Background: We developed an assay to measure DNA-incorporated 6-thioguanine (DNATG) and validated its clinical applicability in Korean pediatric patients with acute lymphoblastic leukemia (ALL) in order to improve individualized thiopurine treatment and reduce the life-threatening cytotoxicity. Methods: The DNA-TG assay was developed based on liquid chromatography-tandem mass spectrometry, with isotope-labeled TG-d3 and guanine-d3 as internal standards.This method was applied to 257 samples of pediatric ALL patients. The DNA-TG level was compared with erythrocyte TG nucleotide (RBC-TGN) level in relation to the TPMT and NUDT15 genotypes, which affect thiopurine metabolism, using Spearman’s rank test and repeated measure ANOVA. Results: For DNA-TG quantification, a linearity range of 10.0-5,000.0 fmol TG/µg DNA;bias for accuracy of –10.4% –3.5%; coefficient of variation for intra- and inter-day precision of 3.4% and 5.8% at 80 fmol TG/µg DNA and of 4.9% and 5.3% at 800 fmol TG/µg DNA, respectively; and recovery of 85.7%–116.2% were achieved without matrix effects or carry-over. The median DNA-TG level in the 257 samples was 106.0 fmol TG/µg DNA (interquartile range, 75.8–150.9). There was a strong correlation between DNA-TG and RBC-TGN levels (ρ = 0.68,ρ < 0.0001). The DNA-TG/RBC-TGN ratio was significantly higher in NUDT15 intermediate metabolizers (*1/*2 and *1/*3) than in patients with wildtype alleles (ρ < 0.0001). Conclusions This simple and sensitive method for measuring DNA-TG level can improve therapeutic drug monitoring for thiopurine treatment.

Purpose: The purpose of this study was to identify the clinical utility of circulating tumor DNA (ctDNA) from ascites and serial plasma samples from epithelial ovarian cancer (EOC) patients. Materials and Methods: Using targeted next-generation sequencing, we analyzed a total of 55 EOC samples including ctDNA from ascites and serial plasma and gDNA from tumor tissues. Tumor tissues and ascites were collected during debulking surgeries and plasma samples were collected before and after the surgeries. Because one EOC patient underwent secondary debulking surgery, a total of 11 tumor tissues, 33 plasma samples, and 11 ascites samples were obtained from the 10 patients. Results: Of the 10 patients, nine (90%) contained somatic mutations in both tumor tissues and ascites ctDNA. This mutational concordance was confirmed through correlation analysis. The mutational concordance between ascites and tumor tissues was valid in recurrent/progressive ovarian cancer. TP53 was the most frequently detected gene with mutations. ctDNA from serial plasma samples identified EOC progression/recurrence at a similar time or even more rapidly than cancer antigen 125, an established serum protein tumor marker for EOC. Conclusion Our data suggest that ascites ctDNA can be used to identify the mutational landscape of ovarian cancer for therapeutic strategy planning.

Legionella species are abundant in the built environment and are increasingly recognized as a cause of Legionnaires' disease (LD). As the number of cases of Legionnaires' disease acquired by local communities in the Seoul metropolitan area in Korea has been increased, there was concern that changes in environmental factors could affect disease outbreaks. We described the association between climatic variables and occurrence of legionellosis in Korea and Legionella detection rate in Seoul area. A total of 418 cases of legionellosis were reported between 2014 and 2017. There was a seasonal peak in summer. LD continuously occurred from early spring to winter every year and rapidly increased in summer. In the regression analysis, the primary variables of interest- PM2.5 (µg/m³), NO₂ (ppb), and a number of the date of issue O₃ warning were not significant except for average temperature (R²=0.8075). The Legionella detection rate in Seoul, Korea showed a trend similar to precipitation (P=0.708, ANOVA). A relatively high proportion of Legionella detection rate was shown, especially cooling tower (17.7%) and public bath (19.3%). This finding is in line with current understanding of the ecological profile of this pathogen and supports the assertion that legionellosis occurs through contamination of water sources.
Baths ; Disease Outbreaks ; Epidemiology ; Korea ; Legionella ; Legionellosis ; Legionnaires' Disease ; Regression Analysis ; Seasons ; Seoul ; Water

