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Background: Advanced colorectal adenoma (ACA) refers to adenomas with the following predictive characteristics: ≥1 cm in diameter, and/or villous component, and/or high-grade dysplasia. ACA has high risk of transforming to colorectal cancer, and the recurrence rate is relatively high., Objective: To assess the outcomes of patients with ACA undergoing endoscopic resection and to identify risk factors for local recurrence and development of metachronous advanced neoplasm., Design: Retrospective cohort study., Setting: Tertiary care medical center., Patients: From 2005 to 2011, the records of 3625 patients who underwent colonoscopic polypectomy at Seoul National University Hospital were retrospectively reviewed. Patients with synchronous colorectal cancers, inflammatory bowel disease, previous colorectal resection, loss to follow-up, and incomplete resection were excluded., Intervention: Endoscopic resection for ACA., Main Outcome Measurements: Local recurrence and metachronous advanced neoplasm., Results: The study included 917 patients with 1206 ACAs. The median duration of follow-up was 28.5 months (interquartile range, 12.8-51.7). Independent risk factors for local recurrence included ACA with 2 or more predictive characteristics (adjusted hazard ratio [HR], 2.46; 95% confidence interval [CI], 1.11-5.48; P = .027) and piecemeal resection (adjusted HR, 6.96; 95% CI, 1.58-30.71; P = .010). Independent risk factors for metachronous advanced neoplasm were male gender (adjusted HR, 1.65; 95% CI, 1.02-2.65; P = .041), ≥3 adenomas (adjusted HR, 2.56; 95% CI, 1.72-3.82; P < .001), and ≥3 ACAs (adjusted HR, 1.44; 95% CI, 1.01-2.06; P = .045)., Limitations: Retrospective design., Conclusion: ACAs with 2 or more predictive characteristics recurred locally at a higher rate than ACAs with 1 predictive characteristic. These results suggest that patients who are found to have ACAs with 2 or more predictive factors at index colonoscopy are at higher risk for local recurrence, and follow-up colonoscopy should be performed sooner., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Aims: Ursolic acid (UA), a natural pentacyclic triterpenoid acid, has been reported to show immunomodulatory activity. This study investigated the effects of UA on nuclear factor-kappa B (NF-κB) signaling in cells and experimental murine colitis., Main Methods: Human intestinal epithelial cells (IECs) COLO 205 and peritoneal macrophages from IL-10-deficient (IL-10(-/-)) mice were pretreated with UA and then stimulated with tumor necrosis factor-α (TNF-α) and lipopolysaccharide (LPS), respectively. The expression of pro-inflammatory cytokines was determined by real-time RT-PCR and ELISA. The effect of UA on NF-κB signaling was examined by immunoblot analysis to detect IκBα phosphorylation/degradation and electrophoretic mobility shift assay to assess the DNA binding activity of NF-κB. For in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis in C57BL/6 wild-type mice and chronic colitis in IL-10(-/-) mice were treated with or without UA. Colitis was quantified by histopathologic evaluation. Immunohistochemical staining for phosphorylated IκBα was performed in the colonic tissue., Key Findings: UA significantly inhibited the production of pro-inflammatory cytokines, IκBα phosphorylation/degradation and NF-κB DNA binding activity in both IEC and IL-10(-/-) peritoneal macrophages stimulated with TNF-α and LPS, respectively. UA significantly reduced the severity of DSS-induced murine colitis, as assessed by the disease activity index, colon length, and histopathology. UA also significantly ameliorated the severity of colitis in IL-10(-/-) mice. Furthermore, UA suppressed IκBα phosphorylation in the colonic tissue., Significance: UA inhibits NF-κB activation in both IECs and macrophages, and attenuates experimental murine colitis. These results suggest that UA is a potential therapeutic agent for inflammatory bowel disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aim: To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients., Methods: This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms., Results: Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients., Conclusion: The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis.

Aim: To investigate the prognostic factors determining the success rate of non-surgical treatment in the management of post-operative bile duct injuries (BDIs)., Methods: The study patients were enrolled from the pancreatobiliary units of a tertiary teaching hospital for the treatment of BDIs after hepatobiliary tract surgeries, excluding operations for liver transplantation and malignancies, from January 1999 to August 2010. A total of 5167 patients underwent operations, and 77 patients had BDIs following surgery. The primary end point was the treatment success rate according to different types of BDIs sustained using endoscopic or percutaneous hepatic approaches. The type of BDI was defined using one of the following diagnostic tools: endoscopic retrograde cholangiography, percutaneous transhepatic cholangiography, computed tomography scan, and magnetic resonance cholangiography. Patients with a final diagnosis of BDI underwent endoscopic and/or percutaneous interventions for the treatment of bile leak and/or stricture if clinically indicated. Patient consent was obtained, and study approval was granted by the Institutional Review Board in accordance with the legal regulations of the Human Clinical Research Center at the Seoul National University Hospital in Seoul, South Korea., Results: A total of 77 patients were enrolled in the study. They were divided into three groups according to type of BDI. Among them, 55 patients (71%) underwent cholecystectomy. Thirty-six patients (47%) had bile leak only (type 1), 31 patients had biliary stricture only (type 2), and 10 patients had both bile leak and biliary stricture (type 3). Their initial treatment modalities were non-surgical. The success rate of non-surgical treatment in each group was as follows: BDI type 1: 94%; type 2: 71%; and type 3: 30%. Clinical parameters such as demographic factors, primary disease, operation method, type of operation, non-surgical treatment modalities, endoscopic procedure steps, type of BDI, time to diagnosis and treatment duration were evaluated to evaluate the prognostic factors affecting the success rate. The type of BDI was a statistically significant prognostic factor in determining the success rate of non-surgical treatment. In addition, a shorter time to diagnosis of BDI after the operation correlated significantly with higher success rates in the treatment of type 1 BDIs., Conclusion: Endoscopic or percutaneous hepatic approaches can be used as an initial treatment in type 1 and 2 BDIs. However, surgical intervention is a treatment of choice in type 3 BDI.

