Novel microbiome signatures for non-invasive diagnosis of adenoma recurrence after colonoscopic polypectomy.

BACKGROUND: We previously reported a panel of novel faecal microbiome gene markers for diagnosis of colorectal adenoma and cancer. AIM: To evaluate whether these markers are useful in detecting adenoma recurrence after polypectomy. METHODS: Subjects were enrolled in a polyp surveillance study from 2009 to 2019. Stool samples were collected before bowel preparation of index colonoscopy (baseline) and surveillance colonoscopy (follow-up). Fusobacterium nucleatum (Fn), Lachnoclostridium marker (m3), Clostridium hathewayi (Ch) and Bacteroides clarus were quantified in baseline and follow-up samples by quantitative polymerase chain reaction (qPCR) to correlate with adenoma recurrence. Recurrence was defined as new adenomas detected >6 months after polypectomy. Faecal immunochemical test (FIT) was performed for comparison. RESULTS: A total of 161 baseline and 104 follow-up samples were analysed. Among patients with adenoma recurrence, Fn and m3 increased (both P < 0.05) while Ch were unchanged in follow-up versus baseline samples. Among patients without recurrence, Fn and m3 were unchanged while Ch decreased (P < 0.05) in follow-up versus baseline samples. Logistic regression that included changes of m3, Fn and Ch at follow-up compared with baseline achieved an area under receiver operating characteristic curve (AUROC) of 0.95 (95%CI: 0.84-0.99) with 90.0% sensitivity and 87.0% specificity for detecting recurrent adenoma. Combination of m3, Fn and Ch at follow-up sample achieved AUROC of 0.74 (95%CI: 0.65-0.82) with 81.3% sensitivity and 55.4% specificity for detecting recurrent adenoma. FIT showed limited sensitivity (8.3%) in detecting recurrent adenomas. CONCLUSION: Our combinations of faecal microbiome gene markers can be potentially useful non-invasive tools for detecting adenoma recurrence.

Scheduled second look endoscopy after endoscopic hemostasis to patients with high risk bleeding peptic ulcers: a Randomized Controlled Trial.

BACKGROUND: The recommendation of second look endoscopy (SLOGD) in selected patients at high risk for rebleeding has been inconclusive. This study aimed to evaluate the benefit of SLOGD in selected patients predicted at high risk of recurrent bleeding. METHODS: From a cohort of 939 patients with bleeding peptic ulcers who underwent endoscopic hemostasis, we derived a 9-point risk score (age > 60, Male, ulcer ≥ 2 cm in size, posterior bulbar or lesser curve gastric ulcer, Forrest I bleeding, haemoglobin < 8 g/dl) to predict recurrent bleeding. We then validated the score in another cohort of 1334 patients (AUROC 0.77). To test the hypothesis that SLOGD in high-risk patients would improve outcomes, we did a randomized controlled trial to compare scheduled SLOGD with observation alone in those predicted at high risk of rebleeding (a score of ≥ 5). The primary outcome was clinical bleeding within 30 days of the index bleed. RESULTS: Of 314 required, we enrolled 157 (50%) patients (SLOGD n = 78, observation n = 79). Nine (11.8%) in SLOGD group and 14 (18.2%) in observation group reached primary outcome (absolute difference 6.4%, 95% CI - 5.0% to 17.8%). Twenty-one of 69 (30.4%) patients who underwent SLOGD needed further endoscopic treatment. No surgery for bleeding control was needed. There were 6 vs. 3 of 30-day deaths in either group (p = 0.285, log rank). No difference was observed regarding blood transfusion and hospitalization. CONCLUSIONS: In this aborted trial that enrolled patients with bleeding peptic ulcers at high-risk of recurrent bleeding, scheduled SLOGD did not significantly improve outcomes. CLINICALTRIALS: gov:NCT02352155.

Comparison of a Hemostatic Powder and Standard Treatment in the Control of Active Bleeding From Upper Nonvariceal Lesions : A Multicenter, Noninferiority, Randomized Trial.

