Metachronous Gastric Cancer Research Articles

Use of Antibiotics and Probiotics Reduces the Risk of Metachronous Gastric Cancer after Endoscopic Resection.

Simple SummaryHelicobacter 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.

Effects of Helicobacter pylori eradication on gastric cancer incidence in the Japanese population: a systematic evidence review.

In Japan, there are ongoing efforts to shift the gastric cancer prevention and control policy priorities from barium-based screening to Helicobacter pylori (H. pylori)-oriented primary prevention. A comprehensive summary of the evidence regarding the effects of H. pylori eradication on the risk of gastric cancer could inform policy decisions. We conducted a systematic review and meta-analysis of published studies evaluating the effectiveness of H. pylori eradication for the prevention of gastric cancer in otherwise healthy individuals (primary prevention) and early gastric cancer patients (tertiary prevention). In total, 19 studies were included. Three moderate-quality observational cohort studies showed that H. pylori eradication may be associated with a decreased risk of gastric cancer in healthy asymptomatic Japanese people. There is moderate certainty regarding the effectiveness of H. pylori eradication in patients with gastrointestinal diseases, such as peptic ulcers. A meta-analysis of 10 observational studies with otherwise healthy individuals (mainly peptic ulcer patients) yielded an overall odds ratio of 0.34 (95% CI: 0.25-0.46). Regarding tertiary prevention, the overall odds ratio for developing metachronous gastric cancer was 0.42 (95% CI: 0.35-0.51) in the eradication group in a meta-analysis of nine studies involving early gastric cancer patients who underwent endoscopic resection. H. pylori eradication is effective in preventing gastric cancer in the Japanese population, regardless of symptoms. Well-designed, large cohort studies are warranted to determine the long-term efficacy and safety of H. pylori eradication in the context of reducing the gastric cancer burden through population-based screening and treatment.

Gastric Adenoma: A High Incidence Rate of Developing Carcinoma and Risk of Metachronous Gastric Cancer according to Long-Term Follow-Up

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.

Comparison of biannual and annual endoscopic gastric cancer surveillance after endoscopic resection.

Patients who received endoscopic resection (ER) for early gastric cancer (EGC) or high-grade dysplasia (HGD) are at high risk for the subsequent development of metachronous gastric cancer (MGC). This study aims to compare the detection rate and stage of MGC between biannual and annual endoscopic surveillance after ER of EGC or HGD. From September 2009 to August 2019, 859 patients who underwent ER for the treatment of EGC or HGD were analyzed, retrospectively. Patients received endoscopic surveillance twice a year (high-intensity group) or annually (low-intensity group) for 3years. A total of 521 patients were enrolled in this study (267 patients in the high-intensity group and 254 patients in the low-intensity group). During a mean follow-up of 5.3 ± 1.6years, MGCs were found in 27 patients (16.9%) in the high-intensity group and 18 patients (7.1%) in the low-intensity group (P = 0.219). In patients with moderate to severe atrophy (Kimura-Takemoto grade C3 ~ O3), detection rates of MGC during 3years from were 8.4% (16/191) and 2.2% (4/186), respectively (P = 0.007). Forty-four patients who received treatment for MGC, including endoscopic or surgical resection, were stage IA. Only one patient in the low-intensity group was diagnosed as stage IIIA advanced gastric cancer. There was no significant difference in the detection rate of MGC between biannual and annual endoscopic surveillance after ER of EGC or HGD. However, biannual surveillance showed a higher detection rate during the first 3years, especially for patients with moderate to severe gastric atrophy.

Incidence and treatment outcomes of metachronous gastric cancer occurring after curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer: Japan Clinical Oncology Group study-post hoc analysis of JCOG1009/1010.

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. 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 3years 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. A total of 198 patients were included in this study. During a median follow-up period of 5.8years, 4 patients (2%) developed MGC. Median time to MGC occurrence was 4.5years (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 1.0cm (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. MGC does not occur commonly after curative ESD of UD-EGC, and repeated ESD could contribute to stomach preservation.

Statin Use Decreases the Risk of Metachronous Gastric Cancer in Patients without Helicobacter pylori Infection.

