Metagenomic Identification of Microbial Signatures Predicting Pancreatic Cancer From a Multinational Study.

BACKGROUND & AIMS: To identify gut and oral metagenomic signatures that accurately predict pancreatic ductal carcinoma (PDAC) and to validate these signatures in independent cohorts. METHODS: We conducted a multinational study and performed shotgun metagenomic analysis of fecal and salivary samples collected from patients with treatment-naïve PDAC and non-PDAC controls in Japan, Spain, and Germany. Taxonomic and functional profiles of the microbiomes were characterized, and metagenomic classifiers to predict PDAC were constructed and validated in external datasets. RESULTS: Comparative metagenomics revealed dysbiosis of both the gut and oral microbiomes and identified 30 gut and 18 oral species significantly associated with PDAC in the Japanese cohort. These microbial signatures achieved high area under the curve values of 0.78 to 0.82. The prediction model trained on the Japanese gut microbiome also had high predictive ability in Spanish and German cohorts, with respective area under the curve values of 0.74 and 0.83, validating its high confidence and versatility for PDAC prediction. Significant enrichments of Streptococcus and Veillonella spp and a depletion of Faecalibacterium prausnitzii were common gut signatures for PDAC in all the 3 cohorts. Prospective follow-up data revealed that patients with certain gut and oral microbial species were at higher risk of PDAC-related mortality. Finally, 58 bacteriophages that could infect microbial species consistently enriched in patients with PDAC across the 3 countries were identified. CONCLUSIONS: Metagenomics targeting the gut and oral microbiomes can provide a powerful source of biomarkers for identifying individuals with PDAC and their prognoses. The identification of shared gut microbial signatures for PDAC in Asian and European cohorts indicates the presence of robust and global gut microbial biomarkers.

Validation of the American Gastroenterological Association guidelines on management of intraductal papillary mucinous neoplasms: more than 5 years of follow-up.

OBJECTIVES: Recent guidelines suggest that imaging surveillance be conducted for 5 years for patients with at most one high-risk feature. If there were no significant changes, surveillance is stopped. We sought to validate this follow-up strategy. METHODS: In study 1, data were analysed for 392 patients with intraductal papillary mucinous neoplasms (IPMNs) and at most one high-risk feature who were periodically followed up for more than 1 year with imaging tests. In study 2, data were analysed for 159 IPMN patients without worsening high-risk features after 5 years (stop surveillance group). RESULTS: In study 1, pancreatic cancer (PC) was identified in 12 patients (27.3%) in the endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) indication group and none in the non-EUS-FNA indication group (P < 0.01). In the EUS-FNA indication group, 11 patients (25%) died, whereas 29 (8.3%) died in the non EUS-FNA indication group (P < 0.01). In study 2 (stop surveillance group), PC was identified in three patients (1.9%) at 84, 103 and 145 months. CONCLUSIONS: PC risk and mortality for IPMNs not showing significant change for 5 years is likely to be low, and the non-EUS-FNA indication can provide reasonable decisions. However, three patients without worsening high-risk features for 5 years developed PC. The stop surveillance strategy should be reconsidered. KEY POINTS: • The AGA guidelines provide reasonable clinical decisions for the EUS-FNA indication. • In stop surveillance group, PC was identified in 3 patients (1.9%). • In stop surveillance group, 2 of 3 PC patients died from PC. • Risk of pancreatic cancer in "stop surveillance" group is not negligible.

Safety and Effectiveness of Early Colonoscopy in Management of Acute Lower Gastrointestinal Bleeding on the Basis of Propensity Score Matching Analysis.

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 < .001) and endoscopic therapy (25.8% vs 8.6%, P < .001), including clipping (17.8% vs 4.9%, P < .001), band ligation (6.1% vs 1.8%, 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 < .001). 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.

Development and Validation of a Risk Scoring System for Severe Acute Lower Gastrointestinal Bleeding.

