History Of Duodenal Ulcer Disease Research Articles

The long-term reinfection rate and the course of duodenal ulcer disease after eradication of Helicobacter pylori in a developing country

OBJECTIVE: The aim of this study was to evaluate the effect of Helicobacter pylori ( H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. METHODS: A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. RESULTS: The radication rate was 76% (95% CI: 67–83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8% ± 3% in yr 1, 11% ± 4% in yr 2, and 13% ± 4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. CONCLUSIONS: In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries.

The long-term reinfection rate and the course of duodenal ulcer disease after eradication of Helicobacter pylori in a developing country.

The aim of this study was to evaluate the effect of Helicobacter pylori (H. pylori) eradication on the natural history of duodenal ulcer disease and the reinfection rate after treatment in a developing country. A total of 111 H. pylori-infected patients with duodenal ulcer were treated with either omeprazole or famotidine plus two antibiotics for 2 wk. Those failed to respond to treatment were retreated with bismuth-based triple therapy. The radication rate was 76% (95% CI: 67-83%). Eventually, H. pylori was eradicated in 96 of the 111 patients (86%), who were followed-up clinically and endoscopically for a mean of 37.2 months. The cumulative reinfection rate after eradication (Kaplan-Meier) was 8%+/-3% in yr 1, 11%+/-4% in yr 2, and 13%+/-4% in yr 3. Nine of the 12 reinfections occurred during yr 1. Recurrence of duodenal ulcer was detected in five patients (5.2%), all of them during yr 1 of follow-up. Histologically, gastritis scores (according to the Sydney system) improved significantly after eradication. In a high prevalence setting, H. pylori eradication and early reinfection rates after treatment are similar to rates observed in a low prevalence environment, whereas the late reinfection rate seems to be higher. However, up to 3 yr after treatment, most treated patients are free of H. pylori infection and/or ulcer activity. Even longer follow-up studies are necessary to determine whether specific retreatment policies are necessary to maintain long term eradication in developing countries.

Lack of Reinfection after Helicobacter Pylori Eradication in Duodenal Ulcer Disease: A Prospective Study from Turin, Italy

Theobjective of our study was to assess the incidence ofreinfection and new ulceration events after demonstratedHelicobacter pylori eradication, in a cohort of patientswith recurrent duodenal ulcers.Materials and MethodsWe followed up the natural history of duodenal ulcerdisease in 115 patients (83 males, mean age 54.8 years).All of them had a previous diagnosis of recurrent duodenalulcer documented by endoscopy, and associated H. pyloriinfection as shown by histology and serology.The starting point of the study was considered theconfirmed eradication of the bacterium and DU absence atthree months after the end of antibiotic treatment. Eachpatient underwent the monitoring scheme at 6, 12 and 24months after the starting point.The presence of Helicobacter pylori infection wasjudged: 1) by histology (Giemsa staining) on biopsiesobtained during endoscopy from the antrum and thefundus; and 2) by measuring specific IgG antibodiesagainst H. pylori by a commercial enzyme-linkedimmunosorbent assay (ELISA).

Triple Versus Dual Therapy for Eradicating Helicobacter pylori and Preventing Ulcer Recurrence: A Randomized, Double-Blind, Multicenter Study of Lansoprazole, Clarithromycin, and/or Amoxicillin in Different Dosing Regimens

