Patients with inflammatory bowel disease (IBD) occasionally need a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) because of medically refractory colitis or dysplasia/cancer. However, pouchitis may develop in up to 70% of patients after this procedure and significantly impair quality of life, more so if the inflammation becomes a chronic condition. About 10% of patients with IBD who develop pouchitis require pouch excision, and several risk factors of the failure have been reported. A phenotype that has features similar to Crohn's disease may develop in a subset of ulcerative colitis patients following proctocolectomy with IPAA and is the most frequent reason for pouch failure. In this review, we discuss the diagnosis and prognosis of pouchitis, risk factors for pouchitis development, and treatment options for pouchitis, including the newer biological agents. (Intest Res 2021;19:1-11)

Sporadic conventional colon adenomas are microscopically built of 2 intertwined compartments: one on top, harboring the dysplastic tissue that defines their histo-biomolecular attributes, and the other below, composed of non-dysplastic crypts with corrupted shapes (CCS). The CCS of 306 colon adenomas revealed asymmetric, haphazardly-distributed proliferating cell-domains (PC). In contrast, the PC-domains in normal controls were symmetric, being limited to the lower thirds of the crypts. In 28% out of 501 sporadic conventional adenomas, foci of p53-upregulated dysplastic tissue were found. The CCS in 30% of 108 sporadic adenomas showed p53-upregulated single cells, suggesting mounting somatic mutations. No p53-upregulated cells were found in the crypts of controls. In polypoid adenomas, the mucosa of the stalk without dysplastic tissue on top disclosed CCS with asymmetrical PC-domains and single p53-upregulated cells. The latter observations suggested that CCS had developed prior to and not after the growth of the dysplastic tissue on top. CCS were also found below colon adenomas in carcinogen-treated rats. It is concluded that the 2 intertwined histo-biological compartments of sporadic conventional colon adenomas are probably interdependent components. These findings may open new directions aimed to uncover the link between the normal colonic mucosa and the histogenesis of, conventional adenomas. (Intest Res 2021;19:12-20)

Differentiating Crohn's disease (CD) from intestinal tuberculosis (ITB) is a diagnostic dilemma, particularly in regions where ITB is prevalent and CD incidence is increasing, because both diseases can present quite similarly, and diagnostic tests to identify Mycobacterium tuberculosis in tissue samples have rather poor sensitivity. Studies that were conducted to determine the factors that differentiate CD from ITB identified some significant characteristics, but none of those characteristics are exclusive to either ITB or CD. Many diagnostic models or scoring systems that use one to several diagnostic parameters have been proposed to help distinguish these two intestinal diseases. Early models consisted of parameters common to routine clinical practice, such as clinical features, and endoscopic and pathologic findings. The later models also include more advanced diagnostic parameters like high-resolution imaging and serological testing. However, the number and types of parameters differ among diagnostic models, and the systems used to calculate scoring also vary from model to model. Enhanced awareness and understanding of the currently available diagnostic models will help physicians determine which model(s) is/are most suitable for differentiating CD from ITB in their clinical practice. (Intest Res 2021;19:21-32)

Molecular imaging is a technique for imaging the processes occurring in a living body at a molecular level in real-time, combining molecular cell biology with advanced imaging technologies using molecular probes and fluorescence. Gastrointestinal endoscopic molecular imaging shows great promise for improving the identification of neoplasms, providing characterization for patient stratification and assessing the response to molecular targeted therapy. In inflammatory bowel disease, endoscopic molecular imaging can be used to assess disease severity and predict therapeutic response and prognosis. Endoscopic molecular imaging is also able to visualize dysplasia in the presence of background inflammation. Several preclinical and clinical trials have evaluated endoscopic molecular imaging; however, this area is just beginning to evolve, and many issues have not been solved yet. In the future, it is expected that endoscopic molecular imaging will be of increasing interest among clinicians as a new technology for the identification and evaluation of colorectal neoplasm and colitis-associated cancer. (Intest Res 2021;19:33-44)

Background/Aims: The inflammatory bowel diseases (IBD), ulcerative colitis (UC), and Crohn's disease (CD) are chronic diseases mostly affecting young patients. As they are diseases accompanying patients for their entire life, and the quality of life (QUOL) interacts with disease activity, improving QUOL should be one of the main goals of therapy. This study aims to identify factors contributing to good or impaired QUOL. Methods: Questionnaires addressing health-related QUOL and other psychological and social features were positioned on our institutions' webpage and on the webpage of the largest self-help group for IBD in Germany. Patients were subdivided according to their QUOL score with a cutoff of <60. We used the Short Inflammatory Bowel Disease Questionnaire, the Assessment of the Demand for Additional Psychological Treatment, and the Fear of Progression Questionnaire Short Form. Results: High numbers of patients in both subgroups showed an impaired QUOL (87.34% in UC, 91.08% in CD). Active extraintestinal manifestations, smoking, high fear of progression and high demand for psychotherapy were associated with reduced QUOL. In addition, polypharmacological interventions did not result in a good QUOL, but ostomies are linked to improved QUOL especially in CD patients. Conclusions: Scores used in clinical day-to-day-practice mainly focusing on somatic factors do not sufficiently address important aspects concerning QUOL. Most importantly, extraintestinal manifestations show a hitherto underestimated impact on QUOL. (Intest Res 2021;19:45-52)

