Metachronous Gastric Neoplasms Research Articles

Gastric microbiome signature for predicting metachronous recurrence after endoscopic resection of gastric neoplasm.

Changes in gastric microbiome are associated with gastric carcinogenesis. Studies on the association between gastric mucosa-associated gastric microbiome (MAM) and metachronous gastric cancer are limited. This study aimed to identify gastric MAM as a predictive factor for metachronous recurrence following endoscopic resection of gastric neoplasms. Microbiome analyses were conducted for 81 patients in a prospective cohort to investigate surrogate markers to predict metachronous recurrence. Gastric MAM in non-cancerous corporal biopsy specimens was evaluated using Illumina MiSeq platform targeting 16S ribosomal DNA. Over a median follow-up duration of 53.8months, 16 metachronous gastric neoplasms developed. Baseline gastric MAM varied with Helicobacter pylori infection status, but was unaffected by initial pathologic diagnosis, presence of atrophic gastritis, intestinal metaplasia, or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence but showed significant difference in β-diversity. The study population could be classified into two distinct gastrotypes based on baseline gastric MAM: gastrotype 1, Helicobacter-abundant; gastrotype 2: Akkermansia-abundant. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype (Cox proportional hazard analysis, adjusted hazard ratio [95% confidence interval]: 5.10 [1.09-23.79]). Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.

Risk Assessment of Metachronous Gastric Neoplasm after Endoscopic Resection for Early Gastric Cancer According to Age at Helicobacter pylori Eradication.

Helicobacter pylori eradication can reduce the incidence of metachronous gastric neoplasm (MGN) after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). This study evaluated the risk of developing MGN after ESD for EGC based on age at H. pylori eradication. Data of patients who underwent curative ESD for EGC with H. pylori infection between 2005 and 2018 were retrospectively analyzed. The patients were allocated to four groups according to age at H. pylori eradication: group 1 (<50 years), group 2 (50-59 years), group 3 (60-69 years), and group 4 (≥70 years). All patients were followed up for at least 5 years after ESD. The 5-year cumulative incidence of MGN was 2.1%, 7.0%, 8.7%, and 16.7% in groups 1, 2, 3, and 4, respectively (p<0.001), and groups 3 and 4 showed a significant increase in the risk of MGN (hazard ratio [HR], 4.66; 95% confidence interval [CI], 1.09 to 19.92 and HR, 10.75; 95% CI, 2.45 to 47.12). After adjustments for moderate to severe intestinal metaplasia based on the updated Sydney system, groups 3 and 4 remained significantly associated with MGN (HR, 4.40; 95% CI, 1.03 to 18.84 and HR, 10.14; 95% CI, 2.31 to 44.57). The incidence of MGN after ESD for EGC increased with age at H. pylori eradication. Age at H. pylori eradication ≥60 years was an independent risk factor for MGN, even after adjusting for the presence of advanced intestinal metaplasia.

Risk Factors for Developing Metachronous Superficial Gastric Epithelial Neoplasms after Endoscopic Submucosal Dissection.

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD.

Gastric microbiome signature to predict metachronous recurrence after endoscopic resection of gastric neoplasms.

399 Background: It is well-established that the gastric microbiota undergoes significant alterations during the process of gastric carcinogenesis. This study aimed to identify gastric mucosa-associated microbiome (MAM) for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms. Methods: Subgroup analyses were conducted for 81 patients (early gastric cancer: dysplasia = 55:26) from a prospective cohort (Clinical Trials No. NCT04830618). Demographic data, and history of Helicobacter pylori eradication therapy, endoscopic and histologic findings were incorporated. The profile of Gastric MAM obtained from non-cancerous corporal biopsy specimens and was analyzed by 16S rDNA sequencing. Results: Over a median follow-up duration of 53.8 months, 16 metachronous gastric neoplasms (10 adenomas and 6 adenocarcinomas) developed. Baseline gastric MAM varied with H. pylori infection status, but was unaffected by the presence of atrophic gastritis, intestinal metaplasia or synchronous lesions. The group with metachronous recurrence did not exhibit distinct phylogenetic diversity compared with the group devoid of recurrence. β-diversity analysis showed significant difference between the two groups (weighted UniFrac distance, PERMANOVA p = 0.006). In the LEfSe analysis, metachronous recurrence group had an increased abundance of Corynebaceriaceae, Comamonadaceae, Corynebacterium, Curvibacter, and a decreased abundance of Helicobacteraceae, and Helicobacter. The total study population were classified into two distinct gastrotypes by baseline Gastric MAM (gastrotype 1: Helicobacter-dominant, gastrotype 2: Akkermansia-abundant). MAM of gastrotype 1 had higher abundance of Helicobacter pylori, and lower abundance of Akkermansia¸ Comamodaceae, Muribaculacae , Streptococcus, Corynebacteriaceae , Cutibaterium. Patients in gastrotype 2 showed higher risk of metachronous recurrence than gastrotype 1 (hazard ratio = 4.621 by Cox proportional hazard model, p-value = 0.0185). Conclusions: Gastric cancer patients can be classified into two distinct gastrotypes by their MAM profiles, which were associated with different risk of metachronous recurrence. MAM profiling of gastric cancer patients is expected give insight into their risk of metachronous recurrence. Clinical trial information: NCT04830618 .

Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study

Background and aimsThe aim of this study was to investigate the association between Helicobacter pylori treatment and the risk of gastric cancer after endoscopic resection (ER) of gastric dysplasia. MethodsPatients who received ER for gastric dysplasia between 2010 and 2020 from Korean nationwide insurance data were included. We verified the occurrence of new-onset gastric cancer and metachronous gastric neoplasm, which encompasses both cancer and dysplasia, more than a year after the index ER. Newly diagnosed gastric cancer ≥3 years and ≥5 years was regarded as late-onset gastric cancer. A multivariable Cox regression model with H. pylori treatment status as a time-dependent covariate was used to determine the risk of gastric cancer and metachronous gastric neoplasms. ResultsOf the 69,722 patients with gastric dysplasia and were treated with endoscopy, 49.5% were administered H. pylori therapy. During the median 5.6 years of follow-up, 2,406 and 3,342 patients developed gastric cancer and metachronous gastric neoplasms, respectively. Receiving H. pylori therapy was closely related to lower gastric cancer risk (adjusted hazard ratio [aHR] 0.88; 95% confidence interval [CI], 0.80-0.96). H. pylori treatment also significantly decreased metachronous gastric neoplasm development (aHR 0.76; 95% CI, 0.70-0.82). Furthermore, H. pylori therapy showed a prominent protective effect for late-onset gastric cancer development (aHR, 0.84 [95% CI, 0.75-0.94] for ≥ 3 years; aHR, 0.80 [95% CI, 0.68-0.95] for ≥ 5 years). ConclusionIn this nationwide cohort, H. pylori therapy after endoscopic resection of gastric dysplasia was associated with a reduced risk of gastric cancer and metachronous gastric neoplasm occurrence.

Impact of Autoimmune Gastritis on Occurrence of Metachronous Gastric Neoplasms after Endoscopic Resection for Gastric Neoplasms.

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Autoimmune gastritis (AIG) is characterized by antibody production against the gastric parietal cells, reducing the number of functional parietal cells. It is also associated with an increased susceptibility to gastric neuroendocrine tumors and gastric cancer. Endoscopic resection (ER) is an effective treatment for early gastric cancer; however, metachronous gastric neoplasms (MGN) can develop. This study aimed to evaluate the clinical effect of AIG on the occurrence of MGN after ER for gastric neoplasms. We retrospectively analyzed patients who underwent ER for gastric neoplasms. Patients with multiple lesions, recurrent lesions, or a history of partial gastrectomy were excluded. The presence of AIG was determined using anti-parietal cell antibody (APCA) testing. Follow-up endoscopy and metachronous tumor occurrence rates were compared between the AIG and non-AIG groups. Of the 569 patients, 282 underwent APCA testing and 20 (7.1%) were diagnosed with AIG. The incidence of MGN was significantly higher in the AIG group than in the non-AIG group (45.0% vs. 18.3%); however, the MGN occurrence pattern was similar between the two groups. Multivariate analysis revealed that AIG (HR 3.32, 95% CI 1.55-7.10, p = 0.002) and a higher body mass index (HR 1.16, 95% CI 1.06-1.27, p = 0.002) were independent factors significantly associated with the occurrence of MGN. Patients with AIG have a higher risk of metachronous lesion occurrence after ER for gastric neoplasms. Positive results of APCA testing have independent clinical implications for predicting MGN. Proper monitoring and management are essential for early detection and treatment of recurrent lesions in patients with AIG.

