Small bowel adenocarcinoma in Crohn's disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes.

BACKGROUND AND AIMS: Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn's disease (CD). This study aims to quantify the prevalence of CD-SBA, review the current evidence of histopathology and molecular analysis findings, and identify the clinical presentation and outcomes of CD-SBA. METHODS: Electronic databases Medline and Embase were searched for articles describing SBA in inflammatory bowel disease patients. The histopathology, molecular analysis findings, clinical presentation, prevalence, and outcomes of CD-SBA were extracted, and results were pooled with random effects. RESULTS: In total, 33 articles were included in the analysis. Prevalence of SBA was 1.15 (CI: 0.31-2.33) per 1000 CD patients. Only 11% (CI: 0.04-0.21) of CD-SBA patients had observable radiological features. CD-SBA was most commonly found in the ileum (84%), diagnosed at stage 2 (36%), with main presenting complaints including obstruction, weight loss, and abdominal pain. Significant histopathological findings included adjacent epithelial dysplasia, and an equal distribution of well-differentiated (49%) and poorly differentiated subtypes (46%). Most prevalent genetic mutation was KRAS mutation (18%), followed by mismatch repair deficiency (9.7%). The 5-year overall survival for CD-SBA patients was 29% (CI: 0.18-0.41), and 33% (CI: 0.26-0.41) for de novo SBA. No statistically significant increase in risk for CD-SBA was noted for treatment with thiopurines, steroids, and 5-ASA. CONCLUSION: Our meta-analysis found the prevalence of CD-SBA to be 1.15 per 1000 CD patients. The 5-year overall survival for CD-SBA was poor. The presenting symptoms were non-specific, and therefore the diagnosis requires a high index of suspicion.

Mindfulness-based cognitive therapy in functional dyspepsia: A pilot randomized trial.

BACKGROUND AND AIM: Patients with functional dyspepsia (FD) often have concomitant anxiety and depression. Mindfulness-based cognitive therapy (MBCT) combines the principles of cognitive behavioral therapy and mindfulness. It is a group-based therapy and has been shown to be efficacious in functional gastrointestinal disorders. There are no randomized controlled trials (RCTs) evaluating MBCT in FD. We aimed to evaluate feasibility and efficacy of MBCT in FD management. METHODS: We performed a mixed-method single-center pilot randomized trial of 28 patients fulfilling ROME-III criteria for FD. Fifteen patients were randomized to an 8-week MBCT program while 13 underwent treatment-as-usual (TAU). Patients completed questionnaires at baseline and at week 8. Two focus-groups were conducted. Feasibility of recruitment, acceptability of randomization, procedures and intervention, handout compliance and feasibility of quantitative measures were assessed. The primary outcome was subjective-clinical-assessment of FD symptoms (SCA-FD). Secondary outcome measures included Short-form Nepean Dyspepsia Index (SF-NDI), subjective-clinical-assessment of general health (SCA-GH), EuroQoL-Visual Analog Scale (EuroQoL-VAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21). RESULTS: Twelve of 15 patients in the MBCT group completed the program. There was a trend towards symptom improvement, with 90% in the MBCT group reporting improvement in SCA-FD compared with 45% in TAU(P = 0.063). Patients who underwent MBCT reported greater improvement in SF-NDI (mean change: -8.8 (SD: 7.5) vs -0.7 (7.2), P = 0.018) and DASS-21 (-19.8 (29.5) vs -5.5 (6.6) P = 0.13) compared with TAU. There was no difference in SCA-GH and EuroQoL-VAS. Based on SCA-FD improvement, the eventual RCT will require 50 patients (25 in each group). CONCLUSIONS: Mindfulness-based cognitive therapy is likely efficacious for FD, and it would be feasible to conduct a RCT.

Crohn's disease associated strictures.

Crohn's disease (CD) is a chronic relapsing and remitting disease that can affect any segments of the gastrointestinal tract. More than 50% of patients with CD develop stricturing or penetrating complications within the first 10 years after diagnosis. Strictures can lead to intestinal obstruction, which is a common indication for surgery. Despite significant advances in the understanding of the pathogenesis of intestinal fibrostenosis, imaging and therapeutic armamentarium of CD, the risk of intestinal surgery remained significantly high. Endoscopic balloon dilation is a promising first-line alternative to surgery as it is less invasive and could preserve intestinal length. In this review, we will evaluate the literature on the mechanism of intestinal fibrosis, emerging imaging techniques, and management strategies for CD associated strictures.