Simple SummaryStatins have been shown to reduce the risk of gastric cancer (GC). Little is known about their effects on metachronous GC in H. pylori negative patients after endoscopic resection for early gastric cancer (EGC). In this cohort study among patients with EGC without H. pylori infection, we found that statins are associated with a decrease in the risk of recurrence of GC. There was a dose-response relationship between the use of statins and the risk of metachronous GC. This study provides evidence about the additional benefits of statins as chemopreventive agents against metachronous GC among patients who underwent endoscopic resection for EGC.Previous studies have shown that statins reduce the risk of gastric cancer; however, their role has not been adequately studied in patients without Helicobacter pylori infection. We aimed to investigate whether statins reduced the risk of metachronous gastric cancer (GC) in H. pylori-negative patients who underwent endoscopic resection for early gastric cancer (EGC). Retrospective data of 2153 patients recruited between January 2007 and December 2016, with no H. pylori infection at baseline, who underwent resection for EGC, were analyzed. Metachronous GC was defined as a newly developed GC at least 1 year after endoscopic resection. Patients who used statins for at least 28 days during the follow-up period were considered as statin users. During a median follow-up of 5 years (interquartile range, 3.5–6.2), metachronous GC developed in 165 (7.6%) patients. In the multivariate Cox regression analysis, statin use was an independent factor associated with GC recurrence (adjusted hazard ratio (HR), 0.46; 95% confidence interval (CI), 0.26–0.82). Moreover, the risk of GC reduced with increasing duration (<3 years: HR 0.40, 95% CI 0.14–1.13; ≥3 years: HR 0.21, 95% CI 0.05–0.90; p trend = 0.011) and the dose of statin (cumulative defined daily dose (cDDD) < 500: HR 0.45, 95% CI 0.16–1.28; cDDD ≥ 500: HR 0.19, 95% CI 0.04–0.80; p trend = 0.008) in the propensity score-matched cohort. Statin use was associated with a lower risk of GC recurrence in H. pylori-negative patients with resected EGC in a dose-response relationship.

Clinical features and risk factors of gastric cancer detected by esophagogastroduodenoscopy in esophageal cancer patients.

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. 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. 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. 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.

Helicobacter pylori eradication prevents secondary gastric cancer in patients with mild-to-moderate atrophic gastritis.

Whether Helicobacter pylori eradication prevents metachronous recurrence after endoscopic resection (ER) of early gastric cancer remains controversial. This multicenter retrospective study aimed to evaluate the long-term (>5years) effects of H.pylori eradication by stratifying patients' baseline degrees of atrophic gastritis. A total of 483 H.pylori-positive patients who had undergone ER for early gastric cancer were divided into two groups-(i) those having undergone successful H.pylori eradication within 1year after ER (eradicated group, n=294) and (ii) those with failed or not attempted H.pylori eradication (non-eradicated group, n=189). The cumulative incidences of metachronous gastric cancer between the two groups were compared for all patients, for patients with mild-to-moderate atrophic gastritis (n=182), and for patients with severe atrophic gastritis (n=301). During a median follow-up of 5.2years (range 1.1-14.8), metachronous cancer developed in 52 (17.7%) patients in the eradicated group and in 35 (18.5%) patients in the non-eradicated group (P=0.11, log-rank test). In patients with mild-to-moderate atrophic gastritis (111 and 71 in the eradicated and non-eradicated groups, respectively), the cumulative incidence of metachronous cancer was significantly lower in the eradicated group than that in the non-eradicated group (P=0.03, log-rank test). However, no significant intergroup difference was observed in patients with severe atrophic gastritis (P=0.69, log-rank test). Helicobacter pylori eradication had a preventive effect on the development of metachronous gastric cancer in patients with mild-to-moderate atrophic gastritis.

Predictive Significance of Promoter DNA Methylation of Cysteine Dioxygenase Type 1 (CDO1) in Metachronous Gastric Cancer.

