PURPOSE: High Gleason score (8 to 10) is a poor prognostic factor regardless of treatment. Pathological downgrading sometimes occurs in high grade prostate cancer. The aim of this study is to evaluate treatment outcomes in patients with high grade prostate cancer on biopsy who were pathological downgrading after radical prostatectomy (RP). The impact on outcomes according to changes in the Gleason score after RP was evaluated. MATERIALS AND METHODS: Of 3,236 men who underwent RP between September 1995 and December 2014, 541 patients with biopsy Gleason score 8 to 10 were retrospectively reviewed. We analyzed incidence and biochemical recurrence (BCR) free probability in this downgraded group according to the Gleason grade of cancer in the RP specimen. RESULTS: Of 541 patients had a prostate biopsy Gleason score of 8 to 10. Two hundred ten patients showed pathological downgrading after RP (38.8%). Five-year BCR-free probability of patients who had Gleason score of 7 or less after RP was 46.8%. However, 5-year BCR-free probability of patients who remained Gleason scores 8 to 10 after RP was 28.5%. There was a significantly higher BCR-free probability in pathological downgrading group (p<0.001). On multivariate analysis, biopsy Gleason 8, lower PSA, clinical T2 stage was a significant predictor of downgrading. CONCLUSIONS: In this study, 38.8% of patients with high grade prostate cancer had a Gleason score of 7 or less in the RP specimen. Downgraded prostate cancer had more favorable treatment outcome. Serum PSA, clinical stage and biopsy Gleason score were the predictive factors for pathological downgrading.
Biopsy* ; Humans ; Incidence* ; Male ; Multivariate Analysis ; Neoplasm Grading* ; Prostate* ; Prostatectomy* ; Prostatic Neoplasms* ; Recurrence ; Retrospective Studies ; Treatment Outcome*

Clinical progression over time and cytokine profiles have not been well defined in patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We included 17 patients with laboratory-confirmed MERS-CoV during the 2015 outbreak in Korea. Clinical and laboratory parameters were collected prospectively. Serum cytokine and chemokine levels in serial serum samples were measured using enzyme-linked immunosorbent assay. All patients presented with fever. The median time to defervescence was 18 days. Nine patients required oxygen supplementation and classified into severe group. In the severe group, chest infiltrates suddenly began to worsen around day 7 of illness, and dyspnea developed at the end of the first week and became apparent in the second week. Median time from symptom onset to oxygen supplementation was 8 days. The severe group had higher neutrophil counts during week 1 than the mild group (4,500 vs. 2,200/µL, P = 0.026). In the second week of illness, the severe group had higher serum levels of IL-6 (54 vs. 4 pg/mL, P = 0.006) and CXCL-10 (2,642 vs. 382 pg/mL, P < 0.001). IFN-α response was not observed in mild cases. Our data shows that clinical condition may suddenly deteriorate around 7 days of illness and the serum levels of IL-6 and CXCL-10 was significantly elevated in MERS-CoV patients who developed severe diseases.
Coronavirus ; Coronavirus Infections* ; Dyspnea ; Enzyme-Linked Immunosorbent Assay ; Fever ; Humans ; Interleukin-6 ; Korea ; Middle East Respiratory Syndrome Coronavirus* ; Middle East* ; Neutrophils ; Oxygen ; Prospective Studies ; Thorax

The expression of hypoxia-inducible factor (HIF) is influenced by reactive oxygen species (ROS). Effect of bilirubin on HIF-1 expression in proximal tubular cells was investigated under physiological oxygen concentration, which is relative hypoxic condition mimicking oxygen content in the medulla of renal tissue. The human kidney (HK2) cells were cultured in 5% oxygen with or without bilirubin. HIF-1alpha protein expression was increased by bilirubin treatment at 0.01-0.2 mg/dL concentration. The messenger RNA expression of HIF-1alpha was increased by 1.69+/-0.05 folds in the cells cultured with 0.1 mg/dL bilirubin, compared to the control cells. The inhibitors of PI3K/mTOR, PI3K/AKT, and ERK 1/2 pathways did not attenuate increased HIF-1alpha expression by bilirubin. HIF-1alpha expression decreased by 10 microM exogenous hydrogen peroxide (H2O2); scavenger of ROS with or without bilirubin in the HK2 cells increased HIF-1alpha concentration more than that in the cells without bilirubin. Exogenous H2O2 decreased the phosphorylation of P70S6 kinase, which was completely reversed by bilirubin treatment. Knockdown of NOX4 gene by small interfering RNA (siRNA) increased HIF-1alpha mRNA expression. In coonclusion, bilirubin enhances HIF-1alpha transcription as well as the up-regulation of HIF-1alpha protein translation through the attenuation of ROS and subunits of NADPH oxidase.
Bilirubin/*pharmacology ; Cell Line ; Epithelial Cells/cytology/metabolism ; Humans ; Hydrogen Peroxide/toxicity ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Kidney Tubules, Proximal/cytology ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; NADPH Oxidase/antagonists & inhibitors/genetics/metabolism ; Oxygen/*pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; RNA Interference ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/metabolism ; Transcriptional Activation/*drug effects ; Up-Regulation/drug effects

