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

BACKGROUND: 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. METHOD: 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. RESULTS: Over a median follow-up duration of 53.8 months, 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 ß-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]). CONCLUSIONS: Gastric cancer patients can be classified into two distinct gastrotype groups by their MAM profiles, which were associated with different risk of metachronous recurrence.

An artificial intelligence system for comprehensive pathologic outcome prediction in early gastric cancer through endoscopic image analysis (with video).

BACKGROUND: Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection. This study aimed to develop an artificial intelligence (AI) model to assess comprehensive pathologic characteristics of EGC using white-light endoscopic images and videos. METHODS: To train the model, we retrospectively collected 4,336 images and prospectively included 153 videos from patients with EGC who underwent endoscopic or surgical resection. The performance of the model was tested and compared to that of 16 endoscopists (nine experts and seven novices) using a mutually exclusive set of 260 images and 10 videos. Finally, we conducted external validation using 436 images and 89 videos from another institution. RESULTS: After training, the model achieved predictive accuracies of 89.7% for undifferentiated histology, 88.0% for submucosal invasion, 87.9% for lymphovascular invasion (LVI), and 92.7% for lymph node metastasis (LNM), using endoscopic videos. The area under the curve values of the model were 0.992 for undifferentiated histology, 0.902 for submucosal invasion, 0.706 for LVI, and 0.680 for LNM in the test. In addition, the model showed significantly higher accuracy than the experts in predicting undifferentiated histology (92.7% vs. 71.6%), submucosal invasion (87.3% vs. 72.6%), and LNM (87.7% vs. 72.3%). The external validation showed accuracies of 75.6% and 71.9% for undifferentiated histology and submucosal invasion, respectively. CONCLUSIONS: AI may assist endoscopists with high predictive performance for differentiation status and invasion depth of EGC. Further research is needed to improve the detection of LVI and LNM.

Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Comparison of anticholinergic burden with chronic polypharmacy on functional decline and mortality in Korean older people: a retrospective nationwide cohort study.

BACKGROUND: We aimed to evaluate the association of anticholinergic burden and chronic polypharmacy with the incidence of functional decline and all-cause mortality, and to determine the difference between anticholinergic burden and chronic polypharmacy among Korean older people. METHODS: This nationwide cohort study included 42,132 older people aged ≥ 65 years who underwent Korean National Health Insurance Service health examinations from 2007 to 2008. Odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal Timed Up and Go (TUG) test results were assessed using multivariate logistic regression analyses. Hazard ratios (HRs) and 95% CIs for all-cause mortality until the end of 2015 were estimated using multivariable Cox proportional hazards regression analysis. RESULTS: Of the participants, 37.19% had abnormal TUG test results, and 7.66% of those died during the 5.7-year mean follow-up. The abnormal TUG test results OR increased by 27% among individuals with Korean Anticholinergic Burden Scale (KABS) scores ≥ 3 (OR 1.27, 95% CI 1.02-1.58) compared to those with KABS scores of 0. The HRs for all-cause mortality increased for individuals with higher KABS scores (P for trend < 0.001) or chronic polypharmacy (P for trend < 0.001) compared to those for individuals without these conditions. The combination of a higher KABS or chronic polypharmacy and abnormal TUG test results increased the risk of all-cause mortality (All P for trend < 0.001). CONCLUSION: Anticholinergic drug burden shows a better association with functional decline than chronic polypharmacy, and the use of medications and functional decline may be important risk factors for all-cause mortality among older people.

Association Between Metabolic Syndrome and the Risk of Colorectal Cancer Diagnosed Before Age 50 Years According to Tumor Location.

