Background/Aims: Several prediction models for evaluating the prognosis of nonmetastatic resected pancreatic ductal adenocarcinoma (PDAC) have been developed, and their performances were reported to be superior to that of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. We developed a prediction model to evaluate the prognosis of resected PDAC and externally validated it with data from a nationwide Korean database. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) database were utilized for model development, and data from the Korea Tumor Registry System-Biliary Pancreas (KOTUS-BP) database were used for external validation. Potential candidate variables for model development were age, sex, histologic differentiation, tumor location, adjuvant chemotherapy, and the AJCC 8th staging system T and N stages. For external validation, the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (AUC) were evaluated. Results: Between 2004 and 2016, data from 9,624 patients were utilized for model development, and data from 3,282 patients were used for external validation. In the multivariate Cox proportional hazard model, age, sex, tumor location, T and N stages, histologic differentiation, and adjuvant chemotherapy were independent prognostic factors for resected PDAC. After an exhaustive search and 10-fold cross validation, the best model was finally developed, which included all prognostic variables. The C-index, 1-year, 2-year, 3-year, and 5-year time-dependent AUCs were 0.628, 0.650, 0.665, 0.675, and 0.686, respectively. Conclusions The survival prediction model for resected PDAC could provide quantitative survival probabilities with reliable performance. External validation studies with other nationwide databases are needed to evaluate the performance of this model.

BACKGROUND: Many epidemiologic studies have reported on the controversial concept of the obesity paradox. The presence of acute kidney injury (AKI) can accelerate energy-consuming processes, particularly in patients requiring continuous renal replacement therapy (CRRT). Thus, we aimed to investigate whether obesity can provide a survival benefit in this highly catabolic condition. METHODS: We conducted an observational study in 212 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. The study end point was defined as death that occurred within 30 days after the initiation of CRRT. RESULTS: Patients were categorized into three groups according to tertiles of body mass index (BMI). During ≥30 days after the initiation of CRRT, 39 patients (57.4%) in the highest tertile died, as compared with 58 patients (78.4%) in the lowest tertile (P = 0.02). In a multivariable analysis adjusted for cofounding factors, the highest tertile of BMI was significantly associated with a decreased risk of death (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37–0.87; P = 0.01). This significant association remained unaltered for 60-day (HR, 0.64; 95% CI, 0.43–0.94; P = 0.03) and 90-day mortality (HR, 0.66; 95% CI, 0.44–0.97; P = 0.03). CONCLUSION: This study showed that a higher BMI confer a survival benefit over a lower BMI in AKI patients undergoing CRRT.
Acute Kidney Injury* ; Body Mass Index* ; Epidemiologic Studies ; Humans ; Mortality* ; Obesity ; Observational Study ; Renal Replacement Therapy*

Endoscopic submucosal dissection (ESD) is a widely accepted treatment for early gastric and esophageal cancer. Compared to endoscopic mucosal resection, ESD has the advantage of enabling en bloc removal of tumors regardless of their size. However, ESD can result in a large artificial ulcer, which may lead to a considerable deformity. Circumferential mucosal defects of more than three-fourths the esophageal circumference, long longitudinal mucosal defects (>30 mm), and lesions in the upper esophagus are significant risk factors for the development of post-ESD strictures of the esophagus. In the stomach, a circumferential mucosal defects more than three-fourths in extent and longitudinal mucosal defects >5 cm are risk factors of post-ESD stricture. If scheduled early, regular endoscopic balloon dilation is effective in controlling and preventing post-ESD stricture. Moreover, intralesional steroid injections or oral steroids can achieve remission of dysphagia or reduce the need for repeated endoscopic balloon dilation. However, further study is needed to improve the prevention of stricture formation.
Congenital Abnormalities ; Constriction, Pathologic* ; Deglutition Disorders ; Esophageal Neoplasms ; Esophagus ; Risk Factors ; Steroids ; Stomach ; Ulcer

