Background: s/Aims: The hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is classified as the advanced stage (BCLC stage C) with extremely poor prognosis, and in current guidelines is recommended for systemic therapy. This study aimed to evaluate the surgical outcomes and long-term prognosis after hepatic resection (HR) for patients who have HCC combined with PVTT. Methods: We retrospectively analyzed 332 patients who underwent HR for HCC with PVTT at ten tertiary referral hospitals in South Korea. Results: The median overall and recurrence-free survival after HR were 32.4 and 8.6 months, while the 1-, 3-, and 5-year overall survival rates were 75%, 48%, and 39%, respectively. In multivariate analysis, tumor number, tumor size, AFP, PIVKA−II, neutrophil-to-lymphocyte ratio, and albumin–bilirubin (ALBI) grade were significant prognostic factors. The risk scoring was developed using these seven factors–tumor, inflammation and hepatic function (TIF), to predict patient prognosis. The prognosis of the patients was well stratified according to the scores (log-rank test, p < 0.001). Conclusions HR for patients who have HCC combined with PVTT provided favorable survival outcomes. The risk scoring was useful in predicting prognosis, and determining the appropriate treatment strategy for those patients who have HCC with PVTT.

BACKGROUND: Bone marrow-derived mesenchymal stem cells (BMSCs) and bone morphogenetic protein-2 (BMP-2) have been studied for bone repair because they have regenerative potential to differentiate into osteoblasts. The development of injectable and in situ three-dimensional (3D) scaffolds to proliferate and differentiate BMSCs and deliver BMP-2 is a crucial technology in BMSC-based tissue engineering. METHODS: The proliferation of mouse BMSCs (mBMSCs) in collagen/poly-γ-glutamic acid (Col/γ-PGA) hydrogel was evaluated using LIVE/DEAD and acridine orange and propidium iodide assays. In vitro osteogenic differentiation and the gene expression level of Col/γ-PGA(mBMSC/BMP-2) were assessed by alizarin red S staining and quantitative reversetranscription polymerase chain reaction. The bone regeneration effect of Col/γ-PGA(mBMSC/BMP-2) was evaluated in a mouse calvarial bone defect model. The cranial bones of the mice were monitored by micro-computed tomography and histological analysis. RESULTS: The developed Col/γ-PGA hydrogel showed low viscosity below ambient temperature, while it provided a high elastic modulus and viscous modulus at body temperature. After gelation, the Col/γ-PGA hydrogel showed a 3D and interconnected porous structure, which helped the effective proliferation of BMSCs with BMP-2. The Col/γ-PGA (mBMSC/BMP-2) expressed more osteogenic genes and showed effective orthotopic bone formation in a mouse model with a critical-sized bone defect in only 3–4 weeks. CONCLUSION The Col/γ-PGA(mBMSC/BMP-2) hydrogel was suggested to be a promising platform by combining collagen as a major component of the extracellular matrix and γ-PGA as a viscosity reducer for easy handling at room temperature in BMSC-based bone tissue engineering scaffolds.

Background and Objectives: The aim of this study was to demonstrate the efficacy and safety of treatment with drug-coated balloon (DCB) in a large real-world population. Methods: Patients treated with DCBs were included in a multicenter observational registry that enrolled patients from 18 hospitals in Korea between January 2009 and December 2017. The primary outcome was target lesion failure (TLF) defined as a composite of cardiovascular death, target vessel myocardial infarction, and clinically indicated target lesion revascularization at 12 months. Results: The study included 2,509 patients with 2,666 DCB-treated coronary artery lesions (1,688 [63.3%] with in-stent restenosis [ISR] lesions vs. 978 [36.7%] with de novo lesions).The mean age with standard deviation was 65.7±11.3 years; 65.7% of the patients were men.At 12 months, the primary outcome, TLF, occurred in 179 (6.7%), 151 (8.9%), 28 (2.9%) patients among the total, ISR, and de novo lesion populations, respectively. A history of hypertension, diabetes, acute coronary syndrome, previous coronary artery bypass graft, reduced left ventricular ejection fraction, B2C lesion and ISR lesion were independent predictors of 12 months TLF in the overall study population. Conclusions This large multicenter DCB registry study revealed the favorable clinical outcome of DCB treatment in real-world practice in patient with ISR lesion as well as small de novo coronary lesion.

Purpose: To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). Materials and Methods: Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. Results: TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines Conclusion Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

BACKGROUND: Patients with acute myocardial infarction (AMI) have worse clinical outcomes than those with stable coronary artery disease despite revascularization. Non-culprit lesions of AMI also involve more adverse cardiovascular events. This study aimed to investigate the influence of AMI on endothelial function, neointimal progression, and inflammation in target and non-target vessels. METHODS: In castrated male pigs, AMI was induced by balloon occlusion and reperfusion into the left anterior descending artery (LAD). Everolimus-eluting stents (EES) were implanted in the LAD and left circumflex (LCX) artery 2 days after AMI induction. In the control group, EES were implanted in the LAD and LCX in a similar fashion without AMI induction. Endothelial function was assessed using acetylcholine infusion before enrollment, after the AMI or sham operation, and at 1 month follow-up. A histological examination was conducted 1 month after stenting. RESULTS: A total of 10 pigs implanted with 20 EES in the LAD and LCX were included. Significant paradoxical vasoconstriction was assessed after acetylcholine challenge in the AMI group compared with the control group. In the histologic analysis, the AMI group showed a larger neointimal area and larger area of stenosis than the control group after EES implantation. Peri-strut inflammation and fibrin formation were significant in the AMI group without differences in injury score. The non-target vessel of the AMI also showed similar findings to the target vessel compared with the control group. CONCLUSION: In the pig model, AMI events induced endothelial dysfunction, inflammation, and neointimal progression in the target and non-target vessels.
Acetylcholine ; Arteries ; Balloon Occlusion ; Constriction, Pathologic ; Coronary Artery Disease ; Drug-Eluting Stents ; Endothelium ; Fibrin ; Follow-Up Studies ; Humans ; Inflammation ; Male ; Myocardial Infarction ; Reperfusion ; Stents ; Swine ; Vasoconstriction

