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Backgrounds/aims Distinguishing gastric ectopic pancreas (GEP) from malignant tumors is relatively difficult. This study evaluated the endosonography findings of pathologically proven GEP. Methods Thirty-one patients diagnosed with GEP based on a histopathological analysis from January 2004 to July 2018 were enrolled in this study. All patients underwent EUS and an endoscopic resection. Results Seventeen patients were female, and the median age was 41.1 years (range, 14-74). The lesions were localized most commonly in the antrum. The mean size of the GEP was 10.6 mm (range, 7-15). Superficial type lesions, lesions with heterogeneous echogenicity, mixed pattern lesions, and lesions with indistinct borders were commonly observed on EUS. Calcification, anechoic duct-like structures, and thickening of the muscularis propria were observed in some patients. Endoscopic mucosal resection (41.9%) and endoscopic submucosal dissection (58.1%) were performed. The mean procedure time was 22.5 minutes. Complete resection was achieved for 71% of patients. No statistically significant results between the endosonography findings and complete resection rates were obtained. The mean follow-up esophagogastroduodenoscopy duration was 4.5 months. None of the patients presented with residual lesions on subsequent endoscopy. Conclusions EUS can help identify the features of GEP. Careful observations of the EUS findings can avoid unnecessary removal of GEP.

Background/Aims Delayed gastric emptying (GE) is associated with high morbidity and mortality in subjects with diabetes. The aim of this study is to investigate associations between GE time and the major cardiovascular events (coronary heart diseases and ischemic stroke) in diabetic subjects with upper gastrointestinal (UGI) symptoms. Methods Among 259 subjects with chronic UGI symptoms who underwent gastric emptying study (GES) over 13 years, 122 diabetic subjects without gastric surgery and/or rapid GE were enrolled in this study. We also gathered data about baseline demographics, clinical characteristics, estimated GE half-time (GE T½) and incidence of cardiovascular events following GES. Results The mean age of subjects was 64.0 ± 17.4 years. There were 86 women and 104 subjects with type 2 diabetes. There were 52 (42.6%) subjects with normal GE, 50 (41.0.%) subjects with mild delayed GE, and 20 (16.4%) subjects with marked delayed GE. During follow-up (median, 207 weeks), cardiovascular events occurred in 7 (13.5%) subjects with normal GE, 4 (8.0%) subjects with mild delayed GE and 7 (35.0%) subjects with marked GE (P = 0.015). Univariate analysis showed that GE T½ was significantly associated with incidence of cardiovascular events (crude OR, 1.74; 95% CI, 1.12-2.69; P = 0.014). In a multivariate model, association between GE T½ and incidence of cardiovascular events remained statistically significant after adjustment for baseline characteristics and comorbidities (adjusted OR, 1.94; 95% CI, 1.21-3.12; P = 0.006). Conclusion A delay of GE was associated with an increased incidence of cardiovascular events in diabetic subjects with chronic UGI symptoms. (J Neurogastroenterol Motil 2019;25:387-393)

Background Silibinin is a flavonoid with antihepatotoxic properties, and exhibits pleiotropic anticancer effects. However, the molecular mechanisms responsible for its anticancer actions in pancreatic cancer cells, and the effects on such cells and normal pancreatic cells, remain unclear. The objective of this study was to determine the effect of silibinin on human pancreatic cancer cells and normal ductal cells.Methods Human pancreatic cancer cells (MIA PaCa-2 and PANC-1) and normal ductal cells (hTERT-HPNE) were cultured with 0–400 μM silibinin for 48 h. Thereafter, the proliferation, invasion, apoptosis, and signaling pathways of the pancreatic cells were evaluated.Results Silibinin significantly inhibited the proliferation, invasion, and spheroid formation of human pancreatic cancer cells in vitro in a dose-dependent manner (p < 0.05). It also induced apoptosis in a dose-dependent manner. Western blot analysis showed that silibinin downregulated extracellular signaling-regulated kinase (ERK) and serine/threonine protein kinase (AKT) in human pancreatic cancer cells. It also upregulated microtubule associated protein 1 light chain 3 β (LC3B) and cleaved caspase-3 via c-Jun N-terminal kinases (JNK) signaling. On the other hand, silibinin increased the mRNA and protein levels of c-Jun, Twist-related protein 1, and Snail. It also decreased exogenous p53 levels, but increased endogenous c-Jun protein levels in human pancreatic cancer cells. However, silibinin did not affect cell viability and endogenous c-Jun levels in pancreatic normal ductal cells. It increased exogenous p53 levels, but decreased stemness-related gene expression in pancreatic normal ductal cells. Silibinin increased Ki-67 levels in pancreatic cancer cells, but decreased them in pancreatic normal ductal cells.Conclusion Silibinin not only exerted anticancer effects by inhibiting AKT–ERK and JNK signaling, but also upregulated cancer stemness–related genes in human pancreatic cancer cells. These results suggest that silibinin should be used as a therapeutic agent for human pancreatic cancer with caution.

Background Little information is available about the relationship between restoration of common bile duct (CBD) diameter after endoscopic stone retraction and recurrence of CBD stones in elderly patients. The present study was to determine whether restoration of CBD diameter is a preventive factor for CBD stone recurrence in elderly patients who underwent endoscopic retrograde cholangiopancreatography (ERCP). Methods From January 2006 to December 2010, 238 patients underwent the first and the second session of ERCP for the removal of CBD stones. Among them, 173 were over 65 years old. These patients were divided into recurrent group and non-recurrent group. Restoration of CBD diameter and patients’ characteristics were compared. Results There was no statistical difference in patients’ characteristics, associated diseases, or ERCP-related complications between the two groups. Reduction of CBD diameter was significantly larger in the non-recurrent group (2.7 ± 1.7 mm) compared to that in the recurrent group (1.4 ± 2.3 mm, P = 0.002). The proportion of patients with restoration of CBD diameter were significantly lower in the recurrent group (6/42, 14.3%) compared with that in the non-recurrent group (67/131, 51.1%) (P Conclusions There is an inverse relationship between restoration of CBD diameter and CBD stone recurrence. Therefore, patients without restoration of CBD diameter within 2 weeks after endoscopic stone removal should be monitored more frequently.