BACKGROUND & AIMS: The increasing prevalence of obesity at younger ages is concurrent with an increased earlier-onset colorectal cancer (CRC) (before age 50 years) incidence, particularly left-sided colon cancer. We investigated whether obesity and metabolic syndrome (MetS) are associated with increased earlier-onset CRC risk according to tumor location. METHODS: Our nationwide population-based cohort study enrolled 9,774,081 individuals who underwent health checkups under the Korean National Health Insurance Service from 2009 to 2010, with follow-up until 2019. We collected data on age, sex, lifestyle factors, body mass index (BMI), waist circumference (WC), blood pressure, and laboratory findings. A multivariate Cox proportional hazards regression analysis was performed. RESULTS: A total of 8320 earlier-onset and 57,257 later-onset CRC cases developed during follow-up. MetS was associated with increased earlier-onset CRC (adjusted hazard ratio, 1.20; 95% CI, 1.14-1.27), similar to later-onset CRC (adjusted hazard ratio, 1.19; 95% CI, 1.17-1.21). The adjusted hazard ratios for earlier-onset CRC with 1, 2, 3, 4, and 5 MetS components were 1.07 (95% CI, 1.01-1.13), 1.13 (95% CI, 1.06-1.21), 1.25 (95% CI, 1.16-1.35), 1.27 (95% CI, 1.15-1.41), and 1.50 (95% CI, 1.26-1.79), respectively (P for trend < .0001). We found that higher body mass index and larger waist circumference were significantly associated with increased earlier-onset CRC (P for trend < .0001). These dose-response associations were significant in distal colon and rectal cancers, although not in proximal colon cancers. CONCLUSIONS: MetS and obesity are positively associated with CRC before age 50 years with a similar magnitude of association as people diagnosed after age 50 years. Thus, people younger than 50 years with MetS require effective preventive interventions to help reduce CRC risk.

A Randomized Controlled Trial of Fibrin Glue to Prevent Bleeding After Gastric Endoscopic Submucosal Dissection.

INTRODUCTION: This study evaluated the efficacy of fibrin glue for preventing postendoscopic submucosal dissection (ESD) bleeding in high-risk patients for bleeding (expected iatrogenic ulcer size ≥40 mm or receiving antithrombotic therapy). METHODS: A multicenter, open-label, randomized controlled trial was performed at 4 tertiary medical centers in South Korea between July 1, 2020, and June 22, 2022. Patients with gastric neoplasm and a high risk of post-ESD bleeding were enrolled and allocated at 1:1 to a control group (standard ESD) or a fibrin glue group (fibrin glue applied to iatrogenic ulcers after standard ESD). The primary outcome was overall bleeding events within 4 weeks. The secondary outcomes were acute bleeding (within 48 hours post-ESD) and delayed bleeding (48 hours to 4 weeks post-ESD). RESULTS: In total, 254 patients were randomized, and 247 patients were included in the modified intention-to-treat population (125 patients in the fibrin glue group and 122 patients in the control group). Overall bleeding events occurred in 12.0% (15/125) of the fibrin glue group and 13.1% (16/122) of the control group ( P = 0.791). Acute bleeding events were significantly less common in the fibrin glue group than in the control group (1/125 vs 7/122, P = 0.034). Delayed bleeding events occurred in 11.2% (14/125) in the fibrin glue group and 7.3% (9/122) in the control group ( P = 0.301). DISCUSSION: This trial failed to show a preventive effect of fibrin glue on overall post-ESD bleeding in high-risk patients. However, the secondary outcomes suggest a potential sealing effect of fibrin glue during the acute period.

Preventive effect of Helicobacter pylori eradication on the coronary heart diseases depending on age and sex with a median follow-up of 51 months.

