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Sequence alterations in microsatellites and an elevated mutational burden are observed in 20% of gastric cancers and associated with clinical response to anti–PD-1 antibodies. However, 50% of microsatellite instability–high (MSI-H) cancers are intrinsically resistant to PD-1 therapies. We conducted a phase II trial of pembrolizumab in patients with advanced MSI-H gastric cancer and included serial and multi-region tissue samples in addition to serial peripheral blood analyses. The number of whole-exome sequencing (WES)–derived nonsynonymous mutations correlated with antitumor activity and prolonged progression-free survival (PFS). Coupling WES to single-cell RNA sequencing, we identified dynamic tumor evolution with greater on-treatment collapse of mutational architecture in responders. Diverse T-cell receptor repertoire was associated with longer PFS to pembrolizumab. In addition, an increase in PD-1+ CD8+ T cells correlated with durable clinical benefit. Our findings highlight the genomic, immunologic, and clinical outcome heterogeneity within MSI-H gastric cancer and may inform development of strategies to enhance responsiveness. Significance: This study highlights response heterogeneity within MSI-H gastric cancer treated with pembrolizumab monotherapy and underscores the potential for extended baseline and early on-treatment biomarker analyses to identify responders. The observed markers of intrinsic resistance have implications for patient stratification to inform novel combinations among patients with intrinsically resistant features. See related commentary by Fontana and Smyth, p. 2126. This article is highlighted in the In This Issue feature, p. 2113

BACKGROUND AND AIM Endoscopic resection is highly effective treatment option for rectal neuroendocrine tumors (NETs) as they usually present as small localized tumors. However, there are no well-established surveillance strategies following endoscopic resection. We established our own protocol for the surveillance of rectal NETs after endoscopic resection since 2013. This study aimed to assess the outcome and to optimize the surveillance strategies after endoscopic resection. METHODS We retrospectively analyzed the data of patients with endoscopically treated rectal NETs between January 2013 and April 2018 at Samsung Medical Center. We analyzed 337 patients with a median follow-up duration of 35.0 months (min-max: 12.0-88.3). RESULTS A total of 329 (97.6%) patients had tumors ≤ 1 cm in size, and eight (2.4%) patients had tumors > 1 cm in diameter. Synchronous rectal NETs were diagnosed in nine (2.7%) patients. Thirteen (3.9%) patients were identified as having positive resection margins. Regardless of the salvage treatment, none of these patients developed recurrence. Metachronous rectal NETs were diagnosed in nine (2.7%) patients. Metachronous lesions were associated with the number of synchronous lesions at initial diagnosis (P

Background and aim Previous studies suggested an association between Helicobacter pylori infection and osteoporosis; however, large-scale longitudinal studies are lacking to elucidate this association. Methods A cohort study of 10 482 women without osteoporosis at baseline who participated in a repeated health-screening examination including an H. pylori-specific immunoglobulin G antibody test was conducted to evaluate the association between H. pylori and osteoporosis development. Osteoporosis was diagnosed using dual-energy X-ray absorptiometry. Results During the 77 515.3 person-years of follow-up, women with H. pylori infection had a higher rate of incident osteoporosis than those who were uninfected. In a multivariable model adjusted for age, body mass index (BMI), menopausal status, smoking status, regular exercise, comorbidities (including hypertension, diabetes mellitus, dyslipidemia, stroke, or ischemic heart disease), and concomitant medications, the hazard ratio (HR) for incident osteoporosis in women with H. pylori infection compared with that in women without infection was 1.23 (95% confidence interval [CI], 1.03-1.45). The association between H. pylori and osteopenia development was also evident. In the multivariable analysis, menopause (HR, 1.68; 95% CI, 1.31-2.16) and increasing age (HR, 1.07; 95% CI, 1.06-1.08) were identified as significant risk factors for osteoporosis, whereas higher BMI (HR, 0.84; 95% CI, 0.81-0.87) was a protective factor for the risk of osteoporosis. Conclusions In this cohort study, H. pylori infection was associated with an increased risk of osteoporosis, independent of risk factors and confounding factors.

BACKGROUND The association between NUDT15 polymorphisms and thiopurine-induced leucopenia is well known. AIM To investigate the association between NUDT15 polymorphisms and time-to-leucopenia in paediatric patients with inflammatory bowel disease (IBD) receiving azathioprine and to determine the relationship between NUDT15 polymorphisms and 6-thioguanine nucleotide (6-TGN) levels. METHODS This retrospective observational study included Korean paediatric patients with IBD who were treated with azathioprine and underwent NUDT15 and TPMT genotyping. Azathioprine doses were adjusted by regular thiopurine metabolite monitoring. Factors associated with time-to-leucopenia and the relationship between NUDT15 polymorphisms and 6-TGN levels were analysed. RESULTS Among the 167 patients included, leucopenia was observed in 16% (19/119), 44% (20/45) and 100% (3/3) of the NUDT15 normal, intermediate and poor metabolisers respectively (P

AIMS: This study explores the effects of various genetic polymorphisms in candidate genes on thiopurine metabolism and toxicity in adult patients with Crohn's disease in Korea. METHODS: A total of 131 adult patients with Crohn's disease receiving thiopurine treatment were included. The TPMT and NUDT15 genes and an additional 116 genetic polymorphisms (in 40 genes and 3 intergenic locations) were screened for genotyping. Among the polymorphisms screened, 91 genetic polymorphisms (in 34 genes and 3 intergenic locations) in addition to TPMT and NUDT15 genotypes were included for statistical analyses to investigate their effects on thiopurine metabolites and adverse outcomes (leukopenia, hepatotoxicity, gastrointestinal intolerance, skin rash and alopecia). RESULTS: The median duration of thiopurine treatment was 47.0 months (range 6.0–153.4 months). Patient sex, maintenance dose of thiopurine, and use of anti‐tumour necrosis factor agents were associated with thiopurine metabolite concentrations (P < .05). In the univariate analysis, the TPMT genotype was associated with 6‐thioguanine level (P < .05), although the significance of this did not remain in multivariate analysis. Genetic polymorphisms in the ATIC (rs3821353 and rs16853834), IMPDH2 (rs11706052) and ITPA (rs6139036) genes were associated with thiopurine metabolism (P < .05). Genetic polymorphisms in the ABCC5 (rs8180093) and NUDT15 genotypes were associated with leukopenia (P < .05). CONCLUSION: The results of this study may help clinicians to understand the effects of other various polymorphisms in addition to TPMT and NUDP15 in thiopurine metabolism for management of Crohn's disease patients.

Background/Aims: An association between obesity and erosive esophagitis has been reported, but the effects of sarcopenia and obesity on erosive esophagitis are unknown. This study examined the relationship between obesity, sarcopenia, sarcopenic obesity, and erosive esophagitis in a large population of asymptomatic men and women. Methods: This study analyzed 32,762 subjects who underwent a comprehensive health check-up, which included upper gastrointestinal endoscopy, from August 2006 to December 2011 by a cross-sectional study. Sarcopenia was defined as a decrease in the appendicular skeletal muscle mass (ASM)/body weight value of two SD or more below the normal means for a younger reference group. Results: The study was carried out on four groups according to obesity and sarcopenic status: normal, obesity, sarcopenic, and sarcopenic obese group. In a multivariable model, the risk of erosive esophagitis was higher in the obese (adjusted OR [aOR] 1.35, 95% CI 1.22-1.49), sarcopenic (aOR 2.12, 95% CI 1.40-3.19), and sarcopenic obese groups (aOR 1.54, 95% CI 1.27-1.87) than in the normal group. The risk of erosive esophagitis was higher in the sarcopenic and sarcopenic obese groups than the obese group; the ORs were 1.63 (95% CI 1.08-2.47) and 1.22 (95% CI 1.01-1.46), respectively. In dose-response analysis, increasing sarcopenia severity showed a positive and graded relationship with the overall, Los Angeles (LA)-B or higher grade, and LA-C erosive esophagitis. Conclusions: This study suggests that sarcopenia is strongly and progressively associated with erosive esophagitis.

