[Show abstract][Hide abstract] ABSTRACT: Therapies of functional dyspepsia (FD) are limited. DA-9701 is a novel prokinetic agent formulated with Pharbitis semen and Corydalis Tuber. We aimed to assess the efficacy of DA-9701 compared with itopride in FD patients.
Patients with FD randomly received either itopride 50 mg or DA-9701 30 mg t.i.d after a 2-week baseline period. After 4 weeks of treatment, 2 primary efficacy endpoints were analyzed: the change from baseline in composite score of the 8 dyspep-tic symptoms and the overall treatment effect. Impact on patients' quality of life was assessed using the Nepean Dyspepsia Index (NDI) questionnaire.
We randomly assigned 464 patients with 455 having outcome data. The difference of the composite score change of the 8 symptoms between the 2 groups was 0.62, indicating that DA-9701 was not inferior to itopride. The overall treatment effect response rate was not different between the groups. When responder was defined as ≥ 5 of the 7 Likert scale, responder rates were 37% of DA-9701 and 36% of itopride group. Patients receiving DA-9701 experienced similar mean percentage of days with adequate relief during the 4-week treatment period compared with those receiving itopride (56.8% vs 59.1%). Both drugs increased the NDI score of 5 domains without any difference in change of the NDI score between the groups. The safety profile of both drugs was comparable.
DA-9701 significantly improves symptoms in patients with FD. DA-9701 showed non-inferior efficacy to itopride with com-parable safety.
Journal of neurogastroenterology and motility 07/2015; 21(3):414-22. DOI:10.5056/jnm14117 · 2.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gut microbiota may be associated with the pathogenesis of nonalcoholic steatohepatitis (NASH). This study aimed to investigate the protective effects and possible mechanisms of Lactobacillus paracasei on NASH.
Thirty male C57BL/6 mice were randomized into three groups and maintained for 10 weeks: control group (standard chow), NASH model group (high fat + 10 % fructose diet), and the L. paracasei group (NASH model with L. paracasei). Liver histology, serum aminotransferase levels, and hepatic gene expression levels were measured. Intestinal permeability was investigated using urinary (51)Creatinine Ethylenediaminetetraacetic acid ((51)Cr-EDTA) clearance. Total Kupffer cell counts and their composition (M1 vs. M2 Kupffer cells) were measured using flow cytometry with F4/80 and CD206 antibodies.
Hepatic fat deposition, serum ALT level, and (51)Cr-EDTA clearance were significantly lower in the L. paracasei group than the NASH group (p < 0.05). The L. paracasei group had lower expression in Toll-like receptor-4 (TLR-4), NADPH oxidase-4 (NOX-4), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin 4 (IL-4), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-δ compared with the NASH group (p < 0.05). The total number of F4/80(+) Kupffer cells was lower in the L. paracasei group than the NASH group. L. paracasei induced the fraction of F4/80(+)CD206(+) cells (M2 Kupffer cells) while F4/80(+)CD206(-) cells (M1 Kupffer cells) were higher in the NASH group (F4/80(+)CD206(+) cell: 44 % in NASH model group vs. 62 % in L. paracasei group, p < 0.05).
Lactobacillus paracasei attenuates hepatic steatosis with M2-dominant Kupffer cell polarization in a NASH model.
Digestive Diseases and Sciences 07/2015; DOI:10.1007/s10620-015-3770-1 · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relationship between visceral obesity and colon cancer outcome has not been well studied. The goal of this study was to determine the impact of visceral obesity on lymph node (LN) metastasis and overall survival (OS) in colon cancer.
Metastatic LN ratio (MLR) was defined as the number of involved nodes by tumor divided by the total number of resected LNs. Visceral (VFA) and subcutaneous fat areas (SFA) were determined by measuring abdominal fat volume distribution via CT scan, and visceral obesity was defined as a VFA to total fat area ratio (V/T) > 0.29.
In a multivariate analysis among 186 patients, there were inverse associations between V/T and MLR (OR = 0.413, 95 % CI = 0.216-0.789, P = 0.007). Furthermore, patients with visceral obesity tended to have significantly better OS than patients with non-visceral obesity.
