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Background: Mucosal healing (MH) was proposed to be an ideal treatment goal for patients with inflammatory bowel disease (IBD). Instead of endoscopy to confirm MH, biomarkers are frequently used and have become an indispensable modality for the clinical examination of patients with IBD. Summary: Common biomarkers of IBD include C-reactive protein (CRP), erythrocyte sedimentation rate, antineutrophil cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, leucine-rich α2 glycoprotein, fecal calprotectin (FCP), and the fecal immunochemical test. Biomarkers play five major roles in the management of IBD: (1) diagnosing and distinguishing between IBD and non-IBD or ulcerative colitis and Crohn’s disease; (2) predicting treatment response, especially before administrating biologics; (3) monitoring and grasping endoscopic or histological disease activity; (4) replacing endoscopy for diagnosing MH, including endoscopic and histological remission; and (5) predicting recurrence before disease activity appears through symptoms. Many reports have demonstrated the usefulness of CRP and FCP for those five roles; however, they have limitations for diagnosing MH or predicting treatment response. In general, FCP has better ability in those positions than CRP; additionally, leucine-rich α2 glycoprotein can diagnose endoscopic disease activity better than CRP. The novel biomarker, prostaglandin E-major urinary metabolite, and anti-αvβ6 antibody are expected to be noninvasive and reliable biomarkers; however, more evidence is required for future studies. Oncostatin M and microRNA are also prospects, in addition to other familiar and novel biomarkers. Key Messages: Each biomarker has a useful feature; therefore, we should consider their features and use appropriate biomarkers for the five roles to enable noninvasive and smooth management of IBD.

A joint effort between the Copernicus Climate Change Service (C3S) and the Group for High Resolution Sea Surface Temperature (GHRSST) has been dedicated to an intercomparison study of eight global gap-free sea surface temperature (SST) products to assess their accurate representation of the SST relevant to climate analysis. In general, all SST products show consistent spatial patterns and temporal variability during the overlapping time period (2003–18). The main differences between each product are located in the western boundary current and Antarctic Circumpolar Current regions. Linear trends display consistent SST spatial patterns among all products and exhibit a strong warming trend from 2012 to 2018 with the Pacific Ocean basin as the main contributor. The SST discrepancy between all SST products is very small compared to the significant warming trend. Spatial power spectral density shows that the interpolation into 1° spatial resolution has negligible impacts on our results. The global mean SST time series reveals larger differences among all SST products during the early period of the satellite era (1982–2002) when there were fewer observations, indicating that the observation frequency is the main constraint of the SST climatology. The maturity matrix scores, which present the maturity of each product in terms of documentation, storage, and dissemination but not the scientific quality, demonstrate that ESA-CCI and OSTIA SST are well documented for users’ convenience. Improvements could be made for MGDSST and BoM SST. Finally, we have recommended that these SST products can be used for fundamental climate applications and climate studies (e.g., El Niño).

Objectives: The aim of this study was to propose an endoscopic classification system for ulcerative lesions on the ileocecal valve and investigate its relevance to the underlying etiology. Methods: Among the 60,325 patients who underwent colonoscopy at our hospital from January 2006 to December 2018, patients with ulcerative lesions on the ileocecal valve were included. The following data were obtained using the hospital’s medical records: sex, age, clinical diagnosis, laboratory data, and endoscopic and histological findings. Patients who have ulcerative colitis and who were not evaluated by histological examination were excluded. Ulcerative lesions on the ileocecal valve were classified into 3 groups according to their endoscopic appearance: small shallow ulcerative lesions without edematous change (group A), lateral spreading shallow ulcerative lesions with edematous change (group B), and deep deformed ulcerative lesions (group C). The association between this endoscopic classification and its clinical diagnosis, clinical course, and the interobserver reliability were evaluated. Results: Of 72 patients who were eligible for analysis, 18 were assigned to group A, 9 to group B, and 45 to group C. Infectious enteritis was mainly assigned to group A (group A, 12; group B, none; and group C, 6; p < 0.0001), inflammatory bowel disease was mainly assigned to group C (group A, none; group B, 5; and group C, 35; p < 0.0001), and malignant tumor was assigned to group C only. Interobserver reliability was extremely high among the 3 examining doctors (kappa value 0.7–0.8). Conclusion: Endoscopic classification was divided into 3 groups for ulcerative lesions on the ileocecal valve, and this system could be beneficial for presuming their clinical diagnoses.

Background and Aims: In gastrointestinal neuroendocrine tumors (GI-NETs), tumor size and grading based on cellular proliferative ability indicate biological malignancy but not necessarily clinically efficient prognostic stratification. We analyzed tumor size- and grading-based prevalence of lymphovascular invasion in GI-NETs to establish whether these are true biological malignancy indicators. Methods: We included 155 cases (165 lesions), diagnosed histologically with GI-NETs, that had undergone endoscopic or surgical resection. Patient age, sex, method of treatment, tumor size, invasion depth, lymphovascular invasion positivity according to Ki-67 index-based neuroendocrine tumor grading, distant metastases, and outcome were evaluated. The primary endpoints were the prevalence of lymphovascular invasion according to tumor size and grading. Results: Overall, 24.8% were positive for lymphovascular invasion. There was a high rate of lymphovascular invasion positivity even among grade 1 cases (22.8%). The rate of lymphovascular invasion was 3.4% for grade 1 cases Conclusions: GI-NETs ≤10 mm had a lymphovascular invasion prevalence exceeding 10%. The lymphovascular invasion impact in GI-NET development is incompletely understood, but careful follow-up, including consideration of additional surgical resection, is crucial in cases with lymphovascular invasion.

