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Aim: To determine the sensitivity and specificity of the 13 C-urea breath test (UBT) in patients taking proton pump inhibitors (PPIs), using a new test meal Refex., Methods: One hundred and fourteen consecutive patients with dyspepsia, 53 Helicobacter pylori ( H. pylori ) positive, 49 H. pylori negative, were included in the study. The patients were then given esomeprazole 40 mg for 29 consecutive days, and the 13 C-UBT with the new test meal was performed the next morning., Results: The sensitivity of the 13 C-UBT with a cut off 2.5‰ was 92.45% (95%CI: 81.79%-97.91%) by per-protocol (PP) analysis and 78.13% (95%CI: 66.03%-87.49%) by intention-to-treat (ITT) analysis. The specificity of the 13 C-UBT test was 96.00% in the ITT population (95%CI: 86.29%-99.51%) and 97.96% in the PP population (95%CI: 89.15%-99.95%)., Conclusion: The new test meal based 13 C-UBT is highly accurate in patients on PPIs and can be used in those unable to stop their PPI treatment., Competing Interests: Conflict-of-interest statement: The authors of this manuscript having no conflicts of interest to disclose.

Purpose: The acceptance and realization of clinical guidelines in daily routine practice is unknown. The aim of this study was to evaluate the behaviour of private gastroenterologists in Germany with respect to the diagnostic and therapeutic management of H. pylori infection in times of increasing antibiotic resistance. Methods: Between 12/2014 and 02/2015 a standardized questionnaire with 19 multiple choice questions were sent to 1507 private gastroenterologists in Germany. The data were electronically captured and analyzed using SurveyMonkey. Results: The response rate was 36 % (540 questionnaires). 65 % of responders prescribe first line therapy by themselves and mainly use standard triple therapies. In patients with intolerance to penicillin, 81 % prescribe Italian triple therapy and 19 % prescribe bismuth quadruple therapy. Risk factors for primary clarithromycin resistance (migrational background, previous macrolide exposure) are routinely assessed by only a minority of responders (22 % and 17 %, respectively). Forty-one percent of responders perform eradication control by themselves mainly using a 13C urea breath test (54 %). In second line therapy, 42 % are prescribing bismuth quadruple therapy and 24 % fluoroquinolone triple therapy. After second line therapy, 58 % of responders are performing eradication control by themselves. Of those, 70 % always take biopsies for antibiotic susceptibility testing. Conclusions: The results of our survey suggest that most private gastroenterologists in Germany adhere to current guidelines for H. pylori management; however, some relevant deviations seem to exist. Our data might be useful for further developments of clinical guidelines and their communication among the medical community., (© Georg Thieme Verlag KG Stuttgart · New York.)

There is progress in endoscopy techniques. While it is not yet possible to detect Helicobacter pylori directly in the stomach, it becomes easier to detect the mucosal changes induced by the bacteria. Some small changes can also increase the sensitivity of the invasive tests, for example culture or histology, but the wide use of proton-pump inhibitors has a negative impact on these tests. Only molecular methods are able to detect a limited load of bacteria, especially by using real-time PCR but also with new methods, for example dual-priming oligonucleotide-based PCR, loop-medicated isothermal amplification, droplet-digital PCR or a multiple genetic analysis system. Among the noninvasive tests, urea breath test remains a test of major interest, while there are attempts to develop an ammonia breath test and other nanosensor devices. A new antigen stool test, a chemoluminescence immunoassay using the LIAISON apparatus has also been tested for the first time with success. Despite its limitations, serology remains the most popular test to detect H. pylori antibodies. It also allows pepsinogen dosage which is of interest for detecting atrophy., (© 2016 John Wiley & Sons Ltd.)

Eradication rates in first-line Helicobacter pylori therapy have been declining over the last decades, mainly due to increasing resistance against the recommended antibiotics clarithromycin and metronidazole. Thus, there is a need to evaluate novel regimens and substances to offer effective alternative treatment strategies. New generation quinolones, like levofloxacin and moxifloxacin, exhibit a broad-spectrum activity against various Gram-positive and Gram-negative strains and are mostly well tolerated. Based on a large number of studies, quinolones have been introduced in second-line and rescue treatment and are recommended for these indications in current guidelines. Various studies have investigated alternative strategies for first-line treatment including quinolone-based regimens. In the context of increasing resistance rates of Helicobacter pylori against quinolones some risks and benefits have to be considered when using quinolones as a first-line strategy. Besides numerous studies investigating levofloxacin and moxifloxacin there are some promising results for the new substance sitafloxacin, which might overcome primary resistance of Helicobacter pylori against conventional quinolones., (© Georg Thieme Verlag KG Stuttgart · New York.)

Recommendation for the diagnosis and treatment of Helicobacter pylori Infection are defined in recent national and international guidelines. In Germany, proton pump inhibitor-based triple therapy with clarithromycin and metronidazole or amoxicillin is still the standard in first line therapy. However, success rates have decreased substantially during the last years due to increasing antibiotic resistance, particularly in patients from Southern Europe. In addition, antimicrobial resistance rates against the standard antibiotics further increases dramatically after failure of first line therapy deeming the repeated use of these antibiotics basically impossible. Against this background, a critical appraisal and eventually adaption of therapeutic options both in first line and rescue treatment appears necessary. This paper gives an overview on the current status of therapeutic options and developments in the treatment of H. pylori infection in the light of increasing antibiotic resistance.

