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The author discusses the effectiveness of germinated barley foodstuff (GBF) in colitis-associated colon cancer prevention and treatment. The author denotes how the inflammatory bowel disease (IBD) can aggravate the risk of acquiring such cancer. The author notes the fermentation of the GBF through gut microbiota and it provokes the growth of prebiotics such as Bifidobacterium, Eubacterium, and Lactobacillus species which can prevent colitis as well as colon cancer.

Background: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis.Methods: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy. Patients were stratified by previous anti-TNFα treatment, and randomly assigned by a computer-generated randomisation schedule to receive a subcutaneous injection of 7·5 mg, 22·5 mg, 75 mg, or 225 mg PF-00547659 or placebo at baseline, then every 4 weeks. Patients, investigators, and sponsors were blinded to the treatment. The primary endpoint was the proportion of patients achieving remission (total Mayo score ≤2 with no individual subscore >1 and rectal bleeding subscore ≤1) at week 12. The efficacy analysis included all patients who received at least one dose of the randomised treatment; the safety analysis was done according to treatment received. All p values were one-sided and multiplicity-adjusted. This study is registered with ClinicalTrials.gov, number NCT01620255.Findings: Between Nov 2, 2012, and Feb 4, 2016, we screened 587 patients; 357 were eligible and randomly assigned to receive placebo (n=73) or PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70). Remission rates at week 12 were significantly greater in three of four active-treatment groups than in the placebo group (2·7% [two of 73]): 7·5 mg (11·3% [eight of 71]), 22·5 mg (16·7% [12 of 72]), 75 mg (15·5% [11 of 71]), and 225 mg (5·7% [four of 70]). These rates corresponded to a stratum-adjusted (anti-TNFα-naive and anti-TNFα-experienced) risk difference versus placebo of 8·0% for 7·5 mg (90% CI 1·9 to 14, p=0·0425), 12·8% for 22·5 mg (5·6 to 19·9, p=0·0099), 11·8% for 75 mg (4·8 to 18·8, p=0·0119), and 2·6% for 225 mg (-1·2 to 6·4, p=0·1803). Four of 73 (5·5%) patients had a serious adverse event in the placebo group, ten of 71 (14·1%) in the 7·5 mg group, one of 70 (1·4%) in the 22·5 mg group, three of 73 (4·1%) in the 75 mg group, and three of 70 (4·3%) in the 225 mg group. No safety signal was observed for the study drug.Interpretation: PF-00547659 was safe and well tolerated in this patient population, and better than placebo for induction of remission in patients with moderate to severe ulcerative colitis. The greatest clinical effects were observed with the 22·5 mg and 75 mg doses.Funding: Pfizer. [ABSTRACT FROM AUTHOR]

Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy. [ABSTRACT FROM AUTHOR]

Background/Aims: To evaluate changes in gut microbiota composition following long-term proton pump inhibitor (PPI) treatment. Methods: Twenty-four-week-old F344 rats were fed diets with (n=6) or without (n=5) lansoprazole for 50 weeks. Profiles of luminal microbiota in the terminal ileum were then analyzed. Pyrosequencing of the 16S rRNA gene was performed using an FLX genome sequencer (454 Life Sciences/Roche). Results: Rats treated with lansoprazole showed significantly reduced body weights compared to controls (lansoprazole-treated rats and controls, 322.3±15.3 g vs 403.2±5.2 g, respectively, p<0.001). However, stool frequencies and consistencies did not differ between the two groups. The composition of the gut microbiota in lansoprazole- treated rats was quite different from that of the controls. In the controls, the microbiota profiles obtained from the terminal ileum showed a predominance of Proteobacteria (93.9%) due to the abundance of Escherichia and Pasteurella genera. Conversely, lansoprazole-treated rats showed an elevated population of Firmicutes (66.9%), which was attributed to an increased ratio of Clostridium g4 to Lactobacillus genera. Conclusions: This preliminary study suggests that long-term administration of PPI may cause weight loss and changes to the microbiota in the terminal ileum. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the effect of a prior gastrectomy on the difficulty of subsequent colonoscopy, and to identify the surgical factors related to difficult colonoscopies. Materials and Methods: Patients with a prior gastrectomy who had undergone a colonoscopy between 2011 and 2014 (n=482) were matched (1:6) to patients with no history of gastrectomy (n=2,892). Cecal insertion time, intubation failure, and bowel clearance score were compared between the gastrectomy and control groups, as was a newly generated comprehensive parameter for a difficult/incomplete colonoscopy (cecal intubation failure, cecal insertion time >12.9 minutes, or very poor bowel preparation scale). Surgical factors including surgical approach, extent of gastrectomy, extent of lymph node dissection, and reconstruction type, were analyzed to identify risk factors for colonoscopy performance. Results: A history of gastrectomy was associated with prolonged cecal insertion time (8.7±6.4 vs. 9.7±6.5 minutes; P=0.002), an increased intubation failure rate (0.1% vs. 1.9%; P<0.001), and a poor bowel preparation rate (24.7 vs. 29.0; P=0.047). Age and total gastrectomy (vs. partial gastrectomy) were found to be independent risk factors for increased insertion time, which slowly increased throughout the postoperative duration (0.35 min/yr). Total gastrectomy was the only independent risk factor for the comprehensive parameter of difficult/incomplete colonoscopy. Conclusions: History of gastrectomy is related to difficult/incomplete colonoscopy performance, especially in cases of total gastrectomy. In any case, it may be that a pre-operative colonoscopy is desirable in selected patients scheduled for gastrectomy; however, it should be performed by an expert endoscopist each time. [ABSTRACT FROM AUTHOR]

