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This study aimed to investigate the initial treatment response and short-term mortality of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with hepatocellular carcinoma (HCC) compared with those without HCC. A total of 245 patients with liver cirrhosis diagnosed with SBP between January 2004 and December 2020 were included. Of these, 107 (43.7%) were diagnosed with HCC. Overall, the rates of initial treatment failure, 7-day and 30-day mortality were 91 (37.1%), 42 (17.1%), and 89 (36.3%), respectively. While the baseline CTP score, MELD score, culture-positive rate, and rates of antibiotic resistance did not differ between both groups, patients with HCC had a higher rate of initial treatment failure than those without HCC patients (52.3% vs. 25.4%, P P P

Acute pancreatitis has two mortality peaks, which occurs within the first 2 weeks due to organ failure and then weeks or months later as result of multi-organ failure and local complications. Although there have been several clinical and multidisciplinary evaluation measures, imaging tests, and serological tests proposed to forecast severe acute pancreatitis, there is still no single test available to reliably predict the disease severity and time of death. Future large-scale studies are required to develop an assessment scale that can accurately predict the prognosis and mortality risk of severe acute pancreatitis.

Background/aimsThis study aimed to investigate the factors associated with prolonged hospital stay and in-hospital mortality in patients with pyogenic liver abscess.MethodsWe retrospectively reviewed data from patients with pyogenic liver abscess who were admitted between 2005 and 2018 at three tertiary hospitals in Jeonbuk province, South Korea. Prolonged hospital stay was defined as a duration of hospital admission of more than 21 days.ResultsA total of 648 patients (406 men and 242 women) diagnosed with pyogenic liver abscess were enrolled in the study. The mean maximal diameter of the liver abscess was 5.4 ± 2.6 cm, and 74.9% of the lesions were single. The three groups were divided according to the maximal diameter of the abscess. Laboratory parameters indicated a more severe inflammatory state and higher incidence of complications and extrahepatic manifestations with increasing abscess size. Rates of percutaneous catheter drainage (PCD) insertion, multiple PCD drainage, and salvage procedures as well as duration of drainage were also higher in the large liver abscess group. Of note, the duration of hospitalization and in-hospital mortality were significantly higher in the large hepatic abscess group. A multivariate analysis revealed that underlying diabetes mellitus, hypoalbuminemia, high baseline high-sensitivity C-reactive protein (hs-CRP) and procalcitonin levels, and large maximal abscess diameter were independent factors associated with prolonged hospital stay. Regarding in-hospital mortality, acute kidney injury at admission and maximal diameter of the abscess were independent factors associated with in-hospital mortality.ConclusionsA large maximal diameter of the liver abscess at admission indicated prolonged hospitalization and poor prognosis. More aggressive treatment strategies with careful monitoring are warranted in patients with large liver abscesses.

Background/aim Intestinal mucositis with diarrhea is a dose-limiting toxicity of 5-fluorouracil (5-FU). M40403, a superoxide dismutase mimetic, was evaluated on whether it improves the mucositis with diarrhea. Materials and methods BALB/c mice were treated with daily intraperitoneal injections of 5-FU±M40403 for five consecutive days. Following treatment, light microscopy (apoptosis), electron microscopy (autophagy), and analyses for the expression of apoptosis/autophagy-related proteins were performed in analysing small intestinal samples. Body weight, diarrhea score, blood cytokine levels, complete blood count, and blood chemistries were measured. The in vivo anti-tumor activity of 5-FU±M40403 was also evaluated. Results M40403 improved 5-FU-induced intestinal mucositis (apoptosis and autophagy) and attenuated 5-FU-induced changes in the expression of apoptosis/autophagy-related proteins, weight loss, diarrhea score, and serum TNF-α levels. M40403 neither added further adverse effects nor compromised the anti-tumor activity during 5-FU treatment. Conclusion M40403 can be useful in improving 5-FU-induced intestinal mucositis with diarrhea.

This study was aimed at investigating the clinical efficacy of probiotics in pneumonia patients. To this end, we enrolled 80 participants diagnosed with pneumonia at Naval Pohang Hospital, Pohang, Korea, from May 2016 to January 2017. The participants were randomly assigned to the control and probiotic groups depending on whether they received probiotics. All participants clinically improved but 22.6% of the participants complained of abnormal stool habits after pneumonia treatment. In comparison, fever duration was significantly shorter in the probiotic group, and the group exhibited an improved general condition. The probiotic group also showed better stool characteristics according to the Bristol stool scale (P = 0.009). Notably, the serum hs-CRP levels were significantly lower in the probiotic group at 2 weeks of treatment (P = 0.015), and all participants in the probiotic group achieved their levels within the normal range. Flow cytometry was used to analyze T-helper 17 (Th17) cells and regulatory T cells (Tregs). Tregs were promoted and the Th17 cell/Treg ratio was suppressed after 2 weeks of treatment in the probiotic group (P = 0.007 and 0.037, respectively). This study demonstrated that probiotics improved clinical symptoms and normalized inflammatory biomarker levels in patients with pneumonia. Early infection and inflammation recovery may be due to the immunomodulatory effects of probiotics by facilitating the subset of Tregs and suppressing the Th17 cell/Treg ratio.