Survivin, a member of the inhibitors of apoptosis protein family, is expressed during development and in various human cancers. However, the clinical relevance of survivin in cancer is still a matter of debate. Genes induced by hepatocyte growth factor (HGF) were screened using cDNA microarray technology in the stomach cancer cell lines, NUGC3 and MKN28. The levels of JunB, survivin, and uro-plasminogen activator (uPA) were up-regulated in cells treated with HGF in a dose-dependent manner. HGF-induced up regulation of JunB, survivin, and uPA was inhibited by pre-treatment with a MEK inhibitor (PD 98059). HGF-induced up-regulation of uPA was repressed by survivin knockdown. HGF enhanced the binding activity of JunB to the survivin promoter in control cells, but not in the JunB-shRNA cells. Transfection with survivin-shRNA resulted in a decrement of cell proliferation, as determined with MTT assays. In an in vitro invasion assay, significantly fewer cells transfected with survivin shRNA than control cells were able to invade across a Matrigel membrane barrier. In conclusion, survivin appeared to play an important role in the up-regulation of uPA induced by HGF via JunB and might contribute to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy.
Apoptosis ; Cell Hypoxia ; Cell Line, Tumor ; *Cytoprotection ; Glutathione Peroxidase/metabolism ; Herbicides/*toxicity ; Humans ; L-Lactate Dehydrogenase/metabolism ; Lung/*cytology/*drug effects/metabolism ; Malondialdehyde/metabolism ; Oxidative Stress ; Paraquat/*toxicity ; Reactive Oxygen Species/*metabolism ; Superoxide Dismutase/metabolism

BACKGROUND/AIMS: The reappearance rates of hepatitis C virus (HCV) RNA after a sustained virological response (SVR) have been reported to be 1-2%. We investigated the reappearance rate of HCV RNA after SVR in chronic hepatitis C (CHC) patients treated with pegylated interferon (PEG-IFN) and ribavirin. METHODS: In total, 292 CHC patients who achieved an SVR after PEG-IFN and ribavirin treatment were included. They were treated with subcutaneous injections of either PEG-IFN-alpha 2a or 2b plus ribavirin orally. Liver function tests and qualitative HCV RNA assays were performed every 6 months during the follow-up period after an SVR. RESULTS: Among the 292 patients, 224 (genotype 1, 92; genotype non-1, 132) were followed up for more than 6 months after SVR. These 224 patients were aged 48.1+/-11.5 years (mean+/-SD), and 129 of them were male. The median follow-up duration was 18 months (range 6-60 months). The reappearance rate of HCV RNA during follow-up was 0%. Two patients who achieved an SVR developed hepatocellular carcinoma during the follow-up period. CONCLUSIONS: An SVR was maintained in all CHC patients treated with PEG-IFN plus ribavirin during a median follow-up of 18 months. However, a screening test for hepatocellular carcinoma is needed for patients with an SVR.
Adult ; Antiviral Agents/*therapeutic use ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Genotype ; Hepatitis C, Chronic/*drug therapy ; Humans ; Interferon-alpha/*therapeutic use ; Liver Function Tests ; Male ; Middle Aged ; Polyethylene Glycols/*therapeutic use ; RNA, Viral/analysis ; Recombinant Proteins/therapeutic use ; Ribavirin/*therapeutic use

