Panel discussion: breaking the link — clinical options to minimize risk
Year: 1999
Type: article
Abstract: “The two presentations we have heard complement each other well in terms of the reviewing the epidemiology and overall phenomena associated with H. pylori, inflammation and gastric cancer, and in helping to establish the underlying mechanisms for these conditions. Now we will discuss how this basic science relates to the practising clinician and I would like to invite our panel and the audience to put forward their questions.” “Dr Kuipers, based on your review of the literature can you give a ‘guestimate’ of how long it takes gastric cancer to develop?” “During my presentation I showed all the stages leading towards gastric cancer in one scheme, however, it generally takes many decades until the end-point is reached and this is reflected in the fact that most gastric cancers occur over the age of 70 years. To give you one example, in general populations who are infected with H. pylori, the annual incidence for atrophy is less than 2% per year, so this is a very slow process; it takes more than 30 years before one out of every three infected subjects has developed atophic gastritis.” “In detecting high-risk individuals who are H. pylori-positive, with a high risk of gastric cancer, do we have any powerful non-invasive tests for gastric atrophy?” “Unfortunately no, we do not. The most commonly used test is pepsinogens and pepsinogen ratios but their predictive values are still very poor.” “We have heard that the risk of developing gastric cancer if you are infected with H. pylori is about 1%; others have suggested that the figure is higher than this, for men probably about 1 in 50 of the general population. That being the case, from a clinical point of view, if we see people in our dyspepsia clinic who are H. pylori-positive, do you think it is desirable to tell patients that there is this risk?” “Obviously, it would be desirable to tell the patient but then the next question from the patient will be: what can you do about it? What we can do is eradicate H. pylori but then, as I mentioned in my presentation, we know that we can eliminate the infection but we do not know how this influences the risk of gastric cancer. In other words, once we eradicate H. pylori in an adult aged 50, H. pylori may have been present in their stomach for the previous 40 years. Even if we know whether, as a result of this, there has been any permanent damage such as atrophy and metaplasia, we still cannot prove that eradicating H. pylori decreases cancer risk.” “That may be correct but most general practitioners, when faced with a patient with a sore throat will treat them with an antibiotic, even though the chances of dying of a sore throat are negligible. In view of this, do you not think that we should use eradication therapy in patients who have a condition that we know increases the risk of more serious diseases.” “I am not saying that we should not treat them at all, what I am saying is that when we treat them we still do not know if we are doing any good in terms of cancer development. Obviously, there are many patients that a clinician would like to treat because they have an infection which increases cancer risk but do you decrease cancer risk once you get rid of the infection? We do not know at present.” “This brings me to the question currently being debated amongst paediatricians, some of whom think that there is not enough evidence to treat the symptoms of recurrent abdominal pain and who are questioning whether it would be interesting to treat children with the aim of preventing disease in adulthood. The prevalence of H. pylori infection in children is quite low but does the panel think that clinicians should consider eradicating H. pylori in children in order to prevent the evolution of severe disease in adulthood, especially gastric cancer?” “Peter Ernst is a Professor of Paediatrics. Professor Ernst, what is your opinion on this matter?” “There are very few studies that have been done in children that would indicate when changes would be reversible. Part of the question is therefore at what age should they be treated? I would hesitate to treat all H. pylori-positive children without knowing at what stage the treatment is going to be effective. It might also be difficult to persuade an 8-year-old to take triple therapy.” “It is not really practical to wait for the results of evidence-based studies when considering the treatment of children and wanting to see what happens when they are adults. We have to live with assumptions, taking into account what we know about the evolution of this infection. Do you agree that we do not have sufficient evidence at present?” “There is another aspect to consider, namely, what is the adverse effect of treating children? The issue of antibiotic resistance should also be considered. There is a much smaller panel of antibiotics used to treat H. pylori than sore throats for example, so we need to conserve our options. Regarding the potential benefit of treatment, there are some studies showing that the decrease in H. pylori infection can cause other problems in the proximal stomach. If you do not know if there is any risk, it is difficult to recommend whether it is beneficial, particularly with our knowledge of the epidemiology.” “As many of you will know, I have been interested in the issue of whether the loss of H. pylori increases the risk of proximal disease. We now know that colonization with H. pylori increases the risk of distal gastric cancer but if it in fact decreases the risk of proximal cancer then the advice that clinicians give to their patients will have to be fairly complex. Perhaps