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: We evaluated health-related quality of life (HRQOL) in long-term survivors of indolent and aggressive non-Hodgkin lymphoma (NHL). MATERIALS AND METHODS: TheHRQOLwas assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) at diagnosis in NHL patients between 2008 and 2011, and follow-up evaluation was conducted from June 2014 to February 2015 using EORTC QLQ-C30 and the quality of life in cancer survivors (QOL-CS) questionnaire. We used linear mixed models to compare changes in HRQOL between indolent and aggressive NHL over time. RESULTS: The HRQOL of long-term survivors with aggressive NHL improved to the similar level of indolent NHL during the follow-up survey. However, survivors of NHL were found to fear the probability of relapse and second malignancy, and the degree of fear was not different between survivors with aggressive stage I/II or III/IV NHL (p > 0.05). Furthermore, a half of survivors reported impaired sense of psychosocial well-being regardless of aggressiveness and stage during follow-up survey. More than 65% of survivors thought they did not receive sufficient support from others, and patients who had financial difficulties at diagnosis were more frequently associated with suffering from insufficient support. Impaired physical and cognitive functioning at diagnosis was significantly associated with lack of life purpose in long-term survivors. CONCLUSION: The HRQOL of aggressive NHL survivors improved to a similar level to that of indolent NHL. However, the majority of survivors still had fear of relapse, and psychosocial well-being remained unmet needs.
Cohort Studies* ; Diagnosis ; Follow-Up Studies ; Humans ; Lymphoma, Non-Hodgkin* ; Neoplasms, Second Primary ; Prospective Studies* ; Quality of Life* ; Recurrence ; Survivors*

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

PURPOSE: We investigated the prognostic factors for distant metastasis (DM) in patients with locally advanced oropharyngeal cancer (OPC) treated with surgery and adjuvant radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Eighty-five patients treated between January 1995 and August 2014 were evaluated retrospectively. Data regarding the pathological tumour and nodal status, human papillomavirus (HPV) status, treatment characteristics, and pretreatment maximum standardized uptake value (SUVmax) of 18-fluoro-2-deoxyglucose positron emission tomography–computed tomography scan (¹⁸F-FDG PET-CT) were evaluated, and their influence on DM and survival outcomes were analyzed. RESULTS: Median follow-up period was 48.0 months. Recurrence was observed in 20 patients, including locoregional recurrence and DM. DM was observed in 13 patients. A multivariate analysis confirmed that the presence of lymphovascular invasion (p=0.031), lower neck lymph node (LN) involvement (p=0.006), SUVmax ≥ 9.7 (p=0.014), and tumour size ≥ 3 cm (p=0.037) significantly affected DM. HPV status was not associated with DM. Perineural invasion (p=0.048), lower neck LNinvolvement (p=0.008), SUVmax ≥ 9.7 (p=0.019), and tumour size ≥ 3 cm (p=0.033) were also significant factors for the DM-free survival rate. CONCLUSION: Lower neck LN involvement, high SUVmax in pretreatment ¹⁸F-FDG PET-CT, and large tumour size were predictive factors for DM in patients of OPC.
Drug Therapy* ; Electrons ; Follow-Up Studies ; Humans ; Lymph Nodes ; Multivariate Analysis ; Neck ; Neoplasm Metastasis* ; Oropharyngeal Neoplasms* ; Radiotherapy* ; Radiotherapy, Adjuvant ; Recurrence ; Retrospective Studies ; Survival Rate

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

PURPOSE: There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. MATERIALS AND METHODS: We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m2 on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR). RESULTS: Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). CONCLUSION: Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.
Carboplatin* ; Dacarbazine* ; Disease Progression ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Melanoma* ; Neutropenia ; Paclitaxel ; Prognosis

