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Background This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. Methods Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. Results Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn’s disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non–reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. Conclusions The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

Purpose: Anemia affects the life quality of inflammatory bowel disease (IBD) patients, but no report from Asian about anemia screening and its impact previously. We aimed to explore the prevalence and impact of anemia among the IBD patients in Taiwan.A retrospective study was conducted from January 2006 to February 2018 at National Taiwan University Hospital. Clinical characteristics and outcomes were analyzed.A total of 1604 IBD patients were enrolled [494 Crohn's disease (CD) and 1110 ulcerative colitis (UC)]. Overall, 95.3% (471/494) of CD and 87.9% (976/1110) of UC patients underwent anemia screening. Anemia screening rate in IBD patients significantly increased from 62.6% (162/259) in 2006 to 77.2% (838/1086) in 2017. The mean time from IBD diagnosis to anemia screening was 122.4 days in CD patients and even longer in UC patients at 216.2 days. Persistent anemia was found in 47.3% (548/1158) of the screened patients. Risk factors of persistent anemia included low body mass index [odds ratio (OR) = 1.96, p 0.01], steroid [OR = 2.96, p 0.01], thiopurine [OR = 2.62, p 0.01], colectomy [OR = 6.3, p 0.01], and small bowel resection [OR = 3.21, p 0.05)] after IBD diagnosis. Compared with those without anemia, anemic IBD patients had higher admission (p 0.01) and mortality rates (p 0.01).The anemia screening rate was acceptable and increased over time in Taiwan. Since anemia is associated with worse outcomes, earlier survey and treatment of anemia in IBD patients is recommended.

Despite the lack of evidence for the benefits of dietary restrictions for ulcerative colitis (UC), the majority of patients with UC restrict their diets to avoid relapses. Few studies have examined information resources that affect patients' dietary beliefs or practices, but none have investigated UC patients in clinical remission from Asia. This survey investigated the dietary beliefs, practices, and information resources of Taiwanese UC patients in clinical remission.A self-reported questionnaire was administered. Fifty UC patients in clinical remission (defined based on having a 2-item patient-reported outcome score of ≤1 with no rectal bleeding for ≥90 days) were recruited from National Taiwan University Hospital between September 2017 and March 2018.In total, 22 patients (45.8%) believed diet to be the initiating factor for UC, and 48.0% of patients believed diet has ever triggered relapses. Forty-two patients (85.7%) avoided specific foods to prevent a relapse. Spicy foods were the most avoided foods (75.5%), following by alcohol (69.4%), carbonated beverages (63.3%), milk or milk products (59.2%), and fatty foods (59.2%). The patients' information resources for dietary beliefs and practices consisted mainly of their own experience. Approximately one-third of the patients have avoided the same menu with their family or avoided outdoor dining to prevent UC relapses.This is the first dietary belief survey focusing on clinical remission UC patients from Asia. Most clinical remission UC patients spontaneously avoided specific foods based on their own experiences. Dietary restrictions may negatively affect patients' social lives. Further dietary counseling is necessary to minimize the possible negative impacts on UC patients in clinical remission.

Background/Aims: Incidences of inflammatory bowel disease (IBD), ulcerative colitis (UC), and Crohn’s disease (CD), have been increasing in Asia. In this study, we report the relevant clinical characteristics and determined the epidemiological trend of IBD in Taiwan from 2001 to 2015. Methods: A retrospective study was conducted to analyze data recorded from January 2001 through December 2015 in the registered database compiled by the National Health Insurance and provided by the Ministry of Health and Welfare, Taiwan. Results: A total of 3,806 patients with catastrophic IBD illness were registered from 2001 to 2015 in Taiwan (CD, 919; UC, 2,887). The crude incidence of CD increased from 0.17/100,000 in 2001 to 0.47/100,000 in 2015, whereas that of UC increased from 0.54/100,000 in 2001 to 0.95/100,000 in 2015. The prevalence of CD increased from 0.6/100,000 in 2001 to 3.9/100,000 in 2015, whereas that of UC increased from 2.1/100,000 in 2001 to 12.8/100,000 in 2015. The male-to-female ratio in the study sample was 2.19 for CD and 1.62 for UC. The median age of those registered with CD was lower than that of those registered for UC: 38.86 and 44.86 years, respectively. A significantly greater increase in CD incidence rate was identified among 20 to 39-year-old compared with other age groups. Conclusions: Using Taiwan’s nationwide insurance database, we de termined that the number of patients with CD increased more rapidly during the study period than the number of patients with UC, especially among age 20 to 39-year-old, resulting in a decreased UC-to-CD ratio. (Intest Res 2019;17:54-62)

