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Background and Objectives: This study aimed to elucidate the cytologic characteristics and diagnostic usefulness of endoscopic ultrasonography–fine needle aspiration cytology (EUS-FNAC) by comparing it with liquid-based preparation (LBP) and conventional smear (CS) in pancreas. Methods: The diagnostic categories (I through VII) were classified according to the World Health Organization Reporting System for Pancreaticobiliary Cytopathology. Ten cytologic features, including nuclear and additional features, were evaluated in 53 cases subjected to EUS-FNAC. Nuclear features comprised irregular nuclear contours, nuclear enlargement, hypochromatic nuclei with parachromatin clearing, and nucleoli. Additional cellular features included isolated atypical cells, mucinous cytoplasm, drunken honeycomb architecture, mitosis, necrotic background, and cellularity. A decision tree analysis was conducted to assess diagnostic efficacy. Results: The diagnostic concordance rate between LBP and CS was 49.1% (26 out of 53 cases). No significant differences in nuclear features were observed between categories III (atypical), VI (suspicious for malignancy), and VII (malignant). The decision tree analysis of LBP indicated that cases with moderate or high cellularity and mitosis could be considered diagnostic for those exhibiting nuclear atypia. Furthermore, in CS, mitosis, isolated atypical cells, and necrotic background exerted a more significant impact on the diagnosis of EUS-FNAC. Conclusions: Significant parameters for interpreting EUS-FNAC may differ between LBP and CS. While nuclear atypia did not influence the diagnosis of categories III, VI, and VII, other cytopathologic features, such as cellularity, mitosis, and necrotic background, may present challenges in diagnosing EUS-FNAC.

Background/Aims: This study aimed to investigate the patterns of preferred endoscopic procedure types and techniques for managing difficult common bile duct (CBD) stones in South Korea. Methods: The Committee of Policy and Quality Management of Korean Pancreatobiliary Association (KPBA) conducted a survey containing 19 questions. Both paper and online surveys were carried out; with the paper survey being conducted during the 2019 Annual Congress of KPBA and the online survey being conducted through Google Forms from April 2020 to February 2021. Results: The response rate was approximately 41.3% (86/208). Sixty-two (73.0%) worked at tertiary hospitals or academic medical centers, and 60 (69.7%) had more than 5 years of endoscopic retrograde cholangiopancreatography experience. The preferred size criteria for large CBD stones were 15 mm (40.6%), 20 mm (31.3%), and 30 mm (4.6%). For managing of large CBD stones, endoscopic papillary large balloon dilation after endoscopic sphincterotomy was the most preferred technique (74.4%). When performing procedures in those with bleeding diathesis, 64 (74.4%) respondents favored endoscopic papillary balloon dilation (EPBD) alone or EPBD with small endoscopic sphincterotomy. Fifty-five respondents (63.9%) preferred the doubleguidewire technique when faced with difficult bile duct cannulation in patients with periampullary diverticulum. In surgically altered anatomies, cap-fitted forward viewing endoscopy (76.7%) and percutaneous transhepatic cholangioscopy (48.8%) were the preferred techniques for Billroth-II anastomosis and total gastrectomy with Roux-en-Y anastomosis, respectively. Conclusions: Most respondents showed unifying trends for the management of difficult CBD stones. The current practice patterns could be used as basic data for clinical quality improvements in the management of difficult CBD stones.

Background/Aims: Although endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) and fine needle biopsy (FNB) are widely used for tissue acquisition of pancreatic solid mass, the optimal strategy of this procedure has not been established yet. The aim of this nationwide study was to investigate the current practice patterns of EUS-FNA/FNB for pancreatic solid mass in Korea. Methods: The Policy-Quality Management of the Korean Pancreatobiliary Association (KPBA) developed a questionnaire containing 22 questions. An electronic survey consisting of the questionnaire was distributed by e-mail to members registered to the KPBA. Results: A total of 101 respondents completed the survey. Eighty respondents (79.2%) performed preoperative EUS-FNA/FNB for operable pancreatic solid mass. Acquire needles (60.4%) were used the most, followed by ProCore needles (47.5%). In terms of need size, most respondents (>80%) preferred 22-gauge needles regardless of the location of the mass. Negative suction with a 10-mL syringe (71.3%) as sampling technique was followed by stylet slow-pull (41.6%). More than three needle passes for EUS-FNA/FNB was performed by most respondents (>80%). The frequency of requiring repeated procedure was significantly higher in respondents with a low individual volume (

Objectives The hypertriglyceridaemic waist (HTGW) phenotype, an indicator to assess metabolic syndrome, could be a useful predictive marker for the risk of acute pancreatitis. This study aimed to evaluate the association between the HTGW phenotype and the risk of acute pancreatitis with a nationwide population-based cohort.Design A retrospective, nationwide cohort study.Setting Registry of health check-up result from Korean National Health Insurance Service.Participants A total of 3 912 551 adults who underwent health checkups under the National Health Insurance Service in 2009 were enrolled in this study.Interventions Subjects with both increased waist circumference (WC) and elevated blood triglyceride concentrations were defined as the HTGW phenotype. The participants were divided into four groups, classified as NWNT (normal WC-normal triglycerides), EWNT (elevated WC-normal triglycerides), NWET (normal WC-elevated triglycerides) and HTGW. The WC triglyceride index (WTI) is a quantitative indicator of the HTGW phenotype which is calculated by multiplying WC (cm) by triglyceride levels (mmol/L).Primary outcome measure The subjects were followed until 31 December 2018. The adjusted HRs of acute pancreatitis in each group were estimated.Results During the follow-up, there were a total of 8933 of acute pancreatitis occurrences. The incidence of acute pancreatitis in all subjects was 0.278 per 1000 person-year. The HTGW group had the highest incidence (0.444), followed by the NWET (0.381), and EWNT (0.316) groups. The HTGW group had a significant higher incidence of acute pancreatitis than the NWNT groups (HR 1.364 (95% CI 1.279 to 1.454)). The risk of acute pancreatitis steadily increased as the WTI increased (HR 1.847 (95% CI 1.657 to 2.058) in 10th decile).Conclusions The HTGW phenotype is confirmed to be an independent risk factor that increases the risk of acute pancreatitis.