This guideline updates a prior consensus recommendation of the German Society for Digestive and Metabolic Diseases (DGVS) from 1996. It was developed by an interdisciplinary cooperation with representatives of the German Society for Hygiene and Microbiology, the Society for Pediatric Gastroenterology and Nutrition (GPGE), and the German Society for Rheumatology. The guideline is methodologically based on recommendations of the Association of the Scientific Medical Societies in Germany (AWMF) for providing a systematic evidence-based S 3 level consensus guideline and has also implemented grading criteria according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) process. Clinical applicability of study results as well as specifics for Germany in terms of epidemiology, antibiotic resistance status, diagnostics, and therapy were taken into account.

Background: Gastrin and pepsinogens reflect the functional state of the gastric mucosa., Aim: To evaluate whether serum gastrin and pepsinogens correlate with the different grades of severity of gastro-oesophageal reflux disease (GERD)., Methods: In all, 388 patients with heartburn not taking any form of acid suppressive therapy were matched-controlled for age and gender and sub-classified into four groups: group 1 non-erosive reflux disease (NERD); group 2, erosive reflux disease (ERD) Los Angeles (LA) A and B, group 3, ERD LA C and D; group 4 Barrett's oesophagus (BO). Fasting serum was analysed for gastrin 17, pepsinogen I, pepsinogen II und Helicobacter pylori using specific EIA tests (GastroPanel; Biohit, Plc)., Statistics: Kruskal-Wallis test and analysis of variance., Results: There was a significant difference among the four groups with respect for pepsinogen I, but not for pepsinogen II, the pepsinogen I pepsinogen II ratio, H. pylori serology and gastrin levels. Pepsinogen I was the lowest in NERD and the highest in BO (median 91.6, mean +/- standard deviation 106.2 +/- 51.6 vs. median 114.7, mean +/- standard deviation 130.4 +/- 70.6; P = 0.046). Pepsinogen I levels were higher in H. pylori positive subjects. After adjusting for H. pylori status, the differences in pepsinogen I across patient groups were no longer statistically significant (P = 0.298)., Conclusions: Serum gastrin and pepsinogen I and II do not correlate with the different grades of severity of GERD. The non-invasive GastroPanel is not useful for the differentiation of the various forms of GERD.

Successful Helicobacter pylori eradication therapy remains a challenge in medical practice. Currently, a proton pump inhibitor-based triple therapy containing clarithromycin, amoxicillin or nitroimidazole for 7 days is the recommended first-line treatment approach with an expected eradication success rate of approximately 80%. As a second-line treatment option in the case of failure, a ranitidine bismuth citrate-based quadruple therapy is currently recommended curing another 80% of patients, leaving a subset of patients with persistent H. pylori infection. For these patients, promising rescue options have been evaluated including regimens that contain rifabutin, quinolones, furazolidone or high-dose amoxicillin. The role of susceptibility testing is still under discussion. It is not generally recommended prior to first-line treatment but guidelines propose a role for culture and antibiotic sensitivity testing after failure of the second attempt. Meanwhile, data on the geographic distribution of resistance pattern are available and may guide therapeutic decisions with regard to the combination of antibiotics chosen for the individual patients aiming at 100% cure rate in each individual patient.

Background: Adequacy of acid suppression is a critical factor influencing healing in gastro-oesophageal reflux disease (GORD). The European prospective study ProGORD was set up to determine the endoscopic and symptomatic progression of GORD over five years under routine care, after initial acid suppression with esomeprazole. We report on factors influencing endoscopic healing and symptom resolution during the acute treatment phase., Methods: Patients with symptoms suggestive of GORD underwent endoscopy and biopsies were obtained from the oesophagus for diagnosis of abnormalities, including Barrett's oesophagus (BO). Data from 6215 patients were included in the "intention to treat" analysis, 3245 diagnosed as having erosive reflux disease (ERD) and 2970 non-erosive reflux disease (NERD). ERD patients were treated with esomeprazole 40 mg for 4-8 weeks for endoscopic healing while NERD patients received 20 mg for 2-4 weeks for resolution of heartburn symptoms., Results: Endoscopic healing occurred overall in 87.7% of ERD patients although healing was significantly lower in those with more severe oesophagitis (76.9%) and in those with BO (72.4%), particularly in Helicobacter pylori negative BO patients (70.1%). Age, sex, and body mass index appeared to have no significant impact on healing. Complete heartburn resolution was reported by 70.4% of ERD patients and by 64.8% of NERD patients at the last visit. Only H pylori infection had a significant influence on complete heartburn resolution in the NERD group (68.1% and 63.7% for H pylori positive and H pylori negative, respectively; p = 0.03)., Conclusion: The presence of Barrett's mucosa, as well as severe mucosal damage, exerts a negative impact on healing. H pylori infection had a positive influence on healing in ERD patients with coexistent BO but no influence on those without BO.

Background: There is much controversy as to whether or not treatment of Helicobacter pylori reduces the occurrence of peptic ulcers during therapy with a non-steroidal anti-inflammatory drug (NSAID)., Aim: To assess the efficacy of triple therapy or omeprazole on the occurrence of diclofenac associated ulcers in H pylori positive patients., Methods: This was a randomised, double blind, placebo controlled, multicentre trial in H pylori positive patients requiring NSAID therapy who had no past or current peptic ulcer. They received diclofenac 50 mg twice daily for five weeks in combination with one of the four randomly assigned treatments: anti-H pylori treatment for one week (omeprazole 20 mg+clarithromycin 500 mg+amoxicillin 1 g, all twice daily) followed by placebo for four weeks (OAC-P); anti-H pylori treatment for one week followed by antisecretory treatment with omeprazole 20 mg once daily for four weeks (OAC-O); omeprazole 20 mg once daily for five weeks (O-O); or placebo for five weeks (P-P). Patients were endoscoped before and after treatment., Results: Data from 660 patients were included in an intention to treat analysis. The occurrence of peptic ulcers in the four treatment groups during the study period was: 1.2% for OAC-P, 1.2% for OAC-O, 0% for O-O, and 5.8% for P-P (p<0.05 between placebo and all active treatment groups). Patients who received active treatment developed therapy requiring dyspeptic symptoms less frequently than those who received placebo (p<0.05 between placebo and all active treatment groups)., Conclusions: In H pylori infected patients, all three active therapies reduced the occurrence of NSAID associated peptic ulcer and dyspeptic symptoms requiring therapy.