PURPOSE: To provide the insight into the role of LXR alpha on the progression of diabetic nephropathy, we measured the production of extracellular matrix in the cultured mesangial cells treated with the LXR agonist. METHODS: With the mesangial cells extracted from C57BL6 mice, we cultured them in the presence of 25 mM glucose with or without TO901317, an agonist of LXRalpha We transfected siRNAs of SREBP1 and LXR alpha into the mesangial cell to suppress the activity of the two genes. RESULTS: TO901317 increased expressions of LXR alpha, SREBP-1, TGF beta-1, and collagen IV and triglyceride amount in mesangial cells cultured in 25mM glucose. These effects of TO901317 were attenuated by inhibiting transcription of LXR alpha or SREBP-1 with transfection of siRNAs. In mesangial cells transfected with siRNA of SREBP-1, changes by TO901317 were attenuated regardless of increased expression of LXR alpha. That suggested the activation of SREBP-1, an downstream gene of LXR alpha, would be more important to induce changes in mesangial cells by TO901317. CONCLUSION: The TO901317, an agonist of LXR alpha, increases extracellular matrix, collagen IV, and TGF beta-1 production in cultured mesangial cells. The SREBP-1 as well as dyslipidemia in mesangial cells enhanced by LXR agonist would be the important mechanism to induce those changes.
Animals ; Collagen ; Diabetic Nephropathies ; Dyslipidemias ; Extracellular Matrix ; Glucose ; Hypertriglyceridemia ; Liver ; Mesangial Cells ; Mice ; Orphan Nuclear Receptors ; RNA, Small Interfering ; Sterol Regulatory Element Binding Protein 1 ; Transfection

No abstract available.
Atrioventricular Block

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy.
Adult ; Bilirubin/*blood ; Disease Progression ; Female ; Glomerular Filtration Rate ; Glomerulonephritis, IGA/*blood/complications ; Humans ; Hypertension/complications ; Incidence ; Kidney Failure, Chronic/*blood/complications ; Male ; Middle Aged ; Risk ; Risk Factors ; Treatment Outcome

OBJECTIVE: The purpose of this study is to evaluate the efficacy and safety of mirtazapine treatment in multicenter population consisting of Korean patients suffering from moderate-to-severe depression. METHODS: Total 163 of in and outpatients with a diagnosis of major depressive disorder (DSM-IV) and 18 or over scores of 17-items Hamilton Rating Scale for Depression (HAMD) received treatment with mirtazapine (15-45 mg/day) for 6 weeks. Efficacy was assessed by HAMD, Montgomery and Asberg Depression Rating Scale (MADRS), Beck's Depression Inventory (BDI), and Clinical Global Impression (CGI) scales and statistical analyses were performed on the intent-to-treat sample (143 patients) using the last-observation-carried-forward method. In addition, reported adverse events, routine laboratory parameters, and vital signs were investigated to evaluate the safety of mirtazapine. RESULTS: Mean daily dose of mirtazapine was 28.4 mg. At the end of the study, the response rate (50% or more reduction from baseline in HAMD scores) was 75.5% and the remission rate (7 or less in HAMD score) was 42.7%. Mirtazapine treatment induced significant reduction in depressive symptoms at the 4(th) day and substantial reduction along the treatment period, as assessed by changes in HAMD, MADRS, BDI, and CGI scales. At the 4(th) day and first week of mirtazapine treatment, the mean HAMD-17 total score was significantly reduced compared that of the baseline and the response rates were 11.9% and 28.7%, respectively. Mirtazapine was well tolerated in general, and somnolence and sedation were the most common adverse events reported. In addition, there were no clinically relevant changes in laboratory parameters and vital signs, although body weight was increased. CONCLUSION: Although this trial had many limitations of open non-comparative study, mirtazapine was demonstrated to an effective treatment for moderate to severe major depressive disorder and was well tolerated. A potentially rapid onset of overall therapeutic efficacy of mirtazapine was suggested by significant changes in all major variables of efficacy after 4(th) day of treatment.
Body Weight ; Depression ; Depressive Disorder, Major ; Diagnosis ; Humans ; Outpatients ; Vital Signs ; Weights and Measures

