Pellino3 ubiquitinates RIP2 and mediates Nod2-induced signaling and protective effects in colitis.

Mutations that result in loss of function of Nod2, an intracellular receptor for bacterial peptidoglycan, are associated with Crohn's disease. Here we found that the E3 ubiquitin ligase Pellino3 was an important mediator in the Nod2 signaling pathway. Pellino3-deficient mice had less induction of cytokines after engagement of Nod2 and had exacerbated disease in various experimental models of colitis. Furthermore, expression of Pellino3 was lower in the colons of patients with Crohn's disease. Pellino3 directly bound to the kinase RIP2 and catalyzed its ubiquitination. Loss of Pellino3 led to attenuation of Nod2-induced ubiquitination of RIP2 and less activation of the transcription factor NF-κB and mitogen-activated protein kinases (MAPKs). Our findings identify RIP2 as a substrate for Pellino3 and Pellino3 as an important mediator in the Nod2 pathway and regulator of intestinal inflammation.

Endoscopic Gastrointestinal Placement of Capsule Endoscopy to Investigate the Small Bowel: a Multicentric European Retrospective Series of 630 Procedures in Adult Patients.

BACKGROUND AND AIMS: Small bowel (SB) capsule endoscopy (CE) is a first line procedure for exploring the SB. Endoscopic GastroIntestinal PlacemenT (EGIPT) of SB CE is sometimes necessary. While the experience of EGIPT is large in pediatric populations, we aimed to describe the safety, efficacy and outcomes of EGIPT of SB CE in adult patients. METHODS: The international CApsule endoscopy REsearch (iCARE) group set up a retrospective multicenter study. Patients over 18 year-old who underwent EGIPT of SB CE before May 2022 were included. Data were collected from medical records and capsule recordings. The primary endpoint was the technical success rate of the EGIPT procedures. RESULTS: 630 patients were included (mean age 62.5 years old, 55.9% female) from 39,565 patients (1.6%) issued from 29 centers. EGIPT technical success was achieved in 610 procedures (96.8%). Anesthesia (moderate/deep sedation or general anesthesia) and centers with intermediate or high procedure loads were independent factors of technical success. Severe adverse events occurred in three (0.5%) patients. When technically successful, EGIPT was associated with a high SB CE completion rate (84.4%) and with a substantial diagnostic yield (61.1%). Completion rate was significantly higher when the capsule was delivered in the SB compared to when delivered in the stomach. CONCLUSION: EGIPT of SB CE is highly feasible, safe and comes with high completion rate and diagnostic yield. When indicated, it should rather be performed under anesthesia and the capsule should be delivered in the duodenum rather than in the stomach, for better SB examination outcomes.

Management Strategies for Malignant Left-Sided Colonic Obstruction: A Systematic Review and Network Meta-analysis of Randomized Controlled Trials and Propensity Score Matching Studies.

BACKGROUND: The optimal treatment strategy for left-sided malignant colonic obstruction remains controversial. Emergency colonic resection has been the standard of care; however, self-expanding metallic stenting as a bridge to surgery may offer short-term advantages, although oncological concerns exist. Decompressing stoma may provide a valid alternative, with limited evidence. OBJECTIVE: To perform a systematic review and Bayesian arm random-effects model network meta-analysis comparing the approaches for management of malignant left-sided colonic obstruction. DATA SOURCES: A systematic review of PubMed, Embase, Cochrane Library, and Google Scholar databases was conducted from inception to August 22, 2023. STUDY SELECTION: Randomized controlled trials and propensity score-matched studies. INTERVENTIONS: Emergency colonic resection, self-expanding metallic stent, and decompressing stoma. MAIN OUTCOME MEASURES: Oncologic efficacy, morbidity, successful minimally invasive surgery, primary anastomosis, and permanent stoma rates. RESULTS: Nineteen of 5225 articles identified met our inclusion criteria. Stenting (risk ratio 0.57; 95% credible interval, 0.33-0.79) and decompressing stomas (risk ratio 0.46, 95% credible interval: 0.18-0.92) resulted in a significant reduction in the permanent stoma rate. Stenting facilitated minimally invasive surgery more frequently (risk ratio 4.10; 95% credible interval, 1.45-13.13) and had lower overall morbidity (risk ratio 0.58; 95% credible interval, 0.35-0.86). A pairwise analysis of primary anastomosis rates showed increased stenting (risk ratio 1.40; 95% credible interval, 1.31-1.49) compared with emergency resection. There was a significant decrease in the 90-day mortality with stenting (risk ratio 0.63; 95% credible interval, 0.41-0.95) compared with resection. There were no differences in disease-free and overall survival rates, respectively. LIMITATIONS: There is a lack of randomized controlled trials and propensity score matching data comparing short-term and long-term outcomes for diverting stomas compared to self-expanding metallic stents. Two trials compared self-expanding metallic stents and diverting stomas in left-sided malignant colonic obstruction. CONCLUSIONS: This study provides high-level evidence that a bridge-to-surgery strategy is safe for the management of left-sided malignant colonic obstruction and may facilitate minimally invasive surgery, increase primary anastomosis rates, and reduce permanent stoma rates and postoperative morbidity compared with emergency colonic resection.