Objective: The efficacy and safety of dual and triple therapies with a proton pump inhibitor and antibiotic(s) for therapy of Helicobacter pylori-associated duodenal ulcer disease have been compared using results from independent studies using different methods and regimens, making interpretation difficult. In a large, double-blind, multicenter study conducted in the United States, we compared a triple therapy regimen with four dual therapy and one monotherapy regimens in the eradication of H. pylori and the prevention of ulcer recurrence. Methods: Patients with active duodenal ulcer disease or history of duodenal ulcer disease within the past year and H. pylori infection were randomized to receive one of six 14-day treatment regimens: lansoprazole 30 mg, clarithromycin 500 mg, and amoxicillin 1 gm b.i.d.; lansoprazole 30 mg b.i.d. and either clarithromycin 500 mg b.i.d. or t.i.d.; lansoprazole 30 mg b.i.d. or t.i.d. with amoxicillin 1 gm t.i.d.; or lansoprazole 30 mg t.i.d. alone. No additional acid suppression therapy followed eradication therapy. Primary efficacy endpoints were eradication of H. pylori and ulcer recurrence. Results: Of 396 patients enrolled in the study, 352 met the entry criteria for duodenal ulcer status and H. pylori positivity. At 4–6 wk after the end of therapy, H. pylori was eradicated from 94% (44 of 47) of patients receiving lansoprazole, clarithromycin, and amoxicillin triple therapy, 77% (39 of 51) of those receiving lansoprazole t.i.d./amoxicillin t.i.d., 75% (36 of 48) of those receiving lansoprazole b.i.d./clarithromycin t.i.d., 57% (28 of 49) of those receiving lansoprazole b.i.d./clarithromycin b.i.d., 53% (26 of 49) of those receiving lansoprazole b.i.d./amoxicillin t.i.d., and 2% (1 of 53) of those receiving lansoprazole monotherapy ( p ≤ 0.05, triple therapy vs each dual therapy and each dual therapy vs monotherapy). Of those patients who were documented as free of ulcer at 4–6 wk after treatment, ulcers recurred within 6 months in 7% of patients receiving triple therapy, as compared with 13–23% of patients receiving dual therapy, and 69% of patients receiving lansoprazole monotherapy. Patients who were H. pylori negative at 4–6 wk after treatment were less likely to have an ulcer recurrence than were patients who were H. pylori positive (11% [10 of 95] vs 47% [20 of 43], respectively, across treatment groups). For triple therapy and dual therapy, a similar proportion of patients reported a drug-related adverse event (23% vs 17–33%, respectively). Conclusions: In patients with active or a recent history of duodenal ulcer, a 14-day course of lansoprazole-based triple therapy without additional acid suppression therapy is highly effective in the eradication of H. pylori and in preventing ulcer recurrence. Among the dual therapies, higher eradication rates occurred when lansoprazole (with amoxicillin) or clarithromycin (with lansoprazole) was administered t.i.d. vs b.i.d., but the rates were still significantly lower than with lansoprazole triple therapy with all three drugs administered b.i.d.

Helicobacter pylori eradication in the African setting, with special reference to reinfection and duodenal ulcer recurrence.

The aim of this study was to determine the effect of Helicobacter pylori eradication on the natural history of duodenal ulcer disease, and to determine the incidence of reinfection in adult patients where H pylori had been eradicated in a community with a high prevalence of the infection. An investigator blinded study, with 24 month endoscopic follow up, in subjects where H pylori had been eradicated, and similarly treated subjects where it had not been eradicated was conducted at a tertiary referral hospital. The patients consisted of a volunteer sample of 48 patients with endoscopically proved active duodenal ulcer disease. Duodenal ulcers were healed with omeprazole, 20 mg/day. After endoscopically confirmed healing, patients were treated with either one (17 patients) or two weeks (31 patients) of 'triple therapy'. H pylori status (urease reaction, histological tests, and culture of antral biopsy specimens) was determined at entry, four weeks after the finish of triple therapy and six, 12, and 24 months after this, or whenever an endoscopically proved recurrent duodenal ulcer was found. The main outcome measures were the recurrence of duodenal ulceration, over 24 months in the eradicated and non-eradicated groups and the incidence of reinfection by H pylori in the eradicated group during this follow up period. Five patients in the eradicated group experienced a duodenal ulcer relapse, of which only three were unexplained (1 = reinfected, 1 = gastrinoma). Fifteen of 21 patients in the non-eradicated group relapsed over the same period (p < 0.001). Only two of 27 patients in the eradicated group were reinfected during the 24 month follow up period. It is concluded that H pylori eradication is an effective treatment strategy for the longterm treatment of duodenal ulcer disease, even in the high prevalence, African setting. Reinfection is uncommon.

Evidence for the essential role of Helicobacter pylori in gastric ulcer disease.

Helicobacter pylori (H pylori) eradication heals chronic active type B gastritis and dramatically changes the natural history of duodenal ulcer disease. There are few data concerning the role of anti-H pylori treatment in gastric ulcer disease. A total of 83 patients presenting with H pylori positive active gastric ulcer disease were treated with omeprazole and antibiotics (amoxicillin, ciprofloxacin, roxithromycin) in seven different clinical protocols, each of which included the attempt to eradicate H pylori infection and to evaluate the post-therapeutic course of ulcer disease. The overall proportion of H pylori eradication was 67.9% (53 of 78 patients available for follow up). Best results were obtained with two week treatment regimens comprising omeprazole 20 mg twice daily and amoxicillin 500 mg four times a day or 1000 mg twice daily (eradication > 80%). Eradication of H pylori speeds up ulcer healing, with a six week healing rate of 84.9% compared with 60% in patients with persistent H pylori infection (p = 0.0148). In a subgroup of 11 patients with refractory ulcers, H pylori eradication (n = 10) was associated with ulcer healing on continued acid suppression in nine cases. One male patient with chronic antral ulcer did not respond to treatment within the next six months (H pylori and ulcer persistence), and in one female patient a resistant body ulcer was identified as gastric lymphoma. Fifty patients with healed ulcers were followed up for one year. Patients with (n = 32) and without (n = 18) bacterial eradication had similar demographic and clinical characteristics. H pylori eradication was associated with a statistically significant reduction of ulcer recurrences (3.1 v 55.6%, p<0.001). This study concludes that H pylori eradication considerably changes the natural history of H pylori associated gastric ulcer disease. In addition, H pylori eradication speeds up ulcers healing and is associated with healing of previously refractory ulcers. Thus, treatment aimed at bacterial eradication should be considered in all patients with gastric ulcers severe enough to contemplate further treatment options.