Background Detox diet are known as a popular dieting strategies that helps toxins elimination and weight manage but there is very little clinical evidence. The Wellnessup diet (WD) used in the present study designed as a healthy meals based on organic plant based diets including various vegetables, fruits, whole grains, nuts and phytonutrients. Methods To evaluate the effects of 4 week intake of the WD on toxic trace element detoxification, body fat reduction, and safety parameters. Forty-five women with body mass index (BMI) of 23.5–30 kg/m2 were recruited. Thirty of them were assigned 1:1 to the test group (WD, 15 subjects) and control group 1 (calorie-restricted diet, CRD, 15 subjects) in a single blind and randomized, and the remaining 15 subjects were assigned to control group 2 (maintaining regular diet, MRD). The primary outcome were toxic trace element levels in hair (29 types of heavy metals), and the secondary outcomes were changes in anthropometric and urinary organic acids. Results The levels of four toxic trace elements in hair decreased in the WD group after the diet compared to before the diet. Ni, Rh, Sn, and Ga were significantly lower in the WD group than in the CRD or MRD group (p p p p Conclusions Use of WD might have several beneficial effects and safety such as body fat reduction and improving some the element detoxification through caloric restriction but did not reducing body fat mass more than calorie-restricted diet. Trial registration This study was registered at Clinical Research Information Service (CRIS) of Republic of Korea (KCT0003002).

The guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMNs) recommend surgical resection of all main-duct (MD) and mixed-type IPMNs in surgically fit patients. We conducted this study to identify the rates of high-grade dysplasia (HGD) and invasive carcinoma according to the morphological features of the main pancreatic duct (MPD) in patients with MD and mixed IPMN.We performed a retrospective study of 259 patients with histologically proven MD and mixed-type IPMNs who underwent surgery at six academic institutions.The rate of HGD and invasive carcinoma was 11.1% (24/216) in patients without enhancing mural nodules (MNs) and 69.8% (30/43) in patients with MNs. Multivariate analysis showed that MPD diameter of ≥10 mm [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.155-5.505; P = 0.02], diffuse MPD dilatation (OR, 3.2; 95% CI, 1.152-8.998; P = 0.02), and presence of enhancing MNs in MPD (OR, 9.6; 95% CI, 3.928-23.833, P 0.0001) were significant predictors of HGD and invasive carcinoma. Of the 216 patients without enhancing MNs, 79 patients (36.6%) having both segmental MPD dilatation and MPD diameter of10 mm showed significantly lower rates of HGD and invasive carcinoma (3/79, 3.8%) than patients having both diffuse MPD dilatation and MPD diameter ≥10 mm (9/36, 25%, P = 0.001).MD and mixed-type IPMNs having segmental MPD dilatation with MPD dilation10 mm and no enhancing MNs on imaging showed a significantly lower rate of HGD and invasive carcinoma, and watchful follow-up instead of immediate surgical resection might be possible in these patients.

The goal of treatment for mild cognitive impairment (MCI) is to reduce the existing clinical symptoms, delay the progression of cognitive impairment and prevent the progression to Alzheimer’s disease (AD). At present, there is no effective drug therapy for AD treatment. However, early intake of dietary supplements may be effective in alleviating and delaying the MCI. This study aims to evaluate the effects of sesame oil cake extract (SOCE) supplementation on cognitive function in aged 60 years or older adults with memory impairment. A total of 70 subjects received either SOCE (n = 35) or placebo (n = 35) for 12 weeks based on random 1:1 assignment to these two groups. Cognitive function was evaluated by a computerized neurocognitive function test (CNT), and changes in the concentrations of plasma amyloid β (Aβ) proteins and urine 8-OHdG (8-hydroxy-2′-deoxyguanosine) were investigated before and after the experiment. Verbal learning test index items of the CNT improved markedly in the SOCE group compared to the placebo group (p &lt, 0.05). Furthermore, plasma amyloid-β (1–40) and amyloid-β (1–42) levels in the SOCE group decreased significantly compared to that in the placebo group (p &lt, 0.05). There was no statistically significant difference in urine 8-OHdG between the two groups (p &gt, 0.05). Collectively, intake of SOCE for 12 weeks appears to have a beneficial effect on the verbal memory abilities and plasma β-amyloid levels of older adults with memory impairment.