BACKGROUND: The association between Helicobacter pylori (HP) infection and coronary heart disease (CHD) is controversial. This study aimed to investigate the effect of H. pylori eradication on CHD, especially in terms of age and sex. MATERIALS AND METHODS: From May 2003 to March 2022, 4765 subjects with H. pylori infection and without CHD (median follow-up: 51 months) were prospectively enrolled. The participants were categorized into two groups: H. pylori eradication and H. pylori non-eradication. After propensity-score matching (PSM), the effect of H. pylori eradication on CHD was analyzed using Cox proportional hazards. RESULTS: There were no significant differences in age, sex, alcohol consumption, smoking habits, history of diabetes, hypertension, and dyslipidemia, and aspirin intake between the eradication and non-eradication groups (3783 vs. 982) before and after PSM. Multivariate analysis after PSM showed that H. pylori eradication (HR: 0.489, CI: 0.314-0.761, p = .002), age (HR: 1.027, CI: 1.007-1.047, p = .007), hypertension (HR: 2.133, CI: 1.337-3.404, p = 001), dyslipidemia (HR: 1.758, CI: 1.086-2.848, p = .022), and aspirin intake (HR: 2.508, CI: 1.566-4.017, p < .001) were associated with CHD development. H. pylori eradication prevented CHD in males ≤65 years (HR: 0.133, CI: 0.039-0.455, p = .001), but not in those aged >65 years (p = .078) (p for interaction = .022). In contrast, females aged >65 years (HR: 0.260, CI: 0.110-0.615, p = .002) were protected by H. pylori eradication and not those ≤65 years (p = .485) (p for interaction = .003). This preventive effect increased more after PSM, particularly in males ≤65 years and females >65 years. CONCLUSIONS: H. pylori eradication prevented CHD and this effect was different depending on age and sex.

Risk of gastric cancer among long-term proton pump inhibitor users: a population-based cohort study.

PURPOSE: To elucidate whether long-term proton pump inhibitor (PPI) users have an increased gastric cancer (GC) risk. METHODS: We searched the 2009-2019 Korean National Health Insurance Services Database for patients aged > 40 years who claimed for Helicobacter pylori eradication (HPE) during 2009-2014. The GC incidence following a PPI exposure of > 180 cumulative defined daily dose (cDDD) and that following an exposure of < 180 cDDD were compared. The outcome was GC development at least 1 year following HPE. A propensity score (PS)-matched dataset was used for analysis within the same quartiles of the follow-up duration. Additionally, dose-response associations were assessed, and the mortality rates were compared between long-term PPI users and non-users. RESULTS: After PS matching, 144,091 pairs of PPI users and non-users were analyzed. During a median follow-up of 8.3 (interquartile range, 6.8-9.6) years, 1053 and 948 GC cases in PPI users and non-users, respectively, were identified, with the GC incidence (95% confidence interval (CI)) being 0.90 (0.85-0.96) and 0.81 (0.76-0.86) per 1000 person-years, respectively. The adjusted hazard ratio (aHR) for GC with PPI use was 1.15 (95% CI, 1.06-1.25). Among PPI users, patients in the highest tertile for annual PPI dose showed higher GC development than those in the lowest tertile (aHR (95% CI): 3.87 (3.25-4.60)). GC-related mortality did not differ significantly between PPI users and non-users. CONCLUSION: In this nationwide analysis in Korea, where the GC prevalence is high, long-term PPI use after HPE showed a significant increase in GC, with a positive dose-response relationship.

Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids.

BACKGROUND/AIMS: A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. METHODS: Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. RESULTS: HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. CONCLUSIONS: The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.

Sex differences in gastrointestinal dysfunction among patients with Parkinson's disease.

BACKGROUND AND OBJECTIVE: Sex differences in gastrointestinal dysfunction have not been systematically analyzed in patients with Parkinson's disease (PD). This study was aimed to investigate the sex differences in gastrointestinal dysfunctions among the patients with PD using a multicenter trial dataset. METHODS: We analyzed the baseline data of prospectively enrolled set of patients with gastrointestinal dysfunctions. Possible sex differences in gastrointestinal symptoms assessed on the Nepean Dyspepsia Index-Korean Version (NDI-K), gastrointestinal symptom diary, and Bristol stool scale were analyzed in association with clinical PD severity and antiparkinsonian drug dosages by multiple linear regression models. We also performed post hoc analysis of the dyspepsia symptom sub-items, adjusting for multiple comparisons. RESULTS: Sixty-six of the 144 participants were female (45.8%). There were no differences in age, PD duration, Hoehn and Yahr stage, and daily dopaminergic medication dosages between sexes. NDI-K symptom and dyspepsia scores were correlated with the activity of daily living in females but not in males. In the multiple regression analysis controlling for all possible variables, female patients were shown to have worse gastrointestinal symptoms than males. When we performed post hoc analysis of the dyspepsia symptoms, inability to finish a regular meal and nausea were significantly worse in female patients. Gastrointestinal symptom diary supported that female patients more frequently complained of early fullness and bloating in the upper abdomen after meals than males, and burning pain in upper abdomen was more severe in female patients. CONCLUSION: Gastrointestinal dysfunctions may differentially affect female and male PD patients.