PURPOSE: Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected. MATERIALS AND METHODS: In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions. RESULTS: Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. GNAQ/11 mutation showed 100% homogeneity in uveal melanoma patients. CONCLUSION: Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.
Cohort Studies ; Genetic Heterogeneity ; Genotype ; Humans ; Incidence ; Melanoma* ; Phenotype ; Population Characteristics* ; Prognosis

PURPOSE: Genexol-PM is a Cremophor EL–free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). MATERIALS AND METHODS: Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m² or Genexol 175 mg/m² intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). RESULTS: The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m² (95.0%), and that of Genexol was 168.3±10.6 mg/m² (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p(non-inferiority)=0.021, p(superiority)=0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. CONCLUSION: Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Neutropenia ; Paclitaxel* ; Peripheral Nervous System Diseases ; Polymers* ; Treatment Outcome

BACKGROUND: Lentigo maligna melanoma (LMM) is a subtype of melanoma that typically develops on sun-damaged skin. LMM is estimated to comprise 4~15% of melanomas, but the prevalence is known to be relatively lower in the Korean population than in the Caucasian population. OBJECTIVE: To review the clinico-pathologic features and treatment outcomes of Korean patients with LMM. METHODS: Nineteen patients diagnosed with LMM during 2003~2015, in the Yonsei University Health System, were included in this study. The age and sex of the patients, lesion location, thickness (Breslow), stage, treatment methods, BRAF, NRAS, and KIT mutation status, and survival rates were analyzed. RESULTS: Among the 19 Korean patients, 11 were male and 8 were female. The median age was 59.2 years. The most common site was the cheek (47.4%), followed by the scalp, eyelid, nose, forehead, lip, and neck. At the time of diagnosis, 13 patients were in localized stages (5 patients, stage 0; 3 patients, stage I; and 5 patients, stage II) and 6 patients were in advanced stages (3 patients, stage III; and 3 patients, stage IV). Patients in the localized stages showed better overall survival (OS) than those in the advanced stages (p=0.012). Nine patients were treated with a wide excision, and 6 using Mohs micrographic surgery. Three patients received high-dose interferon-α therapy; 6, chemotherapy; and 4, radiotherapy. Two patients in stage 0 were treated with topical ingenol mebutate. Two patients had BRAF V600E mutation; 1, NRAS G12R mutation; and 1, KIT mutation. Median OS of the patients was 40.8 months. CONCLUSION: Our analysis provides additional information about clinical characteristics, treatment, and prognosis of LMM in Korean patients.
Cheek ; Diagnosis ; Drug Therapy ; Eyelids ; Female ; Forehead ; Humans ; Hutchinson's Melanotic Freckle* ; Lentigo* ; Lip ; Male ; Melanoma* ; Mohs Surgery ; Neck ; Nose ; Prevalence ; Prognosis ; Radiotherapy ; Retrospective Studies* ; Scalp ; Skin ; Survival Rate

BACKGROUND: Genetic alterations have been identified in melanomas according to different levels of sun exposure. Whereas the conventional morphology-based classification provides a clue for tumor growth and prognosis, the new classification by genetic alterations offers a basis for targeted therapy. OBJECTIVE: The purpose of this study is to demonstrate the biological behavior of melanoma subtypes and compare the two classifications in the Korean population. METHODS: A retrospective chart review was performed on patients found to have malignant melanoma in Severance Hospital from 2005 to 2012. Age, sex, location of the tumor, histologic subtype, tumor depth, ulceration, lymph node invasion, visceral organ metastasis, and overall survival were evaluated. RESULTS: Of the 206 cases, the most common type was acral melanoma (n=94, 45.6%), followed by nonchronic sun damage-induced melanoma (n=43, 20.9%), and mucosal melanoma (n=40, 19.4%). Twenty-one patients (10.2%) had the chronic sun-damaged type, whereas eight patients (3.9%) had tumors of unknown primary origin. Lentigo maligna melanoma was newly classified as the chronic sun-damaged type, and acral lentiginous melanoma as the acral type. More than half of the superficial spreading melanomas were newly grouped as nonchronic sun-damaged melanomas, whereas nodular melanoma was rather evenly distributed. CONCLUSION: The distribution of melanomas was largely similar in both the morphology-based and sun exposure-based classifications, and in both classifications, mucosal melanoma had the worst 5-year survival owing to its tumor thickness and advanced stage at the time of diagnosis.
Classification ; Diagnosis ; Humans ; Hutchinson's Melanotic Freckle ; Lymph Nodes ; Melanoma* ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Solar System ; Ulcer

