Family History of Gastric Cancer and Helicobacter pylori Treatment.

BACKGROUND: Helicobacter pylori infection and a family history of gastric cancer are the main risk factors for gastric cancer. Whether treatment to eradicate H. pylori can reduce the risk of gastric cancer in persons with a family history of gastric cancer in first-degree relatives is unknown. METHODS: In this single-center, double-blind, placebo-controlled trial, we screened 3100 first-degree relatives of patients with gastric cancer. We randomly assigned 1838 participants with H. pylori infection to receive either eradication therapy (lansoprazole [30 mg], amoxicillin [1000 mg], and clarithromycin [500 mg], each taken twice daily for 7 days) or placebo. The primary outcome was development of gastric cancer. A prespecified secondary outcome was development of gastric cancer according to H. pylori eradication status, assessed during the follow-up period. RESULTS: A total of 1676 participants were included in the modified intention-to-treat population for the analysis of the primary outcome (832 in the treatment group and 844 in the placebo group). During a median follow-up of 9.2 years, gastric cancer developed in 10 participants (1.2%) in the treatment group and in 23 (2.7%) in the placebo group (hazard ratio, 0.45; 95% confidence interval [CI], 0.21 to 0.94; P = 0.03 by log-rank test). Among the 10 participants in the treatment group in whom gastric cancer developed, 5 (50.0%) had persistent H. pylori infection. Gastric cancer developed in 0.8% of participants (5 of 608) in whom H. pylori infection was eradicated and in 2.9% of participants (28 of 979) who had persistent infection (hazard ratio, 0.27; 95% CI, 0.10 to 0.70). Adverse events were mild and were more common in the treatment group than in the placebo group (53.0% vs. 19.1%; P<0.001). CONCLUSIONS: Among persons with H. pylori infection who had a family history of gastric cancer in first-degree relatives, H. pylori eradication treatment reduced the risk of gastric cancer. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT01678027.).

Interaction between dietary potassium intake and TNF-α rs1800629 genetic polymorphism in gastric cancer risk: a case-control study conducted in Korea.

Mineral consumption has been suggested to have an impact on gastric cancer (GC) prevention. However, the protective effect of potassium against gastric carcinogenesis remains inconclusive. The causal link between inflammation and cancer is well established. Notably, potassium intake and potassium channels may play certain roles in regulating the production of TNF-α (TNF-α). We aimed to determine whether dietary potassium intake is related to the risk of GC. We further observed whether this association was modified by TNF-α rs1800629. We designed a case-control study comprising 377 GC cases and 756 controls. Information on dietary potassium intake was collected using a semiquantitative food frequency questionnaire. Genotyping was performed by the Affymetrix Axiom Exom 319 Array platform. Unconditional logistic regression models were used to assess associations. A significantly reduced GC risk was found for those who consumed higher dietary potassium levels (OR = 0·63, 95 % CI = 0·45, 0·89, P for trend = 0·009). In the dominant model, we observed a non-significant association between TNF-α rs1800629 and GC risk (OR = 1·01, 95 % CI = 0·68, 1·49). In females, those who were homozygous for the major allele (G) of rs1800629 with a higher intake of dietary potassium exhibited a decreased risk of GC (OR = 0·40, 95 % CI = 0·20, 0·78, P interaction = 0·041). This finding emphasises the beneficial effect of potassium intake on GC prevention. However, this association could be modified by TNF-α rs1800629 genotypes. A greater protective effect was exhibited for females with GG homozygotes and high potassium intake.

Risk of upper gastrointestinal cancer and death in persons with negative screening results: results from the National Cancer Screening Program in South Korea.