The regulatory mechanisms for the proliferation and the particular invasive phenotypes of stomach cancers are not still fully understood. Up-regulations of hepatocytes growth factor (HGF), its receptor (c-Met), and urokinase-type plasminogen activator (uPA) are correlated with the development and metastasis of cancers. In order to investigate roles of HGF/c-Met signaling in tumor progression and metastasis in stomach cancers, we determined effects of a specific MEK1 inhibitor (PD098059) and a p38 kinase inhibitor (SB203580) on HGF-mediated cell proliferation and uPA expression in stomach cancer cell lines (NUGC-3 and MKN-28). HGF treatment induced the phosphorylations of ERK and p38 kinase in time- and dose- dependent manners. Pre-treatment with PD098059 reduced HGF-mediated cell proliferation and uPA secretion. In contrast, SB203580 pre-treatment enhanced cell proliferation and uPA secretion due to induction of ERK phosphorylation. Stable expression of dominant negative-MEK1 in NUGC-3 cells showed a decrease in HGF-mediated uPA secretion. These results suggest that interaction of a MEK/ERK and a p38 kinase might play an important role in proliferation and invasiveness of stomach cancer cells.
Cell Line, Tumor ; Cell Proliferation/drug effects ; Culture Media, Serum-Free ; Dose-Response Relationship, Drug ; Enzyme Activation/drug effects ; Enzyme Inhibitors/pharmacology ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Flavonoids/pharmacology ; Hepatocyte Growth Factor/*pharmacology ; Humans ; Imidazoles/pharmacology ; Kinetics ; MAP Kinase Kinase 1/metabolism ; Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism ; Neoplasm Metastasis ; Phosphorylation/drug effects ; Pyridines/pharmacology ; Research Support, Non-U.S. Gov't ; Stomach Neoplasms/*enzymology/*pathology ; Urinary Plasminogen Activator/*secretion ; p38 Mitogen-Activated Protein Kinases/metabolism

BACKGROUND: Up-regulation of the hepatocyte growth factor (HGF), its transmembrane tyrosine kinase receptor (c-Met), and urokinase type plasminogen activator (uPA), is associated with the development and metastasis of various types of cancers. However, the mechanisms by which HGF/c-Met signaling mediates cancer progression and metastasis are unclear. METHODS: We investigated the roles of HGF/c-Met in tumor progression and metastasis in NUGC-3 and MKN-28 stomach cancer cell lines. RESULTS: Treatment with HGF increased c-Met phosphorylation in a dose-dependent manner, as well as increasing cell proliferation. HGF treatment also increased the protein level and the activity of uPA in NUGC-3 and MKN-28 cells. A monoclonal antibody against human uPA receptor (uPAR), mAb 3936, inhibited HGF-mediated tumor cell invasion in a dose-dependent manner. Down-regulation of uPA using uPA-shRNA induced a decrease in in vitro cell invasion in NUGC-3 cells. CONCLUSIONS: These results suggest that NUGC-3 and MKN-28 cells express functional c-Met, which may provide a therapeutic target for interfering with metastases of cancer cells by inhibiting uPA and uPAR-mediated proteolysis.
Urinary Plasminogen Activator/antagonists & inhibitors/*metabolism ; Stomach Neoplasms/drug therapy/*enzymology ; Signal Transduction/*drug effects ; Receptors, Growth Factor/*drug effects ; Receptor Protein-Tyrosine Kinases/*drug effects ; Proto-Oncogene Proteins c-met/*drug effects ; Neoplasm Metastasis ; Humans ; Hepatocyte Growth Factor/*metabolism ; Disease Progression ; Adenocarcinoma/drug therapy/enzymology

Renal involvement is common in systemic lupus erythematosus (SLE). The typical lupus nephropathy demonstrates polyclonal immunoglobulin immune deposits with predominance of IgG, usually heavy polytypic complement factors C1q, C3 and C4. In SLE patients, the superimposition and occurrence of non- lupus nephropathy have rarely been reported. We describe a 28-year-old, 15 weeks pregnant women affected by SLE and IgA nephropathy. She was admitted to our hospital due to generalized edema and arthralgia. The ANA titer was 1: 640, anti-ds DNA levels were 354.2 U/mL and other blood tests included thrombocytopenia and hypoclomplementemia. These clinical and laboratory data allowed the diagnosis of SLE. Renal biopsy showed modest segmental mesangial hypercellularity. Immunofluorescence microscopy revealed distinct mesangial IgA and C3 with absence of IgG, IgM, C1q, and C4. Electron microscopy confirmed the presence of electron-dense deposits throughout the mesangium. These features were consistent with the coexistence of IgA nephropathy. A course of prednisolone (50 mg/day) was given for six months and she responded well with resolution of proteinuria. At the present follow- up time point (48 months), she continues to be treated with prednisolone (5 mg/day); proteinuria and ANA are undetectable.
Adult ; Arthralgia ; Biopsy ; Complement System Proteins ; Diagnosis ; DNA ; Edema ; Female ; Glomerulonephritis, IGA* ; Hematologic Tests ; Humans ; Immunoglobulin A* ; Immunoglobulin G ; Immunoglobulin M ; Immunoglobulins ; Lupus Erythematosus, Systemic ; Lupus Nephritis* ; Microscopy, Electron ; Microscopy, Fluorescence ; Nephrotic Syndrome ; Prednisolone ; Pregnant Women ; Proteinuria ; Thrombocytopenia

