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The introduction of device-assisted enteroscopy (DAE) in the beginning of 21st century has revolutionized the diagnosis and treatment of diseases of the small intestine. In contrast to capsule endoscopy, the other main diagnostic modality of the small bowel diseases, DAE has the unique advantages of observing the region of interest in detail and enabling tissue acquisition and therapeutic intervention. As DAE becomes an essential procedure in daily clinical practice, there is an increasing need for correct guidelines on when and how to perform it and what technical factors should be considered. In response to these needs, the Korean Association for the Study of Intestinal Diseases developed an expert consensus statement on the performance of DAE by reviewing the current evidence. This expert consensus statement particularly focuses on the indications, choice of insertion route, therapeutic intervention, complications, and relevant technical points.

Brain–machine interface (BMI) provides an alternative route for controlling an external device with one’s intention. For individuals with motor-related disability, the BMI technologies can be used to replace or restore motor functions. Therefore, BMIs for movement restoration generally decode the neural activity from the motor-related brain regions. In this study, however, we designed a BMI system that uses sensory-related neural signals for BMI combined with electrical stimulation for reward. Four-channel electrocorticographic (ECoG) signals were recorded from the whisker-related somatosensory cortex of rats and converted to extract the BMI signals to control the one-dimensional movement of a dot on the screen. At the same time, we used operant conditioning with electrical stimulation on medial forebrain bundle (MFB), which provides a virtual reward to motivate the rat to move the dot towards the desired center region. The BMI task training was performed for 7 days with ECoG recording and MFB stimulation. Animals successfully learned to move the dot location to the desired position using S1BF neural activity. This study successfully demonstrated that it is feasible to utilize the neural signals from the whisker somatosensory cortex for BMI system. In addition, the MFB electrical stimulation is effective for rats to learn the behavioral task for BMI.

Background/Aims: Changing trends in the Helicobacter pylori (H. pylori) eradication protocol have not been investigated after the publication of the third-revised Korean guideline in 2013. We aimed to analyze the clinical characteristics of H. pylori-infected patients alongside their treatment protocols using a common data model (CDM).Materials and Methods: A 16-year electronic health record (of 1,689,604 patients from 2004 to 2019) was converted into a CDM in Kangdong Sacred Heart Hospital. We extracted records of patients who underwent the rapid urease test or serum anti-H. pylori IgG assay. The treatment protocols were visualized using a sunburst plot. We investigated the clinical characteristics and medication history of patients who underwent a urea breath test after clarithromycin-based eradication therapy.Results: Out of 29,458 patients tested for H. pylori infection, 7,647 received a treatment protocol. Among them, 72.5% received a 7~14 days protocol comprising a proton pump inhibitor (PPI), amoxicillin, and clarithromycin. The proportion of patients treated with the first-line protocol (PPI, bismuth, tetracycline, and metronidazole) slightly increased from 1.9% (before 2014) to 3.3% (after 2014) (PH. pylori treatment protocol was not significantly modified despite the updates in the clinical guideline. There was only 1.4 percentage point increase in bismuth-based quadruple therapy as first-line eradication therapy even after the announcement of revised Korean guideline in 2013.

Background/Aims: Previous studies have reported an association between Helicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD). Our study examined whether eradication for H. pylori infection reduces the risk of incident NAFLD.Materials and Methods: This retrospective cohort study examined 3,780 adults who had no NAFLD at baseline but were infected with H. pylori. The study population was followed from January 1995 until January 2020. H. pylori infection was determined by an H. pylori-specific IgG antibody test. Fatty liver was diagnosed by ultrasound.Results: During a median follow-up of 7.9 years, 1,294 participants developed NAFLD. In a multivariable model adjusted for age, sex, BMI, smoking status, alcohol intake, and metabolic variables, the uneradicated (for H. pylori) group exhibited a higher risk of incident NAFLD than the eradicated group (hazard ratio [HR], 1.36; 95% CI, 1.18~1.56). The multivariable analysis also demonstrated that higher BMI, current smoking and several metabolic abnormalities were significant risk factors for NAFLD. Subgroup analyses revealed that persistent H. pylori infection correlated with an increased risk of NAFLD. H. pylori eradication was associated with a decreased risk of NAFLD development.Conclusions: H. pylori infection may have a pathophysiological role in NAFLD development. Hence, successful eradication of H. pylori decreases the risk of incident NAFLD.

