Precancerous gastric lesions are one of the most blamed factors in the etiology of gastric cancer (stomach ca) (1,2,3,4). As a result of epidemiology and pathology studies, the sequence of events in gastric carcinogenesis; It is considered to be in the form of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and carcinoma (1,3,4,5,6) (Table-1).
In studies performed on samples taken during autopsy and operation, it has been shown that gastric cancers frequently develop from precancerous conditions (1,4) (Table-2).
Chronic atrophic gastritis, intestinal metaplasia, epithelial dysplasia and gastric polyps are the most important pathologies that cause gastric cancers and especially intestinal type gastric cancers (1,7).
Precancerous gastric lesions are mostly associated with distal gastric cancers (4,7). On the other hand, cardia and distal esophageal adenocarcinomas are associated with Barrett’s esophagus. Studies have also found a strong relationship between the frequency of these cancers and the incidence of Barrett’s esophagus (8).
Gastric cancers are cancers with poor prognostic features. However, when they are caught in the early, treatable period, that is, in the mucosa, a significant difference was found in their prognosis compared to advanced carcinomas (9).
Early detection of gastric cancer development by observing precancerous lesions in the mucosa and following these patients for a long time and at frequent intervals provides the opportunity for early treatment (4,9).
Table-1: Premalignant lesions in which gastric cancer may develop:
Chronic atrophic gastritis
Pernicious anemia
Intestinal metaplasia
Gastric epithelial dysplasia
Partial gastrectomies in benign diseases
Menetrier’s disease
Gastric polyps (980070703) (9800) ) Barrett’s esophagus
Gastric ulcers
“Excess salt causes atrophy of the gastric mucosa.”
1-Chronic Atrophic Gastritis:
Chronic atrophic gastritis (CAG) usually starts multifocally from the distal stomach regions. As a result of decreased gastric acid secretion, focal atrophic foci may merge and turn into metaplasia, dysplasia and eventually gastric carcinoma (4,10).
Excess salt has been shown to cause atrophy in experimental animals (11). In CAG, acid secretion decreases and gastric pH increases. As a result of the increase in pH in the stomach, anaerobic bacteria increase, and these bacteria lead to the formation of N-nitroso compounds, which are mutagenic and carcinogenic. Thus, the risk of carcinoma also increases. Natural antioxidants inhibit the formation of N-nitroso compounds (1,4,12).
Many studies have shown that the prevalence of CAG and intestinal metaplasia is equally high in countries with the highest prevalence of gastric cancer (1,13,14). CAG and intestinal metaplasia (IM) are also associated with environmental risk factors with a high prevalence in countries where gastric cancer is endemic. It is accepted that CAG and IM are an important intermediate step in the pathogenesis of endemic intestinal type gastric cancers (1,13,14). KAG
“In the case of chronic atrophic gastritis, gastric acid secretion
decreases, so that N-nitorso compounds, which are carcinogenic agents, are formed under the influence of anaerobic bacteria.”
and anaerobic bacteria, which often form colonies in the stomach due to IM, contribute to the formation of carcinoma by converting nitrites and nitrates into N-nitroso derivatives, which are more potential carcinogenic agents (15,16). However, it is known that atrophic gastritis and achlorhydria alone cannot cause gastric cancer, and that CAG and IM can also be found in healthy individuals who do not develop gastric cancer (1).
In retrospective examinations of surgical materials of patients with gastric carcinoma, a high rate of CAG was detected in intestinal type gastric cancers (17,18). However, in endoscopic biopsies of individuals over 60 years of age, chronic atrophic gastritis can be seen in 40% of cases without gastric carcinoma (19,20).
Pernicious anemia is a specific type of atrophic gastritis that develops by immune mechanism. In countries where pernicious anemia is common, the prevalence of gastric adenocarcinoma is 3% (21). It is estimated that 2% of all gastric cancers are associated with pernicious anemia. However, it is not certain that pernicious anemia increases the risk of gastric cancer (4). Gastric carcinoid tumors are also more common in these patients. It has been reported that acid suppression, hypergastrinemia and neuroendocrine hyperplasia cause a malignant picture (22,23). Pernicious anemia increases the development of gastric cancer 2-3 times (22,24).
