Clin Endosc > Volume 51(3); 2018 > Article
Abe, Oda, Minagawa, Sekiguchi, Nonaka, Suzuki, Yoshinaga, Bhatt, and Saito: Metachronous Gastric Cancer Following Curative Endoscopic Resection of Early Gastric Cancer


This review article summarizes knowledge about metachronous gastric cancer (MGC) occurring after curative endoscopic resection (ER) of early gastric cancer (EGC), treatment outcomes of patients who developed MGC, and efficacy of Helicobacter pylori eradication to prevent MGC. The incidence of MGC following curative ER increases over time and is higher than in patients undergoing gastrectomy. Increasing age and multifocal EGC are independent risk factors for developing MGC. An MGC following curative ER is usually a small (<20 mm) and differentiated intramucosal cancer. Most MGC lesions are found at an early stage on semiannual or annual surveillance endoscopy and are successfully treated by further ER, with excellent long-term outcomes. Eradication of H. pylori may reduce the risk of MGC following ER of EGC, but further prospective studies with long-term outcomes are required. Surveillance endoscopy following gastric ER should be continued indefinitely, due to the risk of MGC even after successful H. pylori eradication. Risk stratification and tailored endoscopic surveillance schedules need to be developed.


Approximately one million new gastric cancer cases occurred in 2012, making it the fifth most common malignancy and the third leading cause of cancer death worldwide [1]. Development of screening esophagogastroduodenoscopy (EGD) programs has led to the detection of gastric cancer at earlier stages, and approximately half of all gastric cancers in Japan are detected at a stage when they are confined to the mucosa or submucosa [2].
Increasing numbers of early gastric cancer (EGC) cases have been treated with endoscopic resection (ER), as curative resection was defined based on large retrospective cohort in surgery cases and the development of endoscopic submucosal dissection (ESD) has allowed for high en bloc and curative resection rates of EGC, regardless of size and location [3-6]. Several retrospective studies have shown excellent long-term outcomes in EGC patients undergoing curative gastric ESD [7-16]. In addition, ESD preserves stomach function and maintains quality of life in those patients who achieve curative ER [17].
A drawback of ER for EGC is the risk of developing metachronous gastric cancer (MGC) in the remaining native stomach. As the popularity of this technique increases, it is vitally important to characterize risk factors and long-term outcomes for those patients who develop MGC. This review article summarizes the definition, incidence, clinical characteristics, and outcomes of MGC.


Gastric cancer detected on surveillance EGD following curative ER may be a de novo lesion, a previously invisible preclinical lesion, or a missed lesion. Determining which of these possibilities is the case can be extremely difficult. General consensus, based on previous publications, is that gastric cancers detected within 1 year after ER should be regarded as a missed synchronous gastric cancer [18-21]. Thus, MGC is generally defined as a gastric cancer located distant from the original EGC over 1 year following index ESD.


Studies have reported an incidence of MGC following ER for EGC ranging from 2.7% to 15.6% (Table 1) [20,22-30]. In these studies, all MGCs were detected on surveillance EGD, and no study reported detection of EGC by barium contrast or computed tomography. ESD was preferred over endoscopic mucosal resection (EMR) in these series.
Kobayashi et al. reported that MGCs developed in 30 of 234 patients during a median follow-up of 5.0 years [28]. They also demonstrated that a Kaplan-Meier curve of cumulative incidence of MGC stopped increasing after 10 years of follow-up [28]. In contrast, Kato et al. and Min et al. reported that the cumulative incidence curve revealed a linear increase in much larger cohorts [24,29]. We also demonstrated that 5-year, 7-year, and 10-year cumulative incidence of MGC (adjusted for risk of death from other causes) on surveillance endoscopy was 9.5%, 13.1%, and 22.7%, respectively, with a median follow up of 82.2 months [30].
Following gastrectomy, the cumulative incidence of MGC is 0.9%–3.0% [31-34]. The incidence of MGC in patients undergoing ER is much higher. This difference is explained by the organ-sparing nature of ER, as while maintaining luminal continuity offers an improved quality of life, the remaining gastric mucosa continues to be at risk of MGC.