Anorectal variceal bleeding is a rare occurrence; however, in such event, it could be fatal due to large size and high blood flow rate of varices. However, to date, there is no standardized treatment modality. Although endoscopic treatment can be provided, in cases of recurrent anorectal variceal bleeding, other therapeutic modalities for hemostasis are necessary. Here, we present a case of 58-year-old female patient with liver cirrhosis, who suffered from massive bleeding of anorectal varices. Endoscopic variceal band ligation was performed for primary hemostasis. Additionally, transjugular intrahepatic portosystemic shunt (TIPS) with embolization was performed to reduce the risk of rebleeding. Following the procedure, she had no further bleeding episodes, and the size of anorectal varices decreased, as seen on an abdomino-pelvic computed tomography. Our case illustrates the effectiveness of combined radiological intervention of TIPS with embolization after endoscopic hemostasis, for variceal obliteration and prevention of rebleeding.

Background Transdiaphragmatic extension of pyogenic liver abscess is the rarest cause of pericarditis and pleural empyema. It is a rapidly progressive and highly lethal infection with mortality rates reaching 100% if left untreated. However, the transmission route, treatment methods and prognosis have not been well studied. Case presentation A 65-year-old male patient presented with a fever, dyspnea, and right upper quadrant abdominal pain. Computed tomography of the chest and abdomen showed huge liver abscess without full liquefaction in the left lobe, large amount of left pleural effusion, and mild pericardial effusion, and the patient was treated with parenteral antibiotics and pigtail insertion at the left pleura. However, four days later, cardiac tamponade was developed and surgical drainage of the abscess and pericardium was performed. Klebsiella pneumonia was isolated from pleural empyema. Twenty-five days after surgery, the patient was discharged without any complications. Conclusions Herein, we report a rare case of pleural empyema and pericarditis in that resulted from the extension of huge pyogenic liver abscess. Early surgical treatment may have prevented progression of the pericarditis to the more dismal purulent pericarditis. We also review pertinent English literature on pericarditis as a complication of PLA.

Chlorogenic acid (CA) is a phenolic compound purified from coffee, fruits and their associated beverages, which possess various biological properties, such as antioxidant and anticarcinogenic activities. The present study evaluated the effects of CA on lipopolysaccharide (LPS)‑induced inflammation in RAW264.7 cells and the associated intracellular signaling pathways using reverse transcription‑quantitative polymerase chain reaction, western blotting and enzyme‑linked immunosorbent assays. CA pretreatment inhibited LPS‑induced expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and pro‑inflammatory mediators including interleukin (IL)‑6, tumor necrosis factor‑α (TNF‑α), macrophage inflammatory protein‑2 (MIP‑2) and IL‑1β in RAW264.7 cells. In addition, phosphorylation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) with LPS was inhibited by CA pretreatment. CA and STAT3 inhibitor (STAT3i) pretreatment inhibited LPS‑induced nuclear translocation of phosphorylated STAT3. In addition, STAT3i inhibited the LPS‑induced expression of iNOS, NO and IL‑1β similar to the results of CA pretreatment. By contrast, STAT3i did not inhibit the LPS‑induced increase in IL‑6, TNF‑α and MIP‑2 expression. These results indicate that CA may suppress LPS‑induced NO and IL‑1β expression by inhibiting JAK2/STAT3 activation in RAW264.7 cells.

Background : Although previous studies have suggested a high salt intake as a risk factor for precancerous and cancerous lesions of stomach, the evidence is not sufficient to draw a conclusion yet. We aimed to evaluate the association between ‘estimated 24-hour urinary sodium excretion’ and prevalence of synchronous gastric epithelial neoplasm. Methods: Among 2017 patients with gastric epithelial neoplasms, who had test results for estimated 24-hour urinary sodium excretion, 1310 were enrolled. Results: There were 545 (41.6%) patients with high-grade dysplasia and early gastric cancer. The mean age was 64.5 years; 853 (65.1%) were men and 244 (18.6%) were smokers. The rate of Helicobacter pylori infection was 71.0% (797/1123). The incidence of synchronous gastric epithelial neoplasm was 10.6% (139/1310). Significant interactions were seen between estimated 24-hour urine sodium’ and sex ( P -interaction =0.003), with the association largely limited to women; ‘estimated 24-hour urine sodium’ (aOR, 1.26; 95% CI, 1.05 to 1.51, P = 0.012) was an independent risk factor for synchronous gastric neoplasm in women. Conclusions: High ‘estimated 24-hour urinary sodium excretion’ was associated with synchronous gastric epithelial neoplasm in women.

