Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

BACKGROUND: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. RESULTS: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment. CONCLUSION: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient.
Brain ; Central Nervous System ; Chemoradiotherapy ; Diagnosis ; Drug Therapy ; Glioblastoma ; Humans ; Korea ; Radiotherapy

Obesity causes inflammation and impairs thermogenic functions in brown adipose tissue (BAT). The adipokine lipocalin 2 (LCN2) has been implicated in inflammation and obesity. Herein, we investigated the protective effects of caloric restriction (CR) on LCN2-mediated inflammation and oxidative stress in the BAT of high-fat diet (HFD)-fed mice. Mice were fed a HFD for 20 weeks and then either continued on the HFD or subjected to CR for the next 12 weeks. CR led to the browning of the white fat-like phenotype in HFD-fed mice. Increased expressions of LCN2 and its receptor in the BAT of HFD-fed mice were significantly attenuated by CR. Additionally, HFD+CR-fed mice had fewer neutrophils and macrophages expressing LCN2 and iron-positive cells than HFD-fed mice. Further, oxidative stress and mitochondrial fission induced by a HFD were also significantly attenuated by CR. Our findings indicate that the protective effects of CR on inflammation and oxidative stress in the BAT of obese mice may be associated with regulation of LCN2.
Adipokines ; Adipose Tissue, Brown ; Animals ; Caloric Restriction ; Diet, High-Fat ; Inflammation ; Lipocalins ; Macrophages ; Mice ; Mice, Obese ; Mitochondrial Dynamics ; Neutrophils ; Obesity ; Oxidative Stress ; Phenotype

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.
Adult ; Astrocytoma ; Brain ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Follow-Up Studies ; Glioblastoma ; Glioma ; Humans ; Isocitrate Dehydrogenase ; Korea ; Oligodendroglioma ; Radiotherapy ; World Health Organization

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.
Adult ; Astrocytoma ; Brain ; Brain Neoplasms ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Glioblastoma ; Glioma ; Humans ; Isocitrate Dehydrogenase ; Korea ; Lomustine ; Oligodendroglioma ; Radiotherapy ; World Health Organization

Misoprostol is widely used in daily practice for induction of labor and cervical dilatation prior to intrauterine procedures, including dilatation and curettage or hysteroscopy. Anaphylactic shock to intravaginal misoprostol can occur not only in pregnant women, as reported in 2 previous cases, but also in a non-pregnant, perimenopausal woman, as in the case described herein. A 49-year-old woman received vaginal misoprostol for cervical ripening prior to hysteroscopic myomectomy and experienced anaphylactic shock. Two 400 μg doses of misoprostol 6 hours apart caused uncontrolled shaking and high fever followed by shock. In conclusion, the possibility of anaphylactic shock should be considered in patients with sudden hypotension following misoprostol administration. Prompt identification and management are crucial to prevent morbidity and mortality following an anaphylactic shock to misoprostol.
Anaphylaxis* ; Cervical Ripening ; Dilatation and Curettage ; Female ; Fever ; Humans ; Hypotension ; Hysteroscopy ; Labor Stage, First ; Middle Aged ; Misoprostol* ; Mortality ; Pregnancy ; Pregnant Women ; Shock

BACKGROUND/AIMS: Neuroendocrine tumors (NETs) may originate from heterogeneous neuroendocrine cells. The incidence is increasing worldwide, and World Health Organization (WHO) updated its classification in 2010. We investigated clinical characteristics of gastroenteropancreatic NETs in a single center. METHODS: Clinicopathologic characteristics of patients with pathologically confirmed gastroenteropancreatic NET in Seoul St. Mary Hospital from March 2009 to August 2011 were retrospectively analyzed. The grade and stage were determined according to WHO 2010 classification and TNM Staging System for Neuroendocrine Tumors (7th ed., 2010) of American Joint Committee on Cancer. RESULTS: One hundred and twenty-five patients (median age, 50; male, 61.3%) were analyzed. Among 100,000 patients who visited the hospital, incidence was 24.1. Only two patients (1.6%) had a functional NET. The rectum (n = 99, 79.8%) was most common primary site and found in early stage. The prevalence by stages was 84.7% stage I, 8.9% stage IV, 4.8% stage II, and 1.6% stage III. The pathology grading was 74.5% grade 1, 12.7% grade 2, and 12.7% grade 3. Tumor stage correlated positively with pathologic grade (Spearman’s rank correlation coefficient, 0.644). CONCLUSIONS: Wide range of clinicopathological features of Korean gastroenteropancreatic NETs were demonstrated using WHO 2010 classification. Rectal NET was most frequent and found in early stage.
Classification ; Epidemiology ; Humans ; Incidence* ; Joints ; Korea* ; Male ; Neoplasm Staging ; Neuroendocrine Cells ; Neuroendocrine Tumors* ; Pathology ; Prevalence ; Rectum ; Retrospective Studies ; Seoul ; World Health Organization

BACKGROUND/AIMS: Neuroendocrine tumors (NETs) may originate from heterogeneous neuroendocrine cells. The incidence is increasing worldwide, and World Health Organization (WHO) updated its classification in 2010. We investigated clinical characteristics of gastroenteropancreatic NETs in a single center. METHODS: Clinicopathologic characteristics of patients with pathologically confirmed gastroenteropancreatic NET in Seoul St. Mary Hospital from March 2009 to August 2011 were retrospectively analyzed. The grade and stage were determined according to WHO 2010 classification and TNM Staging System for Neuroendocrine Tumors (7th ed., 2010) of American Joint Committee on Cancer. RESULTS: One hundred and twenty-five patients (median age, 50; male, 61.3%) were analyzed. Among 100,000 patients who visited the hospital, incidence was 24.1. Only two patients (1.6%) had a functional NET. The rectum (n = 99, 79.8%) was most common primary site and found in early stage. The prevalence by stages was 84.7% stage I, 8.9% stage IV, 4.8% stage II, and 1.6% stage III. The pathology grading was 74.5% grade 1, 12.7% grade 2, and 12.7% grade 3. Tumor stage correlated positively with pathologic grade (Spearman’s rank correlation coefficient, 0.644). CONCLUSIONS: Wide range of clinicopathological features of Korean gastroenteropancreatic NETs were demonstrated using WHO 2010 classification. Rectal NET was most frequent and found in early stage.
Classification ; Epidemiology ; Humans ; Incidence* ; Joints ; Korea* ; Male ; Neoplasm Staging ; Neuroendocrine Cells ; Neuroendocrine Tumors* ; Pathology ; Prevalence ; Rectum ; Retrospective Studies ; Seoul ; World Health Organization