Purpose: K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and Methods: Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). Results: In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. Conclusion The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

Purpose: The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication. Materials and Methods: Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites. Results: A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases. Conclusion Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.

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

PURPOSE: Advanced hepatocellular carcinoma (HCC) is associated with various clinical conditions including major vessel invasion, metastasis, and poor performance status. The aim of this study was to establish a prognostic scoring system and to propose a sub-classification of the Barcelona-Clinic Liver Cancer (BCLC) stage C. MATERIALS AND METHODS: This retrospective study included consecutive patients who received sorafenib for BCLC stage C HCC at a single tertiary hospital in Korea. A Cox proportional hazard model was used to develop a scoring system, and internal validationwas performed by a 5-fold cross-validation. The performance of the model in predicting risk was assessed by the area under the curve and the Hosmer-Lemeshow test. RESULTS: A total of 612 BCLC stage C HCC patients were sub- classified into strata depending on their performance status. Five independent prognostic factors (Child-Pugh score, α-fetoprotein, tumor type, extrahepatic metastasis, and portal vein invasion) were identified and used in the prognostic scoring system. This scoring system showed good discrimination (area under the receiver operating characteristic curve, 0.734 to 0.818) and calibration functions (both p < 0.05 by the Hosmer-Lemeshow test at 1 month and 12 months, respectively). The differences in survival among the different risk groups classified by the total score were significant (p < 0.001 by the log-rank test in both the Eastern Cooperative Oncology Group 0 and 1 strata). CONCLUSION: The heterogeneity of patientswith BCLC stage C HCC requires sub-classification of advanced HCC. A prognostic scoring system with five independent factors is useful in predicting the survival of patients with BCLC stage C HCC.
Calibration ; Carcinoma, Hepatocellular* ; Cohort Studies* ; Discrimination (Psychology) ; Humans ; Korea ; Liver Neoplasms ; Neoplasm Metastasis ; Population Characteristics ; Portal Vein ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; ROC Curve ; Tertiary Care Centers

BACKGROUND/AIMS: Guidelines recommend surveillance for hepatocellular carcinoma (HCC) recurrence at 3-month intervals during the first year after curative treatment and 6-month intervals thereafter in all patients. This strategy does not reflect individual risk of recurrence. We aimed to stratify risk of recurrence to optimize surveillance intervals 1 year after treatment. METHODS: We retrospectively analyzed 1,316 HCC patients treated with resection/radiofrequency ablation at Barcelona Clinic Liver Cancer stage 0/ A. In patients without 1-year recurrence under 3-monthly surveillance, a new model for recurrence was developed using backward elimination methods: training (n=582)/ validation cohorts (n=291). Overall survival (OS) according to risk stratified by the new model was compared according to surveillance intervals: 3-monthly versus 6-monthly (n=401) after lead time bias correction and propensity-score matching analyses. RESULTS: Among patients without 1-year recurrence, age and international normalized ratio values were significant factors for recurrence (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.00 to 1.03; p=0.009 and HR, 5.63; 95% CI, 2.24 to 14.18; p < 0.001; respectively). High-risk patients stratified by the new model showed significantly higher recurrence rates than low-risk patients in the validation cohort (HR, 1.73; 95% CI, 1.18 to 2.53; p=0.005). After propensity-score matching between the 3-monthly and 6-monthly surveillance groups, OS in high-risk patients under 3-monthly surveillance was significantly higher than that under 6-monthly surveillance (p=0.04); however, OS in low-risk patients under 3-monthly surveillance was not significantly different from that under 6-monthly surveillance (p=0.17). CONCLUSIONS: In high-risk patients, 3-monthly surveillance can prolong survival compared to 6-monthly surveillance. However, in low-risk patients, 3-monthly surveillance might not be beneficial for survival compared to 6-monthly surveillance.
Bias (Epidemiology) ; Carcinoma, Hepatocellular* ; Cohort Studies ; Humans ; International Normalized Ratio ; Liver Neoplasms ; Recurrence ; Retrospective Studies

BACKGROUND: The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (KATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight. METHODS: To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the KATP channel. RESULTS: The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice. CONCLUSION: These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.
Animals ; Appetite ; Blood Glucose ; Body Weight ; Glucose ; Hyperphagia ; Hypothalamus ; Intra-Abdominal Fat ; KATP Channels ; Mice ; Neurons ; Neuropeptide Y ; Obesity ; Potassium ; Social Control, Formal