Background and Aims Recently, a newly designed lumen-apposing metal stent (LAMS) with a conventional delivery system was developed. The purpose of this study was to evaluate the effectiveness and safety of a newly designed LAMS for EUS-guided drainage to treat symptomatic pancreatic pseudocysts. Methods This prospective multicenter cohort study included 34 patients with symptomatic pancreatic pseudocysts from 2016 to 2017. The patients underwent EUS-guided drainage with the newly designed LAMS (Niti-S SPAXUS; Taewoong Medical Co, Ltd, Ilsan, South Korea). Effectiveness outcome measurements included technical success rate, clinical success rate, successful stent removal rate, and procedural time. Safety outcome measurements included procedure and/or stent-related adverse events (AEs) and overall AEs. Patients were prospectively followed, and consecutive data were collected at discharge, at stent removal, and 20 days after stent removal. Results Thirty-four patients (mean age 51.7 ± 13.3 years, 26 men) were enrolled. The mean pseudocyst size was 9.23 ± 3.54 cm. The technical success rate was 97.1% (33/34). The clinical success rate was 94.1% (32/34). All stents were successfully removed. The mean procedural time from needle puncture to stent deployment was 10.3 ± 5.7 minutes. Four patients (11.8%) experienced procedure and/or stent-related AEs, including stent maldeployment (n = 1) and pseudocyst infection (n = 3). All patients completely recovered from the AEs. Bleeding caused by the stent or buried LAMS syndrome was not observed. No unplanned endoscopic procedures were required. Conclusions This study showed that EUS-guided drainage using the newly designed LAMS is technically feasible and effective for the treatment of symptomatic pancreatic pseudocysts. (Clinical trial registration number: NCT02730663.)

Background/Aims: To investigate the treatment efficacy and renal safety of long-term tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients with preserved renal function. Methods: The medical records of 919 CHB patients who were treated with TDF therapy were reviewed. All patients had preserved renal function with an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2. Results: A total of 426 patients (184 treatment-naive and 242 treatment-experienced) were included for analysis. A virologic response (VR) was defined as achieving an undetectable serum hepatitis B virus (HBV) DNA level, and the overall VR was 74.9%, 86.7%, and 89.4% at the 1, 2, and 3-year follow-ups, respectively. Achieving a VR was not influenced by previous treatment experience, TDF combination therapy, or antiviral resistance. In a multivariate analysis, being hepatitis B e antigen positive at baseline and having a serum HBV DNA level ≥2,000 IU/mL at 12 months were associated with lower VR rates during the long-term TDF therapy. The overall renal impairment was 2.9%, 1.8%, and 1.7% at the 1, 2, and 3-year follow-ups, respectively. With regard to renal safety, underlying diabetes mellitus (DM) and an initial eGFR of 60 to 89 mL/min/1.73 m2 were significant independent predictors of renal impairment. Conclusions: TDF therapy appears to be an effective treatment option for CHB patients with a preserved GFR. However, patients with underlying DM and initial mild renal dysfunction (eGFR, 60 to 89 mL/min/1.73 m2) have an increased risk of renal impairment. (Gut Liver 2019;13:93-103.)

Excessive alcohol consumption is one of the most significant causes of morbidity and mortality worldwide. Alcohol is oxidized to toxic and carcinogenic acetaldehyde by alcohol dehydrogenase (ADH) and further oxidized to a non-toxic acetate by aldehyde dehydrogenase (ALDH). There are two major ALDH isoforms, cytosolic and mitochondrial, encoded by ALDH1 and ALDH2 genes, respectively. The ALDH2 polymorphism is associated with flushing response to alcohol use. Emerging evidence shows that Lactobacillus and Bifidobacterium species encode alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) mediate alcohol and acetaldehyde metabolism, respectively. A randomized, double-blind, placebo-controlled crossover clinical trial was designed to study the effects of Lactobacillus and Bifidobacterium probiotic mixture in humans and assessed their effects on alcohol and acetaldehyde metabolism. Here, twenty-seven wild types (ALDH2*1/*1) and the same number of heterozygotes (ALDH2*2/*1) were recruited for the study. The enrolled participants were randomly divided into either the probiotic (Duolac ProAP4) or the placebo group. Each group received a probiotic or placebo capsule for 15 days with subsequent crossover. Primary outcomes were measurement of alcohol and acetaldehyde in the blood after the alcohol intake. Blood levels of alcohol and acetaldehyde were significantly downregulated by probiotic supplementation in subjects with ALDH2*2/*1 genotype, but not in those with ALDH2*1/*1 genotype. However, there were no marked improvements in hangover score parameters between test and placebo groups. No clinically significant changes were observed in safety parameters. These results suggest that Duolac ProAP4 has a potential to downregulate the alcohol and acetaldehyde concentrations, and their effects depend on the presence or absence of polymorphism on the ALDH2 gene.

Cholestasis is a pathological condition involving blockage of bile flow that results in hepatotoxicity, inflammation, and fibrosis. Although recent studies have shown that histone deacetylases (HDACs) are involved in the progression of fibrosis in various organs, the role of HDAC8 on liver fibrosis has until now remained unexplored. This study presents a newly-synthesized, selective HDAC8 inhibitor SPA3014 composed of a vinyl disulfide-sulfoxide core, and evaluates its therapeutic efficacy against cholestatic liver injury and fibrosis in bile duct-ligated (BDL) mice. We first observed the increase in HDAC8 protein levels in mice with BDL and patients with cholestatic liver disease. Mice with BDL that were pretreated with SPA3014 had lower liver damage and fibrosis, based on gross examination, histopathologic findings, and biochemical analyses, than did vehicle-treated mice. Studies with LX-2 human hepatic stellate cells showed that SPA3014 exerted protective effects by inhibiting TGF-β-mediated activation of MAPK-Smad2/3 and JAK2-STAT3 pathways and by upregulating PPARγ expression. Overall, these results strongly suggest that HDAC8 inhibition constitutes a new therapeutic strategy for treatment of cholestatic liver injury.

