INTRODUCTION
Recently, as endoscopy has become more accessible, the detection rate of gastric polyps has improved. Gastric polyps can be broadly described as lesions protruding into the stomach, but more precisely, as neoplastic or hyperplastic lesions arising from the mucosa of the stomach [
1]. The gastric polyps most commonly identified by endoscopy are hyperplastic, fundic gland, and adenomatous. Gastric hyperplastic polyps often exhibit proliferation and expansion of the foveolar epithelium and glands. A well-known cause of these particular histological characteristics is a
Helicobacter pylori infection [
2]. In regions with high
H. pylori prevalence, gastric hyperplastic polyps account for up to 75% of the gastric polyps detected [
3].
Most gastric hyperplastic polyps are asymptomatic and are incidentally detected on endoscopy. Observation through regular follow-up is a possible course of action if the polyp is small. However, the risk of focal adenocarcinoma rises with an increase in the size of the polyp; a previous study reported this risk to be as high as 2.1% [
4]. Therefore, endoscopic resection is recommended for symptomatic or large-sized gastric hyperplastic polyps. In general, for gastric hyperplastic polyps > 10 mm in size, endoscopic resection is recommended to exclude neoplastic foci and prevent neoplastic transformation [
5]. The guidelines of the American Society of Gastrointestinal Endoscopy recommend endoscopic resection for gastric polyps > 5 mm [
6].
As gastric hyperplastic polyps are associated with
H. pylori infection, removal of the underlying conditions that cause mucosal damage can be effective. Hence,
H. pylori eradication may be considered as a treatment option. Case-control studies and randomized controlled trials have reported that
H. pylori eradication in patients with gastric hyperplastic polyps reduces the size of the polyp and improves inflammation in the gastric mucosa [
7–
9]. Guidelines on the management of
H. pylori infection in Japan recommend
H. pylori eradication in patients with multiple gastric hyperplastic polyps (evidence level II) [
10]. Similarly, the British Society of Gastroenterology recommends testing and treatment for
H. pylori when the presence of gastric hyperplastic polyps is noted (high evidence, definite recommendation) [
11]. However, it is not well known whether
H. pylori infection affects the recurrence of hyperplastic polyps after endoscopic resection. For this reason, we evaluated the recurrence rate of gastric hyperplastic polyps based on
H. pylori eradication after endoscopic resection of gastric hyperplastic polyps.
DISCUSSION
In this retrospective multicenter study, the cumulative incidence of gastric hyperplastic polyp recurrence after endoscopic resection was higher in the non-eradication group compared to that in the eradication group. In the non-eradication group, gastric hyperplastic polyps predominantly recurred 1 to 2 years after endoscopic resection, whereas gastric polyps recurred gradually with time in the eradication group. H. pylori eradication therapy significantly reduces the recurrence of gastric hyperplastic polyps after endoscopic resection, whereas anticoagulation therapy increases the risk of recurrence.
This was a retrospective study that investigated whether
H. pylori eradication therapy could prevent the recurrence of hyperplastic polyps after endoscopic resection. Our investigation showed that during a mean follow-up period of 18.3 months, gastric hyperplastic polyps recurred in 22 patients. The cumulative incidence of gastric hyperplastic polyps was higher in the non-eradication group (19.2%) than in the eradication group (8.1%). A reduction in the recurrence of gastric hyperplastic polyps, after
H. pylori eradication, is associated with a reduction or loss of inflammation induced by
H. pylori. Gastric hyperplastic polyps often occur as a result of a prominent, reparative, or regenerative phenomenon, and
H. pylori infection is well known as a causative factor [
14].
H. pylori infection causes damage to the gastric mucosa and increases the expression of inflammatory mediators such as cyclooxygenase-2, interleukin-1β, and hepatocyte growth factor [
7,
15,
16]. It has been reported that these inflammatory mediators cause gastric epithelium proliferation and foveolar hyperplasia, resulting in gastric hyperplastic polyps [
17,
18].