Fluoroscopy is used frequently during endoscopic procedures, such as endoscopic retrograde cholangiopancreatography (ERCP). However, exposure to radiation is an important health concern, primarily because of the potential increase in the lifetime risk of malignancy. This consideration is important for patients and staff exposed to radiation during ERCP. Thus, an understanding of how radiation doses are measured during ERCP and the potential risks of this radiation is important. Additionally, staff must be educated about methods used to minimize the radiation dose, such as the use of different imaging techniques, the general principles of fluoroscopy, and advances in hardware and software. The use of personal protective equipment is also essential to minimize occupational exposure. However, no comprehensive ERCP guideline on the use of X-ray systems in clinical settings or on radiation protection for operators has been established. This review focuses on the properties of fluoroscopy systems and methods of radiation protection for physicians and assistants participating in ERCP.

Background/Aims: Helicobacter pylori (H. pylori) infection highly correlates with erythematous/exudative gastritis, which is one of the endoscopic findings of the Sydney classification system. The present study aimed to evaluate the association between endoscopic severity of erythematous/exudative gastritis and H. pylori infection. Methods: We prospectively enrolled asymptomatic adults who were diagnosed with erythematous/exudative gastritis during screening esophagogastroduodenoscopy. A rapid urease test was performed in all participants to diagnose H. pylori infection. The severity of erythematous/exudative gastritis was determined based on the Sydney classification system. Two investigators independently evaluated the endoscopic findings. The primary endpoint was H. pylori infection rate according to the severity of erythematous/exudative gastritis (mild vs. moderate-to-severe). Results: A total of 177 patients with erythematous/exudative gastritis were included. The rate of H. pylori infection was 86.4% in all patients. Of 177 included patients, 78 were at mild degree, 48 were at moderate degree, and 51 were at severe degree. The inter-observer variation was 4.6% and kappa value was 0.593. H. pylori infection rate was similar between patients with mild erythematous/exudative gastritis and those with moderate-to-severe erythematous/exudative gastritis (91.0% vs. 82.8%, p=0.115). Even after adjusting potential confounding variables, the severity of erythematous/exudative gastritis was not associated with H. pylori infection rate. Conclusions: H. pylori infection is commonly observed in patients with erythematous/exudative gastritis. However, the severity of erythematous/exudative gastritis is not associated with H. pylori infection rate.

Background/Aims Endoscopic channels are difficult to clean and can cause infection transmission. We examined the effectiveness of a newly developed channel-cleaning ball brush (BB), which is sucked into the endoscopic channel and scrapes and cleans the lumen as it passes through. Methods The upper and lower gastrointestinal endoscopes used for patient examinations were randomly selected as the conventional brush (CB) or BB group. After manual cleaning, the presence or absence of carbohydrates, proteins, adenosine triphosphate, and hemoglobin was assessed. Results Fifty-six and 58 endoscopes were cleaned with the CB and BB, respectively. Carbohydrate and protein were detected in one (1.8%) and two endoscopes (3.4%) in the CB and BB groups, respectively (p=1.000). Hemoglobin was observed in one (1.8%) and three endoscopes (5.2%) in the CB and BB groups, respectively (p=0.636). The adenosine triphosphate levels were 10.6±15.9 and 12.5±14.3 relative light units in the CB and BB groups, respectively (p=0.496). Twenty-seven (48.2%) and 19 (32.8%) endoscopes were positive for microbial cultures in the CB and BB groups, respectively (p=0.136). Conclusions The efficacy of BB was not significantly different from that of CB in the endoscopic channel-cleaning process.

Background/Aims: We examined the efficacy and safety of tegoprazan as a part of first-line triple therapy for Helicobacter pylori eradication. Methods: A randomized, double-blind, controlled, multicenter study was performed to evaluate whether tegoprazan (50 mg)-based triple therapy (TPZ) was noninferior to lansoprazole (30 mg)- based triple therapy (LPZ) (with amoxicillin 1 g and clarithromycin 500 mg; all administered twice daily for 7 days) for treating H. pylori. The primary endpoint was the H. pylori eradication rate. Subgroup analyses were performed according to the cytochrome P450 (CYP) 2C19 genotype, the minimum inhibitory concentration (MIC) of amoxicillin and clarithromycin, and underlying gastric diseases. Results: In total, 350 H. pylori-positive patients were randomly allocated to the TPZ or LPZ group. The H. pylori eradication rates in the TPZ and LPZ groups were 62.86% (110/175) and 60.57% (106/175) in an intention-to-treat analysis and 69.33% (104/150) and 67.33% (101/150) in a per-protocol analysis (non-inferiority test, p=0.009 and p=0.013), respectively. Subgroup analyses according to MICs or CYP2C19 did not show remarkable differences in eradication rate. Both first-line triple therapies were well-tolerated with no notable differences. Conclusions: TPZ is as effective as proton pump inhibitor-based triple therapy and is as safe as first-line H. pylori eradication therapy but does not overcome the clarithromycin resistance of H. pylori in Korea (ClinicalTrials.gov identifier NCT03317223).