Background/Aims This study aimed to identify the demographic and clinical factors associated with positive breath-test results and to assess the relationship between hydrogen and methane production in patients with suspected irritable bowel syndrome (IBS). Methods The demographic and clinical factors of 268 patients with suspected IBS, who had undergone a lactulose breath test, were analyzed. Results Of 268 patients included in this study, 143 (53.4%) were females. The median age and BMI of the patients was 58.0 years (range, 18.0-80.0 years) and 22.5 kg/m2 (range, 14.4-34.3 kg/m2), respectively. A weak positive correlation was observed between the BMI and baseline hydrogen level (rho=0.134, p=0.031). Women were significantly more likely to show a ≥20 ppm increase in hydrogen within 90 min (early hydrogen increase, p=0.049), a ≥10 ppm increase in methane within 90 min (early methane increase, p=0.001), and a ≥10 ppm increase in methane between 90 min and 180 min (late methane increase, p=0.002) compared to men. The baseline hydrogen level was related to the baseline methane level (rho=0.592, p

Several studies have demonstrated a correlation between the expression of early growth response gene-1 (EGR-1) and the progression of gastric cancers at advanced stages. However, the effects of EGR-1 expression on human gastric cancer progression, particularly on precancerous lesions, have not been investigated. In this study, we evaluate EGR-1 expression levels in target mucosa from patients with early gastric cancer and precancerous lesions, and assess whether EGR-1 expression affects the oncogenic phenotypes of human gastric cancer cells. EGR-1 protein levels were measured in tissues from subjects with normal mucosa (n=6), low-grade dysplasia (n=6), high-grade dysplasia (n=4) and adenocarcinoma (n=3) using enzyme-linked immunosorbent assay and immunohistochemistry analyses. We also investigated the role of EGR-1 in tumor cell behavior by transiently expressing a dominant active EGR-1 variant in cultured cells. A positive correlation was observed between EGR-1 expression and gastric carcinogenesis (P=0.016). Furthermore, there was an increase in nuclear and cytoplasmic expression of EGR-1 in accordance with the histological grade (P for trends=0.003 and 0.003, respectively), and a positive association between the sum of the nuclear and cytoplasmic EGR-1 expression values and the histological grade (P=0.003). In addition, transient overexpression of EGR-1 enhanced cell proliferation, stimulated cell migration, and promoted the phosphorylation of p38 MAPK and AKT in gastric cancer cells in vitro. Our findings demonstrate that EGR-1 may contribute to the early stages of gastric carcinogenesis via the alteration of tumor cell behaviors.

Background/Aims The effect of proton pump inhibitors (PPI) in Asian functional dyspepsia (FD) patients has not been well established as in Western countries. DA-9701, a novel prokinetic agent, stimulates gastric emptying and modulates visceral hypersensitivity in vivo and in human studies. This study was conducted to compare the efficacy of DA-9701 with a conventional PPI in mono or combination therapy in patients with FD. Methods In this double-blind, randomized, non-inferiority trial, 389 patients diagnosed with FD using Rome III criteria were allocated among 3 groups: 30-mg DA-9701 t.i.d (means 3 times a day), 40-mg pantoprazole, and 30-mg DA-9701 t.i.d + 40-mg pantoprazole. The primary efficacy end-point was a global assessment of the patient binary response or response on a 5-Likert scale after 4 weeks. Results The global symptomatic improvement was 60.5% in the DA-9701 group, 65.6% in the pantoprazole group, and 63.5% in the DA-9701 + pantoprazole group using a 5-Likert scale at week 4 with no significant difference among 3 groups (P = 0.685). Symptom improvement measured by binary outcome was significantly achieved in each of the 3 groups, but not different among groups. Patients in all treatment groups reported significant improvement in the response rate and symptoms according to FD subtypes and dyspepsia-related quality of life (P < 0.001), but there were no significant differences among the 3 groups. Conclusions DA-9701 improves global and individual symptoms and increases dyspepsia-specific quality of life in patients with FD. The efficacy of DA-9701 monotherapy is comparable with pantoprazole and there is no additive effect with combination of DA-9701 and pantoprazole in patients with FD.

Background/Aims: Endoscopic retrograde biliary drainage (ERBD) has become a standard procedure in patients with a biliary obstruction. Intraductal ultrasonography (IDUS) has emerged as a new tool for managing extrahepatic biliary diseases. IDUS-directed ERBD can be performed without conventional cholangiography (CC). The goal of this study was to assess the effectiveness and safety of IDUS-directed ERBD compared to CC-directed ERBD in patients with an extrahepatic biliary obstruction. Methods: A total of 210 patients who had undergone IDUS-directed ERBD (IDUS-ERBD, n = 105) and CC-directed ERBD (CC-ERBD, n = 105) between October 2013 and April 2014 were analyzed retrospectively. The primary outcome measure was the procedural success rate. Secondary outcome measures included clinical outcomes, total procedure time, radiation exposure time, and overall complication rates. Results: The total technical success rate of ERBD was 100% (105/105) in the IDUS-ERBD and CC-ERBD groups. Mean procedure time was slightly prolonged in the IDUS-ERBD group than that in the CC-ERBD group (32.1 ± 9.9 minutes vs. 28.4 ± 11.6 minutes, p = 0.023). Mean radiation exposure time was one-third less in the IDUS-ERBD group than that in the CC-ERBD group (28.0 ± 49.3 seconds vs. 94.2 ± 57.3 seconds, p < 0.001). No significant differences in complication rates were detected between the groups. Conclusions: IDUS-ERBD was equally effective and safe as CC-ERBD in patients with an extrahepatic biliary obstruction. Although IDUS-ERBD increased total procedure time, it significantly decreased radiation exposure.

Supplemental Digital Content is available in the text, Rationale: Endoscopic resection of superficial non-ampullary duodenal epithelial neoplasm (SNADEN) is a challenging procedure owing to the high recurrence rate and considerable incidence rate of adverse events. Patient concerns: SNADEN accidentally found during a medical examination in a 56-year-old man Diagnosis: The patient was diagnosed as having a 20-mm-sized flat elevated SNADEN at the superior duodenal angle. Interventions: First, we tried to perform conventional EMR (CEMR). However, the submucosal injection interrupted the endoscopic view and did not provide enough space for CEMR because of its angulated location. Therefore, we chose to perform endoscopic resection using the “loop-and-let-go” technique. Follow-up duodenoscopy after 2 days revealed post CEMR ulcer with suspicious remnant lesion. Underwater endoscopic mucosal resection (UEMR) was successfully performed 3 months after the first session of endoscopic resection. Outcomes: Complete endoscopic en bloc resection and histological complete resection were achieved with UEMR. Follow-up duodenoscopy revealed no recurrence. Lessons: Step-by-step endoscopic treatment with UEMR following loop-and-let-go technique may be a good strategy for SNADEN over 20-mm in diameter.

