Kim W.L. Au

High Incidence of Mortality and Recurrent Bleeding in Patients With Helicobacter pylori–Negative Idiopathic Bleeding Ulcers

BACKGROUND & AIMS The long-term prognosis of peptic ulcers associated with neither Helicobacter pylori nor nonsteroidal anti-inflammatory drugs (NSAIDs) is unknown. METHODS This 7-year prospective cohort study recruited patients with bleeding ulcers from January to December 2000. H pylori-negative idiopathic bleeding ulcers were defined as having tested negative for H pylori, having no exposure to aspirin or analgesics within 4 weeks before endoscopy, and having no other identifiable causative factors. After ulcers healed, patients were divided into 2 groups: patients with prior H pylori-negative idiopathic bleeding ulcers (H pylori-negative idiopathic ulcer cohort; n = 120) and those with H pylori-positive, NSAID-negative bleeding ulcers who received eradication therapy (H pylori ulcer cohort; n = 213). Both groups were followed for <or=7 years without gastroprotective therapy. The primary endpoints were recurrent ulcer bleeding and mortality. RESULTS The 7-year cumulative incidence of recurrent ulcer bleeding was 42.3% (95% CI, 36.5%-48.1%) in the H pylori-negative idiopathic ulcer cohort and 11.2% (95% CI, 8.8%-13.6%) in the H pylori ulcer cohort (a difference of 31.1%; 95% CI, 27.7%-34.5%; P < .0001). Significantly more patients died in the H pylori-negative idiopathic ulcer cohort (87.6%; 95% CI, 83.0%-92.2%) than in the H pylori ulcer cohort (37.3%; 95% CI, 34.0%-40.6%) with a difference of 50.3% (95% CI, 49.0%-51.6%; P < .0001). CONCLUSIONS Patients with history of H pylori-negative idiopathic bleeding ulcers have a high risk of recurrent ulcer bleeding and mortality.

A comparison of angiographic embolization with surgery after failed endoscopic hemostasis to bleeding peptic ulcers

BACKGROUND In patients with bleeding peptic ulcers in whom endoscopic hemostasis fails, surgery usually follows. Transarterial embolization (TAE) has been proposed as an alternative. OBJECTIVE To compare the outcomes of TAE and salvage surgery for patients with peptic ulcers in whom endoscopic hemostasis failed. DESIGN Retrospective study. SETTING A university hospital. PATIENTS Patients with peptic ulcer bleeding in whom endoscopic hemostasis failed. INTERVENTIONS TAE and surgery as salvage of peptic ulcer bleeding. MAIN OUTCOMES MEASUREMENTS All-cause mortality, rebleeding, reintervention, and complication rate. RESULTS Thirty-two patients underwent TAE and 56 underwent surgery. In those who underwent TAE, the bleeding vessels were gastroduodenal artery (25 patients), left gastric artery (4 patients), right gastric artery (2 patients), and splenic artery (1 patient). Active extravasation was seen in 15 patients (46.9%). Embolization was attempted in 26 patients, and angiographic coiling was successful in 23 patients (88.5%). Bleeding recurred in 11 patients (34.4%) in the TAE group and in 7 patients (12.5%) in the surgery group (P=.01). More complications were observed in patients who underwent surgery (40.6% vs 67.9%, P=.01). There was no difference in 30-day mortality (25% vs 30.4%, P=.77), mean length of hospital stay (17.3 vs 21.6 days, P=.09), and need for transfusion (15.6 vs 14.2 units, P=.60) between the TAE and surgery groups. LIMITATIONS Retrospective study. CONCLUSIONS In patients with ulcer bleeding after failed endoscopic hemostasis, TAE reduces the need for surgery without increasing the overall mortality and is associated with fewer complications.

Gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN): an industry-independent, double-blind, double-dummy, randomised trial

BACKGROUND Present guidelines are conflicting for patients at high risk of both cardiovascular and gastrointestinal events who continue to require non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesised that a cyclooxygenase-2-selective NSAID plus proton-pump inhibitor is superior to a non-selective NSAID plus proton-pump inhibitor for prevention of recurrent ulcer bleeding in concomitant users of aspirin with previous ulcer bleeding. METHODS For this industry-independent, double-blind, double-dummy, randomised trial done in one academic hospital in Hong Kong, we screened patients with arthritis and cardiothrombotic diseases who were presenting with upper gastrointestinal bleeding, were on NSAIDs, and require concomitant aspirin. After ulcer healing, an independent staff member randomly assigned (1:1) patients who were negative for Helicobacter pylori with a computer-generated list of random numbers to receive oral administrations of either celecoxib 100 mg twice per day plus esomeprazole 20 mg once per day or naproxen 500 mg twice per day plus esomeprazole 20 mg once per day for 18 months. All patients resumed aspirin 80 mg once per day. Both patients and investigators were masked to their treatments. The primary endpoint was recurrent upper gastrointestinal bleeding within 18 months. The primary endpoint and secondary safety endpoints were analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, number NCT00153660. FINDINGS Between May 24, 2005, and Nov 28, 2012, we enrolled 514 patients, assigning 257 patients to each study group, all of whom were included in the intention-to-treat population. Recurrent upper gastrointestinal bleeding occurred in 14 patients in the celecoxib group (nine gastric ulcers and five duodenal ulcers) and 31 patients in the naproxen group (25 gastric ulcers, three duodenal ulcers, one gastric ulcer and duodenal ulcer, and two bleeding erosions). The cumulative incidence of recurrent bleeding in 18 months was 5·6% (95% CI 3·3-9·2) in the celecoxib group and 12·3% (8·8-17·1) in the naproxen group (p=0·008; crude hazard ratio 0·44, 95% CI 0·23-0·82; p=0·010). Excluding patients who reached study endpoints, 21 (8%) patients in the celecoxib group and 17 (7%) patients in the naproxen group had adverse events leading to discontinuation of treatment. No treatment-related deaths occurred during the study. INTERPRETATION In patients at high risk of both cardiovascular and gastrointestinal events who require concomitant aspirin and NSAID, celecoxib plus proton-pump inhibitor is the preferred treatment to reduce the risk of recurrent upper gastrointestinal bleeding. Naproxen should be avoided despite its perceived cardiovascular safety. FUNDING The Research Grant Council of Hong Kong.