Although methods used to analyze risk factors for MGC vary among studies, older age, multiple initial EGCs and persistent Helicobacter pylori infection are considered to be common risk factors (Table 2) [25,28-30,35-37]. As older age is a greater potential risk factor for gastric cancer and multifocal lesions tend to develop in gastric mucosa with high risk field changes, these factors are unsurprising. Persistence of H. pylori infection as a risk factor is less straightforward. Persistence should be positively correlated with recurrence risk; however, Lim et al. reported that the absence of H. pylori infection is an independent risk factor for metachronous neoplasms, including dysplasia [38]. One possible explanation for this divergent finding is that long-term H. pylori infection may result in severe atrophic gastritis with intestinal metaplasia, such that H. pylori is no longer detectable. Long-term infection might have had more effect on metachronous tumorigenesis than newly developed H. pylori infections that can be easily detected [39].


According to recent publications, MGCs are commonly characterized as small, differentiated intramucosal cancers <20 mm in size [26-28]. MGCs often develop when the initial lesion is a differentiated EGC. This suggests that this type of cancer tends to develop in gastric mucosa during field cancerization [40,41].
Regular endoscopic surveillance detects MGC at an early stage, allowing for repeat curative ESD resection in the majority of cases, according to absolute or expanded indications based on the Japanese Gastric Cancer Treatment Guidelines [5,23-25,29,30]. Kato et al. reported that only 4 of 175 synchronous or metachronous cancers invaded the submucosa or deeper layers [24]. Our study showed that 215 of 238 patients with MGC underwent ER (mostly ESD), and the en bloc resection, R0 resection, and curative resection rates were 99.3%, 94.3%, and 88.8%, respectively [30].
In addition, excellent long-term outcomes have been shown by Kato et al. in his multicenter, retrospective cohort study, in which no patients died of gastric cancer during a mean follow-up period of 26.8 months [24]. Our study showed a 5-year disease-specific survival rate of 99.2% in patients undergoing curative gastric ESD; of the 238 patients who developed MGC, only 7 died of MGC during a median follow-up of 82.2 months. The patients who died from MGC were lost to follow-up, and did not undergo the surveillance endoscopy that may have detected their cancers at an earlier and more treatable stage. Five of the patients died from MGC more than 5 years after their index ESD.30 These studies support the clinical validity of an organ-preserving strategy with surveillance endoscopy and repeated ESD.
Treatment outcomes for gastric cancer are generally evaluated with 5-year overall and disease-specific survival. A limited 5-year follow-up may be reasonable for patients undergoing gastrectomy, as a majority of postoperative lymph node or distant recurrences occur within 5 years, and the risk of MGC development is much lower than in those treated with ER [42]. On the other hand, indefinite endoscopic surveillance is required to detect and remove MGCs in patients treated endoscopically.


H. pylori infection is characterized by progression through the following stages: chronic active gastritis, atrophy, intestinal metaplasia, and dysplasia, followed by the development of gastric adenocarcinoma. H. pylori infection is considered one of the most important risk factors for gastric cancer [43-47]. In 1994, the International Agency for Research on Cancer, a subsidiary of the World Health Organization, categorized H. pylori as a group 1 carcinogen for gastric cancer [48]. Uemura et al. concluded that gastric cancer develops in persons infected with H. pylori, but not in uninfected persons [49]. Take et al. showed that H. pylori eradication has preventative effects on the occurrence of initial gastric cancer [50]. In addition, persistent H. pylori infection was considered to a risk factor for MGC after ER in a number of retrospective studies, as shown in Table 2 [36,37].
Thus, it would seem reasonable to assume that H. pylori eradication would have a potential prophylactic effect on MGC following ER [51]. However, two recent large, prospective randomized trials have shown contradictory results. Fukase et al. reported that the cumulative incidence of MGC was 6.5% during a 3-year follow-up, and patients receiving H. pylori eradication treatment showed significantly lower MGC rates than patients without eradication therapy (3.5% vs. 9.6%, p=0.003) [52]. On the other hand, Choi et al. concluded that the cumulative incidence of MGC was comparable in patients with and without H. pylori eradication treatment during a 3-year follow-up (2.3% vs. 3.9%, p=0.24) [53]. Other retrospective studies showed similarly controversial conclusions (Table 3) [35-37,54-58], but meta-analyses by Jung et al. and Yoon et al. concluded that H. pylori eradication could play a preventative role by reducing the occurrence of MGC in patients who have undergone ER [59,60].
Therefore, H. pylori eradication should be considered as preventative of MGC after ER. It should be noted that the definitions of MGC were not consistent among the studies and that some previous studies did not distinguish MGC from synchronous gastric cancer. In addition, the median follow-up periods were less than 5 years in a majority of previous publications and the timing of H. pylori eradication could affect the results. Further prospective studies in the ESD era with long follow-up periods might help clarify the preventative effect of H. pylori eradication for MGC occurrence.


