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Abstract There is insufficient evidence comparing the outcomes of tacrolimus-based remission induction therapy with infliximab in refractory ulcerative colitis (UC) and evidence regarding optimal strategies after tacrolimus-based remission induction therapy. We conducted a multi-institutional retrospective study of patients with UC treated with tacrolimus or infliximab between January 2010 and March 2019. The proportion of clinical remission at week 8 and cumulative colectomy-free rate were examined using propensity score matching analysis. The predictors for colectomy after tacrolimus induction were also investigated. Ninety patients in the tacrolimus group and 151 in the infliximab group were enrolled. The proportion of patients in clinical remission at week 8 was 65.2% in the matched tacrolimus group and 37.3% in the matched infliximab group (P = 0.0016), and the long-term colectomy-free rate was lower in the matched tacrolimus group than in the matched infliximab group (P = 0.0003). After clinical remission with tacrolimus, a serum albumin level of ≤ 3.5 g/dL at week 8 was extracted as a factor predicting colectomy (area under the curve: 0.94). Tacrolimus showed a higher remission induction effect for UC compared to infliximab. However, a high rate of colectomy after transition to maintenance treatment was found to be a concern for tacrolimus therapy.

Abstract Serum leucine-rich alpha-2 glycoprotein (LRG) can monitor disease activities during biologics treatment in patients with inflammatory bowel disease (IBD). It is unclear whether the pretreatment serum LRG level can predict clinical effectiveness including serum trough levels of ustekinumab in patients with IBD. This multicenter prospective cohort study included 184 patients (Crohn’s disease, 104; ulcerative colitis, 80) who received ustekinumab (n = 119) or anti-tumor necrosis factor (n = 65) between January 2019 and March 2023. Multivariate logistic regression analysis revealed serum LRG level at week 0 (0w-LRG, odds ratio 0.12, 95% confidence interval 0.02–0.68) as one of significant factors for clinical remission at week 8. We divided patients into the low- and the high-LRG groups by the median 0w-LRG (18.2 µg/mL) and compared the effectiveness. In patients who received ustekinumab, the proportion of clinical remission at week 8 was significantly different between in the low- (76.9%) and in the high-LRG group (59.3%, P = 0.038), and median serum trough level at week 8 was significantly different between in the low- (10.9 µg/mL, interquartile range 6.7–13.4) and the high-LRG group (5.3 µg/mL, interquartile range 2.4–8.3, P

Abstract Background and aim Various techniques for direct biopsy from gastrointestinal subepithelial tumors (SETs) have been reported, although no standard method has been established. A common feature of these techniques is the removal of overlaying mucosa to enable direct biopsies from the SETs. These methods have been synthesized under the collective term “unroofing technique”. We conducted a multicenter retrospective study to assess its efficacy and identify potential complications. Methods This study was conducted in 10 hospitals and involved all eligible patients who underwent unroofing techniques to obtain biopsies for gastrointestinal SETs between April 2015 and March 2021. The primary endpoint was the diagnostic accuracy of the unroofing technique, and the secondary endpoints were the incidence of adverse events and the factors contributing to the accurate diagnosis. Results The study included 61 patients with 61 gastrointestinal SETs. The median tumor size was 20 mm, and the median procedure time was 38 min, with 82% successful tumor exposure. The rate of pathological diagnosis was 72.1%. In 44 patients with a pathological diagnosis, two showed discrepancies with the postresection pathological diagnosis. No factors, including facility experience, organ, tumor size, or tumor exposure, significantly affected the diagnostic accuracy. There was one case of delayed bleeding and two cases of perforation. Conclusion The diagnostic yield of the unroofing technique was acceptable. The unroofing technique was beneficial regardless of institutional experience, organ, tumor size, or actual tumor exposure.

