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Ampullary adenoma is a rare premalignant lesion, but its incidence is increasing. Endoscopic papillectomy has become the first treatment of choice for ampullary adenomas due to its safety and effectiveness, thereby replacing surgical resection. However, recurrence rates and adverse events after endoscopic papillectomy were reported in up to 30% of cases.To review the long-term outcomes of endoscopic papillectomy and investigate the factors that affect these outcomes.We retrospectively analyzed the data of patients who underwent endoscopic papillectomy for ampullary adenoma at five tertiary hospitals between 2013 and 2020. We evaluated clinical outcomes and their risk factors. The definitions of outcomes were as follow: (1) curative resection: complete endoscopic resection without recurrence; (2) endoscopic success: treatment of ampullary adenoma with endoscopy without surgical intervention; (3) early recurrence: reconfirmed adenoma at the first endoscopic surveillance; and (4) late recurrence: reconfirmed adenoma after the first endoscopic surveillance.A total of 106 patients were included for analysis. Of the included patients, 81 (76.4%) underwent curative resection, 99 (93.4%) had endoscopic success, showing that most patients with non-curative resection were successfully managed with endoscopy. Sixteen patients (15.1%) had piecemeal resection, 22 patients (20.8%) had shown positive/uncertain resection margin, 11 patients (16.1%) had an early recurrence, 13 patients (10.4%) had a late recurrence, and 6 patients (5.7%) had a re-recurrence. In multivariate analysis, a positive/uncertain margin [Odds ratio (OR) = 4.023,Endoscopic papillectomy is a safe and effective treatment for ampullary adenomas. Careful selection and follow-up of patients is mandatory, particularly in cases with positive/uncertain margin and piecemeal resection.

Background/Aims: Subepithelial tumors (SETs) are small, mostly asymptomatic lesions with normal overlying mucosa, usually identified incidentally on endoscopy. The aim of this study was to evaluate the pathologic diagnosis of SETs, and to assess the diagnostic yield and impact of endoscopic submucosal dissection (ESD) biopsy on the management of patients with SETs.Materials and Methods: We included 52 subepithelial lesions in this study during the study period. Inclusion criteria included size of the SET >2 cm, and a gastrointestinal stromal tumor (GIST) that cannot be excluded using EUS. We performed an endoscopic biopsy of each SET using the ESD technique.Results: The mean diameter of the lesions was 24.15±6.0 mm. The diagnostic yield of this method was 96.15%. Among the 52 participants, 45 were located in the stomach, four in the esophagus, and three in the duodenum. The pathologic diagnoses included: 17 leiomyomas, 13 GISTs, 11 ectopic pancreases, two carcinomas, two inflammatory fibroid polyps, two Brunner’s gland hyperplasia, two lipomas, one glomus tumor, and two remained undiagnosed. The mean duration of the procedure was 13.44±2.41 minutes. Three complications were associated with the procedure.Conclusions: Deep biopsy via ESD is useful in determining the histopathologic nature of SETs. This method minimizes the need for unnecessary surgery in benign SETs.

Common bile duct (CBD) stone is one of the most frequent biliary diseases. Recurrence after the complete removal of CBD stones is high, and we aim to evaluate the rate and risk factors for symptomatic recurrence of CBD stones after endoscopic retrograde cholangiopancreatography (ERCP). We, retrospectively, reviewed the database of patients who underwent ERCP for CBD stones and subsequent cholecystectomy between January 2015 and December 2017 at a tertiary hospital. The recurrence of symptomatic CBD stones was defined as the presence of a CBD stone with related symptoms at least 6 months after the ERCP procedure. The primary outcomes were recurrence of symptomatic CBD stones and its risk factors. Among the 362 enrolled patients, 60 experienced a symptomatic recurrence of CBD stones between 6 months and 5 years after the procedure. The mean duration of follow-up was 32.3 ± 8.1 months. The patients with recurrences were older and had a longer follow-up duration. Low insertion of the cystic duct (HR = 2.893, p = 0.016), distal CBD angulation (HR = 1.015, p = 0.034), maximum CBD diameter (HR = 1.070, p = 0.012), number of ERCP sessions at first admission (HR = 1.558, p = 0.032), and cannulation time (HR = 1.030, p = 0.008) were the independent risk factors for symptomatic recurrent CBD stones. Patients with risk factors, especially those with low cystic duct insertion, are more prone to symptomatic recurrent CBD stones and should be followed more carefully.

