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Editor,—The Maastricht Consensus Report (Gut 1997;41:8–13) is a welcome benchmark summarising current opinion and scientific evidence regarding the role of Helicobacter pylori in gastroduodenal disorders. Whereas the management of peptic ulcer disease is no longer controversial and is very evidence-based the same is not yet true for the syndrome of non-ulcer dyspepsia and the management of the uninvestigated dyspeptic patient. The recommendation of the Maastricht Report reflects this uncertainty. They recommend that at the specialist level, eradication therapy for H pylori infected non-ulcer dyspepsia is “advisable”, based on supportive scientific evidence, but only after “full investigation” including endoscopy, ultrasound and other tests. However, in the management algorithm for the uninvestigated dyspeptic in primary care, non-invasive testing (with a breath test) and treatment is recommended for patients who are at a low risk of gastric carcinoma. Why such a difference? If it is recommended that a breath test is investigation enough of dyspepsia in primary care then an endoscopy and biopsy should be adequate in specialist practice if there are no other clinical indicators of another diagnosis (such as biliary colic) and the patient is at low risk of malignancy. The difficulty is that non-ulcer dyspepsia will remain a hard target and even several studies of symptom response after eradication therapy due to be reported shortly will not resolve the issues as there will be perennial debate about inclusion and exclusion criteria in such trials and these will have a great bearing on outcomes. Moreover, the ability to quantitate the lifetime risk reduction of peptic ulcer disease and perhaps even gastric carcinoma in patients who have eradication therapy will remain contentious. Medico-legal issues and patient preferences will also continue to be important factors influencing the decision to investigate and treat. At present the suggested test and treat strategy of uninvestigated patients seems reasonable for well-informed, low-risk patients with endoscopy the recourse if needed. Further investigation and the decision to test and treat for H pylori in uninvestigated dyspeptics and investigated dyspeptics who fit the criteria for non-ulcer dyspepsia will no doubt remain a decision that is assessed on a “case by case” basis as suggested in the recent report of the American Digestive Health Initiative.1
Functional dyspepsia in the young
Editor,—I read with interest the Maastricht Consensus Report on the diagnosis and treatment of Helicobacter pylori infection (Gut 1997;41:8–13). Whereas the role of H pylori in peptic ulcer disease, gastric carcinoma and mucosa associated lymphoid tissue type lymphoma is established, its role in functional dyspepsia is still controversial. Recent data indicate that H pylori positive patients with functional dyspepsia benefit from eradication therapy.
In 1989, we published a treatment algorithm in which serological screening had a key part in the decision whether or not to endoscope patients presenting with dyspepsia.1-1 We suggested that endoscopy was not essential and advocated anti-H pyloritreatment in seropositive dyspeptic patients. In our original algorithm there were several unanswered questions regarding coincidental non-helicobacter related disorders. These questions would have to be answered before serological screening could be used in routine practice. At that time this algorithm was refuted.1-2Nevertheless since then several papers have been published in which serological screening was used. However no data were available on non-helicobacter related disorders of the upper gastrointestinal tract and also real screening was not done as selected patient populations were used.1-3-1-5
Much to my surprise the Maastricht Consensus Report advocates anti-H pylori therapy in seropositive dyspeptic patients under 45 years of age without the need for endoscopy. Although, from a clinical point of view I fully agree with this statement, it is based on common sense and not on scientific evidence. To the best of my knowledge, no prospective studies have been done in which seropositive patients did not undergo endoscopy. Selected patient populations were studied in all of the references quoted in the report. Endoscopy should be omitted, in retrospective analysis, on seronegative cases.
If serology is used and endoscopy is not performed in selected cases, whether H pylori positive or negative, it is inevitable that some cases of non-helicobacter related disease will be missed, reflux oesophagitis being the most important. It is essential that a non-selected patient population is assessed to determine how many cases of reflux oesophagitis would be missed if endoscopy was not done. This is especially true as the clinical presentation of reflux oesophagitis is far from specific. We showed in a recent paper that the majority of dyspeptic patients with reflux oesophagitis were H pylorinegative,1-6 and that, at least in theory, the best screening strategy seemed to be to omit endoscopy in seronegative patients.
