A case-control study examining the association of smad7 and TLR single nucleotide polymorphisms on the risk of colorectal cancer in ulcerative colitis.

AIM: Ulcerative colitis (UC) is characterized by chronic mucosal inflammation and an increased risk of colorectal cancer. smad7, TLR2 and TLR4 modulate intestinal inflammation and their polymorphisms affect the risk of development of sporadic colorectal cancer. The aim of the current study was to examine the association between single nucleotide polymorphisms (SNPs) in smad7, TLR2 and TLR4 and the development of colorectal cancer in patients with UC. METHOD: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 90 patients with UC who had undergone panproctocolectomy between 1985 and 2013 (30 with UC-associated colorectal cancer and 60 control UC patients). Control cases were matched 2:1 for age at diagnosis of colitis, duration of disease and gender. Genotyping was performed for the smad7 rs4464148, rs11874392, rs12953717 and rs4939827 SNPs, the TLR2 rs5743704 and rs5743708 SNPs and the TLR4 rs4986790 and rs4986791 SNPs. RESULTS: Sixty three of the 90 patients (70%) were men and the mean age at diagnosis of UC was 38.6 ± 1.6 years. The mean time to the diagnosis of UC-associated colorectal cancer was 13.5 ± 1.9 years. The 5-year recurrence-free and cancer-specific survival rates were 76% and 88%, respectively. All eight SNPs were in Hardy-Weinberg equilibrium. None of the eight SNPs assessed in smad7, TLR2 or TLR4 were associated with the development of UC-associated colorectal cancer at an allelic or genotypic level. CONCLUSIONS: These data do not support an association between polymorphisms in smad7, TLR2 or TLR4 and the development of UC-associated colorectal cancer.

Acceptance and Commitment Therapy Reduces Psychological Stress in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Patients with Crohn's disease or ulcerative colitis have relatively high levels of stress and psychological dysfunction. Acceptance and commitment therapy (ACT) is a psychological intervention that comprises acceptance and mindfulness procedures, along with commitment and behavior change strategies, to increase psychological flexibility and reduce stress. We performed a randomized controlled trial to investigate the effect of ACT on stress in patients with inflammatory bowel diseases (IBD). METHODS: A total of 122 patients with quiescent or stable, mildly active IBD were randomly assigned to an 8-week ACT program or treatment as usual (control group). Clinical, demographic, disease activity, and psychological data and blood and feces were collected at baseline and at 8 weeks and 3 months after the intervention (week 20). Scalp hair was collected at baseline and week 20 for measurement of steroid concentrations. The primary endpoint was change in stress symptoms, assessed with the Depression Anxiety Stress Scale. Secondary endpoints included changes in perceived stress, anxiety, depression, quality-of-life domains, disease activity, and cortisol concentration in hair. RESULTS: Overall, 79 participants were included in the complete case intention-to-treat analysis. There were 39% and 45% reductions in stress in the treatment group from baseline to 8 and 20 weeks, respectively, compared with 8% and 11% in the control group (group × time interaction, P = .001). ACT was associated with reduced perceived stress (P = .036) and depression (P = .010), but not anxiety (P = .388), compared with control individuals. In the intention-to-treat analysis, changes in all 4 quality-of-life domains over time were similar in the ACT and control groups. In the per-protocol analysis, the overall well-being quality-of-life domain improved in the ACT group compared with the control group (P = .009). Subjective and objective disease activity measurements were similar between groups over the study period (all P values >.05). Hair cortisol concentrations correlated with stress (rs = 0.205, P = .050) and anxiety (rs = 0.208, P = .046) at baseline but did not change significantly in the ACT group over the study period compared with the control group (P = .831). CONCLUSION: In a randomized controlled trial of patients with IBD, an 8-week ACT therapy course improved stress and other indices of psychological health.ClinicalTrials.gov Identifier: NCT02350920.

Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Impact of a higher fecal immunochemistry test cut-off on pathology detected in subsequent rounds of a colorectal screening program.

