PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

Destruction of dopaminergic neurons in the substantia nigra pars compacta (SNpc) is a common pathophysiology of Parkinson's disease (PD). Characteristics of PD patients include bradykinesia, muscle rigidity, tremor at rest and disturbances in balance. For about four decades, PD animal models have been produced by toxin-induced or gene-modified techniques. However, in mice, none of the gene-modified models showed all 4 major criteria of PD. Moreover, distinguishing between PD model pigs and normal pigs has not been well established. Therefore, we planned to produce a pig model for PD by chronic subcutaneous administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), neurotoxin. Changes in behavioral patterns of pigs were thoroughly evaluated and a new motor scoring system was established for this porcine model that was based on the Unified Parkinson's Disease Rating Scale (UPDRS) in human PD patients. In summary, this motor scoring system could be helpful to analyze the porcine PD model and to confirm the pathology prior to further examinations, such as positron emission tomography-computed tomography (PET-CT), which is expensive, and invasive immunohistochemistry (IHC) of the brain.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine* ; Animals ; Brain ; Dopaminergic Neurons ; Electrons ; Humans ; Hypokinesia ; Immunohistochemistry ; Injections, Subcutaneous* ; Mice ; Models, Animal ; Muscle Rigidity ; Parkinson Disease* ; Pathology ; Substantia Nigra ; Swine ; Tremor

Dysferlinopathy is caused by mutations in the DYSF gene. To characterize the clinical spectrum, we investigated the characteristics of 31 Korean dysferlinopathy patients confirmed by immunohistochemistry. The mean age of symptom onset was 22.23 +/- 7.34 yr. The serum creatine kinase (CK) was highly increased (4- to 101-fold above normal). The pathological findings of muscle specimens showed nonspecific dystrophic features and frequent inflammatory cell infiltration. Muscle imaging studies showed fatty atrophic changes dominantly in the posterolateral muscles of the lower limb. The patients with dysferlinopathy were classified by initial muscle weakness: fifteen patients with Miyoshi myopathy phenotype (MM), thirteen patients with limb girdle muscular dystrophy 2B phenotype (LGMD2B), two patients with proximodistal phenotype, and one asymptomatic patient. There were no differences between LGMD2B and MM groups in terms of onset age, serum CK levels and pathological findings. Dysferlinopathy patients usually have young adult onset and high serum CK levels. However, heterogeneity of clinical presentations and pathologic findings upon routine staining makes it difficult to diagnose dysferlinopathy. These limitations make immunohistochemistry currently the most important method for the diagnosis of dysferlinopathy.
Adolescent ; Adult ; Age of Onset ; Creatine Kinase/blood ; Distal Myopathies/pathology ; Female ; Humans ; Immunohistochemistry ; Male ; Membrane Proteins/genetics ; Middle Aged ; Muscle Proteins/genetics ; Muscular Atrophy/pathology ; Muscular Dystrophies, Limb-Girdle/*diagnosis/genetics/pathology ; Mutation ; Phenotype ; Republic of Korea ; Tomography, X-Ray Computed ; Young Adult

BACKGROUND/AIMS: The aim of this study was to identify changes in left ventricular (LV) performance in patients with a myocardial bridge (MB) in the left anterior descending coronary artery during resting and in an inotropic state. METHODS: Myocardial strain measurement by speckle-tracking echocardiography and conventional LV wall-motion scoring was performed in 18 patients with MB (mean age, 48.1 +/- 1.7 years, eight female) during resting and intravenous dobutamine challenge (10 and 20 microg/kg/min). RESULTS: Conventional LV wall-motion scoring was normal in all patients during resting and in an inotropic state. Peak regional circumferential strain increased dose dependently upon dobutamine challenge. Longitudinal strains of the anterior and anteroseptal segments were, however, reduced at 20 microg/kg/min and showed a dyssynchronous pattern at 20 microg/kg/min. Although there were no significant differences in radial strain and displacement of all segments at rest compared with under 10 microg/kg/min challenge, radial strain and displacement of anterior segments at 20 microg/kg/min were significantly reduced compared with posterior segments at the papillary muscle level (44.8 +/- 14.9% vs. 78.4 +/- 20.1% and 5.3 +/- 2.3 mm vs. 8.5 +/- 1.8 mm, respectively; all p < 0.001), and showed plateau (40%) or biphasic (62%) patterns. CONCLUSIONS: Reduced LV strain of patients with MB after inotropic stimulation was identified. Speckle-tracking strain echocardiography identified a LV myocardial dyssynchrony that was not demonstrated by conventional echocardiography in patients with MB.
Adrenergic beta-1 Receptor Agonists/*diagnostic use ; Adult ; Aged ; Chest Pain ; Coronary Angiography ; Diastole ; Dobutamine/*diagnostic use ; Echocardiography, Stress/instrumentation/*methods ; Female ; Humans ; Male ; Middle Aged ; *Myocardial Contraction ; *Myocardium ; Physical Exertion ; Systole ; *Ventricular Dysfunction, Left ; Ventricular Function, Left/*drug effects

