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

Advances in genomic technologies and the development of targeted therapeutics are making the use of precision medicine increasingly possible. In this study, we explored whether precision medicine can be applied for the management of refractory/relapsed pediatric solid tumors by discovering actionable alterations using targeted panel sequencing. Samples of refractory/relapsed pediatric solid tumors were tested using a targeted sequencing panel covering the exonic DNA sequences of 381 cancer genes and introns across 22 genes to detect clinically significant genomic aberrations in tumors. The molecular targets were tiered from 1 to 5 based on the presence of actionable genetic alterations, strength of supporting evidence, and drug availability in the Republic of Korea. From January 2016 to October 2018, 55 patients were enrolled. The median time from tissue acquisition to drug selection was 29 d (range 14–39), and tumor profiling was successful in 53 (96.4%) patients. A total of 27 actionable alterations in tiers 1–4 were detected in 20 patients (36.4%), and the majority of actionable alterations were copy number variations. The tiers of molecular alterations were tier 1 (clinical evidence) in 4 variants, tier 2 (preclinical evidence) in 8 variants, tier 3 (consensus opinion) in 2 variants, and tier 4 (actionable variants with a drug that is available in other countries but not in the Republic of Korea) in 9 variants. In one patient with relapsed neuroblastoma with ALK F1174L mutation and ALK amplification, lorlatinib was used in a compassionate use program, and it showed some efficacy. In conclusion, using a targeted sequencing panel to discover actionable alterations in relapsed/refractory pediatric solid tumors was practical and feasible. [ABSTRACT FROM AUTHOR]

We aimed to investigate the incidence of sugammadex-induced anaphylaxis in a large Korean population. We retrospectively investigated the incidence of sugammadex-induced anaphylaxis between 2013 and 2019 from the database of the Korea Institute of Drug Safety-Risk Management-Korea Adverse Event Reporting System (KIDS-KAERS). We estimated the incidence of sugammadex-induced anaphylaxis from the KIDS-KAERS database, assuming that the reporting efficiency was 10%, 50%, and 100%, respectively. We also investigated its annual sales volume in Korea and assumed that the exposure to sugammadex was 95% of the estimated sales volume. During the study period, 1,401,630 sugammadex vials were sold, and 19 cases of sugammadex-induced anaphylaxis were identified in the KIDS-KAERS database. The estimated incidence of sugammadex-induced anaphylaxis was 0.0143%, 0.00279%, and 0.0014%, assuming a reporting efficiency of 10%, 50%, and 100%, respectively. All patients, except for one with a missing record, fully recovered after anaphylaxis. The incidence of sugammadex-induced anaphylaxis identified in the national pharmacovigilance database was lower than previously reported rates in other countries. Therefore, its use in general anesthesia should not be hindered by concerns about the resulting risk of anaphylaxis in Korea. [ABSTRACT FROM AUTHOR]

Background/Aims Despite numerous studies on the relation of genetic polymorphisms with irritable bowel syndrome (IBS), the results still remain inconclusive. The aim of this study was to assess the possible association between SLC6A4 serotonin transporter gene linked polymorphic region (5-HTTLPR), ADRA2A -1291C>G, GNB3 825C>T, CCK1R intron 779T>C and TRPV1 945G>C polymorphisms and IBS based on Rome III criteria in Korea. Methods Study subjects were prospectively recruited from visitors to Seoul National University Bundang Hospital between July 2009 and January 2014. Ninety-nine IBS patients and 171 healthy controls were enrolled. Polymorphisms of above-mentioned 5 genes were genotyped. Serum serotonin from 101 participants was measured by ELISA and compared according to SLC6A4 5-HTTLPR polymorphisms and IBS subtypes. Results Regarding SLC6A4 5-HTTLPR polymorphism, L/L genotype was significantly associated with the total IBS, constipation predom - inant IBS (IBS-C) and mixture of diarrhea and constipation IBS (IBS-M) (adjusted OR: 4.35, 95% CI: 1.04-16.67; adjusted OR: 11.11, 95% CI: 1.69-50.00 and adjusted OR: 5.56, 95% CI: 1.05-33.33, respectively). Carrying ADRA2A -1291G allele was significantly associated with total IBS and diarrhea predominant IBS (adjusted OR: 3.37, 95% CI: 1.16-9.77 and adjusted OR: 5.64, 95% CI: 1.18-27.01, respectively). IBS-C patients showed reduced level of serum serotonin compared to controls and patients with diarrhea predominant IBS (50.2 ng/mL vs. 69.0 ng/mL and 92.9 ng/mL, P = 0.017 and P = 0.001, respectively). Conclusions Genetic polymorphisms of SLC6A4 5-HTTLPR and ADRA2A -1291C>G could be one of the pathophysiological factors of IBS in Korea. Reduced serum serotonin shown in the IBS-C group suggested a role of serotonin in IBS, but large study is needed for confirming genotypic difference in serum serotonin level. [ABSTRACT FROM AUTHOR]