Introduction: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) is an alternative treatment option for patients with acute cholecystitis, especially for those who are unsuitable for cholecystectomy. Recently used luminal apposing metal stents (LAMS) in EUS-GBD has several advantages over standard metal stents. However, there is no current guideline on where to locate the LAMS when transgastric approach is required. This study reports a case of gastric outlet obstruction (GOO) by placing LAMS too close to the pyloric ring. Patient concerns: A 79-year-old female patient was referred to our department for evaluation of a large hepatic mass on abdominal ultrasound. Abdominal pain on right upper quadrant and spiking fever up to 38 °C appeared after liver biopsy. Abdominal ultrasound showed thickened GB wall and positive sonographic Murphy sign. Diagnoses: Intrahepatic cholangiocarcinoma with multiple lung and intrahepatic metastasis, acute cholecystitis, and pyloric ring obstruction caused by flange of LAMS in EUS-GBD. Interventions: EUS-GBD via transgastric approach was performed with LAMS. After complete deployment of stent, esophagogastroduodenoscopy showed complete GOO by flange of LAMS. A gastroduodenal metal stent was inserted to relieve the GOO. Outcomes: The patient recovered well. She did not complain about obstruction induced symptom such as vomiting or abdominal fullness after gastroduodenal stent insertion. Conclusion: To the best of our knowledge, this is the first case report of EUS-GBD induced GOO. If physicians use LAMS as a transgastric approach in EUS-GBD, the puncture site should be carefully selected considering the size of the flange.

Background Candida sp. osteoarticular infection is rare and most often due to hematogenous seeding during an episode of candidemia in immunocompromised patients. However, the diagnosis can be delayed in patients with subtle symptoms and signs of joint infection without a concurrent episode of candidemia. Case presentation A 75-year-old woman presented with a three-year history of pain and swelling of the left knee. Candida pelliculosa was detected from the intraoperative tissue when the patient had undergone left total knee arthroplasty 32 months ago, but no antifungal treatment was performed. One year after the total knee arthroplasty, C. pelliculosa was repeatedly isolated from the left knee synovial fluid and antifungal treatment comprising amphotericin B deoxycholate and fluconazole was administered. However, joint infection had extended to the adjacent bone and led to progressive joint destruction. The patient underwent surgery for prosthesis removal and received prolonged antifungal treatment with micafungin and fluconazole. Conclusions This case shows that C. pelliculosa, an extremely rare non-Candida albicans sp., can cause fungal arthritis and lead to irreversible joint destruction owing to delayed diagnosis and treatment.

Recent therapeutic strategies to suppress restenosis after biliary stent placement are insufficient. Here, we demonstrate the usefulness of a self-expandable metal stent (SEMS), a stent mesh coated with silver nanoparticles (AgNPs), for suppression of both stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. The AgNP-coated SEMSs were prepared using a simple bio-inspired surface modification process. Then, the prepared SEMSs were successfully placed in 22 of 24 rabbits. Sludge formation in the AgNP-coated SEMS groups was significantly decreased compared to the control group on gross findings. Cholangiographic and histologic examinations demonstrated significantly decreased tissue hyperplasia in the AgNP-coated SEMS groups compared with the control group (p &lt, 0.05 for all). There were no differences between the AgNP-coated SEMS groups (p &gt, 0.05 for all). However, in the group coated with the greatest concentration of AgNPs (Group D), submucosal fibrosis was thicker than in the other AgNP-coated groups (p &lt, 0.05 for all). The AgNP-coated metallic stent mesh significantly suppressed stent-induced tissue hyperplasia and biliary sludge formation in the rabbit bile duct. Taken together, the AgNP coating strategy developed in this study could be widely utilized in non-vascular medical devices for anti-bacterial and anti-inflammatory responses.

Background We aimed to investigate the efficacy of the lifestyle intervention (LSI) program in controlling blood glucose regulation and health promotion in type 2 diabetic (T2D) patients. Methods Thirty adults with a diagnosed with diabetes were randomly assigned to LSI and control groups. The LSI group maintained their daily routines after participating twice in the LSI program, while control group maintained 4 weeks of daily life without participating in an intervention. Results HbA1c levels in the LSI group decreased significantly after participation (p = 0.025) compared with levels before the study, but there was no significant difference between the groups. The weight and body mass index (BMI) of the LSI group tended to decrease significantly compared with the control group (p = 0.054 and p = 0.055, respectively), and the waist circumference (WC) of the LSI group decreased significantly compared with that of the control group (p = 0.048). In the effects of the LSI program according to the polymorphism of GCKR genes, changes in glycated albumin (GA) (%), HbA1c, WC, BMI, and weight showed a significant decrease in the non-risk (TT genotype) GCKR group compared with the risk group (CC and TC genotype). Conclusion Application of the four-week LSI program to diabetics revealed positive effects on blood-glucose control and improvement in obesity indicators. In particular, the risk group with variations in the GCKR gene was associated with more genetic effects on indicators such as blood glucose and obesity than was the non-risk group.

