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Objectives: The Cancer Control Act requires the maintenance of regional cooperation pathways (RCP) for cancer treatment. In 2008, we started RCP for early detection of new gastric cancer after endoscopic submucosal dissection (ESD). In gastric cancer treatment, RCP after surgical resection had been widely used, but little is known about RCP after ESD. This study aimed to evaluate the effectiveness of RCP after ESD. Methods: This study included 465 patients on whom our RCP was implemented from 2008 to 2018. A regional family physician performed surveillance endoscopy at 3 months and 1 year after ESD and annually thereafter. We retrospectively evaluated the cumulative incidence and treatment outcomes of new gastric cancer and compared them with previous reports. Results: During a median follow-up period of 70.5 months (3–120 months), 58 patients developed new gastric cancers, and metachronous gastric cancer was detected in 55 patients more than 1 year after ESD. The 5-year cumulative incidence rate was 9.8%. Three patients did not want treatment. Among the remaining 55 patients, the initial treatment was ESD in 51 and surgical resection in 4. Eventually, 50 patients (48 in the ESD group and 2 in the surgical resection group) fulfilled the pathologic criteria for curative ESD. There were no deaths due to gastric cancer. Conclusion: Our study was the first to reveal the incidence of new gastric cancer after ESD using RCP. Most lesions were cured with ESD, and no patients died of gastric cancer. Therefore, we consider RCPs to be an option for surveillance after ESD. [ABSTRACT FROM AUTHOR]

ObjectivesA systematic review and meta-analysis was performed to evaluate the preventive effectiveness of Helicobacter pylori eradication against metachronous gastric cancer (MGC) or dysplasia following endoscopic resection (ER) for early gastric cancer (EGC) or dysplasia.MethodsPubMed, Cochrane Library, MEDLINE, and EMBASE were searched until 31 October 2023, and randomized controlled trials or cohort studies were peer-reviewed. The incidence of metachronous gastric lesions (MGLs) including MGC or dysplasia was compared between Helicobacter pylori persistent and negative groups, eradicated and negative groups, and eradicated and persistent groups.ResultsTotally, 21 eligible studies including 82,256 observations were analyzed. Compared to those never infected, Helicobacter pylori persistent group (RR = 1.58, 95% CI = 0.98–2.53) trended to have a higher risk of MGLs and significantly in partial subgroups, while the post-ER eradicated group (RR = 0.79, 95% CI = 0.43–1.45) did not increase the risk of MGLs. Moreover, successful post-ER eradication could significantly decrease the risk of MGLs (RR = 0.54, 95% CI = 0.44–0.65) compared to those persistently infected. Sensitivity analysis obtained generally consistent results, and no significant publication bias was found.ConclusionThe persistent Helicobacter pylori infection trends to increase the post-ER incidence of MGC or dysplasia, but post-ER eradication can decrease the risk correspondingly. Post-ER screening and eradication of Helicobacter pylori have preventive effectiveness on MGC, and the protocol should be recommended to all the post-ER patients.Systematic review registration: The PROSPERO registration identification was CRD42024512101.

Objectives: Japanese guidelines recommend posttreatment endoscopy once or twice a year after endoscopic submucosal dissection (ESD) for early gastric cancer. However, the impact of endoscopy intervals on metachronous gastric cancer (MGC) remains unclear, especially the difference between 1‐year and half‐a‐year intervals. We aimed to investigate this difference. Methods: This study retrospectively investigated 2429 patients who underwent gastric ESD between May 2001 and June 2019 at our hospital. Patients who developed MGC were classified based on those who underwent the previous endoscopy within at least 7 months (short‐interval group) and within 8–13 months (regular‐interval group). Propensity score matching (PSM) was used to adjust for possible confounders. The primary outcome was the proportion of MGC beyond curative ESD criteria established in the guidelines. Results: A total of 216 eligible patients developed MGC. The short‐ and regular‐interval groups included 43 and 173 patients, respectively. Overall, no patients in the short‐interval group had MGC beyond curative ESD criteria, while 27 patients in the regular‐interval group did. The proportion of MGC beyond curative ESD criteria was significantly lower in the short‐interval group than in the regular‐interval group before (P = 0.003) and after (P = 0.028) PSM. Although not significant, the short‐interval group tended to have a higher stomach preservation rate than the regular‐interval group (P = 0.093). Conclusion: Our study indicated a possible benefit of biannual surveillance endoscopy in the early post‐ESD period. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim The incidence of metachronous gastric cancer (MGC) after endoscopic treatment for early gastric cancer (EGC) is high, but a method of risk assessment for MGC based on endoscopic findings has not been established. In this study, we focused on endoscopic intestinal metaplasia (IM) and investigated the risk for MGC after endoscopic submucosal dissection (ESD) for EGC. Methods This retrospective observational study involved patients who underwent curative ESD for EGC from April 2015 to January 2021. We assessed endoscopic IM using the pretreatment endoscopic examination images. The severity of endoscopic IM was classified into four levels: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Four different gastric areas were evaluated. We divided the patients into a low‐score group and a high‐score group, and compared the cumulative incidence of MGC. Results In total, 156 patients who met the inclusion criteria were followed up for at least 12 months after ESD, and MGC developed in 14 patients during a mean period oof 41.5 months. The endoscopic IM scores in the lesser curvature of the antrum, lesser curvature of the corpus, and greater curvature of the corpus were higher in patients with MGC than in those without MGC. In the corpus, the 5‐year cumulative incidence of MGC was significantly higher in the high‐score group than in the low‐score group (29.8% vs 10.0%, P = 0.004). Conclusion The severity of endoscopic corpus IM was associated with MGC. Thus, patients with severe corpus IM at the time of ESD require careful examination and intensive follow‐up.