Background/Aim: Malignant lymphoma (ML) cases with overlapping gastrointestinal (GI) lesions are often encountered. We aimed to elucidate the importance of examining the GI tract in patients with ML and assess the overlap rate. Patients and Methods: We analysed 190 patients diagnosed with GI MLs. We compared the overlap rates among the different histopathological types. Results: Twenty-five (13.2%) patients had overlapping GI lesions in more than two segments. The overlap rates were 100% in mantle cell lymphomas (MCL), 27.6% in follicular lymphomas (FL), and 16.3% in diffuse large B-cell lymphomas (DLBCL). MCL, FL, and DLBCL cases showed significantly higher overlap rates than mucosa-associated lymphoid tissue lymphoma cases (p

Ulcerative colitis (UC) is usually detected by clinical symptoms, such as bleeding and diarrhea; however, it is rather difficult to assess during asymptomatic clinical remission (CR). Hence, there is a need for a biomarker that can reliably detect UC during remission. We previously reported on the utility of the prostaglandin E-major urinary metabolite (PGE-MUM) as a biomarker reflecting UC activity. In this study, we evaluated the effectiveness of the PGE-MUM in the diagnosis of endoscopic, histological, and histo-endoscopic mucosal remission of UC, comparing with fecal tests.This prospective study was conducted at the Jikei University Hospital between August 2017 and January 2021. Patients with UC in CR scheduled to undergo colonoscopy were included. The association between the PGE-MUM with endoscopic remission (ER), histological remission (HR), and complete mucosal healing (CMH, defined as histo-endoscopic remission) was analyzed. We also compared the area under the curve (AUC) for the receiver operating characteristic curves between PGE-MUM, fecal calprotectin (FC), and fecal immunochemical test (FIT).In total, 128 patients were analyzed. PGE-MUM differed significantly in ER versus non-ER (14.5 vs 16.7, P = 0.028), HR versus non-HR (14.2 vs 17.4, P = 0.004), and CMH versus non-CMH (14.3 vs 16.7, P = 0.021). There were no significant differences between the AUCs for PGE-MUM, FC, and FIT for ER, HR, or CMH.The PGE-MUM can determine CMH in UC even during CR, regardless of the disease phenotype, indicating its clinical benefit for non-invasive monitoring.

Japan has the largest aging society, where many elderly people have intractable diseases including ulcerative colitis (UC). Along with the increasing total number of UC patients, the number of elderly UC patients has also been increasing and will continue to do so in the future. Although the clinical features and natural history of UC in the elderly have many similarities with UC in the non-elderly population, age-specific concerns including comorbidities, immunological dysfunction, and polypharmacy make the diagnosis and management of elderly UC challenging compared to UC in non-elderly patients. Based on increasing data related to elderly UC patients from Japan, as well as other countries, we reviewed the epidemiology, clinical course, differential diagnosis, management of comorbidities, surveillance, medical therapy, and surgery of UC in the elderly.

Background and study aims We evaluated the utility of esophagogastroduodenoscopy (EGD) or capsule endoscopy (CE) as the next diagnostic approach after negative colonoscopy (CS) results in acute-onset hematochezia. Patients and methods We retrospectively analyzed 401 patients emergently hospitalized for acute hematochezia who underwent CS within 48 hours of arriving at two large emergency hospitals and in whom a definitive bleeding source was not identified. The positive endoscopic findings, requirement for additional therapeutic procedures, and 30-day rebleeding rates were compared among three strategies: EGD following CS (CS-EGD), CE following CS (CS-CE), and CS alone. Predictors of positive endoscopic findings in the CS-EGD strategy were determined. Results The rates of positive endoscopic findings and requirement for additional therapeutic procedures were 22 % and 16 %, respectively, in CS-EGD and 50 % and 28 % in CS-CE. The 30-day rebleeding rate did not significantly decrease in CS-EGD (8 %) or CS-CE (11 %) compared with CS alone (12 %). The rate of additional endoscopic therapies was lower in patients with a colonic diverticulum than in those without (CS-EGD: 3 % vs. 33 %, P = 0.007; CS-CE: 11 % vs. 44 %, P = 0.147). A history of syncope, low blood pressure, blood urea nitrogen/creatinine ratio of ≥ 30, and low albumin level significantly predicted EGD findings after negative CS results (P Conclusions When the definitive bleeding source is not identified by colonoscopy in patients with acute hematochezia, adjunctive endoscopy helps to identify the etiology and enables subsequent therapy, especially for patients without a colonic diverticulum. Upper gastrointestinal endoscopy is indicated for severe bleeding; other patients may be candidates for capsule endoscopy.