Higher V/T ratios which indicate referring to visceral obesity was significantly associated with decreased MLR and better OS for CRC.
Journal of Gastrointestinal Surgery 05/2015; DOI:10.1007/s11605-015-2834-z · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.
[Show abstract][Hide abstract] ABSTRACT: Aminotransferase activity is a surrogate marker of liver injury showing strong correlations with obesity and metabolic syndrome. However, elevated aminotransferase activity is not uncommon in non-obese and non-alcoholic patients in clinical practice.
[Show abstract][Hide abstract] ABSTRACT: Background
The relationship between fat distribution and lymph node metastasis has not been well studied. The goal of this study was to determine the impact of visceral obesity on lymph node metastasis in gastric cancer.
Materials and Methods
Metastatic lymph node ratio (MLR) was defined as the number of involved nodes by tumor divided by the total number of resected lymph nodes. Visceral (VFA) and subcutaneous fat areas (SFA) were determined by measuring abdominal fat volume distribution via CT scan, and visceral obesity was defined as a VFA to total fat area ratio (V/T) >0.29.
With lymph node metastasis as a dependent variable, the following factors were significant in multivariate analysis among 495 patients: pathologic T stage (P
Journal of Gastrointestinal Surgery 10/2014; 19(2). DOI:10.1007/s11605-014-2682-2 · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim: Although numerous animal studies suggest that probiotic therapy has beneficial effects in various liver diseases, the evidence for beneficial effects in human liver disease is controversial. This study was carried out to investigate the efficacy of probiotic therapy in alleviating small intestinal bacterial overgrowth (SIBO) and permeability in chronic liver disease. Methods: Fifty-three patients with chronic liver disease were randomized to either probiotic therapy or placebo. Six bacterial species were used: Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus. After 4 weeks, changes in the composition of fecal bacteria, SIBO, intestinal permeability, and clinical symptoms were examined. Results: Three of the six probiotic species, B. lactis, L. rhamnosus, and L. acidophilus, increased in the feces of the probiotic therapy group (P<0.001), whereas there was no change in fecal microbiota in the placebo group. SIBO disappeared in many individuals of the probiotic therapy group, but none in the placebo (24 vs. 0%, P<0.05). General gastrointestinal symptoms also improved more in the probiotic group and improvement in intestinal permeability was slightly but not significantly more frequent in the probiotic arm than the placebo arm (50 vs. 31.3%, P=0.248). Numbers of lactobacilli in stool were correlated negatively with intestinal permeability (P for trend<0.05). Liver chemistry did not improve significantly in either group. Conclusions: We conclude that short-term probiotic administration in chronic liver disease is effective in alleviating SIBO and clinical symptoms, but ineffective in improving intestinal permeability and liver function. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
European Journal of Gastroenterology & Hepatology 09/2014; 26(12). DOI:10.1097/MEG.0000000000000214 · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and study aims: Preoperative pathological diagnosis may improve clinical management decisions in patients with upper gastrointestinal subepithelial tumors (SETs). The aims of this study were to evaluate the diagnostic yield of deep biopsy via an endoscopic submucosal dissection (ESD) technique, the complications associated with the procedure, and the impact on management of patients with upper gastrointestinal SETs. Patients and methods: A total of 68 patients with SETs in the stomach or esophagus were voluntarily assigned to two groups. One group underwent endoscopic ultrasound (EUS) and endoscopic deep biopsy using the ESD technique (40 patients), and the other group (28 patients) underwent surgical resection after EUS without obtaining preoperative pathological diagnosis, in accordance with accepted clinical management algorithms. Results: The diagnostic yield of deep biopsy was 90 % (36/40). The results of deep biopsy changed the treatment plans in 14/40 patients (35 %). One patient with lymphoepithelial carcinoma was scheduled for surgical resection, and 13 patients with benign SETs of diameter ≥ 2 cm avoided surgery. Of the 28 patients who underwent surgical resection without preoperative pathological diagnosis, 12 (42.9 %) were confirmed to have benign lesions. The mean procedure time for deep biopsy was 13.7 minutes. There were no procedure-related complications in the deep biopsy group. Conclusions: Deep biopsy by the ESD technique is a safe, high-yield, diagnostic method in patients with upper gastrointestinal SETs. Pathologic confirmation could improve clinical decision making in the management of patients with upper gastrointestinal SETs. Clinical trial registration: NCT 01993199.
