Chien-Chih Tung

Intestinal stricture in Crohn's disease.

Crohns disease (CD) is a disease with chronic inflammation of unknown etiology involving any part of the gastrointestinal tract. The incidence and prevalence of CD are increasing recently in Asia. Half of the CD patients will have intestinal complications, such as strictures or fistulas, within 20 years after diagnosis. Twenty-five percentage of CD patients have had at least one small bowel stricture and 10% have had at least one colonic stricture and lead to significant complications. Most of these patients will require at least one surgery during their lifetime. Early diagnosis and evaluation with adequate managements for the patients can prevent disability and mortality of these patient. Here, we reviewed the current incidence of CD with stricture, the etiology of stricture, and how to diagnose and manage the stricture.

Combining TNFSF15 and ASCA IgA can be used as a predictor for the stenosis/perforating phenotype of Crohn's disease.

Focusing on TNFSF15 instead of NOD2, we set out to evaluate whether combining serologic and genetic markers could distinguish between Crohns disease (CD) and ulcerative colitis (UC), and whether they could be used to stratify the disease behavior of Taiwanese CD patients.

Clinicopathological and prognostic significances of EGFR, KRAS and BRAF mutations in biliary tract carcinomas in Taiwan

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.

Elderly Adults with Late‐Onset Ulcerative Colitis Tend to Have Atypical, Milder Initial Clinical Presentations but Higher Surgical Rates and Mortality: A Taiwan Society of Inflammatory Bowel Disease Study

To the Editor: There is considerable controversy over the clinical presentation and prognosis of ulcerative colitis (UC) in elderly adults. An earlier study found a prevalence of left colitis over extensive forms, whereas the latest studies show that proctitis and left-sided UC are more common in elderly adults. Some studies suggest that there is no association between mortality and age, whereas others have found greater risk of death in elderly adults. Moreover, most of these studies are from Western countries. Because the aging population and the incidence and prevalence of inflammatory bowel disease have recently begun to increase rapidly in Taiwan, this multicenter study was conducted to examine the clinical features and outcomes of UC in older adults in Taiwan.

Distinctive roles of unsaturated and saturated fatty acids in hyperlipidemic pancreatitis.

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 Ca(2+) 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 Ca(2+) 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 Ca(2+) 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.

Experience of patients with inflammatory bowel disease in using a home fecal calprotectin test as an objective reported outcome for self-monitoring

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, P<0.0001). After the test, 56% patients found IBDoc easy to perform, and 96% were satisfied with it. Thirty-nine patients (80%) had a strong (>70%) 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.

Cytomegalovirus colitis in hospitalized inflammatory bowel disease patients in Taiwan: a referral center study

BackgroundColitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients.MethodsA retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients’ demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed.ResultsA total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn’s disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p < 0.005). Higher steroid usage was noted in the CMV positive group compared to age and gender matched CMV negative IBD patients (81.8% vs. 51.5%). Eight patients received ganciclovir treatment. Three patients who did not receive antiviral treatment had colitis flare-ups after the index admission.ConclusionsThe prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.

Trends of Medication Usage and Associated Outcomes for Taiwanese Patients with Inflammatory Bowel Disease from 2001 to 2015

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-α 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-α agents are associated with increased risks of hospitalization and hepatitis B and TB reactivation.

Should Asian inflammatory bowel disease patients need routine thromboprophylaxis

cases per 1,000 individuals per year, followed by Europeans (1.03−1.49 cases per 1,000 individuals) and Hispanic populations. The incidence of VTE in Asian-ancestry populations (0.21−0.29 cases per 1,000 individuals) was less than onefifth the incidence of African-Americans. In Western countries, patients with IBD have a nearly 1.5to 4.0-fold higher risk of VTE when compared with the general population. The overall incidence of VTE in patients with IBD has been reported as 2.4−2.6 cases per 1,000 patients per year, and the incidence was revealed to increase to 9 cases per 1,000 patients per year when disease flare-up in the U.K. IBD population. The incidence of VTE among patients with IBD in Taiwan was reported to be 1.38 per 1,000 patients per year in a nationwide study. As moderate−severe disease activity and hospitalization for IBD flares both increase the risk of VTE, routine anticoagulant thromboprophylaxis is recommended in patients hospitalized with moderate-severe IBD flares and in patients who have undergone major abdominal-pelvic surgery during hospitalization (Table 1). For the treatment of VTE, a minimum of 3 months of anticoagulant therapy for IBD patients with a symptomatic deep vein thrombosis, pulmonary embolism, or splanchnic vein thrombosis is strong recommended. Currently, there is no evidence of which anticoagulants is the most effective, treatment choice is depended on consistency and quality of anticoagulation, ease of use, monitoring needs, side-effects and cost. However, these guidelines are based on data gathered from Western populations. In general, the incidence of VTE in Asian populations is lower than that in Western populations. Routine thromboprophylaxis is infrequently used in Asian patients with IBD. Inflammatory bowel disease (IBD) refers to a group of chronic inflammatory diseases—which include CD and UC—that predominantly affect the gastrointestinal tract. The incidence of IBD was reported to be 8−14 per 100,000 persons in the West. The crude annual incidence of IBD was revealed to be 1.96−5.3 per 100,000 persons in Asia. The ratio of UC to CD was 2.0 in Asia. IBD is increasing in both incidence and prevalence in Asian area. IBD is associated with autoimmune disease and increased risk of thromboembolic events. Venous thromboembolism (VTE) includes deep-vein thrombosis and pulmonary embolism. VTE is associated with significant risk of mortality, chronic complications, and recurrence. The 1-year case-fatality rate has been reported to be 22%−29% in Western countries. One-third of patients who survived deep vein thrombosis would experience longterm post-thrombotic syndrome. Symptoms include pain, persistent swelling, and recurrent ulcers of the affected extremity. Patients with pulmonary embolism may develop chronic pulmonary hypertension. In this review, we would discuss the difference in VTE incidence between Asian and Western countries and evaluate whether Asian patients with IBD should receive routine thromboprophylaxis. The incidence of VTE in Western countries has been reported to range from 0.73 to 1.82 per 1,000 persons. The VTE incidence has been reported to be 0.21−0.57 per 1,000 persons in Asia. In North America, VTE was most com-

Incidence and Risk Factor Analysis of Thromboembolic Events in East Asian Patients With Inflammatory Bowel Disease, a Multinational Collaborative Study

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 Crohns 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.