Background/Aims Fecal calprotectin (fC) level is a predictive marker of mucosal healing for patients with inflammatory bowel disease (IBD). Home fC tests are now available. We evaluated the performance of the smartphone-based IBDoc home testing system in patients with IBD and obtained their feedback as an objective patient-reported outcome. Methods This prospective study enrolled consecutive patients with IBD in clinical remission. fC in the same stool sample was assessed by using both the laboratory test (Quantum Blue calprotectin test) and home test (IBDoc). The correlation between the 2 tests was analyzed using the Pearson method. In addition, the patients were asked to fill a questionnaire based on their experience. Results Fifty-one patients with IBD (68 tests and 49 questionnaires) were included. The correlation between Quantum Blue test and IBDoc was good (r=0.776, P70%) probability to use it for future monitoring if the price was acceptable. By using 250 μg/g as the cutoff, the agreement between home test and laboratory results was 80%, and by using 600 μg/g as the cutoff, the agreement increased to 92%. Conclusions The correlation between the laboratory and home tests was good. Most patients found the home test to be feasible and easy to use and preferred it over laboratory test and endoscopy for monitoring. Therefore, the home test could be used as an objective patient-reported outcome.

Background/Aims: Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD). We aimed to evaluate the prevalence, clinical manifestation, and outcomes of PSC in Taiwanese patients with IBD. Methods: This retrospective study enrolled patients with IBD admitted from January 1, 1996, to December 31, 2018, to National Taiwan University Hospital. A case-matched analysis was performed comparing patients with IBD with and without PSC according to age, sex, and time of admission, with ratios of 1:4 and 1:2 in the adult and pediatric groups, respectively.Results: In total, 763 patients with IBD were enrolled, 12 of whom were also diagnosed with PSC (1.57%). All these patients had ulcerative colitis (UC). A greater incidence of IBD with PSC was observed in younger patients than in older patients. Male sex was a risk factor for PSC in pediatric patients with IBD (P=0.015); 75% of these patients were diagnosed with PSC along with or after the diagnosis of UC. There was no significant difference in colitis extent and severity between the groups; however, a higher proportion of rectal sparing was observed in patients with PSC (P=0.001). There was no significant difference in cancer development between the groups (P=0.679). Conclusions: A 1.57% prevalence of PSC was observed in Taiwanese patients with IBD. The majority of patients with IBD and PSC were men and were diagnosed at a younger age. Hence, routine evaluation of biliary enzymes and liver imaging is recommended in young male patients with IBD.

Background: Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, usually diagnosed at advanced stage with poor outcomes. We aimed to find possible diagnostic clues in order to help diagnosis. Methods: A retrospective study of PSRCCR patients from 1993 to 2018 was reviewed at a single tertiary center. Colorectal adenocarcinoma patients as control group with 1:4 ratio was also enrolled. Results: 18 patients with PSRCCR were identified. The prevalence rate was 0.16% (18 of 11,515). The mean age was 50.2 years-old in PSRCCR group and 63 years-old in non-SRCC colorectal cancer patients ( p < 0.001). Diagnosis tool depends on CFS were much less in PSRCCR group than control group (44.4 % vs 93 %, p < 0.001). SRCC patients had higher level of CEA (68.3 vs 17.7 ng/mL, p =0.004) and lower level of Albumin (3.4 vs 4.3 g/dL, p < 0.001). The majority of PSRCCR tumor configuration was ulcerative and infiltrative. More PSRCCR pathology presented as high-grade carcinoma (66.7 vs 1.4 %, p < 0.001) and lymphovascular invasion (77.8 vs 44.4 %, p = 0.011) than control group. More PSRCCR patients were diagnosed at advanced stage (88.8 vs 40.3 %, p = 0.001). Higher mortality was also noticed in PSRCCR group than control group (72.2 vs 20.8 %, p < 0.001). Conclusion: For young patients with long segment colonic stenosis and ulcerative/ infiltrative mucosa but endoscopic biopsy failed to identify malignant cells, earlier operation or non-colon site biopsy is suggested for diagnosing the PSRCCR.

