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Background/Aims Noninvasive objective monitoring is advantageous for optimizing treatment strategies in patients inflammatory bowel disease (IBD). Fecal calprotectin (FCP) is superior to traditional biomarkers in terms of assessing the activity in patients with IBD. However, there are the differences among several FCP assays in the dynamics of FCP. In this prospective multicenter trial, we investigated the usefulness of FCP measurements in adult Japanese patients with IBD by reliable enzyme immunoassay using a monoclonal antibody. Methods We assessed the relationship between FCP levels and disease or endoscopic activity in patients with ulcerative colitis (UC, n=64) or Crohn’s disease (CD, n=46) compared with healthy controls (HCs, n=64). Results FCP levels in UC patients strongly correlated with the Disease Activity Index (rs=0.676, P

Background/Aims: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD).Methods: One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing.Results: None of the 5 variants were associated with gastrointestinal intolerance to AZA. However, NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (

Objective: To evaluate the influence of low-dose, enteric-coated aspirin tablets (100 mg/day for 2 years) on colorectal tumour recurrence in Asian patients with single/multiple colorectal tumours excised by endoscopy. Design: A double-blinded, randomised, placebocontrolled multicentre clinical trial was conducted. Participants: 311 subjects with single/multiple colorectal adenomas and adenocarcinomas excised by endoscopy were enrolled in the study (152 patients in the aspirin group and 159 patients in the placebo group). Enrolment began at the hospitals (n=19) in 2007 and was completed in 2009. Results: The subjects treated with aspirin displayed reduced colorectal tumourigenesis and primary endpoints w th an adjusted OR of 0.60 (95% CI 0.36 to 0.98) compared with the subjects in the placebo group. Subgroup analysis revealed that subjects who were nonsmokers, defined as those who had smoked in the past or who had never smoked, had a marked reduction in the number of recurrent tumours in the aspirin-treated group. The adjusted OR for aspirin treatment in nonsmokers was 0.37 (CI 0.21 to 0.68, p<0.05). Interestingly, the use of aspirin in smokers resulted in an increased risk, with an OR of 3.44. In addition, no severe adverse effects were observed in either group. Conclusions: Low-dose, enteric-coated aspirin tablets reduced colorectal tumour recurrence in an Asian population. The results are consistent with those obtained from other randomised controlled trials in Western countries. [ABSTRACT FROM AUTHOR]

Activation of the NOD-Like Receptor Family, Pyrin Domain-Containing 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1, triggers pro-caspase-1 cleavage promoting the processing of pro-interleukin (IL)-1β into mature IL-1β, which is critical for the development of non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. We investigated the effects of isoliquiritigenin, a flavonoid derived from the roots of Glycyrrhiza species, on NSAID-induced small intestinal damage and the inflammasome activation. To induce enteropathy, mice were administered indomethacin by gavage with or without isoliquiritigenin pretreatment. Some mice received an intraperitoneal injection of recombinant murine IL-1β in addition to isoliquiritigenin and indomethacin. Indomethacin induced small intestinal damage and increased protein levels of cleaved caspase-1 and mature IL-1β in the small intestine. Treatment with 7.5 and 75 mg/kg isoliquiritigenin inhibited indomethacin-induced small intestinal damage by 40 and 56%, respectively. Isoliquiritigenin also inhibited the indomethacin-induced increase in cleaved caspase-1 and mature IL-1β protein levels, whereas it did not affect the mRNA expression of NLRP3, ASC, caspase-1, and IL-1β. Protection against intestinal damage in isoliquiritigenin-treated mice was completely abolished with exogenous IL-1β. NLRP3–/– and caspase-1–/– mice exhibited resistance to intestinal damage, and isoliquiritigenin treatment failed to inhibit the damage in NLRP3–/– and caspase-1–/– mice. Isoliquiritigenin prevents NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Background and Aim In patients with ulcerative colitis ( UC), colonoscopy is an essential procedure for evaluating mucosal damage, and treatment outcomes. A new flexible ultrathin colonoscope ( PCF- PQ260) has been developed to readily pass through tortuous and narrow lesions of the colon and cause minimum patient discomfort. The objective of the present study was to evaluate the comfort and performance of this new type of scope in UC patients who underwent colonoscopy for estimation of mucosal inflammation, basically without sedation. Methods In a prospective, single-center setting, among 107 UC patients who were to undergo colonoscopy, 84 eligible cases were randomly assigned to the new ultrathin flexible colonoscope, PCF- PQ260 ( n = 42) or to a conventional colonoscope, PCF- Q260A ( n = 42). Main outcome measure was patient pain level determined by visual analogue scale ( VAS) with 0 = none, and 100 = extremely painful. Other outcomes were cecal intubation time, rate of complete intubation (to reach the cecum) and rate of procedural complications. Results VAS score was significantly lower in the new-scope group as compared with the conventional-scope group: mean ± SD, median (range): 19.3 ± 16.9, 14 (0-62) vs 32.0 ± 21.6, 31.8 (0-100, P = 0.005). However, cecal intubation rate (97.6%) and time (4 min) were similar in the two groups. There was no procedure-related serious complication in either group. Conclusion The findings indicated that the flexible ultrathin colonoscope PCF- PQ260 has significantly better tolerability in UC patients compared to a conventional colonoscope. [ABSTRACT FROM AUTHOR]