Aims: Intestinal alkaline phosphatase (IAP) is an intestinal brush border enzyme that is shown to function as a gut mucosal defense factor, but its defensive mechanism remains unclear. The aims of this study were to evaluate the effect of IAP on intestinal epithelial cells and macrophages, and on chronic colitis in interleukin-10-deficient (IL-10(-/-)) mice., Main Methods: Human intestinal epithelial cells COLO 205 and peritoneal macrophages from IL-10(-/-) mice were pretreated with IAP and then stimulated with lipopolysaccharide (LPS). IL-8 secretion from COLO205 cells and TNF-α, IL-6, IL-12 from peritoneal macrophages were measured by ELISA. Electrophoretic mobility shift assay was used to assess the DNA binding activity of NF-κB and IκBα phosphorylation/degradation was evaluated by immunoblot assay in COLO 205. For the in vivo study, colitis was induced in IL-10(-/-) mice with piroxicam, the mice were then treated with 100 or 300 units of IAP by oral gavage for 2 weeks. Colitis was quantified by histopathologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry., Key Findings: IAP significantly inhibited LPS-induced inflammatory cytokine production in both IECs and peritoneal macrophages. IAP also attenuated LPS-induced NF-κB binding activity and IκBα phosphorylation/degradation in IECs. Oral administration of IAP significantly reduced the severity of colitis and down-regulated colitis-induced IκBα phosphorylation in IL-10(-/-) mice., Significance: IAP may inhibit the activation of intestinal epithelial cells and peritoneal macrophages, and may attenuate chronic murine colitis. This finding suggests that IAP supplementation is a potential therapeutic option for inflammatory bowel disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Enalapril, an angiotensin-converting enzyme (ACE) inhibitor, has pleiotropic effects such as anti-inflammatory effects. This study investigated the effect of enalapril on the nuclear factor-kappa B (NF-κB) pathway and on experimental colitis., Main Methods: The human intestinal epithelial cell (IEC) line COLO 205 and peritoneal macrophages from C57BL/6 wild-type mice and IL-10-deficient (IL-10(-/-)) mice were prepared and subsequently stimulated with lipopolysaccharide (LPS) alone or LPS plus enalapril. The effect of enalapril on NF-κB signaling was examined by western blotting to detect IκBα phosphorylation/degradation; an electrophoretic mobility shift assay (EMSA) to assess the DNA binding activity of NF-κB; and ELISAs to qualify IL-8, TNF-α, IL-6, and IL-12 production. In in vivo studies, dextran sulfate sodium (DSS)-induced acute colitis in wild-type mice and chronic colitis in IL-10(-/-) mice were treated with or without enalapril. Colitis was quantified by histologic scoring, and the phosphorylation of IκBα in the colonic mucosa was assessed using immunohistochemistry., Key Findings: Enalapril significantly inhibited LPS-induced IκBα phosphorylation/degradation, NF-κB binding activity, and pro-inflammatory cytokine production in both IEC and peritoneal macrophages. The administration of enalapril significantly reduced the severity of colitis, as assessed based on histology in both murine colitis models. Furthermore, in colon tissue, the up-regulation of IκBα phosphorylation with colitis induction was attenuated in enalapril-treated mice., Significance: Enalapril may block the NF-κB signaling pathway, inhibit the activation of IECs and macrophages, and attenuate experimental murine colitis by down-regulating IκBα phosphorylation. These findings suggest that enalapril is a potential therapeutic agent for inflammatory bowel disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Gastric mucosal inflammation can develop after challenge with noxious stimuli such as alcohol. Specially, alcohol stimulates the release of inflammatory cytokines but does not increase gastric acid secretion, leading to gastric mucosal damage. The plant sterol guggulsterone and its novel derivative GG-52 have been reported to inhibit nuclear factor-κB (NF-κB) signaling in intestinal epithelial cells and experimental colitis. In the present study, we investigated the anti-inflammatory effects of GG-52 on gastric epithelial cells and on ethanol-induced gastric mucosal inflammation in mice. GG-52 inhibited the expression of interleukin-8 (IL-8) in gastric epithelial AGS and MKN-45 cell lines stimulated with tumor necrosis factor (TNF)-α in a dose-dependent manner. Pretreatment with GG-52 suppressed TNF-α-induced activation of IκB kinase (IKK) and NF-κB signaling in MKN-45 cells. In contrast, the inactive analog GG-46 did not produce significant changes in IL-8 expression or NF-κB activation. In a model of ethanol-induced murine gastritis, administration of GG-52 significantly reduced the severity of gastritis, as assessed by macroscopic and histological evaluation of gastric mucosal damage. In addition, the ethanol-induced upregulation of chemokine KC, a mouse homolog of IL-8, and phosphorylated p65 NF-κB signals were significantly inhibited in murine gastric mucosa pretreated with GG-52. These results indicate that GG-52 suppresses NF-κB activation in gastric epithelial cells and ameliorates ethanol-induced gastric mucosal lesions in mice, suggesting that GG-52 may be a potential gastroprotective agent.