Background/Aims: Several biologic therapies are approved in Japan to treat moderately to severely active ulcerative colitis (UC), but there are no published comparative efficacy studies in a Japanese population. We compared the efficacy of biologics approved in Japan (adalimumab, infliximab, golimumab, and vedolizumab) for treating biologic-naïve patients with UC at their approved doses. Methods: A targeted literature review identified 4 randomized controlled trials of biologics for UC in biologic-naïve Japanese patients. For each study, efficacy outcome data from induction (weeks 6-12) and maintenance (weeks 30-60) treatment were extracted for analysis. Treatment effects on clinical response, clinical remission, and mucosal healing relative to the average placebo results across all trials were estimated using network meta-analyses followed by transformation into probabilities and odds ratios (OR). Results: At the end of induction, the likelihood of clinical response and clinical remission was highest with infliximab (OR: 2.12 and 2.35, respectively) and vedolizumab (OR: 2.10 and 2.32, respectively); the likelihood of mucosal healing was highest with infliximab (OR: 2.24) and adalimumab (OR: 1.86). During maintenance, the likelihood of clinical response and clinical remission was highest with vedolizumab (OR: 6.44 and 4.68, respectively) and golimumab (OR: 5.13 and 3.84, respectively); the likelihood of mucosal healing was significantly higher than placebo with all biologics. Conclusions: All active treatments were efficacious compared with placebo. Infliximab and vedolizumab had the highest odds for induction of clinical response, remission, and mucosal healing. Golimumab and vedolizumab had numerically higher odds of achieving efficacy outcomes in the maintenance phase. (Intest Res 2021;19:53-61)

Background/Aims: Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) can serve as biomarkers for diagnosing and assessing disease activity in ulcerative colitis (UC). We investigated their clinical significance in UC. Methods: We analyzed 48 patients with UC who underwent measurement of fecal calprotectin (FC) and endoscopy and 96 age- and sex-matched healthy controls. NLR and PLR were compared between the patients and healthy controls. The endoscopic activity was divided into 2 groups: group 1 (mild to moderate inflammation) and group 2 (severe inflammation) according to the Mayo endoscopic subscore in UC. Results: To diagnose UC, the optimal cutoff of NLR and PLR was 2.26 (sensitivity 54.2%; specificity 90.6%; positive likelihood ratio 5.778, 95% confidence interval [CI] 2.944-11.339; area under the curve [AUC] 0.774, 95% CI, 0.690-0.859) and 179.8 (sensitivity 35.4%; specificity 90.6%; positive likelihood ratio 3.778, 95% CI 1.821-7.838; AUC 0.654, 95% CI 0.556-0.753), respectively. The optimal cutoff to differentiate group 1 and group 2 was 3.44, 175.9, and 453 μg/g for NLR, PLR, and FC, respectively (sensitivity, 63.6% vs. 90.9% vs. 81.8%; specificity, 81.1% vs. 78.4% vs. 73.0%; positive likelihood ratio, 3.364 vs. 4.205 vs. 3.027; AUC, 0.714 vs. 0.897 vs. 0.813). PLR had the highest AUC and positive likelihood ratio. Conclusions: NLR and PLR help differentiate patients with UC from healthy controls. NLR, PLR, and FC indicate endoscopic activity and may reflect intestinal mucosal conditions. (Intest Res 2021;19:62-70)