BACKGROUND AND AIMS: Fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening is superior to the traditional binary fecal occult blood test. Its quantitative nature allows the investigator to choose a positivity threshold to match cost and endoscope capacity. The optimal threshold is still debated. BowelScreen, the Irish national colorectal cancer screening program, has a cut-off of 45 µg Hb/g feces, and in this study we investigated the impact of this threshold on pathology detected in round 2 in individuals who had a negative result for round 1 FIT (FIT1). METHODS: All individuals with a negative FIT1 result who completed a round 2 FIT (FIT2) 2 years later were included. Pathology outcomes for individuals who had positive FIT2 results were correlated with FIT1 levels. RESULTS: A total of 37,877 individuals had negative FIT1 results and completed FIT2. One thousand two hundred thirty (3.2%) had positive FIT2 results (702 men [57%], median age 69, age range 60-70 years). Quantitative analysis showed that at an FIT1 level <5 µg Hb/g feces, 2.3% had positive FIT2 results. At a higher cut-off of 40.1 to 45 µg Hb/g feces, 15.6% of individuals had positive FIT2 results. One thousand two (81.5%) underwent colonoscopy, with clinical outcomes in all cases. Three hundred fifty-one (35%) had normal colonoscopy results. The proportion of individuals with normal colonoscopy results decreased as FIT1 levels rose. Conversely, advanced pathology (CRC + high-risk adenomas) rates rose from 7% to 50% when FIT1 was <5 compared with 40.1 to 45 µg Hb/g feces, respectively. There were 51 screen-detected cancers in round 2 among individuals with negative FIT1 results (22 stage I, 12 stage II, 14 stage III, 3 stage IV). All 3 stage IV individuals had FIT1 results <20 µg Hb/g feces. CONCLUSIONS: Varying rates of pathology are observed in round 2 of a screening program based on the quantitative level of a negative round 1 FIT result when the positivity threshold is relatively high. A CRC rate of 5.1% within this group appears acceptable. Although patients with incurable cancer were observed, the positivity threshold to capture these cases within round 1 would have been so sensitive that it would create an unsustainable endoscopy referral burden.

CRP/Albumin Ratio: An Early Predictor of Steroid Responsiveness in Acute Severe Ulcerative Colitis.

INTRODUCTION: Identifying hospitalized patients with acute severe ulcerative colitis (ASUC) who will be refractory to corticosteroid therapy and require rescue therapy remains difficult. Hypoalbuminemia worsens with time during hospitalization and is associated with rapid clearance of and reduced response to infliximab (IFX) rescue. Early use of rescue therapy may therefore be more effective. Simple clinical and laboratory predictors of corticosteroid responsiveness would facilitate earlier use of rescue therapy. MATERIALS AND METHODS: Retrospective study of a prospectively maintained database of 3600 patients attending a single center was conducted. Patients with histologically confirmed ulcerative colitis admitted with ASUC over a 5-year period from January 2010 to December 2014 were identified. All patients initially received intravenous corticosteroids. Patient demographics were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during admission. Receiver operating characteristic statistics were used to determine the optimal stool frequency, CRP, albumin, and CRP/albumin ratio (CAR) to predict steroid response. RESULTS: A total of 124 ASUC patients were admitted during a 5-year period. Median follow-up was 2.3 years. A total of 62 patients (50%) were steroid responsive, 55 patients (44%) received rescue IFX, 22 patients (18%) required colectomy within 30 days of admission, whereas a further 14 (11%) required colectomy during follow-up. By receiver operating characteristic statistics, day 3 CAR was a more accurate marker of steroid responsiveness than day 3 CRP or day 3 albumin alone [area under curve=0.75 (P<0.001)]. The optimal CAR to predict response to steroids on day 3 was 0.85 (sensitivity 70%, specificity 76%). When combined with D3 stool frequency, specificity improved to 83%. If at day 3, CAR was >0.85 and stool frequency was >3, the relative risk of steroid nonresponse was significantly raised at 3.9 (95% confidence interval, 2.1-7.2). CONCLUSIONS: Raised D3 CAR is an early predictor of steroid-refractory ASUC. When combined with D3 stool frequency, its predictive ability improves. In patients with predicted steroid nonresponse, early introduction of rescue IFX at this stage may be more effective, before serum albumin falls profoundly.