Background/Aims: Weekly granulocyte/monocyte adsorption (GMA) to deplete elevated and activated leucocytes should serve as a non-pharmacological intervention to induce remission in patients with ulcerative colitis (UC). This trial assessed the efficacy of monthly GMA as a maintenance therapy to suppress UC relapse. Methods: Thirty-three corticosteroid refractory patients with active UC received 10 weekly GMA sessions as a remission induction therapy. They were then randomized to receive one GMA session every 4 weeks (True, n=11), extracorporeal circulation without the GMA column every 4 weeks (Sham, n=11), or no additional intervention (Control, n=11). The primary endpoint was the rate of avoiding relapse (AR) over 48 weeks. Results: At week 48, the AR rates in the True, Sham, and Control groups were 40.0%, 9.1%, and 18.2%, respectively. All patients were steroid-free, but no statistically significant difference was seen among the three arms. However, in patients who could taper their prednisolone dose to <20 mg/day during the remission induction therapy, the AR in the True group was better than in the Sham (p<0.03) or Control (p<0.05) groups. Conclusions: Monthly GMA may potentially prevent UC relapse in patients who have achieved remission through weekly GMA, especially in patients on <20 mg/day PSL at the start of the maintenance therapy. [ABSTRACT FROM AUTHOR]

Background and aims: Oral mesalazine formulations are effective in the treatment of active ulcerative colitis (UC). It is not clear what induction dose of mesalazine is optimal for treating patients with active UC. We aimed to evaluate the efficacy and safety of 4 versus 2.25 g/day for selected patients with active UC. Methods: A multicenter, randomized, double-blind, parallel-group clinical study in 39 Japanese medical institutions. A total of 123 patients with moderately active UC received 4 g/day (two divided doses) versus 2.25 g/day (three divided doses) for 8 weeks. Primary endpoint was the ulcerative colitis-disease activity index (UC-DAI) score before and after 8 weeks of treatment. The improvement of each individual UC-DAI variable, remission, and efficacy rates were secondary endpoints. Safety was determined by laboratory data, vital signs, subjective symptoms, and objective findings. Results: Patients receiving 4 g/day achieved a change in UC-DAI score significantly superior to those receiving 2.25 g/day [−3.0 (95% confidence intervals (CI) −3.8 to −2.3) vs. −0.8 (95% CI −1.8 to 0.1), respectively]. There were significant differences in all UC-DAI variables between the groups. Remission rates were 22.0% (4 g/day) and 15.3% (2.25 g/day). The efficacy rate was significantly better with 4 versus 2.25 g/day [76.3 vs. 45.8%, respectively (95% CI 13.8-47.2); P = 0.001]. No difference was seen in adverse events or adverse drug reactions. Conclusions: A dose of 4 g/day was significantly superior to 2.25 g/day in terms of UC-DAI score for patients with moderately active UC. Safety profiles were similar for both doses. [ABSTRACT FROM AUTHOR]