Background An association between Helicobacter pylori infection and colorectal neoplasia has been reported in cross-sectional studies. Goals We examined the association between H. pylori infection and the development of advanced colorectal neoplasia (AN) in a screening cohort. Study We identified 3753 adults, who underwent screening and subsequent surveillance colonoscopies. The primary outcome was the development of metachronous AN, as confirmed by surveillance colonoscopy. H. pylori infection status was assessed by an H. pylori-specific immunoglobulin G antibody test. Sensitivity analysis was also performed by H. pylori infection status on the basis of histology. Results During a median follow-up of 41 months, the incidence of AN was 3.2% and 1.7% in participants with and without H. pylori infection, respectively. In multivariable analysis adjusted for age, body mass index, smoking status, alcohol intake, family history of colorectal cancer, and baseline adenoma characteristics, the hazard ratio [95% confidence interval (CI)] for metachronous AN was 1.74 (1.11-2.73) in participants with H. pylori seropositivity, compared with those without H. pylori seropositivity. The association was consistent with H. pylori infection status on the basis of histology (adjusted hazard ratio, 3.51; 95% CI, 1.64-7.51). In the subgroup analysis, the positive association was observed in both no-adenoma and adenoma removal subgroups. Conclusions In a cohort study, H. pylori infection was associated with an increased risk of AN development. This association was consistent in both the serological and histologic assessment of H. pylori infection. Prospective studies are necessary to determine whether H. pylori eradication can reduce the risk of colorectal neoplasia.

Postoperative gastrointestinal bleeding (PGIB) is a serious complication with expensive medical costs and a high mortality rate. This study aims to analyze the incidence of PGIB and its associated factors, including its relationship with postoperative analgesic use. Patients aged ≥20 years who received various kinds of surgery from 2013 to 2017 were included (n = 1,319,807). PGIB was defined by admission with ICD-10 codes of gastrointestinal bleeding plus transfusion within 2 months after surgery. A total of 3505 (0.27%) subjects had PGIB, and the incidence was much higher for those who underwent major gastrointestinal and major cardiovascular surgery (1.9% for both), followed by major head and neck (0.7%), major genitourinary (0.5%), and orthopedic surgery (0.45%). On multivariate analysis, older age, male sex, lower income, comorbidities, peptic ulcer disease, and congestive heart failure were associated with a higher risk of gastrointestinal bleeding. Among analgesics, steroid use was associated with increased postoperative bleeding risk (adjusted OR: 1.36, 95% CI: 1.25–1.48). Acetaminophen/nonsteroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors, anticonvulsants, antidepressants, and opioids were not associated with increased risk. PGIB is considerable for major surgeries, and its risk should be considered, especially for patients with older age and comorbidities and use of steroids.

Background: An association between Helicobacter pylori (H. pylori) infection and dementia was reported in previous studies; however, the evidence is inconsistent. Objective: In the present study, the association between H. pylori infection and brain cortical thickness as a biomarker of neurodegeneration was investigated. Methods: A cross-sectional study of 822 men who underwent a medical health check-up, including an esophagogastroduodenoscopy and 3.0 T magnetic resonance imaging, was performed. H. pylori infection status was assessed based on histology. Multiple linear regression analyses were conducted to evaluate the relationship between H. pylori infection and brain cortical thickness. Results: Men with H. pylori infection exhibited overall brain cortical thinning (p = 0.022), especially in the parietal (p = 0.008) and occipital lobes (p = 0.050) compared with non-infected men after adjusting for age, educational level, alcohol intake, smoking status, and intracranial volume. 3-dimentional topographical analysis showed that H. pylori infected men had cortical thinning in the bilateral lateral temporal, lateral frontal, and right occipital areas compared with non-infected men with the same adjustments (false discovery rate corrected, Q

This report describes the case of a 60-year-old man who developed acute parotitis with abscess formation. The causative agent of the parotid abscess was Candida glabrata, which is an unusual cause of salivary gland pathology because it typically inhabits the oral cavity as a commensal microo

Sessile serrated adenomas/polyps (SSA/Ps) are precancerous lesions that account for one-third of colorectal cancers. The endoscopic and pathologic differentiation between SSA/Ps without dysplasia (SSA/POs) and SSA/Ps with dysplasia or adenocarcinoma (SSA/PDAs) can be difficult. This study aimed to assess the clinical characteristics of SSA/PDs. This multicenter retrospective cohort study included 532 patients who underwent endoscopic resection and were pathologically diagnosed with SSA/POs and SSA/PDAs. Initially, medical, endoscopic, and histopathological records of patients who underwent endoscopic resection of SSA/POs and SSA/PDAs at eight university hospitals in Korea between January 2005 and December 2015 were reviewed. A total of 307 (57.7%) patients were detected in men and 319 (60.0%) were located in the proximal colon. Most SSA/Ps had a flat, slightly elevated, or sessile morphology. The most prevalent endoscopic findings of SSA/Ps were nodular surface (244, 45.9%), disrupted vascular pattern (232, 43.6%), altered fold contour (141, 26.5%), dome-shaped morphology (135, 25.4%), and pale color (115, 21.6%). SSA/POs were more commonly found in the proximal colon, compared to SSA/PDAs. SSA/PDAs displayed 0-Ip, Isp, IIb or IIa + IIc morphologies more frequently, while SSA/POs displayed 0-Is or IIa morphology more frequently. The frequency of a rim of debris/bubbles was significantly higher in SSA/POs, while nodular surface and disrupted vascular pattern were significantly higher in SSA/PDAs. In the univariate analysis of endoscopic features, SSA/PDAs were significantly associated with the distal colon location, 0-Isp and IIb morphologies, nodular surface, and disrupted vascular pattern. In the multivariate analysis, 0-IIb, nodular surface, and disrupted vascular pattern were significantly associated with SSA/PDAs. SSA/Ps with 0-IIb morphology, nodular surface and disrupted vascular pattern are associated with an increased risk of dysplasia or adenocarcinoma.