2-Intestinal Metaplasia
Intestinal metaplasia (IM) means the replacement of normal gastric epithelium with columnar epithelium similar to that in the small intestine or colon (25,26). Metaplasia is mostly seen in the antrum. IM areas can spread to large areas as well as infrequently as foci (27). IM begins and spreads from the neck of the mucosal cell. When fully developed, the gastric mucosa takes on the appearance of the small intestine mucosa. IM is often associated with chronic atrophic gastritis (28). Demirtürk et al. detected 89.4% of IM on the basis of chronic atrophic gastritis (29).
“Helicobacter pylori is one of the important factors leading to the development of chronic atrophic gastritis and intestinal metaplasia from chronic gastritis.”
In the area of IM, the gastric mucosa has both morphological and biochemical features of the small intestinal epithelium. The IM developed stomach has turned from being a secretory organ to an intestinal area that can absorb some substances such as lipids from the gastric lumen. It is stated that this event occurs as a result of the histological change chain of chronic gastritis, chronic atrophic gastritis (5,27,30).
Helicobacter pylori (Hp) infection has been reported to be an important cause of chronic gastritis resulting in atrophy and metaplasia (5,27).
IM is seen endoscopically as irregular areas that are hyperemic compared to normal mucosa. It is very difficult to distinguish this appearance from the endoscopic appearance of gastritis (25,27).
Three types of intestinal metaplasia have been described according to morphological and histochemical criteria (25,31).
Type I (complete) IM has brushy-edged mature absorbent cells and acid sialomucin-secreting goblet cells. The appearance of the epithelium is similar to the small intestinal epithelium, sometimes even the villi structure can be seen. The most characteristic feature is that Paneth cells are seen in the lower part of the gland
In Type IIa (incomplete) intestinal metaplasia, mature absorbent cells and generally Paneth cells are absent. There are goblet cells that secrete acidic sialomucin and columnar mucus cells that secrete neutral mucin or neutral mucin-sialomucin.
In Type IIb (incomplete) intestinal metaplasia, large goblet cells may secrete sialomucin or sulfomucin, or both. There are less differentiated columnar mucus cells that secrete sulfomucin.
Matsahura et al. examined intestinal metaplasia in 2 groups as complete and incomplete. While the complete type consists of glandular structure in the small intestine, the incomplete type is dominated by colonic gland structures (25,31).
Intestinal metaplasias cause changes not only in the morphological appearance of the gastric mucosa, but also in cell kinetics, immunological and enzymatic structures (25,26). Of these lesions, especially incomplete, those containing sulfomucin,
“Every year, 6.7% of those with chronic atrophic gastritis develop intestinal metaplasia and 3.2% of those with intestinal metaplasia develop dysplasia.”
intestinal type gastric carcinomas have been shown to be precursor lesions in histogenesis in a wide variety of studies (32,33,34).
In a study, 7290 patients with gastric pathology were followed for an average of 5.1 years (3-16 years). It has been reported that chronic atrophic gastritis (CAG) develops at a rate of 7.5% per year in patients with normal gastric histology in biopsies at baseline, IM develops in 6.7% of patients with CAG, and dysplasia develops in 3.2% of patients with IM. In the same study, it was determined that the rate of patients with normal gastric histology at the beginning and developing gastric carcinoma during follow-up was 0.03% (35).
In another study, during long-term follow-up of 1788 cases, it was determined that a faster progression was observed in patients with high pH in gastric juice, high nitrate and nitrite values, and in parallel with this, in precancerous gastric lesions such as CAG, IM and dysplasia (13). ). In another retrospective study, the preparations of 234 cases that were previously evaluated as IM were re-evaluated and gastric cancer was detected in 9 (3.8%) cases, while gastric cancer was detected in only 1 (0.89%) of 116 cases without intestinal metaplasia (36). ).
Histopathological studies have shown that intestinal metaplasia often accompanies intestinal type gastric cancers. Again, in these studies, it was shown that the prevalence of intestinal metaplasia in patients with diffuse type gastric carcinoma is equal to the prevalence in the general population (15).