The rapidly increasing incidence of colorectal cancer in Japan poses a great challenge to researchers to develop preventive strategies against this disease. Thus far, several clinical trials for this purpose have been planned in Japanese subjects; some have been completed and documented while others are still ongoing. Also, the Ministry of Health, Labour and Welfare of Japan recognizes the significance of cancer prevention studies, especially against colorectal cancer, including it as one of the pillars in the “Third Research Project on General Strategies against Cancer” and funding several large-scale projects. Among them are two chemoprevention studies currently being performed: in patients with previous sporadic colorectal tumors (J-CAPP study) and in patients with familial adenomatous polyposis (J-FAPP study II). Both are double-blind randomized controlled trials with low-dose aspirin (100 mg/day), which is generally considered to be safe for long-term use. This article outlines relevant past clinical data and gives a brief introduction to these two studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Background. Recently, the acquisition by Helicobacter pylori of resistance to antibiotics has become a serious problem. Therefore, nonantibiotic substances are required to diminish H. pylori -induced gastric lesions. In the present study, the effects of Cladosiphon fucoidan were examined in terms of H. pylori attachment to porcine gastric mucin in vitro and Helicobacter pylori -induced gastritis in vivo. Methods. The inhibitory effect of Cladosiphon fucoidan and other polysaccharides on H. pylori attachment to porcine gastric mucin was assayed in vitro with mucin-coated microtiter plates. The effect of Cladosiphon fucoidan on H. pylori -induced gastritis was examined in vivo using Mongolian gerbils. H. pylori- inoculated gerbils were given fucoidan in drinking water. Six weeks after H. pylori -inoculation, gerbils were sacrificed for macroscopic and microscopic examination of gastric lesions and counting of viable H. pylori in the gastric mucosa. Results. Cladosiphon fucoidan inhibited the H. pylori attachment to porcine gastric mucin at pH 2.0 and 4.0. Two other sulfated polysaccharides, Fucus fucoidan and dextran sulfate sodium, also inhibited the attachment but only at pH 2.0. Inhibitory effects of these three sulfated polysaccharides were not observed at pH 7.2 and nonsulfated polysaccharides, such as mannan and dextran, exerted no influence at any pH. In the in vivo experiment, the H. pylori -induced gastritis and the prevalence of H. pylori infected animals were markedly reduced by fucoidan in a dose-dependent manner, at doses of 0.05 and 0.5% in the drinking water. Conclusion. Cladosiphon fucoidan may deserve particular attention as a safe agent that can prevent H. pylori infection and reduce the risk of associated gastric cancer. [ABSTRACT FROM AUTHOR]

The article lists the topics to be released in the "Journal of Gastroenterology & Hepatology" in December 2012 including one on therapeutic armamentarium of ulcerative proctitis, management of hepatic incidentalomas, and balloon enteroscopy.

Aim: To clarify the usefulness of postsurgical capsule endoscopy (CE) in the diagnosis of recurrent small bowel lesions of Crohn's disease (CD)., Methods: This prospective study included 19 patients who underwent ileocolectomy or partial ileal resection for CD. CE was performed 2-3 wk after surgery to check for the presence/absence and severity of lesions remaining in the small bowel, and for any recurrence at the anastomosed area. CE was repeated 6-8 mo after surgery and the findings were compared with those obtained shortly after surgery. The Lewis score (LS) was used to evaluate any inflammatory changes of the small bowel., Results: One patient was excluded from analysis because of insufficient endoscopy data at the initial CE. The total LS shortly after surgery was 428.3 on average (median, 174; range, 8-4264), and was ≥ 135 (active stage) in 78% (14 of 18) of the patients. When the remaining unresected small bowel was divided into 3 equal portions according to the transition time (proximal, middle, and distal tertiles), the mean LS was 286.6, 83.0, and 146.7, respectively, without any significant difference. Ulcerous lesions in the anastomosed area were observed in 83% of all patients. In 38% of the 13 patients who could undergo CE again after 6-8 mo, the total LS was higher by ≥ 100 than that recorded shortly after surgery, thus indicating a diagnosis of endoscopic progressive recurrence., Conclusion: Our pilot study suggests that CE can be used to objectively evaluate the postoperative recurrence of small bowel lesions after surgery for CD.