PURPOSE: Cetuximab demonstrates improved efficacy outcomes in patients with metastatic colorectal cancer (mCRC) harboring wild-type KRAS exon 2. Resistance to cetuximab is mediated by activating less frequent mutations in the RAS genes beyond KRAS exon 2. We performed extended RAS Mutational analysis using a high-throughput genotyping platform (OncoMap) and evaluated extended RAS analysis for predicting cetuximab efficacy in patients harboring wild-type KRAS exon 2 tumors following Sanger sequencing. MATERIALS AND METHODS: Extended RAS analysis was performed on 227 wild-type KRAS exon 2 mCRC patients who received cetuximab as salvage treatment using OncoMap ver. 4.0. Targeted genes included exon 2, exon 3, and exon 4, both in KRAS and NRAS, and included BRAF exon 15. We assessed efficacy by the new RAS mutation status. RESULTS: The OncoMap detected 57 additional mutations (25.1%): 25 (11%) in KRAS exon 2 and 32 (14.1%) beyond KRAS exon 2. Survival differences were observed after dividing patients into the wild-type RAS group (n=170) and mutant RAS group (n=57) using OncoMap. Progression-free survival was 4.8 months versus 1.8 months (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.32 to 0.61), and overall survival was 11.9 months versus 8.4 months (HR, 0.65; 95% CI, 0.47 to 0.88). CONCLUSION: Sanger sequencing is not sufficient for selecting candidates for cetuximab treatment. High-throughput extended RAS genotyping is a feasible approach for this purpose and identifies patients who might benefit from cetuximab treatment.
Cetuximab* ; Colorectal Neoplasms* ; Disease-Free Survival ; Exons ; Genes, ras ; High-Throughput Nucleotide Sequencing ; Humans ; Salvage Therapy

BACKGROUND/AIMS: To investigate the predictive factors for complete response (CR) and recurrence after CR in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). METHODS: Among 691 newly diagnosed HCC patients, 287 were treated with TACE as a first therapy. We analyzed the predictive factors for CR, recurrence after CR, and overall survival (OS). RESULTS: Eighty-one patients (28.2%) achieved CR after TACE, and recurrence after CR was detected in 35 patients (43.2%). In multivariate analyses, tumor size (≤5 cm) and single nodularity were predictive factors for CR, with hazard ratios (HRs) of 0.35 (p=0.002) and 0.41 (p<0.001), respectively. Elevated serum α-fetoprotein (AFP) (>20 ng/mL) level and multinodularity exhibited significant relationships with recurrence after CR, with HRs of 2.220 (p=0.026) and 3.887 (p<0.001), respectively. Tumor size (>5 cm), multinodularity, elevated serum AFP (>20 ng/mL) level, Child-Turcotte-Pugh score (B and C), and portal vein thrombosis were significant factors for OS. CONCLUSIONS: In patients treated with TACE as a first therapy, tumor size (≤5 cm) and single nodularity were predictive factors for CR, and multinodularity and elevated serum AFP (>20 ng/mL) levels were predictive factors for recurrence after CR. These factors were also significant for OS.
Carcinoma, Hepatocellular* ; Chemoembolization, Therapeutic ; Humans ; Multivariate Analysis ; Recurrence* ; Venous Thrombosis

BACKGROUND: The dot-like hippocampal signal intensity in diffusion-weighted MR images is well-known as a characteristic imaging feature in transient global amnesia, a neurological syndrome in which sudden forward-and-backward memory loss occurs that is slowly recovered within 24 hours. We here report on patients with this dot-like hippocampal hyperintensity who did not present with anterograde amnesia except for headaches. CASE REPORT: Two women without a specific medical history presented with sudden-onset headaches on the same day. Neither had any trauma or infection history before the symptom or any sudden emotional or postural changes. Brain MRI showed tiny hippocampal high signal intensity on diffusion-weighted images (DWI). CONCLUSIONS: Dot-like hippocampal lesions seen on DWI may be present without memory impairment, and more studies are needed to determine whether there is any association with headache as in this case.
Amnesia, Anterograde ; Amnesia, Transient Global* ; Brain ; Diffusion* ; Female ; Headache* ; Hippocampus ; Humans ; Magnetic Resonance Imaging ; Memory ; Memory Disorders

