Effect of Probiotics in Stress-Associated Constipation Model in Zebrafish (Danio rerio) Larvae.

The pathophysiology of functional bowel disorders is complex, involving disruptions in gut motility, visceral hypersensitivity, gut-brain-microbiota interactions, and psychosocial factors. Light pollution, as an environmental stressor, has been associated with disruptions in circadian rhythms and the aggravation of stress-related conditions. In this study, we investigated the effects of environmental stress, particularly continuous light exposure, on intestinal motility and inflammation using zebrafish larvae as a model system. We also evaluated the efficacy of probiotics, specifically Bifidobacterium longum (B. longum), at alleviating stress-induced constipation. Our results showed that continuous light exposure in zebrafish larvae increased the cortisol levels and reduced the intestinal motility, establishing a stress-induced-constipation model. We observed increased inflammatory markers and decreased intestinal neural activity in response to stress. Furthermore, the expressions of aquaporins and vasoactive intestinal peptide, crucial for regulating water transport and intestinal motility, were altered in the light-induced constipation model. Administration of probiotics, specifically B. longum, ameliorated the stress-induced constipation by reducing the cortisol levels, modulating the intestinal inflammation, and restoring the intestinal motility and neural activity. These findings highlight the potential of probiotics to modulate the gut-brain axis and alleviate stress-induced constipation. Therefore, this study provides a valuable understanding of the complex interplay among environmental stressors, gut function, and potential therapeutic strategies.

Comparison of the Pharmacokinetics of CT-P13 Between Crohn's Disease and Ulcerative Colitis.

BACKGROUND: We aimed to compare trough infliximab levels and the development of antidrug antibody (ADA) for 1 year between Crohn's disease (CD) and ulcerative colitis (UC) patients who were biologic-naive, and to evaluate their impact on clinical outcomes. METHODS: This was a prospective, multicenter, observational study. Biologic-naive patients with moderate to severe CD or UC who started CT-P13, an infliximab biosimilar, therapy were enrolled. Trough drug and ADA levels were measured periodically for 1 year after CT-P13 initiation. RESULTS: A total of 267 patients who received CT-P13 treatment were included (CD 168, UC 99). The rates of clinical remission (72% vs. 32.3%, P <0.001) at week 54 were significantly higher in CD than in UC. The median trough drug level (µg/mL) was significantly higher in CD than in UC up to week 14 (week 2, 18.7 vs. 14.7, P <0.001; week 6, 12.5 vs. 8.6, P <0.001; week 14, 3.4 vs. 2.5, P =0.001). The median ADA level (AU/mL) was significantly lower in CD than in UC at week 2 (6.3 vs. 6.5, P =0.046), week 30 (7.9 vs. 11.8, P =0.007), and week 54 (9.3 vs. 12.3, P =0.032). Development of ADA at week 2 [adjusted odds ratio (aOR)=0.15, P =0.026], initial C-reactive protein level (aOR=0.87, P =0.032), and CD over UC (aOR=1.92, P <0.001) were independent predictors of clinical remission at week 54. CONCLUSION: Infliximab shows more favorable pharmacokinetics, including high drug trough and low ADA levels, in CD than in UC, which might result in better clinical outcomes for 1-year infliximab treatment in CD patients.

Ten-year trends of utilizing palliative care and palliative procedures in patients with gastric Cancer in the United States from 2009 to 2018 - a nationwide database study.