Background and Aim: The incidence of metachronous gastric cancer (MGC) after endoscopic treatment for early gastric cancer (EGC) is high, but a method of risk assessment for MGC based on endoscopic findings has not been established. In this study, we focused on endoscopic intestinal metaplasia (IM) and investigated the risk for MGC after endoscopic submucosal dissection (ESD) for EGC. Methods: This retrospective observational study involved patients who underwent curative ESD for EGC from April 2015 to January 2021. We assessed endoscopic IM using the pretreatment endoscopic examination images. The severity of endoscopic IM was classified into four levels: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Four different gastric areas were evaluated. We divided the patients into a low‐score group and a high‐score group, and compared the cumulative incidence of MGC. Results: In total, 156 patients who met the inclusion criteria were followed up for at least 12 months after ESD, and MGC developed in 14 patients during a mean period oof 41.5 months. The endoscopic IM scores in the lesser curvature of the antrum, lesser curvature of the corpus, and greater curvature of the corpus were higher in patients with MGC than in those without MGC. In the corpus, the 5‐year cumulative incidence of MGC was significantly higher in the high‐score group than in the low‐score group (29.8% vs 10.0%, P = 0.004). Conclusion: The severity of endoscopic corpus IM was associated with MGC. Thus, patients with severe corpus IM at the time of ESD require careful examination and intensive follow‐up. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to clarify characteristics of metachronous endoscopic curability C2 (eCura C2) cancer during post-endoscopic submucosal dissection (ESD) follow-up. Methods: Of 4,355 gastric lesions treated by ESD at our hospital during 2005–2021, 657 were metachronous. After excluding lesions found ≥2 years since the prior examination or in the gastric remnant, the remaining 515 were analyzed. Study 1: We compared 35 eCura C2 cancers and 480 eCura A-C1 cancers. Study 2: Endoscopic findings of the 35 lesions were examined to determine why they had been missed. Results: Mean tumor size was larger (34.0 mm vs. 12.1 mm, p < 0.01) and the proportions of mixed-type and poorly differentiated cancers were higher (highly:mixed:poorly, 34.3:57.1:8.6 vs. 94.2:5.0:0.8, p < 0.01) in the eCura C2 group. Study 2: At the prior examination, 4 lesions were noticed but considered benign, 2 lacked sufficient imaging, 19 were detectable on imaging but missed, and 10 were not detectable on imaging. Over half the lesions that were detectable but missed at the prior examination were in the lesser curvature, many being type IIa–IIb lesions with color similar to the background mucosa. All lesions not detectable on imaging at the prior examination were mixed-type or poorly differentiated type. Discussion: Metachronous cancer detected as eCura C2 cancers was significantly larger, and a significantly higher proportion was mixed-type or poorly differentiated cancers, compared with eCura A-C1 cancers. Possible reasons why these lesions were missed include rapid progression of mixed-type and poorly differentiated cancers, and poor recognition that lesions showing only slight color changes may be present at the lesser curvature. [ABSTRACT FROM AUTHOR]

Background and Aims: The natural course of early gastric cancer (EGC) following endoscopic submucosal dissection (ESD) remains unclear. This study aimed to clarify the long-term clinical outcomes and risk factors of metachronous gastric neoplasm (MGN) 5 years after ESD for EGC. Methods: We performed a retrospective analysis of patients who underwent ESD for EGC from July 2005 to October 2015 in Seoul National University Hospital. Long-term clinical outcomes and risk factors of MGN after 5 years post-ESD were evaluated. Results: Among the 2059 patients who underwent ESD for EGC, 1102 were followed up for > 5 years. MGN developed in 132 patients 5 years after ESD. During the median follow-up period of 85 months, the cumulative incidences of MGN and metachronous gastric cancer were 11.7, 16.9, and 27.0 and 7.6, 10.8, and 18.7% after 5, 7, and 10 years, respectively. In multivariable analysis, male sex (odds ratio 1.770; P = 0.042), severe intestinal metaplasia (odds ratio 1.255; P = 0.000), tumor-positive lateral margin (odds ratio 2.711; P = 0.008), < 5 mm lateral safety margin (odds ratio 1.568; P = 0.050), and synchronous adenoma (odds ratio 2.612; P = 0.001) were positive predictive factors, and successful eradication of Helicobacter pylori (odds ratio 0.514; P = 0.024) was a negative predictive factor for MGN after 5 years post-ESD. Conclusion: The cumulative MGN incidence was high even 5 years post-ESD for EGC. Meticulous long-term endoscopic follow-up is mandatory, especially in male patients with underlying intestinal metaplasia, tumor-positive lateral margins, lateral safety margins of < 5 mm, and synchronous adenomas. [ABSTRACT FROM AUTHOR]