Background Inflammatory bowel disease (IBD) was emerging as a worldwide epidemic disease, and the advanced therapy changed the clinical course and possibly the outcomes. Our previous study reported a higher mortality rate from (IBD) in Taiwan than in Western countries. We proposed to analyze the trend and risk factors of mortality in order to improve the care quality of IBD patients. Methods This retrospective study was conducted to analyze data for January 2001 to December 2015 from a registered database, compiled by the Taiwan’s National Health Insurance. Results Between 2001 and 2015, a total of 3806 IBD patients [Crohn’s disease (CD): 919; ulcerative colitis (UC): 2887] were registered as having catastrophic illness, and 8.2% of these patients died during follow-up. The standardized mortality ratios (SMRs) of CD and UC were 3.72 (95% CI 3.02–4.55) and 1.44 (95% CI 1.26–1.65), respectively, from 2001 to 2015, respectively. A comparison of the periods of 2011–2015 and 2001–2005 revealed a decrease in the mortality rates from both UC and CD. Multivariate Cox proportional hazards analysis identified elderly individuals; sepsis and pneumonia were the risk factors for IBD mortality. The specific risk factors of mortality were liver cancer for UC and surgeries for CD. Conclusion For further decreasing IBD-related mortality in Taiwan, we need to pay special attention toward elderly individuals, infection control, cancer screening and improvement in perioperative care.

Background Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism (VTE) events. However, the incidence and necessity of prophylaxis for VTE in Asian IBD patients is unknown. We examined the incidence of VTE in East Asian IBD patients and analyze the possible risk factors. Methods We conducted a multinational retrospective study of 2562 hospitalized IBD patients from 2010 to 2015. Moreover, a nationwide cohort study from 2001 to 2013 from the Taiwan National Health Insurance Research Database (NHIRD) was conducted to analyze the incidence rate of VTE in IBD and non-IBD patients. Results In the hospitalized cohort, 24 IBD patients [17 ulcerative colitis (UC) and 7 Crohn's disease (CD)] received a VTE diagnosis (0.9%). These patients had a higher proportion of extensive UC (P = 0.04), penetrating-type CD (P < 0.01), and bowel operation history (P = 0.01). VTE was associated with low hemoglobin (P < 0.01), low platelet (P < 0.01), and low albumin (P < 0.01) levels. For the nation-wide cohort study, 3178 IBD patients and 31,780 age- and sex-matched non-IBD patients were analyzed. The average incidence rate was 1.15 per 1000 person-years in the IBD cohort and 0.51 in the non-IBD cohort. The relative risk was 2.27 (95% CI, 1.99-2.60). Conclusions East Asian IBD patients carry a 2-fold increased risk of VTE than the general population. The incidence of VTE in the East Asian IBD patients is still lower than that in Western countries. Therefore, close monitoring rather than routine prophylaxis of VTE in East Asian IBD patients is recommended.