The pattern of metachronous recurrence after endoscopic submucosal dissection for gastric adenocarcinoma and dysplasias.

Metachronous recurrence incidences and risk factors following endoscopic submucosal dissection (ESD) for gastric adenocarcinoma and dysplasias were investigated. Retrospective review of electronic medical records of patients who underwent gastric ESD at The Catholic University of Korea, Yeouido St. Mary's Hospital. A total of 190 subjects were enrolled for analysis during the study period. The mean age was 64.4 years-old and the male sex occupied 73.7%. The mean observation period following ESD was 3.45 years. The annual incidence rate of metachronous gastric neoplasms (MGN) was about 3.96%. The annual incidence rate was 5.36% for the low-grade dysplasia group, 6.47% for the high-grade dysplasia group, and 2.74% for the EGC group. MGN was more frequent in the dysplasia group than in the EGC group (p<0.05). For those with MGN development, the mean time interval from ESD to MGN was 4.1 (±1.8) years. By using the Kaplan-Meier model, the estimated mean MGN free survival time was 9.97 years (95% confidence interval, 8.53-11.40) The histological types of MGN were not related to the primary histology types. MGN following ESD developed in 3.96% annually and MGN was more frequent in the dysplasia group. The histological types of MGN did not correlate with those of primary neoplasm.

Effect of Helicobacter pylori Eradication Treatment on Metachronous Gastric Neoplasm Prevention Following Endoscopic Submucosal Dissection for Gastric Adenoma.

The long-term effect of Helicobacter pylori eradication on metachronous gastric neoplasm prevention after endoscopic submucosal dissection (ESD) of gastric adenoma is unclear. This study included patients with confirmed H. pylori infection after ESD with curative resection for gastric adenoma. Patients were divided based on the success of H. pylori eradication treatment into two groups: eradication and non-eradication. Patients with any newly detected lesion within 1 year after ESD and recurrence at the ESD site were excluded from the analysis. Further, 1:1 propensity score matching was also performed to eliminate baseline differences between the two groups. H. pylori eradication treatment was administered to 673 patients after ESD (163 in the successful eradication group and 510 in the non-eradication group). During the median follow-up periods of 25 and 39 months in the eradication and non-eradication groups, metachronous gastric neoplasm was identified in 6 (3.7%) and 22 patients (4.3%), respectively. Adjusted Cox analysis revealed that H. pylori eradication was not associated with increased risk of metachronous gastric neoplasm after ESD. Kaplan-Meier analysis in the matched population yielded similar findings (p = 0.546). H. pylori eradication treatment was not associated with metachronous gastric neoplasm after ESD with curative resection for gastric adenoma.

Metachronous gastric neoplasm beyond 5years after endoscopic resection for early gastric cancer.

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) 5years after ESD for EGC. 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 5years post-ESD were evaluated. Among the 2059 patients who underwent ESD for EGC, 1102 were followed up for > 5years. MGN developed in 132 patients 5years after ESD. During the median follow-up period of 85months, 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 10years, 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), < 5mm 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 5years post-ESD. The cumulative MGN incidence was high even 5years 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 < 5mm, and synchronous adenomas.

Safety of pylorus-preserving gastrectomy for gastric cancer combined with antral high-risk lesions: a comparison with endoscopic submucosal dissection.

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. 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. 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. 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.

Aberrant DNA Methylation Maker for Predicting Metachronous Recurrence After Endoscopic Resection of Gastric Neoplasms.