Background: The optimal second-line treatment after failed Helicobacter pylori therapy has not been established., Aims: To ascertain whether quadruple therapy or triple therapy with omeprazole, clarithromycin and amoxicillin is the superior re-treatment after triple therapy containing a macrolide and a nitroimidazole, and to determine the impact of microbial in vitro resistance., Methods: Patients after failed triple therapy were randomly allocated to one of two 1-week second-line treatments: omeprazole, 40 mg, clarithromycin, 500 mg, and amoxicillin, 1 g, all b.d.; or omeprazole, 20 mg b.d., bismuth subsalicylate, 600 mg q.d.s., metronidazole, 400 mg t.d.s., and tetracycline, 500 mg q.d.s. Post-therapeutic Helicobacter pylori status was assessed by 13C-urea breath test at least 4 weeks after treatment., Results: The study was terminated after including 84 patients. H. pylori cure rates differed significantly: omeprazole-clarithromycin-amoxicillin: intention-to-treat, 43%; per protocol, 50%; omeprazole-bismuth subsalicylate-metronidazole-tetracycline: intention-to-treat, 68%; per protocol, 69%. The frequencies of resistance after first-line therapy were: metronidazole, 90%; clarithromycin, 71%; both combined, 68%. For clarithromycin resistance, H. pylori cure with omeprazole-clarithromycin-amoxicillin was 30% vs. 83% for clarithromycin susceptibility., Conclusions: Omeprazole-bismuth subsalicylate-metron- idazole-tetracycline was superior to omeprazole-clarithromycin-amoxicillin, but both therapies yielded unsatisfactory results. The high rate of post-therapeutic dual resistance has a negative impact on omepraz- ole-clarithromycin-amoxicillin, and probably also on omeprazole-bismuth subsalicylate-metronidazole-tetracycline, and limits the choice for second-line treatment.

Background and Aim: Rapid blood tests for diagnosis of Helicobacter (H.) pylori infection enable to detect antibodies against H. pylori instantly without laboratory equipment. Primary aim: to validate the Helisal Rapid Whole Blood Test (HRBT) with endoscopic bioptic methods as reference. Secondary aim: to compare the HRBT with ELISA IgG serology., Patients and Methods: The HRBT was performed in 145 consecutive dyspeptic patients (median age 59 years) before undergoing esophagogastroduodenoscopy including biopsies from gastric antrum and corpus. A positive H. pylori status was defined by a positive culture or the combination of a positive rapid urease test and a positive histology. Serum for ELISA IgG testing was available from 92 patients., Results: The H. pylori status was positive in 66% of the patients. The sensitivity of the HRBT resulted at 80%, the specificity at 82%. The sensitivity of the HRBT for a positive ELISA test amounted to 87%, the specificity to 96%., Conclusions: The diagnostic validity of the HRBT is insufficient for clinical application. False test results add up by the general discrepancy between serological and bioptic methods and by diminished sensitivity compared to ELISA serology.

Helicobacter pylori induces chronic active gastritis that may progress to atrophy. Serious clinical consequences are peptic ulcer disease and gastric malignancies. Today, treatment of the infection is an appropriate option and is strongly recommended in various clinical situations. Although many antibiotics are effective against H. pylori in vitro, few substances are suitable for use in vivo. This is because H. pylori lives in a unique environment in which several factors may affect the pharmacokinetic and pharmacodynamic properties of the anti-microbial agents. One of the most important factors is gastric acidity. This article reviews the effects of acid suppression on H. pylori and the associated gastritis, the potential mechanisms by which anti-secretory drugs such as proton pump inhibitors might enhance the activity of anti-microbials in vivo, and the results of clinical trials supporting the current view that proton pump inhibitors are a mainstay in the treatment of this infection.

Aim: To test the hypothesis that Helicobacter pylori eradication alone can reduce the incidence of gastric cancer in a subgroup of individuals with an increased risk for this fatal disease., Methods: It is a prospective, randomized, double blind, placebo controlled multinational multicenter trial. Men between 55 and 65 years of age with a gastric cancer phenotype of Helicobacter pylori gastritis are randomized to receive a 7 day course of omeprazole 2 X 20mg, clarithromycin 2 X 500mg, and amoxicillin 2 X 1g for 7 days, or omeprazole 2 X 20mg plus placebo. Follow-up endoscopy is scheduled 3 months after therapy, and thereafter in one-year intervals. Predefined study endpoints are gastric cancer, precancerous lesions (dysplasia, adenoma), other cancers, and death., Results: Since March 1998, 1524 target patients have been screened, 279 patients (18.3%) had a corpus dominant type of H. pylori gastritis, and 167 of those were randomized (58.8%). In the active treatment group (r = 86), H. pylori infection infection was cured in 88.9% of patients. Currently, the cumulative follow-up time is 3046 months (253.38 patient years, median follow up 16 months). So far, none of the patients developed gastric cancer or any precancerous lesion. Three (1.8%) patients reached study endpoints other than gastric cancer., Conclusion: Among men between 55 and 65 years of age, the gastric cancer phenotype of H. pylori gastritis appears to be more common than expected. Further follow up and continuing recruitment are necessary to fulfil the main aim of the study.

