This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.
Adolescent ; Antineoplastic Agents/therapeutic use ; Central Nervous System Neoplasms/diagnosis/drug therapy/radiotherapy ; Child ; Child, Preschool ; Disease-Free Survival ; Hospitals ; Humans ; Infant ; Leukemia, Myeloid, Acute/diagnosis/epidemiology/mortality/therapy ; Myelodysplastic Syndromes/diagnosis/epidemiology/mortality/therapy ; Neoplasms, Second Primary/*diagnosis/epidemiology/mortality/therapy ; Osteosarcoma/diagnosis/epidemiology ; Retrospective Studies ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Autologous ; Young Adult

This retrospective study investigated the clinical characteristics and outcomes of second malignant neoplasms (SMNs) in survivors of childhood cancer from multiple institutions in Korea. A total of 102 patients from 11 institutions who developed SMN after childhood cancer treatment between 1998 and 2011 were retrospectively enrolled. The most common primary malignant neoplasms (PMNs) were central nervous system (CNS) tumors (n = 17), followed by acute lymphoblastic leukemia (n = 16), non-Hodgkin lymphoma (n = 13), and osteosarcoma (n = 12). The most common SMNs were therapy-related myeloid neoplasms (t-MNs; acute myeloid leukemia [AML], 29 cases; myelodysplastic syndrome [MDS], 12 cases), followed by thyroid carcinomas (n = 15) and CNS tumors (n = 10). The median latency period was 4.9 years (range, 0.5-18.5 years). Among 45 patients with solid tumors defined as an SMN, 15 (33%) developed the lesion in a field previously subjected to radiation. The 5-year overall survival (OS) rate of patients with an SMN was 45% with a median follow-up time of 8.6 years. Patients with AML, MDS, and CNS tumors exhibited the poorest outcomes with 5-year OS rates of 18%, 33%, and 32%, respectively, whereas those with second osteosarcoma showed comparable outcomes (64%) to patients with primary counterpart and those with second thyroid carcinoma had a 100% OS rate. Further therapeutic efforts are recommended to improve the survival outcomes in patients with SMNs, especially in cases with t-MNs and CNS tumors.
Adolescent ; Antineoplastic Agents/therapeutic use ; Central Nervous System Neoplasms/diagnosis/drug therapy/radiotherapy ; Child ; Child, Preschool ; Disease-Free Survival ; Hospitals ; Humans ; Infant ; Leukemia, Myeloid, Acute/diagnosis/epidemiology/mortality/therapy ; Myelodysplastic Syndromes/diagnosis/epidemiology/mortality/therapy ; Neoplasms, Second Primary/*diagnosis/epidemiology/mortality/therapy ; Osteosarcoma/diagnosis/epidemiology ; Retrospective Studies ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Autologous ; Young Adult

BACKGROUND: The use of several biochemical markers has improved the diagnosis of neonatal bacterial infection, which remains an important cause of morbidity and mortality. Recently, serum procalcitonin (PCT) has been investigated as a new marker for the detection of bacterial infection. The aim of this study was to assess the usefulness of PCT in early neonatal bacterial infection and compare the diagnostic utility of PCT with that of C-reactive protein (CRP). METHODS: We retrospectively studied 216 neonates (109 full term, 107 preterm) whose PCT was measured 24 hr after birth. Thirty-five were clinically classified into an infected group, of which 17.4% had positive cultures. Clinical data, PCT, CRP, leukocyte, and neutrophil counts were evaluated. The diagnostic performance of PCT and CRP was studied using receiver operating characteristic analysis. RESULTS: Compared to the non-infected group, the infected group displayed significantly higher median PCT (0.82 vs. 12.29 ng/mL, P<0.0001) and CRP (1.0 vs. 5.0 mg/L, P<0.0001) values, but similar leukocyte and neutrophil counts. The thresholds for PCT and CRP were 2.75 ng/mL (sensitivity, 97.1%; specificity, 76.7%) and 3.1 mg/L (sensitivity, 68.6%; specificity, 83.3%), respectively. The area under the curve for PCT was 0.937 (95% confidence interval [CI], 0.896-0.965) and 0.781 for CRP (95% CI, 0.720-0.834). CONCLUSIONS: During the first 24 hr after birth, PCT is a more sensitive marker than CRP for bacterial infection and has predictive value for early neonatal bacterial infection.
Bacterial Infections* ; Biomarkers ; C-Reactive Protein ; Diagnosis* ; Humans ; Infant, Newborn ; Leukocytes ; Mortality ; Neutrophils ; Parturition ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity

