Wai Mo Hui

A retrospective and prospective study on the safety of discharging selected patients with duodenal ulcer bleeding on the same day as endoscopy

BACKGROUNDnLow risk of rebleeding has been observed in patients with gastrointestinal bleeding due to peptic ulcer without high-risk stigmata of recent hemorrhage. We aimed to evaluate the safety and acceptability of an aggressive early discharge policy in those patients admitted with upper gastrointestinal bleeding due to duodenal ulcers without high-risk stigmata of recent hemorrhage.nnnMETHODnRetrospective analysis was carried out in bleeding ulcer patients less than 60 years of age with stable vital signs and no stigmata or only flat spots on endoscopy. A prospective study was then performed that included only duodenal ulcer patients less than 60 years of age with stable vital signs, no concomitant serious medical illness, and no stigmata of recent hemorrhage. These patients were discharged on the same day that endoscopy was performed.nnnRESULTSnDuring a period of 18 months, 72 patients satisfied the criteria in the retrospective study. The mean hospital stay was 1.4 days (range, 1 to 5). There were no episodes of rebleeding nor significant drops in hemoglobin level 2 weeks after discharge (10.8 gm/dL +/- 1.4 vs 11.0 gm/dL +/- 1.5). Seventy-five patients were recruited into the prospective study. None of them had rebleeding nor significant drops in hemoglobin 1 week after discharge (12.1 gm/dL +/- 1.8 vs 11.7 gm/dL +/- 2.5).nnnCONCLUSIONnWe conclude that patients with gastrointestinal bleeding who have clean-based duodenal ulcers and are stable on admission can be safely discharged on the same day as endoscopy.

Prostaglandin E1 (Misoprostol) overcomes the adverse effect of chronic cigarette smoking on duodenal ulcer healing

Chronic cigarette smoking adversely affects duodenal ulcer healing despite treatment by potent gastric acid-reducing agents. Prostaglandins of the E series possess antisecretory and cytoprotective properties and theoretically offer advantages over existing therapeutic agents. A double-blind randomized study was performed to compare complete duodenal ulcer healing as assessed by endoscopies every two weeks for up to 12 weeks. Two hundred twenty-nine patients were randomized to receive misoprostol, an orally stable synthetic derivative of prostaglandin E1, in 200-μg or 300-μg qid dosages, or placebo. Life-table analysis showed that (1) both regimens of misoprostol were significantly more effective than placebo, achieving healing rates of 61% and 71%, respectively, at four weeks, and (2) cigarette smoking significantly impaired healing by placebo but not by misoprostol. In fact, the time-healing curves of smokers and nonsmokers on the higher dose of misoprostol completely overlapped. Furthermore, delayed treatment and large ulcer diameter adversely affected healing by misoprostol in smokers, whereas in nonsmokers, high basal and maximal acid output were unfavorable. Misoprostol is recommended for the treatment of duodenal ulcer, particularly in chronic smokers early in a given period of symptoms.

High prevalence of mixed infections by Helicobacter pylori in Hong Kong: Metronidazole sensitivity and overall genotype

Diversity in metronidazole susceptibility and genotypes of Helicobacter pylori have been reported with varying results in different areas.

E-cadherin promoter hypermethylation induced by interleukin-1β treatment or H. pylori infection in human gastric cancer cell lines

Interleukin-1beta is up-regulated in the presence of Helicobacter pylori infection. H. pylori infection was associated with E-cadherin methylation. In this study, we examined if IL-1beta could induce promoter methylation of E-cadherin in human gastric cancer cell lines TMK-1, MKN-74 and MKN-7. Cells were treated with IL-1beta (0.025, 0.1, 0.25, 1.0, 2.5 ng/mL) for 6, 12 and 24h. Methylation status was determined by MSP and sequencing. The effects of IL-1beta or H.pylori on the cells, and after blockade with interleukin-1 receptor antagonist (IL-1ra) were tested. Promoter methylation of E-cadherin was induced in all three cells treated with IL-1beta or co-cultured with H. pylori. Treatment of IL-1ra could reverse the phenomena. Our study indicated that IL-1beta is an important step in mediating E-cadherin methylation.