BACKGROUND: The Korea National Cancer Screening Program (KNCSP) offers upper endoscopy or upper gastrointestinal series (UGIS) biannually for people aged ≥ 40 years. This study aimed to assess the effect of negative screening results on the incidence of and mortality from upper gastrointestinal (GI) cancer. METHODS: A population-based retrospective cohort of 15,850,288 men and women was constructed using data from 3 national databases. The participants were followed until the end of 2017 for data on cancer incidence and in 2019 for data on the vital status. Cox proportional hazard model with time-varying exposure was used to assess the association. RESULTS: By the end of the follow-up period, 230,783 upper GI cancer cases and 99,348 upper GI cancer deaths were recorded. Negative gastric cancer screening was significantly associated with a lower risk of upper GI cancer in both UGIS (adjusted hazard ratio [aHR] = 0.81, 95% CI = 0.80-0.82) and upper endoscopy (aHR = 0.67, 95% CI = 0.67-0.68) groups. The HRs for upper GI mortality were 0.55 (95% CI = 0.54-0.56) and 0.21 (95% CI = 0.21-0.22) for the UGIS and upper endoscopy groups, respectively. The most significant reductions in the risk of upper GI cancer (UGIS: aHR = 0.76, 95% CI = 0.74-0.77; upper endoscopy: aHR = 0.60, 95% CI = 0.59-0.61) and death (UGIS: aHR = 0.54, 95% CI = 0.52-0.55; upper endoscopy: aHR = 0.19, 95% CI = 0.19-0.20) were observed among individual aged 60-69 years. CONCLUSION: Negative screening cases, especially in upper endoscopy of the KNCSP, were associated with an overall reduction in the risk of and mortality from upper GI cancer.

An Approach to the Primary and Secondary Prevention of Gastric Cancer in the United States.

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of mortality among certain racial, ethnic, and immigrant groups in the United States (US). The majority of GCs are diagnosed at advanced stages, and overall survival remains poor. There exist no structured national strategies for GC prevention in the US. METHODS: On March 5-6, 2020 a summit of researchers, policy makers, public funders, and advocacy leaders was convened at Stanford University to address this critical healthcare disparity. After this summit, a writing group was formed to critically evaluate the effectiveness, potential benefits, and potential harms of methods of primary and secondary prevention through structured literature review. This article represents a consensus statement prepared by the writing group. RESULTS: The burden of GC is highly inequitably distributed in the US and disproportionately falls on Asian, African American, Hispanic, and American Indian/Alaskan Native populations. In randomized controlled trials, strategies of Helicobacter pylori testing and treatment have been demonstrated to reduce GC-specific mortality. In well-conducted observational and ecologic studies, strategies of endoscopic screening have been associated with reduced GC-specific mortality. Notably however, all randomized controlled trial data (for primary prevention) and the majority of observational data (for secondary prevention) are derived from non-US sources. CONCLUSIONS: There exist substantial, high-quality data supporting GC prevention derived from international studies. There is an urgent need for cancer prevention trials focused on high-risk immigrant and minority populations in the US. The authors offer recommendations on how strategies of primary and secondary prevention can be applied to the heterogeneous US population.

Riboflavin intake, MTRR genetic polymorphism (rs1532268) and gastric cancer risk in a Korean population: a case-control study.

The vitamin B group, including riboflavin, plays paramount roles in one-carbon metabolism (OCM), and disorders related to this pathway have been linked to cancer development. The variants of genes encoding OCM enzymes and the insufficiency of B vitamins could contribute to carcinogenesis. Very few observational studies have revealed a relationship between riboflavin and gastric cancer (GC), especially under conditions of modified genetic factors. We carried out a study examining the association of riboflavin intake and its interaction with MTRR (rs1532268) genetic variants with GC risk among 756 controls and 377 cases. The OR and 95 % CI were evaluated using unconditional logistic regression models. We observed protective effects of riboflavin intake against GC, particularly in the female subgroup (OR = 0·52, 95 % CI 0·28, 0·97, Ptrend = 0·031). In the MTRR (rs1532268) genotypes analysis, the dominant model showed that the effects of riboflavin differed between the CC and CT + TT genotypes. Compared with CC carriers, low riboflavin intake in T+ carriers was significantly associated with a 93 % higher GC risk (OR = 1·93, 95 % CI 1·09, 3·42, Pinteraction = 0·037). In general, higher riboflavin intake might help reduce the risk of GC in both CC and TC + TT carriers, particularly the T+ carriers, with marginal significance (OR = 0·54, 95 % CI 0·28, 1·02, Pinteraction = 0·037). Our study indicates a protective effect of riboflavin intake against GC. Those who carry at least one minor allele and have low riboflavin intake could modify this association to increase GC risk in the Korean population.

Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for undifferentiated-type early gastric cancer meeting the expanded criteria: a systematic review and meta-analysis.