Background/Aims The study aimed to investigate the current practice patterns in the management of pancreatic cystic neoplasms in Korea. Methods An electronic survey was systematically distributed by email to members of the Korean Pancreatobiliary Association from December 2019 to February 2020. Results In total, 115 (110 gastroenterologists, five surgeons) completed the survey, 72.2% of whom worked in a tertiary/academic medical center. Most (65.2%) followed the 2012/2017 International Association of Pancreatology guidelines for the management of pancreatic cystic neoplasms. A gadolinium-enhanced magnetic resonance imaging/magnetic resonance cholangiopancreatography was the most common first-line diagnostic modality (42.1%), but a contrast-enhanced computed tomography scan was preferred as a subsequent surveillance tool (58.3%). Seventy-four percent of respondents routinely performed endoscopic ultrasound-guided fine needle aspiration for pancreatic cystic neoplasms with suspicious mural nodules. Endoscopic ultrasound-guided fine needle aspiration cytology (94.8%) and cystic fluid carcinoembryonic antigen (95.7%) were used for cystic fluid analysis. Most (94%) typically recommended surgery in patients with high-risk stigmata, but 18.3% also considered proceeding with surgery in patients with worrisome features. Most (96.5%) would continue surveillance of pancreatic cystic neoplasms for more than 5 years. Conclusions According to this survey, there was variability in the management of pancreatic cystic neoplasms among the respondents. These results suggest that the development of evidence-based guidelines for pancreatic cystic neoplasms that fit the Korean practice is needed to create an optimal approach to the management of pancreatic cystic neoplasms.

Background: This study aimed to compare the diagnostic accuracy of the Ki-67 labeling index (LI) between endoscopic ultrasonography-fine-needle aspiration cytology/biopsy (EUS-FNAC/FNB) and surgical specimens of pancreatic neuroendocrine neoplasms (PanNENs). Methods: Conventional meta-analysis and diagnostic test accuracy (DTA) reviews were performed on 17 eligible studies. The DTA review involved calculating the sensitivity, specificity, diagnostic odds ratio (OR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve. In addition, subgroup analysis was conducted based on EUS-FNAC and FNB, tumor grade, and tumor size. Results: The overall concordance rate of WHO grade based on Ki-67 LI between the EUS-FNAC/FNB and the surgical specimen was 0.767 (95% confidence interval (CI), 0.713–0.814). Concordance rates of the EUS-FNAC and EUS-FNB subgroups were 0.741 (95% CI, 0.681–0.794) and 0.839 (95% CI, 0.738–0.906), respectively. In the DTA review for grade 3, the sensitivity and specificity were calculated to be 0.786 (95% CI, 0.590–0.917) and 0.998 (95% CI, 0.987–1.000), respectively. The diagnostic OR and AUC of the SROC curve were 150.220 (95% CI, 46.145–489.000) and 0.983, respectively. The sensitivity and specificity were observed to be highest in the grade 1 and 3 subgroups, respectively. Conclusions: Higher concordance of tumor grade based on Ki-67 LI was observed between EUS-FNAC/FNB and surgical specimens, indicating the potential usefulness of Ki-67 LI in predicting PanNEN tumor grade in EUS-FNAC/FNB.

Background/Aims: The work environment in which endoscopic retrograde cholangiopancreatography (ERCP) is conducted has influence on its efficacy and safety. We aimed to assess the current status of ERCP work environments and to investigate the trends associated with the basic techniques of ERCP in Korea. Methods: The work environment and information on the basic techniques of ERCP were acquired by the Korean Pancreatobiliary Association (KPBA) through a national survey in 2019. The survey was performed at the KPBA conference in 2019. The contents of survey comprised of the current environment of ERCP, preparation before ERCP, and the preferred basic techniques used in ERCP. Results: Completed questionnaires were returned from 84 KPBA members. The mean ERCP volume per year was approximately 500. About 60% (50/84) reported that they worked with a dedicated ERCP team with experienced nurses. Two-thirds (57/84, 68%) answered that they had a fluoroscopy room used solely for ERCP procedures. All respondents intravenously hydrated the patient to prevent post-ERCP pancreatitis (84/84, 100%). The preferred procedural sedations were balanced propofol sedation (50%) and midazolam-only sedation (47%). Wire-guided cannulation was most commonly used for selective cannulation (81%). Endoscopic retrograde biliary drainage was preferred over endoscopic nasobiliary drainage (60% vs 22%). The initial method of ampullary intervention was endoscopic sphincterotomy in 60%. Conclusions: Data from the survey involving a large number of Korean ERCP doctors revealed considerable variabilities with regard to the work environment and basic techniques of ERCP in Korea. The study provides information regarding the current trends of ERCP that can be used to establish ERCP standards in Korea.