we are in a transition period at this present time in which we cannot give a clear answer to patients and have to just wait and see. This is especially relevant to children.” “Listening to Dr Kuiper's presentation, the gastroenterologist in a district general hospital is left between the horns of a dilemma. If a patient is H. pylori-positive and you eradicate the organism, the risk of distal cancer is decreased. If you don’t eradicate, the virulent cagA-positive H. pylori strains could be protective against proxi-mal cancer. My question is: what do you do in practical terms? Also, the results of a number of studies have recently been presented suggesting that no excess gastro-oesophageal reflux disease occurs once H. pylori is eradicated, which is in contrast to what has been put forward previously. How good is the evidence? Just be-cause you find that H. pylori is more prevalent in patients with proximal cancer, does this really mean that this is causing proximal cancer, or is it just a confounder?” “My position is quite clear on this. The data suggesting that H. pylori causes distal cancer is, in my view, strong. If I had the infection, I would certainly treat it in myself. I would therefore take the view that I would want to treat it in my patients as well, and that is usually what they want.” “I agree with Professor Axon: there is strong evidence for a link between H. pylori and distal gastric cancer, however, evidence for a protective effect on proximal cancer is much weaker.” “I think that data regarding H. pylori and proximal gastric cancer are relatively strong. We do not really understand the underlying mechanism, however, where there is a decreasing prevalence of H. pylori, there is an increasing incidence of proximal cancer. There are now consistent studies showing a negative association between H. pylori cagA-positive antibodies and the presence of Barrett's oesophagus and proximal carcinoma. In considering whether or not you should give eradication therapy to an H. pylori-positive patient who has no symptoms, we need to tell the patient that they have a 1% chance of developing gastric cancer but that we do not know the influence of the treatment in that risk.” “This is an interesting question. I had an H. pylori test which turned out to be positive so I was treated, however, if my children were infected it would be a very difficult decision. A lot of the changes in the distal stomach are reversible up to a certain age, possibly the second decade. I would probably delay the decision to treat as long as possible. Hopefully, the research will give us the answers soon.” “To summarize, the evidence linking H. pylori to distal gastric cancer is clear and indisputable, however, the rise of proximal cancers is increasing in what could be described as epidemic proportions in western countries and there are many data, although preliminary, that point in the same direction, so we need to be cautious.” “I would like to add another dimension to what has been discussed. If you look at what has been going on, we are currently in an evolutionary process during which these diseases have changed. We have had the change from gastric ulcer to duodenal ulcer then probably to an increase in reflux. The factor in this equation is that populations, for a variety of reasons, are probably increasing their acid output. The recent paper by Kinoshita et al. was totally consistent with this. If we look at Japan as an example of the change from gastric to duodenal ulcer, ultimately we would expect that with a loss of H. pylori an increased reflux would be produced. There is another dimension to this evolution: we are changing. Looking at the patterns of disease it appears that we are in fact changing the nature of our acid output. If our H. pylori colonization remained the same but the population was making more acid, we would be likely to see a lot more duodenal ulcer disease. This is not happening in fact because we are losing H. pylori, but it is another factor in the equation when we look at the issue of proximal cancers.” “I agree that there are a lot of factors involved. A lot of the studies are based in populations in Asia, South America Europe, etc. and the results can be very confusing and it is difficult to know how they apply to other populations. We can compare with other pathogens, for example EB virus, and see that they behave differently in different populations.” “There are only a few cases of gastric cancer, but a lot of premalignant lesions, for example intestinal metaplasia. In view of this, is it necessary to take intestinal metaplasia or atrophy into account when managing H. pylori-positive patients?” “I think that is something that would be quite logical to do. If you have a patient who has already developed atrophy or metaplasia, you would suppose that this patient was at increased risk of developing cancer and you would want to treat them. Once again, we know that atrophy and metaplasia do not seem to regress but we do not know what this means for cancer risk.” “It does not regress but this means that there is also no evolution. If you eradicate H. pylori you could expect that the condition would remain stable, which is good. Similarly, if you stop smoking your risk of developing lung cancer will probably decrease to a certain extent. In addition to eradicating H. pylori, is there anything else that can be done in a patient with intestinal metaplasia?” “I would make a distinction between what is reversible and what is not. My pathology training taught me that fibrosis is rarely reversible. Inflammatory atrophy is more likely to be linked to cancer and is reversible, which gives us an opportunity for intervention. The only