OBJECTIVES: Little is known about the current status and the changing trends of hospitalization and palliative care consultation of patients with gastric cancer in the United States. The aim of this study was to evaluate the changing trend in the number of hospitalization, palliative care consultation, and palliative procedures in the US during a recent 10-year period using a nationwide database. METHODS: This was a retrospective study that analyzed the National Inpatient Sample (NIS) database of 2009-2018. Patients aged more than 18 years who were diagnosed with a gastric cancer using International Classification of Diseases (ICD)-9 and 10 codes were included. Palliative care consultation included palliative care (ICD-9, V66.7; ICD-10, Z51.5) and advanced care planning (ICD-9, V69.89; ICD-10, Z71.89). Palliative procedures included percutaneous or endoscopic bypass, gastrostomy or enterostomy, dilation, drainage, nutrition, and irrigation for palliative purpose. RESULTS AND DISCUSSION: A total of 86,430 patients were selected and analyzed in this study. Using a compound annual growth rate (CAGR) approach, the annual number of hospitalizations of gastric cancer patients was found to be decreased during 2009-2018 (CAGR: -0.8%, P = 0.0084), while utilization rates of palliative care and palliative procedures increased (CAGR: 9.3 and 1.6%, respectively; P < 0.0001). Multivariable regression analysis revealed that palliative care consultation was associated with reduced total hospital charges (-$34,188, P < 0.0001). CONCLUSION: Utilization of palliative care consultation to patients with gastric cancer may reduce use of medical resources and hospital costs.

Incidence and risk factors for postoperative common bile duct stones in patients undergoing endoscopic extraction and subsequent cholecystectomy.

BACKGROUND AND AIMS: In patients who undergo cholecystectomy after endoscopic common bile duct (CBD) stone extraction, CBD stones found postoperatively could be problematic. This study aimed to investigate the incidence and risk factors of postoperative CBD stones after cholecystectomy. METHODS: A total of 278 patients (mean age, 59.2 years; 71 men [51.1%]) who underwent endoscopic removal of CBD stones followed by cholecystectomy from January 2013 to December 2017 were included. An endoscopic nasobiliary drainage (ENBD) tube was placed immediately after endoscopic clearance of the CBD stones in all patients until cholecystectomy. An ENBD tubogram was obtained in all patients to determine the presence of postoperative CBD stones. RESULTS: Postoperative CBD stones were detected in 20.1% (56/278). An ENBD tubogram was obtained after an average of 2.42 days postoperatively. Based on univariate analysis, the statistically significant risk factors for postoperative CBD stone were CBD stones >2, CBD stone size >10 mm, cholesterol stone, maximum diameter of CBD >15 mm, treatment with endoscopic sphincterotomy alone, and use of endoscopic mechanical lithotripsy (EML). In multivariate analysis, cholesterol stone, CBD stones >2, CBD stone size >10 mm, and EML were related to postoperative CBD stones after cholecystectomy. CONCLUSIONS: Based on the relatively high rate of postoperative CBD stones after cholecystectomy, careful follow-up should be considered in patients with high-risk factors to detect CBD stones early.

High-Definition Chromoendoscopy Versus High-Definition White Light Colonoscopy for Neoplasia Surveillance in Ulcerative Colitis: A Randomized Controlled Trial.

OBJECTIVES: Although chromoendoscopy is currently the recommended mode of surveillance in patients with long-standing ulcerative colitis, it is technically challenging and requires a long procedure time. The aim of this study was to compare the dysplasia detection rate of high-definition white light endoscopy with random biopsy (HDWL-R) vs high-definition chromoendoscopy with targeted biopsy (HDCE-T). METHODS: This was a multicenter, prospective randomized controlled trial involving 9 tertiary teaching hospitals in South Korea. A total of 210 patients with long-standing ulcerative colitis were randomized to undergo either the HDWL-R group (n = 102) or HDCE-T group (n = 108). The detection rates of colitis-associated dysplasia (CAD) or all colorectal neoplasia from each trial arm were compared. RESULTS: There was no significant difference in the CAD detection rate between HDCE-T and HDWL-R groups (4/102, 3.9% vs 6/108, 5.6%, P = 0.749). However, HDCE-T showed a trend toward improved colorectal neoplasia detection compared with HDWL-R (21/102, 20.6% vs 13/108, 12.0%, P = 0.093). The median (range) time for colonoscopy withdrawal between the 2 groups was similar (17.6 [7.0-43.3] minutes vs 16.5 [6.3-38.1] minutes; P=0.212; for HDWL-R and HDCE-T, respectively). The total number of biopsies was significantly larger in the HDWL-R group (34 [12-72]) compared with the HDCE-T group (9 [1-20]; P < 0.001). DISCUSSION: On the basis of our prospective randomized controlled trial, HDCE-T was not superior to HDWL-R for detecting CADs.