BACKGROUND: Colloid solutions are used to treat hypovolemia and expanding plasma, but they may inhibit platelet function and reduce the level of coagulation factors during surgery. This study was conducted to compare the effects of hydroxyethyl starch (HES) on adenosine diphosphate (ADP)- and collagen-induced platelet aggregation in patients undergoing total intravenous anesthesia. METHODS: Patients undergoing endoscopic sinus surgery under total intravenous anesthesia with propofol and remifentanil were divided into a group that underwent fluid management with only crystalloid solution (n = 15) and a group that was managed with crystalloid solution that included 6% HES (130/0.4) (n = 15). ADP- and collagen-induced platelet aggregation were measured 5 minutes before induction, after the first intraoperative hour, and one hour postoperatively. RESULTS: Significantly diminished ADP- and collagen-induced aggregation values were observed intraoperatively when compared with the preoperative value in the patients that were managed with colloid solution that included HES. In addition, significantly diminished collagen-induced aggregation values were observed intraoperatively when compared with the preoperative value in the group that was managed with the solution that only contained the crystalloid. However, ADP- and collagen-induced platelet aggregation were recovered postoperatively in both groups. CONCLUSIONS: The results of this study indicated that fluid therapy with colloid solution that contained 6% HES (130/0.4) may diminish ADP-induced platelet aggregation intraoperatively in patients subjected to total intravenous anesthesia.
Adenosine Diphosphate ; Anesthesia, Intravenous ; Blood Coagulation Factors ; Blood Platelets ; Colloids ; Fluid Therapy ; Hetastarch ; Humans ; Hypovolemia ; Isotonic Solutions ; Piperidines ; Plasma ; Platelet Aggregation ; Propofol

OBJECTIVE: This study examined the prevalence and correlates of depressive symptoms in North Korean defectors who have been living in South Korea for more than one year. METHODS: We used questionnaires developed by the authors to collect sociodemographic data in addition to the Center for Epidemiologic Studies Depression Scale (CES-D), the Psychosocial Well-being Index to measure stress, and a social support scale. A total of 367 subjects were included in this study. RESULTS: The results showed that 30.5% of the men and 34.7% of the women reported depressive symptoms, and 33.1% of the men and 36.1% of the women exhibited signs of severe distress. Correlates of depressive symptoms were lack of occupation [odds ratio (OR)=2.198, 95% confidence interval (CI), 1.247-3.873], having escaped without family (OR=1.725, 95% CI, 1.006-2.959), and a poor subjective sense of health status (OR=3.111, 95% CI, 1.591-6.085). CONCLUSION: Continuing vocational training and career management, psychological support programs, and intensive physical health services are needed to improve the mental health of this population.
Depression ; Epidemiologic Studies ; Female ; Health Services ; Humans ; Male ; Mental Health ; Occupations ; Prevalence ; Surveys and Questionnaires ; Republic of Korea ; United Nations

Neurenteric cysts are rare congenital lesions of the spine that are lined with endodermal epithelium. Their most common location is the cervico-dorsal region, and the mass usually lies ventral to the spinal cord. However the conus medullaris area location is an uncommon location. Neurenteric cysts are best treated by decompression and as near total excision of cyst membrane as possible. We report a case of a 7 year-old-girl with a neurenteric cyst in the conus medullaris. The patient had a history of meningitis and a gait disturbance. Magnetic resonance imaging (MRI) showed an intramedullary mass lesion in the conus medullaris with syringomyelia. There was no associated bone or soft-tissue anomaly. The mass was subtotally removed through a posterior approach. However 4 months later, meningeal irritation signs developed and MRI showed recurrence of the cyst. At the second operation, the cystic membrane was totally removed and the patient's neurological symptoms improved postoperatively. We reports a case of recurred neurenteric cyst occurred in unusual location with the review of literature.
Conus Snail* ; Decompression ; Endoderm ; Epithelium ; Gait ; Humans ; Magnetic Resonance Imaging ; Membranes ; Meningitis* ; Neural Tube Defects* ; Recurrence ; Spinal Cord ; Spine ; Syringomyelia

OBJECTIVE: Cerebral palsy may induce harmful spastic hip adduction. We report the result of microsurgical selective obturator neurotomy, performed on 12 spastic hip adductions of 6 patients, followed clinically for at least 26 months postoperatively. METHODS: Microsurgical selective obturator neurotomies, involving microsurgical resection of the anterior obturator nerve branches were performed on 6 patients from January 2000 through June 2003. All patients presented with the inability to sit and 2 patients complained of persistent, intractable pain. We used intraoperative bipolar stimulation to identify selected motor branches. RESULTS: The procedure was performed bilaterally in all patients. In the 3 patients in whom contractures were present, microsurgical selective obturator neurotomies were accompanied by an additional tenotomy of the adductor muscles. Selective tibial neurotomy was performed on three of six patients who originally presented with a spastic ankle. Postoperatively, all spastic hip adductions were corrected more than 60 degrees in passive abduction-adduction amplitude. However, one patient who did not receive active postoperative physiotherapy demonstrated a decreased passive abduction-adduction amplitude upon follow-up. There were no surgical complications. CONCLUSION: We think microsurgical selective obturator neurotomy may be an effective procedure in the treatment of localized, harmful spastic hip adduction after failure of well conducted conservative treatment. As muscular contractions are often associated with spasticity of the hip adductors, an adjunctive tenotomy may be an option. Comprehensive postoperative physiotherapy is essential to improve long-term results.
Ankle ; Cerebral Palsy ; Contracture ; Follow-Up Studies ; Hip* ; Humans ; Muscle Contraction ; Muscle Spasticity* ; Muscles ; Obturator Nerve ; Pain, Intractable ; Paralysis ; Tenotomy