As industry develops in modern society, many chemicals are being used. The safety of chemicals is an important issue because humans are constantly exposed to chemicals throughout their daily life. Through a risk assessment, the hazardous human effects of chemicals can be identified. Recently, the adverse outcome pathway (AOP) framework has been used to predict the adverse effects of chemicals. As a conceptual framework for organizing existing biological knowledge, the AOP consists of a molecular initiating event, key events, and an adverse outcome. These independent elements represent biological responses and are connected by key event relationships. This AOP framework provides intuitive hazard identification that can be helpful for carcinogenic risk assessment of chemicals. In this review, we introduce the application of the AOP framework to risk assessment for predicting carcinogenicity of chemicals and illustrate the utility of this approach for cancer prevention.
Carcinogenesis ; Chemical Safety ; Humans ; Risk Assessment

This paper presents a case of an early malignant transformation of untreated ulcers in a patient with diabetes. This case shows that Marjolin's ulcer can occur not only after chronic injury, but can also develop in the early stages after the onset. Hence, an early biopsy for diabetic foot ulcers that fail to heal with acute treatment can enable an earlier diagnosis and treatment without amputation, resulting in a better quality of life for the patient.
Amputation ; Biopsy ; Diabetic Foot* ; Diagnosis ; Humans ; Quality of Life ; Ulcer*

Glycogen storage disease (GSD) IV is a rare autosomal recessive inherited disorder caused by mutations in the gene coding for glycogen branching enzyme leading to progressive liver disease. GSD IV is associated with mutations in GBE1, which encodes the glycogen branching enzyme. We report a case of GSD IV with rare homozygous mutations in the GBE1 gene (c.791G>A (p.Gly264Glu), which was successfully treated by liver transplantation.
1,4-alpha-Glucan Branching Enzyme* ; Clinical Coding ; Glycogen Storage Disease Type IV ; Glycogen Storage Disease* ; Glycogen* ; Liver Diseases ; Liver Transplantation

OBJECTIVES: This study was conducted to examine the effects of hormone therapy on serum lipid levels in postmenopausal Korean women. METHODS: This retrospective cohort study included 154 healthy postmenopausal Korean women. Seventy-nine women took oral estrogen (conjugated equine estrogen 0.625 mg/day or equivalent), and 75 applied estrogen transdermally using 0.1% 17beta-estradiol gel. Micronized progesterone (MP) was added to 40 women of oral group and 49 women in transdermal group. Serum levels of triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and lipoprotein (a) were measured before, 3 and 6 month after hormone therapy. RESULTS: At baseline, mean body mass index (BMI) were lower (22.76 vs. 23.74 kg/m2) and proportion of family history of cardiovascular disease (CVD) (61 vs. 39%) were higher in oral group. In oral group, LDL-C and lipoprotein(a) levels decreased, and triglyceride and HDL-C levels increased significantly after 3 and 6 months. There was no significant change in lipoprotein levels compared to the baseline in transdermal group. There were also no differences with additional MP. Changing pattern of HDL-C during 6 months was significantly different by the route of estrogen administration. CONCLUSION: Oral estrogen therapy might be more beneficial than transdermal estrogen in terms of lipid in postmenopausal Korean women. The estrogen effects are not influenced by adding MP.
Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Cohort Studies ; Drug Administration Routes ; Estrogens ; Female ; Hormone Replacement Therapy ; Humans ; Lipoprotein(a) ; Lipoproteins ; Progesterone ; Retrospective Studies ; Triglycerides

Microscopic anthracotic pigment (MAP) is frequently observed in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen in non-small cell lung cancer, but its clinical interpretation is not well-known. The aim of this study was to evaluate the clinical implication of MAP in mediastinal staging of non-small cell lung cancer. From May 2010 to July 2011, consecutive potentially operable non-small cell lung cancer patients who underwent EBUS-TBNA for mediastinal staging were recruited. Of the total 133 patients, 102 (76.7%) were male patients. Median age was 68 yr. Total 279 mediastinal lymph nodes were sampled by EBUS-TBNA; station 4R (100, 35.8%) and station 7 (86, 30.8%) were the most common sites. Malignant lymph nodes were 100 (35.8%). MAP was observed in 61 (21.7%) lymph nodes, and among them only 3 were malignant lymph nodes (P < 0.001). The lymph nodes with MAP were smaller (9.0 vs 10.8 mm, P = 0.001) and showed low standard uptake values on FDG-PET (4.4 vs 4.7, P = 0.256). In multivariate analysis, MAP was negatively associated with malignant lymph node (adjusted OR, 0.12; 95% CI, 0.03-0.42; P < 0.001). In potentially operable non-small cell lung cancer patients, MAP in endobronchial ultrasound-guided transbronchial needle aspiration specimens is strongly associated with benign mediastinal and hilar lymph nodes.
Adult ; Aged ; Aged, 80 and over ; Bronchoscopy ; Carbon/chemistry ; Carcinoma, Non-Small-Cell Lung/*pathology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Lung Neoplasms/*pathology ; Lymph Nodes/pathology ; Lymphatic Metastasis ; Male ; Mediastinal Neoplasms/*pathology ; Middle Aged ; Multivariate Analysis ; Neoplasm Staging ; Positron-Emission Tomography