Prognostic assessment using a new substaging system for Barcelona clinic liver cancer stage C hepatocellular carcinoma: A nationwide study.

AIM & BACKGROUND: Advanced hepatocellular carcinoma (HCC) (Barcelona clinic liver cancer [BCLC] stage C) needs subclassification to more accurately predict survival. This study aims to establish a substaging system of BCLC stage C HCC patients for accurate prognosis. METHODS: Data from 564 patients with newly diagnosed BCLC stage C HCC from three tertiary-care hospitals affiliated with the Korea University (training set) were assessed retrospectively. Variables affecting overall survival (OS) were analysed, and patients were substaged according to the number of prognostic factors they fulfilled. The substaging system was validated using a nationwide database from the Korean Liver Cancer Association (validation set; n = 742). RESULTS: In the training set, tumour factors such as tumour burden ≥10 cm, major portal vein invasion and distant metastasis, as well as underlying liver function, were independently associated with OS. BCLC stage C was classified into four substages (C1-4) according to the number of prognostic factors. Substages C1, C2, C3 and C4 showed a median OS of 17.50 months (95% confidence interval [CI], 8.57-26.43), 10.13 months (95% CI, 8.17-12.09), 4.20 months (95% CI, 3.42-4.98), and 2.90 months (95% CI, 2.34-3.46) respectively (P < 0.05). This substaging system also had good discriminative ability in predicting survival in the validation set. In addition, it was considered that the BCLC substaging is better than Hong Kong liver cancer substaging in predicting the OS for patients with advanced HCC. CONCLUSION: Our substaging for BCLC stage C might help predict patients' prognosis better.

Comparative study of Helicobacter pylori eradication rates of concomitant therapy vs modified quadruple therapy comprising proton-pump inhibitor, bismuth, amoxicillin, and metronidazole in Korea.

BACKGROUND: The standard triple Helicobacter pylori regimen now shows unacceptably low treatment success in Korea. Administration of the concomitant therapy for 10 days, which has a high cure rate, is recommended as an alternative first-line treatment in areas of high clarithromycin resistance including Korea. Recently, modified bismuth-containing quadruple therapy with amoxicillin (PAM-B therapy) showed excellent results, regardless of dual clarithromycin and metronidazole resistance. This study compared the concomitant therapy with PAM-B therapy as a first-line treatment for H. pylori infection. METHOD: Subjects infected with H. pylori and naïve to treatment were performed a head-to-head comparison between 10-day concomitant therapy [rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily] and 14-day PAM-B therapy [rabeprazole 20 mg, amoxicillin 1 g, metronidazole 750 mg, and tripotassium dicitrato bismuthate 600 mg (elemental bismuth 240 mg) twice daily]. Six weeks after treatment, H. pylori eradication was assessed. RESULTS: Two hundred and seventy subjects were randomized. Both regimens achieved high cure rates: 83.0% (112/135) and 88.1% (119/135) by the intention-to-treat analysis and 95.5% (106/111) and 96.6% (114/118) by the per-protocol analysis, respectively. The intention-to-treat and per-protocol analyses revealed no statistically significant difference in the eradication rate (P = .299 and P = .743, respectively). Rates of adverse events were similar between groups (25.2% vs 23.0%, P -value: .776) Adverse events, which resulted in poor compliance, occurred in six patients of each group, but there were no serious complications. CONCLUSIONS: PAM-B therapy is as effective as concomitant therapy for eradicating H. pylori with comparative safety. PAM-B therapy is regarded as a promising alternative to standard triple therapy for a first-line eradication in Korea.

Role of IL-1ra and Granzyme B as biomarkers in active Crohn's disease patients.