PURPOSE: To evaluate the effectiveness and safety of fentanyl-TTS in the management of radiotherapy induced acute pain and cancer pain treated with radiotherapy. MATERIALS AND METHODS: Our study was open labelled prospective phase IV multi-center study. the study population included patients with more 4 numeric rating scale(NRS) score pain although managed with other analgesics or more than 6 NRS score pain without analgesics. Patients divided into two groups; patients with radiotherapy induced pain (Group A) and patients with cancer pain treated with radiotherapy (Group B). All patients received 25 ug/hr of fentanyl transdermal patch. Primary end point was pain relief; second end points were change in patient quality of life, a degree of satisfaction for patients and clinician, side effects. RESULTS: Between March 2005 and June 2005, 312 patients from 26 participating institutes were registered, but 249 patients completed this study. Total number of patients in each group was 185 in Group A, 64 in Group B. Mean age was 60 years and male to female ratio was 76:24. Severe pain NRS score at 2 weeks after the application of fentanyl was decreased from 7.03 to 4.01, p=0.003. There was a significant improvement in insomnia, social functioning, and quality of life. A degree of satisfaction for patients and clinician was very high. The most common reasons of patients' satisfactions was good pain control. Ninety six patients reported side effect. Nausea was the most common side effect. There was no serious side effect. CONCLUSION: Fentanyl-TTS was effective in both relieving pain with good tolerability and improving the quality of life for patients with radiotherapy induced acute pain and cancer pain treated with radiotherapy. The satisfaction of the patients and doctors was good. There was no major side effect.
Academies and Institutes ; Acute Pain ; Analgesics ; Female ; Fentanyl* ; Humans ; Male ; Nausea ; Prospective Studies ; Quality of Life ; Radiotherapy* ; Sleep Initiation and Maintenance Disorders ; Transdermal Patch*

BACKGROUND/AIMS: Several lines of evidences suggest that the distribution of colorectal adenomatous polyps are different according to age and gender. Therefore, the efficacy of screening sigmoidoscopy for colorectal cancer not considering age and gender necessitates reappraisal. We aimed to evaluate the distributions of colorectal adenomatous polyps according to age and gender. METHODS: Total of 1,886 patients (1,322 men, 564 women) who underwent colonoscopy at Severance hospital, Seoul, Korea between July 1995 and September 2002, were included. The proximal colon was defined as the colon proximal to the sigmoid-descending junction. The advanced polyp was defined as the adenomatous polyp with one or more of the following features: (1) 1 cm or larger in diameter, (2) villous histology, (3) high grade dysplasia or adenocarcimoma. RESULTS: The risk of adenomatous polyps in the proximal colon was higher in men than women (OR, 1.63; 95% CI, 1.33~1.99, p < 0.05), and increased with age (p < 0.05). The risk of advanced polyps in the proximal colon tended to be higher in men than women, and to increase with age, but did not reach statistical significance. Among 1,886 patients with colorectal adenomatous polyps, 587 patients (31.1%) had polyps only in the proximal colon. Among 814 patients with advanced colorectal adenomatous polyps, 217 patients (26.7%) had advanced polyps only in the proximal colon. The risks of adenomatous polyps or advanced polyps found only in the proximal colon were not different according to sex, but tended to increase with age. CONCLUSIONS: The risk of adenomatous polyps in the proximal colon was higher in men compared to women and increased with age. About one third of the patients with colorectal adenomatous polyps had polyps only in the proximal colon. Colonoscopy is a better strategy for endoscopic screening for colorectal cancer compared with sigmoidoscopy, especially, in elderly male.
Adenomatous Polyps* ; Aged ; Colon* ; Colonoscopy ; Colorectal Neoplasms ; Female ; Humans ; Korea ; Male ; Mass Screening ; Polyps ; Seoul ; Sigmoidoscopy

We report a case of a mediastinal pseudocyst with a pleural effusion that developed in a patient suffering from alcohol-related chronic pancreatitis. A 53-year-old man was admitted to another institution complaining of pleuritic chest pain and coughing. A chest X-ray revealed a pleural effusion with a collapse of the right middle and lower lobes. Pleural fluid taken by thoracentesis was exudative, and the patient was transferred to our institution. A CT scan showed a loculated cystic lesion in the mediastinum and pancreatic changes that were consistent with chronic pancreatitis. The endoscopic retrograde cholangiopancreatography (ERCP) findings were compatible with chronic pancreatitis showing severe pancreatic ductal stricture at the head with an upstream dilation and distal bile duct stricture. After a one week of treatment with fasting and octreotide without improvement, both pancreatic and biliary stents were placed endoscopically. After stenting, the pleural effusion and pseudocyst rapidly resolved. The stents were changed 3 months later, at which time a repeated CT demonstrated a complete resolution of the pseudocyst. Since the initial stenting, he has been followed up for 7 months and is doing well with no recurrence of the symptoms, but he will need to undergo regular stent changes. Overall, endoscopic pancreatic stenting appears to be a good option for managing selected cases of mediastinal pancreatic pseudocysts.
*Endoscopy ; Human ; Male ; Mediastinal Neoplasms/*complications/radiography/therapy ; Middle Aged ; *Pancreatic Ducts ; Pancreatic Pseudocyst/*complications/radiography/therapy ; Pleural Effusion/*complications/therapy ; Radiography, Thoracic ; *Stents ; Tomography, X-Ray Computed ; Treatment Outcome