Enders K. Ng

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.

Screening for gastric cancer in Asia: current evidence and practice

Gastric cancer is the second most common cause of death from cancer in Asia. Although surgery is the standard treatment for this disease, early detection and treatment is the only way to reduce mortality. This Review summarises the epidemiology of gastric cancer, and the evidence for, and current practices of, screening in Asia. Few Asian countries have implemented a national screening programme for gastric cancer; most have adopted opportunistic screening of high-risk individuals only. Although screening by endoscopy seems to be the most accurate method for detection of gastric cancer, the availability of endoscopic instruments and expertise for mass screening remains questionable--even in developed countries such as Japan. Therefore, barium studies or serum-pepsinogen testing are sometimes used as the initial screening tool in some countries, and patients with abnormal results are screened by endoscopy. Despite the strong link between infection with Helicobacter pylori and gastric cancer, more data are needed to define the role of its eradication in the prevention of gastric cancer in Asia. At present, there is a paucity of quality data from Asia to lend support for screening for gastric cancer.

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...

Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication

Background and aim: Gastric intestinal metaplasia (IM) is generally considered to be a precancerous lesion in the gastric carcinogenesis cascade. This study identified the risk factors associated with progression of IM in a randomised control study. Subjects and methods: A total of 587 Helicobacter pylori infected subjects were randomised to receive a one week course of anti-Helicobacter therapy (omeprazole, amoxicillin, and clarithromycin (OAC)) or placebo. Subjects underwent endoscopy with biopsy at baseline and at five years. Severity of IM was graded according to the updated Sydney classification and progression was defined as worsening of IM scores at five years in either the antrum or corpus, or development of neoplasia. Backward stepwise multiple logistic regression was used to identify independent risk factors associated with IM progression. Results: Of 435 subjects (220 in the OAC and 215 in the placebo group) available for analysis, 10 developed gastric cancer and three had dysplasia. Overall progression of IM was noted in 52.9% of subjects. Univariate analysis showed that persistent H pylori infection, age >45 years, male subjects, alcohol use, and drinking water from a well were significantly associated with IM progression. Duodenal ulcer and OAC treatment were associated with a reduced risk of histological progression. Progression of IM was more frequent in those with more extensive and more severe IM at baseline. With multiple logistic regression, duodenal ulcer (odds ratio (OR) 0.23 (95% confidence interval (CI) 0.09–0.58)) was found to be an independent protective factor against IM progression. Conversely, persistent H pylori infection (OR 2.13 (95% CI 1.41–3.24)), age >45 years (OR 1.92 (95% CI 1.18–3.11)), alcohol use (OR 1.67 (95% CI 1.07–2.62)), and drinking water from a well (OR 1.74 (95% CI 1.13–2.67)) were independent risk factors associated with IM progression. Conclusion: Eradication of H pylori is protective against progression of premalignant gastric lesions.

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.

Cyclooxygenase-2 Expression in Helicobacter pylori-Associated Premalignant and Malignant Gastric Lesions

Expression of cyclooxygenase-2 (COX-2) in various stages of the Helicobacter pylori-associated gastric carcinogenesis pathway has not been elucidated. We investigated the distribution and intensity of COX-2 expression in premalignant and malignant gastric lesions, and monitored the changes after H. pylori eradication. Gastric biopsies from H. pylori-infected patients with chronic active gastritis, gastric atrophy, intestinal metaplasia (IM), gastric adenocarcinoma, and noninfected controls were studied. Expression of COX-2 was evaluated by immunohistochemistry and in situ hybridization. Endoscopic biopsies were repeated 1 year after successful eradication of H. pylori in a group of IM patients for comparing COX-2 expression and progression of IM. In all H. pylori-infected patients, COX-2 expression was predominantly found in the foveolar and glandular epithelium and, to a lesser extent, in the lamina propria. In the noninfected group, only 35% of cases demonstrated weak COX-2 expression. Intensity of COX-2 was not significantly different between the chronic active gastritis, gastric atrophy, IM, and gastric adenocarcinoma groups. In 17 patients with IM, COX-2 expressions in the epithelial cells and stromal cells were reduced 1 year after H. pylori eradication. However, the changes in COX-2 expression did not correlate with progression/regression of IM. Both premalignant and malignant gastric lesions demonstrate strong COX-2 expression. Successful eradication of H. pylori leads to down-regulation of COX-2 expression but failed to reverse IM at 1 year.