Background and aims: Resting heart rate is an independent predictor of colorectal cancer (CRC) development and CRC-related mortality. However, little is known about the relationship between resting heart rate and colorectal adenoma development. We aimed to investigate this association in a population who underwent screening colonoscopy. Methods: Among 39,021 patients who underwent both electrocardiogram and screening colonoscopy during routine health examinations at the Seoul National University Bundang Hospital, Health Promotion Center, Korea from January 2014 to July 2019, 1,344 patients had advanced adenoma. We performed 1:1 propensity score (PS) matching to establish a control group that mitigated the confounding effects of age and sex. We performed multivariate logistic regression analyses to identify the independent risk factors of advanced adenoma development. Results: Resting heart rate was significantly higher in the advanced adenoma group than in the control group. The prevalence of advanced polyp increased across the quartiles of resting heart rate. Patients with higher resting heart rates were more likely to be older, smokers, and have increased blood pressure and DM and less likely to engage in active exercises than those with lower resting heart rates. Patients with higher resting heart rates had higher serum glucose, triglyceride, hemoglobin A1C, and insulin levels and lower high-density lipoprotein cholesterol levels. Patients with resting heart rate in the highest quartile (≥71 bpm) still showed significantly increased odds ratio (OR) of advanced adenoma development (OR: 1.379, 95% confidence interval: 1.099–1.731, p = 0.006). Conclusions: High resting heart rate was a meaningful independent risk factor of advanced adenoma development. [ABSTRACT FROM AUTHOR]

Summary: Background: Inflammatory bowel disease (IBD) is accompanied by various extraintestinal manifestations including systemic inflammation and hypercoagulability, which may increase the risk of atherosclerosis and ischaemic heart disease. Aim: To investigate whether IBD is associated with an increased risk of myocardial infarction (MI), stroke or death Methods: The International Classification of Disease, 10th edition codes and the claim codes for rare diseases were used to identify candidates from National Health Insurance Service (NHIS) of South Korea. Patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2006 and 2009 were age‐matched 1:3 with NHIS enrolees without IBD. The primary outcomes included newly developed MI, stroke and death. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models. Results: We identified 10 708 patients diagnosed with CD and 26 769 with UC. MI risk was higher in CD patients than in controls (incidence ratio (IR) 1.64 per 1000 person‐years, HR, 1.80; 95% CI, 1.47‐2.21), and this trend was more prominent among patients aged <40 years (IR 0.69 per 1000 person‐years, HR, 2.96; 95% CI, 1.96‐4.47) and among female patients (IR 2.35 per 1000 person‐years, HR, 2.18; 95% CI, 1.61‐2.94). In contrast, only female patients with UC had an increased risk of MI (IR 2.01 per 1000 person‐years, HR, 1.33; 95% CI, 1.13‐1.56). Conclusions: The risk of MI risk is higher in patients with CD than in the general population, and this trend is stronger in female patients and those aged <40 years. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic findings of low-volume alcohol consumption in relation to gastrointestinal cancers including gastric cancer are inconsistent. Methods: The association between alcohol intake and esophageal, gastric and colorectal cancer risk was examined in a population-based prospective cohort of 23,323,730 adults in Korea who had undergone a biennial evaluation provided by the National Health Insurance Corporation between the years 2009 and 2012. After median 5.4 years of follow-up, 9,171 esophageal, 135,382 gastric and 154,970 colorectal cancer cases were identified. Cox regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Results: Light drinking as well as moderate to heavy alcohol consumption significantly increased the risks of the three gastrointestinal cancers (HR 1.51; 95% CI, 1.43–1.60; HR 1.08; 95% CI, 1.06–1.09; HR 1.12; 95% CI, 1.11–1.14) compared with non-drinkers after adjusting for age, sex, smoking, exercise, income, body mass index, and diabetes. The synergistically increased cancer risk between excessive amount of alcohol consumption and currently smoking or underweight individuals was observed only in the esophageal cancers. Conclusions: Light drinking including even one alcoholic drink a day is associated with increased risks of esophageal, gastric and colorectal cancer. [ABSTRACT FROM AUTHOR]

The aim of the study is to evaluate the risk of heart disease in individuals who underwent cholecystectomy. This was a retrospective cohort study using the National Health Insurance Service database of South Korea. A total of 146,928 patients who underwent cholecystectomy and 268,502 age- and sex-matched controls were compared. Multivariate Cox proportional hazard regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for heart disease after cholecystectomy. In results, a previous history of cholecystectomy increased the risk of heart disease (congestive heart failure [CHF], myocardial infarction [MI], atrial fibrillation [AF]) (adjusted HR [aHR]: 1.40, 95% CI: [1.36–1.44]). The increased risk was particularly seen for CHF (1.22 [1.16–1.29]) but not for MI and AF (p > 0.05). In the subgroup analyses, cholecystectomy was associated with an increased risk of MI in patients aged <65 years (1.49 [1.16–1.92] and 1.18 [1.05–1.35] in patients aged 40–49 and 50–64 years, respectively), but not in those aged ≥ 65 years (0.932 [0.838–1.037]). Moreover, the risk of MI was increased in patients without diabetes mellitus (DM) (1.16 [1.06–1.27]); however, it was decreased in patients with DM (0.83 [0.72–0.97]). In contrast, cholecystectomy did not modify the risk of AF in the subgroup analyses (all p > 0.05). In conclusion, a history of cholecystectomy is associated with an increased risk of CHF. Cholecystectomy may increase the risk of MI in the younger population without DM. These findings suggest that the alteration of bile metabolism and homeostasis might be potentially associated with the development of some heart diseases. [ABSTRACT FROM AUTHOR]