BACKGROUND: A number of reports have been published regarding the use of imiquimod for the treatment of melanoma in situ and metastatic melanoma. Essential steps in the process of melanoma invasion and metastasis include degradation of basement membranes and remodeling of the extracellular matrix by proteolytic enzymes, including matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). OBJECTIVE: To evaluate the antiinvasive effect of imiquimod in human malignant melanoma cell lines, SK-MEL-2 and SK-MEL-24, in vitro, and to investigate imiquimod-induced changes in the expression of MMPs and TIMPs. METHODS: Invasiveness of melanoma cell lines following imiquimod treatment was evaluated by invasion assays. In order to investigate the mechanism of the anti-invasive effect of imiquimod, mRNA and protein levels of MMP-2, -9, membrane type 1 (MT1)-MMP, TIMP-1, and -2 were assessed by real-time reverse transcription-polymerase chain reaction, gelatin zymography, and western blotting. RESULTS: Imiquimod treatment decreased in vitro viability of melanoma cells in a concentration-dependent manner. Imiquimod also elicited a concentration-dependent suppression of invasion in both melanoma cell lines. A concentration-dependent decrease in MMP-2 and MT1-MMP protein levels and a concentration-dependent increase in TIMP-1 and -2 protein levels by imiquimod was observed in both melanoma cell lines. However, expression of MMP-9 protein was increased in SK-MEL-2 but decreased in SK-MEL-24 with increasing imiquimod concentrations. Imiquimod elicited alterations in MMPs and TIMPs mRNA levels that parallel the observed changes in protein levels. CONCLUSION: Imiquimod may elicit an anti-invasive effect on human melanoma cells by regulating MMPs and TIMPs.
Basement Membrane ; Blotting, Western ; Cell Line ; Extracellular Matrix ; Gelatin ; Humans ; Matrix Metalloproteinase 14 ; Matrix Metalloproteinases* ; Melanoma* ; Membranes ; Metalloproteases* ; Neoplasm Metastasis ; Peptide Hydrolases ; RNA, Messenger ; Tissue Inhibitor of Metalloproteinase-1

Primary biliary cirrhosis (PBC) is occasionally developed in patients with rheumatic diseases, such as systemic sclerosis or Sjogren's syndrome. However, there are a few reports of overlap syndrome with PBC. The authors report a case of a 36 year-old female with PBC and overlap syndrome. Systemic sclerosis was diagnosed in 2007, and rheumatoid arthritis in 2010. Adalimumab stopped because of her pregnancy plan in January 2012. One month after delivery, she felt increased hand joint pain and fatigue. Laboratory findings were as follows: elevated AST, ALT, ALP, r-GTP and positive anti-mitochondrial antibody. Histology of a liver biopsy revealed moderate porto-periportal and mild lobular inflammation with bile duct inflammation, which was consistent with PBC. She was treated with prednisolone and UDCA (urosodeoxycholic acid), but her disease was not controlled. From May 2013, she has been treated with adalimumab. Her arthritis was improved and liver function test normalized up until now.
Adalimumab ; Arthralgia ; Arthritis ; Arthritis, Rheumatoid ; Bile Ducts ; Biopsy ; Fatigue ; Female ; Glycogen Storage Disease Type VI ; Hand ; Humans ; Inflammation ; Liver ; Liver Cirrhosis, Biliary* ; Liver Function Tests ; Prednisolone ; Pregnancy ; Rheumatic Diseases ; Scleroderma, Systemic ; Sjogren's Syndrome

OBJECTIVE: To evaluate the effect of prophylactic therapy on gout flare during urate lowering treatment. METHODS: We retrospectively examined the data derived from 59 patients who had been treated with allopurinol for more than six months after stopping prophylactic medication at our rheumatology clinic. Demographic data (age, sex, disease duration, tophi and comorbidity), clinical and laboratory features, including presence of gout flare during urate lowering treatment, dose of allopurinol, serum uric acid level and creatinine clearance at initiation and six months later, were collected. For the subgroup analysis, the same data were collected in 46 patients who had been followed up at one year after stopping prophylactic medication. RESULTS: Twenty-eight patients among 59 (47.4%) had experienced at least 1 gouty attack during urate lowering therapy. The mean duration of prophylactic medication was not different between the flare group (3.8 months) and the non-flare group (5.9 months, p=0.617). Six months later, the mean serum uric acid level was 6.3 mg/dL (6.1 mg/dL vs. 6.5 mg/dL). According to the duration of prophylactic treatment (<6 months, > or =6 months), there were more frequent flares in the <6 months group than in the > or =6 months group (51.2% vs. 38.9% in the six month follow-up group, 70.6% vs. 50% in the one year follow-up group). CONCLUSION: Prophylactic medication for more than six months could be a favorable factor for the prevention of recurrent gout flare during urate lowering treatment.
Allopurinol ; Creatinine ; Follow-Up Studies ; Gout ; Humans ; Retrospective Studies ; Rheumatology ; Uric Acid