BACKGROUND: The effectiveness of the hemostatic powder TC-325 as a single endoscopic treatment for acute nonvariceal upper gastrointestinal bleeding is uncertain. OBJECTIVE: To compare TC-325 with standard endoscopic hemostatic treatments in the control of active bleeding from nonvariceal upper gastrointestinal causes. DESIGN: One-sided, noninferiority, randomized, controlled trial. (ClinicalTrials.gov: NCT02534571). SETTING: University teaching hospitals in the Asia-Pacific region. PATIENTS: 224 adult patients with acute bleeding from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: TC-325 (n = 111) or standard hemostatic treatment (n = 113). MEASUREMENTS: The primary outcome was control of bleeding within 30 days. Other outcomes included failure to control bleeding during index endoscopy, recurrent bleeding after initial hemostasis, further interventions, blood transfusion, hospitalization, and death. RESULTS: 224 patients were enrolled (136 with gastroduodenal ulcers [60.7%], 33 with tumors [14.7%], and 55 with other causes of bleeding [24.6%]). Bleeding was controlled within 30 days in 100 of 111 patients (90.1%) in the TC-325 group and 92 of 113 (81.4%) in the standard treatment group (risk difference, 8.7 percentage points [1-sided 95% CI, 0.95 percentage point]). There were fewer failures of hemostasis during index endoscopy with TC-325 (3 [2.7%] vs. 11 [9.7%]; odds ratio, 0.26 [CI, 0.07 to 0.95]). Recurrent bleeding within 30 days did not differ between groups (9 [8.1%] vs. 10 [8.8%]). The need for further interventions also did not differ between groups (further endoscopic treatment: 8 [7.2%] vs. 10 [8.8%]; angiography: 2 [1.8%] vs. 4 [3.5%]; surgery: 1 [0.9%] vs. 0). There were 14 deaths in each group (12.6% vs. 12.4%). LIMITATION: Clinicians were not blinded to treatment. CONCLUSION: TC-325 is not inferior to standard treatment in the endoscopic control of bleeding from nonvariceal upper gastrointestinal causes. PRIMARY FUNDING SOURCE: General Research Fund to the University Grants Committee, Hong Kong SAR Government.

Impact of Physicians' and Patients' Compliance on Outcomes of Colonoscopic Polypectomy With Anti-Thrombotic Therapy.

BACKGROUND & AIMS: Although there are international guidelines on the management of antithrombotic therapy in patients undergoing colonoscopic polypectomy, whether clinicians and patients follow these recommendations are largely unknown. We aimed to evaluate clinician adherence and patient compliance to periendoscopic management of antithrombotic therapy and their impact on clinical outcomes. METHODS: Consecutive patients on antithrombotic therapy scheduled for elective colonoscopy in a tertiary referral center were recruited prospectively. Demographic data, indications and periprocedural management of antithrombotic drugs, colonoscopy findings, postpolypectomy bleeding, and serious cardiovascular events were collected systematically. We used Joint Asian Pacific Association of Gastroenterology-Asian Pacific Society for Digestive Endoscopy Practice Guidelines 2018 and assumed clinicians should hold antithrombotics for polypectomy in all colonoscopy patients. Patient compliance was assessed by checking whether discontinuation and resumption of antithrombotic drugs were in accordance with clinician advice. RESULTS: Between December 2017 and October 2019, there were 602 patients recruited who were on antithrombotic drugs undergoing colonoscopy with polypectomy. A total of 98.4%, 41.2%, and 40.0% of clinicians adhered to the guidelines for aspirin alone, clopidogrel alone, and dual-antiplatelet therapy, respectively. Adherence rates were 8.5% for warfarin and 5.2% for direct oral anticoagulants. Compliance to instructions for aspirin alone, clopidogrel alone, dual-antiplatelet therapy, warfarin, and direct oral anticoagulants were achieved in 74.8%, 41.2%, 0%, 36.2%, and 17.5% of patients, respectively. Clinician nonadherence to guidelines was a risk factor for delayed postpolypectomy bleeding (adjusted hazard ratio, 3.54; 95% CI, 1.46-8.58; P = .005), and serious cardiovascular events (hazard ratio, 15.63; 95% CI, 1.83-133.80; P = .012). CONCLUSIONS: Physician adherence to the guideline and patient compliance, with the exception of aspirin, were poor and contributed to adverse clinical outcomes. ClinicalTrials.gov number: NCT03363061.

Prospective colonoscopic study to investigate risk of colorectal neoplasms in first-degree relatives of patients with non-advanced adenomas.