PurposeThis study aimed to investigate whether MOS methylation can be useful for the prediction of metachronous recurrence after endoscopic resection of gastric neoplasms.Materials and MethodsFrom 2012 to 2017, 294 patients were prospectively enrolled after endoscopic resection of gastric dysplasia (n=171) or early gastric cancer (n=123). When Helicobacter pylori was positive, eradication therapy was performed. Among them, 124 patients completed the study protocol (follow-up duration > 3 years or development of metachronous recurrence during the follow-up). Methylation levels of MOS were measured at baseline using quantitative MethyLight assay from the antrum.ResultsMedian follow-up duration was 49.9 months. MOS methylation levels at baseline were not different by age, sex, and current H. pylori infection, but they showed a weak correlation with operative link on gastritis assessment (OLGA) or operative link on gastric intestinal metaplasia assessment (OLGIM) stages (Spearman’s ρ=0.240 and 0.174, respectively; p < 0.05). During the follow-up, a total of 20 metachronous gastric neoplasms (13 adenomas and 7 adenocarcinomas) were developed. Either OLGA or OLGIM stage was not useful in predicting the risk for metachronous recurrence. In contrast, MOS methylation high group (≥ 34.82%) had a significantly increased risk for metachronous recurrence compared to MOS methylation low group (adjusted hazard ratio, 4.76; 95% confidence interval, 1.54 to 14.79; p=0.007).ConclusionMOS methylation can be a promising marker for predicting metachronous recurrence after endoscopic resection of gastric neoplasms. To confirm the usefulness of MOS methylation, validation studies are warranted in the future (ClinicalTrials No. NCT04830618).

Characteristics of metachronous gastric neoplasms after curative endoscopic submucosal dissection for early gastric neoplasms

Background:With the wide application of endoscopic submucosal dissection (ESD) for early gastric neoplasms, metachronous gastric neoplasms (MGN) have gradually become a concern. This study aimed to analyze the characteristics of MGN and evaluate the treatment and follow-up outcomes of MGN patients.Methods:A total of 814 patients were retrospectively enrolled. All these patients were treated by ESD for early gastric cancer or gastric dysplasia between November 2006 and September 2019 at The First Medical Center of Chinese People's Liberation Army General Hospital. The risk factors for MGN were analyzed using Cox hazard proportional model. Moreover, the cumulative incidence, the correlation of initial lesions and MGN lesions, and the treatment and follow-up outcomes of MGN patients were analyzed.Results:A total of 4.5% (37/814) of patients had MGN after curative ESD. The 3-, 5-, and 7-year cumulative incidences of MGN were 3.5%, 5.1%, and 6.9%, respectively, and ultimately reaching a plateau of 11.3% at 99 months after ESD. There was no significant correlation between initial lesions and MGN lesions in terms of gross type (P = 0.178), location (long axis: P = 0.470; short axis: P = 0.125), and histological type (P = 0.832). Cox multivariable analysis found that initial multiplicity was the only independent risk factor of MGN (hazard ratio: 4.3, 95% confidence interval: 2.0–9.4, P < 0.001). Seventy-three percent of patients with MGN were treated by endoscopic resection. During follow-up, two patients with MGN died of gastric cancer with lymph node metastasis. The disease-specific survival rate was significantly lower in patients with MGN than that in patients without MGN (94.6% vs. 99.6%, P = 0.006).Conclusions:The MGN rate gradually increased with follow-up time within 99 months after curative gastric ESD. Thus, regular and long-term surveillance endoscopy may be helpful, especially for patients with initial multiple neoplasms.

Long-term natural history after endoscopic resection for gastric dysplasia.

Natural history after endoscopic resection (ER) for gastric dysplasia is still unclear. The aim of this study was to evaluate the long-term clinical outcomes and risk factors after ER for gastric dysplasia between control and cases with synchronous or metachronous gastric neoplasm. A total of 1090 patients who had undergone ER for gastric dysplasia and been followed up for at least one year from December 2002 to December 2013 were finally analyzed. Risk factors affecting the development of synchronous or metachronous neoplasm (SMN) and long-term clinical outcomes after ER for gastric dysplasia were evaluated. Synchronous and metachronous neoplasms had developed in 126 (11.6%) and 133 patients(12.2%) during the mean follow-up duration of 63.6months, respectively. Five-year and 10-year risk of metachronous neoplasm were 9.8% and 27.2%, respectively. Median duration to the development of metachronous neoplasm was 103.1months. While age (P < 0.001) and mucosal atrophy (P = 0.09) of index cases were associated with the development of synchronous neoplasm, age (P = 0.017), incomplete resection (P = 0.025), and intestinal metaplasia (P = 0.017) of background mucosa of index cases were significantly related to the development of metachronous neoplasm in multivariate analysis. Cumulative incidence of SMN was not significantly different among H. pylori negative, eradicated, and persistent group. Age, incomplete ER, and background intestinal metaplasia of index gastric dysplasia were significantly associated with metachronous recurrence. Endoscopic surveillance for metachronous recurrence after ER for gastric dysplasia is mandatory for longer than 10years.