MGCs following successful H. pylori eradication were mainly characterized as small, differentiated EGCs. Mori et al. showed that MGCs were 15 mm in median tumor size, and were commonly located at the middle or lower third of the stomach [61]. Of these, 97% of MGCs were differentiated EGCs and 90% of these were confined to the mucosa. Curative ESD resection was done for all MGCs according to the Japanese Gastric Cancer Treatment Guidelines, except for one differentiated T1b (submucosal invasion to 80 μm) cancer 4 mm in size with lymphatic involvement [61]. Regular endoscopic surveillance would probably play a significant role in early detection. MGCs following H. pylori eradication were sometimes covered by non-neoplastic epithelium.
This histological alteration made it more difficult to detect MGC and delineate its margin, even with magnified narrow-band imaging [62,63]. Yamamoto et al. reported that the average diameter of an MGC following successful eradication was smaller and the Ki-67 index was lower than in cases with persistent H. pylori infection [64].
Moribata et al. analyzed endoscopic mucosal background features associated with MGC in patients who underwent H. pylori eradication therapy and concluded the absence of intestinal metaplasia prior to ESD was a negative predictor of MGC after ESD, and the emergence of map-like redness after H. pylori eradication was a positive predictor for MGC after ESD [65]. Mori et al. and Shiotani et al. supported this conclusion and showed that widespread gastric mucosal atrophy and multiple gastric cancers before successful H. pylori eradication were risk factors for MGC occurrence following H. pylori eradication [54,61].


There are some established guidelines for surveillance interval in patients undergoing curative ER. The National Comprehensive Cancer Network guidelines state that even for Tis or T1 with N0 lesions achieving R0 with ER or surgery, all patients should be followed up systematically, and follow-up should include a complete history and physical examination every 3 to 6 months for 1 to 2 years, every 6 to 12 months for 3 to 5 years, and annually thereafter all patients [66]. The Japanese gastric cancer treatment guidelines recommend annual or biannual endoscopy after curative ESD for patients with EGC who meet expanded indications criteria [5].
Given that most of the MGCs were found in early stages and were successfully treated with ER in many previous reports, annual or biannual endoscopic surveillance may be reasonable. As the individual risk of MGC can vary greatly among patients, risk stratification and tailored follow-up schedules should be considered, similar to surveillance colonoscopy after endoscopic polyp removal [67]. In addition, we are performing a prospective study to evaluate epigenetic cancer risk prediction of MGC after H. pylori eradication. We hope that these results will provide more detailed data on the stratification of risk factors for MGC following H. pylori eradication [68]. Further prospective studies are warranted to determine appropriate surveillance intervals. Regarding the surveillance period, as the cumulative incidence of MGC linearly increased and some patients died of MGC more than 5 years after treatment, endoscopic surveillance should be performed indefinitely [30]. In addition, Mori et al. reported that the 5-year cumulative incidence of MGC even after successful H. pylori eradication was 15.0% during a 4.5-year median follow-up period [61]. This multicenter, prospective study also showed that 11% of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication [61]. Therefore, continuous surveillance endoscopy should be performed to identify MGC in patients who have undergone ER for EGC, regardless of success or failure of H. pylori eradication.