OBJECTIVE: The risk associated with a family history of non-advanced adenoma (non-AA) is unknown. We determined the prevalence of colorectal neoplasms in subjects who have a first-degree relative (FDR) with non-AA compared with subjects who do not have an FDR with adenomas. DESIGN: In a blinded, cross-sectional study, consecutive subjects with newly diagnosed non-AA were identified from our colonoscopy database. 414 FDRs of subjects with non-AA (known as exposed FDRs; mean age 55.0±8.1 years) and 414 age and sex-matched FDRs of subjects with normal findings from colonoscopy (known as unexposed FDRs; mean age 55.2±7.8 years) underwent a colonoscopy from November 2015 to June 2018. One FDR per family was recruited. FDRs with a family history of colorectal cancer were excluded. The primary outcome was prevalence of advanced adenoma (AA). Secondary outcomes included prevalence of all adenomas and cancer. RESULTS: The prevalence of AA was 3.9% in exposed FDRs and 2.4% in unexposed FDRs (matched OR (mOR)=1.67; 95% CI 0.72 to 3.91; p=0.238 adjusted for proband sex and proband age). Exposed FDRs had a higher prevalence of any adenomas (29.2% vs 18.6%; mOR=1.87; 95% CI 1.32 to 2.66; p<0.001) and non-AA (25.4% vs 16.2%; mOR=1.91; 95% CI 1.32 to 2.76; p=0.001). A higher proportion of exposed FDRs than unexposed FDRs (4.3% vs 2.2%; adjusted mOR=2.44; 95% CI 1.01 to 5.86; p=0.047) had multiple adenomas. No cancer was detected in both groups. CONCLUSION: A positive family history of non-AA does not significantly increase the risk of clinically important colorectal neoplasia. The data support current guidelines which do not advocate earlier screening in individuals with a family history of non-AA. TRIAL REGISTRATION NUMBER: NCT0252172.

Risk of Postpolypectomy Bleeding With Uninterrupted Clopidogrel Therapy in an Industry-Independent, Double-Blind, Randomized Trial.

BACKGROUND & AIMS: Guidelines recommend withholding clopidogrel 7 days before polypectomy to decrease bleeding risk, but these were written based on limited evidence. We investigated whether uninterrupted clopidogrel therapy increases the risk of delayed postpolypectomy bleeding in patients undergoing colonoscopy. METHODS: We identified patients receiving clopidogrel for cardiovascular disease undergoing elective colonoscopies in Hong Kong from February 28, 2012 through April 11, 2018. Eligible patients were instructed to stop taking clopidogrel 7 days before colonoscopy. Then, they were randomly assigned to groups given clopidogrel (75 mg) or placebo daily until the morning of colonoscopy. All patients resumed their usual prescriptions of clopidogrel after colonoscopy. The primary end point was delayed postpolypectomy bleeding that required hospitalization or intervention up to 30 days after colonoscopy. Secondary end points were immediate postpolypectomy bleeding and serious cardio-thrombotic events for as long as 6 months after colonoscopy, according to Antithrombotic Trialists' criteria. All events were adjudicated by an independent masked committee. RESULTS: In total, 387 patients underwent colonoscopy and 216 required polypectomies (106 patients in the clopidogrel group and 110 patients in the placebo group). The cumulative incidence of delayed postpolypectomy bleeding was 3.8% (95% confidence interval 1.4-9.7) in the clopidogrel group and 3.6% (95% confidence interval 1.4-9.4) in the placebo group (P = .945 by log-rank test). There were no significant differences in immediate postpolypectomy bleeding (8.5% vs 5.5%; P = .380) and cardio-thrombotic events (1.5% vs 2%; P = .713). CONCLUSIONS: In a randomized controlled trial of clopidogrel users undergoing colonoscopy, a slightly larger proportion of patients continuing clopidogrel developed delayed and immediate postpolypectomy bleeding, although this difference was not statistically significant. ClinicalTrials.gov, number NCT01806090.

Risk of Advanced Adenomas in Siblings of Individuals With Advanced Adenomas: A Cross-Sectional Study.