This study aimed to elucidate the prognostic implications of intratumoral and peritumoral infiltrating T-lymphocytes in pancreatic ductal adenocarcinoma (PDAC) through a meta-analysis. A total of 18 eligible studies and 2453 PDAC patients were included in the present study. Intratumoral and peritumoral infiltrating lymphocytes were evaluated using various markers, such as CD3, CD4, CD8, FOXP3, and immune cell score. The correlations between these parameters and overall and disease-free survival were investigated and used in the meta-analysis. High intratumoral infiltration of CD3-, CD4-, and CD8-expressing lymphocytes was significantly correlated with better overall survival (hazard ratio (HR) 0.747, 95% confidence interval (CI) 0.620–0.900, HR 0.755, 95% CI 0.632–0.902, and HR 0.754, 95% CI 0.611–0.930, respectively). However, there was no significant correlation between PDAC prognosis and intratumoral FOXP3 or immune cell score (HR 1.358, 95% CI 1.115–1.655 and HR 0.776, 95% CI 0.566–1.065, respectively). Moreover, there was no significant correlation between the prognosis and peritumoral infiltrating T-lymphocytes. In evaluations of disease-free survival, only high intratumoral CD4 infiltration was correlated with a better prognosis (HR 0.525, 95% CI 0.341–0.810). Our results showed that high intratumoral infiltrating lymphocytes were significantly correlated with a better PDAC prognosis. However, among the tumor-infiltrating lymphocytes, CD3, CD4, and CD8 had prognostic implications, but not FOXP3 and immune cell score.

This study aims to examine the clinicopathological and prognostic significance of the YKL-40 immunohistochemical expression of tumor and immune cells through human colorectal cancer (CRC) tissue. We performed immunohistochemistry for YKL-40 and investigated the clinicopathological and prognostic impact of the YKL-40 expression of tumor (T-YKL-40) and immune cells (I-YKL-40) in CRC. We also evaluated the correlation between YKL-40 and PD-L1 expression and the immunoscore. YKL-40 was expressed in 22.6% and 64.2% of T-YKL-40 and I-YKL-40, respectively, out of the 265 CRC tissues. The I-YKL-40 expression significantly correlated with well and moderately differentiated tumors. The PD-L1 expression in immune cells significantly correlated with the I-YKL-40 expression, but not T-YKL-40 expression (p = 0.020 and p = 0.846, respectively). The I-YKL-40 expression significantly correlated with a worse overall survival rate but not recurrence-free survival (p = 0.047 and p = 0.080, respectively). However, there was no significant correlation between the T-YKL-40 expression and survival. In CRCs with a high immunoscore, patients with I-YKL-40 expression demonstrated worse overall and recurrence-free survival than those without I-YKL-40 expression. Our results demonstrated that I-YKL-40 expression significantly correlated with tumor differentiation and PD-L1 expression in immune cells. I-YKL-40 expression can be useful for the prognostic stratification of CRC patients.

Abstract Cancer-associated fibroblasts (CAFs) participate in critical processes in the tumor microenvironment, such as extracellular matrix remodeling, reciprocal signaling interactions with cancer cells and crosstalk with infiltrating inflammatory cells. However, the relationships between CAFs and survival are not well known in lung cancer. The aim of this study was to reveal the correlations of CAFs with survival rates, genetic alterations and immune activities. This study reviewed the histological features of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database. We performed gene set enrichment analysis (GSEA), network-based analysis and survival analysis based on CAFs in four histological types of lung adenocarcinoma: acinar, papillary, micropapillary and solid. We found four hallmark gene sets, the epithelial-mesenchymal transition, angiogenesis, hypoxia, and inflammatory response gene sets, that were associated with the presence of CAFs. CAFs were associated with tumor proliferation, elevated memory CD4+T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, CAFs were related to blood vessel remodeling, matrix organization, negative regulation of apoptosis and transforming growth factor-β signaling. In the survival analysis of each histological type, CAFs were associated with poor prognosis in the solid type. These results may contribute to the development of therapeutic strategies against lung adenocarcinoma cases in which CAFs are present.

Background/Aims: Although the diarrheal disease caused by Campylobacter bacteria has been continuously increasing in Korea, there has been limited study on the clinical aspects of Campylobacter enteritis in adults in Korea. The purpose of this study was to analyze the clinical features and characteristics of adult patients with Campylobacter enteritis. Methods: This retrospective study included patients diagnosed with Campylobacter enterocolitis at Nowon Eulji University Hopsital between January 2016 and December 2017. Campylobacter enterocolitis was diagnosed through polymerase chain reaction of stools from patients with acute diarrhea. Results: Among 630 hospitalized patients with acute diarrhea, Campylobacter enterocolitis was diagnosed in 88 patients (14.0%). The mean age was 37.9±19.1 years. Campylobacter enterocolitis was most prevalent in the summer (52 patients, 59.1%). Patients exhibited more than 10 times of diarrhea in 36 (40.9%), high fever above 39℃ in 19 (21.59%), and abdominal pain above 5 points on the numeric rating scale in 23 (26.14%) cases. In abdominal CT scan, pancolitis was found in 58 patients (65.9%). Small intestine was involved in 37 patients (42.4%). Mean CRP was 10.14 mg/dL (range 0.72-32.27 mg/dL). The duration of diarrhea after antibiotics treatment was 2.34±1.51 days in the ciprofloxacin treatment group and 2.26±1.71 days in the 3rd cephalosporin treatment group. Conclusions: Campylobacter enterocolitis was common during summer. Commonly healthy young adults were hospitalized due to severe symptoms of Campylobacter enterocolitis. Whole colon and small bowel were frequently involved. Most patients were treated with antibiotics, and the efficacy of 3rd cephalosporin treatment was not inferior to that of ciprofloxacin treatment.