Chemotherapy is ubiquitous in first-line treatment of advanced gastric cancer, yet responses are heterogeneous, and little is known about mediators of chemotherapy response. To move forward, an understanding of the effects of standard chemotherapy on the tumor–immune microenvironment (TME) is needed. Coupling whole-exome sequencing, bulk RNA and single-cell transcriptomics from paired pretreatment and on-treatment samples in treatment-naïve patients with HER2-positive and HER2-negative gastric cancer, we define features associated with response to platinum-based chemotherapy. Response was associated with on-treatment TME remodeling including natural killer (NK) cell recruitment, decreased tumor-associated macrophages, M1-macrophage repolarization, and increased effector T-cell infiltration. Among chemotherapy nonresponders, we observed low/absent PD-L1 expression or modulation, on-treatment increases in Wnt signaling, B-cell infiltration, and LAG3-expressing T cells coupled to an exodus of dendritic cells. We did not observe significant genomic changes in early on-treatment sampling. We provide a map of on-treatment TME modulation with standard chemotherapy and nominate candidate future approaches.Significance:Using paired pretreatment and on-treatment samples during standard first-line chemotherapy, we identify chemotherapy-induced NK-cell infiltration, macrophage repolarization, and increased antigen presentation among responders. Increased LAG3 expression and decreased dendritic cell abundance were seen in nonresponders, emphasizing remodeling of the TME during chemotherapy response and resistance.This article is highlighted in the In This Issue feature, p. 873

Supplementary Figure from Early Tumor–Immune Microenvironmental Remodeling and Response to First-Line Fluoropyrimidine and Platinum Chemotherapy in Advanced Gastric Cancer

Supplementary Table from Early Tumor–Immune Microenvironmental Remodeling and Response to First-Line Fluoropyrimidine and Platinum Chemotherapy in Advanced Gastric Cancer

Background The treatment goal of ulcerative colitis (UC) has changed from the control of symptoms to mucosal healing, previously evaluated mainly by endoscopy. Recently, the importance of histologic activity has emerged. Therefore, this study aimed to investigate the risk of clinical relapse according to histologic activity in UC with a Mayo endoscopic subsccore (MES) of 0 or 1. Methods In a retrospective cohort after our center’s biopsy guideline for UC was instituted, 492 UC patients with an MES of 0 or 1 were enrolled and analyzed. The primary outcome was the development of a clinical relapse including changes in medication, hospitalization, colectomy, and the development of colorectal cancer during the follow-up period. Results During the median 549 days of follow-up, 92 (18.7%) patients had a clinical relapse. All the patients changed their medication, including 4 hospitalized patients. Histologic activity defined by a Geboes score of ≧3.1 (hazard ratio [HR], 1.732; P = .035) and steroid use history (HR, 1.762; P = .008) were independent factors associated with clinical relapse. When stratified, the 1- and 2-year incidence rates of clinical relapse were 4.1% and 10.6%, respectively, for patients with histologic improvement and no steroid use history, whereas the rates were 23.9% and 39.4% for patients with histologic activity and steroid use history. Conclusions In UC with an MES of 0 or 1, histologic activity and steroid use history can be used to stratify the risk of clinical relapse.

Background/Aims: Endoscopic submucosal dissection (ESD) of gastric tumors in the mid-to-upper stomach is a technically challenging procedure. This study compared the therapeutic outcomes and adverse events of ESD of tumors in the mid-to-upper stomach performed under general anesthesia (GA) or monitored anesthesia care (MAC).Methods: Between 2012 and 2018, 674 patients underwent ESD for gastric tumors in the midbody, high body, fundus, or cardia (100 patients received GA; 574 received MAC). The outcomes of the propensity score (PS)-matched (1:1) patients receiving either GA or MAC were analyzed.Results: The PS matching identified 94 patients who received GA and 94 patients who received MAC. Both groups showed high rates of en bloc resection (GA, 95.7%; MAC, 97.9%; p=0.68) and complete resection (GA, 81.9%; MAC, 84.0%; p=0.14). There were no significant differences between the rates of adverse events (GA, 16.0%; MAC, 8.5%; p=0.18) in the anesthetic groups. Logistic regression analysis indicated that the method of anesthesia did not affect the rates of complete resection or adverse events.Conclusions: ESD of tumors in the mid-to-upper stomach at our high-volume center had good outcomes, regardless of the method of anesthesia. Our results demonstrate no differences between the efficacies and safety of ESD performed under MAC and GA.