BACKGROUND: There have been concerns over the long-term outcomes of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (UD EGC). We aimed to compare the long-term outcomes of ESD and surgery for patients with UD EGC. METHODS: We searched PubMed, Embase, and Cochrane Library databases through March 2021 to identify studies that compared the long-term outcomes of ESD and surgery for UD EGC meeting expanded criteria for curative resection. The risk of bias was assessed with the Cochrane tool for non-randomized studies. The risk ratio (RR) was estimated using a fixed-effect model. RESULTS: Overall, 1863 patients from five retrospective cohort studies, including 908 patients with propensity score matching (PSM), were eligible for meta-analysis. ESD was associated with inferior overall survival (OS) compared to surgery in the overall cohort (RR 2.11; 95% CI 1.26-3.55) but not in the PSM cohort (RR 1.18; 95% CI 0.60-2.32). In the PSM cohort, ESD had a lower disease-free survival (DFS) (RR 2.49; 95% CI 1.42-4.35) and higher recurrence (RR 12.61; 95% CI 3.43-46.37), gastric recurrence (RR 11.25; 95% CI 3.06-41.40), and extragastric recurrence (RR 4.23; 95% CI 0.47-37.93). Recurrence outcomes were similar between the overall and PSM cohorts. Disease-specific survival was not significantly different between the two groups in both the overall and PSM cohorts. CONCLUSION: Although OS after curative ESD for UD EGC was not different from that after surgery in the PSM cohort, DFS and recurrence were inferior after ESD. Limitations included a lack of randomized trials. Further prospective studies comparing the long-term outcomes of ESD and surgery for UD EGC are needed (PROSPERO CRD 42021237097).

Efficacy of endoscopic management for anastomotic leakage after gastrectomy in patients with gastric cancer.

BACKGROUND: Anastomotic leakage (AL) after gastrectomy in gastric cancer patients is associated with high mortality rates. Various endoscopic procedures are available to manage this postoperative complication. The aim of study was to evaluate the outcome of two endoscopic modalities, clippings and stents, for the treatment of AL. PATIENTS AND METHODS: There were 4916 gastric cancer patients who underwent gastrectomy between December 2007 and January 2016 at the National Cancer Center, Korea. A total of 115 patients (2.3%) developed AL. Of these, 85 patients (1.7%) received endoscopic therapy for AL and were included in this retrospective study. The endpoints were the complete leakage closure rates and risk factors associated with failure of endoscopic therapy. RESULTS: Of the 85 patients, 62 received endoscopic clippings (with or without detachable snares), and 23 received a stent insertion. Overall, the complete leakage closure rate was 80%, and no significant difference was found between the clipping and stent groups (79.0% vs. 82.6%, respectively; P = 0.89). The complete leakage closure rate was significantly lower in the duodenal and jejunal stump sites (60%) than esophageal sites (86.1%) and gastric sites (94.1%; P = 0.026). The multivariate analysis showed that stump leakage sites (adjusted odds ratio [aOR], 4.51; P = 0.031) and the presence of intra-abdominal abscess (aOR, 4.92; P = -0.025) were associated with unsuccessful leakage closures. CONCLUSIONS: Endoscopic therapy using clippings or stents is an effective method for the postoperative management of AL in gastric cancer patients. This therapy can be considered a primary treatment option due to its demonstrated efficacy, safety, and minimally invasive nature.

Prediction model for curative endoscopic submucosal dissection of undifferentiated-type early gastric cancer.

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC. METHODS: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model. RESULTS: Endoscopic tumor size 1-2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54-3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81-28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03-2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1-2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673-0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748-0.803). CONCLUSIONS: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC.

Long-term outcomes of endoscopic resection followed by additional surgery after non-curative resection in undifferentiated-type early gastric cancer: a nationwide multi-center study.

BACKGROUND: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. METHODS: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. RESULTS: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44-8.88) and 0.46 (0.10-2.20), respectively. CONCLUSIONS: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC.

Helicobacter pylori Therapy for the Prevention of Metachronous Gastric Cancer.