BACKGROUND There are no reports to prove the repeatability of gastric transit time (GTT) and small bowel transit time (SBTT) in capsule endoscopy (CE). OBJECTIVE To clarify the repeatability and factors that affect GTT/SBTT in CE. METHODS We analyzed the data of 150 healthy subjects from our previous randomized controlled trial that compared small intestinal injuries between two 14-day treatment groups: 1) celecoxib and 2) loxoprofen + lansoprazole. Correlation of GTT/SBTT with pre- and post-treatment CE was analyzed. In addition, the associations of pre-treatment CE SBTT with physical factors, post-treatment CE SBTT and the presence of small intestinal mucosal injuries were analyzed. RESULTS Analyses of 148 subjects pre-treatment CE and 146 subjects post-treatment CE were performed. There were no significant differences between mean GTT and SBTT before and after treatment. Both GTT (𝜌 = 0.22, p < 0.01) and SBTT (𝜌 = 0.47, p < 0.0001) showed positive correlations between pre- and post-treatment CE. In pre-treatment CE, physical factors and the presence of small intestinal mucosal injury had no associations with SBTT. CONCLUSIONS Moderate correlation in SBTT and slight correlation in GTT were shown on repeated CE. The factors affecting SBTT were not clarified in this analysis.

Background There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy. Aim To identify the SNP that is most significantly involved with NSAID-induced enteropathy. Methods One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation. Results After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10−7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p

Background We developed a predictive model of long-term gastrointestinal (GI) bleeding risk in patients receiving oral anticoagulants and compared it with the HAS-BLED score. Methods We periodically followed a cohort of 508 patients taking oral anticoagulants (66 direct oral anticoagulants users and 442 warfarin users). Absence of GI bleeding at an initial examination, and any subsequent GI bleeding, were confirmed endoscopically. The bleeding model was developed by multivariate survival analysis and evaluated by Harrell's c-index. Results During a median follow-up of 31.4 months, 42 GI bleeds (8.3%) occurred; 42.8% in the upper GI tract, 50.0% in the lower GI tract, and 7.1% in the middle GI tract. The cumulative 5- and 10-year probability of GI bleeding was 12.6% and 18.5%, respectively. Patients who bled had a significantly higher cumulative incidence of all-cause mortality (hazard ratio 2.9, p

AIM To elucidate the rates of recurrence and mortality in acute esophageal variceal bleeding and the associated risk factors. METHODS A cohort of 174 patients emergently hospitalized for esophageal variceal bleeding was analyzed. All patients underwent endoscopic variceal ligation within 3 h of arrival. Comorbidities, vital signs, drug use, laboratory data, etiology, endoscopic findings, transfusion requirement, and follow-up endoscopy were assessed. Cox's proportional hazards model was used to estimate hazard ratios (HR). RESULTS Rebleeding was identified in 49 patients with a mean follow-up of 18 months. The cumulative rebleeding rate at 1 month, 1 year, and 5 years was 10.2%, 30.0%, and 51.0%, respectively. In multivariate analysis, independent risk factors for rebleeding were child-Pugh class C (HR 1.94; P = 0.027), alcoholic liver cirrhosis (HR 2.32; P = 0.01), and no follow-up endoscopy (HR 13.3; P

Background & Aims We investigated the safety and effectiveness of early colonoscopy (performed within 24 hours of hospital admission) for acute lower gastrointestinal bleeding (LGIB) vs elective colonoscopy (performed 24 hours after admission). Methods We conducted a retrospective study by using a database of endoscopies performed at the National Center for Global Health and Medicine in Tokyo, Japan from January 2009 through December 2014. We analyzed data from 538 patients emergently hospitalized for acute LGIB. We used propensity score matching to adjust for differences between patients who underwent early colonoscopy vs elective colonoscopy. Outcomes included rates of adverse events during bowel preparation and colonoscopy procedures, stigmata of recent hemorrhage, endoscopic therapy, blood transfusion requirement, 30-day rebleeding and mortality, and length of hospital stay. Results We selected 163 pairs of patients for analysis on the basis of propensity matching. We observed no significant differences between the early and elective colonoscopy groups in bowel preparation–related rates of adverse events (1.8% vs 1.2%, P = .652), colonoscopy-related rates of adverse events (none in either group), blood transfusion requirement (27.6% vs 27.6%, P = 1.000), or mortality (1.2% vs 0, P = .156). The early colonoscopy group had higher rates than the elective group for stigmata of recent hemorrhage (26.4% vs 9.2%, P P P P = .048), and rebleeding (13.5% vs 7.4%, P = .070). Patients in the early colonoscopy group stayed in the hospital for a shorter mean time (10 days) than patients in the elective colonoscopy group (13 days) ( P Conclusions Early colonoscopy for patients with acute LGIB is safe, allows for endoscopic therapy because it identifies the bleeding source, and reduces hospital stay. However, compared with elective colonoscopy, early colonoscopy does not reduce mortality and may increase the risk for rebleeding.