BACKGROUND & AIMS: We aimed to develop and validate a risk scoring system to determine the risk of severe lower gastrointestinal bleeding (LGIB) and predict patient outcomes. METHODS: We first performed a retrospective analysis of data from 439 patients emergently hospitalized for acute LGIB at the National Center for Global Health and Medicine in Japan, from January 2009 through December 2013. We used data on comorbidities, medication, presenting symptoms, and vital signs, and laboratory test results to develop a scoring system for severe LGIB (defined as continuous and/or recurrent bleeding). We validated the risk score in a prospective study of 161 patients with acute LGIB admitted to the same center from April 2014 through April 2015. We assessed the system's accuracy in predicting patient outcome using area under the receiver operating characteristics curve (AUC) analysis. All patients underwent colonoscopy. RESULTS: In the first study, 29% of the patients developed severe LGIB. We devised a risk scoring system based on nonsteroidal anti-inflammatory drugs use, no diarrhea, no abdominal tenderness, blood pressure of 100 mm Hg or lower, antiplatelet drugs use, albumin level less than 3.0 g/dL, disease scores of 2 or higher, and syncope (NOBLADS), which all were independent correlates of severe LGIB. Severe LGIB developed in 75.7% of patients with scores of 5 or higher compared with 2% of patients without any of the factors correlated with severe LGIB (P < .001). The NOBLADS score determined the severity of LGIB with an AUC value of 0.77. In the validation (second) study, severe LGIB developed in 35% of patients; the NOBLADS score predicted the severity of LGIB with an AUC value of 0.76. Higher NOBLADS scores were associated with a requirement for blood transfusion, longer hospital stay, and intervention (P < .05 for trend). CONCLUSIONS: We developed and validated a scoring system for risk of severe LGIB based on 8 factors (NOBLADS score). The system also determined the risk for blood transfusion, longer hospital stay, and intervention. It might be used in decision making regarding intervention and management.

Development of Pancreatic Cancer, Disease-specific Mortality, and All-Cause Mortality in Patients with Nonresected IPMNs: A Long-term Cohort Study.

PURPOSE: To determine the cumulative incidence, disease-specific mortality, and all-cause mortality of pancreatic cancer (PC) in patients with intraductal papillary mucinous neoplasms (IPMNs) and to identify imaging findings that are associated with these outcomes. MATERIALS AND METHODS: This retrospective study had institutional review board approval, and the need to obtain patient consent was waived. Data from an electronic database were analyzed and supplemented by chart reviews for 285 patients with nonresected IPMNs who were periodically followed up with imaging (1273 multidetector computed tomography and 750 magnetic resonance cholangiopancreatography examinations). The Kaplan-Meier method was used to estimate the cumulative development of PC, PC mortality, and all-cause mortality (factors were compared by using the log-rank test). RESULTS: Over a median imaging follow-up period of 39 months, 12 (4.2%) of 285 patients developed PC; the cumulative 5-year PC incidence was 3.9% for branch duct (BD)-IPMNs, 45.5% for main duct (MD)-IPMNs (P < .01), 7.7% for cysts 30 mm or larger, and 5.3% for cysts smaller than 30 mm (P = .82). Over a median survival follow-up period of 47.5 months, seven (2.5%) of 285 patients died of PC and 14 (4.9%) patients died of other causes. Cumulative 5-year PC mortality was 2.1% for BD-IPMNs, 18.5% for MD-IPMNs (P < .01), 2.6% for cysts 30 mm or larger, and 2.8% for cysts smaller than 30 mm (P = .90). Cumulative 5-year all-cause mortality was 5.5% for BD-IPMNs, 18.5% for MD-IPMNs (P < .01), 12.5% for cysts 30 mm or larger, and 5.9% for cysts smaller than 30 mm (P = .89). CONCLUSION: Five-year PC development, disease-specific mortality, and all-cause mortality were approximately 4%, 2%, and 6% for BD-IPMNs and 46%, 19%, and 19% for MD-IPMNs, respectively. The presence of an MD-IPMN, but not cyst size, was significantly associated with PC development and subsequent mortality.

Recurrence and prognosis of patients emergently hospitalized for acute esophageal variceal bleeding: A long-term cohort study.

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 < 0.001). During the overall mean follow-up of 22 months, 69 patients died (17 due to bleeding), and the cumulative mortality rate at 1 month, 1 year, and 5 years was 12.2%, 26.6%, and 63.0%, respectively. In multivariate analysis, independent risk factors for mortality were child-Pugh class C (HR 2.91; P < 0.001), coexistence of hepatocellular carcinoma (HR 1.92; P = 0.013), and no follow-up endoscopy (HR 23.6; P < 0.001). CONCLUSION: This study revealed more than 50% cumulative rebleeding and mortality in the 5-year period after endoscopic variceal ligation for esophageal variceal bleeding in an emergency setting. Child-Pugh C, alcoholic liver cirrhosis, and no follow-up endoscopy increased the risk of rebleeding; Child-Pugh C, coexistence of hepatocellular carcinoma, and no follow-up endoscopy increased the risk of mortality.