[Show abstract][Hide abstract] ABSTRACT: Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 10(14) cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS.
World Journal of Gastroenterology 07/2014; 20(27):8886-8897. DOI:10.3748/wjg.v20.i27.8886 · 2.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Misoprostol is reported to prevent non-steroidal anti-inflammatory drug (NSAID)-associated gastroduodenal complications. There is, however, limited information regarding the efficacy of DA-9601 in this context. We performed a comparative study on the relative efficacy of DA-9601 and misoprostol for prevention of NSAID-associated complications. In this multicenter, double-blinded, active-controlled, stratified randomized, parallel group, non-inferiority trial, 520 patients who were to be treated with an NSAID (aceclofenac, 100 mg, twice daily) over a 4-week period were randomly assigned to groups for coincidental treatment with DA-9601 (60 mg, thrice daily) (236 patients for full analysis) or misoprostol (200 μg, thrice daily) (242 patients for full analysis). A total of 236 patients received DA-9601 and 242 received misoprostol. The primary endpoint was the gastric protection rate, and secondary endpoints were the duodenal protection rate and ulcer incidence rate. Endpoints were assessed by endoscopy after the 4-week treatment period. Drug-related adverse effects, including gastrointestinal (GI) symptoms, were also compared. At week 4, the gastric protection rates with DA-9601 and misoprostol were 81.4 % (192/236) and 89.3 % (216/242), respectively. The difference between the groups was -14.2 %, indicating non-inferiority of DA-9601 to misoprostol. Adverse event rates were not different between the two groups; however, the total scores for GI symptoms before and after administration were significantly lower in the DA-9601 group than in the misoprostol group (-0.2 ± 2.8 vs 1.2 ± 3.2; p < 0.0001). DA-9601 is as effective as misoprostol in preventing NSAID-associated gastroduodenal complications, and has a superior adverse GI effect profile.
Archives of Pharmacal Research 05/2014; 37(10). DOI:10.1007/s12272-014-0408-3 · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity is associated with certain types of cancer, including gastric cancer. However, it is still unclear whether obesity-related cytokine, leptin, is implicated in gastric cancer. Therefore, we aimed to investigate the role of leptin in gastric cancer. The expression of leptin and its receptor, Ob-R, was assessed by immunohistochemical staining and was compared in patients with gastric adenoma (n=38), early gastric cancer (EGC) (n=38), and advanced gastric cancer (AGC) (n=38), as a function of their clinicopathological characteristics. Gastric cancer cell lines were studied to investigate the effects of leptin on the signal transducer and activator of transcription-3 (STAT3) and extracellular receptor kinase 1/2 (ERK1/2) signaling pathways using MTT assays, immunoblotting, and inhibition studies. Leptin was expressed in gastric adenomas (42.1%), EGCs (47.4%), and AGCs (43.4%). Ob-R expression tended to increase from gastric adenoma (2%), through EGC (8%), to AGC (18%). Leptin induced the proliferation of gastric cancer cells by activating STAT3 and ERK1/2 and up-regulating the expression of vascular endothelial growth factor (VEGF). Blocking Ob-R with pharmacological inhibitors and by RNAi decreased both the leptin-induced activation of STAT3 and ERK1/2 and the leptin-induced expression of VEGF. Leptin plays a role in gastric cancer by stimulating the proliferation of gastric cancer cells via activating the STAT3 and ERK1/2 pathways.
Biochemical and Biophysical Research Communications 04/2014; 446(4). DOI:10.1016/j.bbrc.2014.02.072 · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Besides age, risk factors for colonic diverticular disease include dietary meat intake and Western lifestyles, which are also risk factors for obesity. However, the association between obesity and colonic diverticular disease, including diverticulosis and diverticulitis, is not well established. The aim of this study was to investigate the relationship between colonic diverticulosis and obesity using abdominal fat quantified by abdominal CT scan and lipid profiles, as well as body mass index (BMI).
The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology 04/2014; 25(2):192-197. DOI:10.5152/tjg.2014.4581 · 0.47 Impact Factor