BACKGROUND AND AIM: Altered gene expression in intestinal mucosa is thought to contribute to inflammatory process in Crohn's disease (CD). The present study investigated changes in the expression of genes associated with gut inflammation in CD patients by RNA microarray to identify disease biomarkers. METHODS: Microarray analysis was carried out in formalin-fixed, paraffin-embedded intestinal tissue specimens from six CD patients who underwent surgery without prior treatment and from two healthy control subjects. Transcripts overexpressed in CD patients were validated by enzyme-linked immunosorbent assay (ELISA) using specimens from 46 CD patients and 60 healthy controls. RESULTS: Among the genes over-expressed with statistical significance, five genes including decay-accelerating factor, interleukin-1 receptor (IL1R) A, tumour necrosis factor receptor 2, (C-X-C motif) ligand (CXCL) 1, and granzyme (GZM) B proposed to have functional association with CD were selected to validate the expressed transcripts in serum. Serum concentration of IL1RA, CXCL1, and GZMB measured by ELISA were significantly higher in CD patients. CONCLUSIONS: We identified that IL1RA, CXCL1, and GZMB are overexpressed in CD patients. Serum IL1RA and GZMB levels were markedly increased in CD patients, suggesting that these markers can serve as biomarkers to identify gut inflammation. Further studies will be required to evaluate this possibility.

Helicobacter pylori eradication rates of concomitant and sequential therapies in Korea.

BACKGROUND: The efficacy of the standard triple therapy for Helicobacter pylori eradication has decreased to an unacceptable level. We aimed to compare the efficacy of sequential and concomitant therapies as for the first-line treatments for H. pylori eradication and analyzed the effect of clarithromycin resistance on the eradication rates. MATERIALS AND METHODS: Four hundred and seventy-eight patients with H. pylori infection were randomly assigned to either concomitant therapy (amoxicillin 1000 mg with clarithromycin 500 mg, metronidazole 500 mg, and pantoprazole 40 mg twice daily for 10 days) or sequential therapy (amoxicillin 1000 mg with pantoprazole 40 mg twice daily for 5 days, followed by clarithromycin 500 mg with metronidazole 500 mg and pantoprazole 40 mg twice daily for 5 days). The success of the eradication was evaluated 4-5 weeks after treatment completion. To evaluate the efficacy of the two regimens according to clarithromycin sensitivity, dual-priming oligonucleotide-based multiplex-polymerase chain reaction was also performed in the final third of the enrolled study populations. RESULTS: The eradication rates with concomitant or sequential therapy were 81.9% and 76.6% (P = .153) in intention-to-treat analysis, and 93.4% and 84.8% (P = .004) in per-protocol analysis, respectively. Among the 156 patients for whom dual-priming oligonucleotide-based multiplex-polymerase chain reaction was performed, 17.9% were clarithromycin resistant, and the efficacy of concomitant therapy was better than sequential therapy in the clarithromycin-resistant strains (100% vs 58.3%, P = .010). CONCLUSION: Concomitant therapy was superior to sequential therapy as the first-line treatment for H. pylori eradication, especially in clarithromycin-resistant strains in Korea.

Endoscopic biliary stent insertion through specialized duodenal stent for combined malignant biliary and duodenal obstruction facilitated by stent or PTBD guidance.

OBJECTIVES: Endoscopic stenting for combined malignant biliary and duodenal obstruction is technically demanding. However, this procedure can be facilitated when there is guidance from previously inserted stent or PTBD tube. This study aimed to evaluate the feasibility and clinical success rate of endoscopic placement of biliary self-expandable metal stent (SEMS) through duodenal SEMS in patients with combined biliary and duodenal obstruction due to inoperable or metastatic periampullary malignancy. MATERIALS AND METHODS: A total of 12 patients with combined malignant biliary and duodenal stricture underwent insertion of biliary SEMS through the mesh of specialized duodenal SEMS from July 2012 to October 2016. Technical and clinical success rate, adverse events and survival after completion of SEMS insertion were evaluated. RESULTS: The duodenal strictures were located in the first portion of the duodenum in four patients (Type I), in the second portion in three patients (Type II), and in the third portion in five patients (Type III). Technical success rate of combined metallic stenting was 91.7%. Insertion of biliary SEMS was guided by previously inserted biliary SEMS in nine patients, plastic stent in one patient, and PTBD in two patients. Clinical success rate was 90.9%. There were no early adverse events after the procedure. Mean survival period after combined metallic stenting was 91.9 days (range: 15-245 days). CONCLUSIONS: Endoscopic placement of biliary SEMS through duodenal SEMS is feasible with high success rates and relatively easy when there is guidance. This method can be a good alternative for palliation in patients with combined biliary and duodenal obstruction.