BACKGROUND: Multidrug-resistant (MDR) Acinetobacter spp. acquire antimicrobial agent-resistance genes via class 1 integrons. In this study, integrons were characterized to investigate the antimicrobial resistance mechanisms of MDR Acinetobacter isolates. In addition, the relationship between the integron type and integron-harboring bacterial species was analyzed by using epidemiological typing methods. METHODS: Fifty-six MDR Acinetobacter spp.-A. baumannii (N=30), A. bereziniae (N=4), A. nosocomialis (N=5), and A. pittii (N=17)-were isolated. The minimum inhibitory concentrations (MICs) were determined on the basis of the results of the Epsilometer test (Etest). PCR and DNA sequencing was performed to characterize the gene cassette arrays of class 1 integrons. Multilocus sequence typing (MLST) and repetitive extragenic palindromic sequence (REP)-PCR were performed for epidemiological typing. RESULTS: Class 1 integrons were detected in 50 (89.3%) of the 56 isolates, but no class 2 or 3 integron was found within the cohorts. The class 1 integrons were classified into 4 types: 2.3-kb type A (aacA4-catB8-aadA1), 3.0-kb type B (aacA4-blaI(MP-1)-bla(OXA-2)), 3.0-kb type C (bla(VIM-2)-aacA7-aadA1), and 1.8-kb type D (aac3-1-bla(OXA-2)-orfD). Type A was most prevalent and was detected only in A. baumannii isolates, except for one A. bereziniae isolate; however, type B was amplified in all Acinetobacter isolates except for A. baumannii isolates, regardless of clone and separation time of the bacteria. CONCLUSIONS: Although class 1 integron can be transferred horizontally between unrelated isolates belonging to different species, certain types of class 1 integrons tend to transfer horizontally and vertically among A. baumannii or non-baumannii Acinetobacter isolates.
Acinetobacter/drug effects/isolation & purification/*metabolism ; Acinetobacter Infections/epidemiology/microbiology ; Acinetobacter baumannii/drug effects/isolation & purification/metabolism ; Anti-Bacterial Agents/pharmacology ; DNA, Bacterial/chemistry/metabolism ; Drug Resistance, Multiple, Bacterial ; Humans ; Integrons/*genetics ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; Polymerase Chain Reaction ; Republic of Korea

BACKGROUND: Pseudomonas aeruginosa is a clinically important pathogen that causes opportunistic infections and nosocomial outbreaks. Recently, the type III secretion system (TTSS) has been shown to play an important role in the virulence of P. aeruginosa. ExoU, in particular, has the greatest impact on disease severity. We examined the relationship among the TTSS effector genotype (exoS and exoU), fluoroquinolone resistance, and target site mutations in 66 carbapenem-resistant P. aeruginosa strains. METHODS: Sixty-six carbapenem-resistant P. aeruginosa strains were collected from patients in a university hospital in Daejeon, Korea, from January 2008 to May 2012. Minimum inhibitory concentrations (MICs) of fluoroquinolones (ciprofloxacin and levofloxacin) were determined by using the agar dilution method. We used PCR and sequencing to determine the TTSS effector genotype and quinolone resistance-determining regions (QRDRs) of the respective target genes gyrA, gyrB, parC, and parE. RESULTS: A higher proportion of exoU+ strains were fluoroquinolone-resistant than exoS+ strains (93.2%, 41/44 vs. 45.0%, 9/20; P< or =0.0001). Additionally, exoU+ strains were more likely to carry combined mutations than exoS+ strains (97.6%, 40/41 vs. 70%, 7/10; P=0.021), and MIC increased as the number of active mutations increased. CONCLUSIONS: The recent overuse of fluoroquinolone has led to both increased resistance and enhanced virulence of carbapenem-resistant P. aeruginosa. These data indicate a specific relationship among exoU genotype, fluoroquinolone resistance, and resistance-conferring mutations.
ADP Ribose Transferases/genetics ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/genetics ; Bacterial Toxins/genetics ; Carbapenems/pharmacology ; Drug Resistance, Bacterial/*drug effects ; Fluoroquinolones/*pharmacology ; Genotype ; Humans ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; Mutation ; Pseudomonas aeruginosa/*genetics/isolation & purification/pathogenicity ; Sputum/microbiology ; Virulence