Chinese translation and validation of the Walking Impairment Questionnaire in patients with peripheral artery disease

The Walking Impairment Questionnaire (WIQ) is a frequently used questionnaire to evaluate patients with intermittent claudication on four subscales: pain severity, walking distance, walking speed and the ability to climb stairs. The aim of this study is to translate and validate the WIQ in Chinese. After translation and cultural adaptation of the WIQ, 134 patients with intermittent claudication completed the Chinese WIQ and European Quality of Life 5 Dimension (EQ-5D). Walking distances were determined by the 6-minute walk test (6MWT). Correlations between the WIQ, quality of life questionnaire and walking distances were calculated to determine validity. Reliability and internal consistency were determined using the intra-class correlation coefficient (ICC) and Cronbach’s alpha (α), respectively. Significant correlations were found between the WIQ score, initial claudication distance (ICD), absolute claudication distance (ACD) and all domains of the EQ-5D (all p ≤ 0.01). Test—retest reliability (ICC = 0.74) and the overall internal consistency determined (α = 0.90) showed good agreement. A lower WIQ score corresponded to shorter walking distances. In conclusion, this study showed that the Chinese version of the WIQ is a valid, reliable and clinically relevant instrument for assessing walking impairment in patients with intermittent claudication.

A prospective, randomized study of the patency period of the plastic antireflux biliary stent: an interim analysis

BACKGROUND There is as yet no ideal design of a plastic biliary stent with the longest patency period. OBJECTIVE To study the safety and effective patency period of a new plastic antireflux biliary stent in the clinical setting. DESIGN We conducted a prospective, randomized trial to compare the patency of 2 similar plastic biliary stents, one of which has an antiduodenobiliary reflux property. SETTING The study was conducted at 2 separate tertiary centers in 2 countries. PATIENTS Patients with inoperable distal malignant biliary obstruction were recruited. INTERVENTIONS One of the 2 types of plastic stents under study was randomly chosen and inserted in the common bile duct of the study subjects. The subjects were followed until the end of study or occlusion occurrence. MAIN OUTCOME MEASUREMENTS Our primary endpoint was the time to stent occlusion in days, with stent-related adverse events and all-cause mortality the secondary endpoints. RESULTS A total of 16 subjects were recruited for the study; 7 were allocated to group A (ordinary Tannenbaum stent) and 9 to group B (antireflux biliary stent). Five of 7 subjects (71%) in group B had stent occlusion within 8 days, and the primary end point was reached in all 7 subjects within 30 days, whereas the primary endpoint was not reached within 30 days in any of the subjects in group A. Our data showed a significantly shorter stent patency period in group B compared with group A (P < .003). LIMITATIONS Small sample size. CONCLUSION Routine use of antireflux plastic biliary stents in the palliative management of malignant biliary obstructions cannot be recommended at present. (Clinical trial registration number: NCT01142921.).

Prophylactic angiographic embolisation after endoscopic control of bleeding to high-risk peptic ulcers: a randomised controlled trial

Objectives In the management of patients with bleeding peptic ulcers, recurrent bleeding is associated with high mortality. We investigated if added angiographic embolisation after endoscopic haemostasis to high-risk ulcers could reduce recurrent bleeding. Design After endoscopic haemostasis to their bleeding gastroduodenal ulcers, we randomised patients with at least one of these criteria (ulcers≥20 mm in size, spurting bleeding, hypotensive shock or haemoglobin<9 g/dL) to receive added angiographic embolisation or standard treatment. Our primary endpoint was recurrent bleeding within 30 days. Results Between January 2010 and July 2014, 241 patients were randomised (added angiographic embolisation n=118, standard treatment n=123); 22 of 118 patients (18.6%) randomised to angiography did not receive embolisation. In an intention-to-treat analysis, 12 (10.2%) in the embolisation and 14 (11.4%) in the standard treatment group reached the primary endpoint (HR 1.14, 95% CI 0.53 to 2.46; p=0.745). The rate of reinterventions (13 vs 17; p=0.510) and deaths (3 vs 5, p=0.519) were similar. In a per-protocol analysis, 6 of 96 (6.2%) rebled after embolisation compared with 14 of 123 (11.4%) in the standard treatment group (HR 1.89, 95% CI 0.73 to 4.92; p=0.192). None of 96 patients died after embolisation compared with 5 (4.1%) deaths in the standard treatment group (p=0.108). In a posthoc analysis, embolisation reduced recurrent bleeding only in patients with ulcers≥15 mm in size (2 (4.5%) vs 12 (23.1%); p=0.027). Conclusions After endoscopic haemostasis, added embolisation does not reduce recurrent bleeding. Trial registration number NCT01142180.