Standard and double-dose intravenous proton pump inhibitor injections for prevention of bleeding after endoscopic resection.

BACKGROUND AND AIM: Endoscopic resection is commonly used to remove gastric neoplasms. However, effective dosing or scheduling of proton pump inhibitors for the prevention of delayed bleeding after endoscopic resection remains unclear. METHODS: One hundred sixty-six patients with gastric adenoma or early gastric cancer were enrolled. After an endoscopic procedure, each subject was randomly assigned to 40 mg every 24 h (standard dose group) or 40 mg every 12 h (double-dose group) of intravenous pantoprazole for 48 h. Second-look endoscopy was performed on day 2 after endoscopic resection to compare signs of rebleeding and ulcer status between the two groups. RESULT: Eighty-one patients of the standard dose group and 81 of the double-dose group were analyzed. There were no significant differences in the incidence of delayed bleeding events (1.3% vs 6.2%, P = 0.21) and bleeding ulcer at the second-look endoscopy (6.2% vs 3.9%, P = 0.69) between standard and double-dose groups. There were no other significant variables associated with delayed bleeding or bleeding ulcer on second-look endoscopy. CONCLUSIONS: Intravenous pantoprazole 40 mg every 24 h or 12 h for 2 days after endoscopic resection was equally effective for the prevention of delayed bleeding.

Clinical outcome after enteroscopy for small bowel angioectasia bleeding: A Korean Associateion for the Study of Intestinal Disease (KASID) multiceter study.

BACKGROUND AND AIMS: Angioectasias are the most common sources of bleeding in the small bowel. They can be treated using balloon-assisted enteroscopy (BAE). This study aimed to identify the rebleeding rate and associated factors after BAE in patients with small bowel angioectasia bleeding. METHODS: We retrospectively analyzed the records of patients with bleeding due to small bowel vascular lesion in a multicenter enteroscopy database including 1108 BAEs. Finally, in rebleeding analysis, we analyzed 66 patients with angioectasia on the basis of the Yano-Yamamoto classification. Patients who had undergone endotherapy (ET) were divided into ET (n = 45) and non-ET (n = 21) groups. Rebleeding was defined as evidence of bleeding at least 30 days after BAE. RESULTS: Fifty-three patients (80.4%) underwent only one-side enteroscopy. The most common ET was argon plasma coagulation (87.2%). During a mean follow-up duration of 24.5 months, ET and non-ET groups had rebleeding rates of 15.6% and 38.1% (P = 0.059), respectively. Median rebleeding time of ET and non-ET groups was 32.5 and 62 months, respectively. Liver cirrhosis (LC), low platelet count (< 105 /µL), and transfusions were the rebleeding-associated factors in the univariate analysis. In the multivariate analysis, the presence of LC (HR 4.064, 95% CI 1.098-15.045; P = 0.036) was the only independent rebleeding-associated risk factor. CONCLUSIONS: ET using BAE did not significantly affect the rebleeding rate in patients with small bowel angioectasia bleeding. An independent rebleeding risk factor was the presence of LC. Regardless of ET, careful long-term follow-up may be needed, especially in LC patients with small bowel angioectasia bleeding.

Risk of Vascular Thrombotic Events Following Discontinuation of Antithrombotics After Peptic Ulcer Bleeding.

