Introduction: The Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations guidelines recommend surveillance colonoscopy instead of colectomy after the complete removal of “endoscopically resectable” dysplastic lesions in ulcerative colitis (UC). There are no studies on long-term outcomes of endoscopic submucosal dissection (ESD) for UC-associated neoplasia (UCAN). We aimed to evaluate the clinical outcomes of ESD for UC-associated dysplasia (UCAD) during long-term follow-up. Methods: We retrospectively enrolled 17 consecutive UC patients with 22 UCADs, who underwent initial ESD or total proctocolectomy at the Hiroshima University Hospital. The clinicopathological features of the patients and neoplasias and clinical outcomes of ESD were evaluated and compared with those of total proctocolectomy. Results: UCAD in the ESD and total proctocolectomy groups was mostly noted on the left side of the colon, and most lesions were superficial macroscopic lesions. In the ESD group, en bloc resection and histological complete resection rates were 83 and 67%, respectively. One patient died of malignant melanoma; however, none of the patients died of UC-associated carcinoma in both groups. Metachronous neoplasias developed in 5 of the 7 patients in the ESD group. Among the 5 patients with metachronous UCAN, 4 finally underwent total proctocolectomy and 1 underwent additional ESD. Conclusions: ESD for UCAD is a useful method for total excisional biopsy. UC patients with UCAD resected by ESD have a high risk of developing metachronous UCAN during the follow-up period.

SUMMARY BackgroundChitinase 3-like-1 (CHI3L1) is up-regulated in the inflamed mucosa of inflammatory bowel disease (IBD).

Nitric oxide (NO) is produced from the conversion of L-arginine by NO synthase (NOS) and regulates a variety of processes in the gastrointestinal tract. Considering the increased activity of arginase in colitis tissue, it is speculated that arginase could inhibit NO synthesis by competing for the same L-arginine substrate, resulting in the exacerbation of colitis. We examined the role of arginase and its relationship to NO metabolism in dextran sulfate sodium (DSS)-induced colitis. Experimental colitis was induced in mice by administration of 2.5% DSS in drinking water for 8 days. Treatment for arginase inhibition was done by once daily intraperitoneal injection of N(ω)-hydroxy-nor- arginine (nor-NOHA). On day 8, we evaluated clinical parameters (body weight, disease activity index, and colon length), histological features, the activity and expression of arginase, L-arginine content, the expression of NO synthase (NOS), and the concentration of NO end-product (NOx: nitrite + nitrate). Administration of nor-NOHA improved the worsened clinical parameters and histological features in DSS-induced colitis. Treatment with nor-NOHA attenuated the increased activity of arginase, upregulation of arginase Ι at both mRNA and protein levels, and decreased the content of L-arginine in colonic tissue in the DSS-treated mice. Conversely, despite the decreased expression of NOS2 mRNA, the decreased concentration of NOx in colonic tissues was restored to almost normal levels. The consumption of L-arginine by arginase could lead to decreased production of NO from NOS, contributing to the pathogenesis of the colonic inflammation; thus, arginase inhibition might be effective for improving colitis.

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Background and study aims In colorectal endoscopic submucosal dissection (ESD), the S-O clip improves the accessibility to the submucosal layer of the colon. However, its safety and usefulness in difficult colorectal ESDs are unclear. Thus, in this study, we aimed to assess the effectiveness of the S-O clip in colorectal ESD in the difficult-to-access submucosal layer. Patients and methods From January 2016 to December 2016, 189 consecutive cases of colorectal ESD were performed at Hiroshima University Hospital before the S-O clip was introduced. Between January 2017 and June 2018, among 271 consecutive colorectal ESD cases, 41 cases were performed colorectal ESD using the S-O clip. We compared outcomes between the two groups (41 cases with S-O clip [use group] and 189 cases without S-O clip [non-use group]) using propensity score matching. Results Prior to propensity score matching, 41 cases with the S-O clip (use group) and 189 cases without the S-O clip (non-use group) were extracted. The degree of submucosal fibrosis was more severe and the procedure time was longer in the use group than in the non-use group. In the use and non-use groups, en bloc resection (100 % vs. 94.7 %) and complete en bloc resection (100 % vs. 92.6 %) rates were satisfactory. After propensity score matching, 33 cases in each group were extracted. As a result, complete en bloc resection rate was significantly higher in the use group than in the non-use group (100 % vs. 84.9 %). Conclusion The S-O clip is effective and can be used safely in colorectal ESD in the difficult-to-access submucosal layer.