BACKGROUND: Patients with early gastric cancers that are limited to gastric mucosa or submucosa usually have an advanced loss of mucosal glandular tissue (glandular atrophy) and are at high risk for subsequent (metachronous) development of new gastric cancer. The long-term effects of treatment to eradicate Helicobacter pylori on histologic improvement and the prevention of metachronous gastric cancer remain unclear. METHODS: In this prospective, double-blind, placebo-controlled, randomized trial, we assigned 470 patients who had undergone endoscopic resection of early gastric cancer or high-grade adenoma to receive either H. pylori eradication therapy with antibiotics or placebo. Two primary outcomes were the incidence of metachronous gastric cancer detected on endoscopy performed at the 1-year follow-up or later and improvement from baseline in the grade of glandular atrophy in the gastric corpus lesser curvature at the 3-year follow-up. RESULTS: A total of 396 patients were included in the modified intention-to-treat analysis population (194 in the treatment group and 202 in placebo group). During a median follow-up of 5.9 years, metachronous gastric cancer developed in 14 patients (7.2%) in the treatment group and in 27 patients (13.4%) in the placebo group (hazard ratio in the treatment group, 0.50; 95% confidence interval, 0.26 to 0.94; P=0.03). Among the 327 patients in the subgroup that underwent histologic analysis, improvement from baseline in the atrophy grade at the gastric corpus lesser curvature was observed in 48.4% of the patients in the treatment group and in 15.0% of those in the placebo group (P<0.001). There were no serious adverse events; mild adverse events were more common in the treatment group (42.0% vs. 10.2%, P<0.001). CONCLUSIONS: Patients with early gastric cancer who received H. pylori treatment had lower rates of metachronous gastric cancer and more improvement from baseline in the grade of gastric corpus atrophy than patients who received placebo. (Funded by the National Cancer Center, South Korea; ClinicalTrials.gov number, NCT02407119 .).

Association between bacteria other than Helicobacter pylori and the risk of gastric cancer.

BACKGROUND: The gastric microbiota, including Helicobacter pylori (HP), has a remarkable role in gastric cancer (GC) occurrence. Evidence for the role of non-HP bacteria in GC risk is limited. We aimed to observe the association between bacteria other than HP and risk of GC in a Korean population. METHODS: In this study, 268 GC cases and 288 healthy controls were included. Demographic data and total energy intake data were collected using a general questionnaire and a semiquantitative food frequency questionnaire, respectively. 16S rRNA gene sequencing was performed using DNA extracted from gastric biopsy samples. RESULTS: Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and non-HP Proteobacteria were the five main phyla in the gastric environment. The five phyla were negatively related to the relative abundance of Helicobacter species (all p < 0.001). The Shannon index, richness, and Pilou-evenness were negatively correlated with Helicobacter species (all p < 0.001), while the microbial dysbiosis index was positively correlated with Helicobacter species (p < 0.001). Participants with a higher relative abundance of Actinobacteria species showed a significantly increased risk of GC (OR: 3.16, 95% CI = 1.92-5.19, p-trend<0.001). The non-HP microbiota composition among the four groups (HP+cases, HP- cases, HP+controls, and HP- controls) was significantly different (ANOSIM R = 0.10, p = 0.001). CONCLUSION: Other than HP, several bacterial species might be associated with GC risk. HP status and GC status could determine the differences in microbial compositions. Further large prospective studies are warranted to confirm our findings.

Ten-day bismuth-containing quadruple therapy versus 7-day proton pump inhibitor-clarithromycin containing triple therapy as first-line empirical therapy for the Helicobacter pylori infection in Korea: a randomized open-label trial.

BACKGROUND: This randomized, open-label trial aimed to compare the efficacy of 10-day bismuth-containing quadruple therapy (BQT) with 7-day proton-pump inhibitor-clarithromycin containing standard triple therapy (STT) as an empirical first-line Helicobacter pylori therapy. METHODS: Participants with H. pylori infection were randomly assigned to either 10-day BQT (daily doses of bismuth 300 mg, four times; lansoprazole 30 mg, twice; metronidazole 500 mg, three times; and tetracycline 500 mg, four times) or 7-day STT (lansoprazole 30 mg; amoxicillin 1,000 mg; and clarithromycin 500 mg; each given twice daily). Participants who failed initial therapy were crossed over to the alternative treatment regimen. Primary outcome was the eradication rates of first-line treatment by intention-to-treat analysis. RESULTS: Study participants (n = 352) were randomized to receive either 10-day BQT (n = 175) or 7-day STT (n = 177). The BQT-group achieved a significantly higher eradication rate than the STT-group in the intention-to-treat analysis (74.3% vs 57.1%, respectively; P = 0.001), modified intention-to-analysis (87.2% [130/149] vs 68.7% [101/147], respectively; P < 0.001) and per-protocol analysis (92.9% [105/113] vs 70.1% [94/134], respectively; P < 0.001). Although there was no serious adverse event, the compliance was lower with BQT than STT as a higher proportion of participants in the BQT-group discontinued therapy because of adverse events than those in the STT-group (23.1% vs 9.1%, respectively; P = 0.001) CONCLUSIONS: Ten-day BQT had higher eradication rates compared to that of the 7-day STT as an empirical first-line treatment for H. pylori eradication in Korea. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02557932. Registered 23 September 2015, https://clinicaltrials.gov/ct2/show/NCT02557932?term=NCT02557932&draw=2&rank=1 .