Background: Pylorus-preserving gastrectomy (PPG) is a surgical treatment option for cT1N0M0 gastric cancer located in the middle third of the stomach. However, data for the long-term post-PPG clinical outcomes related to metachronous gastric neoplasms (mGNs) in the residual stomach are currently lacking. Therefore, we aimed to evaluate the safety of PPG by focusing on mGNs. Methods: In this single-center, retrospective study, we reviewed the data for 362 patients who underwent PPG with a 3-cm antral cuff and 139 who underwent endoscopic submucosal dissection (ESD) for middle-third gastric cancer between January 2013 and December 2015. The histopathologic features of the antrum in the ESD group, which could not be determined in the PPG group, were analyzed to investigate the risk factors for mGNs. The estimated and actual incidence of mGNs in the antrum were compared in the PPG group. Results: The incidence of mGNs was 6.5% (9/139) in the ESD group. The presence of a synchronous adenoma (odds ratio [OR], 8.46; 95% confidence interval [CI], 1.55–46.34), carcinoma (OR, 15.71; 95% CI, 2.67–92.56) and moderate-to-severe intestinal metaplasia (OR, 9.77; 95% CI, 1.14–83.92) were associated with a higher risk of overall mGNs. However, when confined to the antrum, no significant association was observed between these factors and mGNs. In the ESD group, 2 of 9 mGNs (1.4%) were located at the 3-cm antral cuff. In the PPG group, both mGNs (0.6%) were located in the proximal remnant stomach. Conclusion: Pylorus-preserving gastrectomy was a safe therapeutic option with regard to the occurrence of metachronous adenomas or carcinomas in our series. Despite the low mGN incidence in the 3-cm antral cuff after PPG, the presence of synchronous neoplasms or moderate-to-severe intestinal metaplasia was a risk factor for mGNs in the ESD group; thus, further studies on longer antral cuffs with long-term follow-up are needed. [ABSTRACT FROM AUTHOR]

Background/Aims: Patients treated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) are at risk of developing metachronous gastric cancer (MGC). The aim of this study was to evaluate the clinical outcomes of MGC after ESD for EGC between the re-ESD and surgery groups. Methods: In total, data from 1,510 patients who underwent ESD for EGC from January 2005 to May 2014 were retrospectively reviewed, and data from 112 patients with MGC were analyzed according to the type of treatment, namely, re-ESD and surgery. The clinicopathological factors affecting the subsequent treatment and outcomes of MGC were evaluated. Results: The median duration to the development of MGC was 47 months. In multivariate analysis, lower body mass index (BMI) (p=0.037) and multiplicity (p=0.014) of index cases were significantly associated with subsequent surgery for MGC. In cases of MGC, a diffuse or mixed-type Lauren classification (p=0.009), the depth of tumor mucosal invasion (p=0.001), and an upper stomach location (p=0.049) were associated with surgery. Overall survival was significantly shorter in the surgery group than in the re-ESD group after treatment for MGC (log-rank test, p=0.01). Conclusions: Lower BMI and multiplicity of index cancers were significantly associated with the surgical resection of MGC. Close follow-up is needed to minimize additional treatment for cases at high risk of advanced MGC after ESD for EGC.

Introduction: Gastric adenomas are histologically defined as benign epithelial tumors. While some of them remain adenomas for a long time, others progress to carcinomas. However, long-term outcomes of such cases are not entirely clear. Here, we explored the risk factors and incidence of developing carcinoma from gastric adenoma as well as metachronous gastric cancer. Methods: This study was conducted at a facility that adopted a follow-up strategy for gastric adenoma. Lesions histologically diagnosed as gastric intestinal-type adenomas between January 2004 and December 2016 were analyzed. Clinicopathological data were collected from patients' medical records, and histological changes from adenoma to carcinoma during endoscopic follow-up and risk factors of cancer development were evaluated. Results: This study involved 409 lesions from 376 patients. The analysis of the development of gastric cancer from adenoma and metachronous gastric cancer was ultimately performed for 282 lesions from 258 patients and 269 lesions from 246 patients, respectively, due to different follow-up periods. The 5-year rate of carcinoma development was 34.0%. Risk factors for carcinoma development upon multivariate analysis were lesion size ≥15 mm and morphological depression. All cases with both factors developed gastric carcinoma, and 50.5% of those with either factor developed carcinoma within 5 years. Gastric adenoma was accompanied by metachronous gastric cancer in 1.5% of the patients annually. The only risk factor for metachronous gastric carcinoma was primary adenoma progressing to carcinoma during the follow-up period. Discussion/Conclusion: Given the high rate of carcinoma development in patients with risk factors, resection of gastric adenoma should be considered during the initial examination. Careful observation and follow-up should also be conducted to detect not only changes in the primary adenoma but also the occurrence of metachronous carcinoma, especially in cases of adenoma progressing to carcinoma. [ABSTRACT FROM AUTHOR]

