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Background and Aim: Linked color imaging (LCI) is an image‐enhanced endoscopy technique that accentuates the color difference between red and white, potentially improving the adenoma detection rate (ADR). However, it remains unclear whether LCI performance in detecting colorectal lesions differs based on endoscopists' experience levels. We aimed to evaluate the differences in LCI efficacy based on the experience levels of endoscopists by conducting an exploratory analysis. Methods: In this post hoc analysis of an international randomized controlled trial comparing the detection of adenoma and other lesions using colonoscopy with LCI and high‐definition white light imaging (WLI), we included patients from 11 institutions across four countries/regions: Japan, Thailand, Taiwan, and Singapore. We retrospectively reviewed differences in the lesion detection of LCI according to endoscopists' colonoscopy history or ADR. Results: We included 1692 and 1138 patients who underwent colonoscopies performed by 54 experts (experience of ≥ 5000 colonoscopies) and by 43 non‐experts (experience of < 5000 colonoscopies), respectively. Both expert and non‐expert groups showed a significant improvement in ADR with LCI compared to WLI (expert, 61.7% vs 46.4%; P < 0.001; non‐expert, 56.6% vs 46.4%; P < 0.001). LCI had no effect on sessile serrated lesion detection rate in non‐experts (3.1% vs 2.5%; P = 0.518). LCI significantly improved detection rates in endoscopists with relatively low detection performance, defined as an ADR < 50%. Conclusions: This exploratory study analyzed data from a previous trial and revealed that LCI is useful for both experts and non‐experts and is even more beneficial for endoscopists with relatively low detection performance using WLI. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusion There are no previous studies in which computer‐aided diagnosis (CAD) diagnosed colorectal cancer (CRC) subtypes correctly. In this study, we developed an original CAD for the diagnosis of CRC subtypes.Pretraining for the CAD based on ResNet was performed using ImageNet and five open histopathological pretraining image datasets (HiPreD) containing 3 million images. In addition, sparse attention was introduced to improve the CAD compared to other attention networks. One thousand and seventy‐two histopathological images from 29 early CRC cases at Kyoto Prefectural University of Medicine from 2019 to 2022 were collected (857 images for training and validation, 215 images for test). All images were annotated by a qualified histopathologist for segmentation of normal mucosa, adenoma, pure well‐differentiated adenocarcinoma (PWDA), and moderately/poorly differentiated adenocarcinoma (MPDA). Diagnostic ability including dice sufficient coefficient (DSC) and diagnostic accuracy were evaluated.Our original CAD, named Colon‐seg, with the pretraining of both HiPreD and ImageNET showed a better DSC (88.4%) compared to CAD without both pretraining (76.8%). Regarding the attentional mechanism, Colon‐seg with sparse attention showed a better DSC (88.4%) compared to other attentional mechanisms (dual: 79.7%, ECA: 80.7%, shuffle: 84.7%, SK: 86.9%). In addition, the DSC of Colon‐seg (88.4%) was better than other types of CADs (TransUNet: 84.7%, MultiResUnet: 86.1%, Unet++: 86.7%). The diagnostic accuracy of Colon‐seg for each histopathological type was 94.3% for adenoma, 91.8% for PWDA, and 92.8% for MPDA.A deep learning‐based CAD for CRC subtype differentiation was developed with pretraining and fine‐tuning of abundant histopathological images. [ABSTRACT FROM AUTHOR]

Background and Aim: Complete endoscopic mucosal healing is defined as a Mayo endoscopic subscore of 0. Some patients diagnosed with a Mayo endoscopic subscore 0 may present with subsequent clinical relapse. Here, we aimed to demonstrate mucosal cytokine profile as a predictor of clinical relapse in ulcerative colitis patients with a Mayo endoscopic subscore of 0 as a marker of mucosal healing. Methods: We conducted prospective observational pilot study to examine the relationship between mucosal cytokine expression and subsequent relapse of UC patients diagnosed with a Mayo endoscopic subscore of 0. We enrolled 55 patients, and expression of cytokines tumor necrosis factor‐α, interferon γ, interleukin‐1β, interleukin‐2, interleukin‐4, interleukin‐5, interleukin‐6, interleukin‐7, interleukin‐8, interleukin‐9, interleukin‐10, interleukin‐12, interleukin‐13, interleukin‐15, interleukin‐17A, interleukin‐17F, interleukin‐18, interleukin‐21, interleukin‐22, interleukin‐23, interleukin‐27, and interleukin‐33 was measured by quantitative real‐time PCR using rectal mucosa biopsy materials. Cytokine expression levels were compared between patients who relapsed between March 1, 2016, and March 30, 2020, of the study period and those who remained in remission. Results: Ten cytokines, including interleukin‐2, interleukin‐4, interleukin‐8, interleukin‐10, interleukin‐12, interleukin‐15, interleukin‐17A, interleukin‐21, interleukin‐23, and interleukin‐33, were significantly elevated in patients with subsequent relapse compared with those who remained in remission. Interleukin‐8 expression was the most useful predictor. Conclusions: In the rectal mucosa of ulcerative colitis patients with Mayo endoscopic subscore 0, levels of several cytokines were elevated in cases of subsequent relapse. Among these, interleukin‐8 expression was the most useful for predicting relapse. [ABSTRACT FROM AUTHOR]