Chemotherapy is ubiquitous in first-line treatment of advanced gastric cancer, yet responses are heterogeneous, and little is known about mediators of chemotherapy response. To move forward, an understanding of the effects of standard chemotherapy on the tumor–immune microenvironment (TME) is needed. Coupling whole-exome sequencing, bulk RNA and single-cell transcriptomics from paired pretreatment and on-treatment samples in treatment-naïve patients with HER2-positive and HER2-negative gastric cancer, we define features associated with response to platinum-based chemotherapy. Response was associated with on-treatment TME remodeling including natural killer (NK) cell recruitment, decreased tumor-associated macrophages, M1-macrophage repolarization, and increased effector T-cell infiltration. Among chemotherapy nonresponders, we observed low/absent PD-L1 expression or modulation, on-treatment increases in Wnt signaling, B-cell infiltration, and LAG3-expressing T cells coupled to an exodus of dendritic cells. We did not observe significant genomic changes in early on-treatment sampling. We provide a map of on-treatment TME modulation with standard chemotherapy and nominate candidate future approaches. Significance: Using paired pretreatment and on-treatment samples during standard first-line chemotherapy, we identify chemotherapy-induced NK-cell infiltration, macrophage repolarization, and increased antigen presentation among responders. Increased LAG3 expression and decreased dendritic cell abundance were seen in nonresponders, emphasizing remodeling of the TME during chemotherapy response and resistance. This article is highlighted in the In This Issue feature, p. 873

Helicobacter pylori (H. pylori) eradication can reduce the risk of gastric diseases such as gastritis, gastric ulcer, and gastric adenocarcinoma. Since H. pylori was discovered more than 30 years ago, many studies have reported associations between H. pylori infection and extragastric diseases such as immune thrombocytopenia and iron-deficiency anemia. Thus, recent guidelines recommended H. pylori eradication in patients with those diseases. In contrast, although the role of H. pylori eradication in other extragastric diseases remains controversial, there is growing evidence of its benefit on them, especially cardiovascular (ischemic heart disease and stroke), metabolic (dyslipidemia, diabetes mellitus, and non-alcoholic fatty liver disease), neurodegenerative (Parkinson’s disease and Alzheimer’s disease), autoimmune (Graves’ disease, Hashimoto’s thyroiditis, Raynaud’s syndrome, rosacea, and chronic urticaria), and other (cap polyposis, colorectal mucosa-associated lymphoid tissue lymphoma, periodontal disease, hyperemesis gravidarum, and osteoporosis) conditions. A recent prospective randomized study reported that H. pylori eradication improved insulin resistance and dyslipidemia. These findings were consistent with the results of a recent meta-analysis. Therefore, well-designed prospective interventional studies are needed to examine the effects of H. pylori eradication on various extragastric diseases.

Few studies have investigated the long-term outcomes of endoscopic resection for early gastric cancer (EGC) in very elderly patients. The aim of this study was to determine the appropriate treatment strategy and identify the risk factors for mortality in these patients.Patients with EGC who underwent endoscopic resection from 2006 to 2017 were identified using National Health Insurance Data and divided into three age groups: very elderly (≥85 years), elderly (65 to 84 years), and non-elderly (≤64 years). Their long- and short-term outcomes were compared in the three age groups, and the survival in the groups was compared with that in the control group, matched by age and sex. We also evaluated the risk factors for long- and short-term outcomes.A total of 8,426 patients were included in our study: 118 very elderly, 4,583 elderly, and 3,725 non-elderly. The overall survival and cancer-specific survival rates were significantly lower in the very elderly group than in the elderly and the non-elderly groups. Congestive heart failure was negatively associated with cancer-specific survival. A significantly decreased risk for mortality was observed in all groups (p0.001). The very elderly group had significantly higher readmission and mortality rates within 3 months of endoscopic resection than the non-elderly and elderly groups. Furthermore, the cerebrovascular disease was associated with mortality within 3 months after endoscopic resection.Endoscopic resection for EGC can be helpful for very elderly patients, and it may play a role in achieving overall survival comparable to that of the control group.