Background and aims: A drawback of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) is the development of metachronous gastric cancer (MGC). While MGC after ESD for differentiated-type (D-) EGC was well understood, little is known about MGC occurring after ESD for undifferentiated-type (UD-) EGC, because ESD had not been indicated. We evaluated the incidence and treatment outcomes of MGC after ESD of UD-EGC. Methods: This study is a post hoc analysis of JCOG1009/1010, a multicenter trial to evaluate the efficacy and safety of ESD for UD-EGC. The patients who underwent curative ESD of index solitary UD-EGC were analyzed. Surveillance endoscopy was performed biannually for the first 3 years and thereafter annually. We assessed the time to MGC occurrence after ESD, lesion characteristics, and treatment outcomes of MGC. Time to MGC occurrence was estimated by cumulative incidence function, with death and total gastrectomy as competing risks. Results: A total of 198 patients were included in this study. During a median follow-up period of 5.8 years, 4 patients (2%) developed MGC. Median time to MGC occurrence was 4.5 years (range: 3.1–5.4). Five-year cumulative incidence of MGC was 1.0% (95% CI: 0.2–3.3%). Two MGCs were histologically D-EGC, and the remaining two were UD-EGC. The median tumor size of MGCs was 1.0 cm (range: 0.7–1.7), and the depth of invasion (M/SM1/SM2) was 2/1/1, respectively. Three patients achieved curative resection with repeated ESD. Conclusions: MGC does not occur commonly after curative ESD of UD-EGC, and repeated ESD could contribute to stomach preservation. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the most frequent primary cancer-associated with esophageal cancer and is most commonly detected by endoscopic surveillance. However, the clinical features of synchronous or metachronous gastric cancer that could be detected by esophagogastroduodenoscopy in esophageal cancer patients are unknown. Methods: We reviewed the clinical records of all esophageal cancer patients (n = 1379) registered in the cancer registration database who underwent initial treatment between April 2010 and October 2015. We retrospectively analyzed the proportions of synchronous and metachronous gastric cancer cases, the cumulative incidence rate of metachronous gastric cancer in total and by esophageal cancer treatments (endoscopic resection, esophagectomy, and chemoradiotherapy), and the clinical features of esophageal cancer patients with synchronous or metachronous gastric cancer. Results: Overall, 67 (5.3% of 1275) esophageal cancer patients with synchronous gastric cancer and 40 (5.1% of 791) esophageal cancer patients with metachronous gastric cancer were analyzed. The 5-year cumulative incidence rate of metachronous gastric cancer was 5.6% in total, 7.8% after endoscopic resection, 4.7% after esophagectomy, and 4.1% after chemoradiotherapy for esophageal cancer. From the results of multivariate analysis, the risk factors for synchronous gastric cancer were male (odds ratio 13.3) and moderate/severe atrophic gastritis (odds ratio 17.9), and the risk factor of metachronous gastric cancer was moderate/severe atrophic gastritis (hazard ratio 27.6) in patients with esophageal cancer. Conclusions: The incidence rates of synchronous and metachronous gastric cancer with esophageal cancer were both over 5%. Careful endoscopic observation is required for moderate and severe atrophic gastritis at detecting concomitant gastric cancer in esophageal cancer patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of metachronous multiple gastric cancer (MMGC) after gastrectomy remains unclear. This study evaluated the incidences of MMGC according to specific gastrectomy types, including pylorus-preserving gastrectomy (PPG), proximal gastrectomy (PG), and function-preserving gastrectomy (FPG), which was categorized as segmental gastrectomy and local resection. Methods: We conducted a questionnaire survey of the Japanese Society for Gastro-Surgical Pathophysiology members, who were asked to report their institutional numbers of radical gastrectomy cases for cancer between 2003 and 2012. The cases were categorized according to whether the remnant stomach's status was followed for > 5 years, confirmation of MMGC, time to diagnosis, and treatment for MMGC. We calculated the "precise incidence" of MMGC by dividing the number of MMGC cases by the number of cases in which the status of remnant stomach was followed up for > 5 years. Results: The responses identified 33,731 cases of gastrectomy. The precise incidences of MMGC were 2.35% after distal gastrectomy (DG), 3.01% after PPG, 6.28% after PG (p < 0.001), and 8.21% after FPG (p < 0.001). A substantial proportion of MMGCs (36.4%) was found at 5 years after the initial surgery. The rates of MMGC treatment using endoscopic submucosal dissection were 31% after DG, 28.6% after PPG, 50.8% after PG (p < 0.001), and 67.9% after FPG (p < 0.001). Conclusions: The incidence of MMGC was 2.4% after DG, and higher incidences were observed for larger stomach remnants. However, the proportion of cases in which MMGC could be treated using endoscopic submucosal dissection was significantly higher after PG and FPG than after DG. [ABSTRACT FROM AUTHOR]

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 (

Background: Helicobacter pylori (H pylori) infection is closely associated with the incidence of gastric cancer. However, whether H pylori eradication prevents metachronous gastric cancer remains uncertain. The aim of our study is to assess how eradicating H pylori influences metachronous gastric cancer onset following treatment of early stage gastric cancer via endoscopic resective surgery. Patients and Methods: We performed a systematic review and meta‐analysis by searching PubMed, Embase, Web of Science, and the Cochrane Library. Cohort studies and randomized controlled trials that compared individuals receiving H pylori eradication with individuals receiving placebo/nontreatment and evaluated the subsequent onset of metachronous gastric cancer as the main outcome were eligible for our study. Two authors reviewed articles and extracted data independently. Integrated results for all data were presented as risk ratio. Results: Thirteen studies containing 3863 patients were consistent with study inclusion criteria. Of the 2480 individuals in whom H pylori was successfully eradicated, 163 (6.57%) developed metachronous gastric cancer, as compared with 176 (12.73%) out of 1383 persistently infected individuals. The pooled risk ratio of metachronous gastric cancer for these studies was 0.46 (95% CI, 0.37‐0.57, P <.001), providing support for the therapeutic elimination of H pylori. Subgroup analyses yielded similar results. Conclusion: Eradicating H pylori via therapeutic treatment can effectively reduce rates of metachronous gastric cancer, and as such, it should be implemented in H pylori‐infected individuals recently treated for early stage gastric cancers via endoscopic resection. [ABSTRACT FROM AUTHOR]