Recurrence and mortality among patients hospitalized for acute lower gastrointestinal bleeding.

BACKGROUND & AIMS: The long-term recurrence of lower gastrointestinal bleeding (LGIB) and associated mortality have not been studied extensively. We investigated rates of recurrence of LGIB, mortality, and associated risk factors. METHODS: In a retrospective study, we analyzed data from 342 patients hospitalized for overt LGIB at the National Center for Global Health and Medicine in Japan from December 2004 through June 2013. All patients underwent colonoscopy. We assessed Charlson comorbidity index scores and the use of nonsteroidal anti-inflammatory drugs, low-dose aspirin, other antiplatelet drugs, or warfarin. Rebleeding, the total number of rebleeding episodes, and mortality were measured. The Cox proportional hazards model was used to estimate hazard ratios (HRs). RESULTS: Rebleeding occurred in 84 patients, at a mean follow-up time of 19 months. The cumulative percentages of patients with rebleeding at 1 and 5 years were 19% and 46%, respectively. During the follow-up period, 29 patients (39%) had secondary rebleeding and 18 patients (62%) had subsequent rebleeding. Multivariate analysis showed age 65 years and older (HR, 1.7; P = .04) and the use of nonsteroidal anti-inflammatory drugs (HR, 2.0; P < .01) and nonaspirin antiplatelet drugs (HR, 1.8; P < .05) as independent risk factors for rebleeding. Dual therapy had a higher risk than single therapy (adjusted HR, 1.8; P < .05). During the mean follow-up period of 28 months, 21 patients died (2 from bleeding). Cumulative mortality rates at 1 and 5 years were 4.2% and 13%, respectively. Mortality was associated significantly with age ≥65 years (P < .05), Charlson comorbidity index score, and warfarin use. CONCLUSIONS: Based on a retrospective analysis of patients with LGIB, 46% of all patients have rebleeding, and the overall mortality rate is 13% within 5 years after hospitalization. Besides age ≥65 years, use of antithrombotic drugs increases the risk of bleeding recurrence and mortality among patients with LGIB.

Visceral Abdominal Obesity Measured by Computed Tomography is Associated With Increased Risk of Colonic Diverticulosis.

GOALS: To investigate whether visceral obesity measured by computed tomography (CT) is a risk factor for colonic diverticulosis. BACKGROUND: The association between colonoscopy-proven diverticulosis and visceral obesity has not been studied. STUDY: A cohort of 1445 participants (1117 nondiverticulosis and 328 diverticulosis) undergoing colonoscopy and CT was prospectively analyzed. Diverticulosis was diagnosed by high-resolution colonoscopy. The associations between body mass index (BMI), visceral adipose tissue (VAT) area, subcutaneous adipose tissue (SAT) area, and diverticulosis were estimated using odds ratios (ORs) adjusted for age, sex, alcohol, smoking, medications, and comorbidities. RESULTS: In multivariate analysis, diverticulosis was significantly associated with VAT area and SAT area for both categorical data and trend (P for trend <0.001), but not BMI.Diverticulosis had a positive association with VAT area and SAT area for both categorical data and trend (P for trend <0.001) in men, but none of these associations were noted in women. In the subanalysis of normal-weight patients (BMI<25), diverticulosis was independently associated with VAT area and SAT area (P for trend <0.001). The adjusted ORs for VAT area ≥100 cm² was significantly increased in right-sided (OR, 1.8), left-sided (OR, 2.3), and bilateral (OR, 3.0) diverticula (P for trend <0.001). CONCLUSIONS: Abdominal obesity measured by CT, not BMI, is associated with colonic diverticulosis, even when body weight was normal. These findings suggest an important role for visceral fat accumulation in diverticulosis development. A high visceral fat was positively associated with the distribution of diverticula.

Predictors for identification of stigmata of recent hemorrhage on colonic diverticula in lower gastrointestinal bleeding.