Background/aims The quality of bowel preparation is important for optimal colonoscopy. It is influenced by medical and personal factors. We aimed to evaluate the effect of bowel habit on the quality of bowel preparation and to identify predictors of inadequate bowel preparation among bowel habit factors. Methods From June 2017 to September 2017, 90 volunteers were enrolled in this study. Each participant answered a questionnaire consisting of multiple questions about personal bowel habits, including stool form, frequency of bowel movements per week, duration, and degree of straining for bowel movement. Then, all volunteers underwent colonoscopic exam. Eleven endoscopists performed colonoscopies and used the Boston Bowel Preparation Scale (BBPS) as the index for bowel preparation. Two expert endoscopists simultaneously reviewed all colonoscopic images to confirm the final BBPS. Univariate and multivariate logistic regression analyses were performed to verify the correlation between bowel preparation adequacy and bowel habit. Results : Among the 90 participants, 20 (22.2%) had inadequate bowel preparation (total BBPS ≤6 or any segmental BBPS ≤1). In univariate analysis, infrequent bowel movement (0-2/week) (odds ratio [OR], 12.60; 95% confidence interval [CI], 1.22 to 129, p=0.03) and moderate straining (more than 1/4 of defecations) (OR, 4.40; 95% CI, 1.44 to 13.39; p=0.01) were significantly associated with inadequate bowel preparation. However, only moderate straining was significantly associated with inadequate bowel preparation in multivariate analysis (OR, 3.99; 95% CI, 1.26 to 12.65; p=0.02). Conclusions Straining is a significant predictor for inadequate bowel preparation. For patients with straining during bowel movements, an intensified preparation regimen should be considered.

BACKGROUND AND AIM Little is known regarding the exact burden of inflammatory bowel disease (IBD) in Asian countries because previous epidemiologic studies were hospital based. We aimed to develop and validate an operational definition of IBD cases from health insurance claims data and to examine the epidemiological features of IBD in Korea. METHODS We analyzed stratified sample data from the Korean Health Insurance Review and Assessment (2010-2016) database using 12 different definitions and applied the best definition to the entire (2007-2016) dataset. RESULTS The definition that combined the International Classification of Disease 10th revision code with IBD-specific medications had the best performance characteristics among the 12 tested definitions. During the 8-year study period, IBD prevalence increased from 25 345 in 2009 to 47 444 in 2016. Over that period, the prevalence of Crohn's disease increased 1.9-fold (from 16.0/100 000 in 2009 to 29.6/100 000 in 2016) and that of ulcerative colitis increased 1.6-fold (from 41.4/100 000 in 2009 to 66.0/100 000 in 2016). Similarly, the estimated incidence of Crohn's disease also increased 1.2-fold (from 2.4 to 2.9 per 100 000) and that of ulcerative colitis rose 1.3-fold (from 4.0 to 5.3 per 100 000). During the study period, the predominant increase in IBD incidence was among younger individuals, especially those aged

Background Although a higher risk of other immune-mediated diseases has been reported in inflammatory bowel disease (IBD) patients, the risk factors of immune-mediated diseases development and the effect of concomitant immune-mediated diseases on outcomes remain poorly defined. Aim To determine the risk factors of incident immune-mediated diseases and the impact of comorbid immune-mediated diseases on outcomes in IBD. Methods Using the National Health Insurance claims data for the entire Korean population, we identified 35 581 IBD patients without immune-mediated diseases and 595 IBD patients with immune-mediated diseases from 2012 to 2013, and follow-up until 2016. We selected four controls by age and sex for comparing with cases. Results A total of 35 581 IBD patients without immune-mediated diseases and 142 324 matched controls without immune-mediated diseases were followed from 2014 to 2016 and of these 239 IBD patients and 357 controls developed immune-mediated disease. The overall immune-mediated diseases risk was higher in IBD patients (HR, hazard ratio, 2.47; 95% confidence interval, CI, 2.09-2.91). In a nested case-control study of the IBD cohort, adult patients aged ≥20 years and frequent hospitalisation ≥1 per year were independent risk factors for incident immune-mediated diseases, in contrast, 5-aminosalicylic acid (5-ASA) use had protective effect (odds ratio, 0.61; 95% CI, 0.41-0.90) for developing immune-mediated diseases. In addition, IBD patients with another immune-mediated disease had an increased risk of needing anti-TNF-α agent (HR, 2.40; 95% CI, 2.02-2.84) and developing acute flare (HR, 1.76; 95% CI, 1.37-2.26). Conclusions The incidence of immune-mediated diseases in IBD patients was higher than that of non-IBD population. 5-ASA use may reduce this risk.

Individuals with advanced adenomas or three or more adenomas have a higher risk of metachronous advanced neoplasia (AN) and are recommended to undergo surveillance colonoscopy at shorter intervals. However, it is questionable whether patients with multiple (three or more) non-advanced diminutive adenomas should be considered as high-risk. We analyzed 5482 patients diagnosed with one or more adenomas during their first colonoscopy screening and who underwent a follow-up colonoscopy. Patients were categorized into four groups based on adenoma characteristics at baseline: Group 1, 1-2 non-advanced adenomas; Group 2, ≥3 non-advanced, diminutive (1 to 5 mm) adenomas; Group 3, ≥3 non-advanced, small (6–9 mm) adenomas; and Group 4, advanced adenomas. During a median follow-up of 38 months, the incidence of metachronous AN at surveillance colonoscopy was 5.6%. The incidence of AN was 3.9% in group 1, 5.9% in group 2, 10.6% in group 3, and 22.1% in group 4. The adjusted hazard ratios (HRs) [95% confidence intervals (CIs)] for metachronous AN between group 2, group 3, and group 4, and low risk group 1 were 1.71 (0.99–2.94), 2.76 (1.72–4.44), and 5.23 (3.57–7.68), respectively. Compared with group 4, the adjusted HRs (95% CIs) for group 1, group 2, and group 3 were 0.19 (0.13–0.28), 0.32 (0.18–0.59), and 0.52 (0.31–0.89), respectively. We found that patients with three or more non-advanced diminutive adenomas had a borderline increased risk of metachronous AN compared with patients with low risk adenomas.

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/ ).

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

Routine prophylaxis for venous thromboembolism (VTE) in Asian IBD patients has been controversial. We aimed to estimate the risk of VTE of Asian patients at different phases of IBD by incorporating patient-specific risk factors. In this cohort study, we analyzed the National Health Insurance claims data between 2012 and 2016 for the entire Korean population. We calculated incidence rates and hazard ratios for VTE. The overall VTE risk was higher in patients with IBD [adjusted hazard ratio (aHR), 2.06; 95% confidence interval (CI), 1.66–2.55], than in controls. When we compare the risk of VTE by different disease phases, the risk of VTE was the highest during post-operation period after IBD-related bowel surgery (aHR, 39.7; 95% CI 9.87–159.3), followed by during hospitalized periods with flare (aHR, 27.2; 95% CI 14.9–49.65) and during hospitalized periods with non-flare (aHR, 16.23; 95% CI 10.71–24.58). The incidence rate (per 1000 person-years) was 15.26 during hospitalized periods with a flare and 9.83 during hospitalized periods with non-flare. According to age groups, the incidence rate (per 1000 person-years) during hospitalized periods with flare was 14.53 in young patients (20–39 years) and 34.58 in older patients (60–80 years). During hospitalized periods with non-flare, the incidence rate was 3.55 in young patients and 23.61 in older patients. The prophylaxis of VTE for Asian patients with IBD should be recommended in older patients admitted to hospital and be considered in young patients who are hospitalized with a flare.