The statement that serological screening is cost effective and leads to more efficient use of endoscopy facilities has yet to be proved in prospective randomised studies. The only study published to date is unsuitable as a selected patient population was used.1-7
Editor,—I was astonished, as I am sure many were, to see publication of the The Maastricht Consensus Report (1997;41:8–13) in Gut. Not only was this surprising, but to see it appear as a leading article was even more amazing particularly in an issue which carried an editorial by yourself on research misconduct, quite rightly condemning similar practices.
Under the circumstances, it does not appear unreasonable to enquire whether you were aware at the time that a synopsis of this event had previously been published in the European Journal of Gastroenterology and Hepatology (1997;9:1–2)? If so, no acknowledgement appears to have been included in this parallel report. Had you been informed that the meeting from which this report had its origins was organised “with an educational grant from Astra-Hässle” with accompanying documentation inferring that travel and hotel expenses were paid for participants and discussions limited to those who were paid for? If so, why is this not acknowledged in the leading article and it registered as a possible “conflict of interest” as seems to be the philosophy of your parent publishing group, and acceptance of financial support within the stated policy of your own journal. Perhaps your readers should further be aware that this publication is the result of discussions by a self-appointed group who have no mandate to represent any official bodies or organisations.
In the light of the above, it will perhaps come as no surprise that the conclusions recommend widespread testing of dyspeptics under the age of 45 years for Helicobacter pylori and subsequent treatment in primary care, supported by no evidence-base whatsoever. The other major conclusion, that a proton pump inhibitor based treatment regimen should usually be used is perhaps also understandable in the light of the conference’s financial support. Indeed, the conclusions are not even supported by data quoted by these authors themselves, which includes a number of studies with various proton pump based triple therapies which, on an “intention to treat” basis have eradication rates less than the stated ideal of 80%.Letters, Book reviews, Notes
It appears that you have either been seriously misled or made a grave error of judgement in publishing this paper. Its contents are confused and misleading, its conclusions restrictive and its appearance in print repetitive, and it does little to guide any of us in the management ofH pylori infections in Europe, or indeed the world, today. Furthermore, its publication does little to enhance the reputation ofGut internationally.
Editor,—We expected that controversy and criticism would follow our attempt to propose European guidelines for the management of a disease as complex as Helicobacter pyloriinfection. Dr Heatley’s letter however goes beyond this and can be only regarded as an example of destructive and uninformed criticism. Dr Heatley incorrectly reports aspects of both the structure and the nature of the Maastricht meeting.
The allegation of dual publication, and to castigate both the authors and the editor, is unfair and misleading. An abstract was published in the European Journal of Gastroenterology and Hepatology, but the complete report with a detailed description of the meeting structure and outcome, including references supporting the various conclusions, was published in Gut. The Consensus Report isnot original work but is of educational value and was intended to be disseminated widely
The group was not self appointed. The Maastricht Conference gathered together an expert faculty from various medical disciplines, the European Helicobacter pylori Study Group, and national representatives, who were nominated by their national gastroenterology societies from 19 European countries. Our aim was to produce management guidelines in this very complex field.3-1 3-2
The European Helicobacter pylori Study Group, since its foundation in 1987,3-3 has been very active in the organisation of educational and scientific meetings both in and beyond Europe initially at a time when H pylori was not widely accepted as a cause of gastric disease and presently when there is increasing demand for guidance in treating the infection.
To blame the organisers for seeking support from industry, which was given in the form of an unrestricted educational grant, is unfair. Representatives from the major pharmaceutical companies with an interest in the treatment of peptic ulcer disease, such as Astra, Byk Gulden, Glaxo Wellcome, and Takeda, were invited and did in fact attend the meeting.
With regard to medical aspects of Dr Heatley’s criticisms, we would like to remind him that treating H pylori positive dyspeptic patients under 45 years of age, without alarm symptoms, with eradication therapy in primary care is not uncommon in the UK.3-4 In the absence of evidence, the best available knowledge and experience should be taken into account in guiding clinical practice. At the Maastricht conference we suggested that general practitioners, gastroenterologists and microbiologists should form an interactive network to implement and sustain our recommendations.
The firm recommendation for the PPI containing regimen at a standard dose given twice daily in combination with amoxycillin, clarithromycin or metronidazole was based on the clinical trials available at that time which showed that this treatment was the most suitable in terms of efficacy, compliance and side effects.
We never intended that the Consensus Report should be the final word on the management of H pylori infection but rather that is would be a starting point and would prompt discussion over the next few years. Certainly, it had enough impact to serve as a model and to inspire other important consensus conferences that have recently taken place in North America, Japan and in the Asia-Pacific region.
