Metachronous Gastric Cancer In Patients Research Articles

Proton pump inhibitor use and the risk of metachronous gastric cancer after H. pylori eradication in patients who underwent endoscopic resection for gastric neoplasms: A population-based cohort study.

The association between proton pump inhibitors (PPI) use and gastric cancer remains controversial. To investigate the impact of long-term PPI use on metachronous gastric cancer after Helicobacter pylori eradication in high-risk patients who underwent endoscopic resection of gastric neoplasms. Using the Korean National Health Insurance Services database, we identified 1836 PPI users and 12,218 non-users among patients who received H. pylori eradication therapy after endoscopic resection for gastric neoplasms between 2009 and 2014. We then compared the incidence of metachronous gastric cancer between the PPI user and non-user groups. We conducted sensitivity analysis using various time lags and propensity score-matched analysis to ensure the robustness of the results. After a median follow-up of 7.3 years, the incidence of metachronous gastric cancer was significantly higher in the PPI user group than in the non-user group, with a crude hazard ratio of 6.20 (95% confidence interval, 5.78-6.65). After adjustment, PPI use was associated with the development of metachronous gastric cancer, with an adjusted hazard ratio of 5.51 (95% confidence interval, 5.12-5.92). The PPI user group was categorised into three subgroups according to the cumulative PPI dose; the increased risk of metachronous gastric cancer remained significant regardless of the PPI dose. Moreover, these results remained robust after applying various time lags and propensity score-matched analyses. Long-term PPI use is associated with an increased risk of metachronous gastric cancer in patients who undergo H. pylori eradication therapy after endoscopic resection of gastric neoplasms.

Effects of activation of an alcohol metabolic gene, cigarette smoking, and alcohol intake on the incidence of metachronous gastric cancer in patients who underwent endoscopic resection for gastric cancer: A multicenter retrospective pilot study.

Metachronous gastric cancer (GC) frequently occurs in patients who have undergone endoscopic resection (ER) for GC. We evaluated the risk for development of metachronous GC following ER for GC based on genetic polymorphisms for alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2), as well as alcohol consumption and smoking habits. We studied 77 patients who underwent ER for GC (median follow-up of 84 months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. Histories of alcohol consumption and smoking before and after ER and Helicobacter pylori eradication were documented. Multivariate analyses revealed that homozygous slow-metabolizing ADH1B (hazard ratio [HR] = 2.38, P < 0.13), heavy smoking (HR = 2.36, P < 0.09), and cigarette smoking after ER (HR = 2.47, P < 0.10) were not independently associated with the risk of secondary GC development. We analyzed the cessation status of the 38 patients who were classified as heavy smokers before ER based on their smoking habits after the ER and divided them into a cessation group (n = 27, non-smokers after ER) and a non-cessation group (n = 11). Cumulative incidence curves of secondary GC in the cessation and non-cessation groups revealed 5-year incidence rates of 19.0% and 45.0%, respectively (P = 0.02). Continued cigarette smoking, at a high level, may be an important risk factor for the development of metachronous GC. Advice for smoking cessation should be given.

Aspirin Use Is Not Associated with the Risk of Metachronous Gastric Cancer in Patients without Helicobacter pylori Infection.

Introduction: Helicobacter pylori (H. pylori) eradication can prevent metachronous gastric cancer (MGC) after the performance of an endoscopic resection for early gastric cancer (EGC). However, 50% of infections persist after eradication, and the identification of MGC protective factors is important. The anti-tumor activity of aspirin has been demonstrated, but its efficacy in preventing MGC remains controversial. We evaluated the effect of aspirin on metachronous recurrence in H. pylori-negative patients. Methods: A total of 4351 patients were evaluated between January 2007 and December 2016, and 2151 patients who met the inclusion criteria were analyzed. The primary outcome was the cumulative incidence of MGC after an endoscopic resection for EGC. Results: During a 5-year median follow-up (interquartile range, 3.5–6.2), MGC developed in 176 (7.7%) patients, with a cumulative incidence of 89.4% in aspirin users and 92.7% in non-users; this difference was not statistically significant (p = 0.64). The duration of aspirin uses and the occurrence of MGC in both groups were not significantly different. There was no significant difference between groups when the duration of aspirin use was categorized into ≤1 year (hazard ratio (HR), 0.64; 0.20–2.01, p = 0.45), 1–4 years (HR, 1.35; 0.66–2.76, p = 0.41), and >4 years (HR, 1.17; 0.67–2.03, p = 0.58). Conclusions: Aspirin use was not associated with a lower risk of MGC in H. pylori-negative patients. Further prospective studies are needed.

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.

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.