Abstract Background Autophagy plays an important role in carcinogenesis and tumor progression in many cancers, including gastric cancer. Cytotoxin-associated gene A (CagA) is a well-known virulent factor in Helicobacter pylori (H. pylori) infection that plays a critical role in gastric inflammation and gastric cancer development. However, its role in autophagy during these processes remains unclear. Therefore, we aimed to clarify the role of CagA in autophagy in CagA-related inflammation. Methods We evaluated the autophagic index of AGS cells infected with wild-type cagA-positive H. pylori (Hp-WT) and cagA-knockout H. pylori (Hp-ΔcagA) and rat gastric mucosal (RGM1) cells transfected with CagA genes. To identify the mechanisms underlying the down regulation of autophagy in AGS cells infected with H. pylori, we evaluated protein and mRNA expression levels of autophagy core proteins using western blotting and quantitative reverse transcription-polymerase chain reaction (RT-PCR). To determine whether autophagy induced the expression of the pro-inflammatory mediator, cyclooxygenase-2 (COX-2), we evaluated COX-2 expression in AGS cells treated with an autophagy inducer and inhibitor and infected with H. pylori. In addition, we evaluated whether COX-2 protein expression in AGS cells influenced beclin-1 (BECN1) expression with si-RNA transfection when infected with H. pylori. Results Autophagic flux assay using chloroquine showed that autophagy in AGS cells was significantly suppressed after H. pylori infection. The autophagic index of AGS cells infected with Hp-WT was decreased significantly when compared with that in AGS cells infected with Hp-ΔcagA. The autophagic index of RGM1 cells transfected with CagA was lower, suggesting that CagA inhibits autophagy. In addition, BECN1 expression levels in AGS cells infected with Hp-WT were reduced compared to those in AGS cells infected with Hp-ΔcagA. Furthermore, COX-2 expression in AGS cells infected with H. pylori was controlled in an autophagy-dependent manner. When AGS cells were transfected with small interfering RNA specific for BECN1 and infected with Hp-WT and Hp-ΔcagA, COX-2 was upregulated significantly in cells infected with Hp-ΔcagA. Conclusions In conclusion, the H. pylori CagA protein negatively regulated autophagy by downregulating BECN1. CagA-induced autophagy inhibition may be a causative factor in promoting pro-inflammatory mediator production in human gastric epithelial cells.

Background and Aims: Japan has experienced 8 waves of the coronavirus disease 2019 (COVID-19) outbreak over the past 3 years, resulting in an increasing number of deaths and incidence of severe infections. This study aimed to analyze the data from the Japanese inflammatory bowel disease (IBD) patients with COVID-19 registry (J-COSMOS) up to the eighth wave to investigate the clinical course of IBD patients with COVID-19 and factors contributing to disease severity. Methods: In this multicenter, observational, cohort study, we analyzed a cohort of 1308 IBD patients diagnosed with COVID-19, enrolled across 77 participating facilities in the J-COSMOS registry from June 2020 to December 2022. Data on age, sex, IBD (classification, treatment, and activity), and COVID-19 (symptoms, severity, and treatment) were analyzed. Results: The majority of patients (76%) were in clinical remission. According to the World Health Organization classification of COVID-19 severity, 98.4% of IBD patients had nonsevere disease, while 1.6% of patients had severe or critical disease. COVID-19 did not affect disease activity in most IBD patients. Stepwise logistic regression analysis revealed that high body mass index, and cerebrovascular disease were risk factors for severe COVID-19. Corticosteroids could affect COVID-19 severity, whereas anti-tumor necrosis factor α antibodies and thiopurines were associated with a reduced risk of severe COVID-19. No deaths were observed among IBD patients with COVID-19 registered in this cohort. Conclusion: The impact of COVID-19 on IBD disease activity and factors associated with COVID-19 severity were consistent with findings of previous reports. No deaths in Japanese patients with IBD were observed.

Abstract The outcomes of patients with elderly onset (EO) inflammatory bowel disease (IBD) treated with anti-tumor necrosis factor (TNF) remains uncertain. The present study evaluated the efficacy and safety of anti-TNF treatment for bio-naïve EO-IBD. Elderly patients were defined as those 60 years and older, and further divided into those with EO (Elderly-EO) and those with non-elderly onset (Elderly-NEO). A total of 432 bio-naïve patients were enrolled in this multicenter observational study, comprising 55 with Elderly-EO (12.7%), 25 with Elderly-NEO (5.8%), and 352 under age 60 (Non-elderly, 81.5%). After 52 weeks of anti-TNF treatment, clinical and steroid-free remission rates were significantly lower in Elderly-EO than in Non-elderly (37.7% and 60.8%; P = 0.001, and 35.9% and 57.8%; P = 0.003, respectively), and comparable between Elderly-NEO and Non-elderly. Multivariate analysis revealed that elderly onset was a significant factor for both clinical remission (OR, 0.49, 95% CI 0.25–0.96) and steroid-free remission (OR, 0.51, 95% CI 0.26–0.99) after 52 weeks of anti-TNF treatment. The rate of cumulative severe adverse events was significantly higher in Elderly-EO than in Non-elderly (P = 0.007), and comparable between Elderly-NEO and Non-elderly. In conclusion, anti-TNF treatment for bio-naïve EO-IBD may be less effective and raise safety concerns.