Background/Aims: To date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of serum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result. Methods: We conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrhosis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups. Results: Serum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 μg/mL vs 1.42 μg/mL, p

Tyrosine kinase inhibitors are widely used as targeted treatments for various malignancies. Sorafenib is an orally active tyrosine kinase inhibitor that blocks the signaling pathways of several growth factors. Its use is approved for various malignancies such as unresectable hepatocellular carcinoma, renal cell carcinoma, and gastrointestinal stromal tumors. Several adverse effects have been reported in the literature; however, cardiotoxicity is rare. We present a case of recurrent coronary vasospasm caused by short-term administration (5 days) of sorafenib. Since it caused refractory ischemia after re-administration, we had no choice but to stop the treatment. (J Liver Cancer 2020;20:67-71)

Background Endoscopic ultrasound fine-needle aspiration (EUS-FNA) is a well-established method for the diagnosis of solid pancreatic lesions. However, the diagnostic yield of EUS-FNA for pancreatic lesions varies at around 70-90%. Samples from EUS-FNA consist of cells and tissues that can be analyzed separately, and the results can be combined for a final diagnosis. Objectives To investigate the effect of cytological and histological analysis of EUS-FNA samples on the final diagnosis, and identify factors that may affect the accuracy of the cytological, histological, and overall analysis. Material and methods A single-center prospective observational study was conducted at a tertiary university hospital from July 2018 to June 2019. Patients who underwent EUS-FNA for pancreatic solid lesions with a 22-gauge EUS-FNA needle were included in our study. Liquid-based cytological analysis of the specimen and histological analysis of the whitish core were performed, and factors that affected the diagnostic accuracy of each analysis were evaluated. Results In 63 EUS-FNA samples, the overall diagnostic accuracy was 87.3%, which was significantly higher than the cytological accuracy of 73.8% (p = 0.031) and the histological accuracy of 69.8% (p = 0.001). Factors that affected the results differed in each group: 1) cytological analysis: size, location, and approach method; 2) histological analysis: specimen weight; and 3) overall analysis: size, location, and approach method. Conclusions Histologic evaluation of core material obtained from EUS-FNA improved diagnostic accuracy, and factors that affected each result were analyzed. Further studies with prospective randomized trials are recommended to support our data.

BACKGROUNDS/AIMS: Interval gastric cancers (GCs) can be encountered during screening gastroscopy. This study investigated the rate of interval GCs and their risk factors. MATERIALS AND METHODS: We retrospectively investigated subjects who underwent screening gastroscopy from 2005 to 2017 in a university hospital and were diagnosed with GC. Subjects were grouped based on their endoscopic images and descriptive results into interval GC and initially diagnosed GC groups. Interval GCs were defined when endoscopic results within the previous 3 years were negative for GC. The clinico-pathological characteristics of the groups and risk factors for interval GCs were evaluated. RESULTS: Of 54 724 subjects who underwent screening gastroscopy, 234 were diagnosed with GC, of which 43 were interval GCs. The rate of interval GCs was 18.4% (43/234, mean age 61.6 years). Interval GCs were smaller than initially diagnosed GCs (1.6 vs 1.9 cm, P = .011). They were located in the low-to-mid-body in 44.2%, antrum in 48.8%, and high body and cardia in 7%. Their observation time was shorter (248.74 vs 410.64 sec, P = .032). In multivariate analysis, they were associated with short observation time (odds ratio [OR] 0.99, 95% CI 0.994-0.998, P < .001) and location in the low-to-mid-body (OR 2.12, 95% CI 1.071-4.181, P = .031), although differentiation, ulcerated type, metaplasia, Helicobacter pylori infection, and endoscopists’ experience were not associated with interval GCs. CONCLUSIONS: The rate of interval GCs was significant during screening gastroscopy. They might be reduced by increasing observation time, focusing on smaller lesions, and observing the low-to-mid-body of the stomach more carefully.

Background Cholecystitis is an important risk factor for gallbladder cancer, but the bile microbiome and its association with gallbladder disease has not been investigated fully. We aimed to analyze the bile microbiome in normal conditions, chronic cholecystitis, and gallbladder cancer, and to identify candidate bacteria that play an important role in gallbladder carcinogenesis. Methods We performed metagenome sequencing on bile samples of 10 healthy individuals, 10 patients with chronic cholecystitis, and 5 patients with gallbladder cancer, and compared the clinical, radiological, and pathological characteristics of the participants. Results No significant bacterial signal was identified in the normal bile. The predominant dysbiotic bacteria in both chronic cholecystitis and gallbladder cancer were those belonging to the Enterobacteriaceae family. Klebsiella increased significantly in the order of normal, chronic cholecystitis, and gallbladder cancer. Patients with chronic cholecystitis and dysbiotic microbiome patterns had larger gallstones and showed marked epithelial atypia, which are considered as precancerous conditions. Conclusion We investigated the bile microbiome in normal, chronic cholecystitis, and gallbladder cancer. We suggest possible roles of Enterobacteriaceae, including Klebsiella, in gallbladder carcinogenesis. Our findings reveal a possible link between a dysbiotic bile microbiome and the development of chronic calculous cholecystitis and gallbladder cancer., Graphical Abstract