Incidence of metachronous gastric cancer in patients whose primary gastric neoplasms were discovered after Helicobacter pylori eradication

The incidence of metachronous gastric cancer (MGC) in patients whose primary gastric neoplasm is discovered after Helicobacter pylori eradication remains unclear. Here, we evaluated the long-term effect of previous H pylori eradication on development of MGC after endoscopic submucosal dissection (ESD). We analyzed prospectively collected data of consecutive patients with successful H pylori eradication more than 1 year before (eradicated group, 180 patients) or after (control group, 602 patients) initial curative ESD. These patients were also followed by endoscopy for over 2 years. Propensity score matching and inverse probability of treatment weighting (IPTW) were used to adjust for confounding variables during data analysis. The main outcome was the incidence of MGC after initial ESD. In a propensity-matched analysis of 174 pairs, the incidence of MGC was similar in the 2 cohorts (33.9 per 1000 person-years vs 40.8 per 1000 person-years in the control group, P= .454) at a median follow-up of 4.1 years (interquartile range, 3.0-5.6). Incidences were also similar in the 2 groups when data were analyzed using IPTW, even after exclusion of 123 patients with successful H pylori eradication<5 years before initial ESD. Multiple Cox regression analysis revealed age, differentiated-type histology, and initial multiplicity were predictors of MGC in patients after initial curative ESD. The frequency of follow-up surveillance after initial curative ESD should be kept constant, irrespective of whether H pylori eradication is performed before or after initial curative ESD.

Gastric cancer: epidemiology, prevention, and therapy.

Gastric cancer (GC) is still the third leading cause of cancer death in both sexes worldwide. Helicobacter pylori infection is the most important risk factor for GC and, in spite of the consistent trend of a decreasing incidence, in 2015 approximately 4.4billion individuals-more than half the world's population-were infected with H.pylori. The birth cohort pattern of decreased H.pylori infection reported in a systematic review contributes to explain the declining GC mortality in Japan. Current trends in estimated annual percentage change of GC incidence foreshadow expected reversals in both falling incidence and male predominance among US non-Hispanic whites. Combining serum pepsinogen 1 and H.pylori serology was shown to be useful for GC risk stratification in a Finnish population. Gastritis staging by operative link on gastritis assessment was confirmed to be reliable in predicting GC risk in a large prospective study. In a randomized trial from South Korea, H.pylori eradication therapy significantly reduced the rates of metachronous GC in patients who received curative endoscopic resection for early GC. A study based on a territory-wide health care database of the Hong Kong Hospital Authority showed that aspirin use is associated with a reduced GC risk. Another study based on the same database showed that proton pump inhibitors increase GC risk, but methodological biases have most likely acted as confounders. Confirmatory data on the role of endoscopic submucosal dissection in patients with early GC have been published. The phase III FLOT4 trial has shown that the FLOT triplet regimen (docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil) improves the outcome of patients with GC and locoregional disease as compared to the ECF triplet (epirubicin, cisplatin, and 5-fluorouracil). In the phase III ATTRACTION-2 trial, nivolumab was shown to be an effective treatment option with a relative safe profile for heavily pretreated patients with advanced GC.

Endoscopic features associated with development of metachronous gastric cancer in patients who underwent endoscopic resection followed by Helicobacter pylori eradication

The preventive effect of Helicobacter pylori (HP) eradication on metachronous gastric cancer development after endoscopic resection remains controversial. The aim of this study was to identify specific endoscopic features that correlated with the risk of metachronous gastric cancer development after endoscopic submucosal dissection (ESD) using both endoscopic findings before ESD and changes of findings after HP eradication. This retrospective study investigated 122 consecutive patients who underwent ESD for early gastric cancer and successful HP eradication after ESD. Endoscopic findings linked with HP before ESD and changes after HP eradication were evaluated according to the development of metachronous cancer. Most patients showed severe atrophy and intestinal metaplasia (IM) before ESD (97% and 83%, respectively). Improvement of spotty redness, improvement of diffuse redness, emergence of patchy redness, and emergence of map-like redness were frequent findings after HP eradication (52%, 50%, 54%, and 32%, respectively). Kaplan-Meier curves indicated that patients without IM before ESD never developed metachronous cancer, while patients with emergence of map-like redness after HP eradication were significantly more likely to develop metachronous cancer (log-rank test, p = 0.031 and p < 0.001, respectively). Multivariate analysis indicated that emergence of map-like redness after HP eradication was the only predictive factor for development of metachronous cancer (hazard ratio, 3.61; 95% confidence interval, 1.41-9.21; p = 0.007). Absence of IM before ESD and emergence of map-like redness after HP eradication were useful endoscopic findings in the negative and positive prediction of metachronous gastric cancer developing after ESD.

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan.

A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1year after successful H. pylori eradication. Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. Kaplan-Meier analysis showed the cumulative incidence of MGC 5years after successful H. pylori eradication was 15.0%; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5years after successful H. pylori eradication. Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.

Effect of Helicobacter pylori eradication on metachronous gastric cancer after endoscopic resection of gastric tumors: a meta-analysis.