Approximately 1 in 10 ambulatory inflammatory bowel disease patients are at risk of malnutrition: A prospective Singapore cohort.

OBJECTIVES: Prevalence of malnutrition among ambulatory inflammatory bowel disease (IBD) patients in Singapore is unknown. We aimed to evaluate the prevalence of ambulatory IBD patients at risk of malnutrition (ARMN) using Malnutrition Universal Screening Tool (MUST) and its clinical outcomes. METHODS: IBD patients were recruited from March to June 2018 and followed up for 6 months. ARMN patients were defined as having a MUST score of 2 or more compared with those not at risk (non-ARMN). RESULTS: Altogether 217 patients were recruited, including 128 (59.0%) with ulcerative colitis (UC) and 89 (41.0%) with Crohn's disease (CD). The mean body mass index (BMI) was 23.5 ± 4.5 kg/m2 ; 35 (16.1%) patients were on biologics, and 52 (24.0%) were on steroids. Among them 25 (11.5%) patients were ARMN, with a predominance of UC (n = 15, 60.0%). The majority of ARMN patients were underweight (n = 23, 92.0%) while 114 (59.4%) non-ARMN patients were overweight. ARMN patients had a significantly lower albumin (38.3 g/L vs 41.9 g/L) and a significantly increased proportion of patients with C-reactive protein ≥5 mg/L (36.0% vs 19.3%). There was a trend towards longer hospital stay among ARMN patients, although this was not statistically significant. Use of biologics or immunomodulators and albumin levels were associated with being ARMN. CONCLUSION: Using MUST, 11.5% of our ambulatory IBD patients in Singapore were identified to be ARMN. Among ARMN patients, a trend was demonstrated towards a longer hospital stays for admitted patients. This underscores the need to actively screen ambulatory IBD patients for malnutrition.

Favorable vaccine-induced SARS-CoV-2-specific T cell response profile in patients undergoing immune-modifying therapies.

BACKGROUNDPatients undergoing immune-modifying therapies demonstrate a reduced humoral response after COVID-19 vaccination, but we lack a proper evaluation of the effect of such therapies on vaccine-induced T cell responses.METHODSWe longitudinally characterized humoral and spike-specific T cell responses in patients with inflammatory bowel disease (IBD), who were on antimetabolite therapy (azathioprine or methotrexate), TNF inhibitors, and/or other biologic treatment (anti-integrin or anti-p40) for up to 6 months after completing 2-dose COVID-19 mRNA vaccination.RESULTSWe demonstrate that a spike-specific T cell response was not only induced in treated patients with IBD at levels similar to those of healthy individuals, but also sustained at higher magnitude for up to 6 months after vaccination, particularly in those treated with TNF inhibitor therapy. Furthermore, the spike-specific T cell response in these patients was mainly preserved against mutations present in SARS-CoV-2 B.1.1.529 (Omicron) and characterized by a Th1/IL-10 cytokine profile.CONCLUSIONDespite the humoral response defects, patients under immune-modifying therapies demonstrated a favorable profile of vaccine-induced T cell responses that might still provide a layer of COVID-19 protection.FUNDINGThis study was funded by the National Centre for Infectious Diseases (NCID) Catalyst Grant (FY2021ES) and the National Research Fund Competitive Research Programme (NRF-CRP25-2020-0003).

Clinical utility of thiopurine metabolite monitoring in inflammatory bowel disease and its impact on healthcare utilization in Singapore.