Background The empiric therapies for H. pylori infection in clinical guidelines have been widely used. However, the cure rate is decreasing due to the increase of antibiotic resistance. The importance of antimicrobial susceptibility test (AST) has been documented in many consensuses. However, the effect of tailored therapy remains controversial because the AST is rarely offered in most areas. We compared the evolution of treatment efficacy among tailored therapy and some recommended empiric therapies through a trend survey from 1999 to 2018. Methods This retrospective survey was performed at 2 medical centers and 3 community hospitals in Taiwan. A total of 16,370 treatment naive or failure patients were recruited. Successful H. pylori eradication was defined as a negative 13C-UBT. The empiric first-line regimens include tailored therapy, clarithromycin-containing triple therapy (CLA-TT), sequential therapy (ST), bismuth-containing quadruple therapy (BQT), and high-dose dual therapy (HDDT). The empiric rescue regimens include tailored therapy, levofloxacin-containing triple therapy (LEV-TT), BQT, and HDDT. We divided the 20 years of follow-up time into 4-year periods for evaluating the trend of treatment efficacies. The E-test was performed to evaluate H. pylori resistance. For the tailored therapy, CLA-TT, LEV-TT, BQT, or HDDT was chosen according to the resistance pattern of each patient. Results The efficacies of tailored therapy, BQT, and HDDT maintain a stable and high efficacy in both first-line and rescue treatment during the study period. However, the efficacies of CLA-TT, ST, and LEV-TT are decreasing year by year. The eradication rate of tailored therapy is significantly higher than that of CLA-TT, ST, LEV-TT, and BQT in recent 4-year period. However, there is no significant difference between the efficacy of tailored therapy and HDDT. The prevalence of H. pylori resistance to CLA and LEV increased gradually. In contrast, the resistance rate to amoxicillin and tetracycline remained low. Conclusions Over the past 20 years, we found that the efficacy of tailored therapy remains relatively stable. Of the recommended empiric therapies, HDDT and BQT have stable therapeutic efficacies and are a good choice of empiric treatment currently.

Objectives: The clinical impact of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) in managing pancreatic cystic neoplasms (PCNs) remains controversial. The aim of this study was...

This study aimed to investigate the drug delivery efficacy and bio-effectiveness of a novel photodynamic therapy (PDT)-matrix drug delivery system for cholangiocarcinoma (CCA). Metallic stents were coated with polyurethane (PU) as the first layer. A 2-hydroxyethyl methacrylate (2-HEMA)/ethylene glycol dimethacrylate (EGDMA)/benzoyl peroxide (BPO) layer and a poly(ethylene-co-vinyl acetate) (PEVA)/poly(n-butyl methacrylate) (PBMA)/polyvinylpyrrolidone K30 (K30) layer containing various concentrations of Photofrin were then incorporated onto the stent as the second and third layers. After incubating the layered membranes with cultured CCA cell line, the release of Photofrin, cell viability, the intracellular uptake of Photofrin, reactive oxygen species (ROS) generation, and apoptosis were determined. Using a single-layer diffusion model, the maximum release of Photofrin from the 5 to 10% K30 formulas was 80 and 100%, respectively, after 24 h. When using the multiple-layer diffusion model, the released Photofrin showed an initial burst of the loading dose from the PEVA/PBMA/K30 layer. In the immobilized model, less than 5% of the Photofrin from the 2-HEMA/EGDMA/BPO layer was released over the 24-h period. Cell viability decreased linearly with increasing Photofrin concentrations, and ROS generation and apoptosis were shown to increase significantly with increasing Photofrin concentrations, until the concentration of Photofrin reached a saturation point of 1.5 μg/ml. This new, multiple-layered, PDT-based stent with dual-release mechanisms is a promising treatment for CCA and cancer-related ductal stenosis.

Background The integrity of the gut barrier in patients with inflammatory bowel disease is known to be impaired but the exact mechanisms remain mostly unknown. SHANK3 mutations are associated with autism, and patients with autism are known to have higher proportions of inflammatory bowel disease. Here, we explore the role of SHANK3 in inflammatory bowel disease, both in vivo and in vitro. Methods Dextran sulfate sodium colitis was induced in SHANK3 knockout mice. Transepithelial electrical resistance, paracellular permeability, and Salmonella invasion assays were used to evaluate epithelial barrier function, in vitro and in vivo. Expression of tight junction proteins, protein kinases, and MAP kinase phosphorylation changes were analyzed by immunoblotting after overexpression or knockdown of SHANK3 expression. SHANK3 expression in intestinal tissue from patients with Crohn's disease was analyzed by quantitative polymerase chain reaction and immunohistochemistry. Results SHANK3 knockout mice were more susceptible to dextran sulfate sodium. SHANK3 knockout resulted in a leaky epithelial barrier phenotype, as demonstrated by decreased transepithelial electrical resistance, increased paracellular permeability, and increased Salmonella invasion. Overexpression of SHANK3 enhanced ZO-1 expression, and knockdown of SHANK3 resulted in decreased expression of ZO-1. Regulation of ZO-1 expression by SHANK3 seems to be mediated through a PKCe-dependent pathway. SHANK3 expression correlated with ZO-1 and PKCe in colonic tissue of patients with Crohn's disease. Conclusions The expression level of SHANK3 affects ZO-1 expression and the barrier function in intestinal epithelial cells. This may provide novel insights in Crohn's disease pathogenesis and treatment.