With the increasing proportion of elderly and diabetic dialysis patients, permanent dual lumen catheters are becoming popular. One of the most frequent causes for the failure of hemodialysis in CRF patients with the tunneled cuffed catheter is the catheter dysfunction. It is thought to be due to encasement of the catheter by fibrin sleeve or fibrin sheath, kinking or malposition of the catheter. Catheter dysfunction due to fibrin sheath formation could sometimes be managed by reversal of arterial and venous lines, urokinase lock or infusion, and catheter exchange. Recently percutaneous fibrin sheath stripping (PFSS) became another modality of salvaging failing tunneled cuffed catheter before attempting catheter exchange. There was no report of applying PFSS to salvage the permanent dual lumen catheter in Korea. Authors recently experienced a case of successful application of PFSS to extend the life of catheter in a CRF patients as a last resort after failure of repeated urokinase trials. It is thought that PFSS is a simple and effective procedure which extends the longevity of permanent dual lumen catheter.
Aged ; Catheters* ; Dialysis ; Fibrin* ; Health Resorts ; Humans ; Korea ; Longevity ; Renal Dialysis ; Urokinase-Type Plasminogen Activator

PURPOSE: To evaluate the application of MRI to the ILAE classification of epilepsies and epileptic syndromes in the setting of epilepsy clinic. METHODS: We reviewed epilepsy registry forms, EEG, and MRI of 300 patients who were consecutively registered to the Yonsei Epilepsy Clinic. The algorhithm of syndromic classification consisted of 3 steps ; 1) clinical diagnosis based on the clinical informations described in the registry form, 2) clinical-EEG correlations, and 3) clinical-EEG-MRI correlations. The interictal epileptiform discharges (IEDs) in EEG were divided into focal, multilobar/multifocal, and generalized. MRI-lesions were divided into focal and non-focal (multilobar/multifocal, and diffuse) lesions. The clinical-EEG, EEG-MRI, and MRI-clinical correlations were categorized as concordant, not discordant, and discordant. RESULTS: Among 300 patients evaluated, 249 patients were found to have epilepsies and both EEG and MRI. By clinical analysis, 190 of 249 patients were diagnosed as localization-related epilepsies (LRE), 24 patients were generalized epilepsies (GE), 34 patients were undetermined epilepsies (UDE), and one patient had alcohol related epilepsy. EEG revealed IEDs in 124 patients and altered the clinical diagnosis in 79 patients. MRI lesions were found in 106 patients with focal lesions in 65 patients and non-focal lesions in 41 patients. MRI lesions were found in 47 of 125 patients with negative EEG. Concordance rates of clinical-EEG, EEG-MRI, and MRI-clinical correlations in 54 patients with lobar epilepsies, who had positive EEG and MRI, were 39%, 54%, and 52%, respectively, and discordant rates were 17%, 11% and 7%, respectively. The complete concordance of all 3 correlations was found in only 33% of them. In 20 patients diagnosed as GE by clinical-EEG correlations, MRI lesions were found in only 3 patients and none of them changed the diagnostic categories due to MRI lesions. CONCLUSION: In lobar epilepsies, the sensitivity of MRI was quite comparable with EEG and the clinical-MRI correlation was superior to the clinical-EEG correlations. MRI provided additional and complimentary informations and should be incorporated to the ILAE-classification system as the category of 'lesional epilepsy'.
Classification ; Diagnosis* ; Electroencephalography ; Epilepsies, Partial ; Epilepsy* ; Epilepsy, Generalized ; Humans ; Magnetic Resonance Imaging*