Background and Aim: Efficient intestinal wound healing is essential for good prognoses of ulcerative colitis (UC). Although bile acids and the transmembrane G‐protein‐coupled receptor (TGR) 5 have been reported to affect wound healing in intestinal epithelial cells, the detailed underlying mechanisms are unclear. Here, we investigated the role of TGR5 in wound healing in the context of colonic epithelial cells in the presence of bile acids. Methods: The expression of TGR5 in the colonic epithelium of both a dextran sulfate sodium (DSS)‐induced colitis mouse model (recovery phase), and UC patients in clinical remission, was evaluated. Young adult mouse colonic epithelial (YAMC) cells were then used to evaluate wound healing after treatment with deoxycholic acid (DCA); TGR5 was silenced in YAMC cells via shRNA‐transfection, and a wound‐healing assay in the presence of DCA was performed. Furthermore, we investigated the role of the activation of AKT in the context of wound healing. Results: The expression of TGR5 was decreased in the colonic epithelium of both mice with DSS‐induced colitis and UC patients. Additionally, DCA significantly delayed wound healing in YAMC cells but not in TGR5 silenced ones. Of note, the DCA‐induced activation of AKT signaling in YAMC cells was inhibited by TGR5 silencing, and AKT inhibitors prevented the wound healing delay induced by DCA. Conclusions: Overall, we show that DCA delays wound healing in the context of colonic epithelial cells through AKT activation. These results may support the development of new therapeutic approaches for epithelial regeneration in UC. [ABSTRACT FROM AUTHOR]

Background and Aim: High‐grade dysplasia (HGD) and T1 lesions are accidentally resected by cold snare polypectomy (CSP) and the characteristics, and follow‐up of them has not been reported. In this study, we analyzed the histopathological findings and recurrence of them. Methods: This was a multicenter retrospective‐cohort study. We collected HGD and T1 lesions of ≤ 10 mm resected by CSP among 15 520 patients receiving CSP from 2014 to 2019 at nine related institutions, and we extracted only cases receiving definite follow‐up colonoscopy after CSP of HGD and T1 lesions. We analyzed these tumor's characteristics and therapeutic results such as R0 resection and local recurrence and risk factors of recurrence. Results: We collected 103 patients (0.63%) and extracted 80 lesions in 74 patients receiving follow‐up colonoscopy for CSP scar. Mean age was 68.4 ± 12.0, and male rate was 68.9% (51/80). The mean tumor size (mm) was 6.6 ± 2.5, and the rate of polypoid morphology and rectum location was 77.5% and 25.0%. The rate of magnified observation was 53.8%. The rates of en bloc resection and R0 resection were 92.5% and 37.5%. The local recurrence rate was 6.3% (5/80, median follow‐up period: 24.0 months). The recurrence developed within 3 months after CSP for four out of five recurrent cases. Comparing five recurrent lesions to 75 non‐recurrent lesions, a positive horizontal margin was a significant risk factor (60.0% vs 10.7%, P < 0.001). Conclusions: High‐grade dysplasia and T1 resected by CSP were analyzed, and the local recurrence rate of them was substantially high. [ABSTRACT FROM AUTHOR]