The aim of this study was to compare celecoxib with loxoprofen for protection of small intestine.RCT studies report that COX-2 selective inhibitor celecoxib induces fewer small intestinal injuries than nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Loxoprofen is a prodrug nonselective NSAID developed to protect upper gastrointestinal tract.A total of 150 healthy volunteers (40 to 70 y) were enrolled. After medical checkup including laboratory data, subjects were randomly assigned to celecoxib (200 mg daily) or loxoprofen (180 mg daily) plus lansoprazole (15 mg daily). All drugs were prepared using inactive capsules. After randomization, all subjects were first examined by baseline capsule endoscopy (CE). After 14 days, subjects underwent posttreatment CE. We compared baseline and posttreatment CE findings of the 2 groups. All CE data were evaluated blindly by 3 reviewers. Pretreatment and posttreatment laboratory variables were also compared.A total of 74 subjects (49±6 y, F/M: 36/38) were enrolled in celecoxib group and 76 subjects (49±7 y, F/M: 39/37)in loxoprofen group. Five in celecoxib group and 4 in loxoprofen group were excluded from CE analysis mainly due to incomplete CE. The percentage of subjects with at least 1 posttreatment mucosal break was lower in celecoxib group (10%) than in loxoprofen group (49%) (P0.0001). A total of 0.3±1.0 posttreatment small intestinal mucosal breaks were detected in the celecoxib group, and 6.8±21.5 in the loxoprofen group (P0.0001). Posttreatment hemoglobin concentration in loxoprofen group (5.1% reduction) was lower compared with celecoxib group (2.1% reduction) (P=0.006).In terms of protection of small intestine from NSAIDs toxicity, celecoxib monotherapy was superior to loxoprofen+lansoprazole combination therapy (UMIN: 000007936).

We investigated the spectral refractive indices (RIs) of volcanic ash materials in the wavenumber range of 700–1100 cm− 1 using satellite infrared sounder measurements and radiative transfer calculations. The ash RIs of 10 ash clouds from eight volcanoes were evaluated (Bezymianny on 2 September 2012, Chaiten on 3 May 2008, Kelut on 14 February 2014, Kirishimayama on 27 January 2011, Kliuchevskoi on 30 June 2007 and 18 October 2013, Puyehue–Cordon Caulle on 5 June 2011, Sangeang-Api on 31 May 2014, and Sheveluch on 28 October 2010 and 18 September 2012). We elaborated on a dataset of volcanic ash measurements made by the Atmospheric Infrared Sounder (AIRS) onboard the Aqua satellite. The measured brightness temperatures in the ash cloud data revealed silicate absorption features at around 10 μm. By applying atmospheric profiles from results of a global data assimilation system and using ash cloud properties (ash optical depth, effective radius, and ash cloud height) as parameters for radiative transfer calculations, least squares analyses for the observed and calculated brightness temperatures were conducted using AIRS channels in the wavenumber range of 700–1100 cm− 1, except for the O3 absorption channels in the range of 980–1070 cm− 1. Using the RIs for typical volcanic rocks in the ascending order of SiO2 content, basalt, andesite, and rhyolite, a mixture of basalt and rhyolite and a mixture of andesite and rhyolite for the ash material were considered. The volume fraction of the mixture was used as a retrieval parameter and as the ash cloud parameter. Using the estimated ash cloud parameters as fixed values, and under the assumption that the RI from the estimated volume fraction had some accuracy in the wavenumber ranges of 850–980 cm− 1 and 1070–1100 cm− 1, the RI imaginary part of each eruptive ash cloud captured by AIRS was then determined from iterative calculations at wavenumbers between 750 cm− 1 and 980 cm− 1. In the wavenumber range of 850–980 cm− 1, the observed brightness temperatures could be approximately simulated using the reported RIs from Pollack, Toon, and Khare (1973) for andesite, basalt, and rhyolite, and their combinations. Furthermore, some estimated RIs were consistent with the reported rock types of the volcanoes, which had been previously classified by compositional analyses in the literature. Our analysis also identified weak absorptions around 750–850 cm− 1, which could not be reproduced by the reported RIs. These weak absorptions were likely due to Si–O and/or Al–O vibrations, which have been proposed in reports from previous laboratory experiments for some silicate glass samples. Our results suggest that the detailed RI of volcanic ash can be determined from an analysis of satellite infrared sounder data. The RI of the ash material estimated from satellite infrared sounder data can be used to improve the ash retrieval algorithms of other satellite measurements. Furthermore, an RI retrieved by sounder measurements may provide diagnostic information regarding volcanic activity from comparisons with the ash RIs from past eruptions.

Purpose To demonstrate the usefulness of precolonoscopy intravenous contrast material-enhanced CT for colonic diverticular bleeding (CDB). Materials and Methods A prospective, multicenter, observational study was performed. Patients with acute-onset hematochezia who were admitted to hospital were included, and those without CDB were excluded. CT was performed before colonoscopy. A Mann-Whitney U test, χ2 test, and multivariable logistic regression analysis were performed to determine the accuracy of CT before colonoscopy. Results A total of 442 patients (mean age, 71.2 years; 302 male patients; 68.3% men) were included between January 2014 and December 2015, and 202 patients were diagnosed as having CDB. The positive extravasation rate during CT was 50 of 202 (24.7%) among all patients and five of nine (55.6%) among patients who underwent CT within 1 hour of the last hematochezia. At multivariable analysis, the interval from the last hematochezia until CT was a predictor of extravasation (beta coefficient, -.0038 ± 0.0014 [standard deviation]). Extravasation at CT had a sensitivity of 38 of 66 (57.6%; 95% confidence interval: 44.8%, 69.7%) and a specificity of 124 of 136 (91.2%; 95% confidence interval: 85.1%, 95.4%) for the prediction of stigmata of recent hemorrhage of diverticula during colonoscopy. The sensitivity was higher in patients who underwent CT examination within 4 hours of hematochezia, compared with those examined after 4 hours (64.7% [33 of 51] vs 33.3% [five of 15]; P < .01). Conclusion Extravasation findings for CT with intravenous contrast material had high specificity for the prediction of stigmata of recent hemorrhage of diverticula during colonoscopy, regardless of the timing of the CT examination. Although the sensitivity was relatively low, it was higher when the CT examination was performed within 4 hours after the last hematochezia. Therefore, urgent precolonoscopy CT may contribute to decision making regarding whether an urgent colonoscopy should be performed.

