James Y. Lau

Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

BACKGROUND After endoscopic treatment of bleeding peptic ulcers, bleeding recurs in 15 to 20 percent of patients. METHODS We assessed whether the use of a high dose of a proton-pump inhibitor would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels were treated with an epinephrine injection followed by thermocoagulation. After hemostasis had been achieved, they were randomly assigned in a double-blind fashion to receive omeprazole (given as a bolus intravenous injection of 80 mg followed by an infusion of 8 mg per hour for 72 hours) or placebo. After the infusion, all patients were given 20 mg of omeprazole orally per day for eight weeks. The primary end point was recurrent bleeding within 30 days after endoscopy. RESULTS We enrolled 240 patients, 120 in each group. Bleeding recurred within 30 days in 8 patients (6.7 percent) in the omeprazole group, as compared with 27 (22.5 percent) in the placebo group (hazard ratio, 3.9; 95 percent confidence interval, 1.7 to 9.0). Most episodes of recurrent bleeding occurred during the first three days, which made up the infusion period (5 in the omeprazole group and 24 in the placebo group, P<0.001). Three patients in the omeprazole group and nine in the placebo group underwent surgery (P=0.14). Five patients (4.2 percent) in the omeprazole group and 12 (10 percent) in the placebo group died within 30 days after endoscopy (P=0.13). CONCLUSIONS After endoscopic treatment of bleeding peptic ulcers, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding.

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

BACKGROUND Many 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. METHODS We 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. RESULTS We 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). CONCLUSIONS Among 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.

Endoscopic retreatment compared with surgery in patients with recurrent bleeding after initial endoscopic control of bleeding ulcers.

Background and Methods After endoscopic treatment to control bleeding of peptic ulcers, bleeding recurs in 15 to 20 percent of patients. In a prospective, randomized study, we compared endoscopic retreatment with surgery after initial endoscopy. Over a 40-month period, 1169 of 3473 adults who were admitted to our hospital with bleeding peptic ulcers underwent endoscopy to reestablish hemostasis. Of 100 patients with recurrent bleeding, 7 patients with cancer and 1 patient with cardiac arrest were excluded from the study; 48 patients were randomly assigned to undergo immediate endoscopic retreatment and 44 were assigned to undergo surgery. The type of operation used was left to the surgeon. Bleeding was considered to have recurred in the event of any one of the following: vomiting of fresh blood, hypotension and melena, or a requirement for more than four units of blood in the 72-hour period after endoscopic treatment. Results Of the 48 patients who were assigned to endoscopic retreatment, 35 had long-term...

Continuation of Low-Dose Aspirin Therapy in Peptic Ulcer Bleeding: A Randomized Trial

BACKGROUND It is uncertain whether aspirin therapy should be continued after endoscopic hemostatic therapy in patients who develop peptic ulcer bleeding while receiving low-dose aspirin. OBJECTIVE To test that continuing aspirin therapy with proton-pump inhibitors after endoscopic control of ulcer bleeding was not inferior to stopping aspirin therapy, in terms of recurrent ulcer bleeding in adults with cardiovascular or cerebrovascular diseases. DESIGN A parallel randomized, placebo-controlled noninferiority trial, in which both patients and clinicians were blinded to treatment assignment, was conducted from 2003 to 2006 by using computer-generated numbers in concealed envelopes. (ClinicalTrials.gov registration number: NCT00153725) SETTING A tertiary endoscopy center. PATIENTS Low-dose aspirin recipients with peptic ulcer bleeding. INTERVENTION 78 patients received aspirin, 80 mg/d, and 78 received placebo for 8 weeks immediately after endoscopic therapy. All patients received a 72-hour infusion of pantoprazole followed by oral pantoprazole. All patients completed follow-up. MEASUREMENTS The primary end point was recurrent ulcer bleeding within 30 days confirmed by endoscopy. Secondary end points were all-cause and specific-cause mortality in 8 weeks. RESULTS 156 patients were included in an intention-to-treat analysis. Three patients withdrew from the trial before finishing follow-up. Recurrent ulcer bleeding within 30 days was 10.3% in the aspirin group and 5.4% in the placebo group (difference, 4.9 percentage points [95% CI, -3.6 to 13.4 percentage points]). Patients who received aspirin had lower all-cause mortality rates than patients who received placebo (1.3% vs. 12.9%; difference, 11.6 percentage points [CI, 3.7 to 19.5 percentage points]). Patients in the aspirin group had lower mortality rates attributable to cardiovascular, cerebrovascular, or gastrointestinal complications than patients in the placebo group (1.3% vs. 10.3%; difference, 9 percentage points [CI, 1.7 to 16.3 percentage points]). LIMITATIONS The sample size is relatively small, and only low-dose aspirin, 80 mg, was used. Two patients with recurrent bleeding in the placebo group did not have further endoscopy. CONCLUSION Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings.

