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297 Background: Helicobacter pylori is known as the main risk factor for gastric cancer. It is also well known that gastric atrophy which is the result of long-term H. pylori infection induces spontaneous regression of H. pylori infection and such atrophic status with negative H. pylori infection is related with high risk of gastric cancer, as in so called “ABC method”. However the implication of anti- H. pylori antibody titer is not well investigated. This study was designed to identify the risk for gastric cancer according to the combination of level of anti- H. pylori antibody titer and gastric atrophy. Methods: Those who had health checkups including upper endoscopy and serum anti- H. pylori antibody test between 2003 and 2018 were enrolled. Among them, those who had positive results for anti- H. pylori antibody were included in this study and those who had followed up for less than 1 year were excluded. Kimura-Takemoto classification C3 or more was defined as gastric atrophy. Individuals were classified into 4 groups: low B (low titer without atrophy), high B (high titer without atrophy), high C (high titer with atrophy), and low C (low titer with atrophy). Their risks for gastric cancer were compared under adjustment with other risk factors. Results: During median 5.7 years of follow-up, among 28,311 subjects, 231 developed new gastric cancer. Among them, 159 were intestinal type, 68 were diffuse type, and 4 were type-unknown. For intestinal type gastric cancer, high C group and low C group showed significantly high risk compared with low B group (high C: aHR 10.516; 95% CI, 6.485-17.054) (low C: aHR 11.191; 95% CI, 7.096-17.649). However, for diffuse type gastric cancer, high B group showed higher risk compared with low B group (aHR, 1.713; 95% CI, 1.021-2.875). When those two factors were taken separately, grade of atrophy was related with the risk for intestinal type gastric cancer (aHR, 2.047; 95% CI, 1.862-2.251), while the level of anti- H. pylori antibody titer was related with the risk for diffuse type gastric cancer (aHR, 1.158; 95% CI, 1.041-1.288). Conclusions: Among those with current H. pylori infection, high anti- H. pylori antibody titer is related with diffuse type gastric cancer. The risk was prominent especially among those without atrophy. Therefore, those with high level of anti- H. pylori antibody titer need to be considered as high risk group even without atrophy and should be considered as good candidates for H. pylori eradication and intensive screening.

314 Background: Although depression is associated with poor treatment outcomes and lower quality of life in cancer patients, little is known about whether lifestyle modifications could help prevent depression in these patients. This study aimed to identify the effect of lifestyle modifications such as smoking cessation, alcohol abstinence, and starting exercise on depression development in gastric cancer patients who underwent gastrectomy. Methods: Using the Korean National Health Insurance Service database, we identified gastric cancer patients who underwent gastrectomy between 2010 and 2017. Self-reported lifestyle behaviors within two years before and after gastrectomy were analyzed using health examination database. We classified the patients according to changes in lifestyle behaviors and compared their risk of developing depression. Results: Among 18,902 patients who underwent gastrectomy, 2,302 (12.19%) developed depression (26.00 per 1000 person-years). Smoking cessation (Hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.66-0.91) and alcohol abstinence (HR = 0.79, 95% CI: 0.69-0.90) were associated with reduced risk of depression development compared to persistent smoking and persistent drinking, respectively. Starting exercise was not associated with risk of depression. When lifestyle behaviors after gastrectomy were scored from 0 to 3 points (one point each for not smoking, not drinking, and being physically active), the risk of depression showed a decreasing tendency as lifestyle scores increased from 0 (reference) to 1 (HR = 0.69, 95% CI: 0.55-0.83), 2 (HR = 0.60, 95% CI: 0.50-0.76), and 3 (HR = 0.55, 95% CI: 0.45-0.68) points. Conclusions: Smoking cessation and alcohol abstinence can reduce the risk of depression in gastric cancer patients who undergo gastrectomy. [Table: see text]

Gastric papillary adenocarcinoma is considered a differentiated adenocarcinoma in the current endoscopic submucosal dissection indication guidelines. However, the safety of endoscopic submucosal dissection remains controversial. Currently, data regarding which papillary early gastric cancer should be considered for endoscopic submucosal dissection are unavailable. Thus, the aim of this study was to investigate lymph node metastasis and the safety of endoscopic submucosal dissection in patients with papillary early gastric cancer. This observational study recruited 4264 consecutive patients with early gastric cancer who underwent curative gastrectomy between October 2000 and December 2017 at the National Cancer Center, Korea. Of these, 45 had pathologically confirmed papillary early gastric cancer, 2106 had differentiated non-papillary early gastric cancer, and 2113 had undifferentiated early gastric cancer. Logistic regression analysis was performed to identify risk factors for lymph node metastasis. Mucosal tumors were less common in papillary early gastric cancer (37.9%) than in differentiated non-papillary early gastric cancer (48.8%) and undifferentiated early gastric cancer (60.4%) (both P .001). Lymph node metastasis was more common in papillary early gastric cancer (20.0%) than in differentiated non-papillary early gastric cancer (9.2%) and undifferentiated early gastric cancer (11.7%; both P .001). In multivariate analysis, non-mixed-type papillary early gastric cancer showed marginally increased odds of lymph node metastasis than differentiated early gastric cancer (odds ratio [OR]: 2.5, 95% confidence interval [CI]: 1.0-6.3). Rates of lymph node metastasis (1/10, 10%) and angiolymphatic invasion (2/10, 20%) for papillary early gastric cancer meeting expanded criteria were higher than those for other histology types meeting endoscopic submucosal dissection absolute or expanded criteria (P = .03 and P .001, respectively). Endoscopic submucosal dissection should be considered carefully for papillary early gastric cancer, especially if it meets expanded endoscopic submucosal dissection indications since it is associated with high rates of submucosal invasion and lymph node metastasis.