Background and Aim: In Japan, screening colonoscopy for colorectal cancer is expected to reduce colorectal cancer mortality, although its complication rate has not been sufficiently examined. The aim of this study is to analyze severe complications due to colonoscopy. Methods: As a study population, we retrospectively used commercially anonymized health insurance claims data covering 5.71 million patients from January 2005 to August 2018. We extracted patients who received colonoscopy with lesions resection or without treatment. Main outcomes were rates of hemorrhage, perforation, fatal events, and their risk factors. Results: Among 341 852 colonoscopy without treatment in 260 128 patients (mean age: 49.6 ± 11.7 years), the rates of hemorrhage, perforation, and fatal events were 0.0059% (95% confidence interval [CI] 0.0031–0.0085), 0.0032% (95% CI 0.0011–0.0052), and 0.00029% (95% CI 0–0.0012), respectively. Regarding hemorrhage, compared with the rate for patients <50 years old (0.0050%), the rates for those 50–59, 60–69, and ≥70 years old were 0.0095% (P = 0.17), 0.0031% (P = 0.17), and 0%, respectively. Regarding perforation, compared with patients <50 years old (0.0056%), the rates for those 50–59, 60–69, and ≥70 years old were 0%, 0.0015% (P = 0.99), and 0.0102% (P = 0.99), respectively. A multivariate analysis for risk factors showed no significant findings for hemorrhage and perforation without treatment. Among 123 087 colonoscopy with lesions resection in 102 058 patients (mean age: 53.7 ± 9.3 years), the rates of hemorrhage, perforation, and fatal events were 0.136% (95% CI 0.1157–0.1572), 0.033% (95% CI 0.0228–0.0437), and 0.00081% (95% CI 0–0.0035), respectively. Conclusions: The analysis using health insurance claims data demonstrated the safety of colonoscopy. [ABSTRACT FROM AUTHOR]

Background and Aim: The Mayo Endoscopic Subscore (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) are used to assess endoscopic mucosal healing in patients suffering from ulcerative colitis. Although mucosal healing is defined by MES 0, relapse of ulcerative colitis is often observed. Over a 48‐month period, this study investigated the efficacy of linked color imaging (LCI) in predicting the long‐term prognosis of ulcerative colitis patients diagnosed with MES 0. Methods: Overall, 26 patients in ulcerative colitis remission, diagnosed with MES 0, were enrolled. Using a LASEREO endoscopic system (Fujifilm Co., Tokyo, Japan), endoscopic colonic images were assessed with linked color imaging and the colitis endoscopic index of severity. Endoscopic LCI images were separated into three subgroups (A, no redness; B, redness with visible vessels; and C, redness without visible vessels). The Geboes score was used to evaluate histology; active mucosa was defined as GS > 2B.1. Results: Linked color imaging classification subdivided colonic mucosa, which had been diagnosed with MES 0, into two classes. The LCI‐A group did not relapse, and the non‐relapse rate was significantly higher (P = 0.018) than that in the LCI‐B group. No difference in relapse rates was observed between patients with a colitis endoscopic index of severity of 0 and 1 (P = 0.655). There was no statistical difference between the composition of LCI‐A group and the relapse rate between active and inactive mucosa diagnosed by Geboes score. Conclusions: This methodology can be used to evaluate mucosal healing and predict long‐term outcomes in ulcerative colitis patients. [ABSTRACT FROM AUTHOR]