Background/Aims: To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm. Methods: We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms. Results: A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 highgrade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020). Conclusions: In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyze the effect of screening by using endoscopy on the diagnosis and treatment of gastric cancer. Materials and Methods: The clinicopathologic characteristics of gastric cancer were compared in individuals who underwent an endoscopy because of symptoms (non-screening group) or for screening purposes (screening group). The distributions of gastric cancer stages and treatment modalities in 2006 and 2011 were compared. Results: The proportion of patients in the screening group increased from 45.1% in 2006 to 65.4% in 2011 (P<0.001). The proportion of stage I cancers in the entire patient sample also increased (from 60.5% in 2006 to 70.6% in 2011; P=0.029). In 2011, the percentages of patients with cancer stages I, II, III, and IV were 79.9%, 8.2%, 10.9%, and 1.1%, respectively, in the screening group, and 47.9%, 10.8%, 29.8%, and 11.5%, respectively, in the non-screening group. The proportion of laparoscopic and robotic surgeries increased from 9.6% in 2006 to 48.3% in 2011 (P<0.001), and endoscopic submucosal dissection increased from 9.8% in 2006 to 19.1% 2011 (P<0.001). Conclusions: The proportion of patients diagnosed with gastric cancer by using the screening program increased between 2006 and 2011. This increase was associated with a high proportion of early-stage cancer diagnoses and increased use of minimally invasive treatments. [ABSTRACT FROM AUTHOR]

Objective Virtual chromoendoscopy (CE) is expected to enhance adenoma yield and reduce variation in performance between colonoscopists. This study aimed to compare the efficacy of narrow band imaging (NBI), flexible spectral imaging CE (FICE) and white light (WL) colonoscopy and their impact for less experienced endoscopists. Methods We performed a randomised tandem colonoscopy trial controlling for withdrawal time and bowel preparation. Average-risk adults undergoing screening colonoscopy were enrolled and randomly assigned to first withdrawal with one of the three imaging modalities (NBI (NBI-WL group), FICE (FICE-WL group) and WL (WL-WL group)). Eight colonoscopists were categorised into expert and non-expert subgroups. Results 1650 subjects (mean age 51.4 years, 63.9% men) were included (550 in each group). Compared with WL, neither NBI nor FICE increased the mean number of adenomas detected per patient (0.37 vs 0.35 and 0.36; p=0.591) or the percentage of patients with adenoma (25.3% vs 24.5% and 23.6%; p=0.753). For all three modalities, expert subgroups had higher yields of adenomas than non-expert subgroups. Learning curves were observed only for non-expert subgroups with all three modalities. The percentage of missed adenomas did not differ between the three groups (20.8% by WL vs 22.9% by NBI and 26.0% by FICE, p=0.300) and was not affected by endoscopists' expertise. Conclusions Neither NBI nor FICE improved adenoma detection or miss rates, with no difference in diagnostic efficacy between the two systems. Virtual CE had no additional benefits over WL for non-experts. Clinical trial registration number: KCT0000570. [ABSTRACT FROM AUTHOR]

Background/Aims: The accurate preoperative prediction of the risk of malignancy of gastrointestinal stromal tumors (GISTs) is difficult. The aim of this study was to determine whether tumor size and endoscopic ultrasonography (EUS) features can preoperatively predict the risk of malignancy of medium-sized gastric GISTs. Methods: Surgically resected, 2 to 5 cm gastric GIST patients were enrolled and retrospectively reviewed. EUS features, such as heterogeneity, hyperechoic foci, calcification, cystic change, hypoechoic foci, lobulation, and ulceration, were evaluated. Tumors were grouped in 1 cm intervals. The correlations of tumor size or EUS features with the risk of malignancy were evaluated. Results: A total of 75 patients were enrolled. The mean tumor size was 3.43±0.92 cm. Regarding the risk of malignancy, 51 tumors (68%) had a very low risk, and 24 tumors (32%) had a moderate risk. When the tumors were divided into three groups in 1 cm intervals, the proportions of tumors with a moderate risk were not different between the groups. The preoperative EUS features also did not differ between the very low risk and the moderate risk groups. Conclusions: Tumor size and EUS features cannot be used to preoperatively predict the risk of malignancy of medium-sized gastric GISTs. A preoperative diagnostic modality for predicting risk of malignancy is necessary to prevent the overtreatment of GISTs with a low risk of malignancy. [ABSTRACT FROM AUTHOR]