We evaluated the metabolic effects of gastrectomies and endoscopic submucosal dissections (ESDs) in early gastric cancer (EGC) patients with type 2 diabetes mellitus (T2DM). Forty-one EGC patients with T2DM undergoing gastrectomy or ESD were prospectively evaluated. Metabolic parameters in the patients who underwent gastrectomy with and without a duodenal bypass (groups 1 and 2, n = 24 and n = 5, respectively) were compared with those in patients who underwent ESD (control, n = 12). After 1 year, the proportions of improved/equivocal/worsened glycemic control were 62.5%/29.2%/8.3% in group 1, 40.0%/60.0%/0.0% in group 2, and 16.7%/50.0%/33.3% in the controls, respectively (p = 0.046). The multivariable ordered logistic regression analysis results showed that both groups had better 1-year glycemic control. Groups 1 and 2 showed a significant reduction in postprandial glucose (−97.9 and −67.8 mg/dL), body mass index (−2.1 and −2.3 kg/m2), and glycosylated hemoglobin (group 1 only, −0.5% point) (all p &lt, 0.05). Furthermore, improvements in group 1 were more prominent when preoperative leptin levels were high (p for interaction &lt, 0.05). Metabolic improvements in both groups were also observed for insulin resistance, leptin, plasminogen activator inhibitor-1, and resistin. Gastrectomy improved glycemic control and various metabolic parameters in EGC patients with T2DM. Patients with high leptin levels may experience greater metabolic benefits from gastrectomy with duodenal bypass.

Intestinal-type gastric cancer often results from Helicobacter pylori infection through intestinal metaplasia, a transdifferentiated premalignant phenotype. Because H. pylori virulence factor CagA has been associated with aberrant expression of the transcription factor CDX1, which regulates intestinal differentiation, we explored its relationship with H. pylori infection and function during gastric carcinogenesis in normal gastric epithelial cells and gastric cancer cell lines. Infection of HFE 145 cells with CagA+ H. pylori increased expression of CDX1, as well as the epithelial-to-mesenchymal transition (EMT) markers Snail and Slug, increased invasion and migration, but those effects were not found in HFE 145 cells infected with CagA-deficient H. pylori. CDX1 overexpression increased expression of the intestinal markers Villin, sucrose isomaltase (SI), and MUC2, induced spheroid formation, and enhanced expression of the stem cell markers CD44, SOX2, Oct4, and Nanog, while CDX1 knockdown inhibited proliferation and intestinal stemness. Treatment of CDX1-expressing cells with metformin, an antidiabetic drug known to decrease the risk of gastric cancer, decreased expression of EMT and stemness markers, and reduced spheroid formation. In a murine xenograft model, combining metformin or shCDX1 with cisplatin reduced tumor growth, increased caspase-3 cleavage, and reduced expression of CD44 and MMP-9 to a greater degree than cisplatin alone. Patients with more advanced intestinal metaplasia staging exhibited higher CDX1 expression than those with earlier intestinal metaplasia staging (P = 0.039), and those with H. pylori tended to have more CDX1 expression than noninfected patients (P = 0.061). Finally, human tissue samples with higher CDX1 levels showed prominent CD44/SOX2 expression. Our findings indicate CagA+ H. pylori–induced CDX1 expression may enhance gastric cancer tumorigenesis and progression, and support therapeutic targeting of CDX1 in gastric cancer. Implications: This study shows that CDX1 contributes to the tumorigenesis and progression of gastric cancer and suggests the potential of targeting CDX1 to treat this malignancy.

