Patients with Crohn's disease (CD) commonly develop bowel strictures, which may contain various degrees of inflammation and fibrosis. While predominantly inflammatory strictures may benefit from a medical anti-inflammatory treatment approach, fibrotic strictures would require endoscopic balloon dilation or surgery. Cross-sectional imaging surpasses endoscopy for characterization of stenotic segments and potentially may contribute to the optimal clinical management of these patients. This short review aims to discuss the potentialities and limitations of cross-sectional imaging techniques for assessing bowel fibrosis in patients with CD. (Intest Res 2020;18:144-150)

The specific pathogenesis underlining inflammatory bowel disease (IBD) is very complicated, and it is further more difficult to clearly explain the pathophysiology of 2 major forms of IBD, Crohn's disease (CD) and ulcerative colitis (UC), and both disorders affect individuals throughout life. Despite every extensive effort, the interplay among genetic factors, immunological factors, environmental factors and intestinal microbes is still completely unrevealed. Animal models are indispensable to find out mechanistic details that will facilitate better preclinical setting to target specific components involved in the pathogenesis of IBD. Based on many recent reports, dysbiosis of the commensal microbiota is implicated in the pathogenesis of several diseases, not only IBD but also colon cancer, obesity, psoriasis as well as allergic disorders, in both human and animal models. Advanced technologies including cell-specific and inducible knockout systems, which are recently employed to mouse IBD models, have further enhanced the ability of developing new therapeutic strategies for IBD. Furthermore, data from these mouse models highlight the critical involvement of dysregulated immune responses and impaired colonic epithelial defense system in the pathogenesis of IBD. In this review, we will explain from the history of animal models of IBD to the recent reports of the latest compounds, therapeutic strategies, and approaches tested on IBD animal models. (Intest Res 2020;18:151-167)

Colorectal cancer (CRC) is among the most common malignancies and remains a major cause of cancer-related death worldwide. Despite recent advances in surgical and multimodal therapies, the overall survival of advanced CRC patients remains very low. Cancer progression, including invasion and metastasis, is a major cause of death among CRC patients. The underlying mechanisms of action resulting in cancer progression are beginning to unravel. The reported molecular and biochemical mechanisms that might contribute to the phenotypic changes in favor of carcinogenesis include apoptosis inhibition, enhanced tumor cell proliferation, increased invasiveness, cell adhesion perturbations, angiogenesis promotion, and immune surveillance inhibition. These events may contribute to the development and progression of cancer. A biomarker is a molecule that can be detected in tissue, blood, or stool samples to allow the identification of pathological conditions such as cancer. Thus, it would be beneficial to identify reliable and practical molecular biomarkers that aid in the diagnostic and therapeutic processes of CRC. Recent research has targeted the development of biomarkers that aid in the early diagnosis and prognostic stratification of CRC. Despite that, the identification of diagnostic, prognostic, and/or predictive biomarkers remains challenging, and previously identified biomarkers might be insufficient to be clinically applicable or offer high patient acceptability. Here, we discuss recent advances in the development of molecular biomarkers for their potential usefulness in early and less-invasive diagnosis, treatment, and follow-up of CRC. (Intest Res 2020;18:168-183)

Background/Aims: Exclusive enteral nutrition (EEN) is recommended for induction of remission in pediatric Crohn's disease (CD). However, it is not currently recommended for inducing remission in adults. This report describes the use of 12-week EEN for induction of remission in anti-tumor necrosis factor (anti-TNF) refractory adult CD. Methods: This is a retrospective analysis of adults with moderate to severe active (Crohn's Disease Activity Index [CDAI] >220) anti-TNF refractory CD, who received EEN for 12 weeks between April 2018 and March 2019 at Dayanand Medical College and Hospital, Ludhiana, India. Primary outcomes included achievement of clinical remission and fistula healing at 12 weeks. Improvement in inflammatory markers and nutritional status were the secondary end points. Results: Out of 23 patients who received anti-TNF agents, 7 (30.4%) were refractory and were offered EEN as a salvage therapy. Six patients (66.7% females, mean age 25.6±6.5 years) consented. Four patients (66.6%) achieved clinical remission (CDAI <150). Mean CDAI of patients decreased significantly after 12 weeks of EEN (388.8±74.8 vs. 160.0±25.2, P< 0.001). Perianal fistulas showed clinical response (drainage decreased by >50%), though none achieved remission. Entero-enteric fistulae showed complete healing. Mean body mass index improved from 15.6±3.1 to 18.9±1.9 kg/m2 at week 12 (P=0.003). Hemoglobin and serum albumin also improved from 8.2±1.1 g/dL and 2.8±0.3 g/dL at baseline to 12.6±0.6 g/dL and 3.6±0.5 g/dL post-EEN respectively (P<0.001 and P=0.006 respectively). Conclusions: EEN appears to be an effective and well tolerated therapy for induction of remission in anti-TNF refractory adult CD. More data from prospective trials with larger number of patients is required. (Intest Res 2020;18:184-191)