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

Background Exacerbation of inflammatory bowel disease (IBD) is common. Identification of the exacerbating factors could facilitate interventions for forecastable environmental factors through adjustment of the patient’s daily routine. We assessed the effect of natural environmental factors on the exacerbation of IBD. Methods In this systematic review and meta-analysis, studies published from January 1, 1992 to November 3th, 2022 were searched in the MEDLINE, Embase, CINAHL Complete and Cochrane Library databases. We extracted data related to the impact of environmental variations on IBD exacerbation, and performed a meta-analysis of the individual studies’ correlation coefficient χ2 converted into Cramér’s V (φc) with 95% confidence intervals (CI). Results A total of 7,346 publications were searched, and 20 studies (sample size 248–84,000 cases) were selected. A meta-analysis with seven studies was performed, and the pooled estimate of the correlation (φc) between the seasonal variations and IBD exacerbations among 4806 cases of IBD exacerbation was 0.11 (95% CI 0.07–0.14; I2 = 39%; p = 0.13). When divided into subtypes of IBD, the pooled estimate of φc in ulcerative colitis (six studies, n = 2649) was 0.07 (95% CI 0.03–0.11; I2 = 3%; p = 0.40) and in Crohn’s disease (three studies, n = 1597) was 0.12 (95% CI 0.07–0.18; I2 = 18%; p = 0.30). Conclusion There was a significant correlation between IBD exacerbation and seasonal variations, however, it was difficult to synthesize pooled results of other environmental indicators due to the small number of studies and the various types of reported outcome measures. For clinical implications, additional evidence through well-designed follow-up studies is needed. Protocol registration number (PROSPERO) CRD42022304916.

Esophagogastroduodenoscopy (EGD) is effective in reducing gastric cancer mortality through detection of early-stage cancer in areas with a high prevalence of gastric cancer. Although the risk of post-endoscopy advanced gastric cancer (AGC) is low, interval AGC remains a concern. We investigated the characteristics and predictors of interval AGC after negative EGD.We included 1257 patients with gastric cancer within 6 to 36 months of a "cancer-negative" index EGD between 2005 and 2021 at a tertiary university hospital in South Korea. Observation time on the index EGD was used as a quality indicator. We compared the clinical and endoscopic characteristics and quality indicators between interval AGC and screen-detected early gastric cancer (EGC).Within 6 to 36 months of negative EGD, 102 AGCs (8.1%) and 1155 EGCs (91.9%) were identified. The percentage of patients with shorter observation time (3 minutes) in the index EGD was higher in the interval AGC group than in the detected EGC group (P = .002). A multivariable analysis comparing screen-detected EGD and interval AGC was adjusted for age, sex, family history of gastric cancer, H. pylori status, endoscopic findings, and endoscopy-related factors including gastric observation time and interval time. A shorter observation time (3 minutes) (odds ratio, 2.27; 95% confidence interval, 1.20-4.30), and interval time2 years (odds ratio, 1.84; 95% confidence interval, 1.04-3.24) were associated with an increased risk of interval AGC.A shorter observation time during index EGD is an important predictor of interval AGC. Further, withdrawal time longer than 3 minutes may be a quality indicator for screening EGD.

Tae Jun Kim geht in diesem Beitrag der Frage nach, welcher Stellenwert der Sozialepidemiologie in der Problematisierung des dicken Körpers zukommt. Zwar ist es grundsätzlich begrüßenswert, dass hohes Körpergewicht auch als Produkt sozialer Einflussfaktoren diskutiert wird, verengt den Blick jedoch zu sehr auf den eigenen Lebensstil und die Verantwortung des Selbst in der Entstehung von hohem Körpergewicht.