Our previous work showed that in a mouse model of gastric adenocarcinoma with loss of p53 and Cdh1 that adding oncogenic Kras (a.k.a. Tcon mice) accelerates tumorigenesis and metastasis. Here, we sought to examine KRAS activation in epithelial-to-mesenchymal transition (EMT) and generation of cancer stem–like cells (CSC). Transduction of nontransformed HFE-145 gastric epithelial cells with oncogenic KRASG12V significantly decreased expression of the epithelial marker E-cadherin, increased expression of the mesenchymal marker vimentin and the EMT transcription factor Slug, and increased migration and invasion by 15- to 17-fold. KRASG12V also increased expression of self-renewal proteins such as Sox2 and increased spheroid formation by 2.6-fold. In tumor-derived organoids from Tcon mice, Kras knockdown decreased spheroid formation, expression of EMT-related proteins, migration, and invasion; similar effects, as well as reversal of chemoresistance, were observed following KRAS knockdown or MEK inhibition in patient tumor-derived gastric adenocarcinoma cell lines (AGS and KATOIII). KRAS inhibition in gastric adenocarcinoma spheroid cells led to reduced AGS flank xenograft growth, loss of the infiltrative tumor border, fewer lung metastases, and increased survival. In a tissue microarray of human gastric adenocarcinomas from 115 patients, high tumor levels of CD44 (a marker of CSCs) and KRAS activation were independent predictors of worse overall survival. In conclusion, KRAS activation in gastric adenocarcinoma cells stimulates EMT and transition to CSCs, thus promoting metastasis. Implications: This study provides rationale for examining inhibitors of KRAS to block metastasis and reverse chemotherapy resistance in gastric adenocarcinoma patients.

Gastric cancer is one of the most common cancers worldwide. Gastric cancer is a multifactorial disease, and the incidence varies widely by geographic region, with half of new cases occurring in East Asia. Population-based nationwide screening for gastric cancer has been implemented in some Eastern Asian countries such as South Korea and Japan. In these countries, endoscopic screening decreased gastric cancer mortality. Endoscopic screening seems to be a cost-effective modality in countries with high incidence of gastric cancer. However, the usefulness of population-based screening has not yet been proved in countries with low incidence of gastric cancer.

Background and Aims Endoscopic differential diagnoses of gastric mucosal lesions (benign gastric ulcer, early gastric cancer [EGC], and advanced gastric cancer) remain challenging. We aimed to develop and validate convolutional neural network-based artificial intelligence (AI) models: lesion detection (AI-LD), differential diagnosis (AI-DDx), and invasion-depth (AI-ID, pT1a vs. pT1b among EGC) models. Methods This study included 1,366 consecutive patients with gastric mucosal lesions from 2 referral centers in Korea. One representative endoscopic image from each patient was used. Histological diagnoses were set as the criterion standard. The performances of the AI-DDx (training/internal/external validation set, n=1009/112/245) and AI-ID (training/internal/external validation set, n=620/68/155) were compared with visual diagnoses by independent endoscopists (stratified by novice [ 5 years of experience]) and endoscopic ultrasonography (EUS) results, respectively. Results The AI-DDx showed good diagnostic performance for both internal (area under of the receiver operating characteristic curve [AUROC]=0.86) and external validation (AUROC=0.86). The performance of the AI-DDx was better than that of the novice (AUROC=0.82, P=0.01) and intermediate endoscopists (AUROC=0.84, P=0.02), but was comparable to the experts (AUROC=0.89, P=0.12) in the external validation set. The AI-ID showed fair performances in both internal (AUROC=0.78) and external validation sets (AUROC=0.73), which were significantly better than EUS results performed by experts (internal validation: AUROC=0.62, external validation: AUROC=0.56; both P Conclusion The AI-DDx was comparable with experts and outperformed novice and intermediate endoscopists for the differential diagnosis of gastric mucosal lesion. The AI-ID performed better than EUS for the invasion-depth evaluation ( https://aiscopeseoul.com/ ).

The lesion detection rate of esophagogastroduodenoscopy (EGD) varies depending on the degree of experience of the endoscopist and anatomical blind spots. This study aimed to identify gaze patterns and blind spots by analyzing the endoscopist's gaze during real-time EGD.Five endoscopists were enrolled in this study. The endoscopist's eye gaze tracked by an eye tracker was selected from the esophagogastric junction to the second portion of the duodenum without the esophagus during insertion and withdrawal, and then matched with photos. Gaze patterns were visualized as a gaze plot, blind spot detection as a heatmap, observation time (OT), fixation duration (FD), and FD-to-OT ratio.The mean OT and FD were 11.10 ± 11.14 min and 8.37 ± 9.95 min, respectively, and the FD-to-OT ratio was 72.5%. A total of 34.3% of the time was spent observing the antrum. When observing the body of the stomach, it took longer to observe the high body in the retroflexion view and the low-to-mid body in the forward view.It is necessary to minimize gaze distraction and observe the posterior wall in the retroflexion view. Our results suggest that eye-tracking techniques may be useful for future endoscopic training and education.