Antibacterial Treatment of Gastric Ulcers Associated with Helicobacter pylori

BACKGROUND There is a strong association between infection with Helicobacter pylori and gastric ulcers that are unrelated to the use of nonsteroidal antiinflammatory medications. We studied the efficacy of antibacterial therapy without medication to suppress gastric acid for the treatment of patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal agents. METHODS Patients with gastric ulcers seen on endoscopy and with H. pylori infection confirmed by smear or culture were randomly assigned to receive either a one-week course of antibacterial agents (120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, each given orally four times a day) or a four-week course of omeprazole (20 mg orally per day). Follow-up endoscopies were performed after five and nine weeks. The patients and their physicians were aware of the treatment assignments, but the endoscopists were not. RESULTS A total of 100 patients were randomly assigned to treatment, and 85 completed the trial. At five weeks, H. pylori had been eradicated in 41 of the 45 patients in the antibacterial-treatment group (91.1 percent; 95 percent confidence interval, 82.9 to 99.3) and in 5 of the 40 in the omeprazole group (12.5 percent; 95 percent confidence interval, 2.3 to 22.7; P < 0.001). The gastric ulcers were healed in 38 of the patients treated with antibacterial drugs (84.4 percent; 95 percent confidence interval, 73.9 to 95.0) and in 29 of those treated with omeprazole (72.5 percent; 95 percent confidence interval, 58.6 to 86.4; P = 0.28). At nine weeks, ulcer healing was confirmed in 43 of the patients receiving antibacterial therapy and in 37 of those receiving omeprazole (P = 1.0). The mean (+/- SD) duration of pain during the first week of treatment was 1.9 +/- 2.6 days in the omeprazole group, as compared with 3.6 +/- 3.0 days in the antibacterial-treatment group (P = 0.004). One year after treatment, recurrent gastric ulcers were detected in 1 of 22 patients (4.5 percent) in the antibacterial-treatment group and in 12 of 23 (52.2 percent) in the omeprazole group (P = 0.001). H. pylori was detected in the 1 patient with a recurrent ulcer who had received antibacterial treatment and in 10 of the 12 patients with recurrent ulcers who had received omeprazole. CONCLUSIONS In patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal antiinflammatory drugs, one week of antibacterial therapy without acid suppression heals the ulcers as well as omeprazole and reduces the rate of their recurrence.

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

The Effect of Endoscopic Therapy in Patients Receiving Omeprazole for Bleeding Ulcers with Nonbleeding Visible Vessels or Adherent Clots: A Randomized Comparison