Background and Aim Biliary tract carcinomas (BTCs) are difficult to diagnose and treat. Epidermal growth factor receptor (EGFR) represents a therapeutic target for the BTCs. Mutations of the EGFR gene and the activation of its downstream pathways, including KRAS and BRAF, predict the sensitivity to anti-EGFR treatment. The aims of this study were to analyze the EGFR, KRAS and BRAF mutations in BTCs and their association with clinical outcomes. Methods Paraffin-embedded specimens containing 137 BTCs resected at the National Taiwan University Hospital between 1995 and 2004 were analyzed. The exons 18–21 of EGFR gene, the codon 12, 13 and 61 of KRAS gene, and BRAF V600E mutation were analyzed. We examined the correlation between these mutations and the overall survival, tumor location, stage, and differentiation in BTCs. Results Thirteen (9.5%) BTC patients had EGFR mutations while 23 (16.8%) patients had KRAS mutations. Only one patient had BRAF mutation. Factors influencing survival on univariate analysis were tumor stage, tumor differentiation, and EGFR mutation. On multivariate analysis, EGFR mutation and tumor stage were independent prognostic factors. A correlation between KRAS or BRAF mutations and prognosis was not observed. Conclusions EGFR and KRAS mutations are not uncommon in BTCs. BRAF mutation is rare in BTCs. EGFR mutation was an independent prognostic marker in BTCs in addition to tumor stage and differentiation. No simultaneous EGFR and KRAS mutations in extrahepatic cholangiocarcinoma and gallbladder carcinoma were found. EGFR and KRAS mutations should be evaluated when tailoring molecular-targeted therapy to patients with BTCs.

Background and Aim Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn's disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients. Methods Clinical information, serum isolation, and DNA were collected after obtaining informed consent. The serological markers were analyzed by ELISA kits and the genetic analysis for TNFSF15 single-nucleotide polymorphisms (SNPs) by Sequenom. Statistic analyses were conducted by SAS 9.2 (Cary, NC, USA). Results This study included 108 patients (55 CD, 53 UC) and 60 healthy controls. An initial low positive rate and low sensitivity for the serological markers led us to reset the cut-off values. This reset cut-off for ASCA IgA yielded a sensitivity of 0.291 and specificity of 0.925 for differentiating CD from UC patients. The reset cut-off value for p-ANCA (anti-MPO) had a sensitivity of 0.461 and a specificity of 0.817 for differentiating inflammatory bowel disease patients from healthy controls. Among the TNFSF15 SNPs, rs4263839 associated with CD in Taiwan (P = 0.005), haplotype analysis did not increase the association. Combining the genetic marker TNFSF15 (rs4263839) and serological marker ASCA IgA increased the area under the curve from 0.61 to 0.70 for predicting stenosis/perforating phenotype, compared to ASCA IgA alone. Conclusions Serological markers need to be tested and tailored to different countries/ethnicities. Combining the genetic marker TNFSF15 with ASCA IgA increased the power of predicting stenosis/perforating phenotype in CD patients with TNFSF15 but not with a NOD2 genetic background.

To evaluate the correlation between fecal calprotectin (fC), C-reactive protein (CRP), and endoscopic disease score in Asian inflammatory bowel disease (IBD) patients.Stool samples were collected and assessed for calprotectin levels by Quantum Blue Calprotectin High Range Rapid test. Crohn's disease endoscopic index of severity (CDEIS) and ulcerative colitis endoscopic index of severity (UCEIS) were used for endoscopic lesion scoring.A total of 88 IBD patients [36 patients with Crohn's disease (CD) and 52 with ulcerative colitis (UC)] were enrolled. For CD patients, fC correlated with CDEIS (r = 0.465, P = 0.005) and CRP (r = 0.528, P = 0.001). fC levels in UC patients correlated with UCEIS (r = 0.696, P0.0001) and CRP (r = 0.529, P = 0.0005). Calprotectin could predict endoscopic remission (CDEIS6) with 50% sensitivity and 100% specificity (AUC: 0.74) in CD patients when using 918 μg/g as the cut-off. When using 191 μg/g as the cut-off in UC patients, calprotectin could be used for predicting endoscopic remission (UCEIS3) with 88% sensitivity and 75% specificity (AUC: 0.87).fC correlated with both CDEIS and UCEIS. fC could be used as a predictor of endoscopic remission for Asian IBD patients.

Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohn’s disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients.Clinical information, serum isolation, and DNA were collected after obtaining informed consent. The serological markers were analyzed by ELISA kits and the genetic analysis for TNFSF15 single-nucleotide polymorphisms (SNPs) by Sequenom. Statistic analyses were conducted by SAS 9.2 (Cary, NC, USA).This study included 108 patients (55 CD, 53 UC) and 60 healthy controls. An initial low positive rate and low sensitivity for the serological markers led us to reset the cut-off values. This reset cut-off for ASCA IgA yielded a sensitivity of 0.291 and specificity of 0.925 for differentiating CD from UC patients. The reset cut-off value for p-ANCA (anti-MPO) had a sensitivity of 0.461 and a specificity of 0.817 for differentiating inflammatory bowel disease patients from healthy controls. Among the TNFSF15 SNPs, rs4263839 associated with CD in Taiwan (P = 0.005), haplotype analysis did not increase the association. Combining the genetic marker TNFSF15 (rs4263839) and serological marker ASCA IgA increased the area under the curve from 0.61 to 0.70 for predicting stenosis/perforating phenotype, compared to ASCA IgA alone.Serological markers need to be tested and tailored to different countries/ethnicities. Combining the genetic marker TNFSF15 with ASCA IgA increased the power of predicting stenosis/perforating phenotype in CD patients with TNFSF15 but not with a NOD2 genetic background.

Biliary tract carcinomas (BTCs) are difficult to diagnose and treat. Epidermal growth factor receptor (EGFR) represents a therapeutic target for the BTCs. Mutations of the EGFR gene and the activation of its downstream pathways, including KRAS and BRAF, predict the sensitivity to anti-EGFR treatment. The aims of this study were to analyze the EGFR, KRAS and BRAF mutations in BTCs and their association with clinical outcomes.Paraffin-embedded specimens containing 137 BTCs resected at the National Taiwan University Hospital between 1995 and 2004 were analyzed. The exons 18-21 of EGFR gene, the codon 12, 13 and 61 of KRAS gene, and BRAF V600E mutation were analyzed. We examined the correlation between these mutations and the overall survival, tumor location, stage, and differentiation in BTCs.Thirteen (9.5%) BTC patients had EGFR mutations while 23 (16.8%) patients had KRAS mutations. Only one patient had BRAF mutation. Factors influencing survival on univariate analysis were tumor stage, tumor differentiation, and EGFR mutation. On multivariate analysis, EGFR mutation and tumor stage were independent prognostic factors. A correlation between KRAS or BRAF mutations and prognosis was not observed.EGFR and KRAS mutations are not uncommon in BTCs. BRAF mutation is rare in BTCs. EGFR mutation was an independent prognostic marker in BTCs in addition to tumor stage and differentiation. No simultaneous EGFR and KRAS mutations in extrahepatic cholangiocarcinoma and gallbladder carcinoma were found. EGFR and KRAS mutations should be evaluated when tailoring molecular-targeted therapy to patients with BTCs.

Background The incidence of the inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), has been increasing in Asia. We probed the nationwide registered database to assess the incidence, prevalence, gender distribution, age of diagnosis and the survival status of IBD patients in Taiwan. Methods A retrospective study was conducted to analyze the registered database compiled by the National Health Insurance provided by the Department of Health, Taiwan, from January 1998 through December 2008. Results A total of 1591 IBD patients were registered from 1998 to 2008 in Taiwan (CD: 385; UC: 1206). The incidence of CD increased from 0.19/100,000 in 1998 to 0.24/100,000 in 2008. The incidence of UC increased from 0.61/100,000 in 1998 to 0.94/100,000 in 2008. The prevalence of CD increased from 0.19/100,000 in 1998 to 1.78/100,000 in 2008. The prevalence of UC increased from 0.61/100,000 in 1998 to 7.62/100,000 in 2008. Male to female ratio for CD was 2.22 and 1.64 for UC. Age of registered for CD was predominantly between 20 to 39, and for UC between 30 to 49 years of age. The standardized mortality ratio (95% CI) was 4.97 (3.72–6.63) for CD and 1.78 (1.46–2.17) for UC, from 1998 to 2008 in Taiwan. Conclusions Using the Taiwan nationwide database for IBD, the incidence and prevalence of IBD in Taiwan significantly increased from 1998 to 2008. The mortality rate was higher for CD patients than UC patients, and both were higher than the general population.