OBJECTIVES: This study was performed to investigate the service needs of the beneficiaries who had enrolled in home-based management programs for cancer patients. METHODS: From March to May 2009, 676 cancer patients who were registered in home-based cancer patient management programs were selected as subjects for this study. The data were collected using a questionnaire along with a face-to-face interview performed by officers in charge of the home-based care programs of 47 regional health centers. Fifteen patients were excluded due to incomplete data, leaving 661 subjects who were ultimately enrolled in the study. RESULTS: The mean age of subjects was 64.0 +/- 12.5 years, and males comprised 45.1% (298/661) of the sample. The results of factor analysis for service needs showed that there were five main categories and Cronbach's alpha ranged from 0.593 to 0.890 for each factor. The service needs categories in order of importance were social support, information and education, psychological problems, physical symptoms and household chores. The service needs scores were significantly different when subjects were stratified by age, habitation, religion and disease classification. When we divided the subjects into complete remission, under treatment and terminally ill groups, the needs scores of the terminally ill patient group were significantly higher than those of the other groups (p<0.001). CONCLUSIONS: Service provision based on patient and beneficiary needs could be an effective intervention to reduce the economic burden of cancer management and to improve the quality of life of cancer patients receiving home-based care. Therefore, it is recommended that individual cancer patient care programs be developed and administered according to patient age, habitation and disease severity.
Family Characteristics ; Fees and Charges ; Home Care Services ; Humans ; Male ; Needs Assessment ; Patient Care ; Quality of Life ; Terminally Ill ; Surveys and Questionnaires

Hemodynamic depression (hypotension and bradycardia) can occur during or after carotid angioplasty and stenting (CAS) due to stretching of the baroreceptors in the carotid sinus. The predisposing factors of hemodynamic depression have not been reported previously. In general, hemodynamic depression after CAS may continue for up to 3-5 days, but disappears within 7 days. We report herein a 65-year-old man with severe hemodynamic depression after sequential CAS, and discuss the possible causes from an anatomical point of view.
Aged ; Angioplasty ; Carotid Sinus ; Depression ; Hemodynamics ; Humans ; Pressoreceptors ; Stents

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection can lead to gastric adenoma and carcinoma through atrophic gastritis and intestinal metaplasia. Imbalance between apoptosis and proliferation may play a role in gastric carcinogenesis. We tried to investigate H. pylori infection rate, grade of gastritis, environmental risk factors, expression rate of apoptosis and cell proliferation in mucosa adjacent to tumor, and we also tried to find significant factors associated with gastric carcinogenesis. METHODS: Endoscopically diagnosed twenty cases of intestinal type gastric carcinoma, 20 cases of gastric adenoma, and 40 cases of control (normal or gastritis) were enrolled. H. pylori infection rate, histologic grading, apoptosis and immunohistochemical stain (Ki-67 and p53) to check mucosal proliferation were done in endoscopically biopsied tissues at antrum and body at least 2 cm apart from adenoma or carcinoma. RESULTS: In three groups, H. pylori infection rates were not significantly different. In the multivariate analysis, only atrophy of gland was a significant risk factor for adenoma compared to control group (OR 3.7). Intestinal metaplasia in antrum and alcohol drinking were significant risk factors for carcinoma compared to control group (OR 4.4 and 4.9 respectively). Expressions of apoptosis, Ki-67 and p53 were not significantly different in three groups. CONCLUSIONS: Intestinal metaplasia in antrum and alcohol drinking are significant risk factors for gastric carcinoma. Degree of mucosal proliferation and apoptosis in gastric mucosa adjacent to tumor are not significantly different in three groups.
Adenocarcinoma/microbiology/*pathology ; Adenoma/microbiology/*pathology ; Adult ; Aged ; Aged, 80 and over ; *Apoptosis ; *Cell Proliferation ; English Abstract ; Female ; Gastric Mucosa/*pathology ; Gastritis/microbiology/pathology ; Helicobacter Infections/complications/pathology ; Helicobacter pylori ; Humans ; Male ; Middle Aged ; Risk Factors ; Stomach Neoplasms/microbiology/*pathology