Transdiaphragmatic extension of pyogenic liver abscess is the rarest cause of pericarditis and pleural empyema. It is a rapidly progressive and highly lethal infection with mortality rates reaching 100% if left untreated. However, the transmission route, treatment methods and prognosis have not been well studied.A 65-year-old male patient presented with a fever, dyspnea, and right upper quadrant abdominal pain. Computed tomography of the chest and abdomen showed huge liver abscess without full liquefaction in the left lobe, large amount of left pleural effusion, and mild pericardial effusion, and the patient was treated with parenteral antibiotics and pigtail insertion at the left pleura. However, four days later, cardiac tamponade was developed and surgical drainage of the abscess and pericardium was performed. Klebsiella pneumonia was isolated from pleural empyema. Twenty-five days after surgery, the patient was discharged without any complications.Herein, we report a rare case of pleural empyema and pericarditis in that resulted from the extension of huge pyogenic liver abscess. Early surgical treatment may have prevented progression of the pericarditis to the more dismal purulent pericarditis. We also review pertinent English literature on pericarditis as a complication of PLA.

Backgrounds Intestinal alkaline phosphatase (IAP) plays important role in gut homeostasis. We aimed to evaluate the expression of endogenous IAP and to assess the clinical course according to the expression of endogenous IAP in patients with Crohn’s disease (CD). Methods A total of 32 consecutive patients (14 males) with CD were included in the study. We measured the level of endogenous iAP in inflamed and noninflamed colonic mucosa. To verify the inflammation status, we measured the level of mRNA for IL-6, TNF-α, and TLR-4. We monitored the clinical courses of patients during follow-up after acquisition of biopsy specimens. Results Median age of patients was 22.5 years (range, 15–49). Median CD activity index (CDAI, range) was 93.7 (22.8~ 154.9). There were colonic involvements in all patients and perianal involvement in 43.8% patients. The mRNA levels of IL-6 (p = 0.005) and TLR-4 (p = 0.013) in inflamed mucosa were significantly higher than those in non-inflamed mucosa. However, there was no difference of expression of TNF-α mRNA (p = 0.345). During a 14-month follow-up (range, 9 months–54 months), there were 19 patients with clinical recurrences. There were 9 patients (9/19, 47.4%) with IAP expression ratio (inflamed to non-inflamed) ≤ 1.0 in patients with clinical recurrence while there was one patient (1/13, 7.7%) with IAP ratio ≤ 1.0 in patients without clinical recurrence (p = 0.024). Conclusion Lower expression of IAP in inflamed mucosa compared to non-inflamed mucosa may be associated with clinical recurrence in patients with CD.

Background/aim The number of elderly patients diagnosed with hepatocellular carcinoma (HCC) has been increasing. But there is no proper management based on age stratification in elderly patients. Therefore, we evaluated the clinical characteristics and outcomes of elderly HCC patients more than 75 years old in South Korea. Patients and methods Five hundred and fifty elderly patients with HCC were enrolled and divided into the oldest-old (age ≥85 years), middle-old (age between 80 and 85 years), and young-old groups (age between 75 and 80 years). Results Fifty-one, 153, and 346 patients were included in the oldest-old (mean age: 87 years), middle-old (mean age: 82 years), and young-old groups (mean age: 77 years), respectively. There was a significantly lower rate of alcohol-related and hepatitis B virus-related diseases in the oldest-old group than in the other groups, whereas there was no significant difference in other characteristics. With increasing age, conservative treatment was predominantly performed. Transarterial chemoembolization was the main modality of active treatment in all groups. In multivariate analysis, the performance score, model for end-stage liver disease score, modified Union for International Cancer Control staging, Barcelona Clinic Liver Cancer staging, presence of portal vein tumor thrombosis, ruptured HCC, and active treatment were risk factors of overall survival. Conclusion When the therapeutic approach is used in elderly patients with HCC, the patient's performance status, liver function, and stage of cancer should be considered, and its use should not be restricted to those of advanced age.

Background Eradication rate for Helicobacter pylori (H. pylori) has decreased due to antibiotic resistance. Therefore, new strategies are needed to enhance H. pylori eradication, especially for H. pylori with high antibiotic resistance. The objective of this study was to evaluate anti-H. pylori activities of constituents from key lime (Citrus aurantifolia) and their possible inhibitory effects on urease activity of H. pylori. Methods Helicobacter pylori strain ATCC 43526 and triple drug resistant (TDR) H. pylori strains were used in this study. Urease activities of H. pylori strains were measured by ammonia colorimetrical quantification using ELISA reader. Minimum inhibitory concentrations were determined by agar dilution method for antibiotics and by modified media dilution method for each constituent of Citrus aurantifolia (C. aurantifolia). Results Citrus aurantifolia extract decreased the number of colonies of H. pylori strain ATCC 43526 and TDR H. pylori stains. An increasing concentration of C. aurantifolia extract attenuated urease activities of H. pylori strain ATCC 43526 and TDR H. pylori strains. Among constituents of C. aurantifolia, citral and 4-hexen-3-one were found to be able to inhibit the growth of H. pylori strain ATCC 43526 and TDR H. pylori strains. Furthermore, citral and 4-hexen-3-one inhibited urease activities of H. pylori strain ATCC 43526 and TDR H. pylori strains in a dose-dependent manner. Conclusion Citrus aurantifolia has antimicrobial effect on TDR H. pylori strains, suggesting that C. aurantifolia might have therapeutic potential to control antibiotic-resistant H. pylori strains that cause eradication failure using other antibiotics.

