Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Selective cannulation during endoscopic retrograde cholangiopancreatography can be particularly challenging when the papilla is invisible, either due to an intradiverticular papilla (IDP) or because it is covered by a mucosal fold. Endoclipassisted cannulation is an effective and safe technique for everting and fixing the papilla and it can be used alone or in combination with other devices. In this report, we achieved successful papillary cannulation in two cases of IDP and one case where the papilla was covered by a mucosal fold. In two cases, cannulation was accomplished by repositioning the invisible papilla using an endoclip alone, while in one case, we used an endoclip-assisted technique to push a redundant fold with a catheter. Endoclipassisted papillary cannulation can be applied in different situations, either alone or in combination with other devices.

Background: Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. Methods: Clinical parameters and postpartum complications were reviewed in all participants.Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4 + T, CD8 + T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. Results: Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4 + T and CD8 + T cells than the control group. Interestingly, senescent CD4 + T cells tended to increase and CD8 + T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274 + ) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. Conclusion This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

Purpose: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. Materials and Methods: To address such challenges, we have developed a glioma-specific NGS panel, termed “GliomaSCAN,” that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. Results: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. Conclusion We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

PURPOSE: This randomized phase III study was designed to compare the efficacy and safety of irinotecan plus cisplatin (IP) over etoposide plus cisplatin (EP) in Korean patients with extensive-disease small-cell lung cancer (SCLC). MATERIALS AND METHODS: Patients were randomly assigned to receive IP, composed of irinotecan 65 mg/m2 intravenously on days 1 and 8+cisplatin 70 mg/m2 intravenously on day 1 every 3 weeks, or EP, composed of etoposide 100 mg/m2 intravenously on days 1, 2, 3+cisplatin 70 mg/m2 intravenously on day 1, every 3 weeks for a maximum of six cycles, until disease progression, or until unacceptable toxicity occurred. The primary endpoint was overall survival. RESULTS: A total of 362 patients were randomized to IP (n=173) and EP (n=189) arms. There were no significant differences between IP and EP arms for the median overall survival (10.9 months vs. 10.3 months, p=0.120) and the median progression-free survival (6.5 months vs. 5.8 months, p=0.115). However, there was a significant difference in response rate (62.4% vs. 48.2%, p=0.006). The pre-planned subgroup analyses showed that IP was associated with longer overall survival in male (11.3 months vs. 10.1 months, p=0.036), < 65 years old (12.7 months vs. 11.3 months, p=0.024), and Eastern Cooperative Oncology Group performance status 0/1 (12.4 months vs. 10.9 months, p=0.040) patient groups. The severity of treatment-related adverse events such as grade 3/4 anemia, nausea and diarrhea was more frequent in patients treated with IP. CONCLUSION: The IP chemotherapy did not significantly improve the survival compared with EP chemotherapy in Korean patients with extensive-disease SCLC.
Anemia ; Arm ; Cisplatin* ; Diarrhea ; Disease Progression ; Disease-Free Survival ; Drug Therapy ; Etoposide* ; Humans ; Lung Neoplasms ; Male ; Nausea ; Small Cell Lung Carcinoma*

PURPOSE: In the present study, factors related to the recurrence of breast ductal carcinoma in situ (DCIS) in Korean patients were identified, and the prognostic factors for each age group were explored.METHODS: The subjects were 226 patients who were diagnosed with DCIS by histopathologic examination, and the effect of representative prognostic factors that are known already, including estrogen receptor (ER), progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) status, Ki-67 levels, and adjuvant therapy on the recurrence of DCIS was analyzed by using the Cox proportional hazard model.RESULTS: Among the 226 subjects, 11 patients underwent the recurrence of breast cancer. The average follow-up period was 52.7±23.5 months. The average age of the subjects was 50.6±9.3 years. Among the DCIS patients, the recurrence of breast cancer was significantly higher in the ER negative patients and those who have a Ki-67 level over 20%. However, the PR and HER2 status did not significantly affect breast cancer recurrence. The result also showed that only ER negative was a significant factor before the age of 50 years and that only the Ki-67 level over 20% was a significant factor to the patients 50 years of age or older.CONCLUSION: DCIS patients should be appropriately treated and managed depending on their age and clinicopathological factors to prevent the recurrence of DCIS.
Breast Neoplasms ; Breast ; Carcinoma, Ductal ; Carcinoma, Intraductal, Noninfiltrating ; Estrogens ; Follow-Up Studies ; Humans ; Proportional Hazards Models ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Recurrence

