European Helicobacter Pylori Study Group Research Articles

Initial assessment of “Gissell's stain”: A novel histopathological method for the identification of Helicobacter pylori

Introduction and ObjectivesThe histopathological identification of Helicobacter pylori using the routine method (haematoxylin–eosin) is not only very difficult but also has low sensitivity. Giemsa staining is often used in addition, but different protocols do not produce homogeneous results. Furthermore, the Gold Standard recommended by the European Helicobacter Pylori Study Group has been applied in very few studies, thus resulting in uncertain outcomes. Therefore, a new staining method is required to overcome these limitations. The aim of this study was to evaluate the diagnostic capacity and inter-observer agreement of “Gissell's stain”. Material and MethodsA cross-sectional study evaluated 99 gastric paraffin blocks from a private laboratory. Three sections were prepared from each block, and haematoxylin–eosin (HE), Giemsa and “Gissell's stain” methods were applied. The kappa statistics, sensitivity, specificity, and predictive values were calculated. Results“Gissell's stain” obtained the highest inter-observer agreement (kappa=0.87) compared to the other two methods (HE, kappa=0.51; Giemsa, kappa=0.83). It also obtained the best sensitivity and negative predictive value (97.1% and 98.3%, respectively) compared with the other two methods (HE: 68.6% and 85.1%, respectively; Giemsa: 88.6% and 93.9%, respectively). ConclusionsGiven its unique characteristics (fast, cheap, accessible, and easy to use), in addition to its statistical reliability, “Gissell's stain” has great potential for routine use in the identification of H. pylori.

Missing gastric cancer in dyspepsia

Dyspepsia is common in gastric cancer, but also in many benign conditions. European Helicobacter pylori Study Group and American Gastroenterological Association guidelines recommend endoscopy in dyspepsia for patients with alarm symptoms or at age >45 years. However, recommendations are controversial. To investigate whether criteria for endoscopy in patients with dyspepsia are adequate to detect gastric cancer. In 215 patients at initial diagnosis of gastric adenocarcinoma, symptoms were classified as alarm and non-alarm. Cases were staged according to the TNM system. Stages T(1)-T(3)N(x)M(0) were defined as potentially curable. Dyspepsia was present in 128 patients. Among patients with dyspepsia, 15 were < or =45 years and 41 denied alarm symptoms. The combination of both criteria excluded only three (2.3%) patients from endoscopy, but increasing the threshold to >50 and >55 years would have raised the rate of excluded patients to seven (5.5%) and 11 (8.6%). Only 53 potentially curable stages and 18 early gastric cancers occurred, but the tumour stage was not associated with dyspepsia duration, age threshold of 45 years, or alarm symptoms. Our results support current European Helicobacter Study Group and American Gastroenterological Association criteria for endoscopy in patients with dyspepsia to detect gastric cancer. Regardless, most cancers are advanced at detection.

Meta-analysis: comparative efficacy of different proton-pump inhibitors in triple therapy for Helicobacter pylori eradication.

It is not known whether certain proton-pump inhibitors are more efficacious than others when used in triple therapy for Helicobacter pylori eradication. To compare the efficacy of different proton-pump inhibitors in triple therapy by performing a meta-analysis. A MEDLINE search was performed. Abstracts of the European Helicobacter pylori Study Group and the American Gastroenterological Association congresses from 1996 to 2002 were also examined. Randomized studies with at least two branches of triple therapy that differed only in terms of type of proton-pump inhibitor were included in a meta-analysis using Review Manager 4.1. Fourteen studies were included. Intention-to-treat cure rates were similar for omeprazole and lansoprazole: 74.7% vs. 76%, odds ratio (OR) 0.91 [95% confidence interval (CI) 0.69-1.21] in a total of 1085 patients; for omeprazole and rabeprazole: 77.9% vs. 81.2%, OR 0.81 (95% CI 0.58-1.15) in a total of 825 patients; for omeprazole and esomeprazole: 87.7% vs. 89%, OR 0.89 (95% CI 0.58-1.35) in 833 patients; and for lansoprazole and rabeprazole: 81% vs. 85.7%, OR 0.77 (95% CI 0.48-1.22) in 550 patients. The efficacy of various proton-pump inhibitors seems to be similar when used for H. pylori eradication in standard triple therapy.

Yield of endoscopy in dyspepsia and concurrent treatment with proton pump inhibitors: The blind leading the blind?