GOALS: To evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. BACKGROUND: Peptic ulcer bleeding associated with antithrombotics has increased due to the increase in the proportion of elderly population. Little is known about the long-term effects of discontinuing antithrombotics after peptic ulcer bleeding. The aim of this study was to evaluate whether the risk of cardiovascular events increases when antithrombotics are discontinued after ulcer bleeding. STUDY: We reviewed the medical records of patients with ulcer bleeding who were taking antiplatelet agents or anticoagulants at the time of ulcer bleeding. Cox-regression model was used to adjust for potential confounders, and analyzed association between discontinuation of antithrombotic drugs after ulcer bleeding and thrombotic events such as ischemic heart disease or stroke. RESULTS: Of the 544 patients with ulcer bleeding, 72 patients who were taking antithrombotics and followed up for >2 months were analyzed. Forty patients discontinued antithrombotics after ulcer bleeding (discontinuation group) and 32 patients continued antithrombotics with or without transient interruption (continuation group). Thrombotic events developed more often in discontinuation group than in the continuation group [7/32 (21.9%) vs. 1/40 (2.5%), P=0.019]. Hazard ratio for thrombotic event when antithrombotics were continuously discontinued was 10.9 (95% confidence interval, 1.3-89.7). There were no significant differences in recurrent bleeding events between the 2 groups. CONCLUSIONS: Discontinuation of antithrombotics after peptic ulcer bleeding increases the risk of cardiovascular events. Therefore, caution should be taken when discontinuing antithrombotics after ulcer bleeding.

Predictive Factors for Pain After Endoscopic Resection of Gastric Tumors.

BACKGROUND: Abdominal pain is a common complaint following endoscopic resection (ER). AIMS: To investigate the predictive factors for abdominal pain after ER. METHODS: Patients who were scheduled to undergo endoscopic mucosal resection or endoscopic submucosal dissection for the treatment of gastric adenoma or cancer were prospectively enrolled. Pain scores were checked every 6 h after ER and whenever patients complained of pain by using a 0-10 pain scale. If the pain score exceeded 5, 25 mg of intravenous (IV) pethidine was administered. RESULTS: Among 156 patients who underwent ER, 66 (42.3 %) received IV pethidine due to moderate/severe abdominal pain. Both the number of patients complaining of abdominal pain and the pain scores decreased with time following the procedure, with only a few patients complaining of mild abdominal pain 2 days after ER. Multivariate analysis showed that female sex [odds ratio (OR) 2.88; confidence interval (CI) 1.31-6.33], tumor location in the lower third of the stomach (OR 5.46; CI 2.31-12.92), and procedures time more than 60 min (OR 2.96; CI 1.26-6.98) were significant predictive factors for developing pain after ER. CONCLUSIONS: Female sex, tumor location in the lower third of the stomach, and longer procedure time were significantly associated with pain after ER. Close monitoring and active management of pain is recommended for patients who have these risk factors. With these efforts, the majority of patients could experience pain relief within 2 days after the procedure.

Predictive Factors of Atelectasis Following Endoscopic Resection.

BACKGROUND AND AIM: Atelectasis is one of the pulmonary complications associated with anesthesia. Little is known about atelectasis following endoscopic procedures under deep sedation. This study evaluated the frequency, risk factors, and clinical course of atelectasis after endoscopic resection. METHODS: A total of 349 patients who underwent endoscopic resection of the upper gastrointestinal tract at a single academic tertiary referral center from March 2010 to October 2013 were enrolled. Baseline characteristics and clinical data were retrospectively reviewed from medical records. To identify atelectasis, we compared the chest radiography taken before and after the endoscopic procedure. RESULTS: Among the 349 patients, 68 (19.5 %) had newly developed atelectasis following endoscopic resection. In univariate logistic regression analysis, atelectasis correlated significantly with high body mass index, smoking, diabetes mellitus, procedure duration, size of lesion, and total amount of propofol. In multiple logistic regression analysis, body mass index, procedure duration, and total propofol amount were risk factors for atelectasis following endoscopic procedures. Of the 68 patients with atelectasis, nine patients developed fever, and six patients displayed pneumonic infiltration. The others had no symptoms related to atelectasis. CONCLUSIONS: The incidence of radiographic atelectasis following endoscopic resection was nearly 20 %. Obesity, procedural time, and amount of propofol were the significant risk factors for atelectasis following endoscopic procedure. Most cases of the atelectasis resolved spontaneously with no sequelae.

Efficacy of telbivudine compared with entecavir in hepatitis B virus-related cirrhosis: 2 year follow-up data.