Covered self-expanding metal stents for the management of common bile duct stones.

BACKGROUND AND AIMS: Little medical literature exists for the use of fully covered self-expanding metal stents (CSEMSs) in the management of retained common bile duct (CBD) stones. Our aim was to assess the safety and efficacy of CSEMSs for the indication of retained "difficult" CBD stones. METHODS: This retrospective cases series included 44 patients (30 women; median age, 69 years [range, 24-88]) who underwent CSEMS insertion for the indication of retained "difficult" CBD stones in 2 tertiary referral centers. Patients underwent temporary placement of CSEMSs after incomplete stone clearance at ERCP. Follow-up ERCP was arranged for stent removal and subsequent attempt at duct clearance. Procedure-related adverse events were also recorded. RESULTS: Successful biliary drainage was achieved in all cases after CSEMS placement. Forty-two stents were removed with successful duct clearance achieved in 36 cases (82%) after a median in-stent duration of 8 weeks. There were 10 cases (22.7%) of stent migration, all noted incidentally during follow-up. One patient died of nonbiliary causes before attempted removal. CONCLUSION: This is the largest published retrospective case series for use of CSEMSs for management of retained CBD stone disease to date. We have shown high success rates for this indication. A well-designed, multicenter, randomized controlled trial might address the uncertainty of cost-to-benefit ratio and appropriate duration for CSEMSs to be left in situ. Specific stent modification for this indication, including wider distal flare and retrieval purse string loop, may also be useful.

An accelerated infliximab induction regimen reduces the need for early colectomy in patients with acute severe ulcerative colitis.

BACKGROUND & AIMS: Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect. METHODS: We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods. RESULTS: There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03). CONCLUSIONS: In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.

Mortality in inflammatory bowel disease patients under 65 years of age.

OBJECTIVE: To assess mortality in inflammatory bowel disease (IBD) patients under 65 years of age and to identify the factors related to death in this age group. METHODS. We studied 2570 IBD patients who were diagnosed as having disease before 65 years of age and attended a single tertiary referral center area between 1983 and 2012. Follow-up was censored at 65 years. The causes of death were determined from death certificates obtained from the Irish registry office of births, marriages and deaths. Observed all-cause survival was compared with expected survival of persons of the same age and sex in the general population. Expected survival was obtained from national life tables produced by the central statistics office. Survival estimates were calculated for disease type, disease site, gender, the presence of primary sclerosing cholangitis (PSC), immunomodulator use, biologic therapy use, presence of fistulating disease and prior surgery. RESULTS: Fifty-two deaths were reported in the population younger than 65 years, of which 41 were IBD related. We found little difference in survival in the first 25 years of follow-up, but relative survival decreased in both the Crohn's disease (CD) and ulcerative colitis (UC) cohort thereafter, so that 30-year mortality was excessive in both groups. An adjusted multivariate regression analysis of patients with CD identified PSC as the only predictor of premature mortality (p = 0.003). PSC was also identified as the only independent predictor of mortality in UC patients (p = 0.03). CONCLUSIONS: The presence of PSC poses the greatest risk for mortality in both UC and CD.

Microscopic colitis: clinical characteristics, treatment and outcomes in an Irish population.

BACKGROUND AND AIMS: Many aspects of microscopic colitis remain poorly understood. Our aim was to report a single centre experience with this condition. METHODS: Two hundred and twenty-two patients (52 male, 170 female; median age 64 years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes were reviewed, and data on age, gender, clinical features, history of autoimmune diseases, medication use, cigarette smoking, histology and outcome were collected. RESULTS: There were 99 cases of lymphocytic and 123 of collagenous colitis. Diarrhoea was almost invariably present (98 %) while abdominal pain (24 %), weight loss (10 %), faecal incontinence (8 %) and blood PR (5 %) were also described. Twenty-eight percent had concomitant autoimmune diseases, most commonly coeliac disease. Patients were taking a variety of medications at diagnosis thought to be associated with microscopic colitis including NSAIDs (22 %), aspirin (19 %), statins (15 %), proton pump inhibitors (19 %) and SSRIs (10 %) at diagnosis. Prior to the widespread use of budesonide in our institution, 33 % of patients required two or more medications during therapy compared to 15 % following the introduction of budesonide (p = 0.001). Thirty-eight percent of patients achieved spontaneous remission with either no treatment or simple anti-diarrhoeals. Using a multivariate model, the only factor associated with spontaneous remission was male gender (RR 1.9; 95 % CI 1.0-3.6; p = 0.04). Two patients had refractory microscopic colitis; one required a colectomy while a more recent case has responded to anti-TNFα therapy. CONCLUSION: Microscopic colitis is predominantly a benign and self-limiting disorder. The introduction of budesonide has revolutionised treatment of this lesser studied inflammatory bowel disease.

