Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn’s disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of “chronic enteropathy associated with SLCO2A1 gene” (CEAS).

BackgroundChronic enteropathy associated with SLCO2A1 gene (CEAS) is a hereditary disease caused by mutations in the SLCO2A1 gene and characterized by multiple small intestinal ulcers of nonspecific histology. SLCO2A1 is also a causal gene of primary hypertrophic osteoarthropathy (PHO). However, little is known about the clinical features of CEAS or PHO.MethodsSixty-five Japanese patients recruited by a nationwide survey of CEAS during 2012–2016 were enrolled in this present study. We reviewed the clinical information of the genetically confirmed CEAS patients.ResultsWe identified recessive SLCO2A1 mutations at 11 sites in 46 patients. Among the 46 patients genetically confirmed as CEAS, 13 were men and 33 were women. The median age at disease onset was 16.5 years, and parental consanguinity was present in 13 patients (28%). Anemia was present in 45 patients (98%), while a single patient experienced gross hematochezia. All patients showed relatively low inflammatory markers in blood tests (median CRP 0.20 mg/dl). The most frequently involved gastrointestinal site was the ileum (98%), although no patient had mucosal injuries in the terminal ileum. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.ConclusionsThe clinical features of CEAS are distinct from those of Crohn’s disease. Genetic analysis of the SLCO2A1 gene is therefore recommended in patients clinically suspected of having CEAS.Electronic supplementary materialThe online version of this article (10.1007/s00535-017-1426-y) contains supplementary material, which is available to authorized users.

Background and Aim The aim of this investigation was to evaluate the efficacy of Japanese magnifying colonoscopic classifications for ulcerative colitis‐associated neoplasia (UCAN). Methods We reviewed the colonoscopy records from 2011 to 2018 at our institutions and identified cases of endoscopically or surgically resected UCAN observed by magnifying narrow‐band imaging (NBI) endoscopy and magnifying chromoendoscopy. Association between magnifying endoscopic classification and histopathological findings was investigated retrospectively. Japan NBI expert team (JNET) classification and pit pattern classification were applied. Results There were 17 patients who had a diagnosis of UCAN. Tumors of types 2A, 2B and 3 by JNET classification correlated with the histopathological findings of low‐grade dysplasia (LGD)/high‐grade dysplasia (HGD), HGD, and massively submucosal invasive (mSM) carcinoma, respectively. Tumors of types III/IV, VI low irregularity, and VI high irregularity/VN by pit pattern classification were correlated with the histopathological findings of LGD/HGD, HGD, and mSM carcinoma, respectively. Conclusions Japan NBI expert team classification and pit pattern classification may be predictive of the histological diagnosis and invasion depth of UCAN. This needs to be investigated prospectively in a large cohort or in a randomized clinical trial.

Background/Aims:Helicobacter pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) are the main causes of peptic ulcers. The purpose of the present study was to elucidate the time trends of the impact of H. pylori infection and use of NSAIDs and/or antithrombotic agents on peptic ulcer bleeding (PUB) in Japanese patients. Methods: We retrospectively reviewed 719 patients who had received endoscopic hemostasis for PUB between 2002 and 2013. Subjects were divided into either the first-half group (2002-2007, n = 363) or the second-half group (2008-2013, n = 356). The clinical characteristics of the patients, including the prevalence of H. pylori infection and use of NSAIDs and antithrombotic agents, were compared between the two groups. Results: Compared to the first-half group, patients in the second-half group were characterized by older age (proportion of the patients above 60 years old, 63.9 vs. 76.7%, p = 0.0002), less frequent H. pylori infection (71.6 vs. 57.9%, p < 0.001) and more frequent NSAID intake (39.9 vs. 48.6%, p = 0.02). No significant difference was observed regarding the use of antithrombotic agents between the two groups (18.6 vs. 23.3%, p = 0.13). The prevalence of H. pylori infection and proportion of patients above 60 years old were significantly different between the two groups in a multivariate analysis. Conclusion: The main cause of PUB has clearly shifted from H. pylori infection to the use of NSAIDs over the last decade.

Circumferential or longitudinal alignment of diminutive lesions, especially in the upper small bowel, may be a diagnostic clue for CD under SBCE, while inter-observer variations should be cautiously considered when using SBCE.

BackgroundEfficacy of maintenance therapy in ulcerative colitis (UC) in the remission stage has been reported to depend on release profile or dosing regimen of oral 5-aminosalicylic acid (5-ASA) products used. Aim of this study is to investigate real life results in using oral 5-ASA products for maintaining mild to moderate UC patients in Japan.MethodsAdult UC outpatients treated with oral 5-ASA products were enrolled from 379 sites in Japan between July 2012 and July 2013, and followed for 52 weeks. Remission maintenance rate was evaluated by products and dosages. Factors affecting recurrence were also examined.ResultsA total of 5695 UC patients were registered. Among the 4677 patients in whom remission maintenance was observed, remission maintenance rate at week 52 was 80.2%. As for disease duration and dosage, Pentasa® 4000 mg/day in 2 divided doses was administered to 480 (21.0%) patients in remission and 341 (46.6%) patients in active stage, and Asacol® 3600 mg/day in 3 divided doses was administered to 696 (46.4%) patients in remission and 473 (67.3%) patients in active stage.The remission maintenance rate at week 52 by dosage and frequency did not significantly differ between Pentasa® Tablets at 4000 mg/day in 2 divided doses (76.5%) and Asacol® Tablets at 3600 mg/day in 3 divided doses (76.1%, P = 0.7868).Factors affecting the risk of relapse in UC were identified. Significantly persistent remission maintenance was noted in patients in whom duration of remission maintenance until enrollment was 12 to <24 months or ≥24 months relative to the reference category of <3 months (12 to <24 months: HR 0.600 [0.486–0.740], p < 0.0001]; ≥24 months: HR 0.352 [0.289–0.431], p < 0.0001).ConclusionsEfficacy of real life results in using oral 5-ASA products for maintaining mild to moderate UC patients was favorable. Maintaining remission for 12 months or longer after induction therapy was shown to reduce recurrence risk thereafter.Trial registration UMIN 000008563 (the date of registration: July 30, 2012), ClinicalTrials.gov NCT01654783 (the date of registration: July 30, 2012)Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0604-y) contains supplementary material, which is available to authorized users.

Both LDA and NSAIDs are risk factors for upper GI bleeding in patients with gastroduodenal ulcer, while ACs are unrelated to the increased risk. The risk of bleeding with LDA may increase with simultaneous use of APs.

Selective COX-2 inhibitors are not completely safe for the small bowel. The mucosal lesions may be less severe with celecoxib than with meloxicam.