Prevalence and Risk Factors of Constipation Symptoms among Patients Undergoing Colonoscopy: A Single-Center Cross-Sectional Study.

INTRODUCTION: Constipation is one of the most common gastrointestinal symptoms. It may compromise quality of life and social functioning and result in increased healthcare use and costs. We aimed to evaluate the prevalence and risk factors of constipation symptoms, as well as those of refractory constipation symptoms among patients who underwent colonoscopy. METHODS: Over 4.5 years, patients who underwent colonoscopy and completed questionnaires were analyzed. Patients' symptoms were evaluated using the Gastrointestinal Symptoms Rating Scale. RESULTS: Among 8,621 eligible patients, the prevalence of constipation symptoms was 33.3%. Multivariate analysis revealed female sex (odds ratio [OR] 1.7, p < 0.001), older age (OR 1.3, p < 0.001), cerebral stroke with paralysis (OR 1.7, p = 0.009), chronic renal failure (OR 2.6, p < 0.001), ischemic heart disease (OR 1.3, p = 0.008), diabetes (OR 1.4, p < 0.001), chronic obstructive pulmonary disease (OR 1.5, p = 0.002), benzodiazepine use (OR 1.7, p < 0.001), antiparkinsonian medications use (OR 1.9, p = 0.030), and opioid use (OR 2.1, p = 0.002) as independent risk factors for constipation symptoms. The number of patients taking any medication for constipation was 1,134 (13.2%); however, refractory symptoms of constipation were still present in 61.4% of these patients. Diabetes (OR 1.5, p = 0.028) and irritable bowel syndrome (OR 3.1, p < 0.001) were identified as predictors for refractory constipation symptoms. CONCLUSIONS: Constipation occurred in one-third of patients, and more than half of patients still exhibited refractory symptoms of constipation despite taking laxatives. Multiple medications and concurrent diseases seem to be associated with constipation symptoms.

Impact of a Novel Digital Therapeutics System on Nonalcoholic Steatohepatitis: The NASH App Clinical Trial.

INTRODUCTION: Management of nonalcoholic steatohepatitis (NASH) is a currently unmet clinical need. Digital therapeutics (DTx) is an emerging class of medicine that delivers evidence-based therapeutic interventions. This study was aimed at investigating the efficacy of DTx in patients with NASH. METHODS: We conducted a multicenter, single-arm, 48-week trial in 19 patients with biopsy-confirmed NASH. All patients received a DTx intervention with a newly developed smartphone application. The primary endpoint was change in the nonalcoholic fatty liver disease activity score (NAS) without worsening of liver fibrosis. The secondary endpoints included improvement of the NAS by ≥2 points without worsening of liver fibrosis, change in the body weight, and regression of fibrosis. RESULTS: After the 48-week DTx intervention, improvement of the NAS was observed in 68.4% (13/19) of patients. The mean change in the NAS from baseline to the end of the intervention was -2.05 ± 1.96 ( P < 0.001 when compared with the threshold of -0.7). A decrease in the NAS by ≥ 2 points was achieved in 11 (57.9%). The average weight loss at the end of the intervention was 8.3% ( P < 0.001). Reduction of the fibrosis stage was observed in 58.3% when the analysis was limited to patients with stage F2/3 fibrosis. There were no serious adverse events that could be considered as being related to the DTx intervention. DISCUSSION: DTx for NASH was found to be highly efficacious and well-tolerated. Further evaluation of the DTx intervention for NASH in a phase 3 trial is warranted.

Characteristics of patients aged over 75 years with hepatitis C virus infection treated with direct-acting antivirals in Japan: Evidence based on the nationwide, real-world database in Japan.

AIM: Direct-acting antivirals (DAAs) have dramatically changed the treatment of chronic hepatitis C. Their high efficacy helps in eradicating hepatitis C virus with few adverse events. Information on real-world use of DAAs therapy in patients aged 75 years and older is inadequate. METHODS: The Japanese DAAs database was constructed in 2014 as a cooperative system between 18 prefectures. The medical reports filled in by doctors and anonymized at the local government office were collected. The patients' demographic features, viral factors, and treatment characteristics were compared among three groups stratified by age when therapy was initiated: Group A (<60 years old), Group B (60-74 years old), and Group C (≥75 years old). RESULTS: Out of the 22,454 patients whose age upon starting therapy could be identified, 24.8% (n = 5597) belonged to Group C, which was ten times the number in the Japanese Interferon Database. Female patients, advanced stages of liver fibrosis, and past history of hepatocellular carcinoma treatment were significantly higher in the older age groups (Group A < B < C), whereas sustained virologic response (SVR) rates were not different (91%-93%). In Group C, multivariate logistic regression analysis revealed that predicting factors for virologic response varied among DAAs regimens. However, the completion of DAAs therapy commonly contributed to SVR, regardless of DAAs regimen. CONCLUSIONS: DAAs therapy is associated with high SVR rates, even in the oldest age group, and therapy should not be withheld on the basis of old age.