Background: Endoscopic differential diagnoses of gastric mucosal lesions (benign gastric ulcer, early gastric cancer [EGC], and advanced gastric cancer) remain challenging. We aimed to develop and validate convolutional neural network-based artificial intelligence (AI) models: lesion detection (AI-LD), differential diagnosis (AI-DDx), and invasion-depth (AI-ID, pT1a vs. pT1b among EGC) models. Methods: This study included 1,366 consecutive patients with gastric mucosal lesions from two referral centers in Korea. One representative endoscopic image from each patient was used. Histological diagnoses were set as the gold standard. The performances of the AI-DDx (training/internal/external validation set, n=1009/112/245) and AI-ID (training/internal/external validation set, n=620/68/155) were compared with visual diagnoses by independent endoscopists (stratified by novice [ 5 years of experience]) in a prospective manner and by endoscopic ultrasonography (EUS), respectively. Findings: The AI-DDx showed good diagnostic performance for both internal (area under of the receiver operating characteristic curve [AUROC]=0.86) and external validation (AUROC=0.86). The performance of the AI-DDx was better than that of the novice (AUROC=0.82, P=0.01) and intermediate endoscopists (AUROC=0.84, P=0.02), but was comparable to the experts (AUROC=0.89, P=0.12) in the external validation set. The AI-ID showed fair performances in both internal (AUROC=0.78) and external validation sets (AUROC=0.73), which were significantly better than EUS results performed by experts (internal validation: AUROC=0.62, external validation: AUROC=0.56; both P

Chemoresistance is the major cause of gastric adenocarcinoma (GA) treatment failure. The mechanisms underlying chemoresistance remain incompletely understood. Here, we sought to identify genes differentially expressed between chemoresistant and chemosensitive GA and to validate the function of the top hit. High-throughput RNA sequencing was performed to detect chemoresistance-related genes. The function of the only gene overexpressed in both chemoresistant tumors and tumor tissue relative to normal gastric epithelia, forkhead box C1 (FOXC1), was examined in GA cells, mouse xenograft models, and patient-derived organoid (PDO) systems, focusing on cancer stem-like cell (CSC) phenotypes, metastasis, and chemoresistance. FOXC1 was expressed at significantly higher levels in GA patient tumors that were resistant to chemotherapy, and high FOXC1 tumor expression was significantly correlated with poor survival among patients undergoing resection (p = 0.011). FOXC1 activity was significantly higher in spheroid-forming or CD44+ GA CSCs than in unselected cells. Inhibition of FOXC1 decreased the expression of CD44 and Sox2, decreased spheroid size by 78%–82%, and decreased spheroid number (>100 μm) by 75%–86%. GA CSC chemotherapy resistance was reversed with FOXC1 inhibition in vitro and in vivo and in PDOs. Mechanistic studies indicated that FOXC1 acts via the hedgehog and epithelial-to-mesenchymal transition (EMT) pathways. Our results imply that FOXC1 mediates the CSC phenotypes, metastasis, and chemotherapy resistance of GA through hedgehog and EMT signaling. FOXC1 inhibitors may thus represent a novel strategy to overcome chemoresistance.

Introduction We investigated to compare the effect of empirical therapy vs clarithromycin resistance-guided tailored therapy (tailored therapy) for eradication of Helicobacter pylori. Methods In this prospective, single center, open-label randomized controlled trial, we enrolled 72 patients with H. pylori infection from January 2019 through June 2019 in Korea. The patients were randomly assigned to both groups received empirical (n = 36) or tailored therapy (n = 36). Empirical therapy was defined as triple therapy with esomeprazole, amoxicillin, and clarithromycin for 10 days irrespective of clarithromycin resistance. Tailored therapy was triple or quadruple therapy with esomeprazole, metronidazole, tetracycline, and bismuth for 10 days based on genotype markers of resistance determined by gastric biopsy. Resistance-associated mutations in 23S rRNA were confirmed by multiplex polymerase chain reaction. Eradication status was assessed by C-urea breath test, and the primary outcome was eradication rates. Results H. pylori was eradicated in 27 patients (75.0%), given empirical therapy and 32 patients (88.9%) treated with tailored therapy (P = 0.136) in intention-to-treat analysis. In per protocol analysis, the eradication rate was 97.0% and 81.8% in tailoredvs empirical groups (P = 0.046). Although clarithromycin-resistant H. pylori was eradicated in 3/9 (33.3%) with empirical therapy, it was treated in 11/12 (91.7%) with tailored therapy (P = 0.009). There was no difference in compliance between 2 groups. The rate of adverse events of the tailored group was higher than that of the empirical group (P = 0.036) because quadruple therapy had more side effects than those of triple therapy (P = 0.001). Discussion Tailored therapy based on polymerase chain reaction is a good alternative to increase eradication rates in a region of high prevalence of clarithromycin resistance (see Visual Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A342).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