Background The use of antibiotics increases recently. Accordingly, the incidence of antibiotics associated with drug induced liver injury (DILI) also increases. The purpose of this study is to evaluate the proportion and the clinical characteristics of antibiotic associated with DILI. Methods This study is a retrospective study of analyzed adult patients who were referred to the department of hepatology for the elevation of liver function tests and the frequency of elevated liver enzyme of patients with prescribed antibiotics during the same period at outpatient setting as a validation set. Results Antibiotics associated with DILI (64.0%) are the most common reason agent among consulting to hepatology department. Rheumatoid arthritis related drugs (11.0%), health supplements (5.0%), herbal medicines (4.0%), anti-viral drugs, anti-inflammatory analgesics/acetaminophen and lipid-lowering agents (3.0%) were next common causative drug for DILI in inpatients setting (training set). The frequency of antibiotics associated with DILI was high in order of flomoxef, cetrazole, ceftriaxone, vancomycin, piperacillin/tazobactam and amoxicillin/clavulanate. In the same period, 32% of the patients who prescribed flomoxef showed elevated liver enzyme levels above the upper normal limit. The prevalence of flomoxef induced DILI (>3 folds of ALT) was 13% and liver enzyme levels were five times higher than upper normal limits in 5% of flomoxef groups. Hypertension or diabetes was the risk factor of flomoxef associated with DILI. Conclusions The Prevalence of antibiotics associated with DILI was 2-14%. Co-morbidity with diabetes and hypertension was the risk factor of flomoxef associated with DILI.

Endoscopic ultrasound (EUS)-guided tissue acquisition of pancreatic solid tumor requires a strict recommendation for its proper use in clinical practice because of its technical difficulty and invasiveness. The Korean Society of Gastrointestinal Endoscopy (KSGE) appointed a task force to draft clinical practice guidelines for EUS-guided tissue acquisition of pancreatic solid tumor. The strength of recommendation and the level of evidence for each statement were graded according to the Minds Handbook for Clinical Practice Guideline Development 2014. The committee, comprising a development panel of 16 endosonographers and an expert on guideline development methodology, developed 12 evidence-based recommendations in eight categories intended to help physicians make evidence-based clinical judgments with regard to the diagnosis of pancreatic solid tumor. This clinical practice guideline discusses EUS-guided sampling in pancreatic solid tumor and makes recommendations on circumstances that warrant its use, technical issues related to maximizing the diagnostic yield (e.g., needle type, needle diameter, adequate number of needle passes, sample obtaining techniques, and methods of specimen processing), adverse events of EUS-guided tissue acquisition, and learning-related issues. This guideline was reviewed by external experts and suggests best practices recommended based on the evidence available at the time of preparation. This guideline may not be applicable for all clinical situations and should be interpreted in light of specific situations and the availability of resources. It will be revised as necessary to cover progress and changes in technology and evidence from clinical practice. (Gut Liver 2021;15:354-374)

Background : Patients with end-stage renal disease (ESRD) have a higher incidence of clinically relevant complications, such as bleeding and perforation after polyp resection, compared to patients without underlying diseases. Cold snare polypectomy (CSP) is increasingly used for the removal of small polyps and diminutive polyps due to its shorter procedure time and low risk of bleeding and perforation. However, there have been few studies on the effectiveness and safety of CSP in patients with ESRD. The aim of this study was to compare the efficacy and safety of CSP and endoscopic mucosal resection (EMR) in ESRD patients. Methods : This study was a retrospective study. We performed propensity score-matched analysis in patients with ESRD who underwent endoscopic resection for 3-10-mm-sized colorectal polyps at Seoul St. Mary's Hospital, from January 2014 to December 2019. Results : After 1:1 ratio matching, 406 polyps were included: 203 polyps were resected with CSP and 203 polyps with EMR. There was no difference between the CSP group and EMR group in incomplete resection rate (4.43% vs. 1.97%, P = 0.16). There were no differences between the CSP and EMR group for immediate bleeding (5.42% vs. 7.88%, P = 0.32) and delayed bleeding (0% vs. 0.49%, P = 1.00). No perforation occurred in either group. Conclusions : There were no differences between the CSP and EMR group in terms of efficacy and safety. CSP can be one of the standard methods for the removal of 3-10-mm-sized colorectal polyps in patients with ESRD.