Effect of antiplatelet agent number, types, and pre-endoscopic management on post-polypectomy bleeding: validation of endoscopy guidelines.

BACKGROUND: It remains unclear whether type of antiplatelet (AP) therapy, AP combination therapy, and AP continuing or switching strategy affect the risk of post-polypectomy bleeding (PPB). In this study, we sought to elucidate this risk. METHODS: We analyzed 1050 patients who underwent colonoscopic polypectomy: 525 AP users and 525 controls matched for age, sex, comorbidities, concomitant non-steroidal anti-inflammatory drugs use, and polyp characteristics who did not receive antithrombotics. PPB risk was evaluated by AP number, type, and continuing or switching strategies during the peri-endoscopic period. RESULTS: In multivariate analysis, bleeding risk increased significantly as the number of AP agents used increased (monotherapy, adjusted odds ratio [aOR], 3.7; dual antiplatelet therapy (DAPT), 4.6; triple antiplatelet therapy (TAPT), 11.1) compared with controls. With monotherapy, significantly increased PPB risk was found for aspirin (aOR 4.3), thienopyridine (aOR 6.3), and cilostazol (aOR 5.9), but not for eicosapentaenoic acid or other APs (beraprost, limaprost, sarpogrelate, dilazep, or dipyridamole). With DAPT, significantly increased PPB risk was found for combination aspirin plus cilostazol, but not aspirin plus other APs. Bleeding rates for continuing monotherapy were 4.3% for aspirin and 0% for thienopyridine, cilostazol, and other APs, respectively. CONCLUSIONS: Analysis of this large polypectomy dataset showed that the use of low-dose aspirin, thienopyridine, or cilostazol and a combination of these is associated with increased PPB risk. Although PPB risk was high with DAPT or TAPT, PPB rate in any antiplatelet monotherapy even with a continuing strategy was low at < 5%.

Rifaximin-altered gut microbiota components associated with liver/neuropsychological functions in patients with hepatic encephalopathy: An exploratory data analysis of phase II/III clinical trials.

AIMS: Rifaximin (RFX), a non-systemic antibiotic, improves liver/neuropsychological functions in patients with hepatic encephalopathy (HE). We aimed to investigate the clinical profiles associated with gut bacterial loads using exploratory data analysis and the effects of RFX on the gut microbiota of patients with HE. METHODS: We analyzed the data from 17 patients with HE who underwent fecal microbiota examination in phase II/III trials in Japan. Profiles associated with genera Streptococcus, Veillonella, and Lactobacillus loads were analyzed using classification and regression trees (CART). Changes in gut microbial consortia of seven patients with HE were then assessed 2 weeks after RFX treatment by principal component analysis. RESULTS: In the CART, the first and second divergence variables for each higher bacterial load were as follows: (i) in Streptococcus, the number connection test-A ≥39.55 s and presence of portal-systemic shunt; (ii) in Veillonella, serum potassium levels <4.75 mEq/L and total cholesterol level <129.5 mg/dL; and (iii) in Lactobacillus, white blood cell counts ≥3.4 × 103 /µL and aspartate aminotransferase level ≥44.5 U/L. There was no significant change in total bacterial load before and after RFX treatment; however, there was a decrease in Streptococcus, Veillonella, and Lactobacillus counts after RFX treatment. CONCLUSION: We report clinical profiles associated with gut bacterial loads in patients with HE, and showed that RFX altered gut microbiota components associated with liver/neuropsychological functions. Thus, RFX could improve liver/neuropsychological functions through the regulation of the gut microbial consortia in patients with HE.

Increased risk of non-AIDS-defining cancers in Asian HIV-infected patients: a long-term cohort study.

BACKGROUND: Data on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients. METHODS: Subjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox's proportional hazards model was used to estimate hazard ratios (HR). RESULTS: During the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40-59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40-49, 50-59, 60-69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8-0.9, P < 0.001). The higher 10-year incidence rate of NADCs was associated with increasing prediction score. CONCLUSIONS: Liver and colon cancer risk was elevated in Asian HIV-infected individuals, similar to in Western populations, whereas stomach cancer risk was characteristically elevated in Asian populations. Half of Asian NADC patients were aged 40-59 years and had advanced-stage disease at diagnosis. Periodic cancer screening may be warranted for high-risk subpopulations with smoking habit, HIV infection through blood transmission or IDU, and HBV co-infection, and screening should be started over 40 years of age.

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.

Acute Severe Gastrointestinal Tract Bleeding Is Associated With an Increased Risk of Thromboembolism and Death.