Aims: We investigated the diagnostic properties of the (13)C-urea breath test ((13)C-UBT) prospectively. These are well validated in nonresected patients before and after treatment of Helicobacter pylori infection but not in patients with partial gastric resection due to peptic ulcer disease., Methods: Hospitalized patients with previous gastric resection and indications for upper gastrointestinal endoscopy were recruited for the study. Biopsy specimens were obtained from the fundus mucosa and the gastric remnant adjacent to the gastroenteric anastomosis for histological examination and rapid urease test (HUT test). Histological slides were evaluated after hematoxylin and eosin and Warthin-Starry dye staining. 200 ml orange juice was given orally after two baseline breath samples had been taken, and 30 min after ingestion of 75 mg (13)C urea two more breath samples were obtained and analyzed by ratio mass spectrometry. The Warthin-Starry dye-stained sample was taken as reference., Results: 68 patients (47 male, 21 female, mean age 62 years; 52 Billroth II resection, 17 Billroth I resection) were included in the study. The overall prevalence of histologically proven H. pylori infection was 36.7%. The sensitivity of the (13)C-UBT was 52%, the specificity 93%. The positive predictive value was 81.25%, the negative predictive value 76.9% and the accuracy was 77.9%. The sensitivity of the HUT test reached 60%, and the specificity 97%., Conclusion: The diagnostic accuracy of (13)C-UBT compared with the Warthin-Starry dye staining is low. The breath test, performed in the above-described manner, cannot be recommended as a noninvasive diagnostic tool for diagnosis of H. pylori infection in patients after partial gastrectomy as a result of peptic ulcer disease., (Copyright 2001 S. Karger AG, Basel)

Background: Esomeprazole is the first proton pump inhibitor to be developed as an optical isomer for the treatment of acid-related diseases., Methods: Four hundred and forty eight duodenal ulcer patients with Helicobacter pylori infection, confirmed by 13C-urea breath test (UBT), and no current ulcer, were randomised to double-blind treatment with esomeprazole 20 mg twice daily (b.d.) (n=224) or omeprazole 20 mg b.d. (n=224), in combination with amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. for 1 week (EAC and OAC, respectively). A negative UBT at both 4 and 8 weeks after completing therapy indicated successful H. pylori eradication., Results: Intention-to-treat (ITT) analysis comprised 400 patients (EAC, n=204; OAC, n=196) and per protocol (PP) analysis 377 patients (EAC, n=192; OAC, n=185). Eradication rates (95% confidence intervals) for ITT and PP populations were: EAC, 90% (85-94%) and 91% (86-94%); OAC, 88% (82-92%) and 91% (86-95%). Between-group differences in eradication rates were not statistically significant. Both regimens were well tolerated, with an adverse event profile and frequency typical of proton pump inhibitor plus antibiotic combination therapy., Conclusions: Esomeprazole-based triple therapy for 1 week is highly effective in eradicating H. pylori infection in duodenal ulcer disease, offers comparable efficacy to omeprazole-based therapy, and is well tolerated.

In the complex pathogenesis of genuine ulcer disease Helicobacter pylori (H. pylori) is an essential, although not on its own sufficient, causal factor. Eradication of the infection heals the active ulcer and, in the long term, leads to a drastic reduction in ulcer recurrence and attendant complications. Some patients remain symptomatic even without ulcer recurrence, and in these, pre-existing, exacerbated or induced gastro-oesophageal reflux disease is probably of some significance. Possible causes of ulcer relapse are reinfection, the use of ulcerogenic drugs and persistent gastric hypersecretion. In adults, and probably also in children from the age of six years, H. pylori reinfection is rare, provided that a sensitive and specific test for H. pylori is carried out at the earliest 4 weeks after concluding anti-bacterial treatment. The most common cause of the reappearance of H. pylori is recrudescence - true reinfection hardly ever occurs. The healing of H. pylori-associated ulcer disease improves the patient's quality of life and possibly also life expectancy. Computer-aided calculations, together with a randomized controlled study, have shown not only that individual patients benefit, but that also the health system profits financially. The hypothetical negative effects of H. pylori eradication treatment are still being controversially discussed.

Aim: Aim of the present case-control study was to establish whether Helicobacter pylori increases the risk of ulcer bleeding., Patients and Methods: All patients presenting with upper gastrointestinal bleeding between November 1994 and November 1995 were prospectively investigated and compared with hospital controls matched for age, sex, and race. We evaluated the frequency of Helicobacter pylori infection, intake of aspirin or non-steroidal anti-inflammatory drugs, use of alcohol, and smoking habits in patients and controls., Results: Included in the study were 128 patients. In 72 patients, the source of bleeding was a peptic ulcer (duodenal ulcer: n = 33; gastric ulcer: n = 39). Ulcer patients were more frequently infected by Helicobacter pylori than controls (72% vs 42%; p < 0.001) while the incidence of infection was similar in patients with non-ulcer bleeding and controls (52% vs 46%; p = 0.59). Conditional multiple logistic regression analysis showed that Helicobacter pylori infection (odds ratio, 3.3 [Confidence interval, 1.5 to 7.0]; p = 0.002) and regular use of alcohol (odds ratio, 3.1 [Confidence interval, 1.0 to 9.0]; p = 0.041) increased the risk of peptic ulcer bleeding while previous intake of aspirin (> 100 mg) or non-steroidal anti-inflammatory drugs independently increased the risk of bleeding only in the case of gastric ulcer (odds ratio, 8.1 [Confidence interval 1.2 to 56.6]; p = 0.034)., Conclusions: Helicobacter pylori infection increases the risk of peptic ulcer bleeding. Our results suggest that Helicobacter pylori and non-steroidal anti-inflammatory drugs are independent risk factors for peptic ulcer bleeding.