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

Gastric gastrointestinal stromal tumors (GISTs) exhibit various degrees of aggression and malignant potential. However, no systematic preoperative evaluation strategy to predict the malignancy potential of gastric GISTs has yet been developed. This study aimed to develop a reliable and easy-to-use preoperative risk-scoring model for predicting high malignancy potential (HMP) gastric GISTs. The data of 542 patients with pathologically confirmed gastric GISTs who underwent resection were reviewed. Multivariate logistic regression analysis was used to identify significant predictors of HMP. The risk-scoring system (RSS) was based on the predictive factors for HMP, and its performance was validated using a split-sample approach. A total of 239 of 542 (44.1%) surgically resected gastric GISTs had HMP. Multivariate analysis demonstrated that tumor size, location, and surface changes were independent risk factors for HMP. Based on the accordant regression coefficients, the presence of surface ulceration was assigned 1 point. Tumor sizes of 4–6 cm and > 6 cm were assigned 2 and 5 points, respectively. Two points were assigned to cardia or fundus locations. A score of 3 points was the optimal cut-off value for HMP prediction. HMP were found in 19.8% and 82.7% of the low and high-risk groups of the RSS, respectively. The area under the receiver-operating characteristic curve for predicting HMP was 0.81 (95% confidence interval (CI) 0.75–0.86). Discrimination was good after validation (0.75, 95% CI 0.69–0.81). This simple RSS could be useful for predicting the malignancy potential of gastric GISTs and may aid preoperative clinical decision making to ensure optimal treatment.

Background Previous studies have suggested a relationship between Helicobacter pylori infection and dyslipidemia; however, large-scale longitudinal studies have not elucidated this association. This study assessed the longitudinal effects of H. pylori infection and eradication on lipid profiles in a large cohort. Methods This cohort study included 2,626 adults without dyslipidemia at baseline, who participated in a repeated, regular health-screening examination, which included upper gastrointestinal endoscopy, between January 2009 and December 2018. The primary outcome was incident dyslipidemia at follow-up. Results During the 10,324 person-years of follow-up, participants with persistent H. pylori infection had a higher incidence rate (130.5 per 1,000 person-years) of dyslipidemia than those whose infections had been successfully controlled (98.1 per 1,000 person-years). In a multivariable model adjusted for age, sex, waist circumference, smoking status, alcohol intake, and education level, the H. pylori eradication group was associated with a lower risk of dyslipidemia than the persistent group (HR, 0.85; 95% CI, 0.77-0.95; p = 0.004). The association persisted after further adjustment for baseline levels of low-density and high-density lipoprotein cholesterol (HR, 0.87; 95% CI, 0.79-0.97; p = 0.014). Conclusions H. pylori infection may play a pathophysiologic role in the development of dyslipidemia, whereas H. pylori eradication might decrease the risk of dyslipidemia.

Background and aim Proton pump inhibitor (PPI)-induced hypochondria can change the composition of the gut microbiota, inducing overgrowth of small bowel bacteria, which has been suggested to promote the development of fatty liver disease through the gut-liver axis. In this study, we aimed to investigate the association between PPI use and the risk of fatty liver disease. Methods A retrospective cohort study was conducted using the Korean National Health Insurance Service-National Sample Cohort, a nationwide population-based representative sample, from January 1, 2002, to December 31, 2015. PPI use was identified from treatment claims and considered as a time-varying variable. Results During 1 463 556 person-years of follow-up, 75 727 patients had at least one PPI prescription, and 3735 patients developed fatty liver disease. The hazard ratio for fatty liver disease comparing PPI users with non-PPI users was 1.68 (95% confidence interval, 1.61-1.75). When adjusted for multiple confounders, including age, sex, body mass index, smoking, alcohol intake, exercise, income level, and comorbidities, the association was still significant (hazard ratio, 1.50; 95% confidence interval, 1.44-1.57). After considering the amounts of PPIs stratified by cumulative defined daily dose, the dose-response effect was observed until 180 days. Subgroup analysis also revealed that PPI use was correlated to an increased risk of fatty liver disease. Conclusions This current national wide cohort study suggests that PPI use was associated with an increased risk of fatty liver disease compared with non-use of PPIs. Clinicians should consider fatty liver as a potential risk when prescribing PPI.

Background/Aims: The treatment goal of ulcerative colitis (UC) has been changed to achieve endoscopic remission (ER). However, there is insufficient clinical evidence to determine whether a step-up treatment should be performed to achieve ER in clinical remission (CR) without ER, and there are inadequate data on the need to consider the distribution and severity of residual inflammation. This retrospective study aimed to evaluate the prognostic significance of the distribution and severity of residual inflammation in UC patients in CR. Methods: A total of 131 UC patients in CR who underwent endoscopic evaluation for more than three times between January 2000 and December 2018 were reviewed. The patients were allocated by the endoscopic healing state and the distribution of inflammation to ER (n=31, 23.7%), residual nonrectal inflammation with patchy distribution (NRI) (n=17, 13.0%) or residual rectal involvement with continuous or patchy distribution (RI) (n=83, 63.3%) groups. We reviewed clinical characteristics, endoscopic findings, and factors associated with poor outcome-free survival (PFS). Results: In UC patients in CR, PFS was significantly higher in the ER and NRI groups than in the RI group (p=0.003). Patients in the ER and NRI groups had similar PFS (p=0.647). Cox proportional hazard model showed only RI (hazard ratio, 5.76; p=0.027) was associated with a higher risk of poor outcome. Conclusions: We suggest that escalation of treatment modalities may be selectively performed in consideration of the residual mucosal inflammation pattern, even if ER has not been achieved, in UC patients with CR. (Gut Liver 2021;15:401-409)

When non-curative resection is confirmed after endoscopic resection (ER) of early gastric cancer (EGC), delayed surgery is recommended because it provides favorable survival outcomes. Long-term outcome after surgery of EGC with or without previous ER has not been evaluated. The aim of this study was to compare the long-term oncologic safety between primary surgery and delayed surgery after ER. Patients who had undergone curative surgery (R0) for EGC were included and were divided into primary and delayed surgery groups. Primary surgery was defined as gastrectomy without ER for EGC, whereas delayed surgery was defined as additional curative gastrectomy due to non-curative resection after ER; an average delay of 21.5 days (range 1–195) was observed. Propensity score matching was performed. The primary outcome was overall survival (OS) and the secondary outcomes were cancer-specific survival (CSS) and disease-free survival (DFS). After propensity score matching, 1439 patients were included, of whom 1042 (72.4%) were in the primary surgery group and 397 (27.6%) were in the delayed surgery group. The OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.59–1.27; p = 0.459), CSS (HR 0.47, 95% CI 0.15–1.47; p = 0.196), and DFS (HR 0.54, 95% CI 0.15–1.90; p = 0.334) were not different. The long-term outcomes of delayed surgery after non-curative ER for EGC were non-inferior to primary surgery. Therefore, an attempt for ER of EGC that satisfies the absolute and expanded indication seems justified for preventing gastrectomy. In case of non-curative resection after ER, additional delayed surgery should be performed.