Background/Aims: The efficacy and safety of vedolizumab in moderate to severely active ulcerative colitis (UC) have been demonstrated in the GEMINI 1 study (NCT00783718). This post-hoc exploratory analysis sought to establish the efficacy and safety of vedolizumab in a subgroup of patients from Asian countries with UC from GEMINI 1. Methods: Efficacy outcomes of interest were clinical response, clinical remission and mucosal healing at week 6 (induction phase); and clinical remission, durable clinical response, durable clinical remission, mucosal healing and glucocorticoid-free remission at week 52 (maintenance phase). Differences in outcome rates between vedolizumab and placebo in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) were assessed using descriptive analyses, and efficacy and safety compared between Asian and non-Asian countries. Results: During induction, in Asian countries (n=58), clinical response rates at week 6 with vedolizumab and placebo were 55.2% and 24.1%, respectively (difference 31.0%; 95% confidence interval: 7.2%-54.9%). In non-Asian countries (n=316), response rates at week 6 with vedolizumab and placebo were 45.9% and 25.8%, respectively. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 8 weeks, vedolizumab administered every 4 weeks and placebo were 9.1%, 36.8%, and 31.6%, respectively; corresponding rates for mucosal healing were 45.5%, 47.4%, and 47.4%, respectively. Vedolizumab was well-tolerated; adverse event frequency was comparable in Asian and non-Asian countries. Conclusions: In patients from Asian countries, the efficacy and safety of vedolizumab in treatment of UC were broadly consistent with that in the overall study population. (Intest Res 2021;19:71-82)

Background/Aims: The efficacy and safety of vedolizumab in moderate-to-severely active Crohn's disease (CD) were demonstrated in the GEMINI 2 study (NCT00783692). This post-hoc exploratory analysis aimed to assess the efficacy and safety of vedolizumab in the subgroup of patients from Asian countries. Methods: During the induction phase (doses at day 1, 15), clinical remission, enhanced clinical response, and change in C-reactive protein at 6 weeks; during the maintenance phase, clinical remission, enhanced clinical response, glucocorticoid-free remission and durable clinical remission at 52 weeks, were the efficacy outcomes of interest. Efficacy and safety of vedolizumab compared to placebo were assessed in Asian countries (Hong Kong, India, Malaysia, Singapore, South Korea, and Taiwan) using descriptive analyses. Results: During the induction phase, in Asian countries (n=51), 14.7% of the vedolizumab-treated patients achieved clinical remission at week 6 compared to none with placebo (difference, 14.7%; 95% confidence interval, 15.8%-43.5%). In non-Asian countries (n=317), the remission rate at week 6 with vedolizumab was 14.5%. During maintenance, in Asian countries, clinical remission rates at 52 weeks with vedolizumab administered every 4 weeks, vedolizumab administered every 8 weeks and placebo were 41.7%, 36.4%, and 0%, respectively; while enhanced clinical response rates were 41.7%, 63.6%, and 42.9%, respectively. During induction, 39.7% of patients with vedolizumab experienced an adverse event compared to 58.8% of patients with placebo, and vedolizumab was generally well-tolerated. Conclusions: This post-hoc analysis demonstrates the treatment effect and safety of vedolizumab in moderate-to-severely active CD in patients from Asian countries. (Intest Res 2021;19:83-94)

Background/Aims: Vedolizumab is indicated for moderately-to-severely active ulcerative colitis (UC) and Crohn's disease (CD). Because multiple factors may result in different pharmacokinetics and clinical efficacies, understanding determinants of vedolizumab clearance may enhance dose and treatment strategies. The aim was to characterize vedolizumab pharmacokinetics in Asian and non-Asian UC and CD patients. Methods: Population pharmacokinetic analysis for repeated measures, using data from 5 studies, was conducted using nonlinear mixed-effects modeling. A Bayesian estimation approach in NONMEM 7.3 was utilized to leverage the predominantly sparse data available for this analysis with results from a prior population pharmacokinetic analysis of vedolizumab. Results: Vedolizumab pharmacokinetics were described by a 2-compartment model with parallel linear and nonlinear elimination. Using reference covariate values, linear elimination half life of vedolizumab was 24.7 days for anti-vedolizumab antibody (AVA)-negative patients and 18.1 days for AVA-positive patients; linear clearance (CLL) was 0.165 L/day for AVA-negative patients and 0.246 L/day for AVA-positive patients; central (Vc) and peripheral compartment volumes of distribution were 3.16 L and 1.84 L, respectively. Interindividual variabilities (percent coefficient of variation) were 30.8% for CLL and 19% for Vc; interoccasion variability on CLL was 20.3%; residual variance was 17.8%. For albumin, body weight and AVA, only extreme values were identified as potentially clinically important predictors of CLL. The effect of race (Asian/non-Asian) and diagnosis (UC/CD) on CLL was negligible and likely not of clinical importance. Conclusions: Pharmacokinetic parameters were similar in Asian and non-Asian patients with moderately-to-severely active UC and CD. This analysis supports use of vedolizumab flat-fixed dosing in these patients. (Clinicaltrials.gov Identifiers: NCT00783718 (GEMINI 1); NCT00783692 (GEMINI 2). CCT 101; NCT02039505 and CCT-001; NCT02038920) (Intest Res 2021;19:95-105)