PurposePromoter DNA methylation of various genes has been associated with metachronous gastric cancer (MGC). The cancer-specific methylation gene, cysteine dioxygenase type 1 (CDO1), has been implicated in the occurrence of residual gastric cancer. We evaluated whether DNA methylation of CDO1 could be a predictive biomarker of MGC using specimens of MGC developing on scars after endoscopic submucosal dissection (ESD).Materials and Methods CDO1 methylation values (TaqMeth values) were compared between 33 patients with early gastric cancer (EGC) with no confirmed metachronous lesions at >3 years after ESD (non-MGC: nMGC group) and 11 patients with MGC developing on scars after ESD (MGCSE groups: EGC at the first ESD [MGCSE-1 group], EGC at the second ESD for treating MGC developing on scars after ESD [MGCSE-2 group]). Each EGC specimen was measured at five locations (at tumor [T] and the 4-point tumor-adjacent noncancerous mucosa [TAM]).ResultsIn the nMGC group, the TaqMeth values for T were significantly higher than that for TAM (P=0.0006). In the MGCSE groups, TAM (MGCSE-1) exhibited significantly higher TaqMeth values than TAM (nMGC) (P<0.0001) and TAM (MGCSE-2) (P=0.0041), suggesting that TAM (MGCSE-1) exhibited CDO1 hypermethylation similar to T (P=0.3638). The area under the curve for discriminating the highest TaqMeth value of TAM (MGCSE-1) from that of TAM (nMGC) was 0.81, and using the cut-off value of 43.4, CDO1 hypermethylation effectively enriched the MGCSE groups (P<0.0001).ConclusionsCDO1 hypermethylation has been implicated in the occurrence of MGC, suggesting its potential as a promising MGC predictor.

The incidences of metachronous multiple gastric cancer after various types of gastrectomy：analysis of data from a nationwide Japanese survey1）.

The incidences of metachronous multiple gastric cancer after various types of gastrectomy：analysis of data from a nationwide Japanese survey^1）.

Somatic alterations and mutational burden are potential predictive factors for metachronous development of early gastric cancer

The risk of developing metachronous gastric cancer (MGC) following curative endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) remains even after eradicating Helicobacter pylori (HP) successfully. We screened initial EGC and adjacent non-cancerous mucosa ESD-resected specimens for somatic variants of 409 cancer-related genes, assessing their mutational burden (MB) to predict molecular markers for metachronous post-ESD development. We compared variants between ten patients diagnosed with MGC more than 3 years after ESD and ten age-matched patients who did not have MGC developments after successful HP eradication. We found no significant background differences between the two groups. In adjacent non-cancerous mucosa, the MB tended to be higher in the patients with metachronous developments than in the others. Somatic genomic alterations of RECQL4, JAK3, ARID1A, and MAGI1 genes were significantly associated with MGC development. The criteria including both the MB and their variants, which had potential significant values for predicting MGC. In conclusion, combined of assessing specific somatic variants and MB may be useful for predicting MGC development. This study included a limited number of subjects; however, our novel findings may encourage further exploration of the significance of the molecular features of EGC that predict MGC development, thereby promoting focused follow-up strategies and helping elucidate the mechanisms.

Long-term persistence of gastric dysbiosis after eradication of Helicobacter pylori in patients who underwent endoscopic submucosal dissection for early gastric cancer

BackgroundGastric microbiome, other than Helicobacter pylori, plays a role in the tumorigenesis of gastric cancer (GC). Patients who undergo endoscopic submucosal dissection for early GC have a high risk of developing metachronous GC even after successful eradication of H. pylori. Thus, we investigated the microbial profiles and associated changes in such patients after the eradication of H. pylori.MethodsA total of 19 H. pylori-infected patients with early GC who were or to be treated by endoscopic resection, with paired biopsy samples at pre- and post-eradication therapy, were retrospectively enrolled. Ten H. pylori-negative patients were enrolled as controls. Biopsy samples were analyzed using 16S rRNA sequencing.ResultsH. pylori-positive patients exhibited low richness and evenness of bacteria with the deletion of several genera, including Blautia, Ralstonia, Faecalibacterium, Methylobacterium, and Megamonas. H. pylori eradication partially restored microbial diversity, as assessed during a median follow-up at 13 months after eradication therapy. However, post-eradication patients had less diversity than that in the controls and possessed a lower abundance of the five genera mentioned above. The eradication of H. pylori also altered the bacterial composition, but not to the same extent as that in controls. The microbial communities could be clustered into three separate groups: H. pylori-negative, pre-eradication, and post-eradication.ConclusionChanges in dysbiosis may persist long after the eradication of H. pylori in patients with a history of GC. Dysbiosis may be involved in the development of both primary and metachronous GC after the eradication of H. pylori in such patients.