BACKGROUND: An infection known to be a major cause of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). Rapidly progressive dementia is a neurological condition in which dementia progresses in a short period of time. CASE REPORT: We report on a 78-year-old woman presenting with a rapid decline in cognitive function resulting from a scrub typhus infection. Diffusion weighted images showed a signal intensity at the splenium, and subcortical white matter of both hemispheres suggesting MERS. On the neuropsychological test, the patient showed frontal executive dysfunction. CONCLUSIONS: This case suggests that diagnosticians should consider the possibility that a MERS patient with a rapidly cognitive decline could have a scrub typhus infection because early diagnosis of scrub typhus is very important in this aspect of the treatment.
Aged ; Brain Diseases* ; Cognition ; Dementia* ; Diffusion ; Early Diagnosis ; Female ; Humans ; Neuropsychological Tests ; Scrub Typhus* ; White Matter

The original version of this article contained wrong information of an author which should be changed.

Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS. This consensus standard proposal consists of two parts: laboratory guidelines and requirements for clinical NGS laboratories. The laboratory guidelines part addressed several important issues across multistep NGS cancer panel tests including choice of gene panel and platform, sample handling, nucleic acid management, sample identity tracking, library preparation, sequencing, analysis and reporting. Requirements for clinical NGS tests were summarized in terms of documentation, validation, quality management, and other required written policies. Together with appropriate pathologist training and international laboratory standards, these laboratory standards would help molecular pathology laboratories to successfully implement NGS cancer panel tests in clinic. In this way, the oncology community would be able to help patients to benefit more from personalized cancer medicine.
Consensus ; High-Throughput Nucleotide Sequencing ; Humans ; Korea ; Pathology, Molecular ; Practice Guidelines as Topic ; Quality Control

BACKGROUND: Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab-treated patients show clinical benefit regardless of concurrent AA. METHODS: We analyzed 46 PNH patients ≥18 years of age who were diagnosed by flow cytometry and treated with eculizumab for more than 6 months in the prospective Korean PNH registry. Patients were categorized into two groups: PNH patients with concurrent AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of intravascular hemolysis, hematological laboratory values, transfusion requirement, and PNH-associated complications were assessed at baseline and every 6 months after initiation of eculizumab treatment. RESULTS: The median patient age was 46 years and median duration of eculizumab treatment was 34 months. Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month follow-up, LDH decreased to near normal levels in all patients; this effect was maintained until the 36-month follow-up regardless of concurrent AA. Transfusion independence was achieved by 53.3% of patients within the first 6 months of treatment and by 90.9% after 36 months of treatment. The mean number of RBC units transfused was significantly reduced, from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population; this effect was similar in both PNH/AA and classic PNH. CONCLUSION: This study demonstrated that eculizumab is beneficial in the management of patients with PNH/AA, similar to classic PNH.
Anemia, Aplastic* ; Cohort Studies* ; Flow Cytometry ; Follow-Up Studies ; Hemoglobinuria, Paroxysmal* ; Hemolysis ; Humans ; Prospective Studies*

Mercury occurs in various chemical forms, and it is different to health effects according to chemical forms. In consideration of the point, the evaluation of the mercury exposure to human distinguished from occupational and environmental exposure. With strict to manage occupational exposure in factory, it is declined mercury intoxication cases by metallic and inorganic mercury inhalation to occupational exposure. It is increasing to importance in environmental exposure and public health. The focus on the health impact of exposure to mercury is more on chronic, low or moderate grade exposure—albeit a topic of great controversy—, not high concentration exposure by methylmercury, which caused Minamata disease. Recently, the issue of mercury toxicity according to the mercury exposure level, health effects as well as the determination of what mercury levels affect health are in the spotlight and under active discussion. Evaluating the health effects and Biomarker of mercury exposure and establishing diagnosis and treatment standards are very difficult. It can implement that evaluating mercury exposure level for diagnosis by a provocation test uses chelating agent and conducting to appropriate therapy according to the result. but, indications for the therapy of chelating agents with mercury exposure have not yet been fully established. The therapy to symptomatic patients with mercury poisoning is chelating agents, combination therapy with chelating agents, plasma exchange, hemodialysis, plasmapheresis. But the further evaluations are necessary for the effects and side effects with each therapy.
Chelating Agents ; Diagnosis* ; Environmental Exposure ; Humans ; Inhalation ; Mercury Poisoning ; Mercury Poisoning, Nervous System ; Occupational Exposure ; Plasma Exchange ; Plasmapheresis ; Public Health ; Renal Dialysis