other therapy at present, in addition to eradicating the bacteria, is perhaps antioxidant therapy to minimize the damage.” “Clinicians are rightly concerned about the link between H. pylori and gastric cancer but they are even more concerned at present about the possibility that proton pump inhibitor therapy in the presence of H. pylori infection may accelerate the development of atrophic body gastritis. What is the attitude of the panel to this and what possible mechanisms might underlie it, particularly as it seems to occur without an apparent decrease in the density of H. pylori infection?” “The hypothesis is that although the numbers of H. pylori do not increase, they get closer and deeper down into the pits, especially in the body mucosa, where they can induce a greater degree of inflammation. What we need to have are data showing that if you eradicate H. pylori in these patients, you prevent this accelerated progression to atrophy, and these studies are currently ongoing.” “I would like to go back to the issue of children. We always say that early acquisition of H. pylori infection is a risk factor for gastric cancer, however, it should be borne in mind that acquisition is always early: a 70-year-old man will have acquired his infection when he was 5 or 10 years old. We know that there are other risk factors for gastric cancer such as a diet low in antioxidants or rich in salt: should we not put more emphasis on these other factors rather than H. pylori which is already on the decline? Even in children we now have a increasing incidence of gastro-oesophageal reflux disease, so perhaps we should put less emphasis on early acquisition and more on antioxidants in the diet.” “I have been very interested in the question of early acquisition and it is just a hypothesis at present but the basis of the hypothesis is that a child who acquires the organism at 1 year of age is different immunologically from a child who acquires it at 3 or 5 years of age. We know that that is true for many other microorganisms, such as hepatitis B.” “I would just like to mention a study that we are currently undertaking, the Eurohepygast study,1 that will be presented at this Workshop. This does not concern cancer but rather premalignant lesions and the development of atrophy. Taking into account all these parameters, including environmental factors, strain factors and also some genetic factors, it turns out that the factors most strongly associated with the development of atrophy were the characteristics of the strain of the organism.” “We have undertaken considerable research on ascorbic acid. Some time ago it was recognized that the concentration of vitamin C in the gastric juice of individuals infected with H. pylori was low compared with uninfected subjects. We have performed a number of studies dosing people with ascorbic acid. There are two interesting findings: firstly, the level of ascorbic acid within the mucosal cell, which is probably where it is most important in terms of neutralizing the effects of oxygen radicals, is similar in infected and uninfected subjects. It is only in the juice that concentrations are low. When you give vitamin C supplements, there is an increase in vitamin C within the mucosa but unless you eradicate H. pylori, you do not get a very significant rise in the levels of vitamin C in the juice. I cannot speak about other antioxidants but my predication would be that vitamin C on its own is unlikely to have a great deal of benefit.” “I would like to take up the point made by the previous questioner, if we are not positive and clear about the advice we give to patients, their stress levels will increase, their confusion will increase and we will not modify their behaviour at all. Surely, it is important to be clear; to reduce their risk of gastric cancer they need to avoid a lot of salty food, reduce their alcohol consumption, stop smoking, reduce obesity and perhaps if we make them aware that they may need to seek further endoscopies after fairly long intervals, 20 or 30 years. A lot of these patients are worried by the fact of finding that they have an infection that no-one can apparently deal with and that no-one can give them clear answers about.” “You can give a very clear answer: you can say that they are infected with a bacterium that increases their risk for distal gastric cancer but the immediate following question will be: what can you do about my cancer risk? You can say I do not know; I can probably reduce it by eradication therapy. That is all that we can say for now.” “But you cannot alter their overall genetic risk for cancer. There are many people who have a family history of cancer, they may have cancers in other sites and they are now found to be H. pylori-positive — it is just another risk factor for them to deal with. If we are clear about our advice to them that they eat a healthy diet, that they avoid alcohol and tobacco and keep their weight down, and that there is evidence that these factors reduce their overall risk of cancers. If we concentrate solely on H. pylori, we are doing a disservice to these patients.” “I would concur with that point. In think in part we are trying to find one solution to a very heterogeneous group of disorders and a very heterogeneous human population. I think that as the H. pylori era continues, we are going to be looking at a much more indivi-dualized approach, especially if eradication has costs as well as benefits. This will become very complex and require a variety of diagnostic tools, some of which probably do not exist at present.”
Authors: M.J. Blaser, E.J. Kuipers, P. Ernst, A. Axon, F. Mégraud
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1999903765