Background: Detox diet are known as a popular dieting strategies that helps toxins elimination and weight manage but there is very little clinical evidence. Methods: To evaluate the effects of 4 week intake of the Wellnessup diet (WD) on toxic trace element detoxification, body fat reduction, and safety parameters. Forty-five women with body mass index (BMI) of 23.5-30 kg/m 2 were recruited. Thirty of them were assigned 1:1 to the test group (WD, 15 subjects) and control group 1 (calorie-restricted diet, CRD, 15 subjects) in a single blind and randomized, and the remaining 15 subjects were assigned to control group 2 (maintaining regular diet, MRD). The primary outcome were toxic trace element levels in hair (29 types of heavy metals), and the secondary outcomes were changes in anthropometric and urinary organic acids. Results: The levels of four toxic trace elements in hair decreased in the WD group after the diet compared to before the diet. Ni, Rh, Sn, and Ga were significantly lower in the WD group than in the CRD or MRD group (p

Additional file 2: Table S1. Provided mean dietary menu of test meals (per day) samples. Table S2. Changes in organic acid on urine. Table S3. Laboratory profiles of the participants in this study.

Additional file 1. CONSORT 2010 checklist *.

Abdominal ultrasonography uses the transmission and reflection of ultrasound waves to observe the internal organs through the abdominal wall and can visualize various abdominal anatomical structures. Abdominal ultrasound examinations are performed by gastroenterologists or other specialists in internal medicine and radiologists trained for this procedure. Thus far, abdominal ultrasonography has not been included in the standard education of gastroenterologists in Korea. On the other hand, abdominal ultrasonography is being used increasingly, making it necessary to establish a training program in Korea. Abdominal ultrasonography was established as an essential part of education for the resident training program in 2017. In addition, an educational accreditation system for the trainers of ultrasonography in the field of internal medicine, including gastroenterology, was developed in 2018. This article describes the development process of the educational accreditation system for trainers of ultrasonography.

Balsalazide is a colon-specific prodrug of 5-aminosalicylate that is associated with a reduced risk of colon cancer in patients with ulcerative colitis. Parthenolide, a strong NF-κB inhibitor, has recently been demonstrated to be a promising therapeutic agent, promoting apoptosis of cancer cells. In the current study, the antitumor effect of balsalazide combined with parthenolide in human colorectal cancer cells and colitis-associated colon cancers (CAC) was investigated. The results demonstrate that the combination of balsalazide and parthenolide markedly suppress proliferation, nuclear translocation of NF-κB, IκB-α phosphorylation, NF-κB DNA binding, and expression of NF-κB targets. Apoptosis via NF-κB signaling was confirmed by detecting expression of caspases, p53 and PARP. Moreover, treatment of a CAC murine model with parthenolide and balsalazide together resulted in significant recovery of body weight and improvement in histologic severity. Administration of parthenolide and balsalazide to CAC mice also suppressed carcinogenesis as demonstrated by uptake of 18F-fluoro-2-deoxy-D-glucose (FDG) using micro-PET/CT scans. These results demonstrate that parthenolide potentiates the efficacy of balsalazide through synergistic inhibition of NF-κB activation and the combination of dual agents prevents colon carcinogenesis from chronic inflammation. Implications: This study represents the first evidence that combination therapy with balsalazide and parthenolide could be a new regimen for colorectal cancer treatment. Mol Cancer Res; 15(2); 141–51. ©2016 AACR.

AIM To assess the effect of long-term oral nucleos(t)ide analogues (NUCs) therapy on liver volume change in patients with suppress hepatitis B virus (HBV)-related liver cirrhosis. METHODS We reviewed the data of naïve patients with HBV-related liver cirrhosis, who had taken oral NUCs therapy, between 2003 and 2007 at Chonbuk University Hospital. We analyzed two consecutive sets of abdominal computerized tomography scans-one at the time of treatment initiation and another at the second-year follow-up. Liver volume was calculated by 3-dimensional liver extraction volumetry program. RESULTS A total of 55 patients (34 males) were included. There was 114.3 mL ± 167.8 mL (12.9% ± 17.9%) of increase in liver volume during the two years of NUCs therapy (993.8 mL ± 242.8 mL at baseline vs 1108.1 mL ± 263.3 mL at two-year follow-up, P < 0.001). The ratio of the measured baseline liver volume to the estimated standard liver volume was improved from 70.8% to 78.0%. An increase in liver volume was shown not only in patients with compensated cirrhosis (P = 0.046) but also in those with decompensated cirrhosis (P < 0.001). Significant factors for volume increases were Child-Turcotte-Pugh grade and model for end-stage liver disease score improvement without virological breakthrough. In multiple linear regression analysis, delta albumin and delta alanine aminotransferase levels showed a significant association with the increase in liver volume (P = 0.002 and 0.005, respectively). CONCLUSION Long-term oral NUCs therapy in patients with HBV-related liver cirrhosis lead to significant increase in liver volume assessed with 3-dimensional liver extraction volumetry program.