Sample Collection Methods in Upper Gastrointestinal Research.

In recent years, significant translational research advances have been made in the upper gastrointestinal (GI) research field. Endoscopic evaluation is a reasonable option for acquiring upper GI tissue for research purposes because it has minimal risk and can be applied to unresectable gastric cancer. The optimal number of biopsy samples and sample storage is crucial and might influence results. Furthermore, the methods for sample acquisition can be applied differently according to the research purpose; however, there have been few reports on methods for sample collection from endoscopic biopsies. In this review, we suggested a protocol for collecting study samples for upper GI research, including microbiome, DNA, RNA, protein, single-cell RNA sequencing, and organoid culture, through a comprehensive literature review. For microbiome analysis, one or two pieces of biopsied material obtained using standard endoscopic forceps may be sufficient. Additionally, 5 mL of gastric fluid and 3-4 mL of saliva is recommended for microbiome analyses. At least one gastric biopsy tissue is necessary for most DNA or RNA analyses, while proteomics analysis may require at least 2-3 biopsy tissues. Single cell-RNA sequencing requires at least 3-5 tissues and additional 1-2 tissues, if possible. For successful organoid culture, multiple sampling is necessary to improve the quality of specimens.

Total polyp number may be more important than size and histology of polyps for prediction of metachronous high-risk colorectal neoplasms.

BACKGROUND: To evaluate whether the risk of metachronous high-risk colorectal neoplasm (HR-CRN) differs according to the indication for surveillance colonoscopy. METHODS: Patients who underwent polypectomy or endoscopic resection of colorectal neoplasms were enrolled and classified into three groups according to the indication for surveillance colonoscopy: advanced colorectal neoplasm (ACRN: adenoma ≥ 10 mm, adenoma with high-degree dysplasia and/or villous component), advanced serrated polyps (ASP: hyperplastic polyp or sessile serrated lesion ≥ 10 mm, traditional serrated polyp), and high-risk polyps (HRP: 3 or more adenomas or serrated polyps). The primary outcome was the development of metachronous HR-CRN, defined as ACRN, ASP, or HRP at the first follow-up colonoscopy. RESULTS: In total, 367 patients were enrolled (ACRN group: N = 264; ASP group: N = 33; HRP group: N = 70). Among the 160 patients who underwent follow-up colonoscopy, 28 (18%) had HR-CRN. In univariable analysis, indication for surveillance colonoscopy was not found to be associated with the development of metachronous HR-CRN. Instead, the total polyp number at index colonoscopy showed a positive association with the risk of metachronous HR-CRN in trend analysis (p = 0.001). In multivariable analysis, the presence of 5 or more polyps at index colonoscopy was found to be associated with the risk of metachronous HR-CRN (OR, 2.575, p = 0.049) after adjusting for risk factors, such as obesity, diabetes, and smoking. CONCLUSIONS: The risk of metachronous HR-CRN did not differ according to the main indications for surveillance colonoscopy. The presence of 5 or more polyps at index colonoscopy was the only risk factor for metachronous HR-CRN.

Nationwide cohort study: cholesterol level is inversely related with the risk of gastric cancer among postmenopausal women.