Background and aimEnvironmental factors are associated with onset and course of inflammatory bowel disease (IBD). Our previous study by about 1,100 IBD patients revealed half of the patients experienced seasonal exacerbation of disease. We investigated the seasonality of fecal microbiota composition of IBD patients.MethodsFecal samples were consecutively collected in each season from IBD outpatients and healthy controls between November 2015 and April 2019. Participants who were treated with full elemental diet or antibiotics within 6 months or had ostomates were excluded. Bacterial profiles were analyzed by 16S rRNA sequencing, and the changes between the diseases and seasons were compared.ResultsA total of 188 fecal samples were analyzed from 47 participants comprising 19 Crohn's disease (CD) patients, 20 ulcerative colitis (UC) patients, and 8 healthy controls (HC). In CD patients, the phylum Actinobacteria and TM7 were both significantly more abundant in autumn than in spring and winter, but not in UC patients and HC. Moreover, the genera Actinomyces, a member of Actinobacteria, and c_TM7-3;o_;f_;g_ (TM7-3), that of TM7, were significantly more abundant in autumn than in spring, and the abundance of Actinomyces was significantly correlated with that of TM7-3 throughout the year in CD patients, but not in UC patients and HC. CD patients with high abundance of TM7-3 in the autumn required significantly fewer therapeutic intervention than those without seasonal fluctuation.ConclusionsOral commensals Actinomyces and its symbiont TM7-3 were correlatively fluctuated in the feces of CD patients by season, which could affect the disease course.

Abstract Deficiency of p53 in cancer cells activates the transformation of normal tissue fibroblasts into carcinoma-associated fibroblasts; this promotes tumor progression through a variety of mechanisms in the tumor microenvironment. The role of autophagy in carcinoma-associated fibroblasts in tumor progression has not been elucidated. We aimed to clarify the significance of autophagy in fibroblasts, focusing on the TP53 status in co-cultured human colorectal cancer cell lines (TP53-wild-type colon cancer, HCT116; TP53-mutant colon cancer, HT29; fibroblast, CCD-18Co) in vitro. Autophagy in fibroblasts was significantly suppressed in association with ACTA2, CXCL12, TGFβ1, VEGFA, FGF2, and PDGFRA mRNA levels, when co-cultured with p53-deficient HCT116 sh p53 cells. Exosomes isolated from the culture media of HCT116 sh p53 cells significantly suppressed autophagy in fibroblasts via inhibition of ATG2B. Exosomes derived from TP53-mutant HT29 cells also suppressed autophagy in fibroblasts. miR-4534, extracted from the exosomes of HCT116 sh p53 cells, suppressed ATG2B in fibroblasts. In conclusion, a loss of p53 function in colon cancer cells promotes the activation of surrounding fibroblasts through the suppression of autophagy. Exosomal miRNAs derived from cancer cells may play a pivotal role in the suppression of autophagy.

Abstract Background The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. Methods This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. Results A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30–0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

Glycoprotein-2 (GP-2) can protect the intestinal epithelial barrier from bacteria and is associated with protection against Crohn’s disease. Here, the authors show pancreatic GP-2 is the source of the intestine’s luminal GP-2 that binds bacteria and prevents them from attaching to the epithelium, also limiting pathology in a DSS colitis mouse model.

