Commentary on: The management of patients with gastric intestinal metaplasia

Recently, GUT published a review of guidelines for the management of gastric intestinal metaplasia (GIM) with the goal of promoting harmonization of the guidelines regarding indications for endoscopic screening for gastric cancer and gastric intestinal metaplasia detection/staging, metrics for high quality endoscopy and for non-endoscopic interventions for gastric cancer prevention in patients with GIM.[1] GIM is not a disease per se, but rather is a reparative response to gastric mucosal injury that may be present, at least temporarily, as part of healing such as of an ulcer.[2] Clinically, widespread GIM is best considered a manifestation of healing of another disease, typically Helicobacter pylori infection or autoimmune gastritis. When present in autoimmune gastritis, GIM has no malignant potential and is potentially completely reversible.[3] In contrast, when associated with chronic H. pylori infection, GIM is typically permanent and, at most, minimally reversible [4]. The underlying H. pylori-induced inflammation is carcinogenic. H. pylori-related GIM is a manifestation of the duration, extent, and severity of an H. pylori infection which, in turn, is related to the risk of gastric cancer. Because GIM is easily recognized and reflects the extent and severity of the infection, it is a valuable surrogate for the risk of developing gastric cancer. This has given GIM a role in determination of an individual’s cancer risk. However, because GIM is neither a disease nor a cause of cancer, eradication of gastric cancer should focus on the eradication of the cause, i.e., H. pylori infections.

The population risk of finding gastric cancer and H. pylori-associated atrophic gastritis and GIM, here called Hp-GIM, increases logarithmically with age (Figure 1). As also shown, the age-related increase in cancer risk is a reflection of the increase in the extent and severity of the gastric mucosal damage with aging (i.e., the age-related increase in risk is a manifestation of the increasing proportion of the population with severe mucosal injury). Elimination of gastric cancer requires elimination of H. pylori and there are an infinite number of ways to approach achieving that objective.[5] The infection is typically acquired in childhood from one of the parents, typically the mother. As seen in the Figure, the risk is progressive. Delaying treatment of asymptomatic children until teenage years (e.g., between ages 15 and 20) would avoid the issues regarding antibiotic use in children and the likelihood of reinfection, while the risk of developing advanced atrophic gastritis during this period remains low [6]. Curative treatment before extensive damage has occurred will largely eliminate subsequent gastric cancer risk. In addition, cure of the infection will also break the cycle of transmission of the infection to their subsequent children.

Figure: Age as a surrogate for cancer risk.

The plot illustrates the change in the relative proportions of the gastritis of increasing severity a plot of gastric cancer incidence (Japanese men in 1986).

Population-based approaches, although difficult to implement should be considered. For example, a requirement for a negative H. pylori test at the time of obtaining a marriage license (as was previously done for syphilis) could help ensure protection of subsequent children. Ideally, the eradication program would also include a second H. pylori eradication group (e.g., those ages 40 through 45). Eradication at that time would prevent further progression of the gastric mucosal damage for that cohort and thus reduce the incidence of subsequent gastric cancer. After a maximum of 20 years following introduction of the eradication program the majority of the population should be H. pylori free.

It would also be important to plan for dealing with the importation of H. pylori H. pylori infected immigrates from high H. pylori and gastric cancer prevalence populations (e.g., in US immigrants from parts of Asia, Mexico, Central and South America). Dealing with these special populations will be politically difficult as it would likely require determination of H. pylori status. Separate planning will be required regarding how to deal with the information.

GIM is of special interest to gastrointestinal endoscopists and cancer epidemiologists who focus on cancer reduction/prevention and use GIM as a gastric cancer risk marker. [1] This interest presupposes that the pipeline is continuous and that resources should be plentiful as it concerns relatively small and defined populations. Initially, in Japan and Korea where GIM screening is currently practiced, the population at risk was initially very large. However, the incidence of H. pylori in children and the prevalence of GIM among those infected has steadily fallen to where progressively fewer of those undergoing endoscopic screening have atrophic gastritis. The gastric cancer elimination program proposed above for the US would be only required for a relatively short period. However, a version might need to be continued focused on high-risk populations (e.g., immigrants from high-risk countries). A strategy of test and cure as a requirement to remain in the country would be easier to implement but technically and politically difficult.

We appear to be on the cusp of having highly-effective simplified H. pylori therapies (i.e., potassium competitive acid blocker plus amoxicillin or tetracycline dual therapies that would potentially allow short one-off treatments.[7, 8] This approach, following antimicrobial stewardship principles would help minimize unnecessary antibiotic prescriptions and reduce the risk of population exposure to ineffective treatments, thereby preserving the efficacy of the vital antibiotics for future use. [9, 10]

Management based on the presence and severity of GIM requires upper endoscopic examinations which are typically prompted by clinical symptoms, with follow-up endoscopies generally guided by the diagnoses made during the initial examination. Unless specific screening programs are implemented, multiple biopsy-based assessments for GIM will remain opportunistic among patients with various symptoms and mainly serve a research agenda. In countries with an intermediate or high incidence of gastric cancer, or within specific populations in low-incidence countries, H. pylori testing and treatment could also offer a practical opportunity to establish a foundation for integrating secondary prevention of gastric cancer within the treatment-based gastric cancer eradication program (i.e., in the older cohort). In this context, patients can be specifically recruited for gastric cancer prevention and evaluated according to standardized eligibility criteria for upper endoscopy. Standardized biopsy protocols for diagnosing GIM can provide a unified approach to generate new knowledge to optimize the management of patients who continue to face residual gastric cancer risk after H. pylori eradication. Although this addition would significantly add to the cost, the duration would be limited as the pool of H. pylori-infected patients dried up.