BACKGROUND: Recent studies showed inverse relationship between hypercholesterolemia and the risk of gastric cancer, especially among male. However evidence among female is inconsistent. We aimed to investigate the relationship between cholesterol level and the risk of gastric cancer among female according to menopausal status. METHODS: We analyzed the data from a population-based prospective cohort of female ≥ 30 years old who underwent cancer screening and general health screening provided by the Korean National Health Insurance Corporation in 2009. Under quartile stratification of the level of cholesterol components, we calculated the hazard ratio (HR) for gastric cancer incidence until 2018 for each level group according to the menopausal status at 2009. RESULTS: Among total 2,722,614 individuals, 17,649 gastric cancer cases developed after mean 8.26 years of follow-up (premenopausal 3746/1180666; postmenopausal 13,903/1541948). Total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) showed inverse relationship with the risk of gastric cancer among postmenopausal women (adjusted HR (95% confidence interval) for the highest quartile vs. lowest quartile and p-for-trend: 0.88 (0.84-0.92) and < 0.001 for total cholesterol; 0.89 (0.85-0.92) and < 0.001 for HDL-C; 0.92 (0.89-0.97) and 0.001 for LDL-C), whereas none showed statistically significant risk relationship among premenopausal women. Triglyceride was not independently related with gastric cancer risk among both pre- and postmenopausal women. CONCLUSIONS: Cholesterol levels, including total cholesterol, HDL-C, and LDL-C, are inversely related with the risk of gastric cancer among postmenopausal women, but not among premenopausal women.

rs2671655 single nucleotide polymorphism modulates the risk for gastric cancer in Helicobacter pylori-infected individuals: a genome-wide association study in the Korean population.

OBJECTIVE: To identify genetic variations which is associated with gastric cancer (GC) risk according to Helicobacter pylori infection. METHODS: This study incorporated 527 GC patients and 441 controls from a cohort at Seoul National University Bundang Hospital. The associations between GC risk and single nucleotide polymorphisms were calculated, stratified by H. pylori status, adjusting for age, sex, and smoking. mRNA expression from non-cancerous gastric mucosae was evaluated using reverse transcription quantitative polymerase chain reaction. RESULTS: In the entire cohort, genome-wide association study showed no significant variants reached the genome-wide significance level. In the H. pylori-positive group, rs2671655 (chr17:47,468,020;hg19, GH17J049387 enhancer region) was identified at a genome-wide significance level, which was more pronounced in diffuse type GC. There was no significant variant in the H. pylori-negative group, indicating the effect modification of rs2671655 by H. pylori. Among the target genes of GH17J049387 enhancer (PHB1, ZNF652 and SPOP), PHB1 mRNA was expressed more in cases than in controls, who were not affected by H. pylori. By contrast, an increase in ZNF652 and SPOP in GC was observed only in the H. pylori-negative group (P < 0.05). Mediation analysis showed that PHB1 (P = 0.0238) and SPOP (P = 0.0328) mediated the effect of rs2671655 on GC risk. The polygenic risk score was associated with the number of rs2671655 risk alleles only in the H. pylori-positive group (P = 0.0112). CONCLUSION: After H. pylori infection, rs2671655 may increase GC risk, especially in diffuse-type GC, by regulating the expression of several genes that consequently modify susceptibility to GC.

Comparison of endoscopic treatments for small gastric adenomas.

BACKGROUND: Gastric adenomas can be successfully treated with endoscopic resection, including endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The aim of this study was to evaluate and compare the efficacy of ESD and EMR with circumferential precutting (EMR-P) in the treatment of small gastric adenomas. METHODS: This study included 1014 gastric adenomas ≤ 15 mm in diameter treated with ESD or EMR-P from 2012 to 2019, retrospectively. Propensity score matching between the ESD and EMR-P groups (1:1 to 3:1) was performed according to age, sex, tumor size, tumor location (upper, middle, and lower thirds), morphology, and preprocedural histology. The procedure time and the rates of en bloc resection, complete resection, adverse events, and local recurrence were compared between the two groups. RESULTS: After propensity score matching, 478 lesions (ESD: 295, EMR-P: 183) were analyzed. The rates of en bloc resection (94.9% vs. 93.4%, p = 0.498), complete resection (93.6% vs. 90.2%, p = 0.177), bleeding (8.1% vs. 3.8%, p = 0.063), and local recurrence (0.0% vs. 1.4%, p = 0.185) did not significantly differ between the two groups. The procedure time was significantly longer for ESD than for EMR-P (p < 0.001). In the EMR-P group, the complete resection rate was significantly lower in the upper third than in the middle and lower thirds (p < 0.001). CONCLUSION: EMR-P is as effective as ESD for the treatment of small gastric adenomas. However, the efficacy of EMR-P is lower for gastric adenomas in the proximal stomach.