Background and Aim To investigate whether assessment by magnifying narrow‐band imaging (M‐NBI) based on the classification of the Japan Esophageal Society provides additional value to the estimation of the invasion depth of superficial esophageal squamous cell carcinoma (SCC) compared with assessment by white light endoscopy (WLE) alone. Methods Endoscopic images of 211 consecutive superficial esophageal SCCs resected by endoscopic submucosal dissection were separated into WLE and M‐NBI images. Depth estimation was performed independently by five evaluators using the numerical depth estimation scale (0 = epithelium (EP)/lamina propria (LPM), 1 = EP/LPM > muscularis mucosa (MM)/shallow submucosa (SM1), 2 = MM/SM1 > EP/LPM, 3 = MM/SM1, 4 = MM/SM1 > deep submucosa (SM2), 5 = SM2 > MM/SM1, 6 = SM2), using primarily WLE images (step 1), and subsequently both WLE and M‐NBI images (step 2). The discordance scores, determined by the average of the five evaluators' difference between the estimated score (from 0 to 6) and pathological score (0 for histologically proven EP/LPM, 3 for MM/SM1, and 6 for SM2), were analyzed in steps 1 and 2. Results The discordance scores significantly decreased in step 2 (0.53 ± 0.06) compared with those in step 1 (0.79 ± 0.07) (P

Induction therapy with tumor necrosis factor-α (TNF-α) inhibitors is highly effective for the treatment of Crohn’s disease. However, there are primary nonresponders (PNR) of TNF-α inhibitors without clinical response during the induction period. In addition, there are partial responders (PR), who show some efficacy, but clinical remission is not achieved by induction therapy. To date, the definition and clinical management of PNR and PR have not been established. This report summarizes the opinions of 36 Japanese experts attending the Japan Round Table Discussion on IBD Meeting regarding how to determine PNR and PR of TNF-α inhibitors and how to manage these patients in clinical practice. PNR, who do not show any initial improvement of clinical symptoms and serum C-reactive protein (CRP) levels, require re-assessment of intestinal complications. PR can be determined either by clinical symptoms, serum CRP levels, or imaging results. PR need intensification of the treatment with TNF-α inhibitors either with or without optimization of immunomodulators. Optimization of initial TNF-α inhibitor therapy may improve long-term outcomes, but more evidence is required to improve the use of TNF-α inhibitors for the prevention and management of PNR and PR.

Background: The dysbiosis of gut microbiota has been implicated in the pathogenesis of inflammatory bowel diseases; however, the underlying mechanisms have not yet been elucidated. Heavily glycosylated mucin establishes a first-line barrier against pathogens and serves as a niche for microbial growth. Methods: To elucidate relationships among dysbiosis, abnormal mucin utilisation, and microbial metabolic dysfunction, we analysed short-chain fatty acids (SCFAs) and mucin components in stool samples of 40 healthy subjects, 49 ulcerative colitis (UC) patients, and 44 Crohn's disease (CD) patients from Japan. Findings: Levels of n-butyrate were significantly lower in stools of both CD and UC patients than in stools of healthy subjects. Correlation analysis identified seven bacterial species positively correlated with n-butyrate levels; the major n-butyrate producer, Faecalibacterium prausnitzii, was particularly underrepresented in CD patients, but not in UC patients. In UC patients, there were inverse correlations between mucin O-glycan levels and the production of SCFAs, such as n-butyrate, suggesting that mucin O-glycans serve as an endogenous fermentation substrate for n-butyrate production. Indeed, mucin-fed rodents exhibited enhanced n-butyrate production, leading to the expansion of RORgt+Treg cells and IgA-producing cells in colonic lamina propria. Microbial utilisation of mucin-associated O-glycans was significantly reduced in n-butyrate-deficient UC patients. Interpretation: Mucin O-glycans facilitate symbiosynthesis of n-butyrate by gut microbiota. Abnormal mucin utilisation may lead to reduced n-butyrate production in UC patients. Fund: Japan Society for the Promotion of Science, Health Labour Sciences Research Grant, AMED-Crest, AMED, Yakult Foundation, Keio Gijuku Academic Development Funds, The Aashi Grass Foundation, and The Canon Foundation. Keywords: Microbiota, Butyrate, Mucin, Inflammatory bowel disease