The role of defensive information processing in population-based colorectal cancer screening uptake.

BACKGROUND: Internationally, colorectal cancer screening participation remains low despite the availability of home-based testing and numerous interventions to increase uptake. To be effective, interventions should be based on an understanding of what influences individuals' decisions about screening participation. This study investigates the association of defensive information processing (DIP) with fecal immunochemical test (FIT)-based colorectal cancer screening uptake. METHODS: Regression modeling of data from a cross-sectional survey within a population-based FIT screening program was conducted. The survey included the seven subdomains of the McQueen DIP measure. The primary outcome variable was the uptake status (screening user or nonuser). Multivariable logistic regression was used to estimate the odds ratio (OR) for screening nonuse by DIP (sub)domain score, with adjustments made for sociodemographic and behavioral factors associated with uptake. RESULTS: Higher scores (equating to greater defensiveness) on all DIP domains were significantly associated with lower uptake in the model adjusted for sociodemographic factors. In the model with additional adjustments for behavioral factors, the suppression subdomains of "deny immediacy to be tested" (OR, 0.53; 95% confidence interval [CI], 0.43-0.65; p < .001) and "self-exemption" (OR, 0.80; 95% CI, 0.68-0.96; p < .001) independently predicted nonuse of FIT-based screening. CONCLUSIONS: This is the first study outside the United States that has identified DIP as a barrier to colorectal cancer screening uptake, and it is the first focused specifically on FIT-based screening. The findings suggest that two suppression barriers, namely denying the immediacy to be tested and self-exempting oneself from screening, may be promising targets for future interventions to improve uptake.

Small-bowel capsule endoscopy in patients with Meckel's diverticulum: clinical features, diagnostic workup, and findings. A European multicenter I-CARE study.

BACKGROUND AND AIMS: Meckel's diverticulum (MD) may remain silent or be associated with adverse events such as GI bleeding. The main aim of this study was to evaluate indicative small-bowel capsule endoscopy (SBCE) findings, and the secondary aim was to describe clinical presentation in patients with MD. METHODS: This retrospective European multicenter study included patients with MD undergoing SBCE from 2001 until July 2021. RESULTS: Sixty-nine patients with a confirmed MD were included. Median age was 32 years with a male-to-female ratio of approximately 3:1. GI bleeding or iron-deficiency anemia was present in nearly all patients. Mean hemoglobin was 7.63 ± 1.8 g/dL with a transfusion requirement of 52.2%. Typical capsule endoscopy (CE) findings were double lumen (n = 49 [71%]), visible entrance into the MD (n = 49 [71%]), mucosal webs (n = 30 [43.5%]), and bulges (n = 19 [27.5%]). Two or more of these findings were seen in 48 patients (69.6%). Ulcers were detected in 52.2% of patients (n = 36). In 63.8% of patients (n = 44), a combination of double lumen and visible entrance into the MD was evident, additionally revealing ulcers in 39.1% (n = 27). Mean percent SB (small bowel) transit time for the first indicative image of MD was 57% of the total SB transit time. CONCLUSIONS: Diagnosis of MD is rare and sometimes challenging, and a preoperative criterion standard does not exist. In SBCE, the most frequent findings were double-lumen sign and visible diverticular entrance, sometimes together with ulcers.

Small-bowel capsule endoscopy and device-assisted enteroscopy for diagnosis and treatment of small-bowel disorders: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2022.