Ann Kristin Augst und Tae Jun Kim widmen sich in diesem Beitrag der Stigmatisierung und Diskriminierung dicker Körper. Sie beschreiben die Gewordenheit gesellschaftlicher Annahmen über mehrgewichtige Menschen. Dabei betonen die beiden Autor*innen die Verquickung historischer Normen mit folgenreichen Zuschreibungen im Hier und Jetzt.

Tae Jun Kim skizziert in diesem Beitrag zunächst die Entstehungsgeschichte eines sogenannten Fat Activism im US-amerikanischen Raum und diskutiert im Anschluss die heterogenen und vielfältigen Ausrichtungen fat aktivistischer Denkweisen wie auch möglichen Problemlagen, die mit der Etablierung einer gemeinsamen fetten Identität einhergehen.

Treatment ofMedical records were obtained from the Common Data Model-converted sample Cohort of the National Health Insurance Service of Korea (NHIS-CDM). The target cohort included those who had been prescribed HP treatment and the comparator cohort included those who had not. The association between HP treatment and the risk of GC development was assessed using the Cox proportional hazard model. The incidences of GC according to the period after HP treatment in different age groups were analyzed using proportional trend tests.After large-scale 1:4 propensity score matching, 2735 and 5328 individuals were included in the target and comparator cohorts, respectively. During the median follow-up of 6.5 years, the GC incidence was lower in the HP treatment cohort than in the comparator cohort, but this was statistically insignificant (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.50-1.13;In all age groups of the general population, HP treatment could be recommended to reduce the risk of GC.

Background: Several studies have suggested an association between inflammatory bowel disease (IBD) and the risk of prostate cancer development. However, these findings are inconsistent, and studies based on Asian populations are limited. Objectives: We compared the risk of prostate cancer according to IBD status using the Korean National Health Insurance Service database. Design: A population-based retrospective cohort of age-matched 59,044 non-IBD patients and 14,761 IBD patients between January 2009 and December 2011 was analyzed up to December 2017. Methods: The risk of prostate cancer was compared between patients with IBD and controls using the Cox proportional hazards regression model and Kaplan-Meier survival analysis. Results: During a median follow-up of 6 years, the incidence rate of prostate cancer was 264 per 100,000 person-years in non-IBD patients and 242 per 100,000 person-years in patients with IBD. IBD status was not associated with the risk of prostate cancer compared to non-IBD [adjusted hazard ratio (aHR) 0.93, 95% confidence interval (CI): 0.80–1.08, p = 0.32). The cumulative incidence of prostate cancer did not differ by IBD status (non-IBD patients versus IBD patients: log-rank p = 0.27; non-IBD patients versus ulcerative colitis versus Crohn’s disease: log-rank p = 0.42). In multivariate analysis, age was an independent risk factor for the development of prostate cancer (HR 1.03, 95% CI: 1.02–1.03, p Conclusion: In our population-based study, IBD status was not associated with the risk of prostate cancer.

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

403 Background: Few studies have investigated the long-term outcomes of endoscopic resection for early gastric cancer (EGC) in very elderly patients. The aim of this study was to determine the appropriate treatment strategy and identify the risk factors for mortality in these patients. Methods: Patients with EGC who underwent endoscopic resection from 2006 to 2017 were identified using National Health Insurance Data and divided into three age groups: very elderly (≥85 years), elderly (65–84 years), and non-elderly (≤64 years). Their long- and short-term outcomes were compared in the three age groups, and the survival in the groups was compared with that in the control group, matched by age and gender. We also evaluated the risk factors for long- and short-term outcomes. Results: A total of 8,426 patients were included in our study: 118 very elderly, 4,583 elderly, and 3,725 non-elderly. The overall survival (OS) and cancer-specific survival (CSS) rates were significantly lower in the very elderly group than in the elderly and the non-elderly groups. Congestive heart failure was negatively associated with CSS. A significantly decreased risk for mortality was observed in all groups (P-value < 0.001). The very elderly group had significantly higher readmission and mortality rates within 3 months of endoscopic resection than the non-elderly and elderly groups. Further, cerebrovascular disease was associated with mortality within 3 months after endoscopic resection. Conclusions: Endoscopic resection for EGC can be helpful for very elderly patients, and it may play a role in achieving OS comparable to that of the control group.[Table: see text]