Japan has the largest aging society, where many elderly people have intractable diseases including ulcerative colitis (UC). Along with the increasing total number of UC patients, the number of elderly UC patients has also been increasing and will continue to do so in the future. Although the clinical features and natural history of UC in the elderly have many similarities with UC in the non-elderly population, age-specific concerns including comorbidities, immunological dysfunction, and polypharmacy make the diagnosis and management of elderly UC challenging compared to UC in non-elderly patients. Based on increasing data related to elderly UC patients from Japan, as well as other countries, we reviewed the epidemiology, clinical course, differential diagnosis, management of comorbidities, surveillance, medical therapy, and surgery of UC in the elderly.

Background and Aim Visceral adiposity is a strong determinant of insulin resistance, which decreases cholecystokinin response sensitivity, and increases cholesterol saturation in the gallbladder bile; thus, it potentially relates to gallstone disease development. We aimed to investigate whether visceral fat measured by computed tomography (CT) is a risk factor for gallstone disease. Methods A cohort of 717 participants undergoing CT and ultrasonography was analyzed. The associations between body mass index (BMI), visceral adipose tissue (VAT) area, subcutaneous adipose tissue (SAT) area, and gallstone disease were analyzed adjusted for age, sex, hypertension, diabetes, and dyslipidemia. Results In multivariate analysis, gallstone disease was significantly associated with VAT and SAT areas for both categorical data and trend (P for trend

Background It remains unclear whether diverticulosis, absent inflammation, is responsible for chronic bowel symptoms. We examined the association between bowel symptoms and asymptomatic diverticulosis. Method This case-control study included 543 patients with diverticulosis and 1086 age and sex-matched controls (1:2) without diverticulosis on screening colonoscopy. Eleven symptoms (abdominal discomfort, hunger discomfort, borborygmus, abdominal distension, flatus, constipation, diarrhea, loose stools, hard stools, fecal urgency, and incomplete evacuation) were evaluated using a gastrointestinal symptoms rating scale (GSRS) at baseline and second questionnaire. Associations between diverticulosis and symptoms were estimated using odds ratios (ORs) and 95 confidence interval (CI). Results In multivariate analysis, constipation (OR, 0.85 [0.78–0.93]) and hard stools (OR, 0.86 [0.78–0.94]) were negatively associated with diverticulosis. The other nine symptoms showed no association with diverticulosis. Diverticulosis was negatively associated with constipation (OR, 0.93 [0.74–0.93]), hard stools (OR, 0.85 [0.76–0.96]), and incomplete evacuation (OR, 0.88 [0.79–0.99]) in males, and positively associated with diarrhea (OR, 1.39 [1.14–1.69]) and loose stools (OR, 1.28 [1.05–1.55]) in females. No bowel symptoms were positively associated with any of right-sided, left-sided, or bilateral diverticulosis. Test–retest reliability of GSRS (mean interval, 4.4 months) was moderate (Mean Kappa, 0.568) in males and good (Mean Kappa, 0.652) in females. Conclusions This large, colonoscopy-based, case-control study demonstrated that neither constipation nor hard stools were associated with an increased risk of diverticulosis, regardless of diverticulum location. In females, but not males, diarrhea and loose stools were positively associated with diverticulosis. Long-term test–retest reliability suggested that these symptoms remain consistent over a given period.

The aim of this study was to identify predictors for the identification of stigmata of recent hemorrhage (SRH) on colonic diverticula.Several factors influence the identification of SRH in the diagnosis of colonic diverticular bleeding.A total of 396 patients hospitalized for lower gastrointestinal bleeding were analyzed. Comorbidities, medications, timing of colonoscopy [24 h (h); urgent, 24 to 48 h,48 h], preparation, expert colonoscopist, use of a cap, use of a water-jet scope, total colonoscopy, and procedure time (over 60 min) were assessed. A multivariable logistic regression model was used to estimate odds ratio (OR) and 95% confidence interval (CI).Two hundred fifteen patients were diagnosed with colonic diverticular bleeding and 37 (17%) were identified with SRH. Urgent colonoscopy (OR, 8.4; 95% CI, 2.3-30; P0.01), expert colonoscopist (OR, 3.0; 95% CI, 1.2-7.3; P=0.02), use of a cap (OR, 3.4; 95% CI, 1.4-8.0; P=0.01), and use of water-jet scope (OR, 5.8; 95% CI, 2.3-15; P0.01) were found to be independent predictive factors for SRH. The accuracy of these factors in combination was 0.90 (95% CI, 0.85-0.96) as measured by area under the receiver operating characteristic curve (ROC-AUC). SRH identification rate was higher in the urgent (22%) than in the 24 to 48 hours (2.9%, P0.01) and48 hours groups (1.0%, P0.01), showing a tendency to decrease with time (P0.01 for trend).Factors of urgent colonoscopy, expert colonoscopist, use of a cap, and use of water-jet scope are useful for identifying SRH diverticula.

