects, Atrial ; Heart Ventricles ; Humans ; Infant ; Infant, Newborn* ; Male ; Physiology ; Pulmonary Atresia ; Pulmonary Circulation ; Tricuspid Valve Insufficiency