Summary Background & aims Most people with nonalcoholic fatty liver disease (NAFLD) are obese, and they usually eat more while being less physically active as compared to healthy individuals. However, little is known about the lifestyle patterns of non-obese or obese patients with NAFLD. The aim of this study was to investigate nutrition components and behavioral differences between non-obese and obese patients with NAFLD. Methods This is a cross-sectional study comprising of 209 patients. Nutritional components and physical activity status were compared in obese and non-obese subjects with NAFLD against healthy controls. Dietary intake was assessed using the 5-day food diary. Physical activity was measured using the protocol of Korea Health and Nutrition Examination Survey. Total and regional body composition analysis was conducted using anthropometry and tetrapolar multi-frequency bio-impedance. Visceral adipose tissue, total abdominal adipose tissue, abdominal subcutaneous adipose tissue as well as liver fat were measured using abdomen tomography. Results Non-obese subjects with NAFLD had higher levels of ALT, AST, GGT, triglyceride, fasting glucose; higher carbohydrate energy ratio; higher visceral fat area, subcutaneous area, body muscle mass, fat free mass and body fat compared to subjects without NAFLD. Subjects with obesity and NAFLD had higher ALT, AST, visceral fat, fasting glucose and HOMA-IR (homeostatic model assessment-insulin resistance), and less moderate-level physical activity compared to those with obesity who do not have NAFLD. Obese subjects with NAFLD also had higher blood pressure, visceral fat area, subcutaneous fat area, body fat, body fat percent and GGT compared to non-obese subjects with NAFLD. In multivariate analysis, carbohydrate energy ratio and physical activity less than moderate-level ( Conclusions Percentage of carbohydrate intake percent and physical activity, less than moderate-level were independent predictors of NAFLD in non-obese subjects. Meanwhile, physical activity, less than moderate-level, was an independent predictor in obese subjects.

The revised criteria of the 8th American Joint Committee on Cancer (AJCC) cancer staging system consider depth of invasion as one of the factors that determine stage in distal bile duct (DBD) cancer, but exclude adjacent organ invasion. The aims were to evaluate the association between adjacent organ invasion and relapse-free survival (RFS) and overall survival (OS) after curative surgical resection of DBD cancer and to propose optimal criteria for predicting clinical outcomes. In this retrospective cohort study, 378 patients with DBD cancer treated in multi-institutions between 1996 and 2013 were investigated. This study evaluated the relationship between clinicopathologic parameters and adjacent organ invasion and used organ invasion to compare the survival times of each group. Among 204 patients with adjacent organ invasion, 152 were in the single-organ invasion group and 52 were in the dual-organ invasion group based on a review of microscopic slides. In univariate and multivariate analyses, patients with dual-organ invasion had a shorter RFS and OS time than those with single-organ invasion. Organ invasion should be included as one of the factors that determine the AJCC stage; this might ultimately help to predict better the survival rate of patients with DBD cancer.

4020 Background: In the TeloVac study, GV1001 with Gemcitabine/capecitabine (G/C) did not show increased overall survival (OS) than G/C in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDA). But cytokine examination suggested high serum eotaxin level may predict improved survivals in pts received GV1001 with G/C. This phase III trial was designed to assess the efficacy of GV1001 with G/C for previous untreated eotaxin-high Korean pts with advanced PDA. Methods: Eligible pts with histologically proven locally advanced and metastatic PDA (except peritoneal carcinomatosis), age > 18 years, and ECOG PS 0–2 were recruited. Pts were randomly assigned (1:1) to receive either G/C or G/C with GV1001 (G/C/GV). All pts receiving G/C/GV were with high serum eotaxin level (≥81.02 ng/mL), and the pts receiving G/C were randomly assigned again (1:1) to eotaxin-high and eotaxin-low pts. Study was designed according to Korean MFDS guidance for approval of clinical trial. G/C treatment included G (1000 mg/m2, 30 min IVF, D 1, 8, & 15) and C (830 mg/m2 BID for 21 days per month (m). G/C/GV treatment included an intradermal injection of GM-CSF (75 μg) and GV1001 (0.56 mg; D 1, 3, & 5, once on week 2–4, & 6, then monthly thereafter) from the start of G/C. The primary endpoint was OS. The secondary endpoints included time to progression (TTP), objective response rate, and safety. Survival data was analyzed using the copula graphic estimate method under dependent censoring. The response was independently assessed per RECIST v1.1. Under the one-sided significance level of 2.5% and to achieve the power of 80% of the statistical significance with the median OS difference from 7.9 to 14.9 m (HR = 0.53), 85 events and 118 registrations needed. Considering 20% drop-outs, 148 registrations were required. Results: Between Nov 2015 and Apr 2020, of 511 pts screened in 16 centers, eotaxin-high pts were identified as 34.7% (174 / 502 pts). 148 pts randomly assigned to G/C/GV (n = 75; all eotaxine-high) and G/C (n = 73; 37 eotaxine-high, 36 eotaxine-low). Median OS was significantly improved in the G/C/GV group with 11.3m [95% CI 8.6-14.0] than G/C group with 7.5 m [95% CI 5.1-10.0] (p = 0.021). Also, median TTP was significantly improved in the G/C/GV group (7.3 m [95% CI 5.0-9.7]) than in the G/C group (4.5 m [95% CI 3.2-5.8], p = 0.021). In other secondary endpoints, no statistical significance was confirmed between the two groups. Grade 3-4 treatment-emergent adverse events were reported in 49 pts (73.13%) vs. 58 pts (77.33%) in the G/C and G/C/GV group, without significant differences (p = 0.562). Conclusions: G/C/GV treatments significantly extend OS and TTP in advanced PDA than G/C, and specific safety-related issues had not been found. GV1001 should be considered as one of the options in PDA pts with high serum eotaxin levels. Clinical trial information: NCT02854072.