Background and Aims Very few prospective studies with over 100 samples have evaluated the long-term outcomes of endoscopic therapy for colonic diverticular bleeding (CDB). This study sought to elucidate the recurrent bleeding risk of endoscopic band ligation versus clipping for definitive CDB based on stigmata of recent hemorrhage (SRH). Methods Patients emergently hospitalized for acute lower GI bleeding and examined by high-resolution colonoscopy were enrolled. Better visualization of SRH from a diverticulum was obtained using a water-jet device. Endoscopic band ligation or clipping was performed as first-line treatment, and patients were prospectively followed after discharge. Results No statistical difference was found between the ligation (n = 61) and clipping (n = 47) groups in baseline characteristics or follow-up period. The probability of 1-year recurrent bleeding was 11.5% in the ligation group versus 37.0% in the clipping group (P = .018). No patients required surgery or experienced perforation. One patient in the ligation group experienced diverticulitis the next day. In patients with recurrent bleeding within 7 days, the recurrent bleeding site was the same diverticulum, and ulceration was found in the ligation group on repeat colonoscopy. In patients with recurrent bleeding after 2 months, repeat colonoscopy identified that the recurrent bleeding site was different, and scar formation was seen in the ligation group. The left side of the colon was an independent predictor for recurrent bleeding in the ligation group but not in the clipping group. Conclusions Band ligation for definitive CDB has better outcomes than clipping during long-term follow-up after endoscopic therapy, probably because of complete elimination of the diverticulum. CDB can recur at the same diverticulum in the short term but at a different diverticulum in the long term.

Background We investigated the effects of proton-pump inhibitors (PPIs) on lower gastrointestinal bleeding (LGIB) and of their interactions with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, clopidogrel, and warfarin on LGIB risk.

Background and Aim The associations between antithrombotic or antihypertensive drugs and peptic ulcer bleeding (PUB) remain unknown, particularly in Asia, where Helicobacter pylori infection is prevalent. This study aims to evaluate the risks of PUB from antithrombotic drugs, angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, α-blockers, and β-blockers. Methods This prospective hospital-based case-control study included 230 patients with endoscopically verified PUB and 920 age and sex-matched controls (1:4) without bleeding on screening endoscopy. Adjusted odds ratios (AOR) for the risk of PUB were determined by conditional logistic regression analysis. Results In multivariate analysis, alcohol consumption (AOR, 2.2; P

Background Anticoagulant management of acute gastrointestinal bleeding (GIB) during the pre-endoscopic period has not been fully addressed in American, European, or Asian guidelines. This study sought to evaluate the risks of rebleeding and thromboembolism in anticoagulated patients with acute GIB. Methods Baseline, endoscopy, and outcome data were reviewed for 314 patients with acute GIB: 157 anticoagulant users and 157 age-, sex-, and important risk-matched non-users. Data were also compared between direct oral anticoagulants (DOACs) and warfarin users. Results Between anticoagulant users and non-users, of whom 70% underwent early endoscopy, no endoscopy-related adverse events or significant differences were found in the rate of endoscopic therapy need, transfusion need, rebleeding, or thromboembolism. Rebleeding was associated with shock, comorbidities, low platelet count and albumin level, and low-dose aspirin use but not HAS-BLED score, any endoscopic results, heparin bridge, or international normalized ratio (INR) ≥ 2.5. Risks for thromboembolism were INR ≥ 2.5, difference in onset and pre-endoscopic INR, reversal agent use, and anticoagulant interruption but not CHA2DS2-VASc score, any endoscopic results, or heparin bridge. In patients without reversal agent use, heparin bridge, or anticoagulant interruption, there was only one rebleeding event and no thromboembolic events. Warfarin users had a significantly higher transfusion need than DOACs users. Conclusion Endoscopy appears to be safe for anticoagulant users with acute GIB compared with non-users. Patient background factors were associated with rebleeding, whereas anticoagulant management factors (e.g. INR correction, reversal agent use, and drug interruption) were associated with thromboembolism. Early intervention without reversal agent use, heparin bridge, or anticoagulant interruption may be warranted for acute GIB.

Background Detection of human herpesviruses (HHVs) other than cytomegalovirus (CMV) in colonic mucosa of individuals with inflammatory bowel disease (IBD) remains unknown. This study identified eight HHVs in the colonic mucosa of individuals with IBD and compared the results with immunocompetent and human immunodeficiency virus (HIV)-infected individuals. Methods A total of 89 individuals who had colorectal ulcer on colonoscopy were enrolled: 26 with immunocompetency (n = 26), 41 with IBD, and 22 with HIV infection. We examined the colonic ulcers for the presence of eight HHVs—herpes simplex virus (HSV)-1/2, varicella zoster virus (VZV), CMV, Epstein–Barr virus (EBV), HHV-6, HHV-7, and HHV-8—using mucosal PCR. Results The IBD group had positivity rates of 0%, 0%, 0%, 53.7%, 24.4%, 39%, 39%, and 0% for HSV-1, HSV-2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8, respectively. The positivity rates of EBV and CMV in colonic mucosa increased significantly in the order of the immunocompetent, IBD, and HIV groups (EBV: 23.1%, 53.7%, 72.7%, P for trend = 0.0005; CMV, 7.7%, 24.4%, 54.5%, P for trend = 0.0003, respectively), but no increase was found in the other HHVs. Median mucosal EBV DNA values in the immunocompetent, IBD, and HIV groups were 0, 76, and 287 copies/μg DNA, respectively (P for trend = 0.002). Corresponding median mucosal CMV DNA values were 0, 0, and 17 copies/μg DNA (P for trend = 0.0001). There was no significant difference in the positivity rates of the eight HHVs between ulcerative colitis and Crohn’s disease. Conclusion The HHVs of EBV, CMV, HHV-6, and HHV-7, but not of HSV-1, HSV-2, VZV, or HHV-8, were identified in the colonic mucosa of IBD individuals. EBV and CMV in colonic mucosa was correlated with host immune status in increasing order of immunocompetent, IBD, and HIV-infected individuals.