Prognostic factors for ESD of early gastric cancers: a systematic review and meta-analysis.

Background and study aims Gastric neoplasms are one of the leading types of cancer in the world and early detection is essential to improve prognosis. Endoscopy is the gold-standard diagnostic procedure and allows adequate treatment in selected cases. Endoscopic submucosal dissection (ESD) has been reported to safely address most early gastric cancers (EGCs), with high curability rates. However, data on prognostic factors related to ESDs of EGCs are conflicting. Therefore, we aimed to systematically review the available literature and to perform a meta-analysis to identify the relevant prognostic factors in this context. Methods We performed this study according to PRISMA guidelines. Comparative studies assessing the relationship between curative resection or long-term curability rates and relevant prognostic factors were selected. Prognostic factors were demographic data, lesion features (location, morphology of the lesion, size, and depth of invasion), histological findings, Helycobacter pylori (HP) infection, presence of gastric a atrophy and body mass index (BMI). Finally, we also evaluated risk factors related to metachronous gastric neoplasm. Results The initial search retrieved 2829 records among which 46 studies were included for systematic review and meta-analysis. The total sample comprised 28366 patients and 29282 lesions. Regarding curative resection, pooled data showed no significant influence of sex [odds ratio (OR): 1.15 (0,97, 1.36) P = 0.10 I 2 = 47 %] , age [OR: 1.00 (0.61, 1.64) P = 1.00 I 2 = 58 %], posterior vs non-posterior location [OR: 1.35 (0.81, 2.27) P = 0.25 I 2 = 84 %], depressed vs von-depressed macroscopic type[OR: 1.21 (0.99, 1.49) P = 0.07 I 2 = 0 %], non-upper vs upper location [OR: 1.41 (0.93, 2.14) P = 0.10 I 2 = 77 %] and BMI [OR: 0.84 (0.57; 1.26) P = 0.41 I 2 = 0 %]. Differentiated neoplasms presented greater chance of cure compare to undifferentiated [OR: 0.10 (0.07, 0.15) P < 0.00001 I 2 = 0 %]. Ulcerated lesions had lower curative rates compared to non-ulcerated [OR: 3.92 (2.81, 5.47) P < 0.00001 I 2 = 44 %]. Lesions smaller than 20 mm had greater chance of curative resection [OR: 3.94 (3.25, 4.78) P < 0.00001 I 2 = 38 %]. Bleeding during procedure had lower curative rates compared to non-bleeding [OR: 2.13 (1.56, 2.93) P < 0.0001 I 2 = 0 %]. Concerning long-term cure, female gender [OR 1.62 (1.33, 1.97) P < 0.00001 I 2 = 0 %] and the mucosal over SM1 cancers were protective factors [OR: 0.08 (0.02, 0.39) P = 0.002 I 2 = 86 %]. Gastric atrophy [OR: 0.60 (0.45, 0.81) P = 0.0006 I 2 = 42 %] and the pepsinogen I/pepsinogen II ratio [OR 2.29 (1.47, 3.57) P = 0.0002 I 2 = 0 %] were risk factors to metachronous gastric neoplasm. Conclusions Ulcerated lesions, histology, bleeding and size > 20 mm are prognostic factors concerning curative resection. Regarding long-term cure, female gender and mucosal over SM1 cancer are predictive factors. Gastric atrophy and the pepsinogen ratio are risk factors for metachronous gastric neoplasm.

Gastric cancer is highly prevalent in Lynch syndrome patients with atrophic gastritis.