Background/Aims: An excessive inflammatory response is typical in acute pancreatitis and a significant cause of early mortality in severe acute pancreatitis. This is believed to be caused by inflammatory molecules or upregulated cytokine levels in the serum of patients. The aim of this study was to identify the serum-mediated apoptosis-inducing effects in acute pancreatitis patients. Methods: A skin tissue-derived cell line, BJ, was treated for 24 hours with the sera of 22 healthy volunteers (control) and 71 acute pancreatitis patients (22 with gallstone pancreatitis, 16 with alcoholic pancreatitis, and 11 with pancreatitis with other causes) collected at the time of hospital admission (active) and discharge (resolved). Apoptosis was analyzed by flow cytometry. Results: The average percentage of living cells, early apoptotic cells, and late apoptotic cells ranged from 78.8% to 85.0%, 5.5% to 7.3%, and 7.7% to 13.1%, respectively. The number of live cells increased significantly using the serum from the resolved state of gallstone-induced pancreatitis. In addition, the number of early apoptotic cells increased significantly using the serum from the resolved state of pancreatitis with other causes. The number of late apoptotic cells decreased significantly with the serum from the resolved state compared to the active state of gallstone- and alcohol-induced pancreatitis. Conclusions: Serum samples from patients with pancreatitis induced a change in the apoptosis profiles of skin-derived cells. These results indicate changes in the serum components in patients with acute pancreatitis

A thorough disinfection and infection control process associated with gastrointestinal endoscopy is highly important for the health and safety of the examinee and the medical staff involved in the procedure. Endoscopic reprocessing and disinfection are two of the most important steps in quality control of endoscopy. In 2019, the Korean Society of Gastrointestinal Endoscopy updated the Accreditation of Qualified Endoscopy Unit assessment items for these quality indicators. Assessment of disinfection and infection control comprises 28 mandatory items in the categories of disinfection education, pre-cleaning, cleaning, disinfection, rinsing, drying, reprocessing, storage, endoscopic accessories, water bottle and connectors, space/facilities, personal protective equipment, disinfection ledger, and regulations regarding infection control and disinfection. The updated Accreditation of Qualified Endoscopy Unit assessment items are useful for improving the quality of endoscopy by ensuring thorough inspection of endoscopic disinfection and infection control.

High expression of glucose transporter family members, which augment glucose uptake and glycolytic flux, has been shown to play a pivotal role in the proliferation and survival of tumor cells, contributing to the energy supply, biosynthesis and homeostasis of cancer cells. Among the many members, solute carrier family 2 member 1 (SLC2A1) encodes a glucose transporter, GLUT1, that is critical in the metabolism of glucose, which is an energy source for cell growth that contributes to cancer progression and development. The aim of this study was to analyze the survival and genetic changes/immune profiles in patients with gastric cancer with high SLC2A1 expression and to provide treatment for improving prognosis. This study investigated the clinicopathologic parameters, the proportion of immune cells and gene sets affecting SLC2A1 expression in 279 and 415 patients with gastric cancer from the Eulji Hospital cohort and The Cancer Genome Atlas, respectively. We assessed the response to conventional chemotherapy drugs, including fluorouracil, a compound of fluoropyrimidine S-1, oxaliplatin, and all-trans-retinoic acid (ATRA), in gastric cancer cell lines with high SLC2A1 expression. High SLC2A1 expression was associated with poor prognosis, cancer cell proliferation, decreased immune cells, including CD8 T cells and B cells, and a low prognostic nutrition index, representing body nutrition-related status. In pathway network analysis, SLC2A1 was indirectly linked to the retinoic signaling pathway and negatively regulated immune cells/receptors. In the drug response analysis, the drug ATRA inhibited gastric cancer cell lines with high SLC2A1 expression. Treatment involving the use of SLC2A1 could contribute to better clinical management/research for patients with gastric cancer.

This study aims to investigate the prognostic role of the neutrophil-to-lymphocyte ratio (NLR) in pancreatic neuroendocrine tumors (PNETs) using meta-analysis. This study evaluates the correlation between the NLR and the prognosis in PNETs from nine eligible studies. In addition, a subgroup analysis based on the tumor grade, treatment, and evaluation criteria, was conducted. The estimated rate of a high NLR was 0.253 (95% confidence interval (CI) 0.198–0.317). The rate of high NLRs was significantly lower in patients with lower tumor grades (G1) than those with higher tumor grades (G2 or G3). In addition, the mean value of the NLR was significantly lower in lower tumor grades than in higher tumor grades. High NLRs were significantly correlated with worse overall and recurrence-free survivals (hazard ratio (HR) 2.180, 95% CI 1.499–3.169 and HR 2.462, 95% CI 1.677–3.615, respectively). In a subgroup analysis, the prognostic implications of the NLR were found in both higher and lower criteria of a high NLR. Taken together, our results show that the NLR could be useful for predicting the tumor grade and the prognosis in PNETs.