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.

Asia Pacific consensus recommendations for colorectal cancer screening

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5–9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.

Causes of Mortality in Patients With Peptic Ulcer Bleeding: A Prospective Cohort Study of 10,428 Cases

OBJECTIVES:Despite advances in endoscopic and pharmacological treatment for peptic ulcer bleeding (PUB), mortality remains at 5–10% worldwide. Our aim was to investigate the causes of death in a prospective cohort of PUB in a tertiary referral center.METHODS:Between 1993 and 2005, all patients with upper gastrointestinal bleeding (UGIB) admitted to the Prince of Wales Hospital were prospectively registered. Demographic data, characteristics of ulcer, and pharmacological, endoscopic, and surgical therapy, were documented. Mortality cases were classified as (A) bleeding-related death (A1: uncontrolled bleeding, A2: within 48 h after endoscopy, A3: during surgery for uncontrolled bleeding, A4: surgical complications or within 1 month after surgery, and A5: endoscopic related mortality) or (B) non-bleeding-related death (B1: cardiac causes, B2: pulmonary causes, B3: cerebrovascular disease, B4: multiorgan failure, and B5: terminal malignancy).RESULTS:In all, 18,508 cases of UGIB were enrolled; among them, 10,428 cases from 9,375 patients were confirmed to have PUB, and 577 (6.2%) patients died. There were significantly more patients who died of non-ulcer bleeding causes (79.7%) than bleeding causes (18.4%). The mean (s.d.) age of those who died of bleeding-related causes was higher (75.4 (12.6) years) than that of those who died of non-bleeding causes (71.7 (13.1) years) (P=0.010). Most bleeding-related deaths occurred when immediate control of bleeding failed (29.2%) or when patients died within 48 h after endoscopic therapy (25.5%). Among those who died of non-bleeding-related causes, multiorgan failure (23.9%), pulmonary conditions (23.5%), and terminal malignancy (33.7%) were most common.CONCLUSIONS:The majority of PUB patients died of non-bleeding-related causes. Optimization of management should aim at reducing the risk of multiorgan failure and cardiopulmonary death instead of focusing merely on successful hemostasis.

The epidemiology and phenotype of Crohn's disease in the Chinese population.

Background:Inflammatory bowel disease is uncommon in Southeast Asia but is increasing in incidence. The epidemiology and phenotype of Crohn disease (CD) in the Chinese population is not well-known. The purpose of this study was to determine the incidence, temporal trend, clinical features, risk factors, extraintestinal manifestations, and the treatment of CD in the Chinese population of Hong Kong. Methods:We performed a single-center study of consecutive definite CD cases based on internationally accepted criteria, with strict exclusion of infective enterocolitis. Results:Eighty Chinese CD patients were recruited, characterized by male gender predominance (male:female ratio 2.5:1), no association with ever smoking (OR 1.02, 95% CI: 0.54–1.92), absence of familial clustering (0%), high proportion of upper gastrointestinal tract disease proximal to the terminal ileum (19%), and a low proportion of isolated terminal ileal disease (4%). The mean age at diagnosis was 33 years. Forty-five percent of patients had penetrating disease, 18% stricturing disease, and 37% had nonstricturing, nonpenetrating disease. Twenty-five percent of patients had at least 1 extraintestinal manifestation, and there was a high rate of ankylosing spondylitis (9%). The incidence of CD was 1.0 per 100,000 and has increased by 3 fold during the past decade. The age-adjusted incidence was 3.0 per 100,000 (95% CI: 2.3–3.7 per 100,000). Conclusions:The incidence of CD in the Chinese is increasing. There are some notable epidemiological and phenotypic differences between Chinese CD with Caucasian CD including the lack of familial clustering, male predominance, and higher proportion of upper GIT involvement and lower frequency of isolated terminal ileal disease.