Background & Aims The efficacy of treatment of Helicobacter pylori infection has decreased steadily because of increasing resistance to clarithromycin, metronidazole, and levofloxacin. Resistance to amoxicillin is generally low, and high intragastric pH increases the efficacy of amoxicillin, so we investigated whether a combination of a high-dose proton pump inhibitor and amoxicillin (dual therapy) was more effective than standard first-line or rescue therapies in eradicating H pylori . Methods We performed a large-scale multihospital trial to compare the efficacy of a high-dose dual therapy (HDDT) with that of standard therapies in treatment-naive (n = 450) or treatment-experienced (n = 168) patients with H pylori infection. Treatment-naive patients were randomly assigned to groups given HDDT (rabeprazole 20 mg and amoxicillin 750 mg, 4 times/day for 14 days, group A1), sequential therapy for 10 days (group B1), or clarithromycin-containing triple therapy for 7 days (group C1). Treatment-experienced patients were randomly assigned to groups given HDDT for 14 days (group A2), sequential therapy for 10 days (B2), or levofloxacin-containing triple therapy for 7 days (C2). H pylori infection was detected by using the 13 C-urea breath test. We evaluated factors associated with treatment outcomes. Results In the intention-to-treat analysis, H pylori was eradicated in 95.3% of patients in group A1 (95% confidence interval [CI], 91.9%−98.8%), 85.3% in B1 (95% CI, 79.6%−91.1%), and 80.7% in group C1 (95% CI, 74.3%−87.1%). Infection was eradicated in 89.3% of patients in group A2 (95% CI, 80.9%−97.6%), 51.8% in group B2 (95% CI, 38.3%−65.3%), and 78.6% (95% CI, 67.5%−89.7%) in group C2. The efficacy of HDDT was significantly higher than that of currently recommended regimens, irrespective of CYP2C19 genotype. Bacterial resistance to drugs was associated with treatment failure. There were no significant differences between groups in adverse events or patient adherence. Conclusions HDDT is superior to standard regimens as empirical first-line or rescue therapy for H pylori infection, with similar safety profiles and tolerability. ClinicalTrials.gov number: NCT01163435.