Background/aims Helicobacter pylori (H. pylori) infection has been known to cause various extra-gastric diseases, which may be mediated by an increase in systemic inflammation. Thus, we examined the association between H. pylori infection and various markers of systemic inflammation in a large sample of asymptomatic adults. Methods Cross-sectional data were obtained from 17,028 adults who completed routine health check-ups. H. pylori infection status was determined using a serum immunoglobulin G test, and systemic inflammation was assessed using the C-reactive protein (CRP) levels, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). Results Multiple linear regression model-adjusted for potential confounders-revealed that H. pylori infection was not associated with CRP levels (coefficient: -0.012, 95% confidence interval [CI]: -0.037, 0.012, p=0.319), NLR (coefficient: 0.055, 95% CI: -0.027, 0.138, p=0.192), or PLR (coefficient: 1.798, 95% CI: -1.979, 5.574, p=0.351). In a multivariable logistic regression model, H. pylori infection was not associated with the risk of CRP levels being elevated to ≥0.1 mg/dL (odds ratio: 0.96, 95% CI: 0.81, 1.08) or ≥0.3 mg/dL (odds ratio: 1.02, 95% CI: 0.84, 1.19). In the multivariable model, CRP levels elevated to ≥0.1 mg/dL were significantly associated with body mass index, current smoking status, hypertension, and diabetes mellitus. Regular exercise and high-density lipoprotein cholesterol were factors that minimized the elevation of CRP levels. Conclusions Chronic infection with H. pylori was not associated with various inflammatory markers. Further investigation is needed to clarify the interaction between H. pylori infection, systemic inflammation, and extra-gastric disease.

Background and aim Sarcopenia is a pathological condition characterized by the progressive loss of muscle mass and increased amount of visceral fat. Recent evidence has revealed that sarcopenia is associated with certain diseases. However, the impact of sarcopenia on colorectal neoplasia has not been documented clearly. We studied the association between sarcopenia and advanced colorectal neoplasia in a large screening population. Methods This cross-sectional study included 14 024 asymptomatic adults who underwent first-time screening colonoscopy. Sarcopenia (class II) was defined as an appendicular skeletal muscle mass (ASM)/bodyweight (%) value more than two standard deviations below the mean for healthy young adults. ASM was estimated using bioelectrical impedance analysis. Results In a multivariable model adjusted for age, sex, obesity (body mass index ≥ 25), smoking status, alcohol intake, regular exercise, and family history of colorectal cancer, the odds ratio (OR) for advanced colorectal neoplasia on comparing participants with sarcopenia (class II) to those without sarcopenia (class I + II) was 1.52 (95% confidence interval [CI], 1.23-1.86). Further adjustment for metabolic parameters attenuated this association, but the association was still significant (OR, 1.34; 95% CI, 1.07-1.68). Furthermore, the multivariable (traditional risk factors)-adjusted OR associated with a 1% decrease on the introduction of ASM/weight% as a continuous variable in regression models was 1.04 (95% CI, 1.01-1.07) for advanced colorectal neoplasia. Conclusions Our findings indicate that sarcopenia is significantly and progressively associated with the risk of advanced colorectal neoplasia. This association might be explained by metabolic factors that could be potential mediators of the effect of sarcopenia.

In this cross-sectional study, we assessed five anthropometric measurements to determine the most reliable indicator of the erosive esophagitis (EE) risk: body mass index (BMI), waist circumference (WC), waist to height ratio (WHtR), a body shape index (ABSI), and body roundness index (BRI).This study included 182,407 participants who underwent an esophagogastroduodenoscopy as part of a routine health check-up. We used the area under the receiver-operating characteristic curve (AUC) to assess the discriminatory power of each anthropometric measure as an indicator of EE risk.The prevalence of EE increased per quartile for all five anthropometric measurements in patients of both sexes (1st quartile vs. 4th quartile, all P0.05). ABSI had the lowest AUCs for EE in both sexes (AUC: 0.524, 95% CI: 0.519-0.529 for male patients; AUC: 0.524, 95% CI: 0.513-0.535 for female patients). In contrast, BRI was the best predictor of EE in male patients (OR: 2.095, 95% CI: 1.982-2.215, P0.0001), and WC was the best predictor of EE in female patients (OR: 2.028, 95% CI: 1.785-2.307, P0.0001). WC showed the highest AUC values for EE in both male patients (AUC: 0.571, 95% CI: 0.566-0.576) and female patients (AUC: 0.596, 95% CI: 0.585-0.608).BRI and WC were the most relevant indicators of EE risk in male and female patients, respectively. ABSI was the least reliable indicator of EE risk in patients of both sexes.

This cross-sectional study aimed to investigate the association between hyperuricemia and the frequency of coffee, tea, and soft drink consumption, based on data from the Korean Genome and Epidemiology Study (KoGES) (2004–2016). We used the KoGES health examinee data, obtained from urban residents aged ≥ 40 years. Information on the participants’ medical history, nutrition (total calorie, protein, fat, and carbohydrate intake), frequency of alcohol consumption, smoking status, household income, and frequency of coffee/green tea/soft drink intake was collected. A logistic regression model was used to analyze the data. Subgroup analyses were performed according to the participant’s age and sex. Among 173,209 participants, there were 11,750 and 156,002 individuals with hyperuricemia and non-hyperuricemia controls, respectively. In an adjusted model, frequent coffee and green tea consumption did not increase the risk of hyperuricemia, compared to the “no intake” reference group. However, an adjusted odds ratio of hyperuricemia was 1.23 (95% confidence interval, 1.11–1.35, p &lt, 0.001) for participants who reported consuming soft drinks ≥ 3 times per day, compared to the respective “no drink” reference group. Even after adjusting for nutritional and sociodemographic factors, frequent soft drink intake was associated with an increased risk of hyperuricemia. Meanwhile, neither coffee nor green tea intake was associated with an increased risk of hyperuricemia.

We aim to examine (1) variations in the public awareness of poverty as a determinant of health and (2) associations of individual and macro level factors with awareness. Analyses are based on the International Social Survey Programme. Data stem from 23 countries (N = 37,228) that were assigned to six welfare states. Sociodemographic, socio-economic, and health-related factors were considered as individual level characteristics. Gross domestic product, relative poverty rate, Gini coefficient, and magnitude of health inequalities were additionally introduced as macro level factors. About 47% of the respondents in all countries agreed with the statement that people suffer from severe health problems because they are poor (range 30–77%). Multilevel analyses reveal that awareness was least pronounced in Liberal, East European, and East Asian welfare regimes. Moreover, women, older adults, respondents with low education and income, as well as poor health were more likely to show awareness. There is a need to raise public awareness of the adverse health effects of poverty as the public opinion can be an important driver of political will on health and social issues.

Background and aims Although obesity and metabolic abnormalities are known risk factors for cardiovascular disease, the risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as metabolically healthy obese (MHO), remains unclear. We examined the association between body mass index categories and the development of subclinical carotid atherosclerosis in a cohort of metabolically healthy individuals. Methods We conducted a cohort study of 6453 men without subclinical carotid atherosclerosis or metabolic abnormalities at baseline, who underwent repeated health check-up examinations that included carotid ultrasound. A metabolically healthy state was defined as having no metabolic syndrome components and a homeostasis model assessment of insulin resistance Results During the follow-up period of 34,797.9 person-years, subclinical carotid atherosclerosis developed in 1916 participants. Comparing overweight and obese with normal weight participants, the multivariable adjusted hazard ratios (95% confidence intervals) for incident subclinical carotid atherosclerosis were 1.24 (1.12–1.38) and 1.54 (1.38–1.72), respectively. The association persisted after further adjustment for metabolic variables. This association was also evident in MHO men without abdominal obesity (waist circumference > 90 cm) and it did not differ across any clinically relevant subgroups evaluated. Conclusions In a large cohort study of strictly defined metabolically healthy participants, the MHO phenotype was associated with an increased risk of incident subclinical carotid atherosclerosis, providing evidence that the MHO phenotype is not protective from cardiovascular risk.