Background/Aims: With recent changes in the treatment of pancreatic cancer, patients’ active decision-making has become more important. Nevertheless, it is difficult to give patients proper insights into the disease. The purpose of this study was to determine associated factors between pancreatic cancer awareness and treatment decisions as well as how cancer awareness affects the timing of treatment decisions and the desired treatment method. Methods: This is a retrospective study that reviewed and analyzed the electronic medical records of 110 patients who were diagnosed with pancreatic cancer from January 2013 to April 2016. A "patient with pancreatic cancer awareness" means that the patient was informed of their disease state before making the first treatment decision. Results: Of all, only 63.6% of patients (n=70) were shown to have pancreatic cancer awareness before making their first treatment decision. Compared to patients without pancreatic cancer awareness, patients with pancreatic cancer awareness were younger (65.00 vs. 76.98, t=6.70, p

Background/Aims 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) reflects biological aggressiveness and predicts prognoses in various tumors. Evaluating the oncologic significance of the preoperative metabolic phenotype might be necessary for planning the surgical strategy in resectable pancreatic cancers. Methods From January 2010 to December 2015, a total of 93 patients with pathologic T3 (pT3) pancreatic cancer were included in this study. Clinicopathological parameters and PET parameters were evaluated, and transcriptome-wide analysis was performed to identify the oncologic impact and molecular landscape of the metabolic phenotype of resectable pancreatic cancers. Results Preoperative metabolic tumor volume (MTV)2.5 was significantly higher in the pN1 group compared to the pN0 group (11.1±11.2 vs 6.5±7.8, p=0.031). Higher MTV2.5 values (MTV2.5 ≥4.5) were associated with multiple lymph node metastasis (p=0.003), and the lymph node ratio was also significantly higher in resected pT3 pancreatic cancer with MTV2.5 ≥4.5 compared to those with MTV2.5

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.

Genome-wide association study in diffusely infiltrating type cholangiocarcinoma (CC) can be limited due to the difficulty of obtaining tumor tissue. We aimed to evaluate the genomic alterations of diffusely infiltrating type CC using next-generation sequencing (NGS) of bile and to compare the variations with those of mass-forming type CC. A total of 24 bile samples obtained during endoscopic retrograde cholangiopancreatography (ERCP) and 17 surgically obtained tumor tissue samples were evaluated. Buffy coat and normal tissue samples were used as controls for a somatic mutation analysis. After extraction of genomic DNA, NGS analysis was performed for 48 cancer related genes. There were 27 men and 14 women with a mean age of 65.0±11.8years. The amount of extracted genomic DNA from 3cm(3) of bile was 66.0±84.7μg and revealed a high depth of sequencing coverage. All of the patients had genomic variations, with an average number of 19.4±2.8 and 22.3±3.3 alterations per patient from the bile and tumor tissue, respectively. After filtering process, damaging SNPs (8 sites for each type of CC) were predicted by analyzing tools, and their target genes showed relevant differences between the diffusely infiltrating and mass-forming type CC. Finally, in somatic mutation analysis, tumor-normal paired 14 tissue and 6 bile samples were analyzed, genomic alterations of EGFR, FGFR1, ABL1, PIK3CA, and CDKN2A gene were seen in the diffusely infiltrating type CC, and TP53, KRAS, APC, GNA11, ERBB4, ATM, SMAD4, BRAF, and IDH1 were altered in the mass-forming type CC group. STK11, GNAQ, RB1, KDR, and SMO genes were revealed in both groups. The NGS analysis was feasible with bile sample and diffusely infiltrating type CC revealed genetic differences compared with mass-forming type CC. Genome-wide association study could be performed using bile sample in the patients with CC undergoing ERCP and a different genetic approach for accurate diagnosis, pathogenesis study, and targeted therapy will be needed in diffusely infiltrating type CC.

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.

Glutamine, traditionally a non-essential amino acid, now has been considered as essential in serious illness and injury. It is a major precursor for glutathione synthesis. However, the anti-fibrotic effect of glutamine and its molecular mechanism in experimental liver fibrosis have not been explored. In the present study we aimed to examine the potential role of glutamine in carbon tetrachloride (CCl4) induced liver fibrosis and TGF-β1 mediated epithelial mesenchymal transition (EMT) and apoptosis in mouse hepatocytes. Liver fibrosis was induced by intraperitoneal injection of CCl4 three times a week for 10 weeks. Glutamine treatment effectively attenuated liver injury and oxidative stress. Collagen content was significantly decreased in liver sections of glutamine treated mice compared to CCl4 model mice. Furthermore, glutamine decreased expression level of α-SMA and TGF-β in liver tissue. Our in vitro study showed that TGF-β1 treatment in hepatocytes resulted in loss of E-cadherin and increased expression of mesenchymal markers and EMT related transcription factor. In addition, TGF-β1 increased the expression of apoptotic markers. However, glutamine interestingly suppressed TGF-β1 mediated EMT and apoptosis. In conclusion, our results suggest that glutamine ameliorates CCl4 induced liver fibrosis and suppresses TGF-β1 induced EMT progression and apoptosis.