Background/Aims To date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of serum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result. Methods We conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrhosis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups. Results Serum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 μg/mL vs 1.42 μg/mL, p

Background and Aim: The risk and benefit of non-selective propranolol in patients with tense ascites are controversial. This study aimed to investigate the effect of propranolol as secondary prophylaxis on varix rebleeding and overall mortality in patients with tense ascites. Methods: This study used a database of the Health Insurance Review and Assessment Service (HIRAS), which provides health insurance to 97.2% of the total population in Korea. A total of 80,071 patients first variceal bleeding as the first decompensated complication enrolled from 2007 to 2014. Results: There were 2274 patients with large-volume ascites prescribed propranolol as secondary prophylaxis after first varix bleeding. The average prescription dose of propranolol as secondary prophylaxis was 74 mg/day in patients with large-volume ascites. The mean duration of rebleeding was 22.8 months. Result of analysis showed that low-dose propranolol (40&ndash, 120 mg/day) compared to inadequate propranolol dose (&lt, 40 mg/day) as secondary prophylaxis decreased overall mortality and varix rebleeding in patients with tense ascites. Conclusions: Low-dose propranolol (40&ndash, 120 mg/day) as secondary prophylaxis for variceal re-bleeding decreased overall mortality and varix rebleeding recurrence in patients with tense ascites.

Photovoltaic (PV) panels are the most widely used technology for renewable energy production; however, in urban areas, their installation locations are primarily limited to building rooftops. Here, a PV panel design that allows installation on building façades, particularly in elementary school buildings in South Korea, which are widely distributed throughout the country and have a standardized building design, was developed. Elementary schools in Seoul, Gwangju, and Busan were selected, and the energy production efficiency of the PV panels based on latitude and important influencing factors, including installation position, angle, and incoming solar irradiation, were investigated. Further, each targeted elementary school building and the corresponding PV module design were visualized in three dimensions. Thus, solar irradiation was measured, and the potential energy generated by the PV modules was calculated using the Insight software coupled with the Revit software. The building façade position associated with the highest energy production efficiency for each target elementary school was selected based on the optimal PV module tilt angle, and the total energy production was 307,734 kWh∙year−1. The results of this study can be applied to several other public education facilities and can be readily extended to high-rise residential buildings across Asia.

Background/Aims Gallstone pathogenesis is linked to mucin hypersecretion and bacterial infection. Several mucin genes have been identified in gallbladder epithelial cells (GBECs). We investigated MUC expression in cholesterol-associated gallbladder disease and evaluated the relationship between mucin and bacterial infection. Methods The present study involved 20 patients with cholesterol stones with cholecystitis, five with cholesterol stones with cholesterolosis, six with cholesterol polyps, two with gallbladder cancer, and six controls. Canine GBECs treated with lipopolysaccharide were also studied. MUC3, MUC5AC, MUC5B, and MUC6 antibodies were used for dot/slot immunoblotting and immunohistochemical studies of the gallbladder epithelial tissues, canine GBECs, and bile. Reverse-transcription polymerase chain reaction was performed to evaluate MUC3 and MUC5B expression. Results MUC3, MUC5AC, MUC5B, and MUC6 were expressed in the normal gallbladder epithelium, and of those, MUC3 and MUC5B exhibited the highest expression levels. Greatly increased levels of MUC3 and MUC5B expression were observed in the cholesterol stone group, and slightly increased levels were observed in the cholesterol polyp group; MUC3 and MUC5B mRNA was also upregulated in those groups. Canine GBECs treated with lipopolysaccharide also showed upregulation of MUC3 and MUC5B. Conclusions The mucin genes with the highest expression levels in gallbladder tissue in cholesterol-associated diseases were MUC3 and MUC5B. Cholesterol stones and gallbladder infections were associated with increased MUC3 and MUC5B expression.