INTRODUCTION: Endoscopic submucosal dissection (ESD) is a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). However, only few studies compared long-term survival outcomes of ESD with surgery. This study compared the overall survival (OS), recurrence-free survival, and complication rates of ESD with those of surgery. METHODS: We reviewed patients who underwent ESD (n = 70) or surgery (n = 114) for SESCC at Seoul National University Hospital from 2011 to 2017. A propensity score-matched analysis was used to reduce selection bias. To increase the precision of our results interpretation, subgroups were analyzed according to the depth of tumor invasion. RESULTS: In the matching study, the ESD group (n = 34) showed comparable survival outcomes with the surgery group (n = 34). The 5-year OS rates were 89.4% vs 87.8% for the ESD and the surgery groups, respectively; similarly, the 5-year recurrence-free survival rates were 90.9% and 91.6%, respectively. The ESD group showed a lower early major complication rate (2.9% [1 of 34] vs 23.5% [8 of 34], P < 0.001) and shorter hospital stay (median, 3.0 days vs 16.5 days, P < 0.001) than the surgery group. In the tumor in situ (Tis)-subgroup, ESD showed better OS than esophagectomy (P = 0.030). Between-group comparisons of survival outcomes in the T1a and T1b subgroups revealed no significant differences. DISCUSSION: Long-term outcomes of ESD are comparable with surgery for patients with SESCC. For early major complications and duration of hospital stay, ESD was associated with better outcomes than radical surgery. These results support ESD as the preferred treatment option for SESCC.

Natural history after endoscopic resection (ER) for gastric dysplasia is still unclear. The aim of this study was to evaluate the long-term clinical outcomes and risk factors after ER for gastric dysplasia between control and cases with synchronous or metachronous gastric neoplasm. A total of 1090 patients who had undergone ER for gastric dysplasia and been followed up for at least one year from December 2002 to December 2013 were finally analyzed. Risk factors affecting the development of synchronous or metachronous neoplasm (SMN) and long-term clinical outcomes after ER for gastric dysplasia were evaluated. Synchronous and metachronous neoplasms had developed in 126 (11.6%) and 133 patients (12.2%) during the mean follow-up duration of 63.6 months, respectively. Five-year and 10-year risk of metachronous neoplasm were 9.8% and 27.2%, respectively. Median duration to the development of metachronous neoplasm was 103.1 months. While age (P

Background Endoscopic submucosal dissection (ESD) is a curative treatment option for superficial esophageal cancer with a minimal risk for lymph node metastasis. Before ESD, accurate clinical staging is important to select the appropriate candidate. We aimed to estimate the practicality of endoscopic ultrasound (EUS) to select pTis and pT1a. Methods We included patients with squamous esophageal cancers who underwent surgical resection or ESD between 2005 and 2018. Pathologic reports were reviewed retrospectively, and pathologic T staging was compared with clinical stage evaluated by EUS. Results Among 532 patients, 321 had superficial esophageal cancer (pTis: 42; pT1a: 115; and pT1b: 164). Accuracy rates, sensitivity, specificity, positive predicted value, and negative predicted value for selecting cT1a by EUS were 82.3%, 60.5%, 91.5%, 74.8%, and 84.7%, respectively. The rate of overstaged pTis-T1a was 39.5%. Upon multivariable analysis, tumor size (>2 cm), poor differentiation, protruding gross type, and use of conventional EUS (versus miniprobe) were associated factors for overstaging of pTis-T1a. Conclusions The accuracy of prediction of EUS for selecting mucosal esophageal cancer that can be treated with ESD was favorable. Target lesions with a large size (>2 cm), poor differentiation, and protruding morphology were related to T overstaging; precaution should be taken when evaluating the clinical stage for cancers with those conditions. Furthermore, miniprobe EUS provides higher accuracy for squamous esophageal cancers confined to mucosa.

Purpose: Lauren diffuse-type gastric adenocarcinomas (DGAs) are generally genomically stable. We identified lysine (K)-specific methyltransferase 2C (KMT2C) as a frequently mutated gene and examined its role in DGA progression. Experimental Design: We performed whole exome sequencing on tumor samples of 27 patients with DGA who underwent gastrectomy. Lysine (K)-specific methyltransferase 2C (KMT2C) was analyzed in DGA cell lines and in patient tumors. Results: KMT2C was the most frequently mutated gene (11 of 27 tumors [41%]). KMT2C expression by immunohistochemistry in tumors from 135 patients with DGA undergoing gastrectomy inversely correlated with more advanced tumor stage (P = 0.023) and worse overall survival (P = 0.017). KMT2C shRNA knockdown in non-transformed HFE-145 gastric epithelial cells promoted epithelial-to-mesenchymal transition (EMT) as demonstrated by increased expression of EMT-related proteins N-cadherin and Slug. Migration and invasion in gastric epithelial cells following KMT2C knockdown increased by 47- to 88-fold. In the DGA cell lines MKN-45 and SNU-668, which have lost KMT2C expression, KMT2C re-expression decreased expression of EMT-related proteins, reduced cell migration by 52% to 60%, and reduced cell invasion by 50% to 74%. Flank xenografts derived from KMT2C-expressing DGA organoids, compared with wild-type organoids, grew more slowly and lost their infiltrative leading edge. EMT can lead to the acquisition of cancer stem cell (CSC) phenotypes. KMT2C re-expression in DGA cell lines reduced spheroid formation by 77% to 78% and reversed CSC resistance to chemotherapy via promotion of DNA damage and apoptosis. Conclusions: KMT2C is frequently mutated in certain populations with DGA. KMT2C loss in DGA promotes EMT and is associated with worse overall survival.