MicroRNA-9 (miR-9) has been reported to play a suppressive or promoting role according to cancer type. In this study, we investigated the effects of anoctamin-1 (ANO1) and miR-9 on colorectal cancer (CRC) cell proliferation, migration, and invasion and determined the underlying molecular mechanisms. Thirty-two paired CRC tissues and adjacent normal tissues were analyzed for ANO1 expression using quantitative real-time PCR (qRT-PCR). HCT116 cells were transiently transfected with miR-9 mimic, miR-9 inhibitor, or si-ANO1. Cell proliferation was determined by MTT, and flow cytometric analysis, while cell migration and invasion were assayed by trans-well migration and invasion assay in HCT116 cells. ANO1 was validated as a target of miR-9 using luciferase reporter assay and bioinformatics algorithms. We found that ANO1 expression was up-regulated in CRC tissues compared with adjacent normal tissues. ANO1 expression was associated with advanced tumor stage and lymph node metastasis, and there was an inverse relationship between miR-9 and ANO1 mRNA expression in CRC specimens, but no significant difference was found between miR-9 and ANO1 expression. ANO1 is a direct target of miR-9, and overexpression of miR-9 suppressed both mRNA and protein expression of ANO1 and inhibited cell proliferation, migration, and invasion of HCT116 cells. We also showed that overexpression of miR-9 suppressed expression of p-AKT, cyclin D1, and p-ERK in HCT116 cells. We conclude that miR-9 inhibits CRC cell proliferation, migration, and invasion by directly targeting ANO1, and miR-9/ANO1 could be a potential therapeutic target for CRC.

MiRNA (miR)-206 plays a tumor suppressor role in various cancer types. Here, we investigated whether miR-206 is involved in prostaglandin E2 (PGE2)-induced epithelial–mesenchymal transition (EMT) in colorectal cancer (CRC) cells through the targetting of transmembrane 4 L six family member 1 (TM4SF1).The effect of PGE2 on growth and apoptosis of CRC cells was evaluated using the MTT assay and flow cytometry analysis, respectively. TM4SF1 and miR-206 expression levels were determined with quantitative polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The concentration of PGE2 in the serum of CRC patients and healthy controls was measured with an ELISA kit. A miR-206 or TM4SF1 construct was transfected into cells with PGE2. Transwell migration and invasion assays were used to examine cell migration and invasion properties. Additionally, a luciferase assay was performed to determine whether TM4SF1 was directly targetted by miR-206.We found that miR-206 was down-regulated and TM4SF1 was up-regulated in human CRC tissues and cell lines. Moreover, miR-206 was negatively correlated with TM4SF1 expression. Bioinformatics analysis and a luciferase reporter assay revealed that miR-206 directly targetted the 3′-untranslated region (UTR) of TM4SF1, and TM4SF1 expression was reduced by miR-206 overexpression at both the mRNA and protein levels. Additionally, PGE2 significantly suppressed the expression of miR-206 and increased the expression of TM4SF1 in CRC cells. PGE2 induction led to enhanced CRC cell proliferation, migration, and invasion. Moreover, the overexpression of miR-206 decreased CRC cell proliferation, migration, and invasion compared with control group in PGE2-induced cells, and these effects could be recovered by the overexpression of TM4SF1. Overexpression of miR-206 also suppressed the expression of β-catenin, VEGF, MMP-9, Snail, and Vimentin and enhanced E-cadherin expression in PGE2-induced cells. These results could be reversed by the overexpression of TM4SF1. At last, up-regulation of miR-206 suppressed expression of p-AKT and p-ERK by targetting TM4SF1 in PGE2-induced cells.Our results provide further evidence that miR-206 has a protective effect on PGE2-induced colon carcinogenesis.

The purpose of this research was to evaluate if withdrawal time is a useful index in spite of differences in gastroenterologists’ ability and if there are other quality indicators of colonoscopy. A total of 665 consecutive, asymptomatic individuals of average risk between 50 and 75 years of age who underwent screening colonoscopies performed by 12 gastroenterologists were included in this study. The endoscopists were classified to either the experienced group (group A, N = 6) or the under-experienced group (group B, N = 6). The endoscopists were unaware that they were being studied during the two-month study period. In group A, adenoma detection rate was 0.56, while in group B it was 0.43 (P = 0.048). The mean withdrawal time ranged widely from 4.2 to 10.3 min per patient with a mean value of 6.83 for group A and 6.54 for group B. There was a significantly positive relationship between the number of adenomas detected and the withdrawal time for group B (r = 0.827, P = 0.005), but not for group A (r = −0.152, P = 0.584). In the case of group A, the ratio of cecal intubation time to withdrawal time (I/E ratio) less than 1 showed significantly correlated adenoma detection rate compared to I/E ratio greater than 1 (r = −0.308, P = 0.036). In the case of group B, mean I/E ratio was 1.7 and all endoscopists' I/E ratios were greater than 1. For experienced endoscopists, a useful supplementary quality indicator of colonoscopy is to keep intubation/withdrawal time ratio less than 1 and it is necessary for under-experienced endoscopists to try to keep enough withdrawal time.