GOALS: The aim of this study was to identify predictors for the identification of stigmata of recent hemorrhage (SRH) on colonic diverticula. BACKGROUND: Several factors influence the identification of SRH in the diagnosis of colonic diverticular bleeding. STUDY: 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). RESULTS: 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; P<0.01), 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; P<0.01) 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%, P<0.01) and >48 hours groups (1.0%, P<0.01), showing a tendency to decrease with time (P<0.01 for trend). CONCLUSIONS: Factors of urgent colonoscopy, expert colonoscopist, use of a cap, and use of water-jet scope are useful for identifying SRH diverticula.

Combined identifying granuloma and biopsy culture is useful for diagnosing intestinal tuberculosis.

PURPOSES: Differential diagnosis of intestinal tuberculosis (ITB) and inflammatory bowel disease (IBD) can be difficult, but many gastroenterologists may only perform biopsy for pathology and their own experience. This study aimed to identify optimal sample collection and pathogen detection methods for diagnosing ITB. METHODS: A cohort of 182 patients (50 had ITB and 132 had IBD or other colonic diseases) who underwent colonoscopy was analyzed. Sensitivity of acid-fast bacilli (AFB), culture, polymerase chain reaction (PCR), and granuloma pathology on hematoxylin and eosin stain for diagnosing ITB were compared in relation to biopsy, endoscopic aspirated intestinal fluid, or standard stool evaluations. We also evaluated which combination offered the highest yield to diagnose intestinal tuberculosis in addition to granuloma pathology. RESULTS: Between ITB and non-ITB, no significant differences were observed in age, sex, and nationality. In biopsy analysis, sensitivity was as follows: culture (50%), AFB (38%), PCR (25%), granuloma pathology (51%), and caseous granuloma (8.2%), while specificity of granuloma pathology was low (80%), compared to other tests. In intestinal fluid analysis, sensitivity was as follows: culture (46%), AFB (42%), and PCR (35%). In standard stool analysis, sensitivity was as follows: culture (47%), AFB (37%), and PCR (23%). Granuloma pathology plus biopsy culture offered the highest combination sensitivity (77 %), significantly (P < 0.01) higher than that for granuloma pathology alone (51%). CONCLUSIONS: When encountering suspected intestinal tuberculosis or IBD on colonoscopy, biopsy culture is recommended in addition to pathological assessment of granuloma. This diagnostic strategy will lead to accurate differential diagnosis of colonic disease, facilitating appropriate treatment.

Natural history of outpatient-onset ischemic colitis compared with other lower gastrointestinal bleeding: a long-term cohort study.

PURPOSES: The long-term clinical course of outpatient-onset ischemic colitis remains unknown. Our aims are to elucidate the in- and out-of-hospital clinical outcomes of ischemic colitis and compare them with those of lower gastrointestinal bleeding (LGIB). METHOD: A cohort of 370 outpatients was hospitalized for ischemic colitis (n = 57) or other LGIB (n = 313). All patients had undergone colonoscopy. During hospitalization, the need for transfusion or interventions, further bleeding, mortality, and length of hospital stay were measured. After discharge, long-term recurrence and mortality were analyzed by the Kaplan-Meier method. RESULTS: Colonoscopy revealed that 88% of ischemic colitis cases were left sided. Compared with other LGIB, ischemic colitis cases had significantly lower transfusion requirements (p < 0.01), further bleeding (p = 0.02), endoscopic intervention (p < 0.01), and shorter hospital stay (p = 0.03). No significant differences between the groups were noted in the need for surgery, angiographic procedures, or mortality during hospitalization. During a mean follow-up of 22 months, rebleeding was significantly lower (log-rank test; p < 0.01) in ischemic colitis cases (5.3%) than in other LGIB cases (19.4%) after discharge. During the mean follow-up period of 29 months, 1 patient (1.8%) with ischemic colitis and 18 patients (5.8%) with other LGIB died (log-rank test; p = 0.41). CONCLUSIONS: Outpatient-onset ischemic colitis patients usually had left-sided colitis, recovered with conservative short-term treatment and had lower transfusion requirements and further bleeding compared with other LGIB patients. After discharge, patients with outpatient-onset ischemic colitis had lower recurrence over the long term than other LGIB patients.

Visceral fat accumulation affects risk of colonic diverticular hemorrhage.

