4Precancerous lesions in the stomach: From biology to clinical patient management
Introduction
Over the last 25 years, a growing body of evidence has shown that epithelial malignancies are the final step along a complex biological path involving a progressive (multi-factorial) accumulation of genotypic and phenotypic changes, and sporadic gastric cancer is by no means an exception [1], ∗[2].
Less than 10% of gastric cancers (GC) are hereditary. The genetic factors involved in familial malignancies remain largely unknown, although specific, well-characterized mutations have been thoroughly described in a subset of patients.
By far the majority of GCs are sporadic, most of them triggered by long-standing inflammatory conditions (due primarily to infectious, but also to chemical agents or autoimmune diseases) resulting in a mainly-unknown interplay of molecular and phenotypic derangements. Such a natural history, as at first described by Pelayo Correa, is currently known as Correa's multi-stage cascade of gastric oncogenesis. According to Correa, long-standing mucosa inflammation may result into gastric atrophy/intestinalization, which may further progress into advanced precancerous lesions (APLs; currently distinguished into low-grade [LG-IEN] and high-grade intraepithelial neoplasia [HG-IEN]); these spectrum of intraepithelial neoplastic changes may eventually develop into invasive cancer [3]. APLs are conventionally identified as phenotypic alterations bridging the (phenotypic/genotypic) gap between regenerative/metaplastic changes and invasive cancer (Fig. 1) [1], ∗[2]. In the Western literature, these phenotypic lesions were originally labelled as ‘epithelial dysplasia’. For the time being, detecting and ablating gastric APLs represent the most reliable strategy for the secondary cancer prevention.
This paper addresses the basic information (i.e.: epidemiology, pathology, molecular profiling) on the natural history of gastric precancerous lesions, also providing the biological rationale for their follow-up and treatment.
Section snippets
Precancerous conditions & precancerous lesions in the gastric mucosa
As in other areas of the gastrointestinal tract, so too within the gastric mucosa, a basic distinction is drawn between precancerous conditions and precancerous lesions. According to Basil Morson, a precancerous condition, ‘…is best regarded as a clinical state associated with a significantly increased risk of cancer, whereas a precancerous lesion is a histological abnormality in which cancer is more likely to occur … In many clinical conditions with an increased risk of cancer, there is also
Gastric atrophy (& atrophic gastritis)
The two ‘major’ compartments of the gastric mucosa feature different populations of native glands (mucosecreting in the antrum, oxyntic in the corpus). Gastric atrophy is defined as the ‘loss of appropriate glands’ [13]. This definition basically includes two phenotypes of gastric mucosa atrophy: (i) shrinkage or complete disappearance of glandular units, replaced by fibrotic expansion of the lamina propria (i.e. a reduced glandular mass, with no modification of the native cell phenotype); or
Gastric dysplasia: original definition and basic morphology
Gastric adenocarcinoma may coexist with cyto-architectural changes in the adjacent glands, showing a degree of (de-)differentiation somewhere between that of the native mucosa and that of the cancer. The Western literature defined such phenotypic changes as epithelial dysplasia ∗[4], [23], [24], [25], [26], [27], [28], [29], [30], [31], while Japanese authors speak of borderline lesions, atypical epithelium, or Group 3 lesions [32], [33], [34]. The topographical contiguity and morphological
Molecular pathology of gastric intraepithelial neoplasia
Molecular typing of gastric IEN has reinforced the conviction that these lesions belong to the same biological spectrum as their invasive counterpart. The most widely accepted theory is that non-invasive neoplastic cells derived from previously-intestinalized (metaplastic) epithelia. These cancer-oriented cells have recently revealed a stem cell nature. In fact, an experimental model of chronic Helicobacter pylori-related gastritis demonstrated that bone-marrow-derived cells may home onto the
Precancerous lesions: treatment and (possible) reversion
The clinical management of precancerous gastric lesions is controversial. The related ‘operative inconsistency’ results mainly from the unreliable quantification of the cancer risk associated with the precancerous condition, and from the difficulty of assessing the clinical benefit achievable with surveillance strategies.
A nationwide Dutch study on patients with precancerous gastric lesions showed that endoscopic/histological re-assessments were performed in 26%, 28%, 38% and 61% of patients
Screening and surveillance of precancerous gastric lesions
In clinical practice, surveillance strategies for precancerous gastric lesions are currently inconsistent, and are often disregarded ∗[58], [59]. The declining incidence of precancerous gastric lesions (particularly in the industrialized word), variables relating to the health care systems in different countries, inconsistencies in cost–benefit assessments, the identification of different target patient populations, different methods being used to implement screening/surveillance strategies,
Gastric precancerous lesions in clinical practice
No evidence-based guidelines are available as yet to support a particular clinical strategy in response to a histological diagnosis of gastric IEN. Given the differences in the diagnostic criteria, the Japanese experience cannot be wholly exported to the Western world ∗[38], [109], [110].
Based on current knowledge, the following strategies can be considered for the clinical management of atrophic gastritis and intestinal metaplasia:
- 1.
H. pylori eradication is indicated in patients with atrophic
Conflict of interest
The authors have no conflict of interest to declare.
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