Cholangiocytes, the lining epithelial cells in bile ducts, are an important subset of liver cells. They are activated by endogenous and exogenous stimuli and are involved in the modification of bile volume and composition. They are also involved in damaging and repairing the liver. Cholangiocytes have many functions including bile production. They are also involved in transport processes that regulate the volume and composition of bile. Cholangiocytes undergo proliferation and cell death under a variety of conditions. Cholangiocytes have functional and morphological heterogenecity. The immunobiology of cholangiocytes is important, particularly for understanding biliary disease. Secretion of different proinflammatory mediators, cytokines, and chemokines suggests the major role that cholangiocytes play in inflammatory reactions. Furthermore, paracrine secretion of growth factors and peptides mediates extensive cross-talk with other liver cells, including hepatocytes, stellate cells, stem cells, subepithelial myofibroblasts, endothelial cells, and inflammatory cells. Cholangiopathy refers to a category of chronic liver diseases whose primary disease target is the cholangiocyte. Cholangiopathy usually results in end-stage liver disease requiring liver transplant. We summarize the biology of cholangiocytes and redefine the concept of cholangiopathy. We also discuss the recent progress that has been made in understanding the pathogenesis of cholangiopathy and how such progress has influenced therapy.

OBJECTIVES Pancreatic neuroendocrine tumors (pNETs) are diverse diseases with different prognosis. The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) introduced 2 different tumor node metastasis (TNM) stages, and the World Health Organization (WHO) proposed WHO 2010 grading system for pNETs. Therefore, we aimed to validate the prognostic relevance of these 3 systems for pNETs in South Korea. METHODS The Korean Society of Gastrointestinal Cancer created a retrospective registry of pNETs in 153 patients from 15 hospitals between 2002 and 2012. RESULTS On the basis of the WHO 2010 grade, 2-year progression-free-survival (PFS) rates for G1, G2, and G3 were 92%, 62%, and 25% (P < 0.01). According to ENETS and AJCC staging, 2-year PFS rates for stages I through IV were 94%, 87%, 49%, 20%, and 92%, 61%, 60%, 20%, respectively (P < 0.01). A Cox multivariate regression analysis revealed that the only statistically significant prognostic factor was the TNM classification of either the AJCC or the ENETS stage (P < 0.01). In addition, the κ value between the AJCC and the ENETS stages was 0.46 indicating a "moderate" agreement (P < 0.01). CONCLUSIONS The AJCC and ENETS TNM classifications for pNETs are prognostic for PFS and can be adopted in clinical practice in South Korea.

Background and purpose: Gastrointestinal stromal tumors (GISTs) are rare diseases of the gastrointestinal tract but they are the most common gastrointestinal tumors of mesenchymal origin. Since most GISTs have malignant potential, their probability of malignant progression must be evaluated. This study was conducted to examine the correlation between three-dimensional GIST volume measured by CT and malignant potential. Materials and methods: A retrospective study was performed on 70 patients diagnosed with GIST after surgical resection in Hanyang University Seoul Hospital from 2012 to 2017. Linear regression analysis was used to establish which between the length of the long axis of GISTs, originally considered a predictor of malignancy, and their volume was a more accurate predictor of malignancy. Tumor dimensions were measured by CT. Results: Data were analyzed using the chi-square test or Student&rsquo, s t-test and logistic regression. Of the GISTs, 53 (75.71%) were in the stomach, 3 (4.29%) in the small intestine, and 14 (20.0%) in the large intestine. The mean age of the malignant GIST group was significantly higher than that of the benign GIST group (p = 0.032), their tumor long axes were significantly greater (p = 0.073), their tumor volumes were significantly larger (p = 0.001), and the frequency of tumor necrosis was higher (p = 0.001). In multivariate analysis, malignant GIST was associated with location in organs other than the stomach (OR 7.846, 95% CI 1.293&ndash, 47.624, p = 0.025), longer axis (OR 1.037, 95% CI 1.011&ndash, 1.065, p = 0.006), larger volume (OR 1.003, 95% CI 1.000&ndash, 1.006, p = 0.029), and necrosis (OR 12.222, 95% CI 1.945&ndash, 76.794, p = 0.008). The mean age of the recurrent GIST group was higher than that of the non-recurrent group (p = 0.045), their tumor long axes were significantly longer (p = 0.005), and their volumes were greater, but this last difference was not significant (p = 0.072). Conclusions: Tumor volume can be considered an additional risk factor in assessing the malignant potential of GISTs and tends to increase in recurrent GISTs.