Inflammatory Bowel Disease Disability Index is a valid and reliable measure of disability in an English-speaking hospital practice and predicts long-term requirement for treatment escalation.

Objective: The Inflammatory Bowel Disease Disability Index (IBD-DI) was developed according to WHO standards and has been validated in population-based cohorts. However, there are limited data on its relationship to various psychosocial and economic variables or its relevance to hospital clinical practice. The study aims were to determine the validity and reliability of the IBD-DI in an English-speaking hospital out-patient population and to evaluate its association with short and long-term disease activity. Design/Methods: 329 subjects were enrolled in a cross-sectional and longitudinal study assessing the IBD-DI and a range of quality of life, work impairment, depression, anxiety, body image, interpersonal, self-esteem, disease activity, symptom scoring scales in addition to long-term outcome. Results: The IBD-DI had adequate structure, was internally consistent and demonstrated convergent and predictive validity and was reliable in test-retest study. Disability was related to female sex (p=0.002), antidepressant use (p<0.001), steroid use (p<0.001) and disease activity (p<0.001). Higher IBD-DI scores were associated with long-term disease activity and need for treatment escalation in univariate (p<0.001) and multivariate (p=0.002) analyses. Conclusion: The IBD-DI is a valid and reliable measure of disability in English-speaking hospital populations and predicts long-term requirement for treatment escalation.

The influence of CTGF single-nucleotide polymorphisms on outcomes in Crohn's disease.

OBJECTIVE: To examine the association between single-nucleotide polymorphisms (SNPs) in CTGF (connective tissue growth factor) and patient outcomes after terminal ileal resection for Crohn's disease. BACKGROUND: The primary indication for intestinal resection in Crohn's disease is fibrostenotic terminal ileal disease. CTGF is a cytokine overexpressed in the intestine of patients with Crohn's disease that influences outcomes in other disease processes. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 147 patients with Crohn's disease who had undergone terminal ileal resection between 1981 and 2009. Genotyping was performed for 4 CTGF SNPs (rs9402373, rs12526196, rs6918698, and rs9399005), which modulate nuclear factor binding and CTGF production, and a smad3 SNP (rs17293632) involved in the CTGF pathway. Patients were phenotyped using the Montreal Disease Classification. RESULTS: Sixty-seven of 147 patients (45.6%) were male; the mean age at diagnosis was 30.3 ± 12.6 years and the mean follow-up duration was 8.3 ± 7.1 years. Genotype-phenotype analysis demonstrated that the rs6918698GG genotype was associated with an older age of disease onset [>40 years; 30.6% vs 13.2%; odds ratio (OR): 2.891; 95% confidence interval (CI): 1.170-7.147). The rs9402373CC genotype was positively associated with type B1 disease (50.7% vs 26.3%; OR: 2.876; 95% CI: 1.226-6.743) and negatively associated with B2 disease (37.0% vs 65.0%; OR: 0.317; 95% CI: 0.144-0.699). None of the 5 SNPs assessed influenced clinical or surgical recurrence of Crohn's disease after intestinal resection. On multivariate analysis, male sex odds ratio (OR): 0.235; 95% CI: 0.073-0.755; P = 0.015] and never having smoked tobacco (OR: 0.249; 95% CI: 0.070-0.894; P = 0.033) reduced the risk, whereas having a prior appendectomy increased the risk (OR: 5.048; 95% CI: 1.632-15.617; P = 0.005) of surgical recurrence. CONCLUSIONS: These data implicate the rs6918698GG genotype with an age of disease onset of greater than 40 years in Crohn's disease whereas the rs9402373CC genotype is associated with a nonstricturing, nonpenetrating disease phenotype. CTGF SNPs do not influence the rate of recurrence after terminal ileal resection for Crohn's disease.