The Difference of Endoscopic and Histologic Improvements of Atrophic Gastritis and Intestinal Metaplasia After Helicobacter pylori Eradication.

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) is an important risk factor of atrophic gastritis (AG), intestinal metaplasia (IM), and gastric cancer (GC). However, no report to date has described the endoscopic improvement of AG and IM after H. pylori eradication. Thus, the aim of this study was to evaluate the improvement of AG and IM after H. pylori eradication using endoscopic and histologic analyses. METHODS: A total of 380 subjects were prospectively enrolled for up to 12 years and grouped by their H. pylori infection status: negative, non-eradicated, and eradicated. Endoscopic and histologic analyses of AG and IM were performed in the antrum and the corpus, by annual follow-up endoscopy. RESULTS: Endoscopic AG and IM in the antrum and corpus in the eradicated group improved compared to that in the non-eradicated group (AG, P = 0.002 and P = 0.005; IM, P = 0.038 and P = 0.048, respectively). Histologic AG and IM in the antrum and corpus in the eradicated group also improved compared to that in the non-eradicated group (all P < 0.001). Time taken to the endoscopic improvement of AG and IM after H. pylori eradication was significantly longer than time taken to the histologic improvement in the antrum and corpus (AG in antrum: 3.47 ± 2.60 vs. 2.34 ± 1.71 years, P = 0.004; AG in corpus: 3.19 ± 2.30 vs. 1.87 ± 1.48 years, P = 0.002; IM in antrum: 4.40 ± 2.38 vs. 3.62 ± 2.35 years, P = 0.043; and IM in corpus: 4.82 ± 1.08 vs. 3.61 ± 2.22 years, P = 0.007, respectively). CONCLUSIONS: Both endoscopic and histologic improvements of AG and IM were observed after H. pylori eradication, while endoscopic improvement took significantly longer time than histologic improvement.

Association Between ALDH2 Polymorphism and Gastric Cancer Risk in Terms of Alcohol Consumption: A Meta-Analysis.

BACKGROUND: Alcohol may increase gastric cancer risk. Alcohol can be more carcinogenic in persons who possess inactive ALDH2. The aim of this meta-analysis was to evaluate whether ALDH2 polymorphism can affect alcohol-induced gastric carcinogenesis. METHODS: We searched the PubMed, EMBASE, and Cochrane databases to identify relevant articles published between January 2000 and September 2019. Eligible articles were selected according to inclusion and exclusion criteria. The data were analyzed using Review Manager 5.3. RESULTS: A total of 7 case-control studies on ALDH2 rs671 polymorphism consisting of 3,251 gastric cancer cases and 4,943 controls were included in the analysis. Inactive ALDH2 genotypes (G/A or A/A) were associated with an increased risk of gastric cancer (odds ratio [OR] = 1.26, 95% confidence interval [CI]: 1.04 to 1.52, p = 0.02, I2  = 64%), compared with active ALDH2 (G/G genotype). Subgroup analysis by alcohol consumption showed that inactive ALDH2 increased risk for gastric cancer in moderate to heavy drinkers (OR = 1.85, 95% CI: 1.52 to 2.25, p < 0.01, I2 = 6%) more than in nondrinkers or mild drinkers (OR = 1.19; 95% CI: 1.05 to 1.36, p < 0.01, I2  = 6%). Moderate/heavy alcohol consumption increased gastric cancer risk in individuals with inactive ALDH2 (OR = 2.23, 95% CI: 1.63 to 3.05, p < 0.01, I2 = 30%) more than those with active ALDH2 (OR = 1.40, 95% CI: 0.98 to 2.01, p = 0.07, I2 = 85%). CONCLUSIONS: The ALDH2 polymorphism modifies the risk of gastric cancer. Moderate/heavy drinkers are more susceptible to gastric cancer than non-drinkers or light drinkers with inactive ALDH2.