BACKGROUND & AIMS: Entecavir (ETV) is effective in the treatment of chronic hepatitis B virus (HBV) infections, even in patients with underlying cirrhosis. However, there is little information on the effect of telbivudine (TBV) in chronic hepatitis B patients with cirrhosis.This study compared the antiviral efficacy of TBV and ETV in HBV-related cirrhosis. METHODS: We consecutively enrolled 151 treatment-naïve patients with HBV-related cirrhosis who started antiviral therapy with TBV (n = 61) or ETV (n = 90). RESULTS: After 24 months of treatment, per-protocol analysis showed similar virological response rates (HBV DNA <20 IU/ml) in the TBV group (80.6%, 25/31) and in the ETV group (90.2%, 74/82) (P = 0.167). However, intention-to-treat analysis showed lower virological response rates in the TBV group (41.7%, 25/60) than in the ETV group (83.1%, 74/89) (P = 0.001). Mean reduction in HBV DNA levels was greater in the ETV group (-3.72 ± 1.94 vs. -4.87 ± 1.57 respectively, P = 0.001). Serologic and biochemical response rates at month 24 did not differ significantly between the groups. Child-Turcotte-Pugh score was significantly improved after 24 months compared to the pretreatment state without difference between the groups. During 24 months of therapy, 15 patients (27.3%) showed antiviral resistance to TBV while no resistance (0%) was reported in the ETV group (P = 0.001). CONCLUSIONS: Compared to ETV, TBV therapy shows lower efficacy in viral suppression and higher risk of antiviral resistance despite comparable effect on improvement of hepatic function for the treatment of HBV-related cirrhosis.

Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.

OBJECTIVE: Crohn's disease (CD) is an intractable inflammatory bowel disease (IBD) of unknown cause. Recent meta-analysis of the genome-wide association studies (GWAS) and Immunochip data identified 163 susceptibility loci to IBD in Caucasians, however there are limited studies in other populations. METHODS: We performed a GWAS and two validation studies in the Korean population comprising a total of 2311 patients with CD and 2442 controls. RESULTS: We confirmed four previously reported loci: TNFSF15, IL23R, the major histocompatibility complex region, and the RNASET2-FGFR1OP-CCR6 region. We identified three new susceptibility loci at genome-wide significance: rs6856616 at 4p14 (OR=1.43, combined p=3.60×10(-14)), rs11195128 at 10q25 (OR=1.42, combined p=1.55×10(-10)) and rs11235667 at 11q13 (OR=1.46, combined p=7.15×10(-9)), implicating ATG16L2 and/or FCHSD2 as novel susceptibility genes for CD. Further analysis of the 11q13 locus revealed a non-synonymous single nucleotide polymorphism (SNP) (R220W/rs11235604) in the evolutionarily conserved region of ATG16L2 with stronger association (OR=1.61, combined p=2.44×10(-12)) than rs11235667, suggesting ATG16L2 as a novel susceptibility gene for CD and rs11235604 to be a potential causal variant of the association. Two of the three SNPs (rs6856616 (p=0.00024) and rs11195128 (p=5.32×10(-5))) showed consistent patterns of association in the International IBD Genetics Consortium dataset. Together, the novel and replicated loci accounted for 5.31% of the total genetic variance for CD risk in Koreans. CONCLUSIONS: Our study provides new biological insight to CD and supports the complementary value of genetic studies in different populations.

Helicobacter pylori recurrence after first- and second-line eradication therapy in Korea: the problem of recrudescence or reinfection.

BACKGROUND: Recurrence of Helicobacter pylori (H. pylori) infection is the result of either recrudescence or reinfection. Annual recurrence rates per patient-year of follow-up have been reported to vary across countries. The aim of this study was to analyze recurrence rates of H. pylori after first-line and second-line eradication therapies in Korea. MATERIALS AND METHODS: From 2007 to 2010, 2691 patients with H. pylori infection received first-line therapy and 573 patients who failed to respond to first-line therapy received second-line therapy. H. pylori infection and the success of eradication were assessed by endoscopic biopsy and rapid urease test or (13) C-urea breath test. All patients were advised to undergo (13) C-urea breath test or esophagogastroduodenoscopy with biopsy or rapid urease test 6 months after eradication, with annual follow-up thereafter. RESULTS: The eradication rate of the first-line therapy was 79.9% (1283/1605) and that of the second-line therapy was 90.4% (394/436) by per protocol analysis. Annual recurrence rates sharply declined after 2-year follow-up. Annual recurrence rates within and after 2-year follow-up were 9.3 and 2.0% after first-line therapy and those of second-line therapy were 4.5 and 2.9%, respectively. CONCLUSIONS: Annual recurrence rates of H. pylori showed a sharp decline after 2-year follow-up after eradication in Korean adults, which is not higher than that of Western countries. Enough time interval after treatment (i.e., 2 years) is necessary to confirm eradication, and it would not be easy to distinguish between recurrence and recrudescence before 2 years without identifying H. pylori strains.