Helicobacter pylori Eradication in Patients Undergoing Gastrectomy: Diagnosis and Therapy

The role of &lt;i&gt;Helicobacter pylori&lt;/i&gt; (&lt;i&gt;H. pylori&lt;/i&gt;) eradication in patients undergoing gastrectomy for gastric cancer is unclear. Although European and Asian guidelines strongly recommend &lt;i&gt;H. pylori&lt;/i&gt; eradication in patients who undergo endoscopic resection for early gastric cancer, these guidelines do not specify the tests useful for diagnosing &lt;i&gt;H. pylori&lt;/i&gt; infection, the optimal timing and appropriate eradication regimens, and follow-up strategies in patients undergoing gastrectomy for gastric cancer. This review aims to update the guidelines for the diagnosis and management of &lt;i&gt;H. pylori&lt;/i&gt; infection in patients undergoing gastrectomy for gastric cancer. We have focused on the following issues: 1) diagnostic tests for &lt;i&gt;H. pylori&lt;/i&gt; infection in the remnant stomach, 2) optimal timing and regimen for &lt;i&gt;H. pylori&lt;/i&gt; eradication, and 3) role of &lt;i&gt;H. pylori&lt;/i&gt; eradication in reducing the risk of metachronous gastric cancer in the remnant stomach.

Gastric cancer following pancreaticoduodenectomy: Experience from a high-volume center and review of existing literature

BackgroundProlonged survival of patients after pancreaticoduodenectomy can be associated with late complications due to altered gastrointestinal anatomy. The incidence of gastric cancer is increasingly reported. We set out to examine our experience with gastric cancer as a late complication after pancreaticoduodenectomy with a focus on incidence, risk factors, and outcomes. MethodsWe queried our prospectively collected institutional database for patients that developed gastric cancer after pancreaticoduodenectomy and conducted a systematic review of the literature. ResultsOur database revealed 6 patients who developed gastric cancer following pancreaticoduodenectomy, presenting with a mean age of 62.2 years and an even sex distribution. All of those patients underwent pancreaticoduodenectomy for malignant indications with an average time to development of metachronous gastric cancer of 8.3 years. Four patients complained of gastrointestinal discomfort prior to diagnosis of secondary malignancy. All of these cancers were poorly differentiated and were discovered at an advanced T stage (≥3). Only half developed at the gastrointestinal anastomosis. Four underwent surgery with a curative intent, and 2 patients are currently alive (mean postgastrectomy survival = 25.5 months). In accordance with previous literature, biliopancreatic reflux from pancreaticoduodenectomy reconstruction, underlying genetic susceptibility, and adjuvant therapy may play a causative role in later development of gastric cancer. ConclusionLong-term survivors after pancreaticoduodenectomy who develop nonspecific gastrointestinal complaints should be evaluated carefully for complications including gastric malignancy. This may serve as an opportunity to intervene on tumors that typically present at an advanced stage and with aggressive histology.

Long-term outcomes after endoscopic submucosal dissection for differentiated-type early gastric cancer that fulfilled expanded indication criteria: A prospective cohort study.