Background and Aim: Thiopurines are recommended for maintenance of steroid-free remission (SFR) in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the West but remains novel in Singapore, with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate MM's clinical utility and its impact on healthcare resource utilization in Singaporean IBD patients. Methods: A retrospective observational study was conducted at Singapore General Hospital outpatient IBD Centre. Patients with IBD, baseline MM during 2014-2017, and weight-based thiopurine doses for ≥4 weeks were followed up for 1 year. Actions were taken to optimize therapy, and metabolite levels before and after the first action were documented. Outcomes assessed included SFR, no therapy escalation or surgery, healthcare resource utilization, and direct healthcare costs. Results: Ninety IBD patients (50 Crohn's disease, 40 ulcerative colitis) were included. Among them, 40% had baseline metabolite levels within therapeutic range, 31.1% sub-therapeutic, 21.1% supra-therapeutic, and 7.8% shunters. Repeated MM with subsequent dose optimization helped 67.2% of patients achieve therapeutic levels after 1 year. Overall, 87.8% of patients achieved SFR and 90% had no therapy escalation or surgery. Despite greater outpatient visits and laboratory investigations with MM, the median total healthcare costs at 1 year only increased marginally (S$6407.66 [shunters] vs S$5215.20 [supra-therapeutic] vs S$4970.80 [sub-therapeutic] vs S$4370.48 [control (within therapeutic range)], P = 0.592). Conclusion: MM guided timely therapy escalation for non-responders, identification of non-adherence, and reversal of shunting. Therefore, it is a useful clinical tool to optimize thiopurines without significantly increasing healthcare costs.

Practice pattern variability among gastroenterologists in colorectal cancer surveillance and management of colorectal dysplasia in inflammatory bowel disease.

OBJECTIVE: There is debate on the best method of colorectal cancer (CRC) surveillance in inflammatory bowel disease (IBD). We aimed to examine how gastroenterologists around the world practice CRC surveillance and manage dysplastic lesions in IBD. METHODS: A 22-question survey was emailed to gastroenterologists from 34 countries. It included questions on resources for, frequency and mode of CRC surveillance, and management of colorectal dysplasia. Fisher's exact test and logistic regression were used to evaluate the differences among respondents in various domains. RESULTS: There were 217 eligible responses, with most gastroenterologists working in public hospitals (76%), and treating >10 patients with IBD weekly (71%). High-definition white light endoscopy (HDWLE) was available in 93.1% of the centers. The preferred mode of surveillance was HDWLE with dye-spray chromoendoscopy and targeted biopsies (41.2%). Fewer than 50% of physicians reported using chromoendoscopy in >50% of cases, citing time as the limiting factor (73.7%). Of these gastroenterologists 63% infrequently (<25% of cases) performed random biopsies during chromoendoscopy. They would attempt endoscopic mucosal resection for polypoid lesions >10 mm (67.2%), including >20 mm lesions with low grade dysplasia (49.8%), and non-polypoid lesions >10 mm without dysplasia (56.9%). For non-polypoid lesions >20 mm with low- and high-grade dysplasia, referral to expert endoscopists was the preferred option. CONCLUSION: The preferred method of CRC surveillance was HDWLE with chromoendoscopy and targeted biopsies. Random biopsies were infrequently performed. The uptake of chromoendoscopy for surveillance in practice was low. Physicians varied in their approach in removing endoscopically resectable dysplastic lesions.

Systematic review with meta-analysis: The prevalence, risk factors and outcomes of upper gastrointestinal tract Crohn's disease.

AIMS: Upper gastrointestinal Crohn's disease (UGI-CD) is an important subclassification of Crohn's Disease (CD). We performed a systematic review and meta-analysis to evaluate the prevalence, risk factors, and clinical outcomes associated with UGI-CD. METHODS: We searched Embase and Medline for articles reporting the clinical information of UGI-CD in CD patients, through 27 October 2020. Disease location and phenotype were coded according to the Montreal classification, and results were pooled with random effects by DerSimonian and Laird model. RESULTS: 26 articles were included. The prevalence of UGI-CD was 13%. UGI-CD was most commonly found in the stomach (56%) and was associated with concurrent ileocolonic involvement (54%). Non-stricturing, non-penetrating UGI-CD was the most common behavioral phenotype (61%). L4-jejunal disease was associated with the highest rates of surgery. Region of origin did not significantly influence the location and phenotype of UGI-CD. Young, male patients presenting with erythema nodosum, aphthous ulcers and stricturing-phenotype are more likely to have UGI-CD, which in turn is linked to increased risk of hospitalization and surgery. CONCLUSION: UGI-CD is present in 13% of patients with CD, and patients with L4-jejunal disease are more likely to require surgery. Further studies examining the effect of ethnicity and region on UGI-CD are needed.