Background/Aims: The use of complementary and alternative medicine (CAM) is a global phenomenon, including inflammatory bowel disease (IBD) patients. We aimed to assess the change in prevalence and patterns of CAM use, and attitudes towards CAM over an 8-year time interval (2006 vs. 2014) among IBD patients in Korea. Methods: A total of 221 IBD patients (CD=142, UC=79) were asked to complete a questionnaire regarding CAM at two time points: at enrollment (2006) and 8 years later (2014/2015). Results: The proportion of patients ever using CAM increased significantly from 60.2% in 2006 to 79.6% in 2014 (P<0.001), while the proportion of current CAM users increased slightly (35.7% to 38.0%, P=0.635); 21.7% used CAM consistently at both time points. The proportion of patients who felt CAM was less effective (P<0.001) and more expensive (P=0.04) than conventional treatments increased over time. Also, the proportion among ever CAM users who perceived a positive effect from CAM significantly decreased in 2014 compared to 2006 (P=0.004). Higher education (adjusted odds ratio [aOR], 2.10), prior side effects to conventional therapies (aOR, 2.23), and prior use of corticosteroids (aOR, 2.51) were associated with CAM use. Interestingly, use of CAM before IBD diagnosis (aOR, 2.73) was significantly associated with consistent CAM use. Conclusions: Although the attitudes toward CAM have become less favorable, the majority of IBD patients have experienced CAM with an overall increase of current CAM users over time. Moreover, more than half of current CAM users used CAM consistently over time. (Intest Res 2020;18:192-199)

Background/Aims: Crohn's disease (CD) primarily affects young female adults of reproductive age. Few studies have been conducted on this population's ovarian reserve status. The aim of study was to investigate potential risk factors associated with low ovarian reserve, as reflected by serum anti-Müllerian hormone (AMH) in women of reproductive age with CD. Methods: This was a case-control study. Cases included 87 patients with established CD, and healthy controls were matched by age, height and weight in a 1:1 ratio. Serum AMH levels were measured by enzyme-linked immunosorbent assay. Results: The average serum AMH level was significantly lower in CD patients than in control group (2.47±2.08 ng/mL vs. 3.87±1.96 ng/mL, respectively, P<0.001). Serum AMH levels were comparable between CD patients and control group under 25 years of age (4.41±1.52 ng/mL vs. 3.49±2.10 ng/mL, P=0.06), however, serum AMH levels were significantly lower in CD patients over 25 years of age compared to control group (P<0.05). Multivariable analysis showed that an age greater than 25 (odds ratio [OR], 10.03; 95% confidence interval [CI], 1.90-52.93, P=0.007), active disease state (OR, 27.99; 95% CI, 6.13-127.95, P<0.001) and thalidomide use (OR, 15.66; 95% CI, 2.22-110.65, P=0.006) were independent risk factors associated with low ovarian reserve (serum AMH levels <2 ng/mL) in CD patients. Conclusions: Ovarian reserve is impaired in young women of reproductive age with CD. Age over 25 and an active disease state were both independently associated with low ovarian reserve. Thalidomide use could result in impaired ovarian reserve. (Intest Res 2020; 18:200-209)

Background/Aims: Crohn's disease (CD) may involve the upper parts of the gastrointestinal (GI) tract including the esophagus, stomach, and duodenum. Clinical features of upper GI CD (UGICD) are not well characterized in the Gulf region. We therefore aimed to assess the prevalence and clinical characteristics of patients diagnosed with UGICD. Methods: We performed a retrospective analysis of all patients diagnosed with CD who underwent upper GI endoscopy between 2012 and 2017 at King Abdulaziz University Hospital, irrespective of age. Patients who had endoscopy of the upper GI tract at baseline and had histologically confirmed UGICD were included. Data on patients' demographics, clinical characteristics, extraintestinal manifestations and complications were reviewed. Results: We identified 78 CD patients who underwent upper GI endoscopy from our medical records. The mean age was 17.2±8.7 years and 55.1% were males. Of the total, 19 out of 78 patients (24.4%) had histologically confirmed UGICD (3 esophageal, 16 gastric, and 9 duodenal), of which 52.6% were symptomatic. Disease distribution was ileal in 57.8%, colonic in 21.1% and ileo-colonic in 21.1%. A non-stricturing and non-penetrating phenotype was reported in 89.4%, stricturing in 5.3%, and penetrating in 5.3%. Perianal disease was found in 10.5%. UGICD was complicated by stricture formation in 2 patients (esophageal and gastric). Conclusions: The prevalence of UGICD is considered high among CD Saudi patients who undergo upper GI endoscopy at baseline, and is asymptomatic in 47.4% of patients. This reported prevalence is not dissimilar from reports originating from Western countries. (Intest Res 2020;18:210-218)

Background/Aims: Intestinal fibrosis is a major complication of Crohn's disease (CD). The profibrotic protein transforming growth factor-β (TGF-β) has been considered to be critical for the induction of the fibrotic program. TGF-β has the ability to induce not only the expression of extracellular matrix (ECM) including collagen, but also the production of plasminogen activator inhibitor-1 (PAI-1) that prevents enzymatic degradation of the ECM during the onset of fibrotic diseases. However, the significance of PAI-1 in the developing intestinal fibrosis has not been fully understood. In the present study, we examined the actual expression of PAI-1 in fibrotic legion of intestinal inflammation and its correlation with the abnormal ECM deposition. Methods: Chronic intestinal inflammation was induced in BALB/c mice using 8 repeated intrarectal injections of 2,4,6-trinitrobenzene sulfonic acid (TNBS). TM5275, a PAI-1 inhibitor, was orally administered as a carboxymethyl cellulose suspension each day for 2 weeks after the sixth TNBS injection. Results: Using a publicly available dataset (accession number, GSE75214) and TNBS-treated mice, we observed increases in PAI-1 transcripts at active fibrotic lesions in both patients with CD and mice with chronic intestinal inflammation. Oral administration of TM5275 immediately after the onset of intestinal fibrosis upregulated MMP-9 (matrix metalloproteinase 9) and decreased collagen accumulation, resulting in attenuation of the fibrogenesis in TNBS-treated mice. Conclusions: PAI-1-mediated fibrinolytic system facilitates collagen degradation suppression. Hence, PAI-1 inhibitor could be applied as an anti-fibrotic drug in CD treatment. (Intest Res 2020;18:219-228)