PURPOSES: Factors other than antithrombotic drugs associated with diverticular bleeding remain unknown. Visceral adiposity contributes to atherosclerosis and may affect arteriolar change at the diverticulum. We investigated whether visceral adipose tissue (VAT) measured by computed tomography (CT) is a risk factor for diverticular bleeding. METHODS: A cohort of 283 patients (184 with asymptomatic diverticulosis and 99 with diverticular bleeding) undergoing colonoscopy and CT was analyzed. Associations between body mass index (BMI), VAT, subcutaneous adipose tissue (SAT), and diverticular bleeding were assessed by logistic regression models adjusted for age, gender, alcohol, smoking, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, and antithrombotic drugs (nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, and other antiplatelet drugs). RESULTS: In univariate analysis, hypertension, dyslipidemia, chronic kidney disease, and NSAIDs use, low-dose aspirin, non-aspirin antiplatelets, increasing BMI, and increasing VAT area were associated with diverticular bleeding. In multivariate analysis adjusted for confounding factors, VAT area (p = 0.021), but not BMI (p = 0.551) or SAT area (p = 0.635), was positively associated with diverticular bleeding. When BMI was considered simultaneously, VAT area remained positively associated with diverticular bleeding (p = 0.018). However, none of obesity indices including VAT area were associated with recurrence of diverticular bleeding or prolonged hospitalization. CONCLUSIONS: This study presents new information on risk factors for diverticular bleeding. A large volume of visceral adipose tissue, but not BMI or SAT, appears to entail a risk for diverticular bleeding, after age, gender, metabolic factors, and antithrombotic drugs use adjustments.

Association between colonic diverticulosis and bowel symptoms: A case-control study of 1629 Asian patients.

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.

Risk of peptic ulcer bleeding associated with Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs, low-dose aspirin, and antihypertensive drugs: a case-control study.

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 ß-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 < 0.001), history of peptic ulcer (AOR, 4.8; P < 0.001), H. pylori infection (AOR, 2.1; P < 0.001), comorbidity index (AOR, 1.1; P = 0.089), nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR, 2.0; P = 0.025), and low-dose aspirin (AOR, 2.8; P = 0.003) increased the risk of PUB, whereas H. pylori eradication (AOR, 0.03; P < 0.001), proton pump inhibitors (PPIs) (AOR, 0.1; P < 0.001), and histamine 2-receptor antagonists (H2RA) (AOR, 0.1; P < 0.001) reduced it. No significant interactions were observed between H. pylori infection and NSAIDs use for PUB (P = 0.913). ARBs (P = 0.564), ACE inhibitors (P = 0.213), calcium channel blockers (P = 0.215), α-blockers (P = 0.810), and ß-blockers (P = 0.864) were not associated with PUB. CONCLUSION: We found that alcohol consumption, history of peptic ulcer, H. pylori infection, NSAIDs use, and low-dose aspirin use were independent risk factors for PUB, whereas H. pylori-eradication, PPIs use, and H2RA use reduced its risk. Interactions between H. pylori and NSAIDs use in PUB were not observed. No antihypertensive drug was associated with PUB.

Abdominal visceral fat accumulation measured by computed tomography associated with an increased risk of gallstone disease.

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 < 0.001, 0.009), but not body mass index (BMI). Among patients with BMI < 25, gallstone disease remained significantly associated with VAT area (P for trend 0.021) and SAT area (P for trend 0.005). Interactions between the obesity indices and being elderly on the risk of gallstone disease were found; specifically BMI (P = 0.005), SAT (P < 0.001), and VAT (P = 0.154). A significant association between all obesity indices and gallstone disease was seen in patients aged < 65 but not among those aged ≥ 65. However, no significant association was noted between the obesity indices and sex. CONCLUSIONS: CT-measured adipose tissue, rather than BMI, was a better predictor for risk of gallstone disease. This finding applies to younger people or even those with normal body weight, suggesting the importance of abdominal visceral fat accumulation in the development of gallstone disease.

Abdominal Fat Accumulation, as Measured by Computed Tomography, Increases the Risk of Ischemic Colitis: A Retrospective Case-Control Study.