Background and study aims In patients receiving antithrombotic therapy, the risks of delayed bleeding after endoscopic procedures for gastrointestinal neoplasms become a major problem. Few reports have shown the effects of delayed bleeding in patients taking anticoagulants after colorectal endoscopic submucosal dissection (ESD). This study aimed to evaluate the delayed bleeding events after colorectal ESD in patients receiving anticoagulant therapy. Patients and methods We retrospectively analyzed 87 patients taking anticoagulants who underwent colorectal ESD from April 2012 to December 2017 at 13 Japanese institutions participating in the Osaka Gut Forum. Among these patients, warfarin users were managed with heparin bridge therapy (HBT), continued use of warfarin, a temporary switch to direct oral anticoagulation (DOAC), or withdrawal of warfarin, and DOAC users were managed with DOAC discontinuation with or without HBT. We investigated the occurrence rate of delayed bleeding and compared the rates between warfarin and DOAC users. Results The delayed bleeding rate was 17.2 % among all patients. The delayed bleeding rate was higher in DOAC users than in warfarin users (23.3 % vs. 11.4 %, P = 0.14), although no statistically significant difference was observed. In DOAC users, the delayed bleeding rates for dabigatran, rivaroxaban, apixaban, and edoxaban users appeared similar (30 %, 18.2 %, 22.2 %, and 25 %, respectively). The onset of delayed bleeding in both warfarin and DOAC users was late, averaging 6.9 and 9.4 days, respectively. Conclusions Among patients taking anticoagulants, the risk of delayed bleeding after colorectal ESD was relatively high and the onset of delayed bleeding was late.

Abstract Background Chemoradiotherapy effectively treats superficial esophageal cancer and is optimal to preserve organs. However, late toxicity, particularly in cardiac diseases, obstructs clinical outcomes. We revealed the risk factors for cardiac event development post-chemoradiotherapy. Methods Data from 80 patients who were diagnosed with submucosal invasive esophageal cancer without metastasis (confirmed using multiple modalities) and who underwent chemoradiotherapy between 2006 and 2014 were analyzed. Patients were 11% (9/80) female, and the median age and follow-up were 66.5 y and 73 mo, respectively. We calculated the individual radiation dose to the heart and analyzed relationships between the cardiac event occurrence rate and each clinical factor. Results The 5-y overall and recurrence-free survival rates were 74.6 and 62.4%, respectively. Among the total number of deaths, 34.6% was caused by esophageal cancer. During the follow-up, 13 patients developed severe cardiac events (ischemic heart diseases, n = 7; pericardial effusion, n = 3, atrial fibrillation, n = 1; and sudden death, n = 2). The significant risk factor for cardiac events post-chemoradiotherapy was the level of the heart’s exposure to radiation, with higher exposure associated with greater occurrence. History of smoking, obesity, comorbidity, and history of cardiac disease were unrelated to cardiac event occurrence post-chemoradiotherapy. Conclusions Chemoradiotherapy is a favorable intervention for superficial esophageal cancer. Reducing the radiation dose to the heart likely contributes to preventing cardiac toxicity post-chemoradiotherapy.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disease of the gastrointestinal tract, with increasing prevalence worldwide. IBD Ahead is an international educational program that aims to explore questions commonly raised by clinicians about various areas of IBD care and to consolidate available published evidence and expert opinion into a consensus for the optimization of IBD management. Given differences in the epidemiology, clinical and genetic characteristics, management, and prognosis of IBD between patients in Japan and the rest of the world, this statement was formulated as the result of literature reviews and discussions among Japanese experts as part of the IBD Ahead program to consolidate statements of factors for disease prognosis in IBD. Evidence levels were assigned to summary statements in the following categories: disease progression in CD and UC; surgery, hospitalization, intestinal failure, and permanent stoma in CD; acute severe UC; colectomy in UC; and colorectal carcinoma and dysplasia in IBD. The goal is that this statement can aid in the optimization of the treatment strategy for Japanese patients with IBD and help identify high-risk patients that require early intervention, to provide a better long-term prognosis in these patients.