Background and Aim: Mucosal healing is an important clinical goal in patients with inflammatory bowel disease. Recently, short‐chain fatty acids (SCFAs) have been reported to have multifaceted effects to host. However, the effects of SCFAs on wound healing in intestinal epithelial cells are unclear. In the present study, we investigated the effects of acetate, one of the major SCFAs, on the wound healing of murine colonic epithelial cells. Methods: Young adult mouse colonic epithelial cells were used to determine the effect of acetate using wound healing assay. Mitogen‐activated protein kinase and Rho kinase inhibitor were used to elucidate intracellular signal of wound healing treated with acetate. Meanwhile, Rho activation assays were utilized to measure Rho activation levels. To assess in vivo effects, C57B6 mice with dextran sodium sulfate for 7 days were treated with enema administration of acetate for 7 days. Body weight, disease activity index, colon length, and mucosal break ratio in histology were examined. Results: Acetate enhanced wound healing and fluorescence intensity of actin stress fiber compared with control. These effects were canceled with pretreatment of c‐Jun N‐terminal kinase (JNK) inhibitor or Rho kinase inhibitor. Furthermore, JNK inhibitor reduced the activation of Rho induced by acetate. In the dextran sodium sulfate‐induced colitis model, the mice with enema treatment of acetate significantly exhibited recovery. Conclusions: In this study, we demonstrated that acetate promoted murine colonic epithelial cell wound healing via activation of JNK and Rho signaling pathways. These findings suggested that acetate could have applications as a therapeutic agent for patients with intestinal mucosal damage, such as inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background and Aim: Daikenchuto, a traditional Japanese herbal medicine, has been reported to exhibit anti‐inflammatory effects against intestinal inflammation. However, whether daikenchuto has a therapeutic effect against intestinal mucosal injuries remains unclear. Thus, the aim of this study was to determine the effect of daikenchuto on intestinal mucosal healing. Methods: Colitis was induced in male Wistar rats by using trinitrobenzenesulfonic acid. Daikenchuto (900 mg/kg/day) was administered for 7 days after the induction of colitis. Thereafter, intestinal mucosal injuries were evaluated by determining the colonic epithelial regeneration ratio ([area of epithelial regeneration/area of ulcer] × 100). Restoration of rat intestinal epithelial cells treated with daikenchuto and its constituent herbs (Zanthoxylum fruit, processed ginger, and ginseng) and ginsenoside Rb1, which is a ginseng ingredient, was evaluated using a wound‐healing assay. Results: The colon epithelial regeneration ratio in the daikenchuto‐treated rats was significantly higher than that in the control rats. Daikenchuto, ginseng, and ginsenoside Rb1 enhanced wound healing, and the ginsenoside Rb1‐induced enhancement was inhibited by extracellular signal‐regulated kinase and Rho inhibitors. Conclusions: Daikenchuto and its constituent, ginsenoside Rb1, promoted wound healing. Because mucosal healing is one of the most important therapeutic targets in patients with inflammatory bowel disease, ginsenoside Rb1 may be a novel therapeutic agent against intestinal mucosal damage such as that occurring in intestinal bowel disease. [ABSTRACT FROM AUTHOR]

Background and Aim: Adequate mucosal elevation by submucosal injection is important for definitive en bloc resection and prevention of perforation during endoscopic mucosal resection (EMR). The objective of this study is to determine the efficacy of 0.13% hyaluronic acid (HA) solution for high and sustained mucosal elevation during colorectal EMR. Methods: The study was a prospective randomized controlled trial; a total of 196 patients with colon polyps of < 20 mm diameter were enrolled and randomized in a 1:1 ratio to undergo EMR using either 0.13% HA or normal saline (NS). The primary outcome of the study was histopathologically confirmed complete resection. The secondary outcomes such as maintenance of high mucosal elevation and development of complications were also evaluated. Moreover, the relationship between complete resection and the experience of the endoscopist (veteran vs less experienced) was analyzed. Results: Compete resection was achieved in 74 of 93 polyps (79.5%) in the 0.13% HA group and 63 of 96 polyps (65.6%) in the NS group ( P < 0.05). High mucosal elevation was maintained in 83.9% of procedures in the 0.13% HA group and 54.1% in the NS group ( P < 0.01). The frequency of complete resection achieved by less-experienced endoscopists was higher in the 0.13% HA group (79.3%) than in the NS group (62.1%; P < 0.05). Conclusions: Endoscopic mucosal resection using 0.13% HA to colon polyps of less than 20 mm diameter is more effective than NS for complete resection and maintenance of mucosal elevation. [ABSTRACT FROM AUTHOR]

Background and Aims: Recent advancements in capsule endoscopy and double-balloon endoscopy have revealed that non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, can induce small intestinal mucosal damage. However, the precise pathogenesis and therapeutic strategy have not been fully revealed. The aim of the present study was to determine the upregulated proteins in the small intestine exposed to indomethacin. Methods: Indomethacin (10 mg/kg) was administered subcutaneously to male Wistar rats to induce small intestinal damage and the severity of the intestinal injury was evaluated by measuring the area of visible ulcerative lesions. The intestinal mucosal tissue samples were collected and then analyzed by two-dimensional gel electrophoresis, with matrix-assisted laser desorption/ionization time-of-flight spectrometer peptide mass fingerprinting being used to determine the differentially expressed proteins between normal and injured intestinal mucosa. Results: Among several protein spots showing differential expression, one, hemopexin (HPX), was identified as upregulated in indomethacin-induced injured intestinal mucosa using the MASCOT search engine. Conclusion: HPX was identified as upregulated protein in the small intestine exposed to indomethacin. HPX may be responsible for the development of the intestinal inflammation induced by NSAIDs. [ABSTRACT FROM AUTHOR]