Background and Objective: The significance of Helicobacter pylori (Hp) infection in asymptomatic persons is largely unknown. This prospective study was undertaken to evaluate the diagnostic and, if appropriate, therapeutic relevance of a noninvasive screening for Hp. In addition, the practicality and validity of a simple serological test on whole blood was elucidated., Patients and Methods: 100 consecutive patients (29 males, 71 females, median age 46 [18-79] years) of a general medical practice, seen in November of 1997, were included. Three patients had to be subsequently excluded, because they had been treated for Hp infection. All patients were given a standard interview after which a serological whole-blood test (BM-Test Helicobacter pylori; Boehringer Mannheim) and a 13C-urea breath test were performed as noninvasive reference. Endoscopy of the upper gastrointestinal tract was offered if the serology and/or the breath test were gative., Results: The Hp prevalence was 40%, rising significantly with age. The rapid serology test, when related to the breath test, had a negative and positive predictive value of < 80%. 44 of the 47 patients with a positive serological or breath test agreed to endoscopy. Eleven of them had a clinically significant abnormality macroscopically or histologically: four of them were found to have an Hp infection., Conclusions: Asymptomatic Hp-positive persons frequently have clinically abnormal findings in the upper gastrointestinal tract. These data point to the need for a large multi-centre study with cost-effect analysis to evaluate a noninvasive Hp screening test in nonsymptomatic persons as a public health measure. The 13C-urea breath test would be suitable as such a screening method.

Unlabelled: There have been only a few surveys on the prevalence of persistent Helicobacter pylori (Hp) infection in patients who have undergone surgery for peptic ulceration. The aim of the study was to evaluate the prevalence and clinical importance of Hp infection after partial gastric surgery due to peptic ulcer disease., Methods: We examined 50 patients who had partial gastric resection for peptic ulcer disease and years later underwent upper gastrointestinal (GI) endoscopy. 50 controls matched with respect to indication for GI endoscopy, age and gender were also studied. Three specimens from the fundus of gastric remnant were examined for Hp infection (histology and rapid urease test). The prevalence of Hp infection and pathology findings were compared between the two groups using chi-square statistics., Results: 32 men and 18 women were examined (40 x BII, 10 x BI). The prevalence of Hp infection was 38% in the resected group compared to 60% in the control group (p = 0.015). We found a significant association (p = 0.0004) between Hp infection and endoscopic findings in the control group but not in the group of partially resected patients (p = 0.66)., Conclusion: The prevalence of Hp infection in hospitalized patients with partial gastric resection is significantly lower than in matched controls. Hp infection does not play a significant pathogenic role in recurrent ulcer after partial gastric resection in these patients.

Background: It is uncertain whether treatment of Helicobacter pylori infection relieves symptoms in patients with nonulcer, or functional, dyspepsia., Methods: We conducted a double-blind, multicenter trial of patients with H. pylori infection and dyspeptic symptoms (moderate-to-very-severe pain and discomfort centered in the upper abdomen). Patients were excluded if they had a history of peptic ulcer disease or gastroesophageal reflux disease and had abnormal findings on upper endoscopy. Patients were randomly assigned to seven days of treatment with 20 mg of omeprazole twice daily, 1000 mg of amoxicillin twice daily, and 500 mg of clarithromycin twice daily or with omeprazole alone and then followed up for one year. Treatment success was defined as the absence of dyspeptic symptoms or the presence of minimal symptoms on any of the 7 days preceding the 12-month visit., Results: Twenty of the 348 patients were excluded after randomization because they were not infected with H. pylori, were not treated, or had no data available. For the remaining 328 patients (164 in each group), treatment was successful for 27.4 percent of those assigned to receive omeprazole and antibiotics and 20.7 percent of those assigned to receive omeprazole alone (P=0.17; absolute difference between groups, 6.7 percent; 95 percent confidence interval, -2.6 to 16.0). After 12 months, gastritis had healed in 75.0 percent of the patients in the group given omeprazole and antibiotics and in 3.0 percent of the patients in the omeprazole group (P<0.001); the respective rates of H. pylori eradication were 79 percent and 2 percent. In the group given omeprazole and antibiotics, the rate of treatment success among patients with persistent H. pylori infection was similar to that among patients in whom the infection was eradicated (26 percent vs. 31 percent). There were no significant differences between the groups in the quality of life after treatment., Conclusions: In patients with nonulcer dyspepsia, the eradication of H. pylori infection is not likely to relieve symptoms.

There are two lines of thought regarding the interrelationship between the damaging effects of Helicobacter pylori and those of nonsteroidal anti-inflammatory drugs (NSAIDs) on the gastroduodenal mucosa. First, both pathogenic factors exert a damaging effect on the mucosa, and therefore an additive, or even synergistic, effect occurs, leading to aggravation of mucosal damage. Second, mutual antagonism exists, leading to one of the pathogenic factors actually deriving some protection from the damaging potential of the other. Microscopically, H. pylori- and NSAID-associated gastritis are recognized as two separate entities. Furthermore, pathologically, the mechanisms of mucosal damage of the two factors have important differences; for example, H. pylori increases the synthesis of prostaglandins, whereas NSAIDs inhibit prostaglandin synthesis. The role of H. pylori infection in patients with NSAID-associated peptic ulcers has been addressed recently in two large, randomized, multicenter trials. From these studies, it appears that antisecretory drugs are more effective in H. pylori-positive peptic ulcer patients taking NSAIDs than in H. pylori-negative patients taking these drugs. The studies, however, do not provide any evidence that H. pylori infection reduces the pathogenic effects of NSAIDs. Other studies, however, have shown protection against NSAID-associated gastroduodenal damage in H. pylori-negative patients. Thus, there are no firm conclusions on the role of H. pylori infection in patients with NSAID-associated peptic ulcers. Based on the available data, however, practical considerations and guidelines are listed.

