Should we perform surveillance endoscopy after endoscopic submucosal dissection of premalignant gastric adenoma?

Metachronous gastric cancer (MGC) after curative endoscopic resection (ER) of early gastric cancer (EGC)

Endoscopic submucosal dissection (ESD) is an advanced endoscopic technique that allows curative resection of EGC. Several studies reported excellent short-and long-term outcomes in patients undergoing curative resection (1,2). In addition, ER of EGC, as opposed to surgical resection, allows preservation of stomach and in turn provides a better quality of life (3). However development of MGC following curative ER is one of the major issues of gastric ESD. Our retrospective study found that the 5-year, 7-year and 10-year cumulative incidence of MGC were 9.5%, 13.1% and 22.7%, respectively. Furthermore, some patients who lost to follow up were found to have advanced gastric cancer and died of gastric cancer (4). Currently, no standardized recommendations are available for endoscopic surveillance after curative resection of EGC. However, continuous annual or biannual surveillance endoscopies may be reasonable. Regular surveillance is required for early detection of MGCs and thus less invasive treatment option can be curative (4-7).

Surveillance endoscopy after ER of gastric adenoma with low grade dysplasia

Gastric adenoma with low grade dysplasia is classified as category 3 in the Vienna classification and known to transform into malignant lesions (8-11). Approximately 4% to 30% of gastric lesions initially diagnosed as adenomas by endoscopic biopsy are upgraded to gastric cancer after ER (12,13). For these reasons, gastric adenomas are actively resected mainly by ESD in Korea. However, optimal surveillance protocol after ER of gastric adenoma is unknown. The risk of gastric cancer after curative ER has not been well studied.

Given this background, Yoon et al. conducted a retrospective study to investigate the incidence of gastric cancer after ER in patients undergoing ESD of gastric adenoma and EGC (14). This study also compared the incidence of MGC between the adenoma group and the EGC group. The follow-up period after ER in this study ranged from 1.0 to 8.9 years (median, 2.3 years). In this study, the incidence of gastric cancer after ER for gastric adenoma was similar to that of EGC: 14.4 cases per 1,000 person-years in adenoma patients and 18.4 cases per 1,000 person-years in EGC patients (P=0.309 by log-rank test). In addition, the lesion characteristics of newly developed gastric neoplasias (adenoma and MGC) were also similar between the two groups.

This study gave us two important messages. First, patients with gastric adenomas without high grade dysplasia or cancer have an increased risk of MGC. Therefore surveillance endoscopy is necessary after ER of gastric adenoma in order to detect MGC at early stage when endoscopic therapy is feasible. The primary purpose of ER of premalignant gastric adenoma with low grade atypia was cancer prevention similar to the concept of endoscopic removal of colorectal adenomatous polyp to prevent colon cancer (15). In addition, en bloc specimens obtained by ESD facilitate precise histological assessment which could have been understaged at tissue biopsy. This study showed that the risk of development of gastric cancer remained after the endoscopic removal of the index lesions and the cumulative incidence of MGC in the adenoma group was very high. It can be reasonably explained by field cancerization theory and the fact that some gastric adenomas with low-grade dysplasia coexist with gastric cancer.

Second, this study suggested that surveillance endoscopy should be continued indefinitely. The incidence of MGC increased overtime after ESD of gastric adenoma with low grade dysplasia and more aggressive second lesion can develop after ESD of index gastric adenoma even after 5-year follow-up period. It should be noted that 7 patients with gastric adenoma at index endoscopy developed submucosal invasive gastric cancer at long term follow-up. Of these, only one patient fully complied with the surveillance endoscopic schedule, whereas the other irregularly followed their surveillance schedule (14).

The median follow-up period after ER of the adenoma group was shorter than that of the EGC group. The reason for this is unclear. Possibly, both endoscopists and patients may underestimate importance of surveillance endoscopy after ER of gastric adenoma because of its lesser invasiveness. Thus, it is essential to recognize the risk of cancer development in other part of the stomach and adhere to surveillance protocol.

The next issues to be resolved

Both of gastric low grade dysplasia and gastric cancer occur on the similar background, i.e., chronic atrophic gastritis due to the infection of Helicobacter Pylori (H. Pylori). The International Agency for Research on Cancer (IARC), a subsidiary of the World Health Organization (WHO), categorized H. pylori as a group 1 carcinogen for gastric cancer (16). A multicenter prospective randomized control trial by Fukase et al. showed that H. pylori eradication could play a preventative role to reduce the occurrence of MGC in patients who have undergone ER (17). This strategy should be considered for gastric cancer prevention in patients with gastric adenoma following ER, although, further prospective studies are warranted to investigate the clinical impact of H. Pylori eradication in this setting. A prospective study showed that the accumulation of methylation could be an epigenetic cancer risk prediction of MGC after H. pylori eradication (18). The results of this study provided convincing data to stratify the risk factors for MGC including H. pylori eradication (19). The same risk stratification may be applied to patients with gastric adenoma.

Careful and regular surveillance endoscopy is strongly recommended for patients undergoing ER of gastric adenoma with low grade atypia as well as gastric cancer. Large prospective studies are warranted to identify the high risk group of cancer development and determine the optimal surveillance interval.

Acknowledgments

Funding: Part of this work was supported by the National Cancer Center Research and Development Fund (25-A-12 and 28-K-1).

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Annals of Laparoscopic and Endoscopic Surgery. The article did not undergo external peer review.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/ales.2017.04.07). Yutaka Saito serves as an unpaid editorial board member of Annals of Laparoscopic and Endoscopic Surgery from Dec 2016 to Nov 2018. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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