Background Post-procedural bleeding, after gastric endoscopic submucosal dissection (ESD) for high risk thromboembolic cases that require continuous antiplatelet therapy, is challenging. Its incidence rate is > 20 % among those using conventional antacids. We evaluated the efficacy of perioperative management with vonoprazan to prevent post-ESD bleeding. Materials and methods This was a multicenter prospective interventional trial conducted at 10 Japanese referral centers. Patients who regularly used antiplatelet agents (aspirin or thienopyridine derivatives, etc.) and who required continuous antithrombotic medication due to high thromboembolic risk were enrolled. They underwent gastric ESD with continuous aspirin therapy. Oral administration of vonoprazan (20 mg daily) was started from the day of ESD and continued for 28 days. The primary end point was the incidence of post-ESD bleeding. The sample size was 50 patients, and vonoprazan was considered to be effective when the upper threshold of the 95 % confidence interval (CI) for post-ESD bleeding did not exceed 20 %. Results Although 50 patients were enrolled, one patient withdrew consent. Therefore, 49 patients were included in the analysis. One patient who used aspirin and clopidogrel experienced bleeding 11 days after ESD. The overall post-ESD bleeding rate was 2.0 % (1/49; 95 %CI 0.4–10.7 %). Thromboembolic events were not observed. One case of ESD-associated adverse events (perforation) and one case of drug-associated adverse events (drug eruption, possibly due to vonoprazan) were observed. Conclusions Vonoprazan may be efficacious for preventing post-ESD bleeding in patients using continuous antiplatelet therapy, warranting further comparative study to definitively test the effectiveness of the drug.

Background and study aims Patients with esophageal squamous cell carcinoma (SCC) are at high risk of developing second primary SCCs in the hypopharynx. However, such second primary tumors are difficult to observe because of lumen closure. The Valsalva maneuver using a dedicated mouthpiece is a promising technique to visualize the hypopharynx during transoral endoscopy. In the current study, we investigated the utility of this method. Patients and methods The current study was a randomized, controlled, crossover trial. Patients with esophageal SCC were randomly assigned first to undergo pharyngeal observation using the dedicated mouthpiece followed by observation using a conventional mouthpiece, or vice versa. The primary endpoint was complete visualization of the hypopharynx, which was assessed blindly by three external evaluators. Results A total of 68 pharyngeal examinations were analyzed – 34 with the dedicated mouthpiece and 34 with a conventional mouthpiece. Complete visualization was achieved in 68 % of the examinations (23/34) using the dedicated mouthpiece, whereas none of the examinations using the conventional mouthpiece achieved complete visualization of the hypopharynx. Observation scores of the oropharynx were not significantly different between both types of examination (P = 0.50). No serious adverse events (AEs) occurred. Conclusions Endoscopic view of the hypopharynx was markedly improved by the Valsalva maneuver using the dedicated mouthpiece, with no serious AEs. This procedure should be included in the endoscopic examinations for the patients with esophageal SCCs.

BACKGROUND AND AIMS:Psychologic stress can affect the pathogenesis of inflammatory bowel disease (IBD), but the precise contribution of psychologic stress to IBD remains unclear. We investigated the association of psychologic stress with disease activity in patients with IBD, especially in terms of mental state and sleep condition. METHODS:This was a multi-center observational study comprising 20 institutions. Data were collected using survey forms for doctors and questionnaires for patients, and the association of psychologic stress with clinical parameters was investigated. Mental state was evaluated using the Center for Epidemiologic Studies Depression (CES-D) scale, and sleep condition was evaluated by querying patients about the severity of insomnia symptoms. RESULTS:A total of 1078 IBD patients were enrolled, including 303 patients with Crohn's disease and 775 patients with ulcerative colitis. Seventy-five percent of IBD patients believed that psychologic stress triggered an exacerbation of their disease (PSTE group) and 25% did not (non-PSTE group). The CES-D scores were significantly higher for patients with clinically active disease than for those in remission in the PSTE group (median (interquartile range) = 7 (4-9.5) vs. 5 (3-7), p < .0001), but not in the non-PSTE group (5 (2-8) vs. 4 (3-7), p = 0.78). Female sex and disease exacerbation by factors other than psychologic stress were independent factors of psychologic stress-triggered disease exacerbation. Also, patients with insomnia had higher disease activity than those without insomnia, especially in the PSTE group. CONCLUSIONS:A worsened mental state correlates with disease activity in IBD patients, especially those who believe that their disease is exacerbated by psychologic stress.