BACKGROUND/AIMS: Colon transit time (CTT) is a useful diagnostic tool in chronic constipation, but requires good patient compliance. We analyzed the correlation between the gas volume score (GVS) and CTT in patients with chronic constipation. METHODS: The study included 145 consecutive patients (65 men) with chronic constipation. The primary outcome was the correlation be-tween the colon GVS and CTT. Secondary outcomes were the differences in colon GVS according to CTT and subtypes of chronic constipation. RESULTS: There were 81 patients with "CTT < 45 hours" and 64 patients with "CTT ≥ 45 hours." In addition, 88 patients were classi-fied as having functional constipation and 57 were classified as having constipation predominant irritable bowel syndrome (IBS-C). There was no significant correlation between CTT and colon GVS. However, the right colon GVS showed a positive cor-relation with right CTT (r = 0.255, P = 0.007). The median total colon GVS was significantly higher in patients with "CTT ≥ 45 hours" than in those with "CTT < 45 hours" (5.65% vs 4.15%, P = 0.010). There were no significant differences in colon GVS between the functional constipation and IBS-C. CONCLUSIONS: We were unable to detect a correlation between GVS and CTT in patients with chronic constipation. However, total colon GVS may be a method of predicting slow transit in patients with chronic constipation.

Hypoganglionosis is a rare form of intestinal neuronal malformation, which is characterized by reduced number and size of ganglion cells of parasympathetic nerves in the intestinal wall. Pathophysiology is not well known, however intestinal ischemia, inflammation, autoimmune process or neurotoxin may play a role. Here, we report the case of a 56-year-old man with colonic pseudoobstruction and ulcerations in marked dilatedcolon above transitional zone who was later diagnosed with colonic hypoganglionosis.

Background Eradication rate for Helicobacter pylori (H. pylori) has decreased due to antibiotic resistance. Therefore, new strategies are needed to enhance H. pylori eradication, especially for H. pylori with high antibiotic resistance. The objective of this study was to evaluate anti-H. pylori activities of constituents from key lime (Citrus aurantifolia) and their possible inhibitory effects on urease activity of H. pylori. Methods Helicobacter pylori strain ATCC 43526 and triple drug resistant (TDR) H. pylori strains were used in this study. Urease activities of H. pylori strains were measured by ammonia colorimetrical quantification using ELISA reader. Minimum inhibitory concentrations were determined by agar dilution method for antibiotics and by modified media dilution method for each constituent of Citrus aurantifolia (C. aurantifolia). Results Citrus aurantifolia extract decreased the number of colonies of H. pylori strain ATCC 43526 and TDR H. pylori stains. An increasing concentration of C. aurantifolia extract attenuated urease activities of H. pylori strain ATCC 43526 and TDR H. pylori strains. Among constituents of C. aurantifolia, citral and 4-hexen-3-one were found to be able to inhibit the growth of H. pylori strain ATCC 43526 and TDR H. pylori strains. Furthermore, citral and 4-hexen-3-one inhibited urease activities of H. pylori strain ATCC 43526 and TDR H. pylori strains in a dose-dependent manner. Conclusion Citrus aurantifolia has antimicrobial effect on TDR H. pylori strains, suggesting that C. aurantifolia might have therapeutic potential to control antibiotic-resistant H. pylori strains that cause eradication failure using other antibiotics.

Rationale Severe alcoholic hepatitis (AH) has a very high mortality rate. Current guidelines recommend oral corticosteroids as first-line agents in individuals with severe AH to reduce short-term mortality. However, systemic corticosteroids have serious adverse effects. In individuals with AH, infection, which is one of the complications of steroid use, can result in serious outcomes, such as acute-on-chronic liver failure. Pneumocystis pneumonia (PCP) is a life-threatening opportunistic infection which may occur when high-dose corticosteroids are prescribed for more than 1 month. Therefore, when high-dose corticosteroids are used, providing PCP prophylaxis is warranted. Although trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for the prophylaxis of PCP, its hepatotoxicity limits its use in patients with severe AH who are on high-dose corticosteroids. Moreover, there is a lack of consensus on which drugs should be used for PCP prophylaxis in individuals with severe AH who are on glucocorticoid treatment. Herein, we report a case of a 43-year-old male with fatal PCP that occurred after the use of corticosteroids for severe AH. Patient concerns A 43-year-old alcoholic man presented with a hematoma on his right leg. His liver function was poor, and he was he was diagnosed with severe AH and treated with oral corticosteroids for 26 days. After glucocorticoid treatment, he developed a productive cough. Diagnoses A sputum PCR test was positive for Pneumocystis jirovecii. Interventions He was initially treated with TMP-SMX and required artificial ventilation. Outcomes He developed disseminated intravascular coagulation and multi-organ failure, and died 10 days after starting TMP-SMX. Lessons To date, prevention of PCP in individuals with severe AH who are on corticosteroids has been overlooked. This case illustrates the need for prophylaxis of PCP in individuals with severe AH taking corticosteroids.

Background/Aims The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. Methods We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 μg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. Results Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). Conclusions Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.