Background/aims Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. Methods A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. Results A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. Conclusions Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.

Background/Objectives Prediction of malignancy in patients with BD-IPMNs is critical for the management. The aim of this study was to elucidate predictors of malignancy in patients with ‘pure' BD-IPMNs who had a main pancreatic duct (MPD) diameter of ≤5 mm according to the most recent international consensus criteria and in whom MPD involvement was excluded on postoperative histology. Methods We identified 177 patients with ‘pure' BD-IPMNs based on preoperative imaging and postoperative histology from 15 tertiary referral centers in Korea. BD-IPMNs with low-grade ( n = 72) and moderate-grade ( n = 66) dysplasia were grouped as benign and BD-IPMNs with high-grade dysplasia ( n = 10) and invasive carcinoma ( n = 29) were grouped as malignancy. Results On univariate analysis, particular symptoms (jaundice and clinical pancreatitis), CT findings (cyst size > 3 cm, the presence of enhancing mural nodules) and EUS features (the presence of mural nodules, the mural nodule size > 5 mm) were significant risk factors predicting malignant BD-IPMNs. Multivariate analysis revealed that the cyst size > 3 cm (odds ratio = 9.9), the presence of enhancing mural nodules on CT (odds ratio = 19.3) and the mural nodule size > 5 mm on EUS (odds ratio = 14.9) were the independent risk factors for the presence of malignancy in BD-IPMNs ( p Conclusions The cyst size > 3 cm, the presence of enhancing mural nodules on CT, the mural nodule size > 5 mm on EUS are three independent predictors of malignancy in patients with ‘pure' BD-IPMNs.

BACKGROUND/AIM Delayed bleeding is a serious complication that occurs after polypectomy. Many risk factors for delayed bleeding have been suggested, but there is little analysis of procedure-related risk factors. The purpose of this study is to identify a wide range of risk factors for delayed postpolypectomy bleeding (DPPB) and analyze the correlations of those potential DPPB risk factors. MATERIALS AND METHODS In this retrospective cohort study, 5981 polypectomies in 3788 patients were evaluated between January 2010 and February 2012. Patient-related, polyp-related, and procedure-related factors were evaluated as potential DPPB risk factors. RESULTS Delayed bleeding occurred in 42 patients (1.1%). Multivariate analysis revealed that polyp size >10 mm [odds ratio (OR), 2.785; 95% confidence interval (CI), 1.406-5.513; P=0.003], location in the right hemi-colon (OR, 2.289; 95% CI, 1.117-4.693; P=0.024), and endoscopist's experience (

Background Objective evaluation tools for assessing the effectiveness of stenting in palliative treatment of malignant biliary obstruction are not satisfactory. Effects of biliary stenting on liver volume change have never been studied. Objective We aimed to use volumetry to analyze liver volume changes after endoscopic stenting in bile duct cancer according to the location and number of stents. Design Retrospective review. Setting University hospital. Patients Patients with a diagnosis of hilar or distal bile duct cancer and who underwent biliary metal stenting. Interventions ERCP with self-expandable metal stent placement. Main Outcome Measurements Liver volume change after biliary stenting and its comparison according to the location (hilar vs distal common bile duct) and number (hilar bilateral vs hilar unilateral). Results There were 60 patients; 31 were treated for hilar bile duct cancer (13 for bilateral stent and 18 for unilateral stent) and 29 for distal bile duct cancer. Overall mean follow-up duration was 11.7 ± 4.9 weeks. Liver volume increased 17.4 ± 24.1%. The rate of liver growth was rapid during the early period from 4 to 8 weeks. Stenting in hilar bile duct cancer tended to increase liver volume more than distal biliary stents (22.5% vs 11.9%, P = .091). In hilar bile duct cancer, unilateral and bilateral stents showed similar liver volume increases (20.1% and 25.8%, respectively; P = .512). Limitations Single center, retrospective. Conclusions Biliary stenting markedly increased liver volume in both hilar and distal bile duct cancer. Our data suggest that liver volume assessment could be a useful tool for evaluating stent efficacy.

Parthenolide (PT) is responsible for the bioactivities of feverfew (Tanacetum parthenium). Apart from its potent anti-inflammatory effects, this compound has been reported to induce apoptosis in various cancer cells. However, little is known about its role in the process of tumor angiogenesis. In the present study, we investigated the effects and potential mechanisms of action of PT on angiogenesis in human colorectal cancer (CRC). The anti-angiogenic effects of PT were evaluated in cultured human umbilical vein endothelial cells (HUVECs) and in the human CRC cell lines, HT-29, SW620 and HCT116. PT markedly inhibited vascular cell migration and capillary-like structure formation even at a dose which had not effects on cell viability. PT also suppressed the expression of angiogenic biomarker proteins [vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)1 and VEGFR2] in both the HUVECs and CRC cells. Additionally, PT effectively inhibited tumor neovascularization in a HT-29 xenograft model. These results indicate that PT suppresses angiogenesis by reducing the expression of VEGF and its receptors and may be a viable drug candidate in anti-angiogenesis therapies for human CRC.