EGC patients who undergo ER are at significant risk of developing MGC, but with annual or biannual surveillance EGD, MGC can be detected at an early stage when it is amenable to curative ESD resection. H. pylori eradication may reduce the incidence of MGC, but does not completely eradicate risk. Surveillance endoscopy should be continued indefinitely as cumulative incidence of MGC linearly increases. As we gain understanding of MGC, we hope that tailored surveillance intervals are developed, similar to those used to predict colonoscopy surveillance intervals based on the characteristics of the polyps removed. ESD for EGC preserves the quality of life by retaining the native stomach; however, the native stomach is at high risk for developing other gastric cancers. These patients should undergo life-long endoscopic surveillance for detection of MCG at an early and treatable stage.


Conflicts of Interest: The authors have no financial conflicts of interest.


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

Table 1.
Incidence of Metachronous Gastric Cancer following Endoscopic Resection
Study Methods of endoscopic resection Rate of MGC Follow up period (yr) Annual incidence of MGC
Kim et al. (2007) [22] EMRa) 2.70% 11/379 1.9 Median -
Lee et al. (2011) [23] ESD 3.30%b) 15/458 2.2 Median -
Kato et al. (2013) [24] ESD 5.20% 65/1258 2.2 Mean 3.50%
Hahn et al. (2016) [25] ESD 4.30% 58/1347 2.4 Median 2.48%
Nakajima et al. (2006) [26] EMR and ESD 8.20% 52/633 4.4 Mean -
Nasu et al. (2005) [27] EMR 14% 20/143 4.8 Median Approximately 4%
Kobayashi et al. (2010) [28] EMR and ESD 12.80% 30/234 5 Median -
Min et al. (2015) [29] ESD 3.60% 47/1306 5 Median -
Abe et al. (2015) [30] ESD 15.60% 238/1527 6.6 Median -
Arima et al. (1999) [20] EMR 7.90% 6/76 7 -c) -

MGC, metachronous gastric cancer; EMR, endoscopic mucosal resection; ESD, endoscopic submucosal dissection.

a) Only R0 resection in patients with intramucosal cancer was included.

b) Synchronous lesion was included for analysis.

c) All patients were followed up for 7 year.

Table 2.
Intervals of Surveillance Endoscopy and Risk Factors of Metachronous Gastric Cancer following Endoscopic Resection
Study Intervals of Surveillance endoscopy for MGC Risk factors of metachronous gastric cancers
Lee et al. (2011) [23] Biannual then annual -
Kato et al. (2013) [24] Annual or biannual -
Hahn et al. (2016) [25] Annual or biannual Older age, intestinal metaplasia, ESD criteria
Nakajima et al. (2006) [26] Annual -
Nasu et al. (2005) [27] Annual -
Kobayashi et al. (2010) [28] Annual Multiple initial EGC, male, same third of the stomach
Min et al. (2015) [29] Annual or biannual Multiple initial EGC, well differentiated adenocarcinoma of initial EGC
Abe et al. (2015) [30] Annual or biannual Multiple initial EGC, male
Arima et al. (1999) [20] - Multiple initial EGC
Maehata et al. (2012) [35] Annual or biannual Follow-up period over 5 years, severe gastric mucosal atrophy
Kwon et al. (2014) [36] Annual Age ≥60 years old, persistent Helicobacter pylori infection
Kim et al. (2014) [37] Annual Age ≥65 years old, persistent H.pylori infection, family history of gastric cancer

MGC, metachronous gastric cancer; ESD, endoscopic submucosal dissection; EGC, early gastric cancer.