MR1: ESGE recommends small-bowel capsule endoscopy as the first-line examination, before consideration of other endoscopic and radiological diagnostic tests for suspected small-bowel bleeding, given the excellent safety profile of capsule endoscopy, its patient tolerability, and its potential to visualize the entire small-bowel mucosa.Strong recommendation, moderate quality evidence. MR2: ESGE recommends small-bowel capsule endoscopy in patients with overt suspected small-bowel bleeding as soon as possible after the bleeding episode, ideally within 48 hours, to maximize the diagnostic and subsequent therapeutic yield.Strong recommendation, high quality evidence. MR3: ESGE does not recommend routine second-look endoscopy prior to small-bowel capsule endoscopy in patients with suspected small-bowel bleeding or iron-deficiency anemia.Strong recommendation, low quality evidence. MR4: ESGE recommends conservative management in those patients with suspected small-bowel bleeding and high quality negative small-bowel capsule endoscopy.Strong recommendation, moderate quality evidence. MR5: ESGE recommends device-assisted enteroscopy to confirm and possibly treat lesions identified by small-bowel capsule endoscopy.Strong recommendation, high quality evidence. MR6: ESGE recommends the performance of small-bowel capsule endoscopy as a first-line examination in patients with iron-deficiency anemia when small bowel evaluation is indicated.Strong recommendation, high quality evidence. MR7: ESGE recommends small-bowel capsule endoscopy in patients with suspected Crohn's disease and negative ileocolonoscopy findings as the initial diagnostic modality for investigating the small bowel, in the absence of obstructive symptoms or known bowel stenosis.Strong recommendation, high quality evidence. MR8: ESGE recommends, in patients with unremarkable or nondiagnostic findings from dedicated small-bowel cross-sectional imaging, small-bowel capsule endoscopy as a subsequent investigation if deemed likely to influence patient management.Strong recommendation, low quality evidence. MR9: ESGE recommends, in patients with established Crohn's disease, the use of a patency capsule before small-bowel capsule endoscopy to decrease the capsule retention rate.Strong recommendation, moderate quality evidence. MR10: ESGE recommends device-assisted enteroscopy (DAE) as an alternative to surgery for foreign bodies retained in the small bowel requiring retrieval in patients without acute intestinal obstruction.Strong recommendation, moderate quality evidence. MR11: ESGE recommends DAE-endoscopic retrograde cholangiopancreatography (DAE-ERCP) as a first-line endoscopic approach to treat pancreaticobiliary diseases in patients with surgically altered anatomy (except for Billroth II patients).Strong recommendation, moderate quality evidence.

High diagnostic yield despite a lower completion rates for inpatient versus outpatient colon and pan-intestinal capsule endoscopy: a nested case-control study.

BACKGROUND: Increased familiarity with capsule endoscopy (CE) has been associated with a growing demand for urgent inpatient procedures. Limited data exists comparing the effect of admission status on colon capsule (CCE) and pan-intestinal capsule (PIC) performance. We aimed to compare the quality of inpatient versus outpatient CCE and PIC studies. METHODS: A retrospective nested case-control study. Patients were identified from a CE database. PillCam Colon 2 Capsules with standard bowel preparation and booster regimen were used in all studies. Basic demographics and key outcome measures were documented from procedure reports and hospital patient records, and compared between groups. RESULTS: 105 subjects were included, 35 cases and 70 controls. Cases were older, were more frequently referred with active bleeding and had more PICs. The diagnostic yield was high at 77% and was similar in both groups. Completion rates were significantly better for outpatients, 43% (n = 15) v's 71% (n = 50), OR 3, NN3. Neither gender nor age affected completion rates. Completion rates and preparation quality were similar for CCE and PIC inpatient procedures. CONCLUSION: Inpatient CCE and PIC have a clinical role. There is an increased risk of incomplete transit in inpatients, and strategies to mitigate against this are needed.

Validation and Update of the Lémann Index to Measure Cumulative Structural Bowel Damage in Crohn's Disease.

BACKGROUND & AIMS: The Lémann Index is a tool measuring cumulative structural bowel damage in Crohn's disease (CD). We reported on its validation and updating. METHODS: This was an international, multicenter, prospective, cross-sectional observational study. At each center, 10 inclusions, stratified by CD duration and location, were planned. For each patient, the digestive tract was divided into 4 organs, upper tract, small bowel, colon/rectum, anus, and subsequently into segments, explored systematically by magnetic resonance imaging and by endoscopies in relation to disease location. For each segment, investigators retrieved information on previous surgical procedures, identified predefined strictures and penetrating lesions of maximal severity (grades 1-3) at each organ investigational method (gastroenterologist and radiologist for magnetic resonance imaging), provided segmental damage evaluation ranging from 0.0 to 10.0 (complete resection). Organ resection-free cumulative damage evaluation was then calculated from the sum of segmental damages. Then investigators provided a 0-10 global damage evaluation from the 4-organ standardized cumulative damage evaluations. Simple linear regressions of investigator damage evaluations on their corresponding Lémann Index were studied, as well as calibration plots. Finally, updated Lémann Index was derived through multiple linear mixed models applied to combined development and validation samples. RESULTS: In 15 centers, 134 patients were included. Correlation coefficients between investigator damage evaluations and Lémann Indexes were >0.80. When analyzing data in 272 patients from both samples and 27 centers, the unbiased correlation estimates were 0.89, 0,97, 0,94, 0.81, and 0.91 for the 4 organs and globally, and stable when applied to one sample or the other. CONCLUSIONS: The updated Lémann Index is a well-established index to assess cumulative bowel damage in CD that can be used in epidemiological studies and disease modification trials.