Metachronous gastric cancer often occurs after endoscopic resection. Appropriate management, including chemoprevention, is required after the procedure. This study was performed to evaluate the association between medication use and the incidence of metachronous gastric cancer after endoscopic resection. This multicenter retrospective cohort study was conducted with data from nine hospital databases on patients who underwent endoscopic resection for gastric cancer between 2014 and 2019. The primary outcome was the incidence of metachronous gastric cancer. We evaluated the associations of metachronous gastric cancer occurrence with medication use and clinical factors. Hazard ratios were adjusted by age and Charlson comorbidity index scores, with and without consideration of sex, smoking status, and receipt of Helicobacter pylori eradication therapy during the study period. During a mean follow-up period of 2.55 years, 10.39% (140/1347) of all patients developed metachronous gastric cancer. The use of antibiotics other than those used for H. pylori eradication was associated with a lower incidence of metachronous gastric cancer than was non-use (adjusted hazard ratio (aHR) 0.56, 95% confidence interval (CI) 0.38–0.85, p = 0.006). Probiotic drug use was also associated with a lower incidence of metachronous gastric cancer compared with non-use (aHR 0.29, 95% CI 0.091–0.91, p = 0.034). In conclusion, the use of antibiotics and probiotic drugs was associated with a decreased risk of metachronous gastric cancer. These findings suggest that the gut microbiome is associated with metachronous gastric cancer development.

Background/AimsGastric cancers develop even after successful Helicobacter pylori eradication. We aimed to clarify the characteristics of early gastric cancers discovered after H. pylori eradication.Methods : A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dissection were included. After matching the propensity score, we retrospectively investigated the clinicopathological features of 192 patients, including 96 patients who had undergone successful H. pylori eradication (Hp-eradicated group) and 96 patients who had active H. pylori infection (Hp-positive group).Results : In the Hp-eradicated group, early gastric cancers were discovered 1 to 15 years (median, 4.1 years) after H. pylori eradication. Compared with Hp-positive patients, Hp-eradicated patients showed a more frequently depressed configuration (81% vs 53%, respectively, p

Background and purpose: Proximal gastrectomy (PG) is a widely accepted function-preserving surgical procedure; however, the incidence and treatment of metachronous gastric cancer (MGC) after PG have been the subject of a number of reports.Methods: We collected data from 1576 consecutive patients who underwent gastrectomy for gastric cancer between January, 2003 and December, 2010, and analyzed the outcomes of 671 patients treated with PG or distal gastrectomy (DG) for cT1N0 disease. We also discuss the treatments for MGC.Results: MGC was diagnosed within a median follow-up of 52.8 months after PG and DG in six (6.6%) and nine (1.8%) patients, respectively. The cumulative prevalence of MGC after PG was significantly higher than that after DG; P = 0.005. Univariate and multivariate analysis revealed male sex and PG as significant risk factors for MGC (P = 0.014 and P = 0.026, respectively). Five of the six patients who underwent PG were treated by endoscopic submucosal dissection.Conclusions: The incidence of MGC after PG was significantly higher than that after DG. However, most of the MGCs that developed after PG could be treated by endoscopic submucosal dissection. [ABSTRACT FROM AUTHOR]

Background: Whether surveillance strategy after curative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) differs in young patients is unclear. This study aimed to evaluate the risk of metachronous and extragastric recurrence in young patients with EGC after curative ESD.Methods: We retrospectively enrolled 1237 consecutive patients who underwent curative ESD for EGC from 2005 to 2014 at a single tertiary hospital. The patients were divided into group 1 (<50 years of age, n = 86), group 2 (age 50-74, n = 985), or group 3 (≥75 years of age, n = 166). The clinical characteristics and outcomes were compared among the three age groups.Results: Group 1 had more frequent Helicobacter pylori infection (P < 0.001), less frequent intestinal metaplasia (P = 0.021), and more frequent undifferentiated tumors (P = 0.039). Although the 5-year risk of developing metachronous recurrence appeared to be lower in group 1 (2.7%) than in groups 2 (8.6%) or 3 (8.7%), the risk became quite similar at the 7-year follow-up (6.4, 12.7, and 8.7% for groups 1, 2, and 3, respectively; P = 0.409 by log-rank test). Extragastric recurrences developed in only 2 cases in group 2 (0.2%).Conclusions: Surveillance for metachronous and extragastric recurrence after curative ESD in patients <50 years of age should not be different from that in patients ≥50 years of age. Endoscopic surveillance for metachronous recurrence should be continued for longer than 5 years, even in young patients. [ABSTRACT FROM AUTHOR]

We have previously reported that serum pepsinogen (PG) can quantify the level of gastric mucosal atrophy, and that H. pylori eradication reduces cancer development in subjects with mild atrophy identified by serum PG levels. The aim of this study was to elucidate the predictive ability of serum PG levels for the development of metachronous gastric cancer (MGC) after endoscopic resection (ER) of primary cancer in association with H. pylori eradication. A retrospective chart review was performed, and 330 patients who underwent ER for initial early gastric cancer were enrolled. Presence or absence of H. pylori, serum PG levels, and endoscopic atrophy at ER were evaluated. H. pylori eradication was performed at the patient's request after ER. The incidence of MGC in these patients was analyzed. Of 330 patients, 47 developed MGC. Endoscopic extensive atrophy was observed more frequently in patients with MGC ( p = 0.001). Although PG I or PG II alone did not significantly differ according to development of MGC, the proportion of PG I/II ≤ 3.0, which is one of the criteria of PG test-positive, was significantly higher in patients with MGC (83 vs. 69%, p = 0.04). H. pylori eradication after ER did not affect MGC development ( p = 0.2). On multivariate analysis, serum PG I/II ratio ≤ 3.3 was significantly associated with the development of MGC (hazard ratio: 3.66, 95% confidence interval: 1.47-12.25, p = 0.004). The risk of MGC after ER could be quantitatively predicted by the PG I/II ratio regardless of H. pylori status. [ABSTRACT FROM AUTHOR]