DNA replicase polymerase ε (POLE) is critical in proofreading and correcting errors of DNA replication. Low POLE expression plays a pivotal role in accumulation of mutations and onset of cancer, contributing to development and growth of tumor cells. The aim of this study is to reveal the survival, alternative genes and antitumoral immune activities in non-small cell lung cancer (NSCLC) patients with low POLE expression and provide treatment strategies that can increase their survival rates. This study investigated the clinicopathologic parameters, various tumor-infiltrating lymphocytes (TILs), endogenous retrovirus, molecular interactions and in vitro drug screen according to POLE mutation/expression in 168 and 1,019 NSCLC patients from the Konkuk University Medical Center (KUMC) and the Cancer Genome Atlas, respectively. We identified mutations of 75 genes in the sequencing panels, with POLE frame shift p.V1446fs being the most frequent (56.8%) in KUMC based on 170 targeted sequencing panels. Mutant and high expression of POLE correlated with favorable prognosis with increased TILs and tumor mutation burden, compared with wild type and low expression of POLE. We found specific molecular interactions associated with cell cycle and antigen presentation. An in vitro drug screen identified dasatinib that inhibited growth of the NSCLC cell line with low POLE expression. POLE could contribute to the future development of anticancer drugs for patients with NSCLC.

Background/Objective. Gastric carcinoma with lymphoid stroma (GCLS) has been referred to as lymphoepithelioma-like carcinoma and medullary carcinoma. The present study aims at elucidating the clinicopathologic features and prognostic implications of GCLS through a meta-analysis. Methods. This study included 34 eligible studies and 1757 GCLSs. The clinicopathologic characteristics of GCLS were investigated from eligible studies, and the meta-analysis was performed. In addition, we compared the survival rates between GCLS and non-GCLS. Results. The estimated rate of GCLS was 0.062 (95% confidence interval (CI) 0.040-0.097). GCLS was significantly correlated with the diffuse type of Lauren’s classification, proximal tumor location, less-frequent lymphatic invasion, and lower pTNM stage. However, there was no significant difference in age, sex, tumor differentiation, vascular invasion, perineural invasion, pT stage, lymph node metastasis, and distant metastasis between GCLS and non-GCLS patients. EBV positive rates in GCLS and non-GCLS patients were 0.723 (95% CI 0.643-0.791) and 0.064 (95% CI 0.039-0.103), respectively. HER2 expression in GCLS was significantly lower than that in non-GCLS. GCLS patients had a more favorable prognosis than that of non-GCLS patients (hazard ratio 0.500, 95% CI 0.305-0.821). Conclusion. GCLS comprised 6.2% of overall GC and more frequent in the proximal portion of the stomach. Since GCLS was associated with better prognosis, the histologic finding can be useful for predicting the patient’s prognosis.

Background/AimsSyndecan-2 (SDC2) methylation was previously reported as a sensitive serologic biomarker for the early detection of colorectal cancer (CRC). The purpose of this study was to investigate whether SDC2 methylation is detectable in precancerous lesions and to determine the feasibility of using SDC2 methylation for the detection of CRC and precancerous lesions in bowel lavage fluid (BLF).Methods : A total of 190 BLF samples were collected from the rectum at the beginning of colonoscopy from patients with colorectal neoplasm and healthy normal individuals. Fourteen polypectomy specimens were obtained during colonoscopy. A bisulfite pyrosequencing assay and quantitative methylation-specific polymerase chain reaction were conducted to measure SDC2 methylation in tissues and BLF DNA.Results : SDC2 methylation was positive in 100% of villous adenoma (VA) and high-grade dysplasia, and hyperplastic polyp samples; 88.9% of tubular adenoma samples; and 0% of normal mucosa samples. In the BLF DNA test forSDC2 methylation, the sensitivity for detecting CRC and VA was 80.0% and 64.7%, respectively, at a specificity of 88.9%. The BLF of patients with multiple tubular adenomas, single tubular adenoma and hyperplastic polyps showed 62.8%, 26.7% and 28.6% rates of methylation-positive SDC2, respectively.Conclusion : sOur results demonstrated that SDC2 methylation was a frequent event in precancerous lesions and showed high potential in BLF for detecting patients with colorectal neoplasm.

BMI1 is known to play a key role in the regulation of stem cell self-renewal in both endogenous and cancer stem cells. High BMI1 expression has been associated with poor prognosis in a variety of human tumors. The aim of this study was to reveal the correlations of BMI1 with survival rates, genetic alterations, and immune activities, and to validate the results using machine learning. We investigated the survival rates according to BMI1 expression in 389 and 789 breast cancer patients from Kangbuk Samsung Medical Center (KBSMC) and The Cancer Genome Atlas, respectively. We performed gene set enrichment analysis (GSEA) with pathway-based network analysis, investigated the immune response, and performed in vitro drug screening assays. The survival prediction model was evaluated through a gradient boosting machine (GBM) approach incorporating BMI1. High BMI1 expression was correlated with poor survival in patients with breast cancer. In GSEA and in in silico flow cytometry, high BMI1 expression was associated with factors indicating a weak immune response, such as decreased CD8+ T cell and CD4+ T cell counts. In pathway-based network analysis, BMI1 was directly linked to transcriptional regulation and indirectly linked to inflammatory response pathways, etc. The GBM model incorporating BMI1 showed improved prognostic performance compared with the model without BMI1. We identified telomerase inhibitor IX, a drug with potent activity against breast cancer cell lines with high BMI1 expression. We suggest that high BMI1 expression could be a therapeutic target in breast cancer. These results could contribute to the design of future experimental research and drug development programs for breast cancer.

