BACKGROUND/AIMS: Colorectal cancer is associated with different anatomical, biological, and clinical characteristics. We determined the impact of the primary tumor location in patients with metastatic colorectal cancer (mCRC). METHODS: Demographic data and clinical information were collected from 1,115 patients from the Republic of Korea, who presented with mCRC between January 2009 and December 2011, using web-based electronic case report forms. Associations between the primary tumor location and the patient's clinical characteristics were assessed, and factors inf luencing overall survival were analyzed using Cox proportional hazards regression models. RESULTS: Of the 1,115 patients recruited to the study, 244 (21.9%) had right colon cancer, 483 (43.3%) had left colon cancer, and 388 (34.8%) had rectal cancer. Liver and lung metastases occurred more frequently in patients with left colon and rectal cancer (p = 0.005 and p = 0.006, respectively), while peritoneal and ovarian metastases occurred more frequently in patients with right and left colon cancer (p < 0.001 and p = 0.031, respectively). The median overall survival of patients with tumors originating in the right colon was significantly shorter than that of patients whose tumors had originated in the left colon or rectum (13.7 months [95% confidence interval (CI), 12.0 to 15.5] vs. 18.0 months [95% CI, 16.3 to 19.7] or 19.9 months [95% CI, 18.5 to 21.3], respectively; p = 0.003). Tumor resection, the number of metastatic sites, and primary tumor location correlated with overall survival in the univariate and multivariate analyses. CONCLUSIONS: Primary tumor location influences the metastatic sites and prognosis of patients with mCRC.
Colon ; Colonic Neoplasms ; Colorectal Neoplasms* ; Humans ; Liver ; Lung ; Multivariate Analysis ; Neoplasm Metastasis ; Prognosis ; Rectal Neoplasms ; Rectum ; Republic of Korea

BACKGROUND: The skin consists of tightly connected keratinocytes, and prevents extensive water loss while simultaneously protecting against the entry of microbial pathogens. Excessive cellular levels of reactive oxygen species can induce cell apoptosis and also damage skin integrity. Propofol (2,6-diisopropylphenol) has antioxidant properties. In this study, we investigated how propofol influences intracellular autophagy and apoptotic cell death induced by oxidative stress in human keratinocytes. METHOD: The following groups were used for experimentation: control, cells were incubated under normoxia (5% CO₂, 21% O₂, and 74% N₂) without propofol; hydrogen peroxide (H₂O₂), cells were exposed to H₂O₂ (300 µM) for 2 h; propofol preconditioning (PPC)/H₂O₂, cells pretreated with propofol (100 µM) for 2 h were exposed to H₂O₂; and 3-methyladenine (3-MA)/PPC/H₂O₂, cells pretreated with 3-MA (1 mM) for 1 h and propofol were exposed to H₂O₂. Cell viability, apoptosis, and migration capability were evaluated. Relation to autophagy was detected by western blot analysis. RESULTS: Cell viability decreased significantly in the H₂O₂ group compared to that in the control group and was improved by propofol preconditioning. Propofol preconditioning effectively decreased H₂O₂-induced cell apoptosis and increased cell migration. However, pretreatment with 3-MA inhibited the protective effect of propofol on cell apoptosis. Autophagy was activated in the PPC/H₂O₂ group compared to that in the H₂O₂ group as demonstrated by western blot analysis and autophagosome staining. CONCLUSION: The results suggest that propofol preconditioning induces an endogenous cellular protective effect in human keratinocytes against oxidative stress through the activation of signaling pathways related to autophagy.
Apoptosis ; Autophagy* ; Blotting, Western ; Cell Death ; Cell Movement ; Cell Survival ; Humans* ; Hydrogen Peroxide ; Keratinocytes* ; Methods ; Oxidative Stress* ; Propofol* ; Reactive Oxygen Species ; Skin ; Water