Background: Metachronous gastric cancer (GC) can develop after endoscopic resection of GC and cannot be predicted based on clinical signature. Aberrant DNA methylation in noncancerous gastric mucosa is strongly implicated in gastric carcinogenesis and could be a useful biomarker of GC risk. We evaluated the clinical utility of DNA methylation as a biomarker of metachronous GC risk. Method: We carried out scheduled follow-up endoscopy in 129 patients after curative endoscopic resection of GC. Biopsy specimens were collected from noncancerous mucosa in the gastric antrum and body, after which quantitative methylation analysis of miR- 34b/c, SFRP1, SFRP2, SFRP5, DKK2 and DKK3 was carried out using bisulfite pyrosequencing. The utility of the methylation for predicting the risk of metachronous GC development was assessed using Kaplan-Meier and Cox proportional hazards model analyses. Results: During the follow-up period, 17 patients (13 %) developed metachronous GCs. The cumulative incidence of metachronous GC was significantly higher among patients with elevated miR- 34b/c, SFRP2 and DKK2 methylation in their gastric body. MiR- 34b/c showed the strongest association with the risk of metachronous GC, and the cumulative incidence of metachronous GC was much higher in the high- miR- 34b/c-methylation group than the low-methylation group. Multivariate analysis adjusted for age, sex, H. pylori status and pathological findings showed miR- 34b/c methylation in gastric body to be an independent predictor of metachronous GC risk. Conclusion: Our results suggest that methylation of miR- 34b/c in the mucosa of the noncancerous gastric body may be a useful biomarker for predicting the risk of metachronous GC. [ABSTRACT FROM AUTHOR]

We conducted a comprehensive literature review and meta-analysis study on the efficacy of Helicobacter pylori ( H. pylori ) eradication in preventing metachronous gastric cancer after endoscopic resection among an East Asian population. Our results showed that the eradication of this pathogen significantly reduced the risk of susceptibility to metachronous gastric cancer in these patients. However, based on the available evidence, several factors such as increasing age, severe atrophy in the corpus and antrum, and intestinal metaplasia all may increase the risk of metachronous gastric cancer in H. pylori eradicated patients., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Although Helicobacter pylori eradication decreases the incidence of metachronous gastric cancer after endoscopic treatment for early gastric cancer (EGC), metachronous cancer still develops after successful eradication, particularly in patients with severe corpus gastritis. We investigated whether the extent of atrophic fundic gastritis diagnosed by autofluorescence imaging (AFI) videoendoscopy is predictive of development of metachronous gastric cancer after H. pylori eradication in patients treated with endoscopic submucosal dissection (ESD) for EGC. A total of 82 patients who underwent ESD for EGC from 2003 to 2006, who received eradication therapy participated in this study. The extent of chronic atrophic fundic gastritis was evaluated by AFI and categorized into closed and open type. The main outcome was the incidence of metachronous gastric cancer detected by annual surveillance endoscopy. During a median observation period of 55 months, metachronous gastric cancer developed in 12 of 82 patients (14.6%). Multivariate Cox's proportional hazard analysis revealed that open-type, atrophic fundic gastritis diagnosed by AFI was significantly associated with development of metachronous gastric cancer (hazard ratio: 4.88, 95% confidence interval [CI]: 1.32-18.2, P = 0.018) after adjustment for age, sex, histological intestinal metaplasia, serum pepsinogen level, and H. pylori status. Metachronous EGC developed after successful H. pylori eradication, and extensive atrophic fundic gastritis diagnosed by AFI was a significant predictor, thus it could identify patients undergoing ESD for EGC who still required intensive surveillance after eradication. [ABSTRACT FROM AUTHOR]

Background: Clinical effectiveness of Helicobacter pylori eradication in gastric cancer survivors after endoscopic resection of early gastric cancer (EGC) was recently established in a randomized controlled trial. We aimed to establish long-term cost-effectiveness in gastric cancer survivors after endoscopic resection of EGC. Materials and Methods: A Markov model was constructed to compare the costs and outcomes of the two intervention strategies: (1) eradicate H. pylori after complete resection of EGC by endoscopy (2) do not eradicate. Estimates for variables in the model were obtained by extensive review of published reports. Analyses were made from the Korean public healthcare provider’s perspective. Results: Base-case analysis indicated H. pylori eradication costs less (US$ 29,780 vs. US$ 30,594) than no eradication, and save more lives (mean life expectancy from eradication: 13.60 years vs. 13.55 years). One-way and three-way sensitivity analyses showed the robustness of the cost-effectiveness results. Conclusion: In this selective population with very high risk of developing gastric cancer, H. pylori eradication should be considered for reimbursement with priority to prevent subsequent cancer and also reduce health care cost. [ABSTRACT FROM AUTHOR]