The Korean Society of Gastrointestinal Endoscopy (KSGE) issued guidelines for endoscope reprocessing for the first time in 1995, and the version of the guidelines was updated in August 2009, August 2012, and March 2015. Guidelines for endoscope reprocessing should be revised continuously, because new disinfectants and devices are developed and introduced. The current official version of the KSGE guidelines for endoscope reprocessing is explained herein to assist the reader in understanding the KSGE requirements for cleaning and disinfecting endoscopes.

Background: Lysine-specific demethylase 1A (KDM1A) plays an important role in epigenetic regulation in malignant tumors and promotes cancer invasion and metastasis by blocking the immune response and suppressing cancer surveillance activities. The aim of this study was to analyze survival, genetic interaction networks and anticancer immune responses in breast cancer patients with high KDM1A expression and to explore candidate target drugs. Methods: We investigated clinicopathologic parameters, specific gene sets, immunologic relevance, pathway-based networks and in vitro drug response according to KDM1A expression in 456 and 789 breast cancer patients from the Hanyang university Guri Hospital (HYGH) and The Cancer Genome Atlas, respectively. Results: High KDM1A expression was associated with a low survival rate in patients with breast cancer. In analyses of immunologic gene sets, high KDM1A expression correlated with low immune responses. In silico flow cytometry results revealed low abundances of CD8+T cells and high programmed death-ligand 1 (PD-L1) expression in those with high KDM1A expression. High KDM1A expression was associated with a decrease in the anticancer immune response in breast cancer. In pathway-based networks, KDM1A was linked directly to pathways related to the androgen receptor signaling pathway and indirectly to the immune pathway and cell cycle. We found that alisertib effectively inhibited breast cancer cell lines with high KDM1A expression. Conclusions: Strategies utilizing KDM1A may contribute to better clinical management/research for patients with breast cancer.

Background and objectives: This study aimed to elucidate the clinical outcomes of endoscopic resection (ER) through comparison with surgical resection (SR) through a meta-analysis. Materials and Methods: This meta-analysis was performed using 32 studies. The complete resection and recurrence rates of treatment for ampullary tumors were investigated and compared between ER and SR. In addition, complications, including pancreatitis, cholangitis, cholecystitis, perforation, and papillary stenosis, and mortality of ER and SR, respectively, were estimated. Results: The rates of complete resection were 0.812 (95% confidence interval, CI, 0.758–0.856) and 0.929 (95% CI 0.739–0.984) in ER and SR, respectively. Recurrence rates were 0.145 (95% CI 0.107–0.193) and 0.126 (95% CI 0.057–0.257) in ER and SR, respectively. There were no significant differences in complete resection and recurrence rates between ER and SR in the meta-regression tests (p = 0.164 and p = 0.844, respectively). The estimated rates of pancreatitis, cholangitis/cholecystitis, perforation, and papillary stenosis were 12.8%, 4.4%, 5.2%, and 4.3% in ER and 9.9%, 5.6%, 2.3%, and 5.6% in SR, respectively. There was no significant difference in complications between ER and SR. The mortality rate of SR was slightly higher than that of ER (0.041, 95% CI 0.015–0.107 vs. 0.031, 95% CI 0.005–0.162). Our results show that ER had no significant differences in terms of complete resection and recurrence rates compared to SR, regardless of tumor behaviors. Conclusions: By comparing the complication and mortality rates between ER and SR, the safety of ER was proven.

Chronic gastritis could activate a systemic inflammatory response that could result in adverse lipid profiles. To determine the severity of chronic gastritis, Helicobacter pylori (HP), mononuclear cell (lymphocytes and plasma cells), and neutrophil scores were assessed on the basis of the updated Sydney system (USS), which is widely used for histological grading. The aim of this study was to assess the relationships between gastric histological features and lipid profile levels. This study included 15,322 males and 5929 females who underwent a health checkup and gastric biopsy at the Kangbuk Samsung Medical Center (KBSMC). We analyzed whether the HP, mononuclear cell, and neutrophil grades according to the USS were related to serum leukocyte count, unhealthy behaviors, and lipid profile levels. Gastritis with HP, neutrophils, or moderate to severe mononuclear cells was associated with an elevated serum leukocyte count. A high leukocyte count was related to increased low-density lipoproteins (LDL) and triglycerides/very-low-density lipoprotein (VLDL) and decreased high-density lipoproteins (HDL). In multivariate analyses, chronic gastritis with HP or moderate to severe mononuclear cells was significantly associated with decreased HDL in males, while mononuclear cells were significantly related to decreased HDL in females. Chronic gastritis was associated with an increased systemic inflammatory response, which was associated with unfavorable lipid profiles, especially low HDL levels.

This study aimed to determine the incidence and the prognosis of incidental carcinoma of the gallbladder (IGBC) after cholecystectomy through a meta-analysis. This meta-analysis included 51 studies and 436,636 patients with cholecystectomy. The incidence rate of IGBC after cholecystectomy was 0.6% (95% confidence interval (CI) 0.5–0.8%). The incidence rate of recent studies was not significantly different from those of past studies. The mean age and female ratio of the IGBC subgroup were not significantly different from those of the overall patient group. The estimated rates of IGBC were 13.0%, 34.1%, 39.7%, 22.7%, and 12.5% in the pTis, pT1, pT2, pT3, and pT4 stages, respectively. Patients with IGBC had a favorable overall survival rate compared to patients with non-IGBC (hazard ratio (HR) 0.574, 95% CI 0.445–0.739). However, there was no significant difference of disease-free survival between the IGBC and non-IGBC subgroups (HR 0.931, 95% CI 0.618–1.402). IGBC was found in 0.6% of patients with cholecystectomy. The prognosis of patients with IGBC was favorable compared to those with non-IGBC. In the pathologic examination after cholecystectomy for benign diseases, a sufficient examination for histology should be guaranteed to detect IGBC.