Background/Aims: Helicobacter pylori infection induces cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) overexpression, and these factors may engage in cross-talk. The aim of the present study was to evaluate the effect of H. pylori on EGFR signaling pathways and to determine whether celecoxib has an inhibitory effect on this pathway. Methods: The AGS cell line was cocultured with H. pylori G27 and the isogenic cagE- mutant. The expression of COX-2, EGFR, heparin binding-epidermal growth factor (HB-EGF), and transforming growth factor-β (TGF-β) was measured by real time-polymerase chain reaction (RT-PCR). Next, Western blot analyses of COX-2, EGFR, total Akt, phosphorylated Akt (pAkt), and phosphorylated glycogen synthase kinase-3β (pGSK3β) were performed after incubating H. pylori-treated AGS cells for 24 hours with various concentrations of celecoxib (0, 10, 20, and 30 μmol/L). Results: H. pylori infection upregulated the mRNA levels of COX-2, EGFR, HB-EGF, and TGF-β, as detected by RT-PCR. However, AGS cells treated with cagE- mutants, which have a defective type IV secretion system, did not exhibit EGFR upregulation. Celecoxib had inhibitory effects on the H. pylori-induced overexpression of COX-2 (p=0.015), EGFR (p=0.025), pAkt (p=0.025), and pGSK3β (p=0.029) by Western blot analysis. Conclusions: H. pylori with an intact type IV secretion system activated the COX-2 and EGFR-Akt pathways in the AGS cell line. As celecoxib exhibited inhibitory effects on the EGFR signaling pathway, the cross-talk of COX-2 and EGFR likely mediates H. pylori-induced gastric cancer. [ABSTRACT FROM AUTHOR]

Background and aim: The aim of this study was to test the efficacy of 10-day moxifloxacin-based triple therapy versus 2-week quadruple therapy for the second-line treatment of Helicobacter pylori infection. Methods: One hundred and ninety-two patients who had failed previous H. pylori eradication on standard triple therapy were randomized to one of two regimens: 1, moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole (20 mg b.i.d.) for 10 days (the 10MEA group), or 2, esomeprazole (20 mg b.i.d.), tripotassium dicitrate bismuthate (300 mg q.i.d.), metronidazole (500 mg t.i.d.), and tetracycline 500 mg (q.i.d.) for 14 days (the 14EBMT group). The eradication rates, drug compliances, and side-effect rates of these two regimens were compared. Results: Eradication rates by intention-to-treat and per-protocol analyses in the 10MEA and 14EMBT groups were 71.9% and 82.6%, and 71.7% and 90.5% ( p = .973 and .321), respectively. The 10MEA group was significantly superior to the 14EMBT group in terms of side-effect rates (12.2% vs. 39.6%, p = .001), and discontinuation rates due to side-effects were lower in the 10MEA group than in the 14EMBT group (0.7% vs. 13.2%, p < .001). Moreover, compliance was higher in the 10MEA group (94.2% (131/139)) than in the 14EBMT group (83.0% (44/53)) ( p = .014). Conclusion: The 10-day moxifloxacin-based triple therapy was found to have a high eradication rate with few side-effects and good drug compliance. These findings suggest that this regimen is a safe and effective second-line treatment option for H. pylori infection in Korea. [ABSTRACT FROM AUTHOR]

Background and Aim: Metronidazole and tetracycline-based second-line quadruple therapy, widely used for Helicobacter pylori infection, often ends up in failure due to antibiotic resistance and poor compliance in Korea. Our aim is to evaluate the efficacy and tolerability of moxifloxacin-based triple therapy as an alternative second-line treatment for H. pylori infection. Methods: The subjects consisted of 85 patients infected with H. pylori, in whom initial proton pump inhibitor triple therapy had failed. They were randomized to receive the following 7-day therapy: 1, moxifloxacin 400 mg q.d., esomeprazole 20 mg b.i.d., and amoxicillin 1 g b.i.d.; and 2, esomeprazole 40 mg b.i.d., tripotassium dicitrate bismuthate 300 mg q.i.d., metronidazole 500 mg t.i.d., and tetracycline 500 mg q.i.d. Eradication rates, drug compliance, and side-effect rates of each group were evaluated. Results: The eradication rates were 75.6 and 83.8% with moxifloxacin triple therapy, and 54.5 and 72.7% with quadruple therapy by intention-to-treat ( p = .042) and per-protocol analyses ( p = .260), respectively. Moxifloxacin triple therapy was significantly superior to quadruple therapy in terms of side-effect rates ( p = .039). Compliance for therapy, i.e., the percentage of tablets taken (> 85%), was 90.2 and 75.0%, numerically higher in moxifloxacin triple therapy group than in quadruple therapy group, but without statistical difference ( p = .065). Conclusions: Moxifloxacin-based triple therapy showed high eradication rates with few side effects and good drug compliance, suggesting this regimen could be a safe and effective option as second-line therapy for H. pylori infection in Korea. [ABSTRACT FROM AUTHOR]