Clinical outcomes of endoscopic resection for undifferentiated intramucosal early gastric cancer larger than 2 cm.

BACKGROUND: This study investigated the long-term clinical outcomes of endoscopic resection (ER) for undifferentiated-type (UD) early gastric cancer (EGC), with tumor size > 2 cm as the only non-curative factor. METHODS: From among 1123 patients who underwent ER for UD EGC at 18 tertiary hospitals in Korea between 2005 and 2014, we identified 216 patients with UD intramucosal EGC > 2 cm, which was completely resected, with negative resection margins, and absence of ulceration and lymphovascular invasion. The patients were divided into the additional surgery (n = 40) or observation (n = 176) groups, according to post-ER management and were followed up for a median duration of 59 months for recurrence and 90 months for overall survival. RESULTS: Lymph node (LN) or distant metastasis or cancer-related mortality was not observed in the surgery group. In the observation group, two (1.1%) patients developed LN or distant metastasis with a 5-year cumulative risk of 0.7%, and one (0.6%) patient died of gastric cancer. The 5- and 8-year overall survival rates were 94.1% and 89.9%, respectively, in the observation group and 100.0% and 95.2%, respectively, in the surgery group (log-rank P = 0.159). Cox regression analysis did not reveal an association between the observation group and increased mortality. CONCLUSION: The risk of LN or distant metastasis was not negligible, but as low as 1% for patients undergoing non-curative ER for UD EGC, with tumor size > 2 cm as the only non-curative factor. Close observation may be an alternative to surgery, especially for older patients or those with poor physical status.

Risk factors of lymph node metastasis after non-curative endoscopic resection of undifferentiated-type early gastric cancer.

BACKGROUND: This study aimed to investigate risk factors for lymph node (LN) or distant metastasis after non-curative endoscopic resection (ER) of undifferentiated-type early gastric cancer (EGC). METHODS: Of 1124 patients who underwent ER for undifferentiated-type gastric cancer at 18 tertiary hospitals across six geographic areas in Korea between 2005 and 2014, 634 with non-curative ER beyond the expanded criteria were retrospectively enrolled. According to the treatment after ER, patients were divided into additional surgery (n = 270) and follow-up (n = 364) groups. The median follow-up duration was 59 months for recurrence and 84 months for mortality. RESULTS: LN metastasis was found in 6.7% (18/270) of patients at surgery. Ulcer [odds ratio (OR) 3.83; 95% confidence interval (CI) 1.21-12.13; p = 0.022] and submucosal invasion (OR 10.35; 95% CI 1.35-79.48; p = 0.025) were independent risk factors. In the follow-up group, seven patients (1.9%) developed LN or distant recurrence. Ulcer [hazard ratio (HR) 7.60; 95% CI 1.39-35.74; p = 0.018], LVI (HR 6.80; 95% CI 1.07-42.99; p = 0.042), and positive vertical margin (HR 6.71; 95% CI 1.28-35.19; p = 0.024) were independent risk factors. In the overall cohort, LN metastasis rates were 9.6% in patients with two or more risk factors and 1.2% in those with no or one risk factor. CONCLUSIONS: LVI, ulcer, submucosal invasion, and positive vertical margin are independently associated with LN or distant metastasis after non-curative ER of undifferentiated-type EGC. Surgical resection is strongly recommended for patients with two or more risk factors.

Dietary patterns and gastric cancer risk in a Korean population: a case-control study.

PURPOSE: Dietary pattern analysis has been considered as an approach to capture the complex interactions of overall diet, which are often lost in studies of single dietary components (e.g., foods and nutrients). The aim of this study was to identify the major dietary patterns of Koreans via principal component analysis based on the food groups and to investigate the association between dietary patterns and gastric cancer (GC) risk. METHODS: In this study, participants were recruited from the National Cancer Center, Korea. Among them, 415 cases were diagnosed with early GC, and 830 controls were age- and sex-matched at a ratio of 1:2. To determine the subjects' dietary patterns, 34 predefined food groups based on the 106-item semiquantitative food frequency questionnaire (SQFFQ) were used. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated across the tertiles of dietary pattern scores using logistic regression models. RESULTS: The two dietary patterns derived in this study were named westernized and prudent. Those patterns explained 24.83% of the total variation in food intake. Higher scores on the prudent pattern was inversely associated with the risk of GC (OR [95% CI] for the highest vs. lowest tertiles: 0.58 [0.41-0.84], p for trend = 0.004). CONCLUSION: Our findings suggest that adherence to the prudent dietary pattern represented by high loadings of vegetables and fruits, was associated with lower GC risk. Further studies with a prospective design and larger sample sizes are necessary.