Background and AimEndoscopic resection for early gastric cancer (EGC) is widely performed. However, there is still a paucity of strong evidence regarding long‐term outcomes after endoscopic submucosal dissection (ESD) for the expanded indication criteria of the Japanese guidelines (ver. 2010).MethodsEndoscopic submucosal dissection was performed in patients with EGC that met the expanded indication criteria: (i) cT1a, differentiated‐type EGC of 2 to 5 cm, ulcer negative or (ii) cT1a, differentiated‐type EGC of ≤3 cm, ulcer positive. Patients whose pathological examination fulfilled the curative resection criteria were then enrolled in this cohort study: negative vertical margin, negative lymphovascular invasion, and (i) pT1a, differentiated‐type, and ulcer negative; (ii) pT1a, differentiated‐type, ≤3 cm, and ulcer positive; or (iii) pT1b1 (<500‐μm submucosal invasion), differentiated‐type, and ≤3 cm. Patients with only a positive horizontal margin as a noncurative factor were included for follow‐up.ResultsFrom September 2003 to February 2012, a total of 356 patients underwent ESD, and 214 were enrolled in the survival analysis. One hundred twenty patients (56%) had >2 cm in diameter and ulcer‐negative lesions, and 94 (44%) had ≤3 cm and ulcer‐positive lesions. The vital status at 5 years after ESD was confirmed in all (100%) patients. No local or metastatic recurrence was detected; however, 26 metachronous gastric cancers developed, and 1 patient died of metachronous gastric cancer. The 5‐year disease‐specific and overall survival rates were 99.5% (95% confidence interval [CI], 97.2%–100%) and 93.9% (95% CI, 89.8%–96.4%), respectively.ConclusionESD for EGC that fulfills the expanded criteria is feasible and shows favorable long‐term outcomes.

Helicobacter pylori Eradication Induced Constant Decrease in Interleukin- 1B Expression over More Than 5 Years in Patients with Gastric Cancer and Dysplasia.

Background/AimsHelicobacter pylori (Hp) suppresses gastric acid secretion by repressing the expression of the H+, K+-adenosine triphosphatase (H+, K+-ATPase) and stimulating interleukin-1 (IL-1β; encoded by IL-1B). This study was aimed at evaluating the expression of the H+, K+-ATPase and IL-1β after Hp eradication.MethodsTwo hundred twenty-one subjects were categorized as Hp-negative (n=84) or Hp-positive (n=137) according to the results of Hp tests (histology, CLO test, culturing, and serology). The mRNA expression levels of IL-1B and ATP4A (the gene encoding the α-subunit of H+, K+-ATPase) were measured in biopsy specimens from the gastric corpus using real-time polymerase chain reaction.ResultsThe Hp-positive group had significantly higher IL-1B mRNA levels than the whole Hp-negative group and the intestinal metaplasia (IM)-negative subgroup. After Hp eradication, the difference between the Hp-negative and Hp-eradicated groups disappeared, including in the IM-negative subgroup. The IL-1B mRNA level did not significantly change from the baseline level. Within the gastric cancer (GC)/dysplasia subgroup, the IL-1B mRNA levels at 1, 2, 3–4, and ≥5 years after Hp eradication were significantly lower than the baseline level. The difference in ATP4A mRNA levels between the Hp-negative and Hp-positive groups was not significant at baseline, and the changes in the ATP4A mRNA levels after Hp eradication compared to the baseline levels in the whole group and subgroups stratified by the presence of IM and GC/dysplasia were not significant.ConclusionsInfection with Hp has an effect on the level of IL-1B mRNA in IM-negative subjects. The continuous reduction in the IL-1B mRNA level in patients with GC/dysplasia after Hp eradication contributes to the prevention of metachronous GC after Hp eradication.

The incidences of metachronous multiple gastric cancer after various types of gastrectomy: analysis of data from a nationwide Japanese survey

BackgroundThe 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.MethodsWe 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.ResultsThe 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).ConclusionsThe 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.