Raf kinase inhibitor protein expression combined with peritoneal involvement and lymphovascular invasion predicts prognosis in Dukes' B colorectal cancer patients.

AIMS: There is controversy regarding the use of adjuvant therapy in patients with Dukes' B colorectal cancer (CRC). New markers, identifying high-risk Dukes' B patients, are needed. Here, we examine the utility of Raf kinase inhibitor protein (RKIP) as such a marker and promoter methylation as a mechanism of RKIP down-regulation. METHODS AND RESULTS: We used a tissue microarray of 220 patients with Dukes' B CRC to examine the effect of RKIP expression on survival. Pyrosequencing was used to assess RKIP promoter methylation status.RKIP expression correlated inversely with disease-specific survival in this cohort. In multivariate analysis, RKIP was found to be an independent prognostic indicator, along with peritoneal invasion and lymphovascular invasion (LVI). RKIP promoter hypermethylation was seen in only one of 29 tumours analysed by pyrosequencing. CONCLUSIONS: Raf kinase inhibitor protein, peritoneal invasion and LVI provide independent prognostic information in this cohort of Dukes' B CRC patients.This demonstrates the potential utility of RKIP in identifying 'high-risk' Dukes' B patients. It is this high-risk group which is most likely to benefit from close postoperative monitoring and may derive the most benefit from adjuvant therapy.

A comparative study of short- and medium-term outcomes comparing emergent surgery and stenting as a bridge to surgery in patients with acute malignant colonic obstruction.

BACKGROUND: The use of self-expanding metal stents as a bridge to surgery in the setting of malignant colorectal obstruction has been advocated as an acceptable alternative to emergency surgery. However, concerns about the safety of stenting have been raised following recent randomized studies. OBJECTIVES: The aim of the current study was to compare outcomes. DESIGN: This was an observational, comparative study. SETTINGS: This study was conducted at a tertiary referral center and university teaching hospital. PATIENTS AND INTERVENTIONS: Patients with malignant colonic obstruction (n = 49) treated by either emergency surgery (n = 26) or with stent placement (n = 23) as a bridge to surgery were identified and followed. MAIN OUTCOME MEASURES: Short-term outcomes including stoma rates and postoperative morbidity and medium-term oncological outcomes were compared based on an "intention-to-treat" analysis. RESULTS: Patients in both groups were well matched on clinicopathological parameters. Technical and clinical successful stent deployment was achieved in 91% and 83%. This did not adversely impact cancer-specific and overall survival (log rank = nonsignificant). No difference was observed in stoma rates, primary anastomosis rates, perioperative mortality rates, or reoperation rates between the 2 groups. Significantly fewer patients underwent total colectomy in the stent group in comparison with the emergency surgery group (1/23 vs 6/26: p = 0.027). There was no difference in postoperative morbidity (59% vs 66%: p = 0.09). There was a significant reduction in readmission rates in the stent group (5/26 vs 0/23: p = 0.038). LIMITATIONS: The small sample size of this study could lead to type II error. In addition, the study was nonrandomized and demonstrated a limited length of follow-up. CONCLUSION: Despite a high rate of technical and clinical success in selected patients with colonic obstruction, stenting has no impact on stoma rates. Despite concerns about the rate of stent-associated perforation, stenting does not adversely impact disease progression or survival. Future comparative trials are essential to better define the role of stenting in this setting and to ensure that we are not using costly technology to create an elective operative situation without concomitant patient benefits.

Development, validation and clinical assessment of a short questionnaire to assess disease-related knowledge in inflammatory bowel disease patients.

