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Background and Aim: The aim of this study was to elucidate the continuous use of antithrombotic medications during the peri-colorectal endoscopic submucosal dissection (ESD) period., Methods: This study included 468 patients with colorectal epithelial neoplasms treated by ESD, consisting of 82 under antithrombotic medications and 386 patients without the medications. Among patients taking antithrombotic medications, antithrombotic agents were continued during the peri-ESD period. Clinical characteristics and adverse events were compared after propensity score matching., Results: Before and after propensity score matching, post-colorectal ESD bleeding rate was higher in patients continuing antithrombotic medications (19.5% and 21.6%, respectively) than in those not taking antithrombotic medications (2.9% and 5.4%, respectively). In the Cox regression analysis, continuation of antithrombotic medications was associated with post-ESD bleeding risk (hazard ratio, 3.73; 95% confidence interval, 1.2-11.6; P < 0.05) compared with patients without antithrombotic therapy. All patients who experienced post-ESD bleeding were successfully treated by endoscopic hemostasis procedure or conservative therapy., Conclusions: Continuation of antithrombotic medications during the peri-colorectal ESD period increases the risk of bleeding. However, the continuation may be acceptable under careful monitoring for post-ESD bleeding., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Double-balloon endoscopic retrograde cholangiography (DBERC) is a valuable procedure for patients with altered gastrointestinal anatomy. Nonetheless, it is time-consuming and burdensome for both patients and endoscopists, partly because route selection in the reconstructed bowel with complicating loop is challenging. Carbon dioxide insufflation enterography is reportedly useful for route selection in the blind loop. This prospective randomized clinical trial investigated the usefulness of carbon dioxide insufflation enterography for route selection by comparing it with conventional observation., Methods: Patients scheduled to undergo DBERC were consecutively registered. They were divided into carbon dioxide insufflation enterography and conventional groups via randomization according to stratification factors, type of reconstruction methods, and experience with DBERC. The primary endpoint was the correct rate of initial route selection. The secondary endpoints were the insertion time, examination time, amount of anesthesia drugs, and complications., Results: The correct rate of route selection was significantly higher in the carbon dioxide insufflation enterography group (23/25, 92%) than in the visual method (15/25, 60%) (P = 0.018). The insertion time was significantly shorter in the carbon dioxide insufflation enterography group than in the visual group (10.8 ± 11.1 min vs 29.8 ± 15.7 min; P < 0.001). No significant differences in complications were noted between the two groups. The amounts of sedatives and analgesics used were significantly lower in the carbon dioxide insufflation enterography group (P < 0.001 and P < 0.001, respectively)., Conclusions: Carbon dioxide insufflation enterography can reduce the burden of DBERC on patients and endoscopists by shortening the examination time and reducing the amount of medication., (© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Accurate polyp size estimation is essential in deciding the therapeutic strategy of colorectal polyps and endoscopic surveillance intervals. However, many endoscopists frequently make incorrect size estimations without being aware of their errors. This cross-sectional study aimed to clarify the characteristics of endoscopists associated with inaccurate estimation., Methods: We previously conducted a web trial involving 261 endoscopists in 51 institutions in Japan to assess their ability to estimate polyp size. Participants answered questions about polyp size using visual estimates in a test involving images of 30 polyps. Here, we investigated the relationships between inaccurate size estimation and the backgrounds of participants. The rates of overestimation and underestimation of polyp size were also compared to clarify any trends in the answers of participants with low accuracy (< 50%)., Results: Multivariable logistic regression analysis revealed that the number of colonoscopic procedures in the past year was the only factor associated with a low accuracy of polyp size estimation (odds ratio 0.750, 95% confidence interval 0.609-0.925; P = 0.007). Endoscopists with low accuracy had a greater tendency to overestimate polyp size (42.3% overestimation and 21.2% underestimation, P < 0.001) compared with other endoscopists (16.6% overestimation and 17.9% underestimation, P = 0.951)., Conclusions: Endoscopists with limited experience of colonoscopy in the past year were more likely to make frequent errors in size estimation. Furthermore, endoscopists making inaccurate size estimations had a propensity to overestimate polyp size., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Ustekinumab (UST), a fully humanized monoclonal antibody against the p40 subunit of interleukin-12/23, is effective for the treatment of Crohn's disease (CD). The benefit of concomitant use of an immunomodulator (IM) with UST, however, is unclear. This study aimed to provide a systematic review and meta-analysis comparing the