Multicenter prospective registration study of efficacy and safety of capsule endoscopy in Crohn's disease in Japan (SPREAD-J study).

BACKGROUND: Evidence of small-bowel capsule endoscopy (SBCE) for evaluating lesions in Crohn's disease (CD) is lacking. We aimed to clarify the effectiveness and safety of SBCE in a large sample of patients with CD. METHODS: This multicenter prospective registration study recorded the clinical information and SBCE results of patients with definitive CD (d-CD) or suspected CD (s-CD). The primary outcomes were the rates of successful assessment of disease activity using SBCE, definitive diagnosis of CD, and adverse events. Secondary outcomes were the assessment of SBCE findings in patients with d-CD and s-CD and factors affecting SBCE incompletion and retention; and tertiary outcomes included the association between clinical disease activity or blood examination, endoscopic disease activity, ileal CD, and the questionnaire assessment of patient acceptance of SBCE. RESULTS: Of 544 patients analyzed, 541 underwent SBCE with 7 (1.3%) retention cases. Of 468 patients with d-CD, 97.6% could be evaluated for endoscopic activity. Of 76 patients with s-CD, 15.8% were diagnosed with 'confirmed CD'. CD lesions were more frequently observed in the ileum and were only seen in the jejunum in 3.4% of the patients. Male sex and stenosis were risk factors for incomplete SBCE, and high C-reactive protein levels and stenosis were risk factors for capsule retention. In L1 (Montreal classification) patients, clinical remission was associated with endoscopic remission but showed low specificity and accuracy. The answers to the acceptability questionnaire showed the minimal invasiveness and tolerability of SBCE. CONCLUSION: SBCE is practical and safe in patients with CD.

Thiopurine naivety at tacrolimus induction is a predictor of long-term remission in patients with intractable ulcerative colitis who responded to tacrolimus.

BACKGROUND: The short-term efficacy of tacrolimus (Tac) for steroid-dependent and steroid-resistant refractory ulcerative colitis (UC) has been demonstrated; however, its long-term outcomes have not been well documented. Thus, this study aimed to clarify the long-term outcomes of patients who achieved Tac-induced remission and identify its predictors. METHODS: This study included patients with moderate-to-severe active UC who started receiving Tac at our hospital between July 2004 and December 2016. Short-term treatment response was assessed using the Lichtiger index 3 months after starting Tac, and responding patients were further followed up to assess long-term outcomes. The primary endpoint was the relapse-free survival after Tac-induced remission, and the secondary endpoint was the identification of factors associated with relapse after Tac-induced remission. RESULTS: The cumulative relapse-free survival rate at 10 years after Tac-induced remission was 33.2%. Multivariate analysis revealed that being thiopurine naïve at Tac induction was associated with the absence of relapse (hazard ratio: 0.45; 95% confidence interval: 0.22-0.92). CONCLUSIONS: Approximately one-third of patients who achieved Tac-induced remission maintained long-term remission. Being thiopurine naïve at Tac induction was a predictor of the absence of relapse.

Adrenomedullin for biologic-resistant Crohn's disease: A randomized, double-blind, placebo-controlled phase 2a clinical trial.

BACKGROUND AND AIM: Adrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical trial to investigate the efficacy and safety of adrenomedullin in patients with Crohn's disease (CD). METHODS: This was a multicenter, double-blind, placebo-controlled phase 2a trial that evaluated 24 patients with biologic-resistant CD in Japan. Patients were randomly assigned to three groups and were given an infusion of 10 or 15 ng/kg/min of adrenomedullin or placebo for 8 h per day for 7 days. The primary endpoint was the change in the CD activity index (CDAI) at 8 weeks. The main secondary endpoints included changes in CDAI from week 4 to week 24. RESULTS: No differences in the primary or secondary endpoints were observed between the three groups by the 8th week. Changes in CDAI in the placebo group gradually decreased and disappeared at 24 weeks, but those in the adrenomedullin-treated groups (10 or 15 ng/kg/min group) remained at steady levels for 24 weeks. Therefore, a significant difference was observed between the placebo and adrenomedullin-treated groups at 24 weeks (P = 0.043) in the mixed-effects model. We noted mild adverse events caused by the vasodilatory effect of adrenomedullin. CONCLUSION: In this trial, we observed a long-lasting (24 weeks) decrease in CDAI in the adrenomedullin-treated groups. Adrenomedullin might be beneficial for biologic-resistant CD, but further research is needed.

Long-term outcomes of endoscopic balloon dilation for intestinal strictures in patients with Crohn's disease during maintenance treatment with anti-tumor necrosis factor alpha antibodies.

BACKGROUND AND AIMS: Efficacy of endoscopic balloon dilation (EBD) for intestinal strictures in patients with Crohn's disease (CD) receiving anti-tumor necrosis factor alpha antibodies (anti-TNF) as maintenance therapy is unclear. We investigated the long-term efficacy and safety of EBD for intestinal strictures in patients with CD receiving anti-TNF. METHODS: We retrospectively analyzed data from patients with CD who received anti-TNF as maintenance therapy from 2008 to 2017, underwent EBD, and were followed up for ≥6 months. The primary endpoint was the cumulative surgery-free rate. The main secondary endpoints were technical success, repeat EBD rate, risk factors affecting surgical outcomes, and safety. RESULTS: Seventy-two patients with CD were assessed. The median observation period after EBD was 50 months. The technical success rate was 67%. The 3- and 5-year cumulative surgery-free rates were 81.1% and 73.5%, respectively. The repeat EBD rate was 74%. Multivariable analyses showed that risk factors affecting surgical outcomes were age at disease onset ≤16 years (hazard ratio 3.69; 95% confidence interval 1.36-10.01; P = 0.011). Serious complications requiring surgery developed in three patients. CONCLUSIONS: Endoscopic balloon dilation was an effective and safe short-term treatment and a useful long-term treatment for CD patients with intestinal strictures receiving anti-TNF as maintenance therapy.