BACKGROUND: The shortage of human hearts for allotransplantation makes xenotransplantation a possible option for controllable organ providers. To detect acute xenograft rejection, invasive biopsy seems inevitable; however, this occasionally results in poor incision wound healing or infection. To date, no method of noninvasive imaging for early detection of xenograft rejection has been established. We hypothesized that ultrasound speckle tracking would better detect xenograft failure than routine left ventricular ejection fractions (EF). METHODS: From August 2013 to July 2015, a total of six cardiac heterotopic xenotransplants (α 1, 3-galactosyltransferase gene-knockout porcine heart) into cynomolgus monkeys were monitored with echocardiography every 3 to 7 days. M-mode and two-dimensional (2D)-EF measurements and myocardial strain analyses were performed. Cardiac xenograft pathology was reviewed from the immediate postoperative biopsy, as well as the necropsy. RESULTS: Myocardial speckle tracking analysis was feasible in all six cases. The longest survival was 43 days. Only one pathology-proven immunologic rejection occurred. Cardiac xenograft failure appeared as two types: a dilated pattern with decreased EF or a myocardial-thickening pattern with preserved EF. Both antibody-mediated rejection (n=1) and sepsis-induced myocardial dysfunction (n=2) revealed decreased radial or circumferential strains, but normal-range EF. Xenograft functional decline was significant with respect to radial or circumferential strain (P=0.028), but not to conventional M-mode or 2D-EFs (P=0.600, P=0.340, respectively). CONCLUSIONS: Radial and circumferential strains were significantly decreased in both types of xenograft failure, regardless of EF. Further studies are warranted to correlate the strain analysis and immunopathological details.
Biopsy ; Echocardiography ; Heart ; Heart Transplantation ; Heterografts ; Humans ; Macaca fascicularis ; Methods ; Pathology ; Stroke Volume ; Transplantation, Heterologous* ; Transplants* ; Ultrasonography ; Wound Healing

BACKGROUND: Oxidative stress occurs during the aging process and other conditions such as bone fracture, bone diseases, and osteoporosis, but the role of oxidative stress in bone remodeling is unknown. Propofol exerts antioxidant effects, but the mechanisms of propofol preconditioning on oxidative stress have not been fully explained. Therefore, the aim of this study was to evaluate the protective effects of propofol against H2O2-induced oxidative stress on a human fetal osteoblast (hFOB) cell line via activation of autophagy. METHODS: Cells were randomly divided into the following groups: control cells were incubated in normoxia (5% CO2, 21% O2, and 74% N2) without propofol. Hydrogen peroxide (H2O2) group cells were exposed to H2O2 (200 µM) for 2 h, propofol preconditioning (PPC)/H2O2 group cells were pretreated with propofol then exposed to H2O2, 3-methyladenine (3-MA)/PPC/H2O2 cells were pretreated with 3-MA (1 mM) and propofol, then were exposed to H2O2. Cell viability and apoptosis were evaluated. Osteoblast maturation was determined by assaying bone nodular mineralization. Expression levels of bone related proteins were determined by western blot. RESULTS: Cell viability and bone nodular mineralization were decreased significantly by H2O2, and this effect was rescued by propofol preconditioning. Propofol preconditioning effectively decreased H2O2-induced hFOB cell apoptosis. However, pretreatment with 3-MA inhibited the protective effect of propofol. In western blot analysis, propofol preconditioning increased protein levels of collagen type I, BMP-2, osterix, and TGF-β1. CONCLUSIONS: This study suggests that propofol preconditioning has a protective effect on H2O2-induced hFOB cell death, which is mediated by autophagy activation.
Aging ; Antioxidants ; Apoptosis ; Autophagy* ; Blotting, Western ; Bone Diseases ; Bone Remodeling ; Cell Death ; Cell Line ; Cell Survival ; Collagen Type I ; Fractures, Bone ; Humans* ; Hydrogen Peroxide ; Miners ; Osteoblasts* ; Osteoporosis ; Oxidative Stress* ; Propofol

The aim of this study was to determine the beneficial effect of propofol on human keratinocytes that have undergone hypoxia reoxygenation (H/R) injury and to investigate whether autophagy is associated with the protective mechanism. Thus, we evaluated how propofol influences the intracellular autophagy and apoptosis during the H/R process in the HaCaT cells. The cultured human keratinocyte cells were exposed to 24 h of hypoxia (5% CO2, 1% O2, 94% N2) followed by 12 h of reoxygenation (5% CO2, 21% O2, 74% N2). The experiment was divided into 4 groups: (1) Control=Normoxia ; (2) H/R=Hypoxia Reoxygenation ; (3) PPC+H/R=Propofol Preconditioning+Hypoxia Reoxygenation; (4) 3-MA+PPC+H/R=3-MA-Methyladenine+Propofol Preconditioning+Hypoxia Reoxygenation. In addition, Western blot analysis was performed to identify the expression of apoptotic pathway parameters, including Bcl-2, Bax, and caspase 3 involved in mitochondrial-dependent pathway. Autophagy was determined by fluorescence microscopy, MDC staining, AO staining, and western blot. The H/R produced dramatic injuries in keratinocyte cells. In our study, the viability of Propofol in H/R induced HaCaT cells was first studied by MTT assay. The treatment with 25, 50, and 100 microM Propofol in H/R induced HaCaT cells enhanced cell viability in a dose-dependent manner and 100 microM was the most effective dose. The Atg5, Becline-1, LC3-II, and p62 were elevated in PPC group cells, but H/R-induced group showed significant reduction in HaCaT cells. The Atg5 were increased when autophagy was induced by Propofol, and they were decreased when autophagy was suppressed by 3-MA. These data provided evidence that propofol preconditioning induced autophagy and reduced apoptotic cell death in an H/R model of HaCaT cells, which was in agreement with autophagy playing a very important role in cell protection.
Anoxia ; Apoptosis ; Autophagy ; Blotting, Western ; Caspase 3 ; Cell Death ; Cell Survival ; Cytoprotection ; Humans ; Keratinocytes* ; Microscopy, Fluorescence ; Propofol*