BACKGROUND/AIMS Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients with altered gastrointestinal (GI) anatomy. We evaluated the feasibility of cap-assisted ERCP in patients with altered GI anatomy. METHODS The outcome of ERCP procedures (n=136) was analyzed in 78 patients with Billroth II (B-II) gastrectomy (n=72), Roux-en-Y total gastrectomy (n=4), and hepaticoduodenostomy (n=2). The intubation rate for reaching the papilla of Vater (POV), deep biliary cannulation rate, therapeutic interventions and procedure-related complications were analyzed. All of the procedures were conducted using a cap-fitted forward-viewing endoscope. RESULTS The rate of access to the POV was 97.1% (132/136). In cases with successful access, selective biliary cannulation was achieved in 98.5% (130/132) of the patients. The successful biliary cannulation rates were 100% (125/125) for B-II gastrectomy, 50% (2/4) for Roux-en-Y gastrectomy and 100% (3/3) for hepaticoduodenostomy. After selective biliary cannulation, therapeutic interventions, including stone extraction (n=57), sphincterotomy (n=54), stent placement (n=37), nasobiliary drainage (n=20), endoscopic papillary balloon dilatation (n=7) and mechanical lithotripsy (n=15), were performed successfully. The procedure-related complication rate was 8.8% (12/136), including immediate bleeding (5.9%, 8/136), pancreatitis (2.2%, 3/136), and perforation (0.7%, 1/136). There were no procedure-related deaths. CONCLUSIONS Cap-assisted ERCP is efficient and safe in patients with altered GI anatomy.

BACKGROUND/AIMS To evaluate the long-term efficacy and safety of endoscopic injection of N-butyl-2-cyanoacrylate (NBC; Histoacryl) for treatment of bleeding gastric varices. METHODS We retrospectively analyzed the records of 455 patients with gastric variceal hemorrhage (GVH) who were consecutively treated with NBC from January 2004 to July 2013, with a mean follow-up period of 582 days. The patients' endoscopic findings, initial hemostasis, complications, rebleeding rates, and bleeding-related death rates were reviewed. RESULTS Hemostasis was achieved initially in 96.9% (441/455) of patients; rebleeding occurred in 35.2% (160/455), and the bleeding-related death rate was 6.8% (31/455) during follow-up. Complications included fever (6.8%), abdominal pain (3.7%), diarrhea (1.3%), spontaneous bacterial peritonitis (0.7%), bacteremia (0.4%), and embolism (0.2%). A red-color sign on concomitant esophageal varices (EVs) (p = 0.002) and previous history of variceal bleeding (p < 0.001) were significant risk factors for rebleeding within 1 year. The Child-Pugh score (p < 0.001), presence of hepatocellular carcinoma (p = 0.001), and failure of initial hemostasis (p < 0.001) were the risk factors most closely associated with bleeding-related death. CONCLUSIONS This study provides a comprehensive overview of the outcomes and prognostic factors of patients with GVH. The results may help in the selection of effective treatment strategies for patients with GVH.

Misoprostol is reported to prevent non-steroidal anti-inflammatory drug (NSAID)-associated gastroduodenal complications. There is, however, limited information regarding the efficacy of DA-9601 in this context. We performed a comparative study on the relative efficacy of DA-9601 and misoprostol for prevention of NSAID-associated complications. In this multicenter, double-blinded, active-controlled, stratified randomized, parallel group, non-inferiority trial, 520 patients who were to be treated with an NSAID (aceclofenac, 100 mg, twice daily) over a 4-week period were randomly assigned to groups for coincidental treatment with DA-9601 (60 mg, thrice daily) (236 patients for full analysis) or misoprostol (200 μg, thrice daily) (242 patients for full analysis). A total of 236 patients received DA-9601 and 242 received misoprostol. The primary endpoint was the gastric protection rate, and secondary endpoints were the duodenal protection rate and ulcer incidence rate. Endpoints were assessed by endoscopy after the 4-week treatment period. Drug-related adverse effects, including gastrointestinal (GI) symptoms, were also compared. At week 4, the gastric protection rates with DA-9601 and misoprostol were 81.4 % (192/236) and 89.3 % (216/242), respectively. The difference between the groups was −14.2 %, indicating non-inferiority of DA-9601 to misoprostol. Adverse event rates were not different between the two groups; however, the total scores for GI symptoms before and after administration were significantly lower in the DA-9601 group than in the misoprostol group (−0.2 ± 2.8 vs 1.2 ± 3.2; p

Gastrointestinal xanthomas are characterized by foamy cytoplasmic cells containing lipid in lamina propria, and occur almost in the gastric mucosa. Colonic xanthomas have been described in rare case. All reported colonic xanthomas were located in rectosigmoid. Rectosigmoid xanthomas have tended to exhibit small polypoid lesion, on the contrary flat in stomach. We report a case of xanthoma on ascending colon presenting as a laterally spreading tumor resected by endoscopic mucosal resection method.

Purpose To evaluate the risk factors of hepatocellular carcinoma (HCC) extension into the right atrium (RA) and determine poor prognostic factors for HCC extension to the heart. Materials and Methods A total of 665 patients who were newly diagnosed with HCC were analyzed retrospectively from January 2004 to July 2012. The patients were divided into two groups: 33 patients with HCC extending into the RA and 632 HCC patients during the same period. The patients with HCC extending into the RA were subdivided into shorter survival group (3 (p=0.016, OR: 13.89) and active treatment (p=0.024, OR: 0.054) were associated with prognostic factors in patients HCC extending into the RA. Active treatment such as radiation (n=1), transcatheter arterial chemoembolization (TACE) (n=11), Sorafenib (n=1), and combined modalities (n=2) were performed. Conclusion Modified UICC stage higher than IVA, vascular invasion and multinodular tumor type are independent risk factors for HCC extending to the RA. Active treatment may prolong survival in patients HCC extending into the RA.

Capsaicin is known to have tumor suppressive effects. However, the molecular mechanisms and targets of capsaicin involved in exerting anticancer activity are complex and remain to be clarified. The aim of the current study was to investigate the effects of capsaicin on human gastric cancer cells (AGS cells) and demonstrate that capsaicin induced apoptosis in AGS cells. Results of the MTT assay and flow cytometry revealed that capsaicin potentially inhibited the proliferation of AGS cells and induced apoptosis in vitro in a dose-dependent manner. Cleaved caspase-3 was increased and Bcl-2 was reduced by treatment with capsaicin in AGS cells. Capsaicin treatment decreased the expression of phosphorylated ERK 1/2, p38 MAPK or JNK in AGS cells. The results of this study suggest that capsaicin may serve as an anti-tumorigenic agent in human gastric cancer.