Objectives: Surveillance colonoscopy after endoscopic resection (ER) for adenomatous polyps reduces the incidence and mortality of colorectal cancer (CRC). However, its significance in the elderly population is uncertain. The study aimed to determine whether surveillance colonoscopy should be discontinued in the elderly population. Methods: We enrolled 105 patients who underwent baseline colonoscopy between January 2004 and December 2009 and were subsequently followed-up over 5 years in our institution. All had diminutive colorectal polyps and were aged <80 years at baseline colonoscopy and ! 80 years at follow-up in May 2018. Patients who had undergone colectomy or who had inflammatory bowel disease, familial adenomatous polyposis, Lynch syndrome, and no diminutive polyps were excluded. The cumulative incidence of the target lesion was evaluated. Histopathological diagnoses included low-grade dysplasia (LGD), highgrade dysplasia (HGD), and carcinoma. Results: The target lesion was detected in 15% (16/105) of the patients. There was no invasive carcinoma; however, two HGDs were detected. There were three lesions that had increased from previously detected diminutive lesions, all of which were LGDs. There were no target lesions detected after 84 years of age, and the cumulative incidence was 0.20. The cumulative incidence was significantly higher in the group with HGD than in the group with no target lesions at baseline colonoscopy. There was no HGD after age 79 years, and the cumulative incidence was 0.019. Conclusion: Surveillance colonoscopy for patients with diminutive polyps may be discontinued after age 79 years.

Background and study aims  The PCF-H290TI/L produced by Olympus is a novel colonoscope equipped with some advantageous features for endoscopic treatment. It is expected to improve the potential for retroflexion and overall endoscope operability, which can reduce the difficulty of performing colorectal ESD. The aim of this study was to evaluate the utility of the novel colonoscope in colorectal ESD. Methods  Three hundred and forty-eight consecutive colorectal lesions resected via ESD between June 2014 and January 2017 at Hiroshima University Hospital were included in the retroflexion ability analysis. We compared the retroflexion potential of PCF-H290TI to that of a conventional endoscope. Two hundred and twenty-seven colorectal lesions located in the left-sided colon and resected with ESD between April 2009 and February 2018 were enrolled in the treatment outcome analysis. Treatment outcomes using PCF-H290TI compared to those of the conventional colonoscope, and outcomes of the PCF-H290TI with retroflexion compared to those of the conventional colonoscope without retroflexion were evaluated by propensity score matching. Results  The retroflexion rate with the PCF-H290TI was 76 %, which was significantly higher than the 44 % rate with the conventional scope. Endoscope operability was better and dissection speed was faster when using the PCF-H290TI with retroflexion compared to the conventional colonoscope without retroflexion. There were no significant differences between the groups in en bloc resection rate and adverse events. Conclusion  Compared to the conventional colonoscope, the PCF-H290TI/L made it easier to perform ESD via a retrograde approach regardless of tumor location, and thus may be useful for performing colorectal ESD.

Backgrounds Colorectal neoplasias (CRN)s developing from the ulcerative colitis (UC) mucosa include both colitic and sporadic neoplasias. Although several genomic analyses of advanced colitis-associated cancer are available, such studies do not distinguish between colitic and sporadic cases, and the early-stage genomic alterations involved in the onset of colitic cancer remain unclear. To address this, we performed a genomic analysis of early-stage CRN developing from the UC mucosa (CRNUC). Methods We extracted DNA from 36 early-stage CRNUCs (T1 cancer, 10; dysplasia, 26) from 32 UC patients and performed targeted sequencing of 43 genes commonly associated with colitis-associated cancer and compared the results with sequencing data from the Japanese invasive colitis-associated cancer. Results The most frequently mutated gene in the CRNUC cohort was APC (mutated in 47.2% of the cases), followed by TP53 (44.4%), KRAS (27.8%), and PRKDC (27.8%). None of the TP53 mutations occurred at any of the hotspot codons. Although the TP53 mutations in The Cancer Genome Atlas of Colorectal Cancer were dispersed throughout the gene, those detected here in CRNUC cases were concentrated in the amino terminal part of the DNA-binding domain. Interestingly, the mutations in KRAS and TP53 were mutually exclusive in CRNUC, and CRNUCs with KRAS mutations had histologically serrated lesions in the gland duct. Mayo endoscopic subscore was higher in TP53-mutated CRNUCs and lower in KRAS-mutated CRNUCs. Conclusions Our findings suggest that early-stage CRNUC can be classified into 2 groups: those developing through the carcinogenic pathway via TP53 mutations and those developing through the carcinogenic pathway via KRAS mutations.