Context Endoscopic hemostasis plus omeprazole in patients with actively bleeding ulcers prevents recurrent bleeding. Are both needed if endoscopy shows a nonbleeding vessel or nonbleeding clot? Contribution This randomized trial included 156 patients admitted for bleeding whose endoscopies, performed within 24 hours of admission, showed ulcers with nonbleeding vessels or adherent clots. Approximately 12% of patients receiving omeprazole alone had recurrent bleeding within 30 days compared with approximately 1% who received endoscopic hemostasis (thermocoagulation and epinephrine injection) plus omeprazole. Implications Endoscopic hemostasis plus omeprazole better prevents recurrent bleeding than does omeprazole alone in patients who have recently bled from an ulcer but do not have actively bleeding vessels at endoscopy. The Editors Endoscopic hemostasis is effective in controlling bleeding from peptic ulcers. The optimal treatment of ulcers with nonbleeding visible vessels and adherent clots, however, is unclear. The controversy arises from variability in endoscopic diagnosis as well as in the standard treatment strategies adopted by endoscopists for ulcers with adherent clots. At least two studies have shown that even experienced endoscopists have different definitions of stigmata at the ulcer base (1, 2). Among the stigmata of hemorrhage, clot and protuberant vessels are the most difficult to differentiate. After a clot has been diagnosed, approaches to management are quite different. Some clinicians flush the clot with a syringe or oral irrigator, which in general produces rather weak irrigate (3), whereas others advocate targeted irrigation using thermal probes (4). With these methods of irrigation, the success rates for exposing the underlying stigmata range from 9% (3) to 57% (4). Even after removal of blood clots, it is not certain whether endoscopic therapy prevents recurrent bleeding or actually provokes it. Randomized, controlled trials of endoscopic therapy versus no endoscopic therapy have yielded conflicting results (5, 6), and meta-analysis does not support routine use of endoscopic therapy (7). The advent of proton-pump inhibitors changed the standard of practice in the management of bleeding ulcers. Two studies from India have demonstrated the benefit of high-dose oral omeprazole for peptic ulcer bleeding. Khuroo and colleagues (8) demonstrated that a 5-day course of oral omeprazole, 40 mg twice daily, reduced recurrent bleeding even without endoscopic therapy. The benefit of omeprazole was most remarkable among patients with visible vessels or adherent clots at the ulcer bases. Javid and associates (9) showed that the same omeprazole regimen in combination with endoscopic injection prevented recurrent bleeding. Their study, however, failed to demonstrate a distinct advantage of omeprazole in patients with nonbleeding visible vessels and adherent clots. A recent randomized study by Jensen and coworkers (10) compared twice-daily administration of an oral proton-pump inhibitor with endoscopic therapy in 32 patients who were at high risk for ulcer hemorrhage. Six of 17 medically treated patients had recurrent bleeding compared with none of 15 patients treated endoscopically. The study was discontinued prematurely because of the dramatic difference in clinical outcome. Study limitations included small sample size, unequal distribution of confounding factors, and lack of difference in clinical end points (11). The effectiveness of proton-pump inhibitors alone for ulcers that are not actively bleeding but have stigmata of a nonbleeding visible vessel or an adherent clot remains undetermined. We previously demonstrated that high-dose intravenous omeprazole as an adjunct to endoscopic therapy substantially reduced risk for recurrent bleeding, repeated endoscopy, frequency of blood transfusion, and duration of hospitalization (12). Subgroup analysis suggested that actively bleeding ulcers, as well as ulcers with a nonbleeding visible vessel or an adherent clot, benefited from the treatment. In the current study, we compared high-dose intravenous omeprazole infusion plus endoscopic therapy with intravenous omeprazole infusion alone for prevention of recurrent bleeding from ulcers with a nonbleeding visible vessel or an adherent clot. Methods Description of the Study and Patients We performed a single-center randomized trial comparing the combination of endoscopic therapy and high-dose omeprazole infusion with high-dose omeprazole infusion alone for treatment of ulcers with a nonbleeding visible vessel or an adherent clot. This study was conducted at the Endoscopy Center of the Prince of Wales Hospital in Hong Kong. The clinical trials ethics committee of the faculty of medicine of the Chinese University of Hong Kong approved the study protocol. Consecutive patients who presented with signs of upper gastrointestinal bleeding underwent endoscopic examination within 24 hours of hospital admission. Patients who were in shock or were vomiting fresh blood at presentation underwent urgent endoscopy as soon as their hemodynamic conditions stabilized. All endoscopic examinations were performed by using a dual-channel endoscope (Olympus 2T200, Olympus Japan Co., Tokyo, Japan). All participants provided written informed consent before the endoscopic examinations. At endoscopy, gastric or duodenal ulcers were examined to determine whether they were actively bleeding (spurting or oozing) or showed nonbleeding visible vessels or adherent clots. A nonbleeding