Skin neoplasms can result in large skin defects after surgical removal. Skin grafting has been used commonly to repair large defects, but it is associated with esthetic and functional problems. Herein, we report three cases with application of the keystone island flap in large skin defects of the trunk and extremities. A 53-year old male with recurred dermatofibrosarcoma protuberans on his thigh was repaired by the keystone island flap after Mohs micrographic surgery, and a 52-year old male with malignant melanoma on his back was successfully reconstructed by the keystone island flap after wide excision. Lastly, a 59-year old male diagnosed with dermatofibrosarcoma protuberans on the inguinal area was closed by the keystone island flap with commendable cosmetic outcome. Due to the ease of performance, excellent cosmetic and functional results, we recommend the keystone island flap for the reconstruction of large skin defects on the trunk and extremities.
Dermatofibrosarcoma ; Extremities ; Humans ; Male ; Melanoma ; Mohs Surgery ; Skin Neoplasms ; Skin Transplantation ; Skin* ; Thigh

PURPOSE: In this study, we attempted to analyze the effectiveness of the atopic dermatitis camp for primary school students in the Seoul area. METHODS: Seoul city's atopy camp 2010 was conducted 10 times from May 22nd to October 24th for primary school students at an atopy friendly school and their parents. A total of 374 atopic dermatitis patients participated in the camp and questionnaires for 363 were analyzed, except 11 participants who had left several questions unanswered. In a 3-month follow-up survey, 167 participants out of 374 responded to the mailing questionnaire to evaluate the efficiency of the camp. The response rate was 44.7%. RESULTS: Satisfaction with the educational program of the camp was higher for lower grade students than for higher grade students.(P<0.001) Before camp, higher grade students (P<0.001) or students with severe symptoms were more knowledgeable of atopic dermatitis.(P<0.01) After the camp, the higher the grade, the more the knowledge the student had about atopic dermatitis.(P<0.001) Three months after the camp, there was positive change in the lifestyle of atopic dermatitis patients.(P<0.001) CONCLUSION: Knowledge on atopic dermatitis increased and the lifestyle of atopic dermatitis patients was improved due to the camp. Consequently, Seoul city's atopy camp can be utilized as a method to improve the quality of life of atopic dermatitis patients and their family. And Seoul city's atopy camp is expected to be a model for atopy camps in other local communities.
Dermatitis, Atopic ; Follow-Up Studies ; Humans ; Life Style ; Parents ; Patient Education as Topic ; Postal Service ; Quality of Life ; Surveys and Questionnaires

As the usage of biologics for rheumatic diseases increases, such as rheumatoid arthritis and ankylosing spondylitis, various cutaneous adverse events are also being increasingly reported. We experienced a case of development of vitiligo during a TNF-alpha antagonist therapy in a 22-year-old woman with rheumatoid arthritis. The patient was presented with vitiligo lesions on the dorsum of both hands after 1 month of treatment with etanercept. Vitiligo improved with topical tacrolimus ointment and excimer laser treatment without the discontinuation of etanercept. No clearly defined mechanism for vitiligo induced by TNF-alpha antagonist exits. However, considering that vitiligo is an autoimmune disorder, the development of this skin lesion in association with the TNF-alpha antagonist could be explained by a paradoxical induction of the autoimmune process.
Arthritis, Rheumatoid ; Biological Agents ; Female ; Hand ; Humans ; Immunoglobulin G ; Lasers, Excimer ; Receptors, Tumor Necrosis Factor ; Rheumatic Diseases ; Skin ; Spondylitis, Ankylosing ; Tacrolimus ; Tumor Necrosis Factor-alpha ; Vitiligo ; Young Adult ; Etanercept