efficacy and safety of concomitant use of an IM with UST as an induction therapy for CD patients., Methods: A systematic literature search was performed using PubMed/MEDLINE, the Cochrane Library, and the Japana Centra Revuo Medicina from inception to October 31, 2019. The main outcome measure was achievement of clinical efficacy (remission, response, and clinical benefit) at 6-12 weeks. The quality of the included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) tools. The fixed-effects model was used to calculate the pooled odds ratios., Results: From 189 yielded articles, six including a total of 1507 patients were considered in this meta-analysis. Concomitant use of an IM with UST was significantly effective than UST monotherapy as an induction therapy (pooled odds ratio in the fixed-effects model: 1.35, 95% confidence interval [1.06-1.71], P = 0.015). The heterogeneity among studies was low (I 2  = 2.6%). No statistical comparisons of the occurrence of adverse events between UST monotherapy and concomitant use of an IM with UST were performed., Conclusion: The efficacy of concomitant use of an IM with UST as an induction therapy for CD was significantly superior to that of monotherapy with UST., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Anti-tumor necrosis factor (TNF) α agents are now well known to function as effective treatments for Crohn's disease (CD). Several meta-analyses have revealed the efficacy of anti-TNF therapy for preventing recurrence after surgery; however, the efficacies reported in some prospective studies differed according to the outcomes. Moreover, adverse events (AEs) were not well evaluated. We conducted this systematic review and meta-analysis to evaluate both the efficacy of anti-TNF therapy after stratification by the outcome of interest and the AEs., Methods: We performed a systematic literature review of studies investigating anti-TNF therapy, CD, and postoperative recurrence. Meta-analyses were performed for endoscopic and clinical recurrence and AEs., Results: A total of 570 participants, including 254 patients in the intervention group and 316 patients in the control group, in eight studies, were analyzed for recurrence. Based on the results of the meta-analysis, the efficacies of anti-TNF therapy at preventing endoscopic and clinical recurrence were as follows: relative risk (RR) 0.34, 95% confidence interval (CI) 0.22-0.53 and RR 0.60, 95% CI 0.36-1.02, respectively. The RR of AEs with anti-TNF therapy was 1.75 (95% CI 0.81-3.79)., Conclusions: Anti-TNF therapy after surgery for CD displays efficacy at preventing endoscopic recurrence for 1-2 years, without increasing the incidence of AEs. However, clinical recurrence was not significantly reduced. The efficacy of postoperative anti-TNF therapy may differ in terms of the outcomes, which include long-term prevention, the avoidance of further surgery, and cost-effectiveness., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Although surveillance colonoscopy is recommended by several guidelines for Crohn's disease (CD), the evidence is insufficient to support the validity of this recommendation. Moreover, the efficacy of surveillance colonoscopy for anorectal cancer remains unclear. Therefore, we performed a systematic review of cancer in patients with CD before considering the proper surveillance methods., Methods: We conducted a systematic review and meta-analysis examining the incidence of intestinal cancer and a literature review to clarify the characteristic features of cancer in CD. We performed the systematic literature review of studies published up to May 2019., Results: Overall, 7344 patients were included in eight studies. The standardized incidence ratios (95% confidence intervals) of colorectal cancer (CRC) and small bowel cancer (SBC) were 2.08 (1.43-3.02) and 22.01 (9.10-53.25), respectively. The prevalence of CRC and SBC was 57/7344 (0.77%) and 17/7344 (0.23%), respectively, during a median follow-up of 12.55 years. Additionally, 54 studies reporting 208 anorectal cancer cases were identified. In patients with anorectal cancer, the prognosis for survival was 2.1 ± 2.3 years, and advanced cancer greater than stage T3 occurred in 46/74 patients (62.1%). Many more reports of anorectal cancer were published in Asia than in Western countries., Conclusion: Although we were unable to state a recommendation for surveillance for SBC, we should perform cancer surveillance for CRC in patients with CD. However, the characteristics of cancer may differ according to geography or race. We must establish proper and effective surveillance methods that are independently suitable to detect these differences., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: A risk-stratification score may be useful for colorectal cancer (CRC) screening, alongside screening colonoscopy (CS) and fecal immunochemical test (FIT). This study aimed to evaluate the effectiveness and cost-effectiveness of population-based CRC screening strategies using CS, FIT, and the Japanese CRC screening score., Methods: The effectiveness in quality-adjusted life years (QALYs), cost-effectiveness, and required number of CS procedures were evaluated for screening strategies with primary screening CS (strategy 1), FIT (strategy 2), and the risk score (strategy 3), using a simulation model analysis with two scenarios. In scenario 1, uptake rates for all tests were 60%. In scenario 2, uptake rates for FIT and a risk score were 