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- stomach neoplasms
- metachronous second primary neoplasms
- endoscopic mucosal resection
- standardised incidence ratio
The development of gastric epithelial neoplasia is closely linked to precursor conditions in the background mucosa.1–3 Recently, endoscopic mucosal resection (EMR) has become widely used for the treatment of gastric neoplasia,4 resulting in almost complete conservation of the patient’s stomach. To determine the risk of a second cancer in the stomach that once gave rise to epithelial neoplasia, we conducted a long term retrospective cohort study of 255 patients with primary gastric epithelial neoplasia who underwent curative resection by EMR between 1983 and 2002 at our hospital.
Characteristics of the subjects at the initial treatment are shown in table 1. Synchronous multiple neoplasias were confirmed in 19 (7.5 %) of the 255 subjects; 56 patients had adenomas and 199 had cancer. In the eight patients with both gastric cancer and adenoma, cancer was taken as the representative histology. In this study, we defined lesions classified as category 3 in the Vienna classification5 as “adenoma” and categories 4 and 5 as “cancer”.
A second gastric cancer developed in 43 of the 255 patients. The crude incidence rate of the second gastric cancer was 3.9 per 100 person years. Kaplan-Meier estimates showed that the three year and six year cumulative incidence rates of newly developed gastric cancers were 10% and 20%, respectively. The cumulative incidence of subsequent cancer increased steadily throughout the observation.
To compare the risk of new development of gastric cancer in our patients with that of general population in Japan,10 the standardised incidence ratio (SIR) was calculated. SIR for newly developed cancer in our patients was 10.4 (95% confidence interval 7.0–14.9). SIRs stratified according to sex, age, and synchronous multiplicity at the initial treatment are also shown in fig 1A.
Furthermore, we analysed the factors predicting subsequent gastric cancer development. Ten of the 56 adenoma and 33 of the 199 cancer patients had newly developed gastric cancer. The crude incidence rates of the second cancer were exactly the same (3.9 per 100 person years) in both groups, and the cumulative incidences did not differ between the two groups using the Kaplan-Meier method (p = 0.97; fig 1B). Patients with synchronous multiple lesions were at a significantly higher risk than those with a solitary lesion (p<0.01; fig 1C). Multivariate analysis confirmed the above findings (table 1).
All of our patients were positive for Helicobacter pylori but did not receive eradication therapy because many underwent EMR before the mid 1990s. Thus a very high rate of H pylori infection appears to be at least partly responsible for the high incidence of the second cancer in our patients.6 However, the incidence in our patients was much higher than H pylori positive Japanese3,7 and Chinese8 patients without a history of gastric neoplasia. Thus factors other than H pylori infection were also involved in the development of the second gastric cancer in our patients with previous gastric neoplasia.
An important finding of our study was that patients with gastric adenoma had the same risk for the development of a subsequent gastric cancer as those with gastric cancer. In addition, we found that a considerable number of our patients with gastric adenoma (12.5%) had concurrent gastric cancer. Thus although gastric adenoma may rarely progress to cancer,9 it is likely that gastric cancers and adenomas develop in the same background of the gastric mucosa, probably with similar genetic alterations or environmental conditions.
Taken together, our results indicate that patients with a previous history of either gastric adenoma or cancer are at a higher risk of subsequent development of gastric cancer. Once neoplasia develops, the gastric mucosa should be considered to have an exceedingly high potential to develop cancers.
We thank Professor T Fujimori of the Department of Surgical and Molecular Pathology, Dokkyo University School of Medicine, Tochigi, Japan, for useful advice on histopathology.
Conflict of interest: None declared.
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