H pylori Eradication and Gastric Cancer
H pylori Eradication and Gastric Cancer
Helicobacter pylori infection continues to play a key role in gastric diseases. Colonization of the gastric mucosa with the bacterium invariably results in the development of chronic gastritis and subsets of patients have a progression of the chronic gastritis to either ulcer or cancer. Epidemiological evidence indicates that the proportion of all gastric cancers attributable to H. pylori infection, and hence potentially preventable upon elimination of this risk factor, is somewhere in the range of 60% to 90%. This portends significant benefit in terms of morbidity and mortality, not least in populations with high prevalence of H. pylori infection coupled with high incidence of gastric cancer. The effect of prophylactic H. pylori eradication on gastric cancer incidence in humans remains unknown, however. Results from randomized trials are eagerly awaited, but availability of strong conclusive results may take many years. A growing number of studies show considerable variation in risk for gastric cancer development, depending on H. pylori strain type and the genetic predisposition of the host. There is also a remote possibility that elimination of the infection may have adverse health implications (e.g., antibiotic resistance), and therefore "simple" risk stratification and targeted chemoprevention is required. Based on "in depth" evidence presented at this workshop, the majority of the scientific task force favored a search-and-treat strategy in first-degree relatives of gastric cancer patients and an overwhelming majority felt that a more general screen-and-treat strategy should be focused in the first instance on a population with a high incidence of H. pylori-associated diseases.
It is now more than 10 yr since Helicobacter pylori was cited as a gastric carcinogen. In the latest available epidemiological studies, based on the most accurate methodology, the presence of H. pylori infection combined with CagA antibody status increases the risk of gastric cancer 20-fold, compared with controls. One estimate attributed 70% of distal gastric cancers to H. pylori, while the highest estimate claimed that H. pylori is a condition sine qua non for gastric cancer development.
There is, however, no conclusive evidence that H. pylori eradication prevents gastric cancer. Supportive data could, theoretically, be obtained from prospective trials of eradication, but, in practice, such trials do not exist and may be impossible to conduct for reasons of duration, ethics, etc. Consequently, decisions may be based on the biological plausibility, and on indirect evidence which shows a beneficial effect of eradication on conditions and lesions of the stomach mucosa that precede overt gastric cancer. There is no doubt that the pathogenesis of gastric cancer is associated with a variety of environmental factors, of which H. pylori infection appears to be the most prominent and with genetic predisposition, a variety of gene errors and abnormal gene expression. Changes in biology, growth, and death of the cancer cells have been observed in conjunction with H. pylori infection. It is also a known fact that these same genomic and cellular lesions also occur in the benign gastric epithelium long before the appearance of an overt cancer, and that these lesions predispose to the development of cancer. It is conceivable, therefore, and highly probable, that any beneficial effects of eradication therapy on these precancerous conditions, lesions, or cellular and genomic changes (i.e., reversal) should also prevent gastric cancer.
This review represents a state-of-the-art critique of evidence obtained from many experimental investigations conducted in animal models as well as in human tissues and cells. In order to assess what preclinical and clinical evidence is currently available, a number of statements were formulated and discussed at a workshop with experts in the field of H. pylori research, held in Lejondal, near Stockholm. The evidence for each suggested statement was presented by one of the experts in that particular field and a vote was taken concerning the validity of the statement and the level of supportive documentary evidence. In view of the depth of information required for each statement, two parallel workshops took place, one dealing with experimental and microbiological evidence and the other with clinical evidence. These were followed by a joint plenary session with all experts present, at which they were invited to vote on all statements under discussion and to agree/disagree with the suggested level of the evidence. The methods used for voting and for assessing documentary evidence are summarized in Table 1 .
The document is based largely on information available at the time of the workshop, but has also been updated with more recent relevant literature. In view of the magnitude of the gastric cancer problem in China and Japan, provision was also made for additional comments from the perspective of specialists practicing in these geographical areas (Professors Xiao and Sugano).