Background and Aims: Acid hyposecretion may enhance Helicobacter pylori colonization. We tested the hypothesis that maintenance therapy with ranitidine after cure of Helicobacter pylori infection increases the risk of recurrence of infection., Patients and Methods: Sixty-six patients with duodenal ulcer and cured Helicobacter pylori infection were randomly assigned to 12 months maintenance treatment with ranitidine 150 mg daily (group A) or no treatment (group B). Follow-up consisted of clinical and endoscopic controls with biopsies for histology and rapid urease test every 4 months., Results: Six patients, 3 in each group, were lost to follow up. Helicobacter pylori recurrence occurred in 9 patients in group A and in 2 patients in group B (30% versus 7%; p < 0.05). Duodenal ulcer recurred in one patient in group A and in 2 in group B, all three patients were reinfected with Helicobacter pylori. A corpus-predominant gastritis was observed in all reinfected patients in group A but in none in group B., Conclusions: Long-term inhibition of gastric acid secretion after eradication of Helicobacter pylori increases the risk of recurrence of infection. Our data imply that gastric acid not only influences the pattern of Helicobacter pylori localization in gastric mucosa, but also plays a key role in preventing recurrence of infection with Helicobacter pylori.

Objectives: Helicobacter pylori has a predilection for antral colonization. Local acid production is the major determinant of colonization. Because production is low in the antrum and cardia, H. pylori should also colonize the cardia. We therefore investigated the histologic pattern of gastritis and the prevalence of H. pylori in the cardia compared with the antrum and corpus., Methods: From 135 H. pylori-infected patients with gastritis, ulcer disease, or reflux esophagitis, biopsies were obtained from the antrum, corpus, and cardia. The prevalence, topography, and histologic parameters of gastritis were examined., Results: All 135 patients had active antral H. pylori gastritis: in the cardia, 132 of these patients (97.7%) showed active gastritis, and 124 patients (91.9%) had H. pylori visible on staining. Gastritis of the cardia in most patients resembled antral gastritis, but the density of bacteria and the inflammatory responses were less marked. The most striking finding in the cardia of patients with gastroesophageal reflux was a lower density of bacteria compared with antrum and corpus. Intestinal metaplasia was found in 32 patients in antral mucosa (23.7%) versus 28 patients in the cardia (20.7%), versus 11 patients in the corpus (8.1%), and was multifocal in 17 patients (12.6%)., Conclusions: H. pylori gastritis commonly involves the cardia. The histologic density of the bacteria and inflammatory responses are lower than in the antrum. Intestinal metaplasia in the cardia is a common finding in H. pylori gastritis. The cause of the lower bacterial density in the cardia of patients with reflux esophagitis needs further investigation.

Background: In patients with duodenal ulcer cure of Helicobacter pylori infection resulted in a pronounced decrease in intragastric pH during treatment with omeprazole., Aim: To test the hypothesis that treatment of H pylori adversely affects the pH response to ranitidine., Patients: Eighteen patients with duodenal ulcer who were infected with H pylori were studied., Methods: Twenty four hour pH recordings were performed during treatment with ranitidine (300 mg) at night before and four to six weeks after cure of H pylori infection. Presence of H pylori was assessed by a rapid urease test, culture, histology, and a 13C urea breath test. Also, the fasting gastrin concentrations were measured before and after treatment for H pylori infection., Results: Cure of H pylori infection resulted in a considerable improvement in both antral and corpus gastritis and a decrease in fasting gastrin concentrations. As a result of the cure the night time intragastric pH during treatment with ranitidine decreased (median pH 6.8 v 5.4; p = 0.007), whereas the acidity during the daytime was not affected., Conclusions: In patients with duodenal ulcer the intragastric pH during treatment with ranitidine depends on H pylori. However, the loss of effectiveness in altering pH seems to be less pronounced than previously found with omeprazole.

Background: Several studies have shown that dual therapy with omeprazole and amoxycillin may cure Helicobacter pylori infection. However, the optimum dose of omeprazole has still to be established., Methods: An international, randomized, double-blind multicentre trial was conducted in patients with duodenal ulcers to compare the H. pylori cure rates obtained by dual therapy consisting of either omeprazole 20 mg b.d. plus amoxycillin 750 mg b.d. or omeprazole 40 mg b.d. plus amoxycillin 750 mg b.d. for 2 weeks. Dual therapy was followed by omeprazole 20 mg once daily for 2 weeks. Before entering the trial and 4 weeks after cessation of treatment H. pylori infection was assessed by histology and a 13C-urea breath test., Results: 381 patients were randomized into the study, of whom 345 were evaluable for the all-patients-treated analysis of efficacy and 378 were valid for the evaluation of safety. Histology results showed that H. pylori infection was cured in 64 out 174 patients treated with omeprazole 20 mg b.d. plus amoxycillin and in 102 out of 171 patients treated with omeprazole 40 mg b.d. plus amoxycillin (37% vs. 60%; P < 0.001). Both treatment regimens were well tolerated, with adverse events reported by 29 (15.2%) and 35 patients (18.7%), respectively., Conclusions: This study has shown that dual therapy with amoxycillin 750 mg b.d. and omeprazole 40 mg b.d. is superior to dual therapy with amoxycillin and omeprazole 20 mg b.d. in patients with H. pylori-positive duodenal ulcers. Thus, a true dose-response relationship exists between omeprazole and treatment success. However, a combination of omeprazole with two of amoxycillin, clarithromycin and nitroimidazole is a preferable alternative for routine clinical use.

