Background: Glucagon-like peptide-1 (GLP-1) analogues regulate glucose homeostasis and have anti-inflammatory properties, but cause gastrointestinal side effects. The fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism that has poor pharmacokinetic properties, including a short half-life. To overcome these limitations, we investigated the effect of a low-dose combination of a GLP-1 analogue and FGF21 on atherosclerosis-related molecular pathways. Methods: C57BL/6J mice were fed a high-fat diet for 30 weeks followed by an atherogenic diet for 10 weeks and were divided into four groups: control (saline), liraglutide (0.3 mg/kg/day), FGF21 (5 mg/kg/day), and low-dose combination treatment with liraglutide (0.1 mg/kg/day) and FGF21 (2.5 mg/kg/day) (n=6/group) for 6 weeks. The effects of each treatment on various atherogenesisrelated pathways were assessed. Results: Liraglutide, FGF21, and their low-dose combination significantly reduced atheromatous plaque in aorta, decreased weight, glucose, and leptin levels, and increased adiponectin levels. The combination treatment upregulated the hepatic uncoupling protein-1 (UCP1) and Akt1 mRNAs compared with controls. Matric mentalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were downregulated and phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated in liver of the liraglutide-alone and combination-treatment groups. The combination therapy also significantly decreased the proliferation of vascular smooth muscle cells. Caspase-3 was increased, whereas MMP-9, ICAM-1, p-Akt, and p-ERK1/2 were downregulated in the liraglutide-alone and combination-treatment groups. Conclusion Administration of a low-dose GLP-1 analogue and FGF21 combination exerts beneficial effects on critical pathways related to atherosclerosis, suggesting the synergism of the two compounds.

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.

BACKGROUND: Bone strength is impaired in patients with type 2 diabetes mellitus despite an increase in bone mineral density (BMD). Thiazolidinedione (TZD), a peroxisome proliferator activated receptor γ agonist, promotes adipogenesis, and suppresses osteoblastogenesis. Therefore, its use is associated with an increased risk of fracture. The aim of this study was to examine the in vitro and in vivo effects of lobeglitazone, a new TZD, on bone. METHODS: MC3T3E1 and C3H10T1/2 cells were cultured in osteogenic medium and exposed to lobeglitazone (0.1 or 1 µM), rosiglitazone (0.4 µM), or pioglitazone (1 µM) for 10 to 14 days. Alkaline phosphatase (ALP) activity, Alizarin red staining, and osteoblast marker gene expression were analyzed. For in vivo experiments, 6-month-old C57BL/6 mice were treated with vehicle, one of two doses of lobeglitazone, rosiglitazone, or pioglitazone. BMD was assessed using a PIXImus2 instrument at the baseline and after 12 weeks of treatment. RESULTS: As expected, in vitro experiments showed that ALP activity was suppressed and the mRNA expression of osteoblast marker genes RUNX2 (runt-related transcription factor 2) and osteocalcin was significantly attenuated after rosiglitazone treatment. By contrast, lobeglitazone at either dose did not inhibit these variables. Rosiglitazone-treated mice showed significantly accelerated bone loss for the whole bone and femur, but BMD did not differ significantly between the lobeglitazone-treated and vehicle-treated mice. CONCLUSION: These findings suggest that lobeglitazone has no detrimental effects on osteoblast biology and might not induce side effects in the skeletal system.
Adipogenesis ; Alkaline Phosphatase ; Animals ; Biology ; Bone and Bones ; Bone Density* ; Diabetes Mellitus, Type 2 ; Femur ; Gene Expression ; Humans ; In Vitro Techniques ; Infant ; Mice* ; Osteoblasts ; Osteocalcin ; Peroxisomes ; RNA, Messenger ; Thiazolidinediones ; Transcription Factors