The study developed a predictive model of long-term gastrointestinal (GI) bleeding risk in patients receiving oral anticoagulants and compared it with the HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratios, Elderly, Drugs/alcohol concomitantly) score.The study periodically followed a cohort of 508 patients taking oral anticoagulants (66 direct oral anticoagulants users and 442 warfarin users). Absence of GI bleeding at an initial examination and any subsequent GI bleeding were confirmed endoscopically. The bleeding model was developed by multivariate survival analysis and evaluated by Harrell's c-index.During a median follow-up of 31.4 months, 42 GI bleeds (8.3%) occurred: 42.8% in the upper GI tract, 50.0% in the lower GI tract, and 7.1% in the middle GI tract. The cumulative 5 and 10-year probability of GI bleeding was 12.6% and 18.5%, respectively. Patients who bled had a significantly higher cumulative incidence of all-cause mortality (hazard ratio 2.9, P 0.001). Multivariate analysis revealed that absence of proton pump inhibitor therapy, chronic kidney disease, chronic obstructive pulmonary disease, history of peptic ulcer disease, and liver cirrhosis predicted GI bleeding. The c-statistic for the new predictive model using these five factors was 0.65 (P 0.001), higher than the HAS-BLED score of 0.57 (P = 0.145).Gastrointestinal bleeding increased the risk of subsequent mortality during follow-up of anticoagulated patients, highlighting the importance of prevention. The study developed a new scoring model for acute GI bleeding risk based on five factors (no-proton pump inhibitor use, chronic kidney disease, chronic obstructive pulmonary disease, history of peptic ulcer disease, and liver cirrhosis), which was superior to the HAS-BLED score.

Background Faecal calprotectin (FC) and faecal immunochemical tests (FIT) have the disadvantage of requiring faecal samples. It has been reported that prostaglandin E–major urinary metabolite (PGE-MUM) values correlate with Mayo endoscopic scores (MESs) for ulcerative colitis (UC). However, there has been no report that PGE-MUM can determine endoscopic remission under remission phase UC, nor comparative study of PGE-MUM with FC and FIT. Thus, we aimed to examine the association between PGE-MUM values and the colonoscopy (CS) results of patients in the remission phase of UC, and to compare the accuracy of using PGE-MUM vs. that of using FC or FIT values for determining endoscopic remission. Methods Patients diagnosed with UC who were under clinical remission and had planned to undergo CS from August 2017 to March 2019 were enrolled. FC levels were measured and FITs were performed on the day of CS; PGE-MUM was measured either the day before or after CS. Three physicians independently scored the CS findings (MES, Modified Mayo Endoscopic Score [MMES], and UC endoscopic index of severity [UCEIS]) while blinded from clinical information. We analysed the differences in PGE-MUM values between two groups, which were divided between those that did achieve and those that did not achieve the following scores: (1) MES 0 point, (2) MES 1 point, (3) modified MES 0 point, (4) modified MES ≤1 point, (5) UCEIS 0 point, (6) UCEIS ≤2 points. In addition, the accuracy of PGE-MUM, FC, and FIT with respect to determining the achievement of (1) through (6) were compared by using areas under the receiver operating characteristics curves. Patients with altered UC activity between the day of PGE-MUM measurement and CS, and those who received NSAIDs on the day of PGE-MUM measurement, were excluded from the analysis. Results Of the 125 enrolled subjects, 30 patients were excluded (urine specimens not submitted, 11; poor stool specimens, 6; NSAIDs users, 10; clearly altered UC activity, 3). The remaining 95 patients (average age 48.2 years, 57 males, and 54 patients with total colitis type), were eligible for analysis. The median PGE-MUM values (in µg/g·Cr) for groups that did or did not achieve (1) through (6) were as follows: (1) 14.6/17.2, p = 0.106; (2) 14.9/20.5, p = 0.039; (3) 14.5/17.4, p = 0.059; (4) 14.1/21.8, p < 0.001; 5) 14.5/17.4, p = 0.059; (6) 14.7/22.2, p = 0.003. The areas under the receiver operating characteristics curves for PGE-MUM/FC/FIT used for determining the achievement of 1) through 6) were as follows: (1) 0.597/0.664/0.682, (2) 0.692/0.74/0.825, (3) 0.613/0.686/0.692, (4) 0.794/0.82/0.786, (5) 0.613/0.686/0.692 and (6) 0.778/0.824/0.825. Conclusion PGE-MUM is equally as effective as FC and FIT for determining the achievement of endoscopic remission.