BACKGROUND/AIMS: Providers may be hesitant to perform double-balloon enteroscopy (DBE) in the elderly because the increased number of co-morbidities in this population poses a greater risk of complications resulting from sedation. There are limited data on the use of DBE in the elderly. Here, we assessed the safety and efficacy of DBE in the elderly compared to those in younger patients. METHODS: We retrospectively analyzed the medical records of 158 patients who underwent 218 DBEs. Patients were divided into an elderly group (age > or =65 years; mean 71.4+/-5.4; n=34; 41 DBEs) and a younger group (age <65 years; mean 39.5+/-13.5; n=124; 177 DBEs). RESULTS: In both groups, the most common indication for DBE was obscure gastrointestinal bleeding. Mucosal lesions (33.3% vs. 60.9%; P=0.002) were the most common finding in both groups, followed by tumors (30.8% vs. 14.1%; P=0.036). The elderly were more likely to receive interventional therapy (51.3% vs. 23.5%; P=0.001). The diagnostic yield of DBE was slightly higher in the elderly group (92.3% vs. 86.5%; P=0.422), but was not statistically significant. The therapeutic success rate of DBE was 100% in the elderly group compared to 87.5% in the younger group (P=0.536). The overall DBE complication rate was 1.8% overall, and this rate did not differ significantly between the groups (2.6% vs. 1.7%; P=0.548). CONCLUSIONS: DBE is safe and effective in the elderly, and has a high diagnostic yield and high therapeutic success rate.
Aged* ; Double-Balloon Enteroscopy* ; Hemorrhage ; Humans ; Medical Records ; Retrospective Studies

Death by drowning is one of the most common cause of death worldwide, and the diagnosis of fatal drowning through postmortem examination is not always confirmative. Although many autopsy findings of drowning have been described so far, all these macroscopical signs are non-specific and moreover disappear quite rapidly in the process of decomposition. The combination of autopsy findings and diatom test can provide useful indication for the tentative diagnosis of drowning, but the value of the diatom analysis is still argued. The aim of the present study is to investigate the diagnostic usefulness of diatom test for the drowning death in Korea. The authors reviewed the result of 87 cases of diatom test in the autopsy file and analyzed it by parameters of the common diatom species, monthly frequency, the difference between sea and land water, and the correlation between the test result and the decision of cause of death. The result revealed no definite seasonal variation of diatom detection or no species difference between sea water cases and fresh water cases. The detection rate of diatoms in systemic organs of all cases was 11.49% and that of drowning cases was 9.43%.
Autopsy ; Cause of Death ; Diatoms ; Drowning ; Fresh Water ; Korea ; Seasons ; Seawater ; Water