The present study aimed to compare the diagnostic accuracy between conventional smear (CS) and liquid-based preparation (LBP) in endoscopic ultrasonography-fine needle aspiration cytology (EUS-FNAC) of pancreatic lesions. Using 31 eligible studies, the diagnostic accuracy of cytologic examination in CS and LBP was evaluated through a conventional meta-analysis and diagnostic test accuracy review. Overall concordance rates were 82.8% (95% confidence interval [CI], 79.8–85.5%) and 94.0% (95% CI, 84.4–97.8%) in CS and LBP, respectively. CS with rapid on-site evaluation (ROSE) showed a higher concordance rate than CS without ROSE. In CS, the pooled sensitivity and specificity were 89.8% (95% CI, 85.2–93.1%) and 95.0% (95% CI, 90.0–97.6%), respectively. The diagnostic odds ratio (OR) and area under curve (AUC) of the summary receiver operating characteristic (SROC) curve were 90.32 (95% CI, 43.85–147.11) and 0.945, respectively. In LBP, the pooled sensitivity and specificity were 80.9% (95% CI, 69.7–88.7%) and 99.9% (95% CI, 1.5–100.0%), respectively. The diagnostic OR and AUC of the SROC curve were 57.21 (95% CI, 23.61–138.64) and 0.939, respectively. Higher concordance rates were found in CS with ROSE and LBP in EUS-FNAC of pancreatic lesions. Regardless of the cytologic preparation method, EUS-FNAC is a useful and accurate diagnostic tool for pancreatic lesions.

Ninety percent of patients with scrub typhus (SC) with vasculitis-like syndrome recover after mild symptoms; however, 10% can suffer serious complications, such as acute respiratory failure (ARF) and admission to the intensive care unit (ICU). Predictors for the progression of SC have not yet been established, and conventional scoring systems for ICU patients are insufficient to predict severity. We aimed to identify simple and robust indicators to predict aggressive behaviors of SC. We evaluated 91 patients with SC and 81 non-SC patients who were admitted to the ICU, and 32 cases from the public functional genomics data repository for gene expression analysis. We analyzed the relationships between several predictors and clinicopathological characteristics in patients with SC. We performed gene set enrichment analysis (GSEA) to identify SC-specific gene sets. The acid-base imbalance (ABI), measured 24 h before serious complications, was higher in patients with SC than in non-SC patients. A high ABI was associated with an increased incidence of ARF, leading to mechanical ventilation and worse survival. GSEA revealed that SC correlated to gene sets reflecting inflammation/apoptotic response and airway inflammation. ABI can be used to indicate ARF in patients with SC and assist with early detection.

BACKGROUND:Matrix metalloproteinase-9 (MMP-9) is associated with remodelling of the extracellular matrix and invasion in various cancers. Identifying proteins connected to high MMP-9 expression is important in explaining its mechanisms. Our study aims to shed light on genes associated with high MMP-9 expression and to discuss their clinical impact in breast cancer. METHODS:We evaluated 173 breast cancer cases from the Kangbuk Samsung Hospital, with 1964 cases from the Molecular Taxonomy of Breast Cancer International Consortium database serving as a validation cohort. We investigated relationships between MMP-9 expression and clinicopathological characteristics. We then used gene set enrichment analyses to detect the association of genes with MMP-9 overexpression, and performed survival analyses to determine the significance of the gene in three independent cohorts. RESULTS:High MMP-9 expression correlated with poor prognosis in univariate and multivariate analyses. Using gene set enrichment analysis, we found that tumour necrosis factor receptor superfamily member 12A (TNFRSF12A) was linked to high MMP-9 expression. In the survival analysis of three published data sets (METABRIC, GSE1456, GSE20685), high TNFRSF12A was relevant to a poor survival rate. CONCLUSIONS:High levels of TNFRSF12A associated with MMP-9 overexpression may be important to explain the progression of breast cancer, and survival could be improved using therapy targeting TNFRSF12A.

Background/Objectives. This meta-analysis is aimed at investigating the prognostic roles of the inflammatory markers neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with pancreatic cancer. Methods. The correlations between high inflammatory marker expression levels and prognosis in 7105 patients with pancreatic cancer from 34 eligible studies were investigated. Additionally, subgroup analyses based on study location, tumor stage, treatment, and value cutoffs were performed. Results. High NLR and PLR values were considered to be 2.0–5.0 and 150–200, respectively. Using a random-effects model, the estimated rates of high NLR and PLR were 0.379 (95% confidence interval [CI] 0.310–0.454) and 0.490 (95% CI 0.438–0.543), respectively. High NLRs were frequently found in patients with lower tumor stages and in those who underwent surgery. There were significant correlations between high NLR and PLR and poor survival rates (hazard ratio [HR] 1.737, 95% CI 1.502–2.009 and HR 1.143, 95% CI 1.037–1.259, resp.). Interestingly, the NLR and PLR had no prognostic value in patients who underwent chemoradiotherapy. Conclusion. Taken together, our results showed that inflammatory markers are useful for predicting prognosis in patients with pancreatic cancer. The NLR is a more suitable parameter for predicting prognosis regardless of the patient’s condition.