Promising aberrant DNA methylation marker to predict gastric cancer development in individuals with family history and long-term effects of H. pylori eradication on DNA methylation.

OBJECTIVE: It remains unknown whether individuals with a family history (FH) of gastric cancer (GC) are associated with aberrant DNA methylation. The aim of this study was to investigate the association between aberrant DNA methylation and FH of GC. DESIGN: Using quantitative MethyLight assay, MOS, miR124a-3, NKX6-1, EMX1, CDH1, and TWIST1 methylation levels in the noncancerous gastric mucosa was compared between subjects with and without FH based on GC and Helicobacter pylori (Hp) infection. Changes in the methylation levels were evaluated over time after Hp eradication. RESULTS: In Hp-positive GC patients, MOS (P < 0.001), CDH1 (P < 0.001), and TWIST1 (P = 0.004) methylation were decreased in subjects with FH (n = 64) than in those without FH (n = 58). In Hp-positive controls, MOS methylation was lower in subjects with FH (n = 73) than in those without FH (n = 50) (P = 0.042), while miR124a-3 (P = 0.006), NKX6-1 (P < 0.001), and CDH1 (P < 0.001) methylation were higher in subjects with FH. CDH1 methylation constantly decreased from 2 years in GC patients and 3-4 years in controls after Hp eradication (all P < 0.001). A persistent decrease in methylation over time was not observed in other genes after eradication. CONCLUSION: The methylation of MOS and CDH1 provided an association between aberrant DNA methylation and gastric carcinogenesis in FH of GC, a useful marker for GC risk in individuals with FH. Furthermore, CDH1 methylation decreased after Hp eradication.

Different effects of p53 protein overexpression on the survival of gastric cancer patients according to Lauren histologic classification: a retrospective study.

BACKGROUND: Inactivation of TP53, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the correlation between the overexpression of p53 and survival in different Lauren-type GCs. METHODS: From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression. RESULTS: Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (P = 0.026) and Early gastric cancer (P = 0.044) in intestinal-type GC, and with advanced TNM stage (P < 0.001) and Advanced gastric cancer (P < 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio [aHR] = 1.423, P = 0.022; OS in diffuse-type: aHR = 1.401 P = 0.035; cancer recurrence in diffuse-type: aHR = 1.502, P = 0.039). CONCLUSION: p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.

Sleep disorders in patients with functional dyspepsia: A multicenter study from the Korean Society of Neurogastroenterology and Motility.

BACKGROUND AND AIM: The few studies concerning the association between sleep disorders and functional dyspepsia (FD) have yielded inconsistent results. We compared the prevalence of sleep disorders in patients with FD and healthy controls, and evaluated whether FD was independently associated with sleep disorders, and the risk factors for sleep disorders in patients with FD. METHODS: This prospective, multicenter, cross-sectional study was conducted from August 2014 to December 2017 at 12 hospitals in South Korea. The inclusion criterion was the presence of FD (for ≥18 years) according to the Rome III criteria. Healthy controls were recruited from among patients who visited the Health Examination Center for check-ups. RESULTS: In total, 526 subjects were prospectively enrolled in this study (201 with FD and 325 healthy controls). The prevalence of sleep disorders was significantly higher among the patients with FD than among the healthy controls (41.8% vs 18.8%, P = 0.000). In a multivariate analysis, FD (odds ratio [OR] = 1.851; 95% confidence interval [CI] 1.194-2.870; P = 0.006), female sex (OR = 1.672; 95% CI 1.063-2.628; P = 0.026), and anxiety (OR = 3.325; 95% CI 2.140-5.166; P = 0.000) were independent risk factors for sleep disorders in the overall cohorts. In patients with FD only, low body mass index, heartburn, and anxiety were independent risk factors for sleep disorders in a further multivariate analysis. CONCLUSION: Sleep disorders were common in patients with FD. FD was significantly associated with sleep disorders in our patient population, irrespective of the presence of heartburn or psychiatric disorders.