This report deals with the acute onset of an abortion outbreak and high sow mortality in one pig herd consisted of 1,200 pigs and 120 sows on Jeju Island, Korea. Affected pregnant sows showed clinical signs, including high fever, gradual anorexia, vomiting, depression, recumbency, prostration, abortion, and a few deaths. Four dead sows, five aborted fetuses from the same litter, and 17 sera collected from sows infected or normal were submitted to the Pathology Division of the National Veterinary Research and Quarantine Service for diagnostic investigation. Grossly, hepatomegaly and splenomegaly were observed in sows. Multiple necrotic foci were scattered in the lungs, liver, spleen, and lymph nodes. Microscopically, multifocal necrotizing lesions and protozoan tachyzoites were present in the lesions. Tachyzoites of Toxoplasma (T.) gondii were detected immunohistochemically. Latex agglutination showed that the sera of 7 of 17 (41.2%) sows were positive for antibody to T. gondii. The disease outbreak in this herd was diagnosed as epizootic toxoplasmosis. To our knowledge, this is the first report of porcine toxoplasmosis with a high abortion rate and sow mortality in Korea.
Aborted Fetus ; Abortion, Veterinary/blood/epidemiology/*parasitology/pathology ; Animals ; Antibodies, Protozoan/blood ; Disease Outbreaks/*veterinary ; Female ; Hepatomegaly/parasitology/veterinary ; Immunohistochemistry/veterinary ; Korea/epidemiology ; Latex Fixation Tests/veterinary ; Pregnancy ; Splenomegaly/parasitology/veterinary ; Swine ; Swine Diseases/blood/epidemiology/*parasitology/pathology ; Toxoplasma/*isolation & purification ; Toxoplasmosis, Animal/blood/epidemiology/parasitology/*pathology

BACKGROUND: As the wound healing is a multi-factorial process, the anesthetic agent and the duration of its exposure may influence the healing process after surgery. This study investigated the effect of anesthetic agents and duration of its exposure on the wound healing process after operation. METHODS: Total 32 rats weighing 200-300 g were randomly allocated to one of eight groups according to the exposure time (1, 2, 4, 8 hours) of sevoflurane or propofol (n = 4 each). After wounding under the each anesthetic, anesthesia was maintained for 1, 2, 4 and 8 hours in each group. We compared the skin blood flow around the wound and the wound size at baseline, 3 days, and 7 days postoperatively. RESULTS: In sevoflurane group, short exposure group (1, 2 hours) showed higher wound blood flow than long exposure (4, 8 hours) at 3 days after wounding (P < 0.05), but not at 7 days after wounding. For the wound size, there was no difference at 3 days after wounding in sevoflurane group, but 8 hours exposure group had the largest wound at 7 days after wounding. In propofol group, wound blood flow showed no difference at 3 days after wounding, but that of 4, 8 hours exposure group was higher than 2 hours exposure group at 7 days after wounding. There was no difference in wound size in propofol group. CONCLUSIONS: This study implicates that sevoflurane might influence the wound healing process more prominently than propofol according to the duration of exposure time.
Anesthesia ; Anesthetics ; Animals ; Methyl Ethers ; Propofol ; Rats ; Skin ; Wound Healing

BACKGROUND AND OBJECTIVES: The traditional indexes of heart rate (HR) variability may lack the ability to detect subtle, but important changes in HR behavior. Nonlinear heart rate variability (HRV) analysis methods that are based on chaos theory can reveal subtle abnormalities in the HR dynamics of patients with cardiovascular diseases. Therefore, we tested the validity of nonlinear analysis methods as markers to differentiate normal and abnormal HR dynamics in the cardiovascular disease state. SUBJECTS AND METHODS: One-hundred patients were studied: 70 patients with left ventricular dysfunction (LVD), including 40 post-myocardial infarct patients (PMI) and 30 dilated cardiomyopahty patients (DCM), and 30 age and gender-matched controls. One-hour, 6-hours (day and night each) and 24 hours of R-R interval data from 24-hour Holter recordings were subjected to the conventional time and frequency-domain analysis. The ApEn, short-term (alpha1) and long-term (alpha2) scaling exponents of the detrended fluctuation analysis (DFA) and the power-law exponent (beta) were also measured. RESULTS: Conventional linear measures did not show a significant difference except for the VLF, lnLF and the LF/HF ratio between the controls and the LVD patients. Among the analyzed parameters, beta, beta2 and alpha1 were the most powerful discriminators. The beta of the normal and LVD patients was -1.10+/-0.29 and -0.70+/-0.40, respectively (p<0.001), and the alpha1 was 1.08+/-0.23 and 0.81+/-0.28, respectively (p<0.001). The beta, beta2 and alpha1 can discriminate the etiologic cause of LVD. The length of the R-R interval data did not affect the result, and a significant correlation was observed. The individual values of the fractal and complexity measures were more stable than those of the conventional linear measures. CONCLUSION: We conclude that the measures derived from fractal and complexity methods are useful for detecting altered HR dynamics of LVD and for improving the shortcomings of the conventional measures.
Cardiovascular Diseases ; Fractals* ; Heart Rate* ; Heart* ; Humans ; Nonlinear Dynamics ; Risk Assessment ; Ventricular Dysfunction, Left*