Persistence of Campylobacter pyloridis despite healing of duodenal ulcer and improvement of accompanying duodenitis and gastritis

Campylobacter pyloridis has been associated with antral gastritis and duodenal ulcer. To study the pathogenetic role of these organisms in duodenal ulcer, endoscopic biopsies, two from the first part of duodenum, four from antrum, and four from body and fundus, were taken before and after four weeks of cimetidine treatment (1.2 g/day) from 67 patients with active duodenal ulcer. The biopsies were examined for the presence and severity of any inflammation by two independent pathologists in the absence of any clinical information and for the occurrence and density ofCampylobacter pyloridis by culture and Warthin-Starry stain. Before treatment, inflammation was present in 71.1, 100, and 25.8%, while the organisms were present in 34.3, 91.0, and 79.1% of the duodenal, antral, and fundal biopsies, respectively. With complete healing of duodenal ulcer, inflammation was present in 48.9, 98.2, and 30.2%, while the organisms were present in 25, 76.7, and 63.3% of the respective mucosae. With ulcer healing, duodenitis became significantly milder (P<0.05). With improvement of gastritis and duodenitis, there was no significant change in the occurrence and density ofCampylobacter pyloridis. These findings indicate that healing of duodenal ulcer is not influenced by the presence ofCampylobacter pyloridis, which is frequently found in the gastroduodenal mucosa of patients with duodenal ulcer, but does not appear to be associated with mucosal inflammation except in the antrum.

Association between Helicobacter pylori infection and interleukin 1β polymorphism predispose to CpG island methylation in gastric cancer

Interleukin1β (IL1β) is upregulated in the presence of Helicobacter pylori infection.1 IL1β polymorphisms with T/T and T/C genotypes enhance IL1β production, and are associated with an increased risk of H pylori -induced hypochlorhydria2 and gastric cancer.3 The relationship between H pylori and CpG island methylation has been repeatedly reported.4–6 It has been reported that IL1β can modulate CpG island methylation through activation of DNA methyltransferase and hence repress gene expression.7 We therefore hypothesised that patients with H pylori infection and IL1 polymorphism, by the production of IL1β, are predisposed to gastric cancer development through the CpG island methylation pathway.nnWe obtained surgical specimens and their corresponding peripheral blood from 98 consecutive patients with gastric cancer admitted to Queen Mary Hospital, Hong Kong. This study was approved by the ethics committee. The …

Effect of sucralfate and cimetidine on duodenal ulcer-associated antral gastritis and Campylobacter pylori☆

The course of gastritis and Campylobacter pylori was studied in a single-blind randomized trial comparing cimetidine 200 mg three times a day and 400 mg at night and sucralfate 1 g four times a day orally for four weeks in 140 patients with proved duodenal ulcer. At least two antral biopsies were performed during endoscopy before entry and at the end of four weeks. The activity and the degree of chronic inflammation, as assessed histologically by the degree of infiltration of, respectively, polymorphs and chronic inflammatory cells, were graded blindly by two pathologists as nil, mild, moderate, or severe. The density of C. pylori, as assessed after Warthin-Starry stain, was similarly graded. Ulcer-healing rates were comparable in the cimetidine (73.2 percent) and sucralfate (79.7 percent) groups. Improvement of the activity of gastritis occurred significantly (p less than 0.05) more frequently in the sucralfate (33.3 percent) than in the cimetidine group (18.3 percent), and remained so (p less than 0.05) when only patients with healed ulcer were compared. The density of C. pylori decreased significantly in the sucralfate group after treatment (p less than 0.01) but not in the cimetidine group. The 12-month ulcer relapse rates were significantly (p less than 0.05) lower by life-table analysis in patients healed with sucralfate than in those healed with cimetidine and were unaffected by either the density of Campylobacter in either group or the improvement of the gastritis. It is concluded that sucralfate improves duodenal ulcer-associated antral gastritis and decreases the density of C. pylori, and that factors other than bacterial density and antral gastritis may be responsible for the advantage of sucralfate over cimetidine in ulcer relapse.

Pathophysiology of Gastroesophageal Reflux Diseases in Chinese—Role of Transient Lower Esophageal Sphincter Relaxation and Esophageal Motor Dysfunction

BACKGROUND AND AIMS:Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism for gastroesophageal reflux in the Western population. The major reflux mechanism in Chinese patients with GERD has not been studied before.METHODS:Fifty-four patients with GERD and 28 controls underwent stationary baseline manometry and the 24-h ambulatory esophageal pH monitoring. TLESRs were measured before and after an 850 kcal meal in the supine position. Primary peristalsis, secondary peristalsis, and esophageal acid clearance were measured by esophageal manometry.RESULTS:Total time esophageal pH ≤ 4 (7.3 vs 1.5, p = 0.001) was significantly higher in patients with GERD when compared to controls. Majority of acid reflux episodes was due to TLESR in both patients with GERD and controls. The frequency of TLESRs after meal was similar between patients with GERD and controls (1.0 vs 1.3/h, p = 0.34). There was no difference in the distribution of reflux mechanism between patients with GERD and controls. However, patients with GERD had a significantly lower successful primary peristalsis (59% vs 70%, p = 0.043) when compared to controls.CONCLUSION:The frequency of TLESRs was similar between patients with GERD and controls during stationary manometry. Primary peristalsis was impaired in Chinese patients with GERD. Esophageal motor dysfunction may contribute to the pathophysiology of GERD in the Chinese population.