Aminotransferase activity is a surrogate marker of liver injury showing strong correlations with obesity and metabolic syndrome. However, elevated aminotransferase activity is not uncommon in non-obese and non-alcoholic patients in clinical practice.To examine the relationship between sarcopenia and aminotransferase activity in a large population-based cohort.Data from the Korean National Health and Nutrition Examinations were used. A total of 13,431 subjects were included. A whole-body dual X-ray absorptiometry scan was performed on each patient to measure total and regional muscle mass. Appendicular skeletal muscle mass indices were also obtained.The prevalence of sarcopenia was significantly higher in the group with elevated aminotransferase levels than in the normal liver enzyme group (males: 26.5% vs. 16.9%; females: 38.3% vs. 22.1%, p0.05). The skeletal muscle index was negatively correlated with most cardiometabolic risk factors, including fasting glucose and cholesterol levels. The frequency of elevated aminotransferase increased in male patients with sarcopenia after adjusting for potential confounding factors including age, body mass index, fasting glucose level, dietary, and exercise habits. However, the correlation was no longer observed in women after adjusting for body mass index.Sarcopenia is a risk factor for elevated aminotransferase in men, independently of body mass index, dietary habits, and physical activity.

AIM : Although numerous animal studies suggest that probiotic therapy has beneficial effects in various liver diseases, the evidence for beneficial effects in human liver disease is controversial. This study was carried out to investigate the efficacy of probiotic therapy in alleviating small intestinal bacterial overgrowth (SIBO) and permeability in chronic liver disease. METHODS Fifty-three patients with chronic liver disease were randomized to either probiotic therapy or placebo. Six bacterial species were used: Bifidobacterium bifidum, Bifidobacterium lactis, Bifidobacterium longum, Lactobacillus acidophilus, Lactobacillus rhamnosus, and Streptococcus thermophilus. After 4 weeks, changes in the composition of fecal bacteria, SIBO, intestinal permeability, and clinical symptoms were examined. RESULTS Three of the six probiotic species, B. lactis, L. rhamnosus, and L. acidophilus, increased in the feces of the probiotic therapy group (P

Rationale: Recently tenofovir disoproxil fumarate (TDF) has been widely used as a first-line therapy for chronic hepatitis B (CHB) infection. Although TDF demonstrates successful viral suppression, the possibility of renal failure and lactic acidosis has been proposed with TDF administration, especially in human immunodeficiency virus co-infected patients. However, TDF induced lactic acidosis has never been reported in CHB mono-infected patients. Patient concerns: A 59-year-old man received TDF for hepatitis B associated with cirrhosis. After ten days of TDF administration, nausea, vomiting and abdominal pain developed. High anion gap acidosis with elevated lactate level (pH 7.341, pCO2 29.7 mmHg, HCO3- 15.6mmHg, lactate 3.2mmol/L, anion gap 15.4 mEq/L) was developed. Diagnosis: With no infection, normal diagnostic paracentesis, and urinalysis together with high anion gap and increased blood lactate levels suggested lactic acidosis. Interventions: TDF was stopped, and haemodialysis was performed to control lactic acidosis. Outcomes: Although stopping TDF instantly and treating lactic acidosis using hemodialysis, the patient died. Lessons: Although, Fatal lactic acidosis is very rare in TDF patient, however, decompensated cirrhotic patients should be closely observed to keep the possibility of lactic acidosis in mind.

Supplemental Digital Content is available in the text, Background: This phase III trial compared the efficacy and safety of gemcitabine plus capecitabine (GemCap) versus single-agent gemcitabine (Gem) in advanced pancreatic cancer as first-line chemotherapy. Methods: A total of 214 advanced pancreatic cancer patients were enrolled from 16 hospitals in South Korea between 2007 and 2011. Patients were randomly assigned to receive GemCap (oral capecitabine 1660 mg/m2 plus Gem 1000 mg/m2 by 30-minute intravenous infusion weekly for 3 weeks followed by a 1-week break every 4 weeks) or Gem (by 30-minute intravenous infusion weekly for 3 weeks every 4 weeks). Results: Median overall survival (OS) time, the primary end point, was 10.3 and 7.5 months in the GemCap and Gem arms, respectively (P = 0.06). Progression-free survival was 6.2 and 5.3 months in the GemCap and Gem arms, respectively (P = 0.08). GemCap significantly improved overall response rate compared with Gem alone (43.7% vs 17.6%; P = 0.001). Overall frequency of grade 3 or 4 toxicities was similar in each group. Neutropenia was the most frequent grade 3 or 4 toxicity in both groups. Conclusion: GemCap failed to improve OS at a statistically significant level compared to Gem treatment. This study showed a trend toward improved OS compared to Gem alone. GemCap and Gem both exhibited similar safety profiles.