Background/Aims Helicobacter pylori (HP) infection is well known to contribute to the development of gastric cancer (GC). Eradication after endoscopic treatment of early GC is recommended to prevent metachronous cancer in the remnant stomach. In addition, HP eradication therapy after surgical treatment of GC can improve the survival rate of GC patients. In this study, we aimed to investigate the rate of HP diagnosis and eradication treatment after GC surgery in a tertiary institute in Korea. Methods Patients who received surgical treatment after diagnosis of GC at Seoul National University Bundang Hospital from 2003 to 2017 were retrospectively analyzed using Electronic Medical Recording and Clinical Data Warehouse (CDW). HP examinations (histology, CLO test, and urea breath test) before and after surgery, prescription for eradication, and follow-up examination results are reviewed in detail. Results Figure shows the examination for HP and eradication status of GC patients. Total 3,734 patients were diagnosed with GC and received surgical treatment. The 2,272 patients (60.8%) were tested (1,372 patients preoperatively and 905 patients after surgery). The 1,283 patients (56.5%) were positive for HP infection. Among HP+GC patients 354 patients (27.6%) received eradication treatment, and finally 237 patients were successfully eradicated. Seventy-one patients showed fluctuation of test results without eradication (dynamic changes for HP), and 989 patients were persistently negative for HP (Fig. 1). Conclusions Both diagnostic test and eradication treatment rates in patients received GC surgery were significantly low, about one-third patients were not tested even once, and only about 20% of HP-positive patients were successfully eradicated. Considering the high prevalence of GC in Korea and potential benefits of eradication therapy in GC patients, these low rates are disappointing. More attentions and interests of clinicians for GC patients with surgery are needed in terms of HP eradication. [ABSTRACT FROM AUTHOR]

Simple Summary: Helicobacter pylori is the most important cause of gastric cancer, and its eradication reduces the incidence of gastric cancer after endoscopic resection. However, incidence of metachronous gastric cancer is still high. More studies are needed to identify other chemopreventive drugs that may reduce the incidence of this disease. In this study, we focused on the alteration of the intragastric microbiome and examined the association between the use of antibiotics and probiotic drugs and risk of metachronous gastric cancer. Our findings suggest that the gut microbiome is associated with metachronous gastric cancer development. Metachronous gastric cancer often occurs after endoscopic resection. Appropriate management, including chemoprevention, is required after the procedure. This study was performed to evaluate the association between medication use and the incidence of metachronous gastric cancer after endoscopic resection. This multicenter retrospective cohort study was conducted with data from nine hospital databases on patients who underwent endoscopic resection for gastric cancer between 2014 and 2019. The primary outcome was the incidence of metachronous gastric cancer. We evaluated the associations of metachronous gastric cancer occurrence with medication use and clinical factors. Hazard ratios were adjusted by age and Charlson comorbidity index scores, with and without consideration of sex, smoking status, and receipt of Helicobacter pylori eradication therapy during the study period. During a mean follow-up period of 2.55 years, 10.39% (140/1347) of all patients developed metachronous gastric cancer. The use of antibiotics other than those used for H. pylori eradication was associated with a lower incidence of metachronous gastric cancer than was non-use (adjusted hazard ratio (aHR) 0.56, 95% confidence interval (CI) 0.38–0.85, p = 0.006). Probiotic drug use was also associated with a lower incidence of metachronous gastric cancer compared with non-use (aHR 0.29, 95% CI 0.091–0.91, p = 0.034). In conclusion, the use of antibiotics and probiotic drugs was associated with a decreased risk of metachronous gastric cancer. These findings suggest that the gut microbiome is associated with metachronous gastric cancer development. [ABSTRACT FROM AUTHOR]

Background/Aims Early gastric cancer (GC) patients have a good prognosis after radical resection. However, there is risk of metachronous gastric neoplasm (MGN) if the patients have a gastric remnant after the surgery. The aim of this study was to clarify the risk factors for MGN after partial gastrectomy for GC. Methods Data of 680 patients who received surgical treatment after diagnosis of GC at Seoul National University Bundang Hospital from 2003 to 2017 were retrospectively analyzed using Electronic Medical Recording and Clinical Data Warehouse. A univariate Cox proportional hazards model was used to identify possible covariates as significant risk factors for MGN. Then, the variables with p<0.05 were subjected to multivariate Cox proportional hazards model to identify independent contribution. In addition, the variables which were considered to be possible risk factors for MGN based on the previous studies were also analyzed in multivariate model. Results Total 680 patients were diagnosed with GC and received surgical treatment, and 574 patients were received subtotal, partial, or distal gastrectomy. Among these cases, 11 patients (1.6%) were diagnosed as having MGN in the gastric remnant. They underwent curative resection by endoscopic resection (six patients), remnant gastrectomy (four patients) or chemotherapy (one patient). Table 1 shows the clinicopathological characteristics of patients with and without MGN. Multivariate analysis showed that male sex only was independent risk factor. Conclusions Our data suggested that more intensive endoscopic follow-up is needed for the remnant stomach in patients with these risk factors to detect MGN at its early stage. Further study including a higher number of MGN patients may be needed for accurate analysis. [ABSTRACT FROM AUTHOR]

Background/aims: Patients treated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) are at risk of developing metachronous gastric cancer (MGC). The aim of this study was to evaluate the clinical outcomes of MGC after ESD for EGC between the re-ESD and surgery groups., Methods: In total, data from 1,510 patients who underwent ESD for EGC from January 2005 to May 2014 were retrospectively reviewed, and data from 112 patients with MGC were analyzed according to the type of treatment, namely, re-ESD and surgery. The clinicopathological factors affecting the subsequent treatment and outcomes of MGC were evaluated., Results: The median duration to the development of MGC was 47 months. In multivariate analysis, lower body mass index (BMI) (p=0.037) and multiplicity (p=0.014) of index cases were significantly associated with subsequent surgery for MGC. In cases of MGC, a diffuse or mixed-type Lauren classification (p=0.009), the depth of tumor mucosal invasion (p=0.001), and an upper stomach location (p=0.049) were associated with surgery. Overall survival was significantly shorter in the surgery group than in the re-ESD group after treatment for MGC (log-rank test, p=0.01)., Conclusions: Lower BMI and multiplicity of index cancers were significantly associated with the surgical resection of MGC. Close follow-up is needed to minimize additional treatment for cases at high risk of advanced MGC after ESD for EGC.