Cigarette Smoking Inhibits Acid-Stimulated Duodenal Mucosal Bicarbonate Secretion

To determine the effect of cigarette smoking on proximal duodenal mucosal bicarbonate secretion, an important defense mechanism against acid and peptic damage. Prospective study. Clinical research laboratory in a university hospital. Thirteen healthy adults (7 smokers and 6 nonsmokers) who had no history of peptic ulcer disease. Participants smoked (1 cigarette/15 min during a period of 1 hour, smokers only) or sham smoked (puffing on an unlit cigarette) during duodenal perfusion with either saline, hydrochloric acid, or prostaglandin E2 (PGE2). Collection of proximal duodenal secretions using a modified duodenal tube with occluding balloons and quantitation of duodenal mucosal bicarbonate secretion. During sham smoking both smokers and nonsmokers had comparable basal as well as H(+)-stimulated and PGE2-stimulated duodenal mucosal bicarbonate secretion. Compared with sham smoking, smoking did not significantly alter basal bicarbonate secretion (201 mumol/cm per hour [95% CI, 152 to 250 mumol/cm per hour] compared with 178 mumol/cm per hour [CI, 134 to 222 mumol/cm per hour], respectively). However, compared with sham smoking, smoking markedly reduced (P < 0.01) the increase in duodenal bicarbonate secretion in response to luminal acidification by approximately 80% (from 242 mumol/cm per hour [CI, 41 to 443 mumol/cm per hour] to 53 mumol/cm per hour [CI, -107 to 197 mumol/cm per hour]); a decrease was observed in each participant. In contrast, smoking had no significant effect on the response to luminal PGE2. Cigarette smoking markedly inhibited acid-stimulated human duodenal mucosal bicarbonate secretion. This adverse effect of smoking may, at least in part, explain the role of cigarette smoking in the pathogenesis and natural history of duodenal ulcer disease.

Can the natural history of duodenal ulcer disease be altered?

Can the natural history of duodenal ulcer disease be altered?

HELICOBACTER PYLORI IN THE PEDIATRIC PATIENT

H. pylori is the major cause of gastritis in children and adults. Studies in children have demonstrated a specific association between H. pylori and primary gastritis. H. pylori colonization of the gastric mucosa is also important in relation to the natural history of duodenal ulcer disease. Duodenal ulcers do not appear to relapse if H. pylori is cleared from the gastric mucosa. Because of the low incidence of duodenal ulcer disease in children, a multicenter study is required to demonstrate whether this finding is true in children. To date, no specific symptoms have been associated with the presence of H. pylori gastritis in children. H. pylori gastritis may therefore be an asymptomatic condition in the majority of infected children. Further studies in relation to H. pylori gastritis and symptoms in children will be important because it should be easier to identify specific symptoms in children than in adults. H. pylori gastritis in children can be diagnosed by obtaining antral biopsy specimens for culture and histologic study during upper gastrointestinal endoscopy. Serologic study is also a sensitive and specific indicator of H. pylori infection, provided that children's sera are used to standardize the assay. Noninvasive tests such as 13C urea breath tests are very attractive for use in children but are expensive. H. pylori can be cleared from the gastric mucosa in as many as 70% of children by using a combination of metronidazole or amoxicillin with colloidal bismuth subcitrate or bismuth subsalicylate. Studies in children are important in determining the epidemiology of H. pylori. Children in Western societies are not usually colonized. Infection becomes more common with increasing age. Children in underdeveloped countries and those living in poor social conditions in Western countries are much more likely to be infected at a young age. The reason for the increased prevalence of infection among these groups is not known. There is also significant intrafamilial clustering of H. pylori infection. Again, it is unclear why the organism is clustered within households and institutions. Future studies on children will be of importance in determining whether H. pylori gastritis is a cause of specific symptoms, the epidemiology of H. pylori infection, and the possible role of the organism in the natural history of gastric cancer.