Although gastric cancer is one of the Lynch syndrome (LS)-related tumors, the clinicopathological features of gastric cancer in patients with LS remain uncertain. To investigate the incidence risk and clinicopathological features of gastric neoplasms in LS, we conducted a retrospective cohort study in Japanese LS patients. LS patients with pathogenic mismatch repair (MMR) gene variants were extracted from the LS registry of the National Cancer Center Hospital, Japan. Cumulative risks of gastric neoplasm, including dysplasia and cancer, were estimated using the Kaplan-Meier method. Gastric atrophy was evaluated endoscopically and/or histologically. Immunohistochemical staining for MMR proteins was performed for all available specimens. Of 118 eligible patients, 26 patients were diagnosed with 58 gastric neoplasms. The cumulative incidence of gastric neoplasm was 41.0% (95% confidence interval, 26.9-55.0) at the age of 70. Of these, 13 (50%) patients developed synchronous and/or metachronous multiple gastric neoplasms. Among the 49 gastric neoplasms available for detailed pathological evaluation, all were associated with intestinal metaplasia. Immunohistochemically, 42 (86%) were MMR-deficient. The individuals with gastric atrophy had a significantly higher risk of developing gastric neoplasms compared with those without gastric atrophy (26 cases/54 individuals vs. 0 cases/53 individuals) (P = 0.026). LS patients, particularly those with atrophic gastritis, are at high risk of gastric neoplasm and often develop multiple tumors. Endoscopic surveillance for gastric cancer is recommended for LS patients, especially those with atrophic gastritis.

Increased incidence of metachronous gastric neoplasm after endoscopic resection in patients with synchronous gastric neoplasm

BackgroundRecurrence risk is a major concern after endoscopic resection (ER) of gastric neoplasms. This study was to compare metachronous risk in patients with and without synchronous neoplasms after complete ER.MethodsAfter ER for gastric neoplasms, patients were divided into those with and without synchronous neoplasm. The metachronous risk of gastric neoplasms was compared between the two groups.ResultsAfter ER of 678 cancers and 891 adenomas, synchronous neoplasm was found in 11.8% of cancers and 11.4% of adenomas. In the multiple (n = 182) and the single group (n = 1387), metachronous neoplasms occurred in 18.1 and 8.6%, respectively (HR 2.40; 95% CI, 1.62–3.34). When the pathology of the recurred lesion was limited to cancer, metachronous risk was also significantly higher in the multiple than in the single group (HR, 2.2; 95% CI, 1.17–3.85). In the recurred pathology of the multiple group, cancer development was frequently observed in patients with cancer compared to those with only adenomas in the synchronous lesion (67.0% vs. 13.0%, respectively; P = 0.023).ConclusionsThis study demonstrated that metachronous risk was significantly higher in patients with synchronous gastric neoplasms after ER. Therefore, meticulous examination is important in patients with synchronous neoplasm.

Impact of the timing of Helicobacter pylori eradication on the risk of development of metachronous lesions after treatment of early gastric cancer: a population-based cohort study

Helicobacter pylori eradication can reduce the risk of metachronous lesions after the treatment of early gastric cancer. We aimed to analyze the impact of the timing of H pylori eradication on metachronous recurrence. Data of patients who underwent endoscopic resection or partial gastrectomy for early stage gastric cancer and received H pylori eradication therapy were obtained from the Korean National Health Insurance Service database. Patients were classified into 3 groups according to the timing of the prescription for H pylori eradication: preresection; within 1 year postresection; and >1 year postresection. Among 19,767 patients, 7452 and 12,315 underwent endoscopic resection and surgery, respectively. The 5-year cumulative incidence of metachronous lesions after endoscopic resection was 14.0% in the preresection group, 12.3% in the within 1 year postresection group, and 16.9% in the >1 year postresection group. Surgery was performed in 1.2% of the preresection group, 1.3% of the within 1 year postresection group, and 2.9% of the >1 year postresection group. The within 1 year postresection group had a lower risk of development of metachronous lesions than the >1 year postresection group (hazard ratio [95% confidence interval]: after endoscopic resection, 0.79 [0.65-0.95]; after surgery, 0.39 [0.28-0.53]). The risk of development of metachronous lesions did not differ between the preresection and within 1 year postresection groups. Prescription of H pylori eradication therapy within 1 year after gastric cancer treatment reduces therisk of development of metachronous gastric neoplasms compared with a late prescription of eradication therapy in patients undergoing endoscopic resection and those undergoing surgery.