Atrial fibrillation (AF) is an emerging epidemic in both high-income and low-income countries, mainly because of global population aging. Stroke is a major complication of AF, and AF-related ischemic stroke is more disabling and more fatal than other types of ischemic stroke. However, because of concerns about bleeding complications, particularly intracranial hemorrhage, and the limitations of a narrow therapeutic window, warfarin is underused. Four large phase III randomized controlled trials in patients with non-valvular AF (RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE-AF-TIMI 48) demonstrated that new oral anticoagulants (NOACs) are superior or non-inferior to warfarin as regards their efficacy in preventing ischemic stroke and systemic embolism, and superior to warfarin in terms of intracranial hemorrhage. Among AF patients receiving warfarin, Asians compared to non-Asians are at higher risk of stroke or systemic embolism and are also more prone to develop major bleeding complications, including intracranial hemorrhage. The extra benefit offered by NOACs over warfarin appears to be greater in Asians than in non-Asians. In addition, Asians are less compliant, partly because of the frequent use of herbal remedies. Therefore, NOACs compared to warfarin may be safer and more useful in Asians than in non-Asians, especially in stroke patients. Although the use of NOACs in AF patients is rapidly increasing, guidelines for the insurance reimbursement of NOACs have not been resolved, partly because of insufficient understanding of the benefit of NOACs and partly because of cost concerns. The cost-effectiveness of NOACs has been well demonstrated in the healthcare settings of developed countries, and its magnitude would vary depending on population characteristics as well as treatment cost. Therefore, academic societies and regulatory authorities should work together to formulate a scientific healthcare policy that will effectively reduce the burden of AF-related stroke in this rapidly aging society.
Aging ; Anticoagulants* ; Asian Continental Ancestry Group* ; Atrial Fibrillation ; Delivery of Health Care ; Developed Countries ; Embolism ; Health Care Costs ; Hemorrhage ; Humans ; Insurance ; Intracranial Hemorrhages ; Population Characteristics ; Stroke* ; Warfarin

BACKGROUND: We aimed to conduct a systematic review of previously published material to evaluate the diagnostic effectiveness of PCR-based tests in detecting BRAF mutation. METHODS: Eight Korean databases, including KoreaMed, Ovid-MEDLINE, and Ovid-EMBASE were used to identify relevant published studies. Nine studies describing usage of real-time PCR, dual-priming oligonucleotide (DPO)-multiplex real-time PCR and allele-specific PCR were included in the final assessment. Two reviewers screened all references independently for assessing the quality of the included articles and extracted data. RESULTS: The rate of detection of the BRAF mutations was lower in the Korean population (11.1-17.2%) than that in the Western population (36.7-82.2%). The diagnostic accuracy of the BRAF mutation tests was assessed on the basis of four previous reports, all of which employed real-time PCR on malignant melanoma. In fact, the diagnostic accuracy of real-time PCR was found to be higher than that of sequencing tests (pooled sensitivity, 0.96; pooled specificity, 0.83; and summary receiver operating characteristic area under the curve, 0.99). In addition, we found that there was no publication bias in meta-analysis. The concordance rate of the BRAF mutation tests compared with reference tests was 87.9-98.1%. CONCLUSIONS: Real-time PCR for the detection of the BRAF gene mutation is an effective technology for determining the appropriateness of treatment with BRAF kinase inhibitors in terminal stage cancer as well as metastatic and malignant melanoma.
Melanoma* ; Phosphotransferases ; Polymerase Chain Reaction ; Publication Bias ; Real-Time Polymerase Chain Reaction ; ROC Curve ; Sensitivity and Specificity