BACKGROUND: The study aimed to investigate the influence of hyperglycemia on muscle quality in older men with type 2 diabetes. METHODS: This was a subsidiary study of the Korean Longitudinal Study of Health and Aging. Among 326 older men consenting to tests of body composition and muscle strength, 269 men were ultimately analyzed after the exclusion because of stroke (n=30) and uncertainty about the diagnosis of diabetes (n=27). Body composition was measured using dual-energy X-ray absorptiometry and computed tomography. Muscle strength for knee extension was measured using an isokinetic dynamometer. Muscle quality was assessed from the ratio of leg strength to the entire corresponding leg muscle mass. RESULTS: The muscle mass, strength, and quality in patients with type 2 diabetes did not differ significantly from controls. However, when patients with diabetes were subdivided according to their glycemic control status, patients with a glycosylated hemoglobin (HbA1c) level of ≥8.5% showed significantly decreased leg muscle quality by multivariate analysis (odds ratio, 4.510; P=0.045) after adjustment for age, body mass index, smoking amount, alcohol consumption, physical activity, and duration of diabetes. Physical performance status was also impaired in subjects with an HbA1c of ≥8.5%. CONCLUSION: Poor glycemic control in these older patients with diabetes was associated with significant risk of decreased muscle quality and performance status. Glycemic control with an HbA1c of <8.5% might be needed to reduce the risk of adverse skeletal and functional outcomes in this population.
Absorptiometry, Photon ; Aging* ; Alcohol Drinking ; Body Composition ; Body Mass Index ; Diabetes Mellitus, Type 2 ; Diagnosis ; Hemoglobin A, Glycosylated ; Humans ; Hyperglycemia* ; Knee ; Leg ; Longitudinal Studies* ; Male ; Motor Activity ; Multivariate Analysis ; Muscle Strength ; Muscle, Skeletal ; Sarcopenia ; Smoke ; Smoking ; Stroke ; Uncertainty

BACKGROUND/AIMS: The optimal timing for discontinuing oral antiviral therapy in patients with HBeAg-positive chronic hepatitis B (CHB) is unclear. The aim of our study was to investigate sustained remission after stopping antiviral therapy in patients with HBeAg-positive CHB. METHODS: We analyzed the medical records of 58 patients who were HBeAg-positive and had discontinued antiviral therapy. Antiviral therapy was discontinued after HBeAg seroconversion and HBV DNA negativity for 6-12 months with consolidation therapy. Virologic relapse was defined as an increase in serum HBV DNA >2,000 IU/mL. RESULTS: No difference was observed between the virologic non-relapse and virologic relapse groups in baseline HBV DNA level (p=0.441) or duration of seroconversion (p=0.070). Time-to-undetectable HBV DNA during treatment was shorter in the virologic non-relapse group (29 patients) compared to the relapse group (29 patients) (4.9+/-2.6 vs. 13.2+/-12.7 months; p<0.01). Cumulative relapse rates were 12.7 in month 3, 32.7 in month 6, 47.3 in month 12, and 52.7% in month 18. We determined by multivariate analysis that the consolidation period (> or =18 months, p=0.020) and early virologic response (HBV DNA <20 IU/mL) at six months during antiviral therapy (p=0.017) were significant predictors for sustained remission. CONCLUSIONS: A consolidation period of at least 18 months and early virological response at six months during antiviral therapy were associated with sustained remission in patients with HBeAg-positive CHB after treatment.
Adult ; Aged ; Antiviral Agents/*therapeutic use ; DNA, Viral/analysis ; Female ; Hepatitis B e Antigens/*blood ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/*drug therapy ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Withholding Treatment