Background/AimsPeyer's patches (PPs) are aggregates of lymphoid follicles that are mainly located in the distal ileum; they play a major role in mucosal immunity. We recently reported that patients with ulcerative colitis (UC) have alterations in PPs that can be detected using narrow-band imaging with magnifying endoscopy (NBI-ME). However, the usefulness of NBI-ME in UC treatment as a whole is still unknown.MethodsWe collected NBI-ME images of PPs from 67 UC patients who had undergone ileocolonoscopy. We evaluated changes in the villi using the "villi index," which is based on three categories: irregular formation, hyperemia, and altered vascular network pattern. The patients were divided into two groups on the basis of villi index: low (L)- and high (H)-types. We then determined the correlation between morphological alteration of the PPs and various clinical characteristics. In 52 patients who were in clinical remission, we also analyzed the correlation between NBI-ME findings of PPs and clinical recurrence.ResultsThe time to clinical recurrence was significantly shorter in remissive UC patients with H-type PPs than in those with L-type PPs (P

Background and study aims An increasing number of patients have been using anticoagulants including anti-vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs); however, in patients using anticoagulants, limited data are available with regard to the risks of gastrointestinal bleeding and thromboembolic events during the peri-endoscopic period. We aimed to evaluate the peri-endoscopic bleeding and thrombotic risks in patients administered VKAs or DOACs. Patients and methods Consecutive patients using anticoagulants who underwent endoscopic biopsy, mucosal resection, or submucosal dissection were prospectively enrolled across 11 hospitals. The primary outcome assessed was difference in incidence of post-procedural gastrointestinal bleeding in patients using VKAs and DOACs. Duration of hospitalization and peri-procedural thromboembolic events were also compared. Results We enrolled 174 patients using VKAs and 37 using DOACs. In total, 16 patients using VKA were excluded from the analysis because of cancellation of endoscopic procedures and contraindications to the use of DOACs; 128 (81 %) patients using VKAs and 17 (46 %) using DOACs received heparin-bridging therapy (HB). The rate of post-procedural gastrointestinal bleeding in DOAC users was similar to that in VKA users (16.2 % vs. 16.4 %, P = 1.000). Duration of hospitalization was significantly longer in patients using VKAs than in those using DOACs (median 15 vs. 7 days, P

Background and study aims Endoscopic local steroid injection (LSI) has been used to prevent esophageal strictures after endoscopic submucosal dissection (ESD) for superficial esophageal neoplasms (SENs). This study aimed to evaluate the safety and efficacy of LSI therapy. Patients and methods From May 2007 to September 2014, at four institutions, 40 consecutive patients with SENs were treated with ESD that left a mucosal defect of more than three-quarters of the esophageal circumference. Two patients who underwent esophagectomy after ESD were excluded, and 38 patients were analyzed. The incidence of post-ESD strictures and adverse events associated with LSI were retrospectively investigated. Results Prophylactic LSI was administered in 28 patients (LSI group), and not administered in 10 patients (Non-prevention group). Post-ESD stricture rates were significantly lower in the LSI group (43 %) than in the Non-prevention group (90 %) (P = 0.012). Endoscopic balloon dilation (EBD) was conducted in 11 patients (39 %) in the LSI group and in 7 (70 %) in the Non-prevention group. In the LSI group, perforation caused by EBD occurred in five patients, while in the Non-prevention group, it occurred in only one patient who had received subsequent LSI before the perforation. Four patients with perforation successfully recovered after conservative therapy, but the other two patients required surgical treatment. A review of follow-up examinations with endoscopic ultrasonography and narrow-band imaging showed impaired ulcer-healing process after LSI. Conclusion LSI is useful for preventing post-ESD strictures, but it appears to increase the risk of perforation in cases of EBD.

This paper presents a gastric contraction imaging system for assessment of gastric motility using a 3-D endoscope. Gastrointestinal diseases are mainly based on morphological abnormalities. However, gastrointestinal symptoms are sometimes apparent without visible abnormalities. One of the major factors for these diseases is abnormal gastrointestinal motility. For assessment of gastric motility, a gastric motility imaging system is needed. To assess the dynamic motility of the stomach, the proposed system measures 3-D gastric contractions derived from a 3-D profile of the stomach wall obtained with a developed 3-D endoscope. After obtaining contraction waves, their frequency, amplitude, and speed of propagation can be calculated using a Gaussian function. The proposed system was evaluated for 3-D measurements of several objects with known geometries. The results showed that the surface profiles could be obtained with an error of ${ of the distance between two different points on images. Subsequently, we evaluated the validity of a prototype system using a wave simulated model. In the experiment, the amplitude and position of waves could be measured with 1-mm accuracy. The present results suggest that the proposed system can measure the speed and amplitude of contractions. This system has low invasiveness and can assess the motility of the stomach wall directly in a 3-D manner. Our method can be used for examination of gastric morphological and functional abnormalities.