PURPOSE: While the Trastuzumab for Gastric Cancer (ToGA) trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2-positive metastatic gastric cancer, the overall survival (OS) benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy. MATERIALS AND METHODS: Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively. RESULTS: A total of 168 Asian patients were included. The median age was 60 years (range, 27 to 85 years) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly-differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI], 8.7 to 11.7), and the median OS was 18.5 months (95% CI, 16.4 to 50.6). Next, we investigated the effect of poorly-differentiated histology (PDH, poorly-differentiated tubular adenocarcinoma+signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p=0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p=0.025). CONCLUSION: While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2-positive gastric cancer.
Adenocarcinoma ; Asian Continental Ancestry Group ; Carcinoma, Signet Ring Cell ; Disease-Free Survival ; Drug Therapy* ; Ethnic Groups ; Humans ; Receptor, erbB-2 ; Retrospective Studies* ; Stomach Neoplasms*

BACKGROUND/AIMS: Transient lower esophageal sphincter relaxation (TLESR) is the main mechanism of gastroesophageal reflux disease (GERD). The aim of this study was to investigate the characteristics of transient lower esophageal sphincter movement in patients with or without gastroesophageal reflux by high-resolution manometry (HRM). METHODS: From June 2010 to July 2010, we enrolled 9 patients with GERD (GERD group) and 9 subjects without GERD (control group), prospectively. The manometry test was performed in a semi-recumbent position for 120 minutes following ingestion of a standardized, mixed liquid and solid meal. HRM was used to identify the frequency and duration of TLESR, esophageal shortening length from incomplete TLESR, upper esophageal sphincter (UES) response, and the related esophageal motor responses during TLESR. RESULTS: TLESR occurred in 33 in the GERD group and 34 in the control group after 120 minutes following food ingestion. Duration of TLESR and length of esophageal shortening did not differ between 2 groups. UES pressure increase during TLESR was mostly detected in patients with GERD, and UES relaxation was observed frequently in the control group during TLESR. TLESR-related motor responses terminating in TLESR were predominantly observed in the control group. CONCLUSIONS: Increased UES pressure was noted frequently in the GERD group, suggesting a mechanism for preventing harmful reflux, which may be composed mainly of fluid on the larynx or pharynx. However, patients with GERD lacked the related motor responses terminating in TLESR to promote esophageal emptying of refluxate.
Eating ; Esophageal Sphincter, Lower ; Esophageal Sphincter, Upper ; Esophagus ; Gastroesophageal Reflux ; Humans ; Larynx ; Manometry ; Meals ; Pharynx ; Prospective Studies ; Relaxation

Prevalence of dizziness has been reported to be as high as nearly twenty percent and one half of these population had social handicap to some degree. The diagnostic approach of dizziness heavily relies on the premise that dizziness type predicts the underlying etiology-e.g, vertigo with vestibular causes and presyncope with cardiovascular causes. However, such symptomatological approach sometimes delays correct diagnosis as the presenting symptom of individual patient is typically vague to designate the type. In this paper, a case of a 57-year-old woman who has experienced recurrent rotatory vertigo of cardiovascular origin was discussed. When her head were turned to the left, a fast downbeat nystagmus following a slow upward eye deviation was recorded using video nystagmogram. Hence, we report this single case of syncope presented as peripheral vertigo type with literature review.
Dizziness ; Eye ; Female ; Head ; Humans ; Middle Aged ; Nystagmus, Pathologic ; Prevalence ; Syncope ; Vertigo