Yield of endoscopy in dyspepsia and concurrent treatment with proton pump inhibitors: The blind leading the blind?

The clinical role of cytochrome p450 genotypes in Helicobacter pylori management

Objective The aim of this pharmacogenomics study was to investigate the influence of different cytochrome P450 (CYP) genotypes in Helicobacter pylori eradication therapy. Methods The study involved 143 consecutive Italian Caucasian patients with H. pylori infection diagnosed and treated with 1-wk triple therapy according to European Helicobacter Pylori Study Group guidelines. Using human genomic DNA, CYP2C19 (*2 and *3) and CYP3A4 alleles (*1B, *2, and *3) were evaluated by polymerase chain reaction–restriction fragment length polymorphism assays and confirmed by sequencing the amplicons. Results According to the endoscopy-based gold standard, 93 patients achieved H. pylori eradication. Regarding CYP2C19 genotype, the 50 patients who remained infected were all homozygous or heterozygous extensive metabolizers (homEM or hetEM). Carriers of homEM fared significantly less well than those of hetEM; homEM genotype was also predictive of failure at univariate/multivariate analysis. Carriers of CYP3A4 polymorphisms achieved favorable eradication rates similar to patients bearing CYP2C19. All four patients with single CYP3A4*2 polymorphism achieved eradication, and only 29% (5/17) of all CYP3A4*1B carriers did not achieve eradication. All nine patients carrying CYP3A4 polymorphisms in the CYP2C19 hetEM subgroup were cured, suggesting the possibility of a positive synergism between CYP3A4 and CYP2C19. Conclusions This first pharmacogenomics study on the influence of different CYP genotypes on H. pylori therapy suggests that, as in Asian populations, CYP2C19 genotype patterns are probably also relevant in Caucasians receiving H. pylori eradication regimens that include omeprazole. The possibility of a favorable drug interaction mediated by CYP2C19 and CYP3A4 requires investigation.

Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis.

Triple therapies combining a double dose of proton pump inhibitor plus two antibiotics are the standard treatment for Helicobacter pylori infection. Some reports suggest that the use of half the dose of proton pump inhibitor is equally effective. To compare the efficacy of a single vs. double dose of proton pump inhibitor in triple therapy. We conducted a MEDLINE search. The search strategy included the words (pylori) AND (triple, PPI, proton pump, omeprazole, rabeprazole, pantoprazole, lansoprazole, clarithromycin, amoxicillin, amoxycillin or metronidazole). Abstracts of the articles obtained and papers presented at the European Helicobacter pylori Study Group and American Gastroenterological Association congresses from 1996 to 2001 were examined. Inclusion criteria were: (i) randomized studies with at least two branches of triple therapy including a proton pump inhibitor and two standard antibiotics; (ii) branches could differ only in terms of proton pump inhibitor dosage. A meta-analysis was conducted using conventional shareware (Review Manager 4.1). Thirteen studies met the inclusion criteria with a total of 2391 patients. Cure rates with double doses of proton pump inhibitor were higher in both the intention-to-treat analysis (83.9% vs. 77.7%; Peto odds ratio, 1.51; 95% confidence interval, 1.23-1.85; P < 0.01) and per protocol analysis (89% vs. 81%; Peto odds ratio, 1.96; 95% confidence interval, 1.55-2.47; P < 0.01). Triple therapies containing a single dose of proton pump inhibitor are less effective than those containing a standard double dose of proton pump inhibitor.

Announcing the Creation of the Paediatric European Register for Treatment of Helicobacter pylori (PERTH)

Announcing the Creation of the Paediatric European Register for Treatment of Helicobacter pylori (PERTH)

The Maastricht recommendations and their impact on general practice.

At a meeting organized in Maastricht by the European Helicobacter Pylori Study Group, European consensus guidelines for the treatment of Helicobacter pylori were established by determining what relevant information from research could be translated into clinical practice. Many of the patients infected with H. pylori can be diagnosed and treated in the primary care setting. Dyspeptic patients under 45 years of age, with no alarm symptoms or risk of gastric or oesophageal malignancy, can be tested non-invasively and treated in the primary care setting. For diagnosis, a validated non-invasive method is recommended, such as the 13C-urea breath test or laboratory-based serology if properly validated in the region in which it is used. The meeting strongly recommended that all patients with peptic ulcer are treated with eradication therapy. Patients over the age of 45 years and those with alarm symptoms should be referred with no hesitation to the specialist After full consideration of the treatments used to date, it was strongly recommended that treatment should be with proton-pump inhibitor-based triple therapy, consisting of a proton-pump inhibitor and two of the following: clarithromycin, a nitroimidazole (metronidazole or tinidazole) and amoxycillin. The evidence supporting the use of these therapies has been substantiated in large clinical trials that were recently completed.