Duodenal neuroendocrine tumors (NETs) are rare neoplasms. In this study, the medical records of 14 patients with duodenal NETs diagnosed at Chonnam National University Hospital from July 2001 to August 2011 were reviewed and analyzed retrospectively. Four patients were diagnosed in the first 5 years, and 10 patients were diagnosed in the latter 5 years of the study. Ten of 12 patients (83.3%) who underwent endoscopic biopsy were confirmed to have NET before resection. Endoscopic resection was performed in 12 patients, surgical resection in one patient, and regular follow-up in one patient who refused resection. None of the patients showed recurrence or distant metastasis. Duodenal NETs are increasingly observed and are mostly detected during screening upper gastrointestinal endoscopy. Careful endoscopic examination and biopsy can improve the diagnostic yield of NETs. Most well-differentiated, nonfunctional duodenal NETs that are limited to the mucosa/submucosa can be treated effectively with endoscopic resection.

The aim of this study was to compare the efficacy, rebleeding rates, survival, and complications of endoscopic variceal ligation (EVL) with those of endoscopic variceal obliteration (EVO) in patients with acute type 1 gastroesophageal variceal (GOV1) bleeding. Data were collected retrospectively at a single center. A total of 84 patients were selected (20 patients underwent EVL; 64 patients underwent EVO) from February 2004 to September 2011. Their clinical characteristics, laboratory results, vital signs, Child-Pugh score, Model for End-stage Liver Disease (MELD) score, and overall mortality were evaluated. There were no significant differences in baseline characteristics between the two groups. The success rate in initial control of active bleeding was not significantly different between the EVL and EVO groups (18/20 EVL, or 90.0%, compared with 62/64 EVO, or 96.9%; p=0.239). The early rebleeding rate was also not significantly different between the groups (3/18 EVL, or 16.7% compared with 17/62 EVO, or 27.4%; p=0.422). The late rebleeding rate of the EVL group was lower than that of the EVO group (3/18 EVL, or 16.7%, compared with 26/59 EVO, or 44.1%; p=0.042). The time-to-rebleeding was 594 days for the EVL group and 326 days for the EVO group (p=0.054). In the multivariate analysis, portal vein thrombosis (PVT) was a significant risk factor for early rebleeding. Hepatocellular carcinoma (HCC) and previous history of bleeding were significant risk factors for very late rebleeding. In conclusion, EVL is better than EVO in reducing late rebleeding in acute GOV1 bleeding. HCC, PVT, and previous bleeding history were significant risk factors for rebleeding.

Background/Aims: Gastroesophageal reflux (GER) has been implicated in the pathogenesis of chronic cough. The aims of this study were to evaluate the diagnostic usefulness of multichannel intraluminal impedance combined with pH monitoring (MII/pH monitoring) in patients with suspected symptoms of gastroesophageal reflux disease (GERD) and to assess the correlation between GER symptoms and refl ux nature. Methods: Seventy patients with suspected symptoms of GERD (such as heartburn, acid regurgitation, noncardiac chest pain, globus and chronic cough) were enrolled. All patients were asked to discontinue medications that would infl uence esophageal motor function and gastric acid secretion at least one week ago. All subjects underwent MII/pH monitoring. Results: Forty-five patients (64.3%) were diagnosed with GERD. Among these patients, eleven patients (15.7%) had pathologic acid refl ux by pH data and thirty-four patients (48.6%) had pathologic bolus exposure by impedance. Subjects with chronic cough had a higher De- Meester score (p=0.009), percentage of acid exposure time (p=0.007), acid bolus exposure % time (p=0.027), distal acid refl ux episodes (p=0.015) and proximal acid refl ux episodes (p=0.030) than subjects without chronic cough. Conclusions: The results of this study showed that the impedance monitoring enhanced diagnostic sensitivity than pH-monitoring alone by 48.6%. In addition, refl ux episodes at the distal and proximal esophagus were noted to be important factors associated with chronic cough. (Gut Liver 2012;6:197-202)

Pegylated-interferon plus ribavirin is the standard treatment for chronic hepatitis C. Sustained virological response (SVR) rates of up to 80% are reported in genotype 2 and 3 chronic hepatitis C cases. Obesity, a modifiable risk factor, may have a deleterious effect on antiviral treatment. We performed this study to examine the efficacy and safety of pegylated-interferon and ribavirin therapy in Korean patients with genotype 2 and 3 chronic hepatitis C and to investigate the risk factors for nonresponse to antiviral treatment. A total of 121 patients were treated with peginterferon alpha-2a 180 mcg/week plus ribavirin 800 mg/day for 24 weeks. The end-of-treatment virologic response (ETVR), the SVR, the end-of-treatment biochemical response (ETBR), the sustained biochemical response (SBR), and the adverse events were analyzed. The ETVR and SVR were 94.1% and 89.1%, respectively. The ETBR was 80.2% and the SBR was 96%. Multivariate analysis showed that a body mass index of 25 and over was the only independent factor that affected the SVR (odds ratio=10.5, 95% confidence interval: 2.006-54.948, p=0.005). Twenty patients (16.5%) dropped out at the end of treatment, and 7 (5.8%) patients discontinued treatment because of treatment-related adverse events. Our study showed that combination therapy with pegylated-interferon and ribavirin as an initial treatment for genotype 2 and 3 chronic hepatitis C is very effective and safe, and that body mass index is an independent risk factor for nonresponse to antiviral treatment in patients with genotype 2 and 3 chronic hepatitis C.