BACKGROUND/AIMS: Pain is one of the most troublesome symptoms of pancreatitis. Transdermal fentanyl patches (TFPs) are long-acting analgesics with a reduced risk of dependency. This prospective study evaluated the effect of TFPs on sphincter of Oddi (SO) motility for the management of pain in pancreatitis. METHODS: SO manometry (SOM) was performed using triple-lumen catheters anterogradely inserted through the percutaneous transhepatic route during cholangioscopy in 16 patients. The basal pressure, amplitude, and frequency of the SO were assessed before and after applying a TFP at 24 hour at doses of 25 and 12.5microgram/hr, respectively. RESULTS: Two of 16 patients receiving a 25microgram/hr. TFP were excluded because of adverse side effects (headache and/or nausea). The mean basal pressure, amplitude, and frequency of SOM did not change significantly in the 25microgram/hr TFP group (n=4 patients). Parameters of SO function also did not significantly change in the 12.5microgram/hr TFP group (n=11 patients). CONCLUSIONS: TFPs below a dose of 25microgram/hr may not affect the motility of the SO. Administration of TFPs at lower dosages seems to be a safe analgesic treatment for the pain control of patients with pancreatitis without affecting the function of the SO.
Analgesics ; Catheters ; Dependency (Psychology) ; Fentanyl ; Humans ; Manometry ; Pancreatitis ; Prospective Studies ; Sphincter of Oddi

BACKGROUND/AIMS: Propofol is widely used for sedation during endoscopy. Because propofol may cause hepatic encephalopathy, hemodynamic compromise, and respiratory depression, cautious use is required in patients with liver cirrhosis. We evaluated the safety and efficacy of propofol in compensated cirrhosis during endoscopic examination. METHODS: Thirty-nine cirrhotic patients (19 and 20 cases of Child Pugh classes A and B, respectively) and 56 control subjects were included. The initial dose of propofol (40 mg) was increased by 20-mg increments until moderate sedation was achieved. The number connection test, flapping tremor test, blood pressure, heart rate, oxygen saturation, liver enzymes, and prothrombin time were evaluated before and after endoscopy. RESULTS: No significant change was observed in any parameter compared to baseline in either group. The mean dose of propofol was significantly lower in cirrhotic versus control subjects (49.7+/-15.8 versus 65.0+/-17.9 mg, respectively; p<0.001). Scores based on a visual analog scale evaluating patient satisfaction did not differ between groups (72+/-27 versus 64+/-26, respectively; p=0.196), nor did mean recovery time (16.4+/-9.8 versus 14.2+/-6.7 min, respectively; p=0.186). CONCLUSION: Propofol is safe and effective for moderate sedation in compensated liver cirrhosis.
Child ; Conscious Sedation ; Endoscopy ; Fibrosis ; Heart Rate ; Hematologic Tests ; Hemodynamics ; Hepatic Encephalopathy ; Humans ; Liver ; Liver Cirrhosis ; Oxygen ; Patient Satisfaction ; Propofol ; Prothrombin Time ; Respiratory Insufficiency ; Tremor

BACKGROUND/AIMS: The removal of esophageal and gastric submucosal tumors is difficult using conventional endoscopic mucosal resection methods. This study examined the usefulness of an endoscopic subtumoral dissection for an en-bloc resection of submucosal tumors. METHODS: An endoscopic subtumoral dissection was attempted for an en-bloc resection in 15 submucosal tumors (M: F=10 : 5, 13 stomach, 2 esophagus). Before the procedures, endoscopic ultrasonography was performed in all cases. The procedure was carried out using various electrosurgical knives, such as an endoscopic submucosal dissection. RESULTS: Pathological and immunohistochemical studies confirmed a gastrointestinal stromal tumor in 6 cases. Other pathological diagnoses were made in 9 patients with submucosal lesions: leiomyoma (4), ectopic pancreas (3), lipoma (1), and hemangioma (1). An en-bloc resection was performed in 13 of the 15 tumors (86.7%). The mean specimen size was 29.5x21.1 mm. The mean procedure time was 49.4 minutes (range: 8~103 minutes). Gastric perforation was a complication in 2 cases with GIST. However, the two perforated cases were treated with endoscopic closure using endoclips and recovered without the need for surgery. CONCLUSIONS: An endoscopic subtumoral dissection technique is useful for an en-bloc resection of esophageal and gastric submucosal tumors. However, sufficient attention should be paid to the detection of perforations in the case of tumors with a proper muscle origin.
Endosonography ; Gastrointestinal Stromal Tumors ; Hemangioma ; Humans ; Leiomyoma ; Lipoma ; Muscles ; Pancreas ; Stomach