PURPOSE: In Korea, the incidence of breast cancer peaks in the fifth decade, which is younger than that observed in the Western world. We conducted this study to compare the clinical characteristics and prognostic factors of breast cancer in women < 35 and ≥35 years old.METHODS: The medical records of 969 patients treated for breast cancer at the Gil Medical Center from 2008 through 2012 were reviewed. Tumor characteristics, surgical methods, and adjuvant therapies were compared in two groups.RESULTS: Number of childbirths, family history, the proportion of postmenopausal women were lower among those aged < 35 years. However, tumor size, number of metastatic lymph nodes, and surgical procedures were similar in two groups. The rate of triple negative status in younger patients was higher than in older patients. Adjuvant chemotherapy was effective in patients positive for hormone receptors and no lymph nodal invasion, and it was effective in patients negative for hormone receptors and lymph nodal invasion in patients aged >35 years old. Postoperative radiotherapy was statistically effective in patients aged < 35 and ≥35 years old that underwent breast-conserving surgery. Pregnancy were significantly associated with survival in younger patients. While lymph node stage, presence of progesterone receptor, and triple negative status were significantly associated with survival on older patients.CONCLUSION: The prognostic factors of breast cancer in patients younger than 35 years old were pregnancy. Triple negative status rate was higher in younger patients than in older patients. Adjuvant therapy had similar effects in patients aged < 35 or ≥35 years old.
Breast Neoplasms ; Breast ; Chemotherapy, Adjuvant ; Female ; Humans ; Incidence ; Korea ; Lymph Nodes ; Mastectomy, Segmental ; Medical Records ; Parturition ; Pregnancy ; Prognosis ; Radiotherapy ; Receptors, Progesterone ; Western World ; Young Adult

BACKGROUND/AIMS: This study analyzed the diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for pancreatic solid masses in patients with or without chronic pancreatitis as well as the clinical parameters relevant to a malignancy when EUS-FNA was negative or inconclusive. METHODS: A total of 97 patients, who underwent EUS-FNA for solid pancreatic masses over 2 years at a single institution, were evaluated. All patients underwent EUS-FNA for 3-5 passes with 22 or 25 G needles without an on-site cytopathologist. The final diagnosis was obtained by surgery or compatible clinical outcomes for a more than 12 month follow-up. The diagnostic yields in the patients with or without chronic pancreatitis were compared and the histories and laboratory data relevant to pancreatic ductal adenocarcinoma (PDAC) or pseudo-tumor were analyzed. RESULTS: The final diagnoses were adenocarcinoma in 88 patients (90.7%) and inflammatory pseudo-tumor in 9 (9.3%). The results of EUS-FNA were adenocarcinoma (74), suspicious (7), atypical (5), negative (10), and inadequate specimen (1). The diagnostic accuracies were 76.9% and 91.6% in patients with or without chronic pancreatitis, respectively. Among the 23 cases with non-diagnostic results of EUS-FNA, PDAC was finally diagnosed in 5 out of 7 suspicious, 3 out of 5 atypical, and 5 out of 10 negative cytology cases. The clinical parameters related to a pseudo-tumor were a history of alcohol consumption and pancreatitis, and normal alkaline phosphatase levels. CONCLUSIONS: The diagnostic accuracy of pancreatic masses in the background of chronic pancreatitis was low. When EUS-FNA produced inconclusive results, the histories of alcohol consumption, pancreatitis, and serum levels of alkaline phosphatase are useful for making a final diagnosis.
Adenocarcinoma ; Alcohol Drinking ; Alkaline Phosphatase ; Biopsy, Fine-Needle* ; Diagnosis ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Endosonography ; Follow-Up Studies ; Humans ; Needles ; Pancreatic Ducts ; Pancreatic Neoplasms ; Pancreatitis ; Pancreatitis, Chronic

PURPOSE: Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. MATERIALS AND METHODS: Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. RESULTS: In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). CONCLUSION: Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.
Aspartate Aminotransferases ; Biliary Tract Neoplasms ; Biliary Tract* ; Bilirubin ; Carcinoembryonic Antigen ; Drug Therapy* ; Humans ; Leukocytes ; Methods ; Propensity Score* ; Retrospective Studies ; Sample Size ; Survival Analysis

BACKGROUND/AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and brushing cytology are used worldwide to diagnose pancreatic and biliary malignant tumors. Liquid-based cytology (LBC) has been developed and it is currently used to overcome the limitations of conventional smears (CS). In this study, the authors aimed to compare the diagnostic value of the CellPrepPlus (CP; Biodyne) LBC method with CS in samples obtained using EUS-FNA and brushing cytology. METHODS: This study prospectively enrolled 75 patients with pancreatic or biliary lesions from June 2012 to October 2013. For cytological analyses, including inadequate specimens, benign and atypical were further classified into benign, and suspicious and malignant were subcategorized as malignant. Sensitivity, specificity, accuracy, and positive predictive values (PPV) and negative predictive values (NPV) were evaluated. RESULTS: In the EUS-FNA based cytological analysis of pancreatic specimens, CP had a sensitivity of 60.7%; specificity, 100%; accuracy, 77.1%; PPV, 100%; and NPV, 64.5%. CS had a sensitivity of 85.7%; specificity, 100%; accuracy, 91.7%; PPV, 100%; and NPV, 83.3%. In the brushing cytology based analysis of biliary specimens, CP had sensitivity of 53.1%; specificity, 100%; accuracy, 54.5%; PPV, 100%; and NPV, 6.3%. CS had a sensitivity of 78.1%; specificity, 100%; accuracy, 78.8%; PPV, 100%; and NPV, 12.5%. CONCLUSIONS: Our study found that CP had a lower sensitivity because of low cellularity compared with CS. Therefore, CP (LBC) has a lower diagnostic accuracy for pancreatic EUS-FNA based and biliary brush cytology based analyses compared with CS.
Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Humans ; Methods ; Prospective Studies ; Sensitivity and Specificity