Helicobacter pylori infection continues to play a key role in gastric diseases. Colonization of the gastric mucosa with the bacterium invariably results in the development of chronic gastritis and subsets of patients have a progression of the chronic gastritis to either ulcer or cancer. Epidemiological evidence indicates that the proportion of all gastric cancers attributable to H. pylori infection, and hence potentially preventable upon elimination of this risk factor, is somewhere in the range of 60% to 90%. This portends significant benefit in terms of morbidity and mortality, not least in populations with high prevalence of H. pylori infection coupled with high incidence of gastric cancer. The effect of prophylactic H. pylori eradication on gastric cancer incidence in humans remains unknown, however. Results from randomized trials are eagerly awaited, but availability of strong conclusive results may take many years. A growing number of studies show considerable variation in risk for gastric cancer development, depending on H. pylori strain type and the genetic predisposition of the host. There is also a remote possibility that elimination of the infection may have adverse health implications (e.g., antibiotic resistance), and therefore "simple" risk stratification and targeted chemoprevention is required. Based on "in depth" evidence presented at this workshop, the majority of the scientific task force favored a search-and-treat strategy in first-degree relatives of gastric cancer patients and an overwhelming majority felt that a more general screen-and-treat strategy should be focused in the first instance on a population with a high incidence of H. pylori-associated diseases.
It is now more than 10 yr since Helicobacter pylori was cited as a gastric carcinogen. In the latest available epidemiological studies, based on the most accurate methodology, the presence of H. pylori infection combined with CagA antibody status increases the risk of gastric cancer 20-fold, compared with controls. One estimate attributed 70% of distal gastric cancers to H. pylori, while the highest estimate claimed that H. pylori is a condition sine qua non for gastric cancer development.
There is, however, no conclusive evidence that H. pylori eradication prevents gastric cancer. Supportive data could, theoretically, be obtained from prospective trials of eradication, but, in practice, such trials do not exist and may be impossible to conduct for reasons of duration, ethics, etc. Consequently, decisions may be based on the biological plausibility, and on indirect evidence which shows a beneficial effect of eradication on conditions and lesions of the stomach mucosa that precede overt gastric cancer. There is no doubt that the pathogenesis of gastric cancer is associated with a variety of environmental factors, of which H. pylori infection appears to be the most prominent and with genetic predisposition, a variety of gene errors and abnormal gene expression. Changes in biology, growth, and death of the cancer cells have been observed in conjunction with H. pylori infection. It is also a known fact that these same genomic and cellular lesions also occur in the benign gastric epithelium long before the appearance of an overt cancer, and that these lesions predispose to the development of cancer. It is conceivable, therefore, and highly probable, that any beneficial effects of eradication therapy on these precancerous conditions, lesions, or cellular and genomic changes (i.e., reversal) should also prevent gastric cancer.
This review represents a state-of-the-art critique of evidence obtained from many experimental investigations conducted in animal models as well as in human tissues and cells. In order to assess what preclinical and clinical evidence is currently available, a number of statements were formulated and discussed at a workshop with experts in the field of H. pylori research, held in Lejondal, near Stockholm. The evidence for each suggested statement was presented by one of the experts in that particular field and a vote was taken concerning the validity of the statement and the level of supportive documentary evidence. In view of the depth of information required for each statement, two parallel workshops took place, one dealing with experimental and microbiological evidence and the other with clinical evidence. These were followed by a joint plenary session with all experts present, at which they were invited to vote on all statements under discussion and to agree/disagree with the suggested level of the evidence. The methods used for voting and for assessing documentary evidence are summarized in Table 1 .
The document is based largely on information available at the time of the workshop, but has also been updated with more recent relevant literature. In view of the magnitude of the gastric cancer problem in China and Japan, provision was also made for additional comments from the perspective of specialists practicing in these geographical areas (Professors Xiao and Sugano).
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