Background The effect of a combined antithrombotic drug regimen on lower GI bleeding (LGIB) remains unknown. Objective To investigate the risk of LGIB associated with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, thienopyridine (ticlopidine or clopidogrel), or other antiplatelets used. Design Prospective study. Setting Emergency hospital, gastroenterology department. Patients A cohort of 319 patients emergently hospitalized for acute, continuous, or frequent LGIB and 3358 patients with no bleeding on colonoscopy. Main Outcome Measurements Odds ratios (ORs) for the risk of LGIB associated with drug exposure adjusting for age, sex, smoking, alcohol, medications, comorbidities, and GI symptom scores. Results After considering antithrombotic drugs by dividing them into single- and combined-use, single use of nonselective NSAID or cyclooxygenase-2 inhibitor was independently associated with LGIB. The combined use of NSAIDs with low-dose aspirin (OR 4.3) or with other antiplatelets (OR 4.9) was more associated with LGIB than the use of NSAIDs alone (OR 2.3). Use of low-dose aspirin, thienopyridine, or other antiplatelets alone was not significantly associated with LGIB, but combined use of low-dose aspirin with thienopyridine (OR 2.2) or with other antiplatelets (OR 3.6) was associated with LGIB. Combined use of different NSAIDs carried a higher risk than single use (combined use, OR 4.9; single use, OR 2.3). Limitations Single-center study. Conclusion The use of nonselective or selective NSAIDs alone was associated with LGIB. Although antiplatelet use alone was not significantly associated with LGIB, combined use of NSAIDs with antiplatelets or of low-dose aspirin with thienopyridine or with nonthienopyridine antiplatelets was independently associated with LGIB.

Background and Aim The effects of various medications on lower gastrointestinal tract remains unknown. Here, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, and antiplatelet drugs associated with diverticular bleeding. Methods This prospective study involved patients with diverticulosis who underwent colonoscopy. Alcohol and smoking, medications, and Charlson comorbidity index and Gastrointestinal Symptom Rating Scale scores were assessed. The medications evaluated were nine kinds of NSAIDs, two kinds of low-dose aspirin, 10 kinds of nonaspirin antiplatelet drugs, three kinds of anticoagulants, acetaminophen, and corticosteroids. Adjusted odds ratios (aOR) were estimated by a logistic regression model. Results A total of 911 patients with non-bleeding diverticula (n = 758) and bleeding diverticula (n = 153) were enrolled. Independent risk factors were alcohol consumption (light drinker, aOR 3.4; ≥ moderate drinker, aOR 3.3), smoking index (≥ 400, aOR 2.0), NSAIDs (aOR 4.6), low-dose aspirin (aOR 1.9), and nonaspirin antiplatelet drugs (aOR 2.2). The drugs significantly associated with bleeding were loxoprofen (aOR 5.0), diclofenac (aOR 3.1), diclofenac suppository (aOR 8.0), etodolac (aOR 4.9), enteric-coated aspirin (aOR 3.9), buffered aspirin (aOR 9.9), clopidogrel (aOR 2.5), and cilostazol (aOR 7.3). Dual therapy carried a higher risk than monotherapy (single NSAID, aOR 3.6, P

We investigated whether visceral adipose tissue (VAT) measured by computed tomography (CT) is a risk factor for colorectal adenoma. For a total of 1,328 patients (857 without adenoma, 471 with colorectal adenoma) undergoing colonoscopy and CT, associations between colorectal adenoma and body mass index (BMI), VAT area and subcutaneous adipose tissue (SAT) were assessed using odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for age, sex, family history, smoking, alcohol intake, diabetes mellitus, aspirin use and nonsteroidal anti-inflammatory drug use. Multivariate analysis showed that colorectal adenoma was marginally associated (p=0.06) with BMI, but not with SAT, while it was significantly associated with VAT and the VAT to SAT ratio (VAT/SAT) for both categorical data and trend (p

Background We aimed to identify the risk factors associated with colonic cytomegalovirus (CMV) infection in ulcerative colitis (UC) and to compare the clinical course between antiviral therapy-treated and -untreated groups in mucosal CMV-polymerase chain reaction (PCR) -positive cases. Methods We retrospectively selected 46 UC patients (>15 years old) in active phase who underwent colonoscopy with biopsy and were analyzed for CMV infection by mucosal PCR between October 2011 and December 2015 at our institution. Colonic CMV in inflamed mucosa was detected using quantitative real-time PCR. The clinical course was evaluated, including need for drug therapy/surgery or drug therapy intensification. In addition, we evaluated the clinical course between CMV-DNA− cases and CMV-DNA+ cases with low viral load. Results At baseline, CMV-DNA+ patients were significantly older, had higher endoscopic scores, and required higher corticosteroid doses during the past 4 weeks than CMV-DNA− patients (p< 0.05). No significant differences were observed in disease duration, disease distribution, laboratory data, or use of other medication between CMV-DNA+ and CMV-DNA− patients. In the anti-CMV-treated group with a median (range) DNA load of 16,000 (9,000–36,400), 3patients achieved remission without additional UC therapy, 2 required additional UC therapy, and 1 required colectomy despite azathioprine and infliximab therapy. In the CMV-untreated group with a median (range) DNA load of 919 (157–5,480), all patients achieved remission with UC therapy alone. No significant difference was observed in the clinical course between CMV-DNA− cases and CMV-DNA+ cases with low viral loads. Conclusions Aging, endoscopic UC activity, and corticosteroid dose predispose to colonic CMV infection, as determined by mucosal PCR, in UC. UC treatment without anti-CMV therapy may be warranted, particularly in patients with low-load CMV-DNA. Anti-CMV therapy alone does not always achieve clinical response in UC even in cases with high-load PCR.