40%, and those for screening CS and CS following a positive FIT or high risk score were 20% and 70%, respectively., Results: In scenario 1, strategy 1 gained the highest QALYs and required the highest cost. The incremental cost-effectiveness ratios per QALY gained for strategy 1 against the others were lower than 5 000 000 JPY. Strategy 1 required more than twice as many CS procedures as the other strategies. In scenario 2, strategy 3 had the highest QALYs and lowest cost, and strategy 1 had the lowest QALYs and highest cost., Conclusions: Screening CS has the potential to be the most effective and cost-effective form of CRC screening, although it requires a large number of CS procedures. However, if non-invasive tests are preferred by recipients, other screening strategies, particularly those using the risk score, can be more effective and cost-effective., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: Indigo naturalis (IN) is a traditional Chinese herbal medicine reported to be effective in inducing remission in ulcerative colitis (UC). We conducted a retrospective observational study to investigate the efficacy and safety of IN for induction and maintenance therapy in patients with inflammatory bowel disease., Methods: Data were collected from the electric medical records of patients with inflammatory bowel disease who had started IN treatment between March 2015 and April 2017 at Kyushu University Hospital. Clinical response and remission rates were assessed based on the clinical activity index determined by Rachmilewitz index or Crohn's disease (CD) activity index. Cumulative IN continuation rates were estimated using the Kaplan-Meier method. Overall adverse events (AEs) during follow-up were also analyzed., Results: Seventeen UC patients and eight CD patients were enrolled. Clinical response and remission rates at week 8 were 94.1% and 88.2% in UC patients and 37.5% and 25.0% in CD patients, respectively. Clinical remission rates, as assessed through non-responders imputation analyses at weeks 52 and 104, were 76.4% and 70.4% in UC patients and 25.0% and 25.0% in CD patients, respectively. Ten patients (40%) experienced AEs during follow-up. Three patients (12%) experienced severe AEs, including acute colitis requiring hospitalization in two patients and acute colitis with intussusception requiring surgery in one patient., Conclusions: Indigo naturalis showed favorable therapeutic efficacy in UC, whereas its therapeutic efficacy in CD appeared to be modest. The risk of severe AEs should be recognized for IN treatment., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: The aim of this study was to clarify the additional effect of a concomitant elemental diet (ED) for patients with Crohn's disease on maintenance anti-tumor necrosis factor-α antibody (anti-TNF)., Methods: Crohn's disease patients who received anti-TNF induction therapy were enrolled. Patients who achieved clinical response (defined as delta Crohn's disease activity index [CDAI] > 70 and CDAI < 200) at 10-14 weeks after the start of infliximab or adalimumab were included. Eligible patients took a tolerability test of ED (900 kcal/day) for 3 days. Then, patients who preferred concomitant ED and whose ED tolerance was confirmed were allocated to the ED group and given Elental 900 kcal/day or more. Other patients were allocated to the non-ED group. The primary endpoint was the cumulative remission rate at 2 years after baseline. Clinical relapse was defined as CDAI > 200 and/or need for additional treatment. Adherence to the ED was confirmed at each visit., Results: Seventy-two patients were included. Thirty-seven were allocated to the ED group, and 35 were allocated to the non-ED group. The cumulative remission rate at 2 years was not significantly different between the two groups (60.9% vs 56.7%, P = 0.98). Adherence to the ED in the ED group was relatively low, and only 11 patients were maintained on an ED of 900 kcal/day., Conclusions: The addition of ED for Crohn's disease patients who responded to initial anti-TNF induction therapy was not found to improve outcomes. The efficacy of concomitant ED in other clinical settings, such as loss of response, needs to be clarified in the future (UMIN000009789)., (© 2018 The Authors Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: The gut microbiota is suggested to play an important role in the pathogenesis of ulcerative colitis (UC). However, interindividual and spatial variations hamper the identification of UC-related changes. We thus investigated paired mucosa-associated microbiota obtained from both inflamed and non-inflamed sites of UC patients and corresponding sites of non-inflammatory bowel disease (IBD) controls., Methods: Mucosal biopsies of both inflamed and non-inflamed sites were obtained from 14 patients with active UC of the left-sided or proctitis type. Paired mucosal biopsies of the corresponding sites were obtained from 14 non-IBD controls. The microbial community structure was investigated using 16S ribosomal RNA gene sequences, followed by data analysis using qiime and LEfSe softwares., Results: Microbial alpha diversity in both inflamed and non-inflamed sites was significantly lower in UC patients compared with non-IBD controls. There were more microbes of the genus Cloacibacterium and the Tissierellaceae family, and there were less microbes of the genus Neisseria at the inflamed site when compared with the non-inflamed site in UC