Table 3.
Incidence of Metachronous Gastric Cancer following Successful Helicobacter pylori Eradication
Study Design Numbera) Follow up Period (yr) Incidence Effect Results
Uemura et al. (1997) [51] NR 65/67 - - 0.0/9.0% Effective p=0.011
Fukase et al. (2008) [52] RCT 255/250 2.9/2.9a) Median 3.5/9.6% Effective p=0.003b), OR=0.34
Shiotani et al. (2008) [54] Single arm -/80 2.8 Median 11.3%
Maehata et al. (2012) [35] Retrospective 177/91 3 Median 8.5/14.3% Non-effective p=0.262
Choi et al. (2014) [53] RCT 439/441 3 Median 2.3/3.9% Non-effective p=0.15
Seo et al. (2013) [55] Retrospective 61/13 2.3 Mean 9.8/23.1% Non-effective p=0.189, OR=0.36
Chon et al. (2013) [56] Retrospective 85/44 2.2 Median 4.7/11.4% Effective p=0.008, HR=0.143
Kwon et al. (2014) [36] Retrospective 214/69 3.4 Median 4.7/14.5% Effective p=0.009
Kim et al. (2014) [37] Retrospective 49/107 5.3/4.6a) Median 4.1/15.0% Effective p=0.006
Bae et al. (2014) [57] Retrospective 485/182 5c) Median 7.0/13.2% Effective p=0.02, HR=1.9
14.7/29.7/1,000 pt yr
Jung et al. (2015) [58] Retrospective 506/169 3.3c) Median 4.2/5.9% Non-effective p=0.29, HR=0.67
Mori et al. (2016) [61] Single arm -/594 4.5 Median 29.9/1,000 pt yr

NR, non-randomized; RCT, randomized controlled trial; OR, odds ratio; HR, hazard ratio.

a) Eradicated group/Persistent infection group.

b) Modified intention to treat analysis.

c) Including gastric dysplasia, including Helicobacter pylori non-infection group.