BACKGROUND AND AIM: Visceral fat contributes to insulin resistance and atherosclerosis. We retrospectively investigated whether abdominal fat accumulation, as measured by computed tomography, is a risk of ischemic colitis and related clinical outcomes. MATERIALS AND METHODS: Outpatient-onset ischemic colitis patients (n = 58) and age- and sex-matched controls (n = 58) underwent colonoscopy and computed tomography. Associations between body mass index, visceral adipose tissue area, subcutaneous adipose tissue area, and ischemic colitis were estimated using odds ratios adjusted for hypertension, diabetes mellitus, and dyslipidemia. RESULTS: In multivariate analysis, ischemic colitis was significantly associated with subcutaneous adipose tissue area (P for trend 0.030) and marginally associated with visceral adipose tissue area (P for trend 0.094), but was not associated with body mass index (P for trend 0.460). The adjusted odds ratios for the highest quartile of subcutaneous and visceral adipose tissue in ischemic colitis were 3.48 (1.06-11.4) and 2.43 (0.74-8.00), respectively, compared with the lowest quartile. When body mass index was considered simultaneously, ischemic colitis remained associated with subcutaneous adipose tissue (P for trend 0.016) and visceral adipose tissue (P for trend 0.077). No significant differences were noted between any of the obesity indices and the distribution type of colitis, blood transfusion requirement, or length of hospital stay. CONCLUSION: Abdominal fat accumulation measured by computed tomography, but not body mass index, was associated with outpatient-onset ischemic colitis. Ischemic colitis remained associated with abdominal fat, even when body mass index was simultaneously considered. However, clinical outcomes of ischemic colitis were not associated with abdominal fat accumulation.

Visceral abdominal fat measured by computed tomography is associated with an increased risk of colorectal adenoma.

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<0.05). When the obesity indices were considered simultaneously, colorectal adenoma remained significantly associated with VAT and VAT/SAT (p<0.05), but not BMI and SAT. In patients with colorectal adenoma, the adjusted OR for the highest quartiles of VAT and VAT/SAT was 1.90 (95% CI 1.16-3.13) and 2.25 (95% CI 1.49-3.41), respectively, compared to the lowest quartiles. Only VAT area was significantly associated with colorectal adenoma in both men and women (p<0.05). Proximal, multiple and advanced adenomas had significantly higher VAT areas (p<0.05) than distal, solitary and nonadvanced adenomas. Our findings implicate abdominal VAT in the development and progression of colorectal adenoma, and it was better obesity index for colorectal adenoma than BMI in both sexes.

Lower GI bleeding risk of nonsteroidal anti-inflammatory drugs and antiplatelet drug use alone and the effect of combined therapy.

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.

Colonic diverticular hemorrhage associated with the use of nonsteroidal anti-inflammatory drugs, low-dose aspirin, antiplatelet drugs, and dual therapy.

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 < 0.01; dual, aOR 23, P < 0.01; single antiplatelet drug, aOR 2.0, P < 0.01; dual, aOR 4.1, P < 0.01). CONCLUSIONS: Besides alcohol and smoking, NSAIDs, low-dose aspirin, and antiplatelet drugs are risk factors for diverticular bleeding. The magnitude of risk may differ between different kinds of NSAIDs and antiplatelet drugs, and dual therapy with NSAIDs or antiplatelet drugs increases the risk of bleeding.

A case of non-esophageal eosinophilic gastrointestinal disease diagnosed by mucosal incision-assisted biopsy.

A 46-year-old woman presented at our hospital with anorexia, vomiting, and diarrhea. Blood tests indicated markedly increased eosinophil counts, and esophagogastroduodenoscopy revealed slight erythema in the gastric body. Computed tomography showed edematous thickening of the stomach and small intestinal walls and peritonitis. Thus, eosinophilic gastrointestinal disease was suspected. Endoscopic biopsies from the esophagus, stomach, and duodenum were collected, but no significant increases in eosinophil counts were observed. Little ascites effusion was detected and puncture cytology was difficult to perform. Thus, a sample of the muscularis propria layer was obtained by mucosal incision-assisted biopsy. Histopathological examination of the biopsy revealed significant eosinophilic infiltration within the muscularis propria layer of the stomach, confirming the diagnosis of non-eosinophilic esophagitis eosinophilic gastrointestinal disease. The patient was treated with a leukotriene receptor antagonist and prednisolone, and her clinical symptoms and gastrointestinal wall thickening rapidly improved. The Japanese diagnostic guideline for non-eosinophilic esophagitis eosinophilic gastrointestinal disease requires endoscopic biopsy or eosinophilic infiltration of ascites fluid. When diagnosis is difficult using conventional methods, as in this case, mucosal incision-assisted biopsy is useful as a next step.