Background/Aims: The indications for colorectal endoscopic submucosal dissection (ESD) vary in clinical practice. To establish colorectal ESD as a standard treatment, standard indications are essential. For establishing standard indications for colorectal ESD, we surveyed the preferences and criteria of endoscopists for colorectal ESD in their practices.Methods: A multiple-choice questionnaire was sent to 27 members of the Korean Society of Gastrointestinal Endoscopy/ESD group. The indications of endoscopists for selecting ESD as a treatment for colorectal tumors ≥2 cm in diameter were surveyed.Results: On the basis of the preprocedural assessment of histology, adenoma with high-grade dysplasia, mucosal cancer, and shallow submucosa invasive cancer were included in the indication for ESD. Based on gross morphology, laterally spreading tumor (LST) granular nodular mixed type, LST-nongranular (LST-NG) flat elevated type, and LST-NG pseudodepressed type were included. On the basis of the pit pattern by Kudo classification, types III, IV, and V-I were included. Based on the narrow band imaging pattern by Sano classification, types II and III-a were included. Other lesions, such as sporadic localized tumors in chronic inflammation and local residual early carcinoma after endoscopic resection, were also included in the indication for ESD.Conclusions: The indications of Korean endoscopists for colorectal ESD are broader than those in recent guidelines, and tend to include more benign-looking tumors. To find the appropriate indications for colorectal ESD, systematic data collection and analysis are required to reach a consensus in a timely manner.

International studies have repeatedly shown that people with lower income are more likely to experience difficulties to access medical services. Less is known on why these relations vary across countries. This study investigates whether the association between income and financial barriers to health care is influenced by national public health expenditures (PHE, in % of total health expenditure). Data from the International Social Survey Programme (2011) was used (28 countries, 23,669 respondents). Financial barriers were assessed by the individual experience of forgone care due to financial reasons. Monthly equivalent household income was included as the main predictor. Other individual-level control variables were age, gender, education, subjective health, insurance coverage and place of living. PHE was considered as a macro-level predictor, adjusted for total health expenditure. Statistically significant associations between income and forgone care were found in 21 of 28 examined countries. Multilevel analyses across countries revealed that people with lower income have a higher likelihood to forgo needed medical care (OR: 3.94, 95%-CI: 2.96-5.24). After adjustments for individual-level covariates, this association slightly decreased (OR: 2.94, 95%-CI: 2.16-3.99). PHE did not moderate the relation between income and forgone care. The linkage between health system financing and inequalities in access to health care seems to be more complex than initially assumed, pointing towards further research to explore how PHE affects the redistribution of health resources in different health care systems.

Obesity increases the risk of colorectal adenoma and colorectal cancer. However, the obesity-related parameters that are best for assessing the risk of colorectal adenoma development remain unclear. We analyzed the parameters that may best describe the association between obesity and colorectal adenoma development. In this retrospective cohort study, 3405 individuals underwent screening colonoscopy during routine health examinations. We measured body mass index; waist circumference; and metabolic parameters such as high-density lipoprotein-cholesterol, glucose, triglyceride, and systolic blood pressure. We analyzed the risk of developing colorectal adenoma, relative to obesity-related parameters, over a mean interval of 5.8 years from baseline colonoscopy. In a multivariate analysis, waist circumference was the only obesity-related marker associated with an increased risk of metachronous colorectal adenoma. Men with waist circumferences ≥85 cm and women with waist circumference ≥82 cm had a 31% increased risk of metachronous colorectal adenoma compared to those with smaller waist circumferences [odds ratio (OR) 1.31; 95% confidence interval (CI, 1.09–1.57)]. Other factors associated with metachronous colorectal adenoma were age (OR, 1.03; 95% CI 1.02–1.04), male sex (OR 1.49; 95% CI 1.17–1.88), alcohol consumption ≥3/week (OR 1.33; 95% CI 1.10–1.62), the number of adenoma at baseline (OR 1.21; 95% CI 1.10–1.33), and the presence of advanced adenoma at baseline (OR 1.60; 95% CI 1.24–2.06). Our findings suggest that central obesity, represented by waist circumference, is a significant predictor of metachronous colorectal adenoma, independent of body mass index and other metabolic variables.

Background The advancement of therapeutic agents has made it possible to achieve endoscopic remission in inflammatory bowel disease. Consequently, the treatment goal of ulcerative colitis (UC) also has been changed to achieve endoscopic remission (ER). However, there was insufficient clinical evidence of whether a step-up treatment should be performed to achieve ER in clinical remission (CR) without ER. And there is inadequate data on the need to consider the distribution and severity of residual inflammation in UC. This retrospective study aimed to evaluate the prognostic significance (such as step-up therapy, hospitalisation, and colectomy) of the distribution and severity of residual inflammation in UC patients with CR. Methods A total of 134 UC patients who underwent endoscopic evaluation in CR and underwent colonoscopy more than 3 times between January 2000 and December 2018 were retrospectively reviewed. Patients were allocated by endoscopic healing state and distribution of inflammation to an ER (n = 33, 24.6%), residual non-rectal inflammation with patchy distribution (NRI) (n = 17, 12.7%) or residual rectal involvement with continuous or patchy distribution (RI) (n = 84, 62.7%). We reviewed the patient’s characteristics, endoscopic findings and ascertain poor outcome-free survival (PFS) until June 2019. Results In UC patient with CR, the PFS was significantly better in ER and NRI (p = 0.003). ER and NRI had similar PFS (p = 0.683). The baseline clinical characteristics of NRI and RI were not significantly different except for the pattern of residual inflammation (p < 0.001). Multivariate analysis showed that NRI was a good prognostic factor of PFS for UC with CR Like ER (hazard ratio 0.53 (0.05–6.30), p = 0.615). Conclusion There was no statistically significant difference in the PFS between ER and NRI in the CR state of UC patients. Therefore, we propose selective escalation of treatment modality in CR patients, even if they do not reach ER.

Background Despite proven efficacy of anti-tumour necrosis factor-α agents (ant-TNF) for inflammatory bowel disease (IBD), some patients have to be discontinuation of anti-TNF for various reasons in a real-world clinical setting. The aim of this study was to evaluate the long-term outcomes and risk factors of relapse after discontinuation of anti-TNF in IBD patients with clinical remission. Methods A retrospective multicenter cohort study was conducted at 10 referral hospitals, affiliated in IBD Study Group of the Korean Association for the Study of Intestinal Diseases. The study population comprised patients diagnosed with Crohn’s disease (CD) or Ulcerative colitis (UC) who had been treated with anti-TNF (infliximab (IFX) or adalimumab (ADA)) to induce remission and in whom ant-TNF had been discontinued after clinical remission was achieved. The patients were excluded for follow-up of Results A total of 125 IBD patients were eligible. Among them, 109 IBD patients including 71 CD and 38 UC were analyzed and median follow-up period was 56 months (interquartile range, 35–90 months). The reasons of discontinuation of anti-TNF was physician’s decision (n = 32, 29.4%), patient’s own preference (n = 30, 27.5%), anti-TNF-related adverse events/opportunistic infection (n = 18, 16.5%), and other reasons (n = 29, 26.6%). After discontinuation of anti-TNF, relapse occurred in 49 CD patients (69%) and 19 UC patients (50%). Relapse-free survival rate at 1, 2, 3, and 5 years in patients with CD were 11.3%, 31.4%, 46.7%, and 62.5%, respectively, and that in patients with UC was 28.9%, 34.8%, 45.3%, and 60.9%, respectively. Multivariate Cox regression analysis identified the risk of relapse was associated with adalimumab use (vs. infliximab: hazard ratio [HR], 4.41; 95% confidence interval [CI], 1.18–16.41; p = .027) and discontinuation due to physician’s decision (vs. patient’s preference: HR, 0.13, 95% CI, 0.04–0.49, p = .002) in patients with CD, whereas that was decreased in UC patients with mucosal healing (vs. non-mucosal healing: HR=0.07, 95% CI, 0.01–0.58, p = .014). Retreatment with anti-TNF was done in 54 patients (49.5%) and effective in 45 patients(83.3%). Conclusion The discontinuation of anti-TNF was associated with increased risk of relapse. Although retreatment of anti-TNF seems to be effective and safe, the discontinuation of anti-TNF should be carefully considered based on the type of anti-TNF, the reason for discontinuation, and the mucosal healing status.