The relationship between fat distribution and lymph node metastasis has not been well studied. The goal of this study was to determine the impact of visceral obesity on lymph node metastasis in gastric cancer. Metastatic lymph node ratio (MLR) was defined as the number of involved nodes by tumor divided by the total number of resected lymph nodes. Visceral (VFA) and subcutaneous fat areas (SFA) were determined by measuring abdominal fat volume distribution via CT scan, and visceral obesity was defined as a VFA to total fat area ratio (V/T) >0.29. With lymph node metastasis as a dependent variable, the following factors were significant in multivariate analysis among 495 patients: pathologic T stage (P

Background and study aims: Preoperative pathological diagnosis may improve clinical management decisions in patients with upper gastrointestinal subepithelial tumors (SETs). The aims of this study were to evaluate the diagnostic yield of deep biopsy via an endoscopic submucosal dissection (ESD) technique, the complications associated with the procedure, and the impact on management of patients with upper gastrointestinal SETs. Patients and methods: A total of 68 patients with SETs in the stomach or esophagus were voluntarily assigned to two groups. One group underwent endoscopic ultrasound (EUS) and endoscopic deep biopsy using the ESD technique (40 patients), and the other group (28 patients) underwent surgical resection after EUS without obtaining preoperative pathological diagnosis, in accordance with accepted clinical management algorithms. Results: The diagnostic yield of deep biopsy was 90 % (36/40). The results of deep biopsy changed the treatment plans in 14/40 patients (35 %). One patient with lymphoepithelial carcinoma was scheduled for surgical resection, and 13 patients with benign SETs of diameter ≥ 2 cm avoided surgery. Of the 28 patients who underwent surgical resection without preoperative pathological diagnosis, 12 (42.9 %) were confirmed to have benign lesions. The mean procedure time for deep biopsy was 13.7 minutes. There were no procedure-related complications in the deep biopsy group. Conclusions: Deep biopsy by the ESD technique is a safe, high-yield, diagnostic method in patients with upper gastrointestinal SETs. Pathologic confirmation could improve clinical decision making in the management of patients with upper gastrointestinal SETs. Clinical trial registration: NCT 01993199

Background/Aims Because of the similarities in the clinical presentations of Crohn's disease (CD) and intestinal tuberculosis (ITB), differential diagnosis is critical. Mesenteric adipose tissue hypertrophy and creeping fat are characteristic features of CD. The purpose of this study was to assess the usefulness of visceral fat for the differential diagnosis of CD and ITB. Methods We conducted a retrospective review of 50 patients with findings of CD or ITB between January 2005 and July 2008. Abdominal computed tomography (CT) was performed on all subjects during their first evaluation. The abdominal fat area was assessed using quantitative abdominal CT. Results The ratio of visceral fat to total fat (VF/TF) was significantly higher in male CD patients than in male ITB patients. The ratio of visceral fat to subcutaneous fat (VF/SF) was also higher in CD patients than in patients with ITB. For a VF/TF cut-off value of 0.46, the sensitivity and specificity for the diagnosis of CD were 42.1% and 93.3% respectively, with positive and negative predictive values of 88.9% and 56.0%, respectively. Conclusion Measurement of the abdominal fat area using CT can be clinically useful for the differential diagnosis of CD and ITB.

The bio-sensor technologies to detect cancer cells have been attracted much attention because detecting the presence of a cancer in a human blood at an early stage can extend the human lifetime. To diagnose a cancer in human normal blood cells, electrical biosensors such as carbon nanotube field-effective transistor, AlGaN/GaN HEMT, reduced graphene oxide TFT, Si nanowire FET, PEDOT:PSS conducting paper, and ZnO nano-rods have been intensively studied because they detect and diagnose the type and amount of cancer cell by estimating the electrical charge amount of the cancer cell in the human blood. However, they have not demonstrated for detecting and diagnosing a cancer cell in circulating cancer stem cell (CCSC). In our study, thus, we cultured breast cancer cell (BCC) line, MDA-MB-231, and designed cancer detecting system in which the detection devices are implemented with a separation device to separate the cancer cell from mixed solution of cancer cell line and normal blood by utilizing both size and deformability of cancer cell. In particular, we designed a real time enumeration image analysis tool to acquire morphology data of breast cancer cell line for image-based cell analysis. For detecting the cancer cell via determining the threshold voltage shift (∆Vth) of field effect transistor (FET), an In-Ga-Zn-Oxide (IGZO) based FET implemented with Au nano-particles (NPs) was fabricated. For the experimental process, the 10-μL solution of separated cancer cell lines connected with the cancer-anti-body (CD-44) was dropped on the IGZO FET channel with Au NPs where a linker (8-Mercaptooctanoic acid) was attached on Au NPs. Consequently, we successfully demonstrated the separation of cancer cell from normal blood sample and after dropping cancer cell on the detection device the ∆Vth value was shifted negative direction. Furthermore, we observed the fluorescent staining image of cancer cell separated from normal blood sample. We report the separation and detection system which enables to separate and detect cancer cell. Figure 1