A burnt-out prostate cancer tumor is a very rare clinical entity. The term 'burnt-out' refers to a primary tumor that has spontaneously and nearly completely regressed without treatment. Since metastasis of prostate cancer is usually encountered in the presence of advanced disease, distant metastasis with an undetectable primary tumor is very rare. We report herein a case of a burnt-out prostate cancer tumor that metastasized to the thoracic (T) spine and caused cord compression. A 66-year-old man visited the Emergency Department due to weakness of both legs for the past two days. His blood and urine tests were normal at the time. His spine magnetic resonance imaging (MRI) scans looked like bone metastasis that involved the T-7 vertebral body and a posterior element, and caused spinal cord compression. Other images, including from the brain MRI, neck/chest/abdomino-pelvic computed tomography (CT) scan and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and endoscopy, revealed no lesions that suggested malignancy. After total corpectomy T-7 and screw fixation/fusion at T5 to T10, the pathology report revealed a metastatic carcinoma that was strongly positive for prostate-specific antigen (PSA). The serum PSA value was 1.5 ng/mL. The transrectal 12-core prostate biopsy and ultrasonography showed no definitive hypoechoic lesion, but one specimen had slight (only 1%) adenocarcinoma with a Gleason score of 6 (3+3). The final diagnosis was burned-out prostate cancer with an initial normal PSA value. Although metastatic disease with an unknown primary origin was confirmed, a more aggressive approach in seeking the primary origin could provide a more specific treatment strategy and greater clinical benefit to patients.
Adenocarcinoma ; Aged ; Biopsy ; Brain ; Diagnosis ; Emergencies ; Endoscopy ; Humans ; Leg ; Magnetic Resonance Imaging ; Neoplasm Grading ; Neoplasm Metastasis ; Pathology ; Prostate* ; Prostate-Specific Antigen ; Prostatic Neoplasms* ; Spinal Cord Compression ; Spine ; Ultrasonography

BACKGROUND: The Coapresta 2000 (Sekisui Medical Co., Japan) is a newly developed, fully automated coagulation analyzer that can perform clotting time assays using the synthetic substrate method and the latex turbidimetric method. In this study, we evaluated the analytical performance of the Coapresta 2000 for measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT), and compared the results to those of the CA-7000 (Sysmex Co., Japan) and ACL-9000 (Instrumentation Laboratory, USA) analyzers. METHODS: The Coapresta 2000 was evaluated for its precision at measuring PT and aPTT in fresh normal plasma and fresh abnormal plasma. Three hundred venous blood specimens were collected in 3.2% sodium citrate tubes, and PT and aPTT results were compared among the Coapresta 2000, ACL-9000, and CA-7000 analyzers. RESULTS: The coefficients of variation of both intra- and inter-assays for the Coapresta 2000 were <5% for PT and aPTT in the normal and pathological ranges. The results obtained using the Coapresta 2000 analyzer correlated well with those obtained using the ACL-9000 analyzer (r in the range of 0.9799-0.9886) except for aPTT (r=0.7626) and with those obtained using the CA-7000 analyzer (r in the range of 0.8258 - 0.9735). CONCLUSIONS: The Coapresta 2000 provided satisfactory precision, and the results obtained correlated well with those obtained using the existing CA-7000 and ACL-9000 coagulation analyzers. We conclude that the Coapresta 2000 would be a useful analyzer for routine coagulation tests.
Citrates ; Citric Acid ; Latex ; Partial Thromboplastin Time ; Plasma ; Prothrombin Time ; Sodium