Risk of metachronous gastric neoplasm occurrence during intermediate-term follow-up period after endoscopic submucosal dissection for gastric dysplasia

After endoscopic resection (ER) of gastric dysplasia, metachronous gastric neoplasm (MGN) appears to have an incidence rate similar to that detected after ER of early gastric cancer (EGC). We investigated whether the risk of MGN after ER for gastric dysplasia is different between patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Between March 2011 and December 2016, 198 patients with LGD (LGD group) and 46 patients with HGD (HGD group) who underwent ER were included in the study. During a median follow-up of 2.5 years, MGNs developed in 21 patients (10.6%) in the LGD group and in 6 patients (13.0%) in the HGD group. Hazard ratios (HRs) for MGNs (HR, 1.45; P = 0.425) and for metachronous HGD or gastric cancer (HR, 2.41; P = 0.214) in the HGD group were not different than those of the LGD group. However, considering patients without Helicobacter pylori infection, those in the HGD group had a significantly increased risk of metachronous HGD or gastric cancer compared to those in the LGD group (HR in HGD-group, 5.23; P = 0.044). These results indicate that meticulous surveillance endoscopy is needed to detect MGNs after ER of gastric dysplasia, especially in patients with HGD, including those without H. pylori infection.

Long‐term follow up of serum pepsinogens in patients with gastric cancer or dysplasia after Helicobacter pylori eradication

Few studies have evaluated the change in serum pepsinogen (sPG) levels after the eradication of Helicobacter pylori. The aim of this study was to evaluate the effect of H.pylori eradication on sPG levels in patients with gastric cancer/dysplasia in comparison to a control group. We prospectively enrolled 368 patients with gastric cancer/dysplasia and 610 control subjects. H.pylori status and sPG levels were measured before and after eradication. The follow-up time points were classified as <12, 12-23, 24-35, and ≥36months. In 179 H.pylori-eradicated patients with gastric cancer/dysplasia and 168 control group subjects, sPG I significantly decreased, and the sPG I/II ratio significantly increased after eradication compared to baseline, and this improvement in sPG values was maintained during all follow-up time points. Significant differences in sPG I and the sPG I/II ratio were observed between the gastric cancer/dysplasia group and the control group <24months after eradication. However, these differences in sPG values disappeared after ≥24months of follow up. Moreover, significant differences in the intestinal metaplasia grade were observed between these two groups before eradication until <24months after eradication. However, these differences in the intestinal metaplasia grade disappeared after ≥24months of follow up in the corpus. The sPG values and intestinal metaplasia grade (corpus) in the gastric cancer/dysplasia group became similar to those in the control group at long-term follow up after H.pylori eradication. It might be related with the reduction of metachronous gastric neoplasm.

Chemoprevention of gastric cancer by Helicobacter pylori eradication and its underlying mechanism.

The cascade of gastric cancer, a leading cause of cancer incidence and mortality, is multifactorial. Helicobacter pylori (HP) infection plays a major role in gastric cancer (GC), and there has been an accumulation of data regarding the chemopreventive effect of HP eradication. However, it remains unclear how HP infection causes GC and how HP eradication prevents GC. To clarify this issue, the following approaches were performed in this review article. First, how HP-induced atrophic gastritis (AG) and intestinal metaplasia (IM) provoke the development of GC is shown, followed by how long HP eradication takes to induce a reversible change in AG and IM. Second, epigenetic studies of PTPN6, MOS, DCC, CRK, and VAV1 were performed in noncancerous gastric specimens in terms of HP status. Among these genes, MOS was found to be a possible surrogate marker for GC development. HP eradication decreased aberrant DNA methylation in a gene-specific manner, and MOS played a role in metachronous gastric neoplasms. Third, transforming growth factor-β1 (TGF-β1) and TGF-β1-induced epithelial-mesenchymal transition (EMT) markers were investigated in gastric mucosa. HP infection triggered the TGF-β1-induced EMT pathway and caused the emergence of GC stem cells, such as CD44v8-10. When HP was eradicated, these two pathways were inhibited. Finally, a 2222 cohort study showed that HP eradication significantly decreased the risk of noncardiac GC. Taken together, HP eradication is effective as a primary GC prevention method, and its underlying mechanism includes reversibility of AG and IM, methylation, EMT, and stem cells.