visible vessel was defined as a protuberant discoloration according to the National Institutes of Health 1989 consensus statement (13). Ulcers with overlying clots were irrigated for 5 minutes with a 3.2-mm heater probe (Olympus CD-10Z, Olympus Japan Co.) to remove loosely attached clots and debris. An adherent clot was defined as a blood clot that remained attached to the ulcer base after the 5-minute period of irrigation (3). Patients met the inclusion criteria if they were at least 16 years of age and had benign gastroduodenal ulcers showing nonbleeding visible vessels or adherent clots at endoscopy. Patients were excluded if they 1) had actively bleeding ulcers, including ulcers in which endoscopic irrigation procedures provoked bleeding before treatment; 2) had had endoscopic therapy for bleeding ulcer within the past 30 days; 3) had a history of gastric surgery; 4) were pregnant; 5) had malignant ulcers; or 6) did not provide written informed consent. Specimens were taken from the antrum for urease biopsy and histologic examination to determine Helicobacter pylori status. Patients found to have malignant ulcers after initial enrollment were excluded from the analysis. Randomization and Treatment Protocol Randomization was performed when ulcers were judged to show a nonbleeding visible vessel or an adherent clot after 5 minutes of irrigation. Patients were randomly assigned to receive endoscopic therapy or sham endoscopic treatment. Randomization was carried out through the use of a computer-generated list of random numbers in blocks of 10. Allocation concealment was performed by an independent research nurse who assigned treatments according to consecutive numbers in sealed opaque envelopes. Patients randomly assigned to endoscopic therapy were treated with epinephrine injection followed by thermocoagulation. Diluted epinephrine (1:10 000 dilution) was injected in 0.5-mL or 1-mL aliquots around the nonbleeding visible vessels or adherent clots to induce tissue blanching and edema. In general, approximately 5 mL of diluted epinephrine was injected. The vessels were then thermocoagulated by using a 3.2-mm heater probe (30 J for 6 seconds). The end point of endoscopic treatment was defined by the flattening or cavitation of protuberances. Adherent clots were removed by cheese-wiring using a mini-snare, and the ulcer base was again examined. Underlying vessels were coagulated in a similar fashion. In the event of provoked bleeding, cessation of bleeding and flattening or cavitation of protuberances constituted successful treatment. Patients randomly assigned to sham endoscopic treatment underwent gentle irrigation of the ulcer base using a syringe but no manipulation with the heater probe, mini-snare, or suction. Any bleeding provoked after randomization was included in the intention-to-treat analysis. All patients received intravenous omeprazole (Losec, AstraZeneca, Molndal, Sweden) after randomization. A bolus injection of omeprazole, 80 mg, was given during the endoscopic procedure and was followed immediately by a continuous infusion of 8 mg/h for 72 hours. Follow-up After the endoscopic procedure, an independent team of physicians who were blinded to treatment assignments monitored the patients in a gastroenterology ward for signs of recurrent bleeding. The endoscopists were not involved in subsequent patient management. A research nurse kept endoscopy records in opaque sealed envelopes that were not accessible to physicians, investigators, or patients. Blood pressure and pulse rate were monitored hourly during the first 24 hours and every 4 hours thereafter until discharge. After finishing 72 hours of omeprazole infusion, patients were prescribed 20 mg of oral omeprazole per day. Those who had no evidence of recurrent bleeding were discharged within 5 days of hospitalization. Patients who had positive results on urease biopsy also received a 1-week course of omeprazole (20 mg twice daily), clarithromycin (500 mg twice daily), and amoxicillin (1 g twice daily). All patients were evaluated for evidence of delayed recurrent bleeding at day 30. End Points The primary end points were recurrent ulcer bleeding before discharge and within 30 days, according to prespecified criteria. Bleeding was considered to have recurred if any of the following were documented: vomiting of fresh blood; shock (defined as a systolic blood pressure < 90 mm Hg or pulse rate > 110 b

Comparison of two-dimensional vs three-dimensional camera systems in laparoscopic surgery

AbstractBackground: The lack of depth perception and spatial orientation in video vision are the drawbacks of laparoscopic surgery. The advent of a three-dimensional camera system enables surgeons to regain binocular vision and may be advantageous in complex laparoscopic procedures. Methods: We prospectively studied two groups of surgeons (with and without experiences in laparoscopic surgery) who performed a designated standardized laparoscopic task using a two-dimensional camera system (Olympus OTV-S4) vs a three-dimensional camera system (Baxter-V. Mueller VS7700) and compared their time performances. Results: The results suggested that only experience in laparoscopic surgery had significant effect on individuals performance. We could not demonstrate any superiority of the 3D system over the 2D system. However, two-thirds of the surgeons commented that the depth perception did improve. Conclusions: With further refinement of the technology, the 3D system may improve its potential in laparoscopic surgery.