Background: The increased primary and acquired resistance rates of H. pylori to clarithromycin, metronidazole, and levofloxacin have resulted in a significant reduction in the efficacy of various anti-H. pylori regimens. We recently demonstrated that an optimized high-dose dual therapy (HDDT) is superior to the standard triple therapy (TT) or sequential therapy (ST) for H. pylori infection in a large-scale multi-hospital, randomized, comparative study (Clinical Gastro & Hepato, in press). Because the global prevalence of primary and acquired resistance to amoxicillin (AMO) is rare, we hypothesize that HDDT can be used repeatedly and empirically for H. pylori treatment without a reduction of eradication efficacy. Aim: To evaluated the cumulative efficacy of repeated HDDT treatment for first-line and rescue antiH. pylori therapy. Methods: A total of 618 patients with H. pylori infection diagnosed by endoscopy with biopsy for histology examination and bacterial culture were recruited in this multi-hospital study and were randomly allocated to receive HDDT, TT, or ST for therapy. As reported in our previous study, H. pylori was eradicated in 143 out of 150 (95.3%; 95% C.I. 92.9-97.8) treatment-naive patients receiving the first course of HDDT (rabeprazole 20 mg + AMO 750 mg, qid for 14 days). Six patients who failed in the first HDDT treatment received the second course of HDDT. For treatment-experienced patients, 68 out of 84 patients failed in TT and 25 out of 45 patients failed in ST received the first course of HDDT. The second course of HDDT was used again if the first course failed. Four to eight weeks after termination of each treatment, H. pylori infection status was examined by the C13-urea breath test. The E-test was used to evaluate the antibiotics resistances of H. pylori strains before and after failed treatment of repeated HDDT. Results: Five out of 6 treatment-naive patients had successfully H. pylori eradication by a second course of HDDT, resulting in a cumulative eradication rate of 98.7% (148/150; 95% C.I. 97.3-100.0) in the intention-to-treat (ITT) analysis, and 99.3% (148/149; 95% C.I. 98.4-100.3) in perprotocol (PP) analysis. For the treatment-experienced patients, H. pylori was successfully eradicated in 90.3% (84/93; 95% C.I. 85.9-94.7) of patients with first course of HDDT treatment. Seven out of 9 patients who failed in the first HDDT treatment achieved H. pylori eradication with a second course of HDDT. The cumulative eradication rate was 97.8% (91/ 93; 95% C.I. 95.7-100.0) in both ITT and PP analyses. The susceptibility of H. pylori to antibiotics did not significantly impact eradication rates. Conclusion: HDDT consisting of a PPI and AMO given four times daily is highly efficacious when it is used repeatedly for H. pylori eradication. Thus, H. pylori susceptibility testing may be avoided by using HDDT.

AIM: To investigate how the saturated and unsaturated fatty acid composition influences the susceptibility of developing acute pancreatitis. METHODS: Primary pancreatic acinar cells were treated with low and high concentrations of different saturated and unsaturated fatty acids, and changes in the cytosolic Ca2+ signal and the expression of protein kinase C (PKC) were measured after treatment. RESULTS: Unsaturated fatty acids at high concentrations, including oleic acid, linoleic acid, palmitoleic acid, docosahexaenoic acid, and arachidonic acid, induced a persistent rise in cytosolic Ca2+ concentrations in acinar cells. Unsaturated fatty acids at low concentrations and saturated fatty acids, including palmitic acid, stearic acid, and triglycerides, at low and high concentrations were unable to induce a rise in Ca2+ concentrations in acinar cells. Unsaturated fatty acids at high concentrations but not saturated fatty acids induced intra-acinar cell trypsin activation and cell damage and increased PKC expression. CONCLUSION: At sufficiently high concentrations, unsaturated fatty acids were able to induce acinar cells injury and promote the development of pancreatitis. Unsaturated fatty acids may play a distinctive role in the pathogenesis of pancreatitis through the activation of PKC family members.

Background & aimsTo date, only one gene (TNFSF15) has been identified and validated as a Crohn's disease (CD)-associated gene in non-Caucasian populations. This study was designed to identify novel CD-associated single nucleotide polymorphisms (SNPs)/genes and to validate candidate genes using a functional assay.MethodsSNPs from 16 CD patients and 16 age- and sex-matched control patients were analyzed using Illumina platform analysis. Subsequently, we expanded the study and followed 53 CD patients and 41 control patients by Sequenom MassArray analysis. Quantitative PCR and immunohistochemical staining were performed to assess mRNA and protein expression of the candidate gene on tissue isolated from CD patients. Genotype was correlated with CD phenotypes. Finally, the candidate gene was cloned and its effect on NF-κB activity assessed using a reporter luciferase assay.ResultsSLCO3A1 (rs207959) reached statistical significance in the first-stage analysis (P = 2.3E-02) and was further validated in the second-stage analysis (P = 1.0E-03). Genotype and phenotype analysis showed that the rs207959 (T) allele is a risk allele that alters SLCO3A1 mRNA expression and is associated with intestinal perforation in CD patients. Higher levels of mRNA and protein expression of SLCO3A1 were seen in CD patients compared with the control group. Overexpression of SLCO3A1 induced increased NF-κB activity and increased phosphorylation of P65, ERK, and JNK. Nicotine augmented the activation of NF-κB in the presence of SLCO3A1.ConclusionsSLCO3A1, a novel CD-associated gene, mediates inflammatory processes in intestinal epithelial cells through NF-κB transcription activation, resulting in a higher incidence of bowel perforation in CD patients.