In previous observational studies, approximately 90% of patients who underwent
H. pylori eradication showed partial loss or complete regression of the lesion [
19]. In a recent randomized controlled trial involving 27 patients with gastric hyperplastic polyps, all patients demonstrated polyp regression in the eradication group, whereas no regression was observed in the non-eradication group [
13]. However, it is rarely reported whether the presence of
H. pylori affects recurrence after endoscopic resection of gastric hyperplastic polyps. In a study conducted in Korea by Kang et al. [
20], 79 patients were followed-up after endoscopic resection of gastric hyperplastic polyps. In this study, the recurrence rate of gastric hyperplastic polyps was higher in the
H. pylori-persistent group (42.9%) than in the
H. pylori-eradicated group (21.7%), but this was not statistically significant. Additionally, the previous study had limitations in that it was a single-center study with a small sample size. Therefore, our study provides sufficient evidence for the relationship between
H. pylori infection and the recurrence of gastric hyperplastic polyps after endoscopic resection.
In this study, neoplastic lesions occurred in four patients during the follow-up period. The non-eradication group had a higher incidence rate (5.8%) of gastric dysplasia than the eradication group (0.7%), but the difference was not statistically significant. This was probably due to the small number of patients. However, previous studies have reported that
H. pylori eradication reduces the incidence of gastric dysplasia. A retrospective study conducted on 282 patients diagnosed with gastric dysplasia reported that
H. pylori eradication therapy was able to reduce the incidence of metachronous gastric neoplasms after endoscopic resection [
21]. In contrast, a study on 129 patients diagnosed with gastric dysplasia reported that
H. pylori eradication did not reduce the recurrence of gastric adenoma after endoscopic resection [
22]. Gastric hyperplastic polyps are thought to be markers for mucosa that is predisposed to developing carcinomas. The incidence of adenocarcinoma developing in the background gastric mucosa, associated with a hyperplastic polyp (but not within the polyp), is 6% [
23,
24]. Therefore, it can be stated that
H. pylori eradication in gastric hyperplastic polyps provides a secondary benefit of preventing gastric neoplasms as well as reducing the recurrence of gastric polyps. However, evidence for this is currently lacking, and further research is required.
Gastric hyperplastic polyps that are 0.5 to 1 cm or more in size are associated with an increased risk of neoplastic lesions; therefore, endoscopic resection and a thorough pathologic examination of the resected tissue are required [
25]. According to the American Society for Gastrointestinal Endoscopy Guideline, gastric polyps ≥ 5 mm in size are known to increase the risk of neoplastic lesions [
6]. In the case of small polyps, follow-up endoscopic examinations are performed according to the results of the histological examination. However, in a cohort study on gastric hyperplastic polyps less than 1 cm diagnosed through Korea’s national cancer screening program, 84% of the polyps disappeared in the group that received treatment for
H. pylori and 34% regressed in the untreated group. Therefore, successful
H. pylori eradication increases the possibility of the disappearance of hyperplastic polyps (adjusted odds ratio, 5.56; 95% CI, 2.63 to 11.11) [
26]. A total of 23 patients had remnant polyps in this study.
This study demonstrated that anticoagulation therapy increased the risk of recurrence of gastric hyperplastic polyps, whereas age, sex, chronic disease, smoking, drinking, nonsteroidal anti-inflammatory drugs, statins, and polyp site were not associated with recurrence of gastric hyperplastic polyps after endoscopic resection. The association between anticoagulants and gastric hyperplastic polyps has never been reported. Therefore, it is difficult to elucidate a clear mechanism behind this association. Anticoagulants are used to treat underlying diseases, such as atrial fibrillation, and have been reported to be associated with atrial fibrillation and inflammatory gastrointestinal conditions. Additionally, it is possible to hypothesize that anticoagulants may influence inflammation and immune responses against
H. pylori infection by inhibiting the coagulation cascade. Fibrin, an end product of the coagulation cascade, is known to play a protective role during infection by limiting bacterial dissemination and activating the antimicrobial properties of monocytes and macrophages [
27,
28]. A previous study showed an increased level of fibrin in the gastric mucosa of
H. pylori-positive patients [
29]. Therefore, the use of anticoagulants has the potential to induce an excessive inflammatory response to
H. pylori infection, along with inhibition of the coagulation pathway. Further research on the relationship between the host immune response to
H. pylori infection and the coagulation pathway is required.
As this was a retrospective study, selection bias was inevitable. However, this study may be of clinical significance in providing evidence for the usefulness of H. pylori eradication therapy after endoscopic resection of gastric hyperplastic polyps. Randomized controlled trials and large-scale studies on the prevention of gastric hyperplastic polyps after endoscopic resection are needed in the future. To our knowledge, this is the first report to show that anticoagulation therapy increases the risk of recurrence of gastric hyperplastic polyps. In the future, the association between anticoagulation therapy and gastric hyperplastic polyps should be investigated.
In conclusion, H. pylori eradication reduces the recurrence of gastric hyperplastic polyps after endoscopic resection. This study provides evidence of the usefulness of H. pylori eradication after endoscopic resection in patients with gastric hyperplastic polyps. Moreover, further studies are required to elucidate the association between anticoagulation therapy and hyperplastic gastric polyps.