Efficacy of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasia in a Large Cohort in North America

Endoscopic submucosal dissection (ESD) is a widely accepted treatment option for superficial gastric neoplasia in Asia, but there are few data on outcomes of gastric ESD from North America. We aimed to evaluate the safety and efficacy of gastric ESD in North America. We analyzed data from 347 patients who underwent gastric ESD at 25 centers, from 2010 through 2019. We collected data on patient demographics, lesion characteristics, procedure details and related adverse events, treatment outcomes, local recurrence, and vital status at the last follow up. For the 277 patients with available follow-up data, the median interval between initial ESD and last clinical or endoscopic evaluation was 364 days. The primary endpoint was the rate of en bloc and R0 resection. Secondary outcomes included curative resection, rates of adverse events and recurrence, and gastric cancer-related death. Ninety patients (26%) had low-grade adenomas or dysplasia, 82 patients (24%) had high-grade dysplasia, 139 patients (40%) had early gastric cancer, and 36 patients (10%) had neuroendocrine tumors. Proportions of en bloc and R0 resection for all lesions were 92%/82%, for early gastric cancers were 94%/75%, for adenomas and low-grade dysplasia were 93%/ 92%, for high-grade dysplasia were 89%/ 87%, and for neuroendocrine tumors were 92%/75%. Intraprocedural perforation occurred in 6.6% of patients; 82% of these were treated successfully with endoscopic therapy. Delayed bleeding occurred in 2.6% of patients. No delayed perforation or procedure-related deaths were observed. There were local recurrences in 3.9% of cases; all occurred after non-curative ESD resection. Metachronous lesions were identified in 14 patients (6.9%). One of 277 patients with clinical follow up died of metachronous gastric cancer that occurred 2.5 years after the initial ESD. ESD is a highly effective treatment for superficial gastric neoplasia and should be considered as a viable option for patients in North America. The risk of local recurrence is low and occurs exclusively after non-curative resection. Careful endoscopic surveillance is necessary to identify and treat metachronous lesions.

Metachronous Gastric Cancer Occurring after Endoscopic Resection of Early Gastric Cancer

Endoscopic resection (ER) has been widely used as a curative treatment for early gastric cancers (EGCs). Especially endoscopic submucosal dissection has several merits such as high en bloc and curative resection rates for EGCs and preservation of the entire stomach. However, ER has the inevitable limitation that the possibility of newly developing gastric cancers in the preserved stomach is still present. Metachronous gastric cancer (MGC) is defined as a newly developed gastric cancer occurring at a previously uninvolved site ≥1 year after the index ER of EGCs. The incidence of MGC is 3.3~15.6% and increases over time after ER. Old age, male sex, current smoking, severe atrophy and intestinal metaplasia, persistent Helicobacter pylori (H. pylori) infection, differentiated-type histology, and multiple initial gastric cancers are risk factors of MGC. As H. pylori eradication could reduce the risk of MGC after ER of EGCs, H. pylori eradication is strongly recommended for the prevention of MGC after ER of EGCs. Most MGCs are found at an early stage on regular surveillance endoscopy after ER and successfully treated with ER, with excellent long-term outcomes.

The Role of Helicobacter pylori and Serum Pepsinogen Levels in Metachronous Gastric Cancer After Endoscopic Gastrectomy.

The current study aimed to explore the role of Helicobacter pylori (Hp) infection and serum pepsinogen (PG) levels in the occurrence of metachronous gastric cancer after endoscopic gastrectomy. Totally, 50 patients with metachronous gastric cancer, 50 patients with chronic atrophic gastritis and 50 healthy subjects were collected from October 2015 to October 2018. Patients in the gastric cancer group underwent endoscopic gastrectomy. Serum samples were collected for detection and correlation analysis of serum PG I, PG II, and Hp. In addition, the contents of serum PG and gastrin and postoperative adverse events were statistically analyzed. There was a statistically significant difference in serum PG I levels, positive Hp infection rate, the number of mast cells, plasma motilin levels and postoperative adverse events among the 3 groups (P<0.01). There was also a significant difference in PG II levels among the groups (P<0.05). On the basis of the results, the amount of inflammatory cells in the gastric cancer group was significantly higher than that in the gastritis group, and there was a remarkable difference in gastric cancer patients before and after operation. Through data analysis, it was found that the levels of PG I and II were the highest in the healthy control group and the lowest in the gastric cancer group, the number of mast cells was the largest in the gastric cancer group, and the level of motilin was the highest in the healthy control group. Hp infection and serum PG levels are associated with metachronous gastric cancer.