Chronic Antral Gastritis in Duodenal Ulcer: Natural History and Treatment With Prostaglandin E1

The natural history of chronic antral gastritis in relation to the healing of duodenal ulcer and its response to treatment, if any, are unknown. We performed a double-blind controlled trial using an oral prostaglandin E1, misoprostol, in 229 patients with active duodenal ulcer randomized to receive placebo (n = 76), misoprostol 200 micrograms (n = 77), or misoprostol 300 micrograms (n = 76), q.i.d. orally. Healing of duodenal ulcer was assessed biweekly up to 12 wk by endoscopy, during which procedures at least two antral and two fundal biopsy specimens were taken. The activity and the degree of chronic inflammation of gastritis, as assessed histologically by the infiltration of polymorphs and chronic inflammatory cells, respectively, was graded blindly by two pathologists as nil, mild, moderate, or severe. Before treatment, 99% of patients had chronic antral gastritis and 1.5% had chronic fundal gastritis. In the placebo group, healed duodenal ulcer was associated with significantly (p less than 0.01, life table analysis) higher incidence of improvement of the activity of the antral gastritis (nil or mild as endpoint) than unhealed ulcer (30% vs. 4% at week 8). Irrespective of whether duodenal ulcer was healed or unhealed, significantly (p less than 0.01) more patients on misoprostol (50% at week 8) showed improvement (nil or mild as endpoint) than the placebo group. The degree of chronic inflammation of the antral gastritis showed similar significant changes in favor of misoprostol. Smoking and alcohol intake had no significant effect on the improvement of chronic antral gastritis. In conclusion, healing of duodenal ulcer was associated with improvement of the activity of chronic antral gastritis, which, as shown for the first time, could be further enhanced by a therapeutic agent--prostaglandin E1.

Maintenance therapy for duodenal ulcer: A randomized controlled comparison of seven forms of treatment

PURPOSEnWe performed a randomized controlled trial to compare the efficacy of seven forms of maintenance treatment of duodenal ulcer, including a mealtime regimen of antacids.nnnPATIENTS AND METHODSnWe randomized 785 patients with healed duodenal ulcer to receive: (1) no treatment; (2) mealtime antacids with an acid-neutralizing capacity of 80 mmol/day; (3) an antidepressant, trimipramine 25 mg; (4) an anticholinergic, pirenzepine 50 mg; (5) cimetidine 200 mg; (6) cimetidine 400 mg; (7) ranitidine 150 mg; or (8) sucralfate 1 g twice a day. Symptomatology and side effects were assessed every 2 months and endoscopy was performed every 4 months up to 1 year.nnnRESULTSnThe patients were comparable in the majority of clinical characteristics before entry. The cumulative percentages of patients with relapse of ulcers at 12 months by life-table analysis were 61% with no treatment, 38% with mealtime antacids, 60% with trimipramine, 52% with pirenzepine, 46% with cimetidine 200 mg, 44% with cimetidine 400 mg, 30% with ranitidine 150 mg, and 40% with sucralfate. Cimetidine 400 mg, antacids, ranitidine 150 mg, and sucralfate were significantly better than no treatment and the other forms of treatment. Ranitidine was significantly better than antacids, cimetidine, and sucralfate in preventing endoscopically documented duodenal ulcer relapse by multiple comparison at 12 months, but not by life-table analysis nor when symptomatic relapses were compared. No significant difference was detected among antacids, cimetidine, and sucralfate. No major side effects occurred with the seven forms of treatment, but those receiving antacids had the highest incidence of minor adverse events (26%).nnnCONCLUSIONnThis study suggests that mealtime antacids are as effective as H2-receptor antagonists and sucralfate in the maintenance treatment of duodenal ulcer disease, but have to be taken three times a day and had the highest incidence of reported minor adverse events. The relapse rate was lower with ranitidine than with cimetidine, sucralfate, and antacids, but the difference was small and may not be clinically important.