From the editor
The authors of the Maastricht Consensus Report were entirely open about the fact that they intended to submit a brief synopsis of the report to the European Journal of Gastroenterology and Hepatology at the time that they submitted their manuscript for consideration for publication in Gut. I regarded this as an “abstract” of the main report and thus did not consider this dual publication. The authors did not disclose the meeting sponsor in the report but this oversight was put right in a subsequent issue of the journal.
We decided to publish the Maastricht Consensus Report because of the importance of Helicobacter pylori in clinical practice. I am not surprised that the views expressed do not necessarily find universal approval but one should never shy away from controversy.
Efficacy of ranitidine bismuth citrate (RBC) dual and triple therapies for the eradication of Helicobacter pylori
Editor,—We write in response to the leading article “Current European concepts in the management of Helicobacter pylori infection. The Maastricht Consensus Report” recently published (Gut 1997;41:8–13).
The phrase “Additionally, no recommendation can be made regarding the role of RBC until more convincing data are available” is somewhat at variance with the conclusion agreed at the meeting in Maastricht in September 1996 which was sponsored by Astra-Hässle.
The data on RBC reviewed at the Maastricht meeting was based on conclusions drawn from limited information on clinical trials which did not have the eradication of H pylori as the primary endpoint. The actual conclusion at the end of the meeting was that “more data are needed to define the role of RBC”. This was disseminated widely in the form of a document handed out at the 5th United European Gastroenterology Week in Paris in November 1996, and in the summary of the Maastricht conclusions printed in January 1997.5-1
In the year since this meeting took place, results from several clinical trials on RBC dual and triple5-2 5-3 therapy have been published or presented at several international congresses. RBC has now been evaluated in clinical trials for the eradication ofH pylori in over 6300 patients. Our conclusions based on all clinical trials to date are that dual therapy of RBC 400 mg twice daily with clarithromycin 500 mg twice daily for 14 days (nine treatment arms from nine clinical studies; six double blind) gave a pooled observed eradication in 946 of 1037 patients (91.2%), a pooled intention to treat eradication in 946 of 1153 patients (82.0%), and the eradication rates were comparable in patients with or without an extra 14 days of RBC 400 mg twice daily added to ensure duodenal ulcer healing. A clinical study evaluating RBC with clarithromycin dual therapy showing a per protocol eradication rate of 95.9% in a large, double blind, randomised study was published in February 1997.5-4
Results of the first two head-to-head, double blind, randomised clinical studies showed that therapy with RBC and clarithromycin gaveH pylori eradication rates which were highly significantly superior, both clinically and statistically, to omeprazole plus either amoxycillin5-5 or clarithromycin.5-6
For those wishing to use three drugs in place of two, triple therapy of RBC 400 mg twice daily with clarithromycin twice daily and a nitroimidazole for seven days (nine treatment arms from eight clinical studies; three double blind) gave a pooled intention to treat eradication in 659 of 751 patients (87.7%). Triple therapy of RBC 400 mg twive daily with clarithromycin 500 mg twice daily and amoxycillin 1000 mg twice daily for seven days (eight treatment arms from seven clinical studies; two double blind) gave a pooled intention to treat eradication in 348 of 417 patients (83.5%). Both these treatment regimens were as effective as a proton pump inhibitor with the same antibiotics.
The latest information available from clinical trials with RBC–antibiotic combinations show that either a 14 day dual therapy of RBC with clarithromycin or a seven day triple therapy of RBC with two antibiotics achieve >80% eradication of H pylori as assessed on an intention to treat basis. Each of these regimens therefore meet the “Maastricht criteria” of simple and effective eradication therapies.
Editor,—While it is true that Astra Hässle provided the grant to the European Helicobacter pyloriStudy Group (EHPSG), it is also true that Drs Duggan and Williamson from Glaxo Wellcome were invited to and took part in the Maastricht meeting.
It was the firm intention of the organisers to collect all available information from clinical trials on H pylori with the aim of producing comprehensive guidelines for the management of H pylori infection. At that time however (September 1996) there were not sufficient data on RBC based seven day treatment for it to be recommended in the Consensus Report. New data are now available. At the recent EHPSG meeting in Lisbon further data were presented on the efficacy of RBC based treatment and it now meets the criteria agreed at Maastricht.
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