1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015;136:E359–E386.
crossref pmid
2. Nashimoto A, Akazawa K, Isobe Y, et al. Gastric cancer treated in 2002 in Japan: 2009 annual report of the JGCA nationwide registry. Gastric Cancer 2013;16:1–27.
crossref pmid pmc
3. Gotoda T, Yanagisawa A, Sasako M, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer 2000;3:219–225.
crossref pmid
4. Hirasawa T, Gotoda T, Miyata S, et al. Incidence of lymph node metastasis and the feasibility of endoscopic resection for undifferentiated-type early gastric cancer. Gastric Cancer 2009;12:148–152.
crossref pmid
5. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011;14:113–123.
crossref pmid pdf
6. Ono H, Yao K, Fujishiro M, et al. Guidelines for endoscopic submucosal dissection and endoscopic mucosal resection for early gastric cancer. Dig Endosc 2016;28:3–15.
crossref pmid
7. Oda I, Saito D, Tada M, et al. A multicenter retrospective study of endoscopic resection for early gastric cancer. Gastric Cancer 2006;9:262–270.
crossref pmid
8. Isomoto H, Shikuwa S, Yamaguchi N, et al. Endoscopic submucosal dissection for early gastric cancer: a large-scale feasibility study. Gut 2009;58:331–336.
crossref pmid
9. Goto O, Fujishiro M, Kodashima S, Ono S, Omata M. Outcomes of endoscopic submucosal dissection for early gastric cancer with special reference to validation for curability criteria. Endoscopy 2009;41:118–122.
crossref pmid
10. Gotoda T, Iwasaki M, Kusano C, Seewald S, Oda I. Endoscopic resection of early gastric cancer treated by guideline and expanded National Cancer Centre criteria. Br J Surg 2010;97:868–871.
crossref pmid
11. Abe S, Oda I, Suzuki H, et al. Short- and long-term outcomes of endoscopic submucosal dissection for undifferentiated early gastric cancer. Endoscopy 2013;45:703–707.
crossref pmid pdf
12. Kosaka T, Endo M, Toya Y, et al. Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: a single-center retrospective study. Dig Endosc 2014;26:183–191.
crossref pmid
13. Tanabe S, Ishido K, Higuchi K, et al. Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: a retrospective comparison with conventional endoscopic resection in a single center. Gastric Cancer 2014;17:130–136.
crossref pmid
14. Oda I, Oyama T, Abe S, et al. Preliminary results of multicenter questionnaire study on long-term outcomes of curative endoscopic submucosal dissection for early gastric cancer. Dig Endosc 2014;26:214–219.
crossref pmid
15. Ohnita K, Isomoto H, Shikuwa S, et al. Early and long-term outcomes of endoscopic submucosal dissection for early gastric cancer in a large patient series. Exp Ther Med 2014;7:594–598.
crossref pmid pmc
16. Suzuki H, Oda I, Abe S, et al. High rate of 5-year survival among patients with early gastric cancer undergoing curative endoscopic submucosal dissection. Gastric Cancer 2016;19:198–205.
crossref pmid
17. Choi JH, Kim ES, Lee YJ, et al. Comparison of quality of life and worry of cancer recurrence between endoscopic and surgical treatment for early gastric cancer. Gastrointest Endosc 2015;82:299–307.
crossref pmid
18. Moertel CG, Bargen JA, Soule EH. Multiple gastric cancers; review of the literature and study of 42 cases. Gastroenterology 1957;32:1095–1103.
crossref pmid
19. Uemura N, Okamoto S. Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer in Japan. Gastroenterol Clin North Am 2000;29:819–827.
crossref pmid
20. Arima N, Adachi K, Katsube T, et al. Predictive factors for metachronous recurrence of early gastric cancer after endoscopic treatment. J Clin Gastroenterol 1999;29:44–47.
crossref pmid
21. Nishida T, Tsujii M, Kato M, et al. Endoscopic surveillance strategy after endoscopic resection for early gastric cancer. World J Gastrointest Pathophysiol 2014;5:100–106.
crossref pmid pmc
22. Kim JJ, Lee JH, Jung HY, et al. EMR for early gastric cancer in Korea: a multicenter retrospective study. Gastrointest Endosc 2007;66:693–700.
crossref pmid
23. Lee H, Yun WK, Min BH, et al. A feasibility study on the expanded indication for endoscopic submucosal dissection of early gastric cancer. Surg Endosc 2011;25:1985–1993.
crossref pmid
24. Kato M, Nishida T, Yamamoto K, et al. Scheduled endoscopic surveillance controls secondary cancer after curative endoscopic resection for early gastric cancer: a multicentre retrospective cohort study by Osaka University ESD study group. Gut 2013;62:1425–1432.
crossref pmid
25. Hahn KY, Park JC, Kim EH, et al. Incidence and impact of scheduled endoscopic surveillance on recurrence after curative endoscopic resection for early gastric cancer. Gastrointest Endosc 2016;84:628–638.e1.
crossref pmid
26. Nakajima T, Oda I, Gotoda T, et al. Metachronous gastric cancers after endoscopic resection: how effective is annual endoscopic surveillance? Gastric Cancer 2006;9:93–98.
crossref pmid
27. Nasu J, Doi T, Endo H, Nishina T, Hirasaki S, Hyodo I. Characteristics of metachronous multiple early gastric cancers after endoscopic mucosal resection. Endoscopy 2005;37:990–993.
crossref pmid pdf
28. Kobayashi M, Narisawa R, Sato Y, Takeuchi M, Aoyagi Y. Self-limiting risk of metachronous gastric cancers after endoscopic resection. Dig Endosc 2010;22:169–173.
crossref pmid
29. Min BH, Kim ER, Kim KM, et al. Surveillance strategy based on the incidence and patterns of recurrence after curative endoscopic submucosal dissection for early gastric cancer. Endoscopy 2015;47:784–793.
crossref pmid pdf
30. Abe S, Oda I, Suzuki H, et al. Long-term surveillance and treatment outcomes of metachronous gastric cancer occurring after curative endoscopic submucosal dissection. Endoscopy 2015;47:1113–1118.
crossref pmid pdf
31. Onodera H, Tokunaga A, Yoshiyuki T, et al. Surgical outcome of 483 patients with early gastric cancer: prognosis, postoperative morbidity and mortality, and gastric remnant cancer. Hepatogastroenterology 2004;51:82–85.
32. Hosokawa O, Kaizaki Y, Watanabe K, et al. Endoscopic surveillance for gastric remnant cancer after early cancer surgery. Endoscopy 2002;34:469–473.
crossref pmid pdf
33. Ikeda Y, Saku M, Kishihara F, Maehara Y. Effective follow-up for recurrence or a second primary cancer in patients with early gastric cancer. Br J Surg 2005;92:235–239.
crossref pmid
34. Nozaki I, Hato S, Kobatake T, et al. Incidence of metachronous gastric cancer in the remnant stomach after synchronous multiple cancer surgery. Gastric Cancer 2014;17:61–66.
