Bing Yee Suen

Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen

BACKGROUNDnMany patients who have had upper gastrointestinal bleeding continue to take low-dose aspirin for cardiovascular prophylaxis or other non-steroidal antiinflammatory drugs (NSAIDs) for musculoskeletal pain. It is uncertain whether infection with Helicobacter pylori is a risk factor for bleeding in such patients.nnnMETHODSnWe studied patients with a history of upper gastrointestinal bleeding who were infected with H. pylori and who were taking low-dose aspirin or other NSAIDs. We evaluated whether eradication of the infection or omeprazole treatment was more effective in preventing recurrent bleeding. We recruited patients who presented with upper gastrointestinal bleeding that was confirmed by endoscopy. Their ulcers were healed by daily treatment with 20 mg of omeprazole for eight weeks or longer. Then, those who had been taking aspirin were given 80 mg of aspirin daily, and those who had been taking other NSAIDs were given 500 mg of naproxen twice daily for six months. The patients in each group were then randomly assigned separately to receive 20 mg of omeprazole daily for six months or one week of eradication therapy, consisting of 120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, all given four times daily, followed by placebo for six months.nnnRESULTSnWe enrolled 400 patients (250 of whom were taking aspirin and 150 of whom were taking other NSAIDs). Among those taking aspirin, the probability of recurrent bleeding during the six-month period was 1.9 percent for patients who received eradication therapy and 0.9 percent for patients who received omeprazole (absolute difference, 1.0 percent; 95 percent confidence interval for the difference, -1.9 to 3.9 percent). Among users of other NSAIDs, the probability of recurrent bleeding was 18.8 percent for patients receiving eradication therapy and 4.4 percent for those treated with omeprazole (absolute difference, 14.4 percent; 95 percent confidence interval for the difference, 4.4 to 24.4 percent; P=0.005).nnnCONCLUSIONSnAmong patients with H. pylori infection and a history of upper gastrointestinal bleeding who are taking low-dose aspirin, the eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Omeprazole is superior to the eradication of H. pylori in preventing recurrent bleeding in patients who are taking other NSAIDs.

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

BACKGROUNDnGuidelines 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.nnnMETHODSn441 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.nnnFINDINGSnCombination 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.nnnINTERPRETATIONnPatients 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

n n n n Background & Aims:n 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.n n n Methods:n 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.n n n Results:n 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).n n n Conclusions:n In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.n n

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

BACKGROUND & AIMSnCurrent 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.nnnMETHODSnIn 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnThe 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.

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.

Increased Risk of Advanced Neoplasms Among Asymptomatic Siblings of Patients With Colorectal Cancer

BACKGROUND & AIMSnColorectal 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.nnnMETHODSnPatients 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).nnnRESULTSnThe 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).nnnCONCLUSIONSnIn 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.

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

BACKGROUND & AIMSnThe 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.nnnMETHODSnIn 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.nnnRESULTSnBaseline 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.nnnCONCLUSIONSnIn 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.

Risk of Post-polypectomy Bleeding With Uninterrupted Clopidogrel Therapy in an Industry-independent, Double-blind, Randomized Trial

BACKGROUND & AIMSnGuidelines 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.nnnMETHODSnWe 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.nnnRESULTSnIn 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 (Pxa0= .945 by log-rank test). There were no significant differences in immediate postpolypectomy bleeding (8.5% vs 5.5%; Pxa0= .380) andxa0cardio-thrombotic events (1.5% vs 2%; Pxa0= .713).nnnCONCLUSIONSnIn 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.

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