OBJECTIVES: Only two inflammatory bowel disease (IBD) knowledge scales are available, both primarily aimed at evaluating the effectiveness of clinical education programs. The aim of this study was to develop and validate a short knowledge questionnaire for clinical and academic research purposes. MATERIAL AND METHODS: Following initial development, the questionnaire was tested on junior doctors, nurses and administrative staff to assess validity. The questionnaire was then assessed and compared with a previous questionnaire in 31 IBD patients. Three hundred and three further patients completed the questionnaire to establish reliability and determine factors independently associated with disease-related knowledge. RESULTS: Doctors answered more questions correctly than nurses who scored better than administrative staff (p < 0.001). There was a fair correlation in scores between the short knowledge questionnaire and a previously validated long survey (r = 0.488; p = 0.005). The short knowledge questionnaire was quicker to complete (p < 0.001), was rated as less difficult to understand (p = 0.004) and induce less anxiety (p = 0.004). Both questionnaires were rated similarly with regard to relevance (p = 0.71). Internal consistency was demonstrated with a Cronbach's alpha of 0.73. In clinical testing on 301 patients, the final multivariate model identified young age, Crohn's disease, higher educational status and the presence of a first-degree family member with IBD as being independently and significantly associated with disease-related knowledge. CONCLUSIONS: The short knowledge questionnaire is a simple, valid, reliable and easy to understand research instrument for rapidly assessing knowledge in IBD patients.

Satisfaction with telemedicine-delivered inflammatory bowel disease care depends on disease activity, personality and economic factors.

Objective: Patients with inflammatory bowel disease (IBD) traditionally receive follow-up care at face-to-face outpatient clinics. During the COVID-19 pandemic, gastroenterology societies recommended IBD clinics to be carried out remotely where possible using telephone or telemedicine-delivered virtual clinics. Previous studies have demonstrated patient satisfaction with virtual clinics but few studies have examined factors that impact satisfaction or assessed patient's personal perception of the virtual clinic experience. Design/method: Patients who had their IBD clinic appointment changed from face-to-face to telephone virtual clinic completed a questionnaire relating to their clinical experience and preference for future care. Qualitative data were also collected and evaluated using content analysis to identify major themes associated with the patient experience. Results: 141 patients were included for analysis. The virtual clinic satisfaction questionnaire was found to be valid while patients expressed high-satisfaction levels with virtual clinics (median satisfaction score 18, range 0-20). Multivariate analysis identified open personality type (p=0.004), short disease duration (p=0.047) and higher cost to attend clinic (p=0.047) as predictors of high-satisfaction levels, with active disease (p=0.035) and an agreeable personality type (p=0.042) associated with low satisfaction levels. Content analysis of the qualitative data identified three major themes connected to virtual clinic convenience, lack of physical interaction and disease activity. Conclusion: Patients expressed high levels of satisfaction with telemedicine-delivered IBD clinics, with most wishing to continue their use. Personality type should be recognised as an important variable affecting clinical satisfaction, in addition to socioeconomic and disease-related factors.

Implementation of BSG/ACPGBI/PHE polypectomy surveillance guidelines safely reduces the burden of surveillance in a screening cohort: a virtual model study.

OBJECTIVE: To evaluate the impact of British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England (BSG/ACPGBI/PHE) 2019 polypectomy surveillance guidelines within a national faecal immunochemical test-based bowel cancer screening (BS) cohort on surveillance activity and detection of pathology by retrospective virtual application. DESIGN: A retrospective review of BS colonoscopies performed in 2015-2016 with 5 years prospective follow-up in single institution. Index colonoscopies were selected. Incomplete colonoscopies were excluded. Histology of all resected polyps was reviewed. Surveillance intervals were calculated according to BSG/ACPGBI/PHE 2019 guidelines and compared with pre-existing 'European Guidelines for Quality Assurance in Colorectal Cancer Screening and Diagnosis' (EUQA 2013). Total number of colonoscopies deferred by virtual implementation of BSG/ACPGBI/PHE 2019 guidelines were calculated. Pathology identified on procedures that would have been deferred was reviewed. RESULTS: Total number of index BS colonoscopies performed in 2015-2016 inclusive was 890. 115 were excluded (22 no caecal intubation, 51 inadequate bowel preparation, 56 incomplete polyp clearance). N=509 colonoscopies were scheduled within a 5-year interval following index colonoscopy surveillance rounds based on EUQA guidelines. Overall, volume of surveillance was significantly reduced with retrospective application of BSG/ACPGBI/PHE 2019 guidelines (n=221, p<0.0001). No cancers were detected within the 'potentially deferred' procedures who attended for follow-up (n=330) with high-risk findings found in<10% (n=30) of colonoscopies within the BSG/ACPGBI/PHE cohort. CONCLUSION: BSG/ACPGBI/PHE 2019 guidelines safely reduce the burden of colonoscopy demand with acceptable pathology findings on deferred colonoscopies.