Objective: To determine how often gastroenterologists know their own Helicobacter pylori status, how they diagnose the infection and what consequences they draw from the findings., Methods: Between November 1995 and March 1996 questionnaires were sent to gastroenterologists in hospitals (592, with five not reached) or private practice in Germany (431, 12 not reached), with a response rate of 24.4% and 55.4%, respectively., Results: Of the 375 respondents 27 were female; the average age was 47.6 +/- 7.8 years. 151 knew their own H. pylori status (40.3%), with an infection rate of 55.6%. Most of the doctors had used noninvasive diagnostic tests (serology: 18.5%, breath test: 37.7%, serology + breath test 2.0%). 54 doctors (among them three without prior testing) had treated themselves between 1992 and 1995, ulcer or dyspepsia having been the most common indication (in 60%). Between 1992 and 1994 omeprazole plus amoxycillin was the most common form of treatment, while in 1995 a triple regimen with omeprazole and two antibiotics was most common during 1995. Either regimen was well tolerated in 85% of those treated, but about a quarter of doctors reported difficulties in compliance. Only half of the participants tested the result of treatment, similar numbers using either the breath test (n = 14) or biopsy (n = 13) for confirmation., Conclusions: A significant percentage of gastroenterologists in Germany knew their own H. pylori status. However, the diagnostic procedures and indications for treatment often did not respond to recommended guidelines. The frequency of treatment and the regimen used mirrored the improved knowledge of the significance of H. pylori infection and the development of antibacterial treatment during the last few years.

Background & Aims: We have shown previously that cure of Helicobacter pylori infection leads to the disappearance of acid-neutralizing substances. Also, patients with ulcer after cure may gain weight. The aim of this study was to investigate whether cure of the infection increases the risk of reflux esophagitis., Methods: Patients with duodenal ulcer without reflux esophagitis at the time of Helicobacter treatment were followed up prospectively after cure of the infection (n = 244) or after diagnosis of persisting infection (n = 216). All patients underwent endoscopy at 1-year intervals or when upper gastrointestinal symptoms recurred. H. pylori infection was assessed by rapid urease test and histology., Results: The estimated incidence of reflux esophagitis within 3 years was 25.8% after cure of the infection and 12.9% when the infection was ongoing (P < 0.001). Patients who developed reflux esophagitis after the cure had a more severe body gastritis before cure (odds ratio, 5.5; 95% confidence interval [CI], 2.8-13.6), gained weight more frequently after cure (odds ratio, 3.2; 95% CI, 1.2-9.4), and were predominantly men (odds ratio, 3.6; 95% CI, 1.1-10.6)., Conclusions: A considerable proportion of patients with duodenal ulcer treated for H. pylori will develop reflux esophagitis; risk factors are male sex, severity of corpus gastritis, and weight gain.

Objective: We have previously shown that, in duodenal ulcer patients, pH control by omeprazole is less pronounced after cure of Helicobacter pylori infection. The present study was designed to test the hypothesis that this response to omeprazole persists 1 yr after cure of H. pylori infection., Methods: In 12 duodenal ulcer patients, intragastric acidity was measured with a glass electrode during treatment with omeprazole (20 mg) once daily before, and 4-6 wk and 1 yr after, cure of H. pylori infection. H. pylori infection was assessed by [13C]urea breath test, culture, histology (Warthin Starry stain), and rapid urease test., Results: Cure of H. pylori infection resulted in a lowered pH during omeprazole treatment. This effect persisted after 1 yr. Median 24-h gastric pH before H. pylori treatment was 5.6; 4-6 wk after cure of the infection it was 2.9 (p = 0.003), and 1 yr after cure of the infection it remained unchanged (pH = 2.5; p = 0.5). Accordingly, twice as much time was spent above pH 3 and pH 4 before H. pylori treatment than 1 or 12 months after cure (percent of time > or = pH 3: 82.7 vs. 49.7 vs. 43.1; percent of time > or = pH 4: 72.7 vs. 38.3 vs. 26.4)., Conclusion: In duodenal ulcer patients, cure of H. pylori infection resulted in a marked rapid and persistent decrease of the pH increasing effect of omeprazole. Therefore, H. pylori is a determinant of the pH achieved in response to omeprazole treatment in duodenal ulcer patients.

Basic Problem and Objective of Study: The situation of pretherapeutical antimicrobial drug resistance of Helicobacter pylori has therapeutical implications. For this reason the present study was designed to evaluate the frequency of resistance in Germany., Material and Methods: A total of 201 H. pylori isolates cultured on the basis of biopsies taken by routine gastroscopies were tested for resistance by E-test. The antibiotics examined were amoxicillin, tetracycline, clarithromycin and metronidazole. For further analysis the last 101 patients were asked for demographical and clinical data that were evaluated for a correlation with metronidazole resistance., Results: Pretherapeutical resistance against amoxicillin and tetracycline was not detected. The rate of drug resistance against clarithromycin came to 3% and against metronidazole to 29%. There was a higher incidence of metronidazole resistance in female patients (Odds ratio 1.71; p = n.s.). Reliable predictors for metronidazole resistance, however, could not be identified., Conclusions: About 30% of H. pylori isolates are pretherapeutically resistant to metronidazole. Resistance to clarithromycin is still rare, but further monitoring remains necessary to detect changes in the community.

