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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.

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/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 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.

Background: No nationwide, long-term follow-up study has assessed medication-associated outcomes for Asian patients with inflammatory bowel disease (IBD). This study examined medication-associated outcomes for Taiwanese patients with IBD. Methods: In this nationwide cohort study, 3806 patients who had received catastrophic illness registration for IBD from 2001 to 2015 were enrolled. Results: A higher accumulated dosage of 5-aminosalicylic acid (5-ASA) was associated with decreased risks of hospitalization (hazard ratio (HR) = 0.6) and operation (HR = 0.5). Thiopurine was associated with increased risks of hospitalization (HR = 2.1 in the high-dosage group) and tuberculosis (TB, HR = 3.6) reactivation but not with operation risk. A higher accumulated dosage of anti-TNF-&alpha, agents was associated with increased risks of hospitalization (HR = 3.3), operation (HR = 2.9), hepatitis B (HR = 4.3), and TB (HR = 5.1) reactivation. Corticosteroids were associated with increased risks of hospitalization (HR = 3.5 in the high-dosage group), risk of operation, hepatitis B (HR = 2.8) and TB (HR = 2.8) reactivation. Conclusions: 5-ASA usage is associated with decreased risks of hospitalization and operation for patients with IBD, whereas thiopurine, corticosteroids, and anti-TNF-&alpha, agents are associated with increased risks of hospitalization and hepatitis B and TB reactivation.

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.

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.

Summary Here we present a 50-year-old man who suffered from progressively bloody diarrhea for 2 months. A colonoscopy revealed pancolonic mucosal inflammation, ulceration, and spontaneous bleeding. Ulcerative colitis was initially diagnosed and sulfasalazine was prescribed. Hypoalbuminemia and renal function deterioration developed 1 year later. Steroids were prescribed for suspected nephrotic syndrome. His bloody diarrhea and abdominal symptoms worsened after steroid use. Progressive sepsis and acute renal function deterioration also developed. Positive human immunodeficiency virus (HIV) antibody was found during routine hemodialysis screening. An episode of colon perforation occurred and surgery was performed. The resected colon showed amoeba, cytomegalovirus, and fungal infection. The patient died of sepsis. In this report, we discuss how to diagnose ulcerative colitis. It is important to exclude infection before using an immunosuppressive agent.