We propose an interface-engineered oxide-supported Pt nanoparticle-based catalyst with improved low-temperature activity toward CO oxidation. By wet-impregnating 1 wt % Ce on TiO

Background and aims: Previous studies have reported that metformin use in patients with diabetes mellitus may reduce the risk of colorectal cancer (CRC) incidence and prognosis; however, the evidence is not definite. This population-based cohort study aimed to investigate whether metformin reduces the risk of CRC incidence and prognosis in patients with diabetes mellitus using a common data model of the Korean National Health Insurance Service database from 2002 to 2013. Methods: Patients who used metformin for at least 6 months were defined as metformin users. The primary outcome was CRC incidence, and the secondary outcomes were the all-cause and CRC-specific mortality. Cox proportional hazard model was performed and large-scaled propensity score matching was used to control for potential confounding factors. Results: During the follow-up period of 81,738 person-years, the incidence rates (per 1000 person-years) of CRC were 5.18 and 8.12 in metformin users and non-users, respectively (p = 0.001). In the propensity score matched cohort, the risk of CRC incidence in metformin users was significantly lower than in non-users (hazard ratio (HR), 0.58; 95% CI (confidence interval), 0.47–0.71). In the sensitivity analysis, the lag period extending to 1 year showed similar results (HR: 0.63, 95% CI: 0.51–0.79). The all-cause mortality was significantly lower in metformin users than in non-users (HR: 0.71, 95% CI: 0.64–0.78); CRC-related mortality was also lower among metformin users. However, there was no significant difference (HR: 0.55, 95% CI: 0.26–1.08). Conclusions: Metformin use was associated with a reduced risk of CRC incidence and improved overall survival.

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

Proton pump inhibitors (PPIs) are commonly used for the treatment of gastric acid-related disorders, and are generally well tolerated. However, by reducing the secretion of gastric acid in the long term, PPI can increase the risk of inducing an imbalance in the gut microbiome composition. Moreover, gastric hypochlorhydria that is caused by PPIs favors the survival and migration of oral bacteria in the lower part of the gastrointestinal tract, with a possible induction of pro-inflammatory microenvironment. Therefore, gut dysbiosis that is associated with the use of PPI has been found to cause adverse infectious and inflammatory diseases. In this regard, adverse effects of the PPI-related gut dysbiosis have been reported in different observational studies, but their clinical relevance remains unclear. Therefore, the aim of this review was to explore the available data on the PPI-related gut dysbiosis in order to better understand its clinical significance.

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.

In this study, the regional climate of East Asia was dynamically downscaled using Hadley Centre Global Environmental Model version 3-Regional Atmosphere (HadGEM3-RA) forced by the historical simulation data (1979–2005) of HadGEM2-AO produced by the National Institute of Meteorological Sciences (NIMS). To understand the impact of corrected SST on regional climate simulation, we integrated the experiments using uncorrected (UC_SST) and Bias- and Variance-corrected (BCVC_SST) HadGEM2-AO SST and used the simulated data driven by the ERA-Interim reanalysis data and HadGEM2-AO data. Examination of the spatial distribution, statistics, and interannual variation on wintertime precipitation over East Asia indicates that BCVC_SST reduced the overestimation of the climatological mean precipitation. In order to understand the impact of corrected SST on variability, we investigated the relationship between winter snowfall in South Korea and SST over East Asia. The negative correlation coefficient between the winter precipitation and the SST of the seas surrounding Korea appears in the result of observation data. The experiment result using BCVC_SST simulated the negative correlation between the winter snowfall and the SST around Korea more realistically than that of the simulations using UC_SST and HadGEM2-AO data. These results indicate that corrected SST helps to improve the variability of snowfall and SST simulated by HadGEM3-RA. However, time lag about the years when had peak point of SST appeared in the results compared between BCVC_SST experiment and observation data. The peak years shown in the result of the BCVC_SST experiment were similar to that of HadGEM2-AO data. At these results, even though the corrected SST improves climatological mean and variability of simulated data, it has the limitation not to overcome the error such as time lag showed in GCM SST. Additionally, the analysis of the snowfall in South Korea describes that SST is passively used for the source of snowfall and atmospheric variables mainly lead the intensity and the amount of snowfall.