We investigated the effect of gastrectomy on blood pressure (BP) in early gastric cancer survivors with hypertension and whether well-controlled BP was due solely to surgery-induced weight loss. The study enrolled 66 early gastric cancer patients with hypertension, undergoing endoscopic submucosal dissection (ESD), or gastrectomy. Blood analyses, 24-h ambulatory BP monitoring, brachial ankle pulse wave velocity (baPWV), and echocardiography were measured prior to, 3 months after, and 1 year after ESD or gastrectomy. The primary endpoint was remission of hypertension at 1 year. The remission rate of hypertension was significantly higher in the gastrectomy group than in the ESD group (p = 0.006). Those with remission of hypertension had a significant weight loss (p

Endoscopic screening has been adopted in South Korea for the national screening of gastric cancer (GC). This study aimed to assess the effect on overall survival of GC patients and determine the optimal endoscopic screening interval. The baseline characteristics and overall survival of GC patients treated at the National Cancer Center, Korea, between 2010 and 2016 were compared between those without a history of endoscopic evaluation (group N) and those in whom the interval between the last endoscopic evaluations and diagnosis of GC was ≤ 1, 1–2, 2–3, 3–4, or > 4 years (groups 1–5, respectively). A total of 2362 patients met the criteria for the study (1060 in group N and 1302 in groups 1–5). More patients in groups 1–5 were diagnosed with stage I GC (83.7, 83.7, 71.8, 78.2, and 71.6%, respectively) than in group N (62.4%, P

Background/Aims: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. Methods: In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. Results: Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. Conclusions: Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall. (Gut Liver 2018;12:278-287)

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 modifie...

Background/Aims: Optimal culture conditions for Helicobacter pylori have not been established. We compared the effectiveness of four different agar-based media for the growth of H. pylori. Materials and Methods: G27, ATCC #43504 and 60190, and primary cultured strains were used. H. pylori strains were cultured for four days under four culture conditions: chocolate agar, Thayer-Martin (TM) agar containing vancomycin-colistin-nystatin inhibitor (VCNI), Brucella agar, and brain heart infusion (BHI) agar containing 5% horse blood and IsoVitaleX (BBL™ BD, USA). Culture of cells in each medium was repeated fourteen times. The growth of H. pylori was measured by using a spectrophotometer. Results: TM, Brucella, and BHI agars showed mean absorbance values of 0.099, 0.059, 1.410, and 0.913, respectively. These values were significantly different (P=0.030). After post-adjustment by Bonferroni correction, similar growth was noted for in chocolate, Brucella, and BHI agars; however, TM agar significantly suppressed H. pylori growth compared with Brucella agar (P=0.031). Conclusions: Chocolate, Brucella, and BHI agars provided effective culture conditions for the growth of H. pylori. TM agar containing VCNI suppressed the growth of H. pylori and other organisms.

Background/Aims The adoption of colonoscopy as a primary colorectal cancer (CRC) screening technique has been argued for in Korea, without evidence of patient preferences. This study aimed to investigate patients’ preferences for the primary CRC screening test for the National Cancer Screening Program (NCSP). Methods Between June and August 2016, 414 individuals aged ≥50 years who participated in the NCSP were prospectively invited to complete a questionnaire regarding their preferences for the primary CRC screening test and the reasons for their selection. Results Among the 396 respondents who completed the questionnaire, 124 individuals (31.3%) preferred the fecal immunochemical test (FIT), whereas 272 individuals (68.7%) preferred colonoscopy. Elderly participants preferred the FIT (p