Gastric H+, K+-ATPase as a therapeutic target in peptic ulcer disease

The presence of unbuffered acid appears to be an essential contributory factor in the pathogenesis of peptic ulcer disease. Treatment has concentrated therefore on the reduction of acidity, and the last decade has seen the widespread and effective use of H2 antagonists. They are, at low doses, more successful in improving the natural history of duodenal ulcer disease than of gastric or esophageal ulceration. The H2 receptor plays a central role in activation of parietal cell acid secretion, and antagonists at this receptor block most (but not all) of the acid secretion due to even gastrinergic or muscarinic (vagal) stimulation. In hypergastrinemic states such as Zollinger-Ellison syndrome, or where acid secretion has to be inhibited by more than 20% over a 24-hr period, such as for treatment of esophagitis, NSAID damage, or gastric ulcers, the dose and frequency of administration of the currently available antagonists must be increased to achieve reliable therapy. This has led to a search for an alternative target for acid inhibitory drugs, such as the gastric acid pump, the H+,K(+)-ATPase. This article focuses on the function of this ATPase and suggests that inhibition of this pump will provide a more efficacious means of reduction of acid secretion by the stomach, hence improving and simplifying therapy of acid related diseases.

1. Introduction: Aims of the Study and a Review of the Natural History of Duodenal Ulcer Disease

The aims of the study were to determine the efficacy and safety of long-term maintenance treatment of patients with duodenal ulcer disease with ranitidine. To provide a background against which the results of this study can be judged, a review of the natural history of duodenal ulcer disease is given, together with an account of the influence that surgery and maintenance treatment with H2-receptor antagonists have had on ulcer disease. It is concluded that duodenal ulcer disease constitutes a chronic disposition to develop ulcer recurrence which persists for many decades and that patients with this condition remain at risk of developing haemorrhage, perforation, and pyloric stenosis for many years.

Duodenal ulcer disease: what role does Campylobacter pylori play?

Duodenal ulcer is a chronic relapsing condition which only became common early this century. Many pathogenic factors have been identified including excess gastric acid secretion, cigarette smoking, non-steroidal anti-inflammatory drugs and reduced mucosal defence. There is a strong association of duodenal ulceration, gastric Campylobacter pylori and antral (type-B) gastritis. The link between ulceration in the duodenum and C. pylori-associated antral gastritis may lie in the formation of gastric-type epithelium in the duodenum (gastric metaplasia). This metaplastic tissue is susceptible to C. pylori colonization and therefore to the local effects of these bacteria. Several reports suggest that duodenal ulcer relapse is more frequent in patients infected with C. pylori. These data are reviewed and a brief history of duodenal ulcer disease is presented.

Dynamic Visick grading after highly selective vagotomy.

AbstractA continuous way of assessing the results after highly selective vagotomy (HSV) is presented, as applied in 262 patients operated on for duodenal ulcer. Regrading of all patients who showed recurrences at any time is permitted according to their actual condition at each grading moment. The dynamic Visick grading shows the same percentage of success at each assessment in spite of an ever increasing percentage of recurrences— many defined failures appear to be temporary failures—which is accounted for in this type of presentation.The conclusion is that HSV appears to favorably change the natural history of duodenal ulcer disease in 94% of patients at any time of assessment and that 3% of patients in the present series are graded as permanent failures.

Duodenal ulceration: review of 110 cases.

This paper describes 110 cases of childhood duodenal ulcer, which were diagnosed over 26 years: 63 were diagnosed by barium meal examination; 47 by upper gastrointestinal endoscopy. The mean age at diagnosis was 11.2 years, with symptoms reported in 46% before 10 years and in 15% before 6 years of age. There was often a considerable delay in diagnosis, particularly in the younger age group. Nocturnal pain (61%) and a close family history of duodenal ulcer disease (62%) were the most valuable pointers to the diagnosis. Fifteen children had required surgery for persistent symptoms. Thirty four had received treatment with an H2 receptor antagonist, and all but four had had a satisfactory initial response. Seventy per cent relapsed within six months of discontinuing treatment, and long term maintenance treatment may therefore be necessary.

Prevention of Duodenal Ulcer Recurrence

Recurrent duodenal ulcers, treated with cimetidine, 400 mg, or ranitidine, 150 mg, once nightly, or with sucralfate, 1 g twice daily, can be prevented in approximately 75% of patients for up to 1 year. Because these drugs are generally of equal efficacy, the choice is based on the patient's previous drug experience and tolerance, potential side effects, risk of drug interaction, frequency of administration, and cost. These medications do not alter the natural history of duodenal ulcer disease, and therapy may need to continue for longer than 1 year if there are no long-term side effects. Extra efforts should be made to help cigarette smokers discontinue smoking. Patients who have recurrent duodenal ulcers during maintenance therapy can be retreated with full-dose therapy. If optimal drug therapy is unsuccessful in preventing frequent recurrences or complications, surgical treatment is indicated.

The effect of omeprazole on gastric emptying in patients with duodenal ulcer disease.

The effect of a single oral dose of omeprazole (90 mg) on gastric emptying was assessed with a dual isotope scintigraphic technique in eight patients with a history of duodenal ulcer disease. Omeprazole had no significant effect on solid or liquid gastric emptying. The bioavailability (AUC0-2 h) of omeprazole in all patients was greater than that required for total suppression of acid secretion. No adverse clinical or laboratory effects were observed.