The hepatitis C virus (HCV) core protein induces hepatic steatosis and glucose intolerance in transgenic mice. The aim of this study was to clarify the impact of mutations in the HCV core region on hepatic steatosis and glucose tolerance in patients with chronic hepatitis C. Seventy-four Japanese patients (27 men, 47 women; mean age, 61.9 years) infected with HCV 1b with high viral load (>5 log IU/ml), without cirrhosis and overt diabetes, were enrolled. Substitutions in amino acids 70 and 91 of the HCV genotype 1b core region, the percentage of hepatic steatosis by liver histology, and glucose tolerance evaluated by the oral glucose tolerance test were investigated in all patients. Steatosis was observed in 40 patients (54%). Transaminase activities, γ-glutamyl-transpeptidase, serum ferritin levels, homeostasis model assessment of insulin resistance index, and substitutions of amino acid 70 were significantly associated with the presence of steatosis, upon univariate analysis. Glucose intolerance was more prevalent in patients with steatosis (63%) than in those without steatosis (32%, P = 0.012). Multivariate analysis showed that substitution of amino acid 70 (odds ratio: 4.924; 95% confidence interval: 1.442-16.815; P = 0.014) and glucose intolerance (odds ratio: 3.369; 95% confidence interval: 1.076-10.544; P = 0.040) were independent factors related to liver steatosis. Levels of plasma glucose and serum insulin after glucose load were similar between patients with and without substitutions of amino acids 70 and 91. Amino acid substitutions in the HCV genotype 1b core region are associated with hepatic steatosis in patients with chronic hepatitis C, independent of glucose intolerance. [ABSTRACT FROM AUTHOR]

Endoscopic mucosal resection (EMR) is the standard procedure for colorectal tumors. High mucosal elevation by submucosal injection is important for definite en bloc resection and the prevention of perforation. Hyaluronic acid (HA) is a reportedly useful injection solution for high and long-lasting mucosal elevation, but the ideal HA concentration for optimization of mucosal elevation maintenance, injection pressure, and cost is unknown. In the present study, we assessed the appropriate concentration of HA for EMR. A resected porcine colon and esophagus were used. The injection solutions examined were 0.9% normal saline (NS) and four concentrations of an 800-KDa HA preparation (0.4%, 0.2%, 0.13%, and 0.1%). Each solution (2 mL) was injected into the submucosa; injection pressure was calculated, and elevation was measured. The durations of mucosal elevation and EMR were additionally assessed in the living minipig colon. In the resected porcine colon, the mucosal elevation was measured 0, 2, 4, and 6 min after the submucosal injection. All concentrations of HA solution maintained greater mucosal elevation at all times than NS ( P < 0.05). An almost similar result was obtained in the resected porcine esophagus. The injection pressure correlated with the HA concentration. In the living minipig colon, mucosal elevation diminished 2 min after the submucosal injection with NS, but was maintained 2 min after injection with 0.4%, 0.2%, and 0.13% HA. The average duration of EMR was 139 s. Mucosal elevation by HA was greater than that by NS in resected and living animal models. We recommend 0.13% HA for maintaining mucosal elevation, injection pressure, and cost. [ABSTRACT FROM AUTHOR]

The pathogenesis of enteropathy induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still unclear, and there are no established treatments. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has been associated with the development of chronic inflammatory diseases, including autoimmune diseases. To define the role of IL-17A in small intestinal injury and inflammation, we studied the effects of indomethacin administration in mice with targeted deletions of the IL-17A gene. Male C57BL/6 (wild-type) and homozygous IL-17A C57BL/6 mice were subjected to this study. Indomethacin (10 mg/kg) was subcutaneously administered to induce small-intestinal damage. Indomethacin-induced lesions in the small intestine were evaluated by measuring the injured area and by histopathology. Also assessed were myeloperoxidase (MPO) activity, as an index of neutrophil accumulation, and intestinal mRNA expression for inflammatory cytokines. The area of macroscopic ulcerative lesions, the MPO activity and the mRNA expression of inflammatory-associated chemokines, such as keratinocyte chemoattractant (KC), monocyte chemotactic protein-1 (MCP-1), and granulocyte-colony stimulating factor (G-CSF), were significantly increased in indomethacin-treated groups compared with the sham groups. The development of intestinal lesions by indomethacin was inhibited in IL-17A mice compared with wild-type mice, together with significant suppression of the increased levels of MPO activities and KC, MCP-1, and G-CSF levels. These findings demonstrate that IL-17A contributes to the development of indomethacin-induced small intestinal injury through upregulation of G-CSF, KC, and MCP-1. IL-17A might be a promising new therapeutic target to treat NSAID-induced enteritis. [ABSTRACT FROM AUTHOR]