Rac1, a Rho GTPase family member, is dysregulated in a variety of tumor types including gastric adenocarcinoma, but little is known about its role in cancer stem-like cells (CSCs). Therefore, Rac1 activity and inhibition were examined in gastric adenocarcinoma cells and mouse xenograft models for epithelial-to-mesenchymal transition (EMT) and CSC phenotypes. Rac1 activity was significantly higher in spheroid-forming or CD44+ gastric adenocarcinoma CSCs compared with unselected cells. Rac1 inhibition using Rac1 shRNA or a Rac1 inhibitor (NSC23766) decreased expression of the self-renewal transcription factor, Sox-2, decreased spheroid formation by 78%–81%, and prevented tumor initiation in immunodeficient mice. Gastric adenocarcinoma CSCs had increased expression of the EMT transcription factor Slug, 4.4- to 8.3-fold greater migration, and 4.2- to 12.6-fold greater invasion than unselected cells, and these increases could be blocked completely with Rac1 inhibition. Gastric adenocarcinoma spheroid cells were resistant to 5-fluorouracil and cisplatin chemotherapy, and this chemotherapy resistance could be reversed with Rac1 shRNA or NSC23766. The PI3K/Akt pathway may be upstream of Rac1, and JNK may be downstream of Rac1. In the MKN-45 xenograft model, cisplatin inhibited tumor growth by 50%, Rac1 inhibition by 35%, and the combination by 77%. Higher Rac1 activity, in clinical specimens from gastric adenocarcinoma patients who underwent potentially curative surgery, correlated with significantly worse survival (P = 0.017). In conclusion, Rac1 promotes the EMT program in gastric adenocarcinoma and the acquisition of a CSC state. Rac1 inhibition in gastric adenocarcinoma cells blocks EMT and CSC phenotypes, and thus may prevent metastasis and augment chemotherapy. Implications: In gastric adenocarcinoma, therapeutic targeting of the Rac1 pathway may prevent or reverse EMT and CSC phenotypes that drive tumor progression, metastasis, and chemotherapy resistance. Mol Cancer Res; 15(8); 1106–16. ©2017 AACR.

Background: This study was aimed at evaluating the food intake and nutritional status of patients who underwent gastrectomy for gastric cancer based on a large-scale gastric cancer cohort. Methods: An observational prospective cohort study for gastric cancer has been conducted since 2010. From the cohort data, we selected the data for patients who completed at least 2 days of 3-day diet diaries and who underwent subtotal gastrectomy (STG) or total gastrectomy (TG). As a control group, patients who underwent endoscopic submucosal dissection were also included. The collected diet data were converted to macro- and micronutrients using computerized software, and the nutrient intakes were compared. Results: Among 6,556 patients who participated in the cohort study from 2011 to 2016, 1,289 patients who completed at least 2 days of 3-day diet diaries were included in this study. During the postoperative 3-month period, body weight was significantly decreased in the and TG groups. However, there was no difference in nutrient intake among the 3 groups except vitamin D and calcium intake. Similar results were observed during the postoperative 12 months period. Conclusions: Postoperative body weight loss and anemia might originate from altered absorptive function and metabolic change after gastrectomy rather than decreased nutrient intake.

항산화, 항알러지, 항염증, 항암, 항고혈압, 항균 활성을 나타내는 폴리페놀 화합물은 고등식물에 의해 생산되는 2차 대사산물이다. 일반적으로 폴리페놀 화합물은 플라보노이드와 비 플라보노이드 화합물로 나뉘며 병원균에 대한 항균활성은 비 플라보노이드 화합물에 비해 플라보노이드 화합물이 우수하다. 항균활성을 나...

Purpose Endoscopic submucosal dissection (ESD) in early gastric cancer causes an artificial gastric ulcer and local inflammation that has a negative intraprocedural impact on additional laparoscopic gastrectomy in patients with noncurative ESD. In this study, we analyzed the effect of ESD on short-term surgical outcomes and evaluated the risk factors. Materials and methods From January 2003 to January 2013, 1,704 patients of the National Cancer Center underwent laparoscopic gastrectomy with lymph node dissection because of preoperative stage Ia or Ib gastric cancer. They were divided into 2 groups: (1) with preoperative ESD or (2) without preoperative ESD. Clinicopathologic factors and short-term surgical outcomes were retrospectively evaluated along with risk factors such as preoperative ESD. Results Several characteristics differed between patients who underwent ESD-surgery (n=199) or surgery alone (n=1,505). The mean interval from the ESD procedure to the operation was 43.03 days. Estimated blood loss, open conversion rate, mean operation time, and length of hospital stay were not different between the 2 groups. Postoperative complications occurred in 23 patients (11.56%) in the ESD-surgery group and in 189 patients (12.56%) in the surgery-only group, and 3 deaths occurred among patients with complications (1 patient [ESD-surgery group] vs. 2 patients [surgery-only group]; P=0.688). A history of ESD was not significantly associated with postoperative complications (P=0.688). Multivariate analysis showed that male sex (P=0.008) and laparoscopic total or proximal gastrectomy (P=0.000) were independently associated with postoperative complications. Conclusions ESD did not affect short-term surgical outcomes during and after an additional laparoscopic gastrectomy.