BACKGROUND & AIMS: We performed a retrospective cohort study of patients with and without gastrointestinal bleeding (GIB) to determine whether GIB increases the risks of thromboembolism and death. METHODS: We collected data from 522 patients with acute severe GIB and 1044 patients without GIB (control subjects, matched for age, sex, year of diagnosis, history of thromboembolism, and use of antithrombotic drugs) who underwent endoscopy at the National Center for Global Health and Medicine in Japan from January 2009 through December 2014. Hazard ratios of GIB for thromboembolism and mortality risk were estimated, adjusting for confounders. We also compared standardized mortality ratios between the GIB cohort and the age- and sex-matched general population in Japan. RESULTS: During a mean follow up of 23.7 months, thromboembolism was identified in 11.5% of patients with GIB and 2.4% of control subjects (hazard ratio, 5.3; 95% confidence interval, 3.3-8.5; P < .001). Multivariate analysis revealed GIB as a risk factor for all-thromboembolic events, cerebrovascular events, and cardiovascular events. During a mean follow-up of 24.6 months, 15.9% of patients with GIB and 8.6% of control subjects died (hazard ratio, 2.1; 95% confidence interval, 1.6-2.9; P < .001). Multivariate analysis revealed GIB as a risk factor for all-cause mortality. Compared with the general population, patients with GIB were at increased risk of death (standardized mortality ratio, 12.0). CONCLUSIONS: In a retrospective analysis of patients undergoing endoscopy in Japan, we identified acute GIB was a significant risk factor for late thromboembolism and death, compared with patients without GIB. GIB also increased risk of death compared with the general population.

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.

Hepatitis B virus vaccination-related seroprevalence among health-care personnel in a Japanese tertiary medical center.

AIM: Few studies concerning the protective management of hepatitis B virus (HBV) infection among health-care personnel (HCP), excluding occult HBV or carriers, have been reported. Therefore, we undertook a cross-sectional study of the updated status of HBV vaccine management by measuring the antibody to hepatitis B surface antigen (anti-HBs) along with the antibody to hepatitis B core antigen (anti-HBc). METHODS: Both anti-HBs and anti-HBc were assessed in 1085 HCP employed by our institute. Hepatitis B virus vaccination-related histories were recorded using self-administered questionnaires. RESULTS: Of 1085 HCP, 27 (2.5%) were positive for anti-HBc, and its positive rate increased with age. Of the 1058 subjects with negative anti-HBc, 879 (83.1%) were positive for anti-HBs. The median titer of anti-HBs was 71.1 mIU/mL, which was higher in female subjects (P = 0.037). By age group, the positive rate of anti-HBs were 77.5%, 89.3%, 90.8%, and 81.6% in the groups aged ≤29, 30-39, 40-49, and ≥50 years, respectively (P < 0.001). Of the 908 subjects who reported receiving HBV vaccination, 6 (0.7%) were positive for anti-HBc. Among them, one subject was suspected to have a possible subclinical HBV infection after the HBV vaccination. CONCLUSION: We report the current HBV vaccination-related seroprevalence of anti-HBs along with anti-HBc in a Japanese tertiary medical institution consisting of more than 1000 HCP, which was an level comparable to similar sized hospitals in developed countries. Anti-HBc would be important for understanding HBV status, but not necessary for general HBV vaccine management for HCP.

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.

High-dose barium impaction therapy for the recurrence of colonic diverticular bleeding: a randomized controlled trial.

OBJECTIVE: We compared the clinical efficacy of barium therapy and conservative therapy in preventing recurrence in patients with diverticular bleeding. BACKGROUND: Previous case reports have indicated that barium impaction therapy provides initial hemostasis for diverticular bleeding and prevention against rebleeding. METHODS: After spontaneous cessation of bleeding, patients were randomly assigned to conservative treatment (n = 27) or high-dose barium impaction therapy (n = 27). Patients were followed up for 1 year after enrollment of the last patient. The main outcome measure was rebleeding. RESULTS: Median follow-up period was 584.5 days. The probability of rebleeding at 30-day, 180-day, 1-year, and 2-year follow-up in all patients was 3.7%, 14.8%, 28.4%, and 32.7%, respectively. By group, probability at 1 year was 42.5% in the conservative group and 14.8% in the barium group (log-rank test, P = 0.04). After adjustment for a history of hypertension, the hazard ratio of rebleeding in the barium group was 0.34 (95% confidence interval, 0.12-0.98). No complications or laboratory abnormalities due to barium therapy were observed. Compared with the conservative group, the barium group had significantly (P < 0.05) fewer hospitalizations per patient (1.7 vs 1.2), units of blood transfused (1.9 vs 0.7), colonoscopies (1.4 times vs 1.1 times), and hospital stay days (15 days vs 11 days) during the follow-up period. No patients died and none required angiographic or surgical procedures in either group. CONCLUSIONS: High-dose barium impaction therapy was effective in the long-term prevention of recurrent bleeding, and reduced the frequency of rehospitalization and need for blood transfusion and colonoscopic examination. ClinicalTrials.gov Identifier, UMIN 000002832.

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.

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.