Risk of adenomas with high-risk characteristics based on two previous colonoscopy.

BACKGROUND AND AIM: The recommended intervals between surveillance colonoscopies are based on the most recent examination findings. However, whether the two previous colonoscopies affect second surveillance colonoscopic findings is not established. The aim of this study is to estimate the risk of obtaining high-risk findings (HRF) on the next surveillance colonoscopy using the results of two previous colonoscopies, and to estimate the appropriate time interval for the next surveillance colonoscopy. METHODS: Among subjects who underwent screening colonoscopy during January 2002-December 2009, patients who underwent second surveillance colonoscopy before June 2012 were enrolled. "No adenoma" was defined as a hyperplastic polyp or no polyp, "low-risk findings (LRF)" as one or two small (< 1 cm) tubular adenomas, and "HRF" as advanced adenoma, cancer, or any sized multiple (≥ 3) adenomas. RESULTS: Among enrolled 852 subjects, 65 (7.6%) had HRF at second surveillance colonoscopy. Multivariate analysis showed that HRF on second surveillance colonoscopy were associated with male and HRF on screening colonoscopy (all, P < 0.01). In subjects with LRF on first surveillance colonoscopy, HRF on the screening colonoscopy significantly affected the detection of HRF on second surveillance colonoscopy (P < 0.01). Patients with HRF on screening colonoscopy and LRF on the first surveillance colonoscopy had no different risk of HRF on second surveillance colonoscopy from those with HRF on first surveillance colonoscopy (P > 0.05). CONCLUSIONS: The HRF on second surveillance are significantly associated with previous two colonoscopic results. In patients with LRF on first surveillance, screening colonoscopic findings should be considered to determine the optimal surveillance interval.

Synergistic effect of simvastatin plus NS398 on inhibition of proliferation and survival in hepatocellular carcinoma cell line.

BACKGROUND AND AIMS: NS398, a selective cyclooxygenase-2 inhibitor, and simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, both exert an anticancer effect on hepatocellular carcinoma cells, but the effect of co-administration of the two drugs remains unknown. We aimed to investigate the synergistic in vitro anticancer effect of co-administration of NS398 and simvastatin and its mechanism. METHODS: The Hep3B and Huh-7 cell lines were cultured. Cells were treated with simvastatin, NS398, or a combination. 5-bromo-2'-deoxyuridine ELISA assay, flow cytometry, Western blot analyses, and immunofluorescence assay were performed. RESULTS: In both cell lines, co-administration of simvastatin and NS398 resulted in a greater effect on proliferation and apoptosis. In Hep3B cells, co-administration of the two drugs resulted in a greater decrease in procaspase 3 and Bcl-2 and an increase in cleaved caspase 9 than that noted with monotherapy. In Huh-7 cells, co-administration of the two drugs resulted in a greater decrease in procaspase 3 and cyclin D1 and an increase in cleaved caspase 9. Expression of NF-κB and Akt were also decreased to a greater extent when the two drugs were co-administered in both cell lines. Immunofluorescence assay showed suppression of the nuclear localization of NF-κB by simvastatin or NS398. The effect was greater by co-administration. CONCLUSIONS: The co-administration of NS398 and simvastatin produced greater antiproliferative and proapoptotic effects against Hep3B cells and Huh-7 cells. Inhibition of the NF-κB and Akt pathway and activation of caspase cascade, which are considered as the major mechanism of synergistic anticancer properties, were observed in both cell lines.