BACKGROUND & AIMS: The risk of colorectal neoplasms among siblings of patients with advanced adenomas is not clear. We determined the prevalence of advanced adenomas in the siblings of patients with advanced adenomas and compared it with that of siblings of individuals without these lesions. METHODS: In a blinded, cross-sectional study, colonoscopies were performed (from 2010 through 2014), at 2 hospitals in Hong Kong on 200 asymptomatic siblings of patients with advanced adenomas (exposed; mean age, 58.2 ± 6.3 years; adenomas ≥10 mm, high-grade dysplasia, villous, or tubulovillous) and 400 age- and sex-matched siblings of subjects with normal findings from colonoscopies and no family history of colorectal cancer (unexposed; mean age, 58.1 ± 6 years). We recruited 1 sibling per family. The primary outcome was prevalence of advanced adenomas. RESULTS: Baseline demographics (ie, aspirin use, smoking, body mass index, and metabolic diseases) did not differ significantly between exposed and unexposed individuals. The prevalence of advanced adenoma was 11.5% among the exposed subjects and 2.5% among the unexposed subjects (matched odds ratio [mOR] = 6.05; 95% confidence interval [CI]: 2.74-13.36; P < .001). The prevalence of adenomas ≥10 mm was higher among exposed than unexposed siblings (10.5% vs 1.8%; mOR = 8.59; 95% CI: 3.44-21.45; P < .001), as was the prevalence of villous adenomas (5.5% vs 1.3% in unexposed; mOR = 6.28; 95% CI: 2.02-19.53; P = .001) and all colorectal adenomas (39.0% vs 19.0% in unexposed; mOR = 3.29; 95% CI: 2.16-5.03; P < .001). Two cancers were detected in exposed siblings and none in unexposed siblings. CONCLUSIONS: In a cross-sectional study of subjects undergoing colonoscopy in Hong Kong, siblings of individuals with at least 1 advanced adenoma had a 6-fold increased odds of advanced adenoma compared with subjects who had a sibling with a screening colonoscopy with no identified neoplasia. ClinicalTrials.gov, Number: NCT01593098.

Effects of intravenous and oral esomeprazole in the prevention of recurrent bleeding from peptic ulcers after endoscopic therapy.

OBJECTIVES: The use of intravenous proton-pump inhibitors (PPIs) has shown to reduce recurrent bleeding and improve patient outcome after endoscopic hemostasis on patients with peptic ulcer. However, the efficacy of oral PPI is uncertain. Studies from Asia indicated that even oral PPI can achieve the same therapeutic effect. This study is designed to compare the efficacy of high-dose intravenous PPI to oral PPI in preventing recurrent bleeding after endoscopic hemostasis. METHODS: This is a single-center, randomized-controlled, double-blind, and double-dummy study. Patients had Forrest IA/IB or IIA/IIB peptic ulcer bleeding and received endoscopic hemostasis before recruitment into the study. They were randomized to receive either (i) esomeprazole IV bolus at a dose of 80 mg plus infusion at 8 mg/h for 72 h and oral placebo every 12 h (IVP group), or (ii) IV placebo bolus plus infusion for 72 h and high-dose oral esomeprazole at a dose of 40 mg every 12 h (ORP group). Patients were followed up for 30 days after index bleeding. The primary end point was defined as the 30-day recurrent bleeding after successful endoscopic hemostasis. RESULTS: A total of 118 patients were randomized to the IVP group and 126 to the ORP group in this study. In all, 39.8% in the IVP and 42.9% in the ORP group used non-steroidal anti-inflammatory drug and/or aspirin before bleeding. In the IVP group (vs. ORP), Forrest IA represented 1.7% (5.6%), IB 41.5% (38.1%), IIA 52.5% (50.8%), and IIB 4.2% (5.6%). Recurrent bleeding in 30 days was reported in 7.7% of patients in the IVP group and 6.4% of patients in the ORP group, and the difference of recurrent bleeding was -1.3% (95% CI: -7.7%, 5.1%). There was no difference in blood transfusion, repeated endoscopic therapy, and hospital stay between the two groups. CONCLUSIONS: High-dose oral esomeprazole at 40 mg BID may be considered as a useful alternative to IV bolus plus infusion of esomeprazole in the management of ulcer bleeding in patients who are not candidates for high-dose IV infusion. However, as this study was stopped prematurely and was not designed as an equivalency trial, a much larger study would be necessary to document whether there is equivalency or non-inferiority of the two treatments in a heterogeneous patient population.

Effects of Helicobacter pylori infection on long-term risk of peptic ulcer bleeding in low-dose aspirin users.