Establishing Machine Learning Models to Predict Curative Resection in Early Gastric Cancer with Undifferentiated Histology: Development and Usability Study.

BACKGROUND: Undifferentiated type of early gastric cancer (U-EGC) is included among the expanded indications of endoscopic submucosal dissection (ESD); however, the rate of curative resection remains unsatisfactory. Endoscopists predict the probability of curative resection by considering the size and shape of the lesion and whether ulcers are present or not. The location of the lesion, indicating the likely technical difficulty, is also considered. OBJECTIVE: The aim of this study was to establish machine learning (ML) models to better predict the possibility of curative resection in U-EGC prior to ESD. METHODS: A nationwide cohort of 2703 U-EGCs treated by ESD or surgery were adopted for the training and internal validation cohorts. Separately, an independent data set of the Korean ESD registry (n=275) and an Asan medical center data set (n=127) treated by ESD were chosen for external validation. Eighteen ML classifiers were selected to establish prediction models of curative resection with the following variables: age; sex; location, size, and shape of the lesion; and whether ulcers were present or not. RESULTS: Among the 18 models, the extreme gradient boosting classifier showed the best performance (internal validation accuracy 93.4%, 95% CI 90.4%-96.4%; precision 92.6%, 95% CI 89.5%-95.7%; recall 99.0%, 95% CI 97.8%-99.9%; and F1 score 95.7%, 95% CI 93.3%-98.1%). Attempts at external validation showed substantial accuracy (first external validation 81.5%, 95% CI 76.9%-86.1% and second external validation 89.8%, 95% CI 84.5%-95.1%). Lesion size was the most important feature in each explainable artificial intelligence analysis. CONCLUSIONS: We established an ML model capable of accurately predicting the curative resection of U-EGC before ESD by considering the morphological and ecological characteristics of the lesions.

Upregulation of LAMB1 via ERK/c-Jun Axis Promotes Gastric Cancer Growth and Motility.

Gastric cancer is the fifth most common cancer worldwide with a poor survival rate. Therefore, it is important to identify predictive and prognostic biomarkers of gastric cancer. Laminin subunit beta 1 (LAMB1) is involved in attachment, migration, and organization during development, and its elevated expression has been associated with several cancers. However, the role and mechanism of LAMB1 in gastric cancer remains unknown. Here, we determined that LAMB1 is upregulated in gastric cancer tissues and contributes to cell growth and motility. Using a public database, we showed that LAMB1 expression was significantly upregulated in gastric cancer compared to normal tissues. LAMB1 was also found to be associated with poor prognosis in patients with gastric cancer. Overexpression of LAMB1 elevated cell proliferation, invasion, and migration; however, knockdown of LAMB1 decreased these effects in gastric cancer cells. U0126, an extracellular signal-regulated kinase (ERK) inhibitor, regulated the expression of LAMB1 in gastric cancer cells. Additionally, we showed that c-Jun directly binds to the LAMB1 promoter as a transcription factor and regulates its gene expression via the ERK pathway in gastric cancer cells. Therefore, our study indicates that LAMB1 promotes cell growth and motility via the ERK/c-Jun axis and is a potential biomarker and therapeutic target of gastric cancer.

The Suggestion of Revised Criteria for Endoscopic Resection of Differentiated-Type Submucosal Gastric Cancer.