Summary of Problem Alaska Native (AN) people experience higher incidence of, and mortality from, gastric cancer compared to other U.S. populations1, 2. Compared to the general U.S. population, gastric cancer in AN people occurs at a younger age, is diagnosed at later stages, is more evenly distributed between the sexes, and is more frequently signet-ring or diffuse histology3. It is known that the prevalence of Helicobacter pylori (Hp) infection, a risk factor for gastric cancer, is high in AN people4; however, high antimicrobial resistance combined with high reinfection rates in Alaska make treatment at the population level complex5. In addition, health issues in AN people are uniquely challenging due to the extremely remote locations of many residents. A multiagency workgroup hosted a symposium in Anchorage that brought internationally-recognized experts and local leaders together to evaluate issues around gastric cancer in the AN population. The overall goal of this symposium was to identify the best strategies to combat gastric cancer in the AN population through prevention and early diagnosis.

Helicobacter pylori (H. pylori) infection is on the rise as a cause of immune thrombocytopenia (ITP). It has been suggested that platelet recovery can be achieved following successful microbial eradication, although, the exact pathophysiology has yet to be fully elucidated. This study evaluated the long-term effects of H. pylori eradication monotherapy on platelet count recovery in patients with ITP. H. pylori eradication was analysed in 61 ITP patients. Patients who maintained a complete response (CR) for more than six months were classified as sustained responders (SR). The prevalence of H. pylori infection was 54.3% (75/138), and the success rate of eradication with first-line therapy was 71.4% (35/49). Patients who had achieved a CR at 2 months maintained a higher platelet count thereafter. At 1 year following eradication, platelet counts had increased 2.78 times in the eradicated group, 1.36 times in the sustained infection group, and 1.33 times in the no infection group compared with the baseline (P = 0.016).

The eradication rates for Helicobacter pylori have decreased in Korea although the prevalence of this bacterium has also decreased. Antibiotic resistance is likely to be a crucial factor in H. pylori eradication success, and we therefore mapped these resistance patterns nationwide in Korea.Five hundred and ninety adult subjects were prospectively enrolled from 2017 to 2018 from 15 centers across six geographic areas of Korea. A total of 580 biopsy tissues had been sampled from these patients during an upper endoscopy and were frozen at -80°C and delivered to a central laboratory. The agar dilution method was used to determine the minimum inhibitory concentration of amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, and levofloxacin for each H. pylori isolate.The culture success rate was 60.2% (349/580). Resistance rates against clarithromycin, metronidazole, amoxicillin, tetracycline, levofloxacin, and ciprofloxacin were 17.8%, 29.5%, 9.5%, 0%, 37.0%, and 37.0%, respectively. The geographic distribution of metronidazole and quinolone resistance was highly variable. Some subjects had multiple H. pylori strains in the antrum and body of the stomach and showed a heterogeneous resistance profile between these anatomic areas. The H. pylori multidrug resistance (MDR) rate was 25.2% (88/349) among amoxicillin, clarithromycin, metronidazole, tetracycline, and quinolone and 11.2% (39/349) among four of these major antibiotics except for quinolone. The Seoul and Chungcheong areas showed a relatively lower MDR rate.The antibiotic resistance of H. pylori differs by drug and geographic area in Korea. Detailed nationwide antibiotic resistance mapping is needed to develop an effective H. pylori eradication strategy.

Purpose Negative Helicobacter pylori status has been identified as a poor prognostic factor for survival in gastric cancer (GC) patients who underwent surgery. The aim of this study was to examine the effect of H. pylori eradication on long-term outcomes after distal gastrectomy for GC. Materials and methods We analyzed the survival of 169 distal GC patients enrolled in a prospective randomized trial evaluating histologic changes of gastric mucosa after H. pylori eradication in the remnant stomach. The outcomes measured were overall survival (OS) and GC recurrence rates. Results The median follow-up duration was 9.4 years. In the modified intention-to-treat analysis including patients who underwent H. pylori treatment (n=87) or placebo (n=82), 5-year OS rates were 98.9% in the treatment group and 91.5% in the placebo group, and Kaplan-Meier analysis showed no significant difference in OS (p=0.957) between groups. In multivariate analysis, no difference in overall mortality was observed between groups (adjusted hazard ratio [aHR] for H. pylori treatment, 0.75; p=0.495) or H. pylori-eradicated status (aHR for positive H. pylori status, 1.16; p=0.715), while old age, male sex, and advanced stage ≥ IIIa were independent risk factors. Six patients in the treatment group (6.9%) and seven patients in the placebo group (8.5%) had GC recurrences, and GC recurrence rates were not different according to H. pylori treatment (5-year GC recurrence rates, 4.6% in the treatment group vs. 8.5% in the placebo group; p=0.652). Conclusion H. pylori eradication for GC patients who underwent distal gastrectomy did not compromise long-term survival after surgery.