crossref pmid
35. Maehata Y, Nakamura S, Fujisawa K, et al. Long-term effect of Helicobacter pylori eradication on the development of metachronous gastric cancer after endoscopic resection of early gastric cancer. Gastrointest Endosc 2012;75:39–46.
crossref pmid
36. Kwon YH, Heo J, Lee HS, Cho CM, Jeon SW. Failure of Helicobacter pylori eradication and age are independent risk factors for recurrent neoplasia after endoscopic resection of early gastric cancer in 283 patients. Aliment Pharmacol Ther 2014;39:609–618.
crossref pmid
37. Kim YI, Choi IJ, Kook MC, et al. The association between Helicobacter pylori status and incidence of metachronous gastric cancer after endoscopic resection of early gastric cancer. Helicobacter 2014;19:194–201.
crossref pmid
38. Lim JH, Kim SG, Choi J, Im JP, Kim JS, Jung HC. Risk factors for synchronous or metachronous tumor development after endoscopic resection of gastric neoplasms. Gastric Cancer 2015;18:817–823.
crossref pmid
39. Venerito M, Malfertheiner P. Preneoplastic conditions in the stomach: always a point of no return? Dig Dis 2015;33:5–10.
crossref pmid
40. Zaky AH, Watari J, Tanabe H, et al. Clinicopathologic implications of genetic instability in intestinal-type gastric cancer and intestinal metaplasia as a precancerous lesion: proof of field cancerization in the stomach. Am J Clin Pathol 2008;129:613–621.
crossref pmid pdf
41. McDonald SA, Greaves LC, Gutierrez-Gonzalez L, et al. Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells. Gastroenterology 2008;134:500–510.
crossref pmid
42. Feng XY, Chen YB, Wang W, et al. Time-varying pattern of recurrence risk for gastric cancer patients. Med Oncol 2013;30:514.
crossref pmid
43. Fuccio L, Zagari RM, Eusebi LH, et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med 2009;151:121–128.
crossref pmid
44. Sipponen P, Hyvärinen H. Role of Helicobacter pylori in the pathogenesis of gastritis, peptic ulcer and gastric cancer. Scand J Gastroenterol Suppl 1993;196:3–6.
crossref pmid
45. Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology 1998;114:1169–1179.
crossref pmid
46. Eslick GD, Lim LL, Byles JE, Xia HH, Talley NJ. Association of Helicobacter pylori infection with gastric carcinoma: a meta-analysis. Am J Gastroenterol 1999;94:2373–2379.
crossref pmid
47. Sipponen P, Kimura K. Intestinal metaplasia, atrophic gastritis and stomach cancer: trends over time. Eur J Gastroenterol Hepatol 1994;6 Suppl 1:S79–S83.
48. Schistosomes, liver flukes and Helicobacter pylori. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Lyon, 7-14 June 1994. IARC Monogr Eval Carcinog Risks Hum 1994;61:1–241.
pmid pmc
49. Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori infection and the development of gastric cancer. N Engl J Med 2001;345:784–789.
crossref pmid
50. Take S, Mizuno M, Ishiki K, et al. The effect of eradicating helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease. Am J Gastroenterol 2005;100:1037–1042.
crossref pmid
51. Uemura N, Mukai T, Okamoto S, et al. Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer. Cancer Epidemiol Biomarkers Prev 1997;6:639–642.
crossref pmid
52. Fukase K, Kato M, Kikuchi S, et al. Effect of eradication of Helicobacter pylori on incidence of metachronous gastric carcinoma after endoscopic resection of early gastric cancer: an open-label, randomised controlled trial. Lancet 2008;372:392–397.
crossref pmid
53. Choi J, Kim SG, Yoon H, et al. Eradication of Helicobacter pylori after endoscopic resection of gastric tumors does not reduce incidence of metachronous gastric carcinoma. Clin Gastroenterol Hepatol 2014;12:793–800.e1.
crossref pmid
54. Shiotani A, Uedo N, Iishi H, et al. Predictive factors for metachronous gastric cancer in high-risk patients after successful Helicobacter pylori eradication. Digestion 2008;78:113–119.
crossref pmid
55. Seo JY, Lee DH, Cho Y, et al. Eradication of Helicobacter pylori reduces metachronous gastric cancer after endoscopic resection of early gastric cancer. Hepatogastroenterology 2013;60:776–780.
crossref pmid
56. Chon I, Choi C, Shin CM, Park YS, Kim N, Lee DH. Effect of Helicobacter pylori eradication on subsequent dysplasia development after endoscopic resection of gastric dysplasia. Korean J Gastroenterol 2013;61:307–312.
crossref pmid
57. Bae SE, Jung HY, Kang J, et al. Effect of Helicobacter pylori eradication on metachronous recurrence after endoscopic resection of gastric neoplasm. Am J Gastroenterol 2014;109:60–67.
crossref pmid pdf
58. Jung DH, Kim JH, Lee YC, et al. Helicobacter pylori eradication reduces the metachronous recurrence of gastric neoplasms by attenuating the precancerous process. J Gastric Cancer 2015;15:246–255.
crossref pmid pmc
59. Yoon SB, Park JM, Lim CH, Cho YK, Choi MG. Effect of Helicobacter pylori eradication on metachronous gastric cancer after endoscopic resection of gastric tumors: a meta-analysis. Helicobacter 2014;19:243–248.
crossref pmid
60. Jung DH, Kim JH, Chung HS, et al. Helicobacter pylori eradication on the prevention of metachronous lesions after endoscopic resection of gastric neoplasm: a meta-analysis. PLoS One 2015;10:e0124725.
crossref pmid pmc
61. Mori G, Nakajima T, Asada K, et al. Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan. Gastric Cancer 2016;19:911–918.
crossref pmid pdf
62. Ito M, Tanaka S, Takata S, et al. Morphological changes in human gastric tumours after eradication therapy of Helicobacter pylori in a shortterm follow-up. Aliment Pharmacol Ther 2005;21:559–566.
crossref pmid
63. Kobayashi M, Hashimoto S, Nishikura K, et al. Magnifying narrow-band imaging of surface maturation in early differentiated-type gastric cancers after Helicobacter pylori eradication. J Gastroenterol 2013;48:1332–1342.
crossref pmid
64. Yamamoto K, Kato M, Takahashi M, et al. Clinicopathological analysis of early-stage gastric cancers detected after successful eradication of Helicobacter pylori. Helicobacter 2011;16:210–216.
crossref pmid
65. Moribata K, Iguchi JK, Nakachi K, et al. Endoscopic features associated with development of metachronous gastric cancer in patients who underwent endoscopic resection followed by Helicobacter pylori eradication. Dig Endosc 2015 Dec 1 [Epub].
crossref pmc
66. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: gastric cancer version I. 2016 [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; c2016 [cited 2016 Mar 31]. Available from:

67. Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844–857.
crossref pmid
68. Asada K, Nakajima T, Shimazu T, et al. Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study. Gut 2015;64:388–396.
crossref pmid pmc
PDF Links  PDF Links
PubReader  PubReader
ePub Link  ePub Link
XML Download  XML Download
Full text via DOI  Full text via DOI
Download Citation  Download Citation
Web of Science
Related articles
E-learning system to improve the endoscopic diagnosis of early gastric cancer  
Long-Term Outcomes of Endoscopic Submucosal Dissection of Undifferentiated-Type Early Gastric Cancer  2021 March;54(2)
Perforation of a Gastric Tear during Esophageal Endoscopic Submucosal Dissection under General Anesthesia  2021 November;54(6)
Clinical Practice Guideline for Endoscopic Resection of Early Gastrointestinal Cancer  2020 March;53(2)
Pyogenic Liver Abscess Caused by Endoscopic Submucosal Dissection for Early Colon Cancer  2019 November;52(6)
Editorial Office
Korean Society of Gastrointestinal Endoscopy
#817, 156 Yanghwa-ro (LG Palace, Donggyo-dong), Mapo-gu, Seoul, 04050, Korea
TEL: +82-2-335-1552   FAX: +82-2-335-2690    E-mail:
Copyright © Korean Society of Gastrointestinal Endoscopy.                 Developed in M2PI
Close layer