Background and study aims: The number of patients with chronic kidney disease (CKD) is increasing worldwide and gastric cancer sometimes occurs with CKD. However, the safety and feasibility of endoscopic submucosal dissection (ESD) for patients with CKD are not clear. The aim of this study is to clarify the feasibility and safety of gastric ESD for patients with CKD. Patients and methods: This was a multicenter retrospective cohort study. In total, 144 patients with CKD who underwent gastric ESD between May 2003 and October 2012 were enrolled. The patients were divided into three groups: stage 3 (estimated glomerular filtration rate [eGFR]: 30 – 59 mL/min), stage 4 (eGFR: 15 – 29 mL/min), and stage 5 (eGFR:

Objectives. Heparin replacement (HR) is often performed in patients with a high risk of thrombosis undergoing endoscopic procedures. However, information about the influence of HR is scarce. The aim of this study is to assess the clinical impact of HR for gastric endoscopic submucosal dissection (ESD). Methods. This is a retrospective study comprising approximately 1310 consecutive gastric neoplasms in 1250 patients, who underwent ESD in 5 institutes. We assessed the clinical findings and outcomes of ESD under HR, compared to ESD without HR as control. Results. A total of 24 EGC lesions in 24 patients were treated by ESD under HR. In the HR group, the complete en-bloc resection rate was 100%. The delayed bleeding rate was, however, higher in the HR group than in the controls (38% versus 4.6%). The timing of bleeding in the HR group was significantly later than in controls. In the control group, 209 patients discontinued antithrombotic therapy during perioperative period, and their delayed bleeding rate was not different from those without antithrombotic therapy (5.7% versus. 4.4%). A thromboembolic event was encountered in 1 patient under HR after delayed bleeding. Conclusion. ESD under HR is technically feasible but has a high risk of delayed bleeding.

We evaluated whether endoscopic ultrasonography (EUS) image quality affects the accuracy of diagnosing the vertical invasion depth of early gastric cancer (EGC). A total of 75 lesions in 75 patients suspected of having EGC were enrolled. All patients underwent EUS examination. Findings of EUS were compared with histopathologic results. We evaluated the effect of the following clinicopathologic factors: location, diameter, surface pattern, concomitant ulceration, histology type, and EUS image quality score. EUS image quality was scored based on detection repeatability, appropriate probe placement, and clarity of the five gastric wall layers including the lesion. Sixty-three lesions (84%) were pathologically mucosal and 12 lesions (16%) were submucosal cancer. Overall accuracy was 82.7%. Significantly more lesions in the upper and middle portions of the stomach were incorrectly diagnosed than in the lower portion (𝑃=0.0019). Lesion diameter was significantly larger among incorrectly diagnosed lesions (𝑃=0.0257). Low-quality images were significantly more often associated with incorrectly diagnosed lesions than with correctly diagnosed lesions (𝑃=0.0001). Multivariate analysis revealed that EUS image quality was associated with EUS staging accuracy (odds ratio, 21.8; 95% confidence interval, 4.5–137.6). Low-quality EUS images led to an incorrect diagnosis of invasion depth of EGC, independent of tumor location or size.

T cells differentiate into highly diverse subsets and display plasticity depending on the environment. Although lymphocytes are key mediators of inflammation, functional specialization of T cells in inflammatory bowel disease (IBD) has not been effectively described. Here, we performed deep profiling of T cells in the intestinal mucosa of IBD and identified a CD4+ tissue-resident memory T cell (Trm) subset that is increased in Crohn's disease (CD) showing unique inflammatory properties. Functionally and transcriptionally distinct CD4+ Trm subsets are observed in the inflamed gut mucosa, among which a CD-specific CD4+ Trm subset, expressing CD161 and CCR5 along with CD103, displays previously unrecognized pleiotropic signatures of innate and effector activities. These inflammatory features are further enhanced by their spatial proximity to gut epithelial cells. Furthermore, the CD-specific CD4+ Trm subset is the most predominant producer of type 1 inflammatory cytokines upon various stimulations among all CD4+ T cells, suggesting that the accumulation of this T cell subset is a pathological hallmark of CD. Our results provide comprehensive insights into the pathogenesis of IBD, paving the way for decoding of the molecular mechanisms underlying this disease. [ABSTRACT FROM AUTHOR]