PURPOSE: Malignant lymphoma is the primary malignant tumor derived from lymphoid organs. It is composed of Hodgkin's disease and non-Hodgkin lymphoma. Recently, survival rate is on the rise due to improved combination chemotherapy, radiotherapy and high dose chemotherapy followed by hematopoietic stem cell transplantation. In South Korea, no epidemiologic studies concerning malignant lymphoma in the pediatric age group has been performed. Therefore, the Korean Society of Pediatric Hematology-Oncology retrospectively analyzed the incidence, pathologic subtypes, treatment strategies, and survival rates of pediatric malignant lymphomas in South Korea. METHOD: Questionnaires were made and sent to a group of training hospitals, with a return of 580 questionnaires from 24 hospitals. Among them, 517 reports were suitable for analysis. RESULTS: Among the 517 cases, Hodgkin's disease accounted for 58 cases and non-Hodgkin's lymphoma for 459 cases. Male to female ratio for malignant lymphoma was 2.7. Mean age at diagnosis was 8.3 years. Among the pathologic subtypes, mixed cellularity was the most frequent subtype for Hodgkin's disease. Most (70.7%) cases of non-Hodgkins lymphoma belonged to high grade NHL. Burkitt lymphoma accounted for 102 cases, and lymphoblastic lymphoma was found in 58 cases. Peripheral lymphadenopathy was the most common presenting sign upon diagnosis. B symptoms were significantly more frequent in Hodgkin's disease patients than in non-Hodgkin lymphoma patients. The Complete response rate was 62.1% for non-Hodgkin's lymphoma, and 82.8% for Hodgkin's disease. Overall 5 year survival rate was 60.0% in non-hodgkin's lymphoma, and 84.8% in Hodgkin's disease. CONCLUSION: The annual incidence of malignant lymphoma in Korea is 4.7 per million. In cases of chemotherapy-sensitive, refractory or relapsed malinant lymphoma, high dose chemotherapy followed by hematopoietic stem cell transplantation is vital for improved survival. For more systematic analysis of epidemiology on malignant lymphomas, better surveillance mechanisms on the occurrence of malignant lymphomas are crucial, and establishment of standardized treatment protocol for malignant lymphoma is required.
Burkitt Lymphoma ; Child* ; Clinical Protocols ; Diagnosis ; Drug Therapy ; Drug Therapy, Combination ; Epidemiologic Studies ; Epidemiology* ; Female ; Hematopoietic Stem Cell Transplantation ; Hodgkin Disease ; Humans ; Incidence ; Korea* ; Lymphatic Diseases ; Lymphoma* ; Lymphoma, Non-Hodgkin ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Surveys and Questionnaires ; Radiotherapy ; Retrospective Studies* ; Survival Rate

BACKGROUND: Even though the effect of prehydration on the spinal anesthesia-induced hypotension has not yet been concluded, prehydration prior to spinal anesthesia is recommended in order to reduce the incidence and severity of hypotension. We investigated the effects of prehydration on hemodynamic change during spinal anesthesia with isobaric 0.5% tetracaine. METHODS: We prospectively performed this study on 96 patients who underwent elective transurethral surgery from October 2002 to January 2004. Patients were randomly allocated to receive either no prehydration or 10 ml/kg crystalloids administered over 10 15 min prior to spinal anesthesia. We compared dermatomal spreads of spinal anesthesia, hemodynamic parameters (blood pressure, heart rate), incidences of hypotension and bradycardia between two groups. RESULTS: Hemodynamic parameters, incidences of hypotension and bradycardia showed no statistically significant differences during spinal anesthesia between two groups. There were statistically significant differences in the dermatomal spread of sensory levels between two groups from 5 to 90 min after spinal anesthesia. Sensory block levels in prehydration group were statistically lower than no prehydration group. CONCLUSION: We hypothesized that prehydration can be one of factors that influence on dermatomal spread of local anesthetics in isobaric spinal anesthesia. The difference of dermatomal spread between two groups may be caused by brain blood barrier (BBB)-freely passing crystalloids, which may influence on the volume and density of cerebrospinal fluids. To verify this phenomenon found in our study, further investigation is still warranted.
Anesthesia, Spinal* ; Anesthetics, Local ; Blood-Brain Barrier ; Bradycardia ; Cerebrospinal Fluid ; Heart ; Hemodynamics ; Humans ; Hypotension ; Incidence ; Prospective Studies ; Tetracaine

PURPOSE: Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of all cases of childhood leukemia. We investigated epidemiology, clinical and laboratory features and treatment outcome of the children with ALL in Korea during recent 5 years. METHODS: One thousand forty nine patients were enrolled between January 1994 and December 1998 from 37 major hospitals in Korea. The data regarding the clinical and laboratory features including age, WBC counts at diagnosis, immunophenotype, morphology, cytogenetics and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed. The differences between groups analyzed by log-rank test. RESULTS: There were 597 males and 452 females. The distribution between the age 2 and 5 years is most common in 46.1%. The annual incidence rate per 100,000 population varied from 1.6 to 2.2. The 5 year event free survival (EFS) rates according to good prognostic factors were as follows: 67% bet ween 1-9 year of age at diagnosis, 69% in under 10,000/mm3of initial WBC count, 74% in early pre-B cell CALLA ( ) immunophenotype, 65% in L3 morphology, 68% in no CNS invasion. Most of patients were treated by CCG treatment protocol. The 5 year EFS was 63%. Main complications were sepsis (21.8%) and hemorrhage (12.5%). The relapse rate was 15.6%. The common causes of death were sepsis, DIC, pneumonia, relapse. CONCLUSION: Our results could provide the most recent and important information about acute lymphoblastic leukemia of children in Korea.
Cause of Death ; Child ; Clinical Protocols ; Cytogenetics ; Dacarbazine ; Diagnosis ; Disease-Free Survival ; Epidemiology* ; Female ; Hemorrhage ; Humans ; Incidence ; Kaplan-Meier Estimate ; Korea* ; Leukemia ; Male ; Medical Records ; Pneumonia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor Cells, B-Lymphoid ; Recurrence ; Retrospective Studies ; Sepsis ; Treatment Outcome