Recently reported genome-wide association studies have identified more than 20 common low-penetrance colorectal cancer (CRC) susceptibility loci. Recent studies have reported that copy number variations (CNVs) are considered important human genomic variants related to cancer, while the contribution of CNVs remains unclear. We performed array comparative genomic hybridization (aCGH) in 36 CRC patients and 47 controls. Using breakpoint PCR, we confirmed the breakpoint of the PKD1L2 deletion region. High frequency of PKD1L2 CNV was observed in CRC cases. We validated the association between PKD1L2 variation and CRC risk in 1,874 cases and 2,088 controls (OR=1.44, 95% CI=1.04-1.98, P=.028). Additionally, PKD1L2 CNV is associated with increased CRC risk in patients younger than 50 years (OR=2.14, 95% CI 1.39-3.30, P=5.8x10-4). In subgroup analysis according to body mass index (BMI), we found that the CN loss of PKD1L2 with BMI above or equal to 25 exhibited a significant increase in CRC risk (OR=2.29, 95% CI 1.29-4.05, P=.005). PKD1L2 CNV with BMI above or equal to 25 and age below 50 is associated with a remarkably increased risk of colorectal cancer (OR=5.24, 95% CI 2.36-11.64, P= 4.8x10-5). Moreover, we found that PKD1L2 variation in obese patients (BMI>=25) was associated with poor survival rate (P=.026). Our results suggest that the common PKD1L2 CNV is associated with CRC, and PKD1L2 CNV with high BMI and/or age below 50 exhibited a significant increased risk of CRC. In obese patients, PKD1L2 variation was associated with poor survival. This article is protected by copyright. All rights reserved.

Background and aim The role of diabetes mellitus as a risk factor for gastric cancer has been controversial. We studied the association between diabetic biomarkers and the risk of gastric cancer and whether these associations depend on cancer location. Methods In this retrospective cohort study with subjects with negative initial esophagogastroduodenoscopy findings (n = 23 218) during a routine health checkup, we measured fasting glucose and insulin levels, calculated the homeostatic model assessment insulin resistance (HOMA-IR) values, and analyzed the risk of gastric cancer in relation to diabetic biomarker tertiles and the presence of diabetes mellitus. Results The incidence rate of gastric cancer was 9.7 per 10 000 person-years during the mean 6.8-year follow up. Patients with diabetes, higher fasting glucose levels, or higher HOMA-IR levels were older; men, current smokers, and heavy alcohol consumers represented larger proportions of these groups. They also had high body mass index and hemoglobin A1c more often. In the multivariate-adjusted Cox regression analyses, the incidence of gastric cancer was not significantly associated with diabetes mellitus or higher diabetic biomarker levels. Compared with normal glucose levels, lower glucose levels were significantly associated with an increased risk of distal gastric cancer. The hazard ratio for fasting glucose level tertile 1 was 2.39 (95% confidence interval, 1.48-3.85) (reference, tertile 2). Lower glucose levels were not associated with a risk of proximal gastric cancer, compared with a normal glucose level. Conclusions Our findings suggest that fasting glucose levels have a different effect on distal and proximal gastric cancers.

OBJECTIVES: Obesity is an established risk factor of erosive esophagitis, and metabolic unhealthiness has been implicated in the pathogenesis of erosive esophagitis. Yet, the risk of erosive esophagitis among obese individuals without obesity-related metabolic unhealthiness, a condition referred to as “metabolically healthy obese (MHO)”, remains unclear. We examined the association between body mass index (BMI) categories and the development of erosive esophagitis in a cohort of metabolically healthy individuals. METHODS: We conducted a cohort study of 14,725 asymptomatic adults free of erosive esophagitis and metabolic abnormalities, who underwent repeated health checkups including screening endoscopy. A metabolically healthy state was defined as having no metabolic syndrome components and a homeostasis model assessment of insulin resistance

Few maintenance therapeutic options are available for inflammatory bowel disease (IBD). Data on the effects of continuing 5-aminosalicylic acid (5-ASA) treatment in patients who commence on biologics as maintenance treatment remain scarce. We evaluated IBD patient outcomes after continuation/discontinuation of 5-ASA when biologics were administered as maintenance treatment. We retrospectively reviewed the clinical, laboratory, and imaging data of patients diagnosed with IBD (ulcerative colitis (UC), 763; Crohn’s disease (CD), 537) in the Gil Medical Center (GMC) from February 2005 to June 2018. We divided patients administered with biologics as maintenance treatment into those who did and did not continue on 5-ASA and compared the efficacies of the two treatment options using the log-rank test and Cox proportional hazards models. Of 1300 total IBD patients, 128 (UC, 63; CD, 65) were prescribed biologics as induction and maintenance treatments. The median follow-up period was 109.5 weeks. All cases were divided into those who did or did not combine 5-ASA with biologics as maintenance treatments. Kaplan–Meier analysis showed that the event-free survival (exacerbation of disease activity) of UC patients treated with biologics and 5-ASA (n = 42) was not significantly lower than that of those taking biologics alone (n = 21) (log rank test, P = 0.68). The same was true of CD patients (n = 42, biologics and 5-ASA; n = 23, biologics only) (log rank test, P = 0.87). Continuation of 5-ASA after initiation of anti-tumor necrosis factor-alpha agents did not improve prognosis in Korean IBD patients compared with that of those who discontinued 5-ASA during maintenance treatment, particularly in patients who experienced more than two disease aggravations.

Acid suppressants such as histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are effective in preventing gastrointestinal (GI) bleeding in nonsteroidal anti-inflammatory drugs (NSAIDs) users. Despite widespread acid suppressant use, there remain concerns about several potential risks of long-term use. Therefore, we investigated whether gastroprotective agents (GPAs) other than acid suppression therapy are effective in preventing NSAID-related GI injury. To this end, we studied 9,133 patients with osteoarthritis or rheumatoid arthritis who used NSAIDs for ≥1 month. A decrease of 2 g/dL or more in the hemoglobin level was considered a GI injury indicator. The GPAs included acid suppressants and other mucoprotective agents. Acid suppressants included PPIs and H2RAs. Other mucoprotective agents included misoprostol, rebamipide, and eupatilin. During a median follow-up period of 27 (range, 4.3-51.3) weeks, occult GI bleeding occurred in 1,191 (13%) patients. A comparison of patients who used GPAs concomitantly with that of nonusers in a multivariable analysis revealed the hazard ratios (HRs; 95% confidence intervals [CIs]) for occult GI bleeding were 0.30 (0.20-0.44), 0.35 (0.29-0.43), 0.47 (0.23-0.95), 0.43 (0.35-0.51), and 0.98 (0.86-1.12) for PPIs, H2RAs, misoprostol, rebamipide, and eupatilin, respectively. Compared to PPI co-treatment, H2RA, misoprostol, rebamipide, and eupatilin co-treatments were associated with occult GI bleeding HRs (95% CIs) of 1.19 (0.79-1.79), 1.58 (0.72-3.46), 1.44 (0.96-2.16), and 3.25 (2.21-4.77), respectively. Our findings suggest that mucoprotective agents, such as rebamipide and misoprostol, as well as acid suppressants, are effective in reducing the risk for GI injury in NSAID users.