A nationwide, multi-center, retrospective study of symptomatic small bowel stricture in patients with Crohn's disease.

BACKGROUND: Small bowel stricture is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilatation (EBD) is a minimally invasive treatment intended to avoid surgery; however, whether EBD prevents subsequent surgery remains unclear. We aimed to reveal the factors contributing to surgery in patients with small bowel stricture and the factors associated with subsequent surgery after initial EBD. METHODS: Data were retrospectively collected from surgically untreated CD patients who developed symptomatic small bowel stricture after 2008 when the use of balloon-assisted enteroscopy and maintenance therapy with anti-tumor necrosis factor (TNF) became available. RESULTS: A total of 305 cases from 32 tertiary referral centers were enrolled. Cumulative surgery-free survival was 74.0% at 1 year, 54.4% at 5 years, and 44.3% at 10 years. The factors associated with avoiding surgery were non-stricturing, non-penetrating disease at onset, mild severity of symptoms, successful EBD, stricture length < 2 cm, and immunomodulator or anti-TNF added after onset of obstructive symptoms. In 95 cases with successful initial EBD, longer EBD interval was associated with lower risk of surgery. Receiver operating characteristic analysis revealed that an EBD interval of ≤ 446 days predicted subsequent surgery, and the proportion of smokers was significantly high in patients who required frequent dilatation. CONCLUSIONS: In CD patients with symptomatic small bowel stricture, addition of immunomodulator or anti-TNF and smoking cessation may improve the outcome of symptomatic small bowel stricture, by avoiding frequent EBD and subsequent surgery after initial EBD.

Learning Effect of Diagnosing Depth of Invasion Using Non-Extension Sign in Early Gastric Cancer.

BACKGROUND: Determining the depth of invasion is important when considering therapeutic strategies for early gastric cancer (EGC). We determined the effects of learning the non-extension sign, that is, an index of T1b2 in EGC, on identifying its depth of invasion. METHODS: Endoscopic images of 40 EGC cases (20 showing positive non-extension sign on endoscopy as T1b2 and 20 showing negative non-extension sign on endoscopy as T1a-T1b1) were randomly displayed on PowerPoint. Participants read endoscopy findings (pretest) and attended a 60-min lecture on how to read the non-extension sign. Then, they read the same images using the non-extension sign as the marker (posttest). The primary endpoint was a change in accuracy rate for determining the depth of invasion before and after attending the lecture, for nonexperts (< 80%). RESULTS: Among 35 endoscopists, 12 were nonexperts; their test results were used for analyses. Accuracy rates for pretest and posttest among nonexperts were 75.2 and 82.5%, respectively, showing a significant increase in the accuracy rate after learning to read the non-extension sign (p = 0.003). CONCLUSION: Nonexperts' diagnostic ability to determine the depth of invasion of EGC improved by learning to read the non-extension sign. Thus, the non-extension sign is considered a simple and useful diagnostic marker.

Efficacy of enteral nutrition in patients with Crohn's disease on maintenance anti-TNF-alpha antibody therapy: a meta-analysis.

Enteral nutrition (EN) is effective in Crohn's disease (CD) patients and has been shown to have an inhibitory effect on loss of response to anti-tumor necrosis factor (TNF)-alpha antibody therapy; however, the current level of evidence is not sufficient. The objective of this meta-analysis was to determine whether EN in combination anti-TNF-alpha antibody therapy is useful in maintaining remission. PubMed was used to identify all relevant studies. A total of nine articles were identified including one randomized control trial, two prospective cohort studies, and six retrospective cohort studies. We performed a meta-analysis on all these articles to assess the remission maintenance effect of EN (n = 857). The remission or response maintenance effect in the EN group was 203/288 (70.5%), which was higher than 306/569 (53.8%) in the non-EN group. The odds ratio for long-term remission or response using fixed effects model and random effects model were 2.23 (95% CI 1.60-3.10) and 2.19 (95% CI 1.49-3.22), respectively. The usefulness of EN was unclear in two prospective studies that were conducted immediately after remission induction with anti-TNF-alpha antibody therapy was detected. Differences in the definition of relapse and the observation period among articles were considered to be limitations. This analysis suggests that EN is effective for maintaining remission in patients already in remission or response as a result of anti-TNF-alpha antibody maintenance therapy.

[A case of a simple ulcer associated with ulcerative colitis that demonstrated a good clinical response to infliximab].

We present a case of a man in his 60s who had been in clinical remission of ulcerative colitis (UC) after treatment with 5ASA. Over the clinical course, he developed an isolated deep ulcer at the end of the ileum. There were moderate active UC findings in the rectum. We diagnosed a simple ulcer associated with UC and started treatment with azathioprine and infliximab (IFX). Shortly after the treatment, the ulcer began to scar. We report a rare case of a simple ulcer that accompanied UC, and for which IFX was effective.