Reduced Serological Response to COVID-19 Booster Vaccine is Associated with Reduced B Cell Memory in Patients With Inflammatory Bowel Disease; VARIATION [VAriability in Response in IBD AgainsT SARS-COV-2 ImmunisatiON].

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. METHODS: This was a prospective multicentre observational study of patients with IBD [n = 202] and healthy controls [HC, n = 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. RESULTS: Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, p < 0.001] as was ACE2 binding inhibition [p < 0.001]. IBD patients previously infected with COVID-19 [30%] had similar quantitative antibody response as HCs previously infected with COVID-19 [p = 0.12]. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor [anti-TNF] agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 [p = 0.01]. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses. CONCLUSIONS: Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.

Primary sclerosing cholangitis and disease distribution in inflammatory bowel disease.

BACKGROUND & AIMS: The relationship between site of intestinal inflammation and primary sclerosing cholangitis (PSC) development in inflammatory bowel disease (IBD) has not been studied extensively, but may be important in understanding the pathogenesis of PSC. We aimed to determine patterns of disease distribution in IBD patients with and without PSC. METHODS: We performed a 2-part study involving the following: (1) 2754 IBD patients and (2) 82 separate PSC patients attending the Irish National Liver Transplant Unit. RESULTS: Fifty-nine of 2708 (2.2%) IBD patients had PSC. In ulcerative colitis patients, PSC incidence increased with increasing colonic involvement (P = .001) and was relatively rare in those without total colitis. Thirteen Crohn's disease patients had PSC, none with isolated small-bowel disease had PSC (P = .03). In study 2, the majority of ulcerative colitis patients with PSC had total colitis, whereas the remainder had disease extending at least to the left colon. In addition, all 10 PSC patients with Crohn's disease had colonic involvement. CONCLUSIONS: An inflamed colon, but not small bowel, is important in PSC development and it is possible that bacterial translocation and subsequent portal bacteremia is important in PSC development in IBD.

Stage II colonic adenocarcinoma: a detailed study of pT4N0 with emphasis on peritoneal involvement and the role of tumour budding.

AIMS: Evaluation of peritoneal involvement in colonic cancer (CC) can be difficult. We studied pT4N0 cancers and their association with pathological prognostic markers, including tumour budding. METHOD AND RESULTS: Tumours were classified as (i) at the peritoneal surface or free in the peritoneal cavity (pT4a subgroup n = 44); (ii) directly invading adjacent organ (pT4b subgroup n = 8); or (iii) showing inflammatory involvement of the peritoneum (pT4I subgroup n = 25). A published pT3N0 cohort was used to compare Stage II subgroups. Standard pathological markers including tumour budding were assessed. Elastin staining was performed in the pT4I subgroup. Seventy-seven Stage II CCs met inclusion criteria. There was no significant difference in survival across subgroups. pT4b tumours were larger than pT4a tumours (P < 0.001). Over-represented features in pT4a versus pT4b tumours were tumour budding (P = 0.02) and infiltrative margin (P = 0.02). Tumour budding did not predict survival. Using multivariate analysis, neural invasion was the only parameter predictive of survival (hazard ratio = 2.8; 95% CI 1.2-6.4; P = 0.02). CONCLUSION: Stage II pT4I CCs have a similar outcome to T4a/b tumours. Elastin staining is useful in defining this group. Tumour budding may facilitate peritoneal invasion in pT4a tumours, but does not predict outcome in pT4N0 disease. Only neural invasion independently predicted poor outcome.