Background and aim Appropriate bowel cleansing before colonoscopy is an important factor in increasing the detection rate of lesions. Low-volume polyethylene glycol (PEG) plus ascorbic acid (PEG-Asc) reduces the dosage of bowel preparation agent, but still presents discomfort to patients. The primary aim of the present study was to compare the efficacy of bowel cleansing between 2 L PEG-Asc (control) and 1 L PEG-Asc with bisacodyl suppository (suppository) groups, and the secondary aim was to investigate complications and tolerability between the two groups. Methods This was a single-center prospective randomized controlled study. We identified 168 patients scheduled for colonoscopy between August 2017 and January 2018 and randomly assigned them to the control or to the suppository groups. Efficacy of bowel cleansing was assessed using the Boston Bowel Preparation Scale (BBPS), and side-effects were surveyed using questionnaires. Results No significant difference was detected in baseline characteristics including insertion and withdrawal times, and adenoma detection rates between the two groups. Total BBPS score was 7.93 ± 1.06 and 7.74 ± 1.02 in the control and suppository groups, respectively (P = 0.22). Incidence of abdominal pain and nausea was not statistically different, whereas that of sleep disturbance and anal discomfort was higher in the control group. (P = 0.00). Conclusions One liter PEG-Asc with bisacodyl suppository resulted in an equivalent bowel-cleansing outcome with reduced patient discomfort compared to 2 L PEG-Asc. Therefore, PEG-Asc with bisacodyl suppository represents a potential alternative and increases patient compliance with bowel preparation.

Self-expandable metal stent (SEMS) placement has been suggested as a therapeutic modality for treating benign colorectal strictures. Covered stents are generally used, given the concerns regarding the efficacy and safety of uncovered stents. Hence, few studies have evaluated the efficacy and safety of uncovered SEMSs (UCSEMSs) in patients with refractory benign colorectal anastomotic strictures. In this study, 12 patients with postoperative benign symptomatic anastomotic strictures refractory to pneumatic dilation (range, 2–9) and transient indwelling-covered SEMSs were treated using UCSEMS. All enrolled patients were men (mean age, 61 years). Stent placement was successful in all 12 patients, and early clinical success was achieved in 11 (92%) patients. Four patients (25%) showed successful clinical outcomes without further intervention, but eight patients (75%) were clinically unsuccessful, and showed stricture recurrence or functional obstructive symptoms. Three patients underwent surgery, and the remaining five patients required repeat stent procedures. Despite the high reobstruction rate, the median follow-up period after UCSEMS placement was 16.7 months, demonstrating that UCSEMS may be able to achieve medium-term symptom relief without any complications. Therefore, UCSEMS may be an alternative option in exceptional circumstances in carefully selected patients, where invasive surgical treatments, such as stoma diversion, are not an option, thereby improving patients’ quality of life.

Differences in public beliefs about causes of obesity between the USA and Germany are analyzed. We additionally examine the relevance of social characteristics of individuals with obesity for causal attributions in the two countries. National telephone surveys were conducted in both countries (total sample = 2802). Vignettes describing a person with obesity were used and varied according to gender, migration status, and occupational position. Beliefs about causes of obesity were assessed by 12 items, representing four dimensions (‘sociocultural causes’, ‘behavior-related causes’, ‘somatic and psychological causes,’ and ‘educational and financial causes’). Respondents from the USA more strongly support sociocultural as well as educational and financial causes of obesity. When the person with obesity has a low occupational position or is a migrant, sociocultural causes are considered more important, whereas agreement to behavioral as well as somatic and psychological factors is less pronounced. In the USA, external causal attributions (i.e., causes that are beyond individual’s control) seem to play a more important role than in Germany. In both countries, public causal beliefs about obesity vary according to social characteristics of the person afflicted.

IntroductionOver the past decades, obesity stigma has become a substantial public health issue as studies have highlighted its negative consequences for mental and physical health. However, comparative studies are scarce. In this cross-national study, we focus on the following research questions: (1) Are there differences in the magnitude of public obesity stigma between Germany and the United States (US), and (2) are there differences in the associations of sociodemographic as well as experience (i.e. former obesity experience) and contact-related (i.e. contact to a person with obesity) factors with public obesity stigma between these two countries?Material and methodsNational telephone surveys in Germany and the United States were conducted (total sample = 2,802) by using vignettes for the description of a person with obesity. Fat Phobia Scale, negative reactions, and desire for social distance were assessed as components of public obesity stigma. All three stigma components were examined with multilevel linear regression analyses.ResultsOverall, results show that public obesity stigma is significantly more pronounced in the US than in Germany. Relationships between obesity stigma and sociodemographic as well as experience and contact-related factors remain rather inconclusive, though, in general, stronger associations are shown in the US.ConclusionsContrary to the normalization hypothesis, findings indicate that a comparatively high prevalence of obesity like in the US is associated with a higher level of obesity stigma.

Background/aim: The objective of this study is to identify clinical predictors of primary non-response (PNR) and secondary loss of response (LOR), in Crohn’s disease (CD) patients treated with anti-tumor necrosis factor α (anti-TNF) agents. Methods: This retrospective, longitudinal, and observational cohort study included 283 patients with CD who received anti-TNF treatments from November 2006 to July 2017 at Samsung Medical Center, Seoul, Korea. Results: A total of 212 patients with CD were eligible and based on clinical responses, divided into three groups: PNR, LOR, and responder groups. PNR occurred in 13 patients (6.1%). C-Reactive protein (CRP) level at initiation of anti-TNF (baseline CRP) was a possible predictor of PNR compared to the non-PNR group (baseline CRP >1 mg/dl, OR = 4.34, 95% CI = 1.06–17.83, p = .042). During maintenance therapy, incidence of LOR was 12.2% at 1-year, 23.6% at 2-years, 36.3% at 3-years, and 52.1% at 5-years. Combining baseline CRP level and CRP reduction rate [(CRP at 12–14 weeks–baseline CRP)/baseline CRP] was a possible predictor of 1-year LOR compared to the responder group (baseline CRP >1 mg/dl and CRP reduction rate > −70%, OR = 18.86, 95% CI = 3.40–104.55, p = .001). In the Cox hazard proportional model, a combination of baseline CRP level and CRP reduction rate was possible predictors of long-term LOR during maintenance therapy (baseline CRP >1 mg/dl and CRP reduction rate > −70%, HR = 5.84, 95% CI = 2.75–12.41, p < .001). Conclusions: Baseline CRP level and CRP reduction rate might be clinical predictors for PNR or LOR to anti-TNF in patients with CD, and could guide proper therapeutic interventions in patients with CD.