Aim: To test the hypothesis that 1-week low-dose triple therapy for H. pylori is sufficient for relief from dyspeptic symptoms and healing of duodenal ulcers., Methods: Fifty-nine out-patients with duodenal ulcers and positive rapid urease test participated in this randomized, double-blind, two-centre study. All patients were treated for 1 week with omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. In a double-blind fashion, patients were then randomly treated for another 3 weeks with either omeprazole 20 mg once daily or an identical-looking placebo. Patients were investigated endoscopically before treatment for H. pylori, after 2 weeks and after 4 weeks. H. pylori infection was assessed by a 13C-urea breath test at the time of enrollment and 4 weeks after cessation of any study medication., Results: Fifty-two patients were included in the 'all patients treated' analysis of efficacy. The overall H. pylori cure rate was 96% (95% CI = 87-100%), with no difference between the treatment groups. After 2 weeks duodenal ulcer healing was confirmed in 91% (95% CI = 80-100%) of patients treated with omeprazole and in 76% (95% CI = 60-91%) in the placebo group (P = 0.14). After 4 weeks all ulcers had healed. Relief from dyspeptic symptoms and adverse events (13.8 and 16.7%) did not differ between the treatment groups., Conclusions: One-week low-dose triple therapy consisting of omeprazole, clarithromycin and metronidazole is a highly effective and well-tolerated approach to the cure of H. pylori infection in patients with a duodenal ulcer. Our data suggest that continuation of antisecretory drug therapy beyond anti-H. pylori therapy is actually excessive regarding relief from dyspeptic symptoms and healing of duodenal ulcers.

Background: Previous studies have shown that one-week triple therapy consisting of omeprazole, clarithromycin and amoxycillin may cure Helicobacter pylori infection in the vast majority of patients. The present study was designed to test the hypothesis that a triple therapy with pantoprazole, clarithromycin and amoxycillin cures the infection in > or = 80% of duodenal ulcer patients infected with H. pylori., Methods: In an open two-centre study, 60 duodenal ulcer patients were treated with pantoprazole 40 mg b.d., clarithromycin 500 mg b.d. and amoxycillin 1 g b.d. for 1 week. During the second week patients received pantoprazole 40 mg once in the morning. We assessed H. pylori infection before treatment and 4 weeks after cessation of the study medication by a rapid urease test, histology after Warthin-Starry stain and a 13C-urea breath test., Results: Sixty patients (42 males, mean age 47.4 years) entered the trial. All patients were infected with H. pylori. One patient was withdrawn from the study because of allergy to penicillin and six patients were protocol violators. H. pylori infection was cured in 47 out of 53 patients who completed the trial according to the protocol (89%; 95% CI: 80-97%) and in 49 of 60 patients included in the trial (82%; 95% CI: 72-92%). Four weeks after the last administration of study drugs, 55 out of 60 ulcers had healed (92%). Twenty-nine patients reported 51 adverse events that were mostly mild to moderate., Conclusions: One-week triple therapy consisting of pantoprazole, clarithromycin and amoxycillin is a simple and effective approach to the cure of H. pylori infection in patients with duodenal ulcer. In those patients who took the drugs as prescribed the H. pylori cure rate was 89%, with the lower 95% confidence limit being 80%.

Background: Omeprazole treatment produces lower intragastric pH values 4 weeks after cure of Helicobacter pylori infection than before. We therefore investigated the effect of healing H. pylori-associated gastritis on intragastric pH in the presence and in the absence of omeprazole therapy., Methods: Before and on day 8 of omeprazole, 20 mg once daily, 24-h intragastric pH-recordings were performed in 14 subjects with H. pylori infection and repeated 4 and 52 weeks after cure of infection. Gastritis severity in corpus and antrum was graded by using a modified Sydney system., Results: In the absence of omeprazole administration, median 24-h pH values before cure did not differ from those 4 and 52 weeks after cure. On day 8 of omeprazole administration, 24-h pH values were much higher before cure (median, 5.15; 95% confidence interval (CI), 4.3-6.0) than 4 weeks (3.6; 2.1-4.4; P < 0.001) and 52 weeks after cure (3.0; 2.1-4.4; P < 0.001). The activity of corpus and antral gastritis was not associated with the magnitude of H+ change induced by omeprazole., Conclusion: The increased pH produced by omeprazole during H. pylori infection is likely to be due to neutralizing substances produced by H. pylori and not to H. pylori-induced gastritis.

This prospective study was designed to validate a novel biopsy urease test as well as a simplified 13C-urea breath test for the detection of Helicobacter pylori. In addition, the hypothesis was tested that both the reaction velocity of the urease test and the 13CO2 excess of the urea breath test may allow a prediction of the severity of gastritis. Seventy dyspeptic patients with unknown H. pylori status were included. The H. pylori status was assessed by means of culture and histology after Warthin and Starry stain. One antral and one body biopsy specimen were separately analyzed by the novel biopsy urease test (HUT). Also, a 13C-urea breath test using 75 mg 13C-labelled urea and orange juice as test meal was performed in all patients. Forty-seven patients (67%) were H. pylori positive as judged from histology and culture. In 46 patients, H. pylori infection was also detected by the novel biopsy urease test and by the urea breath test as well (sensitivity 97.9%). False-positive results were not observed by either method (specificity 100%). Both the reaction velocity of the urease test and the 13CO2 excess of the breath test significantly correlated with H. pylori density and grade and activity of gastritis. The determination coefficients, however, indicated that both methods allow a reliable prediction of the severity of gastritis only in about 40-50% of the patients. In conclusion, the novel biopsy urease test and the simplified 13C-urea breath test proved to be highly accurate in diagnosing H. pylori infection. Despite a significant correlation, neither the reaction velocity of the urease test nor the 13CO2 excess of the breath test are clinically useful for the prediction of the severity of gastritis.