BACKGROUND: Early gastric cancer that meets the expanded criteria for endoscopic resection (ER) is expected to be associated with a negligible risk for lymph node metastasis (LNM); however, recent studies have reported LNM in submucosal gastric cancer patients who met the existing criteria. In this study, we develop the revised criteria for ER of submucosal gastric cancer with the aim of minimizing LNM. METHODS: We analyzed the clinicopathological data of 2461 patients diagnosed with differentiated, submucosal gastric cancer who underwent surgery at three tertiary hospitals between March 2001 and December 2012, and re-analyzed the pathological slides of all patients. The depth of submucosal invasion was measured histopathologically in two different ways (the classic and alternative methods) to obtain accurate data. RESULTS: Of the enrolled subjects, 306 (17.0%) had LNM. The width of submucosal invasion correlated well with the LNM. We defined the depth and width of submucosal infiltration associated with the lowest incidence of LNM. None of the 254 subjects developed LNM when the following criteria were met: tumor diameter ≤ 3 cm, submucosal invasion depth < 1000 µm (as measured using the alternative method), submucosal invasion width < 4 mm, no lymphovascular invasion, and no perineural invasion; however, LNM was observed in 2.7% of subjects (6/218) who met the existing criteria. CONCLUSIONS: We revised the criteria for ER by adopting the alternative method to measure the depth of submucosal invasion and adding the width of such invasion. Our criteria better predicted LNM than the current criteria used to select ER to treat submucosal gastric cancer.

Comparison of the performance of risk scoring systems for tumor bleeding in patients with inoperable gastric cancer.

BACKGROUND: The Glasgow - Blatchford bleeding score (GBS) and admission and full Rockall scores are widely used risk scoring systems to stratify risk and determine the need for intervention in patients with upper gastrointestinal bleeding. We evaluated the performance of these risk scoring systems in patients with gastric cancer and tumor bleeding. METHODS: This retrospective study included patients with inoperable gastric cancer who presented with tumor bleeding at the National Cancer Center, Korea, between 2001 and 2015. The GBS, and admission and full Rockall scores were calculated. Primary outcome was the performance of the risk scoring systems in predicting the need for urgent interventions (endoscopic therapy, transarterial embolization, and surgery). The risk factors associated with urgent intervention were analyzed. RESULTS: Of 357 patients with tumor bleeding, 118 (33.1 %; 116 endoscopic therapy, 2 trans-arterial embolization) required urgent intervention. The full Rockall score was better at predicting the need for urgent intervention (area under the receiver operating characteristic curve = 0.78; P < 0.001) than the GBS (0.56) and admission Rockall score (0.56). Hemostatic intervention was not performed in patients with a full Rockall score ≤ 6 (103 patients, 28.9 %). On multivariate analysis, endoscopic stigmata of recent hemorrhage of Forrest classes Ia - IIb were significant factors associated with urgent intervention. CONCLUSIONS: The full Rockall score was superior to the GBS and admission Rockall score in predicting the need for urgent intervention for tumor bleeding. Thus, endoscopic evaluation is required to determine the need for urgent intervention in patients with gastric cancer and tumor bleeding.

Online registry for nationwide database of Helicobacter pylori eradication in Korea: Correlation of antibiotic use density with eradication success.

BACKGROUND: The Helicobacter pylori eradication rate has decreased with increasing antibiotic resistance. We conducted a prospective, nationwide, multicenter registry study to monitor the real status of H. pylori eradication therapy and to investigate the association between eradication success and antibiotic use density in Korea. MATERIALS AND METHODS: We enrolled 9318 patients undergoing H. pylori eradication therapy from 37 hospitals through "on-line database registry" from October 2010 to July 2015. Demographic data, detection methods, treatment indications, regimens, durations, compliance, adverse events, and eradication results were collected. The use of all commercially available eradication antibiotics was analyzed through the Korean National Health Insurance data of the Health Insurance Review and Assessment Service. The defined daily dose of antibiotics was used to standardize drug use comparisons. RESULTS: Finally, 6738 patients were analyzed. The overall eradication rate of first-line therapy was 71.8%. The eradication success rates were 71.7%, 86.9%, and 74.0% for standard triple therapy for 7 days, quadruple therapy, and concomitant therapy, respectively. The eradication success rate in naive patients was higher than that in those who previously underwent H. pylori eradication. Eradication success was significantly associated with younger age, female sex, and high compliance. Regional differences in eradication rates were observed. The yearly use density of clarithromycin increased statistically in seven regions across the country from 2010 to 2015. The yearly use density of amoxicillin in the Gyeongsang and Chungcheong areas was significantly increased (P < .01), whereas that of other macrolides was significantly lower in the Gyeonggi area than in other areas (P = .01). The overall use of eradication antibiotics has increased while the eradication rate steadily decreased for 5 years. However, there was no significant correlation between antibiotic use density and eradication. CONCLUSION: There was no relationship between the eradication rate and antibiotic use density in Korea.