BACKGROUND & AIMS: Current guidelines recommend testing for Helicobacter pylori infection among users of low-dose aspirin (ASA) who are at high risk for developing ulcers. However, it is not clear whether this strategy affects long-term risk of ulcer bleeding. We assessed the utility of testing ASA users with a high risk of ulcer bleeding for H pylori infection. METHODS: In a prospective study, we recruited 3 cohorts of ASA users (≤160 mg/day). The first group included H pylori-positive users of ASAs with bleeding ulcers in whom the infections were eradicated (n = 249). They resumed ASA after ulcer healing and H pylori eradication. The second group included H pylori-negative (past and present) users of ASA who developed bleeding ulcers (n = 118). They received enteric-coated ASA after ulcer healing. The average-risk cohort included new users of ASA without a history of ulcers (n = 537). None of the subjects received regular treatment with anti-ulcer drugs. The primary end point was ulcer bleeding with ASA use in 5048 patient-years of follow-up evaluation. RESULTS: The incidence of ulcer bleeding (per 100 patient-years) in the H pylori-eradicated cohort (0.97; 95% confidence interval [CI], 0.53-1.80) did not differ significantly from that of the average-risk cohort (0.66; 95% CI, 0.38-0.99). The H pylori-negative cohort had a high incidence of recurrent bleeding (5.22; 95% CI, 3.04-8.96) (incidence rate ratio, 8.52; 95% CI, 4.29-16.95 vs the average-risk cohort). CONCLUSIONS: The long-term incidence of recurrent ulcer bleeding with ASA use is low after H pylori infection is eradicated. ASA users without current or past H pylori infections who develop ulcer bleeding have a high risk of recurrent bleeding. Tests for H pylori infection can be used to assign high-risk ASA users to groups that require different gastroprotective strategies.

Increased risk of advanced neoplasms among asymptomatic siblings of patients with colorectal cancer.

BACKGROUND & AIMS: Colorectal cancer (CRC) is the second-most common cancer in Hong Kong. Relatives of patients with CRC have an increased risk of colorectal neoplasm. We assessed the prevalence of advanced neoplasms among asymptomatic siblings of patients with CRC. METHODS: Patients with CRC were identified from the Prince of Wales Hospital CRC Surgery Registry from 2001 to 2011. Colonoscopies were performed for 374 siblings of patients (age, 52.6 ± 7.4 y) and 374 age- and sex-matched siblings of healthy subjects who had normal colonoscopies and did not have a family history of CRC (controls, 52.7 ± 7.4 y). We identified individuals with advanced neoplasms (defined as cancers or adenomas of at least 10 mm in diameter, high-grade dysplasia, with villous or tubulovillous characteristics). RESULTS: The prevalence of advanced neoplasms was 7.5% among siblings of patients and 2.9% among controls (matched odds ratio [mOR], 3.07; 95% confidence interval [CI], 1.5-6.3; P = .002). The prevalence of adenomas larger than 10 mm was higher among siblings of patients than in controls (5.9% vs 2.1%; mOR, 3.34; 95% CI, 1.45-7.66; P = .004), as was the presence of colorectal adenomas (31.0% vs 18.2%; mOR, 2.19; 95% CI, 1.52-3.17; P < .001). Six cancers were detected among siblings of patients; no cancers were detected in controls. The prevalence of advanced neoplasms among siblings of patients was higher when their index case was female (mOR, 4.95; 95% CI, 1.81-13.55) and had distally located CRC (mOR, 3.10; 95% CI, 1.34-7.14). CONCLUSIONS: In Hong Kong, siblings of patients with CRC have a higher prevalence of advanced neoplasms, including CRC, than siblings of healthy individuals. Screening is indicated in this high-risk population. ClinicalTrials.gov number: NCT00164944.

Capsule endoscopy or angiography in patients with acute overt obscure gastrointestinal bleeding: a prospective randomized study with long-term follow-up.

OBJECTIVES: Both capsule endoscopy (CE) and angiography have been recommended as first investigation for patients with acute overt obscure gastrointestinal bleeding (OGIB). However, no studies have directly compared the two modalities in patients with overt OGIB. We compared the diagnostic yield and long-term outcomes of patients with overt OGIB randomized to CE or angiogram. METHODS: Consecutive patients presented with acute melena or hematochezia, but nondiagnostic upper and lower endoscopy, were immediately randomized to receive small-bowel CE or angiography. All patients were monitored for rebleeding and anemia for up to 5 years. Primary end point was the diagnostic yield of the assigned investigation. Secondary end points included rebleeding, further transfusion, readmission for bleeding or anemia, and mortality. RESULTS: A total of 60 patients with overt OGIB were randomized. The mean follow-up was 48.5 months. The diagnostic yield of immediate CE was significantly higher than angiography (53.3% vs. 20.0%, P = 0.016). The cumulative risk of rebleeding in the angiography and CE group was 33.3% and 16.7%, respectively (P = 0.10, log-rank test). There was no significant difference in the long-term outcomes between the two groups including further transfusion, hospitalization for rebleeding, and mortality. CONCLUSIONS: In patients with overt OGIB, immediate CE has higher diagnostic yield and comparable long-term outcomes when compared with angiography.