Do young dyspeptics require endoscopy any more?

The main rationale for endoscoping young patients is to diagnose peptic ulcer disease and reassure those with a normal examination. Most peptic ulcers are known to be caused by Helicobacter pylori, leading to novel investigation strategies for young dyspeptic patients. In retrospective studies, screening patients under 45 years for H. pylori and only investigating those who were positive reduced the number of endoscopies without missing significant pathology. The European Helicobacter Pylori Study Group recommends that all dyspeptic patients 45 years of age or younger, without sinister symptoms, are given a non-invasive test for H. pylori. H. pylori-positive patients should receive acid pump inhibitor-based triple therapy, without further investigation. In Leeds, UK, open-access 13C-urea breath testing (UBT) is offered to dyspeptic patients under 40 years who are not taking non-steroidal anti-inflammatory drugs. H. pylori-negative patients are reassured and referred back to their general practitioner; positive patients receive omeprazole-based triple therapy for 1 week. Dyspepsia scores fell significantly following the UBT, reflected by a reduced number of visits to the general practitioner and a fall in H2-receptor antagonist prescriptions. Since introducing this service, there has been a 34% reduction in endoscopies in patients under 40 years in this unit.

A prospective randomised trial of a “test and treat” policy versus endoscopy based management in youngHelicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic

BACKGROUNDManagement of dyspepsia remains a controversial area. Although the EuropeanHelicobacter pylori study group has advised empirical eradication therapy without oesophagogastroduodenoscopy (OGD) in young H pylori positive dyspeptic patients who do...

Helicobacter pylori eradication in patients with non-ulcer dyspepsia.

Epidemiological and pathophysiological studies, as well as clinical trials, attempting to identify a relationship between Helicobacter pylori infection and non-ulcer dyspepsia (NUD), or a subset of NUD, have produced inconsistent and confusing results. While it is possible that H. pylori eradication may be beneficial for symptom relief in a small proportion of patients, routine H. pylori testing and treatment in documented NUD is not currently widely accepted. Despite the lack of convincing evidence, the European Helicobacter pylori Study Group, an Asian Pacific Consensus Meeting, the American Digestive Health Foundation and the American Gastroenterology Association have all recommended considering H. pylori eradication in patients with NUD on a patient-by-patient basis. Recently, large prospective, randomised, double-blind, controlled clinical trials applying highly effective antimicrobial therapy have been conducted with 12 months follow-up. Although these well-designed studies have reached differing conclusions, the results have been largely negative. H. pylori eradication therapy in NUD will fail to relieve symptoms in most patients in the long term.

What Other Regimens Are Under Investigation to Treat Helicobacter pylori Infection?

The most common infection in the world, Helicobacter pylori infection, is very specific, and present experience in treating infectious diseases is not applicable in general for this infection. Animal models (e.g., mouse and ferret) are thus far inadequate as reliable screening models. Old-fashioned trial-and-error treatment of infected humans is still the screening model and the gold standard in the evaluation of regimens aimed at eradication of H. pylori. A variety of studies on treatment of H. pylori infection have been performed with varying results. This pooled analysis of the following therapeutic combinations: proton pump inhibitor (PPI) plus two antibiotics or antimicrobials, quadruple therapies, and nonantibiotic regimens is an attempt to make a fair comparison of tested therapeutic strategies aimed at eradicating H. pylori. Data from treatment groups including specified drug combinations are pooled, regardless of dose or duration. Search methods are: MEDLINE 1984-1996, Digestive Disease Week 1988-1996, United European Gastroenterology Week 1992-1996, European Helicobacter pylori Study Group 1988-1996, Asia Pacific Congress 1996, H. pylori International Workshop Hong Kong 1996, and miscellaneous. Eradication rates (efficacy) are presented as intention-to-treat data (i.e., worst-case analysis). Separate subanalyses with regard to study quality, dose, and duration are performed for some groups. A general cost-efficacy analysis is performed based on pooled efficacy data. Convenience data are presented as total number of tablets, total number of intake occasions, and duration of therapy. Drugs evaluated in the analysis are bismuthdicitrate, tetracycline, amoxicillin, nitroimidazoles, macrolides, H2-receptor antagonists, PPIs, sucralfate, and sofalcone. The most effective and convenient drug combinations are the PPI-based triple therapies. No significant difference was observed between the three PPIs. The cure rate did not improve after addition of bismuth. Cost-effectiveness is closely associated with efficacy.

Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report. European Helicobacter Pylori Study Group.

There is considerable confusion over the management of Helicobacter pylori infection, particularly among primary care physicians, and numerous European countries lack national guidelines in this rapidly growing area of medicine....

O-4-58 - Statistical contribution to prognostic factors in spontaneous intracerebral hematomas. Of v-cramer coefficient and discriminative analysis

The most common infection in the world, Helicobacter pylori infection, is very specific, and present experience in treating infectious diseases is not applicable in general for this infection. Animal models (e.g., mouse and ferret) are thus far inadequate as reliable screening models. Oldfashioned trial-and-error treatment of infected humans is still the screening model and the gold standard in the evaluation of regimens aimed at eradication of H. pylori. A variety of studies on treatment of H. pylori infection have been performed with varying results. This pooled analysis of the following therapeutic combinations: proton pump inhibitor (PPI) plus two antibiotics or antimicrobials, quadruple therapies, and nonantibiotic regimens is an attempt to make a fair comparison of tested therapeutic strategies aimed at eradicating H. pylori. Data from treatment groups including specified drug combinations are pooled, regardless of dose or duration. Search methods are: MEDLINE 1984-1996, Digestive Disease Week 1988-1996, United European Gastroenterolgy Week 1992-1996, European Helicobacter pylori Study Group 1988-1996, Asia Pacific Congress 1996, H. pylori International Workshop Hong Kong 1996, and miscellaneous. Eradication rates (efficacy) are presented as intention-to-treat data (i.e., worstcase analysis). Separate subanalyses with regard to study quality, dose, and duration are performed for some groups. A general cost-efficacy analysis is performed based on pooled efficacy data. Convenience data are presented as total number of tablets, total number of intake occasions, and duration of therapy. Drugs evaluated in the analysis are bismuthdicitrate, tetracycline, amoxicillin, nitroimidazoles, macrolides, H2-receptor antagonists, PPIs, sucralfate, and sofalcone. The most effective and convenient drug combinations are the PPI-based triple therapies. No significant difference was observed between the three PPIs. The cure rate did not improve after addition of bismuth. Cost-effectiveness is closely associated with efficacy.

Conference report: duodenal ulcer trials reported at the European Helicobacter pylori Study Group, Edinburgh 1995.

The abstracts from the 8th International Workshop on Gastro-duodenal Pathology and Helicobacter pylori held in Edinburgh, 7-9 July 1995, are published in Gut 1995; 37 (Suppl. 7). I was privileged to act as reporter to the Plenary Workshop on Duodenal Ulcer Trials chaired by Prof. Seppala. Prof. Roy Pounder and I felt that in such a fast moving field as Helicobacter pylori there would be some merit in briefly reviewing the eight excellent papers presented at the Workshop. The main reason for this being that six of the presentations were well conducted randomized prospective clinical trials of H. pylori eradication therapy and the other two had important clinical messages.

Helicobacter pylori: Beginning the Second Decade

‘Beginning the Second Decade’ - a recent international meeting onHelicobacter pylori- was held in conjunction with the VIIth International Workshop on Gastroduodenal Pathology andH pyloriand with the meeting of the EuropeanHelicobacter pyloriStudy Group in Houston, Texas from September 30 to October 1, 1994. A menu of 476 abstracts, published in the American Journal of Gastroenterology (1994;89:8), highlighted the explosion of advances in this area. The Houston meeting was followed by the Tenth World Congresses of Gastroenterology from October 2 to 7, 1994 in Los Angeles, California, again with scores of presentations and posters on topics ranging from the epidemiology ofH pyloriinfection to steps towards the development of a human vaccine. All this was in addition to important new work presented earlier in 1994 in New Orleans during Digestive Diseases Week. In this digest of these important meetings, the authors will not regurgitate what the informed reader already knows, but will instead focus on the recent developments in important areas, providing selected key published references for background, and referring to this new work in abstract form which is at the cutting edge of “yesterday’s tomorrow today”.