patients. Decreased abundance of the genera Prevotella, Eubacterium, Neisseria, Leptotrichia, Bilophila, Desulfovibrio, and Butyricimonas was evident at the inflamed site of UC patients compared with the corresponding site of non-IBD controls. Among these taxa, the genera Prevotella and Butyricimonas were also less abundant at the non-inflamed site of UC patients compared with the corresponding site in non-IBD controls., Conclusions: Mucosal microbial dysbiosis occurs at both inflamed and non-inflamed sites in UC patients. The taxa showing altered abundance in UC patients might mediate colonic inflammation., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background and Aim: microRNAs (miRNAs) have been suggested to be candidates for biomarkers in various diseases including Crohn's disease (CD). To identify possible biomarkers predictive of the therapeutic effect of infliximab in CD, we investigated serum miRNA levels during the induction therapy by the medication., Methods: Nineteen CD patients who were applied to the induction therapy by infliximab were enrolled. Serum samples for miRNA analyses were obtained at weeks 0 and 6, and the therapeutic efficacy by infliximab was assessed according to the Crohn's disease activity index value at week 14. Exploratory miRNA profiling by low-density array was initially performed in three patients. The levels of candidate miRNA were subsequently determined by real-time polymerase chain reaction (PCR) assays in the remaining 16 patients. The miRNA levels during the induction therapy were compared between the two groups classified by the clinical response to infliximab at week 14., Results: Low-density array analysis identified 14 miRNAs that showed twofold or more altered expression during the induction therapy by infliximab. Subsequent analysis by real-time PCR demonstrated significantly increased levels of five miRNAs (let-7d, let-7e, miR-28-5p, miR-221, and miR-224) at week 6 when compared with those at week 0 (P < 0.05 each). In addition, miRNA levels of let-7d and let-7e were significantly increased in the group of patients who achieved clinical remission by infliximab (P = 0.001 and P = 0.002, respectively)., Conclusion: let-7d and let-7e might be possible therapeutic biomarkers in patients with CD, who are treated by infliximab., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background and Aim: Until the approval of patency capsule, capsule endoscopy (CE) has not been routinely applied for the diagnosis of Crohn's disease (CD) in Japan. We aimed to survey current situation of CE use for patients with CD in Japan., Methods: The nationwide survey of 40 Japanese institutions identified 94 patients with established CD (eCD) and 80 patients with suspected CD (sCD), who were examined by CE. Types and positive rates of mucosal injury under CE and capsule retention rate were investigated. In sCD, final diagnosis after CE was also analyzed., Results: Patients with eCD comprised 82 patients of ileitis or ileocolitis type, while 12 patients had CD of colitis type. CE identified mucosal injuries in 83 of 94 patients. Eight of 12 patients with eCD of colitis type had ileal lesions under CE, thereby being reclassified as ileocolitis type. In patients with sCD, CE detected mucosal injuries in 58 patients. Linear ulceration and cobblestone appearance were depicted in 22 and 3 patients, respectively, thereby resulting in established diagnosis of CD in 23 patients. Mucosal lesion was not found in 22 patients with sCD, who were diagnosed as not having CD. Capsule retention rate was not statistically different between patients with eCD and those with sCD (7.4% vs 6.3%, P = 1.0)., Conclusions: CE is useful for the evaluation of small bowel mucosal injuries in Japanese patients with sCD and eCD. Possible intestinal stricture needs to be carefully evaluated before CE even in patients with sCD., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: The aim of the present study was to elucidate the effect of sulindac on uncolectomized familial adenomatous polyposis (FAP)., Methods: Seven FAP patients (SU group) without proctocolectomy were given sulindac 300 mg/day orally for 12 months. Six FAP patients without sulindac (non-SU group) served as controls. Colorectal lesions were assessed by protrusion index (no. radiolucent areas/cm(2); PI) under barium enema examination and non-polypoid lesion were assessed under chromoscopy prior to and at the end of the observation period. In the SU group, germline adenomatous polyposis coli (APC) mutation was determined by protein truncation test., Results: In the SU group, PI decreased significantly in the distal colon (from 3.0 +/- 1.1 to 1.1 +/- 0.8/cm(2), P < 0.02) and in the proximal colon (from 3.4 +/- 2.4 to 0.9 +/- 1.3/cm(2), P < 0.02). The PI in the non-SU group slightly but significantly increased in the distal colon (from 1.0 +/- 0.8 to 1.2 +/- 0.9/cm(2); P < 0.05) and it remained unchanged in the proximal colon (from 0.6 +/- 0.3 to 0.7 +/- 0.3/cm(2); P > 0.05). Chromoscopy at the end of observation identified non-polypoid lesions in five patients in the SU group, whereas such lesions were not found in the non-SU group (71% vs 0%, P = 0.016). Decrease in PI was not different among distal APC mutation (exons 1-9), proximal APC mutation (exons 10-15) and negative mutation., Conclusion: Sulindac reduces colorectal adenomas of protruding type in uncolectomized FAP. The effect of sulindac may be unrelated to genotype of FAP.