3-Gastric epithelial dysplasias
Gastric epithelial dysplasias (GED) are the most important premalignant lesions. Dysplasia can develop from metaplasic or non-metaplasic mucosa. The macroscopic appearance of the lesion in the mucosa may be in the form of collapse of the mucosa or polypoid, or it may be in the form of a slight discoloration of the flat mucosa. (4,37,38).
There are some difficulties in the diagnosis of GED. In the differential diagnosis, a distinction should be made between regenerative atypia and true dysplasia. In addition, severe dysplasia can be confused with intramucosal carcinoma from time to time. Therefore, GED is considered
“Gastric epithelial dysplasias are the most important premalignant lesions.”
Multiple biopsy samples should be taken from the area and carefully examined. Benign regenerative changes may also be evaluated as mild or moderate dysplasia from time to time. However, severe dysplasia should always be considered as a neoplastic change and cases should be followed at frequent intervals (4,37,38,39).
In studies in which the resection material was re-evaluated retrospectively in patients who were operated for early gastric cancer, the rate of those with moderate or severe dysplasia in regions adjacent to the cancer was found to be 40-100% (39). However, this rate is 3% in patients with operated chronic atrophic gastritis and only 1% in patients with gastric ulcer (40.41.42).
In many prospective studies, dysplasias were followed for 6 years or more and the following conclusions were reached (4,43,44,45):
1)-Dysplasias are divided into 3 groups: Mild, moderate and severe dysplasias
2)-Mild dysplasias are minor lesions and regress over time in 60-70% of patients. They remain intact in 20-30% of cases. In 10% of cases, they progress and the degree of dysplasia increases. Very rarely, carcinoma may develop.
3)-Moderate dysplasias are similar to mild dysplasias. However, the rate of those who develop severe dysplasia and/or carcinoma is 10-14%.
4)-Severe dysplasias are more serious lesions. The regression rate of dysplasia is 30-45%. He often just persists. However, dysplasia is suppressed in 20-80% of patients and some of them turn into gastric carcinoma.
In studies, it has been determined that severe dysplasia is associated with endoscopic lesions such as erosions, ulcers and polyps at a rate of 50-60%. In the same studies, approximately 50% of severe dysplasia with visible endoscopic lesion (eg, gastric ulcer or polyp) was diagnosed as carcinoma in biopsy specimens 3 months after severe dysplasia was detected. Therefore, it is accepted that severe dysplasia often coexists with cancer. Diagnosis of severe dysplasia with endoscopy alone is difficult. Histopathological examination is absolutely necessary (43,44).
The following protocol is generally followed in the follow-up of dysplasia (4,44,45):
“Severe dysplasia should always be considered as a very important premalignant lesion and such patients should be followed at frequent intervals.”
1)-It is usually sufficient to check mild dysplasias at long intervals, especially if they are not accompanied by an important endoscopic lesion. In fact, some researchers do not consider it necessary to follow them.
2)-Moderate dysplasias are similar to mild dysplasias. However, some authors recommend more frequent control and more frequent biopsy.
3)-Severe dysplasias, on the other hand, should be followed up at short intervals since they are often found together with cancer. Even if malignancy is not detected, these patients should be called for regular controls. Some authors even suggest resection in severe dysplasias with large endoscopic lesions (4,43,45). It is hoped that with the widespread use of molecular biological techniques and cell proliferation analyzes, real and new information will be obtained in terms of the malignancy risk in GED and the follow-up of patients (15).
Gastric cancer, which has an important place among the causes of death from cancer and has a poor prognosis, still maintains its importance today despite the developing endoscopic techniques. For this reason, studies all over the world focus on the diagnosis of gastric cancers in the early stage, that is, in the intramural stage. In parallel with these, the importance of early diagnosis of precancerous conditions and precancerous lesions observed in cases where these conditions are present, increases with the determination of the pathogenesis and developmental stages of the disease (1,4).
Today, all attention is focused on precancerous lesions, ie precancerous lesions, in the developmental stages of carcinoma, as well as the recognition of tumors in the curable period. Carcinomas are more likely to develop on the background of these lesions than in the normal mucosa. Recent studies have focused on detecting precancerous changes in the gastric epithelium and early detection of possible malignant development during follow-up. Thus, it will be possible to prevent gastric cancer before it develops or even if it does develop in a very early period (1,4).
