Purpose: The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and Methods: This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. Results: Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]). Conclusion Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Purpose: There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136). Materials and Methods: Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival. Results: Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations. Conclusion Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Background/Aims: A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028. Methods: Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC. Results: The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P<0.001). The estimated CR (17.9 per 100,000 person-years) and ASR (9.7 per 100,000 person-years) of HCC incidence in 2028 was declined, but the number of HCC patients aged ≥80 years in 2028 will be quadruple greater than the number of HCC patients in 2008 (from 521 to 2,055), comprising 21.3% of all HCC patients in 2028. Conclusions The ASRs of HCC in Korea have gradually declined over the past 10 years, but the number, CR, and ASR are increasing in patients aged ≥80 years.

Background and Objectives: A large-scale community-based study of the general population has not been conducted. There have been no studies on the relationship between decreased renal function and the degree of hearing loss. Thus, the purpose was to evaluate the relationship between hearing loss and impaired renal function with a large number of populations.Subjects and Method We performed a cross-sectional population-based cohort study by enrolling 470718 adults, 18 to 80 years old with pure tone audiometry tests who had regular health screening between 2013 and 2018. Hearing loss was defined as a pure-tone average of thresholds at 500, 1000, and 2000 Hz in both right and left ears. Kidney function was evaluated based on eGFR. Chronic kidney disease (CKD) was diagnosed as an eGFR<60 mL/ min/1.73 m². Other predictor variables including noise and age that can affect hearing were also used to evaluate correlation factors. Results: Of Participants with CKD, 14.2% had any hearing loss (>25 dB) and 5.0% had above moderate hearing loss (>40 dB). But those with normal kidney function, 2.0% either had any hearing loss and 0.4% had above moderate hearing loss. The odds ratio (OR) of above moderate hearing loss for participants with CKD was 1.51 (95% confidence interval [CI]: 1.15-2.00, p=0.003) but the OR of mild hearing loss for participants with CKD was 0.82 (95% CI: 0.67- 1.02, p=0.073). The result suggested that CKD and above moderate hearing loss were related even after correcting for potential confounders, but had no statistical significance with mild hearing loss. Conclusion Decreased kidney function is associated with above moderate hearing loss.

Neuroendocrine carcinoma (NEC) is a rare form of hormone-secreting tumor. NECs originate from the epithelial cells of the larynx and account for less than 1% of the laryngeal neoplasm. Most cases of NECs are diagnosed by pathological confirmation after surgery. The terminology of laryngeal NEC has been a source of confusion. In 2017, World Health Organization newly categorized laryngeal NEC; as a result, the large cell type, which has been the main target of disagreement, was finally included into a subtype of poorly differentiated NEC. We report a case of a 58-year-old male with a growing granulomatous mass in the posterior supraglottis. The granuloma was removed by surgical excision when the size of the mass increased. He was diagnosed with the large cell type laryngeal NEC by pathological confirmation. He underwent postoperative radiotherapy and is currently being followed up in our outpatient clinic without evidence of recurrence.

Purpose: The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated. Materials and Methods: A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core. Results: The density of CD8+ T cells, FoxP3- CD4+ helper T cells, and FoxP3+ CD4+ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8+ T cell and FoxP3- CD4+ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3- CD4+ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3- CD4+ helper T cells in the tumor margin was independently associated with favorable PFS and OS. Conclusion The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3- CD4+ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

Background/Aims: PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. Methods: MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. Results: Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. Conclusions Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is becoming a global health problem. Bisphenol A (BPA), one of most widely used environmental chemicals, is suspected to be a contributor to the development NAFLD. This study was performed to examine the relationship between human BPA levels and risk of NAFLD. METHODS: The data (n = 3476 adults: 1474 men and 2002 women) used in this study were obtained from the Korean National Environmental Health Survey III (2015-2017). BPA levels were measured in urine samples. NAFLD was defined using hepatic steatosis index after exclusion of other causes of hepatic diseases. RESULTS: There was a significant linear relationship between the elevated urinary BPA concentrations and risk of NAFLD. In a univariate analysis, odds ratio (OR) of the highest quartile of urinary BPA level was 1.47 [95% confidence interval (CI) 1.11-1.94] compared to the lowest quartile. After adjusted with covariates, the ORs for NAFLD in the third and fourth quartiles were 1.31 [95% CI 1.03-1.67] and 1.32 [95% CI 1.03-1.70], respectively. CONCLUSIONS Urinary BPA levels are positively associated with the risk of NAFLD in adults. Further experimental studies are needed to understand the molecular mechanisms of BPA on NAFLD prevalence.
Asians ; Benzhydryl Compounds/urine* ; Environmental Exposure ; Environmental Health ; Female ; Health Surveys ; Humans ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/epidemiology* ; Phenols/urine* ; Republic of Korea/epidemiology*

Purpose: The objective of this study was to modify and validate an emergency department (ED) triage system with improved prediction performance on hospital outcomes by modifying the Korean Triage and Acuity Scale (KTAS). Materials and Methods: We performed a retrospective observational study at three academic universities in South Korea. The KTAS code, determined by the chief complaint and the selected modifier of a patient, was used to derive the Modified KTAS (MKTAS). We calculated the area under the receiver operating characteristics curve (AUC) and the test characteristics to evaluate the performance of MKTAS to predict hospital mortality, critical outcome, and admission. Results: A total of 272402 and 128831 ED visits were used for the derivation and validation of MKTAS, respectively. Compared to KTAS, MKTAS had significantly higher AUC values for the prediction of hospital mortality [MKTAS 0.826 (0.818–0.835) vs. KTAS 0.794 (0.784–0.803)], critical outcome [MKTAS 0.836 (0.830–0.841) vs. 0.798 (0.792–0.804)], and admission [MKTAS 0.725 (0.723– 0.728) vs. KTAS 0.685 (0.682–0.688)]. The sensitivity for predicting hospital mortality and critical outcome, as well as the specificity for predicting admission, were significantly improved. Conclusion MKTAS was derived by modifying the KTAS, and then validated. Compared with KTAS, MKTAS showed better discriminating ability to predict hospital outcomes. Continuous efforts to evaluate and modify widely used triage systems are required to improve their performance.

Objective: This study described the effectiveness of the one-stop treat system (OTS) and the improvements characterizing the patients who come to an emergency medical center via the one-stop treat system for heavily drunken people Methods: An observational retrospective study was conducted on patients, aged 19 years or older, who visited the emergency department (ED) from January 2014 to December 2017 with alcohol intoxication (AI). The subjects were divided into two groups, that is, AI patients who come to ED directly or those who came via OTS. We compared and analyzed the characteristics of two groups including gender, age, date, mode of the ED visit, level of consciousness, diagnosis, ED length of stay (LOS), hospital LOS, and final outcomes. Results: A total of 8,144 patients were enrolled in the study. There were 2,221 AI patients who visited ED directly and 5,923 AI patients who visited ED via OTS. Patients arriving via OTS had more medical or surgical problems than the patients who came directly from the ED. Discharged patients via OTS showed a longer ED LOS (312 minutes [range, 169-520 minutes], P<0.001). Compared with patients who came directly from ED, the patients via OTS showed a higher admission rate (10.7% vs. 3.4%, respectively; P<0.001), and a higher death rate in ED (0.6% vs. 0%, respectively; P<0.001). Conclusion Compared the characteristics of the patients from ED directly in 2014-2017, the patients via OTS had higher severity and admission rate, and a longer ED LOS. Our findings suggest that we should pay attention to patients via OTS because the patients have high severity of illness.