Repeat-screening colonoscopy 5 years after normal baseline-screening colonoscopy in average-risk Chinese: a prospective study.

OBJECTIVES: Although colonoscopy is considered the most accurate screening tool for colorectal neoplasm, the optimal interval of repeating a screening colonoscopy, particularly in average-risk subjects after a negative colonoscopy, is poorly defined. We determine the 5-year risk of advanced neoplasia on rescreening colonoscopy in a cohort of average-risk Chinese subjects. METHODS: We invited a cohort of asymptomatic average-risk Chinese subjects (aged 55-75 years) who were recruited in our previous screening colonoscopy studies to undergo a repeat colonoscopy at the end of 5 years. The rates of advanced colorectal neoplasia at the end of 5 years in these subjects were determined according to their baseline colonoscopy findings. RESULTS: A total of 511 of the 620 eligible subjects underwent repeat-screening colonoscopy at the end of 5 years. Among them, 401 subjects had no baseline neoplasia (370 with no baseline polyps and 31 with hyperplastic polyps). In subjects with no baseline polyp, 24.6% were found to have at least one adenoma and 1.4% had advanced neoplasia on rescreening. The number needed to rescreen for one advanced neoplasia in subjects with no baseline polyp was 74 (95% confidence interval (CI), 32-168). The prevalence of advanced neoplasia at 5 years in subjects with baseline-advanced neoplasia was 20.7% (relative risk 19.6; 95% CI, 5.2-74.1; vs. subjects with no baseline polyp). The presence of baseline-advanced neoplasia (odds ratio (OR) 13.1; 95% CI, 4.1-41.7) and age in years (OR 1.11; 95% CI, 1.01-1.22) are two independent factors for development of advanced neoplasia at 5 years. CONCLUSIONS: The risk of advanced neoplasia is sufficiently low 5 years after a normal screening colonoscopy in Chinese subjects.

Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial.

BACKGROUND: Guidelines on pain management recommend that patients at risk of ulcers receive either a cyclo-oxygenase (COX 2) inhibitor or a non-steroidal anti-inflammatory drug (NSAID) with a proton-pump inhibitor (PPI). These two treatments have similar effectiveness, but they are insufficient for protection of patients at very high risk for ulcer bleeding. We aimed to test the hypothesis that in patients with previous ulcer bleeding induced by non-selective NSAIDs, combined treatment with the COX 2 inhibitor celecoxib and the PPI esomeprazole would be better than celecoxib alone for prevention of recurrent ulcer bleeding. METHODS: 441 consecutively presenting patients who were taking non-selective NSAIDs for arthritis were recruited to our single-centre, prospective, randomised, double-blind trial after admission to hospital with upper-gastrointestinal bleeding. Patients were enrolled after their ulcers had healed and a histological test for Helicobacter pylori was negative. All patients were given 200 mg celecoxib twice daily. 137 patients were randomly assigned to receive 20 mg esomeprazole twice daily (combined-treatment group), and 136 to receive a placebo (control group) for 12 months. The primary endpoint was recurrent ulcer bleeding during treatment or within 1 month of the end of treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00365313. FINDINGS: Combination treatment was more effective than celecoxib alone for prevention of ulcer bleeding in patients at high risk. The 13-month cumulative incidence of the primary endpoint was 0% in the combined-treatment group and 12 (8.9%) in the controls (95% CI difference, 4.1 to 13.7; p=0.0004). The median follow-up was 13 months (range 0.4-13.0). Discontinuation of treatment and the incidence of adverse events were similar in the two treatment groups. INTERPRETATION: Patients at very high risk for recurrent ulcer bleeding who need anti-inflammatory analgesics should receive combination treatment with a COX 2 inhibitor and a PPI. Our findings should encourage guideline committees to review their recommendations for patients at very high risk of recurrent ulcer bleeding.

Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients.

BACKGROUND & AIMS: In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ. METHODS: We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes. RESULTS: One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12). CONCLUSIONS: In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.