Endoscopic clipping versus injection and thermo-coagulation in the treatment of non-variceal upper gastrointestinal bleeding: a meta-analysis

Background: Hemoclips, injection therapy and thermocoagulation (heater probe or electrocoagulation) are the most commonly used types of endoscopic hemostasis for the control of non-variceal gastrointestinal bleeding. Aim: To compare the efficacy of hemoclips versus injection or thermocoagulation in endoscopic hemostasis by pooling data from the literature. Method: Publications in the English literature (MEDLINE, EMBASE and Cochrane Library) as well as abstracts in major international conferences were searched using the keywords “hemoclips” and “bleeding”, and 15 trials fulfilling the search criteria were found. Outcome measures included: initial hemostasis (after endoscopic intervention); recurrent bleeding; definitive hemostasis (no recurrent bleeding until the end of follow-up); the requirement for surgical intervention; and all-cause mortality. The heterogeneity of trials was examined and the effects were pooled by meta-analysis. Results: Of 1156 patients recruited in the 15 studies, 390 were randomly assigned to receive clips alone, 242 received clips combined with injection, 359 received injection alone, and 165 received thermocoagulation with or without injection. Definitive hemostasis was higher with hemoclips (86.5%) than injection (75.4%; RR 1.14, 95% CI 1.00–1.30), or endoscopic clips with injection (88.5%) compared with injections alone (78.1%; RR 1.13, 95% CI 1.03–1.23), leading to a reduced requirement for surgery but no difference in mortality. Compared with thermocoagulation, there was no improvement in definitive hemostasis with clips (81.5% versus 81.2%; RR 1.00, 95% CI 0.77–1.31). These estimates were robust in sensitivity analyses. There was also no difference between clips and thermocoagulation in rebleeding, the need for surgery and mortality. The reported locations of failed hemoclip applications included posterior wall of duodenal bulb, posterior wall of gastric body and lesser curve of the stomach. Conclusion: Successful application of hemoclips is superior to injection alone but comparable to thermocoagulation in producing definitive hemostasis. There was no difference in all-cause mortality irrespective of the modalities of endoscopic treatment.

Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers

Abstract Objective: To compare endoscopic adrenaline injection alone and adrenaline injection plus heat probe for the treatment of actively bleeding peptic ulcers. Design: Randomised prospective study of patients admitted with actively bleeding peptic ulcers. Setting: One university hospital. Subjects: 276 patients with actively bleeding ulcers detected by endoscopy within 24 hours of admission: 136 patients were randomised to endoscopic adrenaline injection alone and 140 to adrenaline injection plus heat probe treatment. Main outcome measures: Initial endoscopic haemostasis; clinical rebleeding; requirement for operation; requirement for blood transfusion; hospital stay, ulcer healing at four weeks; and mortality in hospital. Results: Initial haemostasis was achieved in 131/134 patients (98%) who received adrenaline injection alone and 135/136 patients (99%) who received additional heat probe treatment (P = 0.33). Outcome as measured by clinical rebleeding (12 v 5), requirement for emergency operation (14 v 8), blood transfusion (2 v 3 units), hospital stay (4 v 4 days), ulcer healing at four weeks (79.1% v 74%), and in hospital mortality (7 v 8) were not significantly different in the two groups. In the subgroup of patients with spurting haemorrhage 8/27 (29.6%; 14.5% to 50.3%) patients from the adrenaline injection alone group and 2/31 (6.5%; 1.1% to 22.9%) patients from the dual treatment group required operative intervention. The relative risk of this was lower in the dual treatment group (0.17; 0.03 to 0.87). Hospital stay was significantly shorter in the dual treatment group than the adrenaline injection alone group (4 v 6 days, P = 0.01). Conclusion: The addition of heat probe treatment after endoscopic adrenaline injection confers an advantage in ulcers with spurting haemorrhage. Key messages Endoscopic injection of adrenaline alone is effective in stopping bleeding peptic ulcers Further bleeding after adrenaline injection alone, however, occurs in 15-20% of patients, and the addition of heat probe thermocoagulation may improve permanent haemostasis and therefore patient outcome When compared with adrenaline injection alone the dual treatment significantly reduced the requirement for operative intervention and the length of hospital stay in the subgroup of patients with spurting ulcer haemorrhage In the endoscopic treatment of spurting ulcer haemorrhage heat probe thermocoagulation should be added after adrenaline injection