Although arteriovenous malformations (AVM) occur frequently in digestive organs, pancreatic AVM is rare. The clinical symptoms of pancreatic AVM are variable and include gastrointestinal bleeding, abdominal pain, jaundice, portal hypertension, pancreatitis, and duodenal ulcer. However, choledochoduodenal or pancreaticoduodenal fistulas complicated with ascending infection and pancreatitis is extremely rare. Herein, we report a case of pancreaticoduodenal fistula associated with a pancreatic AVM that induced recurrent anemia and ascending infection.

Dysphagia aortica is a rare etiology of dysphagia resulting from extrinsic compression of esophagus by thoracic aortic aneurysm or tortuosity and elongation of thoracic aorta. The clinical findings resemble those of esophageal malignancy or esophageal motility disorders. Therefore, primary diagnosis of dysphagia aortica is very difficult. We, herein, report a case of dysphagia aortica aggravated by wearing the abdominal binder in a 70-year-old woman and review the literature pertaining to this condition. Dysphagia aortica should be considered in the differential diagnosis of dysphagia.

Introduction Cholecystokinin (CCK) belongs to a group of endogenous molecules known as brain-gut neuropeptides and functions as a neuropeptide as well as a gut hormone. It remains unclear whether genetic variation of the CCK receptor plays a role in irritable bowel syndrome (IBS). The aim of this study was to determine and compare the allele and genotype frequencies of the CCK1 receptor polymorphisms between healthy controls and patients with IBS.

Background/Aims: Food residue is frequently observed in the gastric remnant after distal gastrectomy, despite adequate preparation. We devised a water-intake method to reduce food residue in the gastric remnant by drinking large quantities of water in a short time. The aims of this study were to identify the risk factors for food residue and to study the effectiveness of this new method for endoscopy preparation. Methods: A cohort of 708 patients who underwent distal gastrectomy for gastric cancer was reviewed prospectively. Sixty patients with large amounts of food residue were randomly divided into two groups: a water-intake group (n=40) and a prolonged fasting group (n=20). Results: The incidences of a large amount of food residue were 15.7%, 5.8%, 7.5%, and 2.8% at 3, 12, 24, and 36 months, respectively, after distal gastrectomy. Independent risk factors for food residue were endoscopy at 3 months, diabetes mellitus, a body mass index of ＜19.5, and laparoscopic surgery. The proportion of successful preparations at follow-up endoscopy was higher for the water-intake group (70%) than for the prolonged fasting group (40%, p=0.025). Conclusions: The water- intake method can be recommended as a preparation for endoscopy in patients who have had repetitive food residue or risk factors after distal gastrectomy. (Gut and Liver 2009;3:186-191)

Summary Background Prospective nationwide multicentre studies that have evaluated endoscopic findings and reflux symptoms using a well-designed questionnaire are very rare. Aim To compare the prevalence rates of and risk factors for erosive oesophagitis and non-erosive reflux disease (NERD) in the Korean population. Methods A gastroscopic examination was performed on 25 536 subjects who visited 40 Healthcare Centers for a health check-up. A gastro-oesophageal reflux questionnaire and multivariate analysis were used to determine the risk factors for erosive oesophagitis and NERD. Results 2019 (8%) and 996 subjects (4%) had erosive oesophagitis and non-erosive reflux disease, respectively; only 58% of subjects with erosive oesophagitis had reflux symptoms. Multivariate analysis showed that the risk factors for erosive oesophagitis and NERD differed, i.e. those of erosive oesophagitis were male, a Helicobacter pylori eradication history, alcohol, body mass index ≥25 and hiatal hernia. In contrast, the risk factors for NERD were female, age

Anti-peptic and anti-inflammatory actions of ecabet sodium might be beneficial in either improving gastritis or relieving dyspeptic symptoms. This study was designed to evaluate the clinical efficacy of ecabet sodium on dyspeptic symptoms and to elucidate the molecular mechanism attributable to symptom relief in patients with chronic gastritis. Two hundred and sixty eight chronic gastritis patients with persistent dyspepsia received ecabet sodium 1 g b.i.d. for 2 weeks, after which dyspeptic symptoms were reassessed with a questionnaires as before. The changes of interleukin-8 (IL-8), inducible nitric oxide synthase (iNOS), prostaglandin E(2) (PGE(2)), and vascular endothelial growth factor (VEGF) levels in gastric juices were measured by ELISA. The changes of nitrotyrosine in gastric mucosa were measured by immunohistochemical staining. The most common dyspeptic symptom in Korean patients with chronic gastritis was epigastric soreness (76.8%), which was improved significantly after ecabet sodium treatment (81.7%, p

Background/Aims Percutaneous coronary intervention (PCI) is often performed therapeutically, and antithrombotic treatment is required for at least 12 months after stent implantation. However, the development of post-PCI upper gastrointestinal bleeding (UGIB) increases morbidity and mortality. We investigated the incidence and risk factors for UGIB in Korean patients within 1 year after PCI. Methods The medical records of 3,541 patients who had undergone PCI between January 2006 and June 2012 were retrospectively reviewed. We identified 40 cases of UGIB. We analyzed the incidence and clinical risk factors associated with UGIB occurring within 1 year after PCI by comparing the results for each case to matched controls. The propensity score matching method using age and sex was utilized. Results UGIB occurred in 40 patients (1.1%). Two independent risk factors for UGIB were a history of peptic ulcer disease (odds ratio [OR], 12.68; 95% confidence interval [CI], 2.70 to 59.66; p=0.001) and the use of anticoagulants (OR, 7.76; 95% CI, 2.10 to 28.66; p=0.002). Conclusions UGIB after PCI occurred at a rate of 1.1% in the study population. Clinicians must remain vigilant for the possibility of UGIB after PCI and should consider performing timely endoscopy in patients who have undergone PCI and are suspected of having an UGIB.