Although endoscopic resection is widely accepted as the curative treatment modality for early gastric cancer, secondary metachronous cancer may subsequently develop in the residual gastric mucosa. The preventive effect of Helicobacter pylori eradication on the development of metachronous gastric cancer in such cases remains controversial. The aim of this study was to determine the effect of H. pylori eradication on the development of metachronous gastric cancer after endoscopic resection of gastric neoplasm by a meta-analysis of all relevant studies. We performed a systematic literature search of PubMed, EMBASE, Google Scholar, and the Cochrane Library without language restrictions through March 31, 2014. We included all relevant articles, including prospective, observational, and retrospective studies. Pooled estimates (odds ratios with 95% confidence intervals) were obtained using a random effects model. Thirteen studies were considered to be appropriate for this meta-analysis. Compared with the control group, the pooled odds ratio in the eradication group was 0.42 (95% confidence interval, 0.32-0.56), and there was no heterogeneity across the studies (p = .853, I(2) = 0%). Subgroup analysis of three prospective trials also showed a lower incidence of metachronous cancer in the eradication group (odds ratio, 0.39; 95% confidence interval, 0.20-0.75). There was no evidence of publication bias in this meta-analysis. Helicobacter pylori eradication reduces the occurrence of metachronous gastric cancer in patients who have undergone endoscopic resection.

Influence of endoscopic submucosal dissection on serum levels of pepsinogens in patients with early gastric cancer

The serum levels of pepsinogens (PG) have been considered to be a useful marker for assessing the risk of metachronous gastric cancer in patients who undergo endoscopic submucosal dissection. However, the influence of endoscopic submucosal dissection (ESD) on serum levels of PG has not yet been examined. The aim of this study was to examine whether the level of PG after ESD can be used to predict the risk of metachronous cancer. The study included of 100 consecutive patients who underwent ESD for gastric cancer at Hirosaki University Hospital from September 2009 to February 2011. Serum levels of PG I and II on the day before and after ESD were compared. Stool antigen test was also performed to examine the presence of Helicobacter pylori infection. The mean serum level of PG I before and after ESD was 34.3 ± 31.6 ng/mL and 70.5 ± 100.0 ng/mL (P < 0.001), respectively. PG I/II ratio before and after ESD was 2.40 ± 1.51 and 2.79 ± 1.70 (P < 0.001). The serum level of PG I and the PG I/II ratio were significantly changed after ESD, regardless of the use of proton pump inhibitor, Helicobacter pylori infection or the location of the tumor. ESD treatment modulates the serum level of PG I and significantly increases the PG I/II ratio. Serum levels of PG should be measured before the ESD procedure is performed to predict the risk of developing metachronous gastric cancer after ESD.

Clinicopathologic Characteristics of Colorectal Cancer Patients with Synchronous and Metachronous Gastric Cancer

We investigated the characteristics of synchronous and metachronous gastric cancer in patients with colorectal cancer. We reviewed 8,680 patients who underwent operations for primary sporadic colorectal cancer from 1989 to 2008. Synchronous gastric cancer was defined as gastric cancer diagnosed within 6 months of a colorectal cancer diagnosis. Gastric cancer diagnosed more than 6 months before or after colorectal cancer was defined as metachronous. The incidences of synchronous and metachronous gastric cancer were 0.93 and 1.4%, respectively (combined 2.4%). The standardized incidence ratio was 1.199 (95% confidence interval [CI] = 1.005-1.420) when the patients with premetachronous gastric cancer were excluded. Patients with synchronous and metachronous gastric cancer were 5 years older on average compared to the control population without gastric cancer. In addition, multivariate analysis revealed an odds ratio (OR) of 3.6 for being male, OR = 2 for positive family history of solid tumors, OR = 2.2 for colonic lesion, and OR = 4 for MSH2 expression loss compared to patients without gastric cancer. Patients with postmetachronous gastric cancer (when compared to synchronous and premetachronous gastric cancer), a preoperative CEA level of less than 6 ng/ml, and a relatively early stage of colorectal cancer had significantly higher overall (p = 0.016, 0.007, and 0.004, respectively) and disease-free survival rates (p = 0.046, 0.003, and 0.004, respectively), only on univariate analysis. Lymphovascular invasion of colorectal cancer and an advanced stage of gastric cancer were independent poor prognostic factors for both overall (p = 0.018) and disease-free survival (p = 0.028). Gastric cancer surveillance is recommended for patients with colorectal cancer, especially when the patient is old and male, has a positive family history of solid tumors, has a colonic lesion, or lacks MSH2 expression.

Risk of Metachronous Gastric Cancer in Patients with Gastric Cancers or Adenomas Those Were Treated Endoscopicallly

Background: It has been known that the risk of metachronous cancer is higher in patients who were treated for their early gastric cancer endoscopically than in naïve patients. Eradication of Helicobacter pylori reportedly reduced gastric cancer incidence after endoscopic resection of early gastric cancer. Gastric adenoma is known as a precancerous legion and can be resected endoscopically. However, little is known about the risk of metachronous gastric tumor after endoscopic treatment for gastric adenoma.