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 (&lt;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.

Background/aims: Gastric cancers develop even after successful Helicobacter pylori eradication. We aimed to clarify the characteristics of early gastric cancers discovered after H. pylori eradication., Methods: A total of 1,053 patients with early gastric cancer treated by endoscopic submucosal dissection were included. After matching the propensity score, we retrospectively investigated the clinicopathological features of 192 patients, including 96 patients who had undergone successful H. pylori eradication ( Hp -eradicated group) and 96 patients who had active H. pylori infection ( Hp -positive group)., Results: In the Hp -eradicated group, early gastric cancers were discovered 1 to 15 years (median, 4.1 years) after H. pylori eradication. Compared with Hp -positive patients, Hp -eradicated patients showed a more frequently depressed configuration (81% vs 53%, respectively, p<0.0001) and a higher trend toward submucosal invasion (18% vs 8%, respectively, p=0.051). A multivariable analysis revealed the macroscopic depressed type to be characteristics of early gastric cancers after H. pylori eradication. Among patients in the Hp -eradicated group, metachronous cancers showed less frequent depressed lesions (68% vs 84%, respectively, p=0.049) and smaller tumor sizes (median, 11 mm vs 14 mm, respectively, p=0.014) than primary cancers., Conclusions: Early gastric cancers after H. pylori eradication are characterized by a depressed configuration. Careful follow-up endoscopies are necessary after H. pylori eradication.

Aim: To investigate the effect of Helicobacter pylori ( H. pylori ) status test and H. pylori eradication on the occurrence of metachronous gastric cancer (MGC) after endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) and risk factors of MGC., Methods: The authors retrospectively reviewed the medical records of 433 patients (441 lesions) who underwent ESD for EGC from January 2005 to January 2015 in Yeungnam University Hospital. Patients were categorized into two groups; the H. pylori tested group ( n = 257) and the H. pylori non-tested group ( n = 176) based on performance of H. pylori status test after ESD of EGC. The H. pylori tested group was further categorized into three subgroups based on H. pylori status; the H. pylori -eradicated subgroup ( n = 120), the H. pylori -persistent subgroup ( n = 42), and the H. pylori -negative subgroup ( n = 95). Incidences of MGC and risk factors of MGC were identified., Results: Median follow-up duration after ESD was 30.00 mo (range, 6-107 mo). Total 15 patients developed MGC during follow-up. MGC developed in 11 patients of the H. pylori tested group (7 in the H. pylori -negative subgroup, 3 in the H. pylori -eradicated subgroup, and 1 in the H. pylori -persistent subgroup) and 4 patients of the H. pylori non-tested group ( P > 0.05). The risk factors of MGC were endoscopic mucosal atrophy in the H. pylori tested group and intestinal metaplasia in all patients., Conclusion: H. pylori eradication and H. pylori status test seems to have no preventive effect on the development of MGC after ESD for EGC. The risk factors of MGC development were endoscopic mucosal atrophy in the H. pylori tested group alone and intestinal metaplasia in all patients., Competing Interests: Conflict-of-interest statement: We have no conflict-of-interest to disclose.

Helicobacter pylori (H. pylori) infection was thought to be the main cause of gastric cancer, and its eradication showed improvement in gastric inflammation and decreased the risk of gastric cancer. Recently, a number of studies reported the occurrence of gastric cancer after successful eradication. Patients infected with H. pylori, even after eradication, have a higher risk for the occurrence of gastric cancer when compared with uninfected patients. Metachronous gastric cancer occurs frequently following the endoscopic removal of early gastric cancer. These data indicate that metachronous cancer leads to the occurrence of gastric cancer even after successful eradication of H. pylori. The pathogenesis of this metachronous cancer remains unclear. Further research is needed to identify biomarkers to predict the development of metachronous gastric cancer and methods for gastric cancer screening. In this article, we review the role of the H. pylori in carcinogenesis and the histological and endoscopic characteristics and risk factors for metachronous gastric cancer after eradication. Additionally, we discuss recent risk predictions and possible approaches for reducing the risk of metachronous gastric cancer after eradication., Competing Interests: Conflict-of-interest statement: No conflict of interests.

Early detection of early gastric cancer (EGC) is important to improve the prognosis of patients with gastric cancer. Recent advances in endoscopic modalities and treatment devices, such as image-enhanced endoscopy and high-frequency generators, may make endoscopic treatment, such as endoscopic submucosal dissection, a therapeutic option for gastric intraepithelial neoplasia. Consequently, short-term outcomes of endoscopic resection (ER) for EGC have improved. Therefore, surveillance with endoscopy after ER for EGC is becoming more important, but how to perform endoscopic surveillance after ER has not been established, even though the follow-up strategy for more advanced gastric cancer has been outlined. Therefore, a surveillance strategy for patients with EGC after ER is needed.