The utility of faecal and urine biomarkers for small bowel diseases.

PURPOSE OF REVIEW: Small bowel diseases pose a unique diagnostic and management challenge and often requires tertiary specialist referral. The use of biomarkers may provide a cheap, noninvasive tool to assess the small bowel in terms of diagnosis, offering a better way to triage referrals and select patients for early management. This review looks at the most recent evidence behind the use of several faecal and urine biomarkers for small bowel diseases. RECENT FINDINGS: Faecal calprotectin shows the most promise, with evidence to support its role in predicting relapse postsurgery and monitoring treatment response in patients with Crohn's disease. A faecal calprotectin less than 50 µg/g may also be used as a cut-off to triage further investigation. Faecal lactoferrin also appears promising as a marker of small bowel inflammation. A positive faecal immunohistochemistry test precapsule may help to prioritize referrals for obscure bleeding. SUMMARY: The use of biomarkers in the diagnosis and management of small bowel disease is still controversial and remains unclear. More studies are required to further develop their potential and before societal guidelines can be developed to direct their appropriate use in clinical practice.

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

MAIN RECOMMENDATIONS: 1. ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. Strong recommendation, high quality evidence. ESGE/ESGAR do not recommend barium enema in this setting. Strong recommendation, high quality evidence.2. ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors. Strong recommendation, low quality evidence. ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete. Weak recommendation, low quality evidence.3. When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms. Strong recommendation, high quality evidence. Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation. Very low quality evidence. ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms. Strong recommendation, high quality evidence. In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms. Weak recommendation, low quality evidence.4. Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors. Strong recommendation, high quality evidence. ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer. Weak recommendation, low quality evidence.5. ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs. Strong recommendation, moderate quality evidence. ESGE/ESGAR also suggest the use of CCE in this setting based on availability. Weak recommendation, moderate quality evidence.6. ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in this setting. Very low quality evidence.7. ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible. Weak recommendation, low quality evidence. There is insufficient evidence to recommend CCE in post-polypectomy surveillance. Very low quality evidence.8. ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation. Strong recommendation, low quality evidence.9. ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥6 mm detected at CTC or CCE. Follow-up CTC may be clinically considered for 6-9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia. Strong recommendation, moderate quality evidence. Source and scope This is an update of the 2014-15 Guideline of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). It addresses the clinical indications for the use of imaging alternatives to standard colonoscopy. A targeted literature search was performed to evaluate the evidence supporting the use of computed tomographic colonography (CTC) or colon capsule endoscopy (CCE). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence.

Negative emotions and cancer fatalism are independently associated with uptake of Faecal Immunochemical Test-based colorectal cancer screening: Results from a population-based study.

Although systematic colorectal cancer screening is efficacious, many programmes suffer from low uptake. Few behavioural or attitudinal factors have been identified as being associated with participation in colorectal cancer screening. We explored knowledge, beliefs about cancer, subjective health literacy, emotional attitudes to screening, and social influences among individuals invited to a population-based screening programme. Regression modelling of a cross-sectional survey of 2299 individuals (users and non-users) of a population-based Faecal Immunochemical Test (FIT) screening programme in Dublin was conducted. Questions were derived from previous theoretically-informed qualitative work and assessed using previously used and validated measures. The primary outcome variable was uptake status (User/Participation or Non-User/Non-participation); multivariable logistic regression was used to estimate the odds ratios (OR) for screening participation. Stronger fatalistic beliefs independently predicted lower uptake (OR = 0.94; 95% CI 0.90-0.98; P = 0.003). Those aged <65 who disagreed that "cancer can often be cured" also had lower uptake (OR = 0.43; 95% CI 0.22-0.82: P = 0.017). Agreement that the test was disgusting and tempting fate predicted lower uptake (OR = 0.16: 95% CI 0.10-0.27: p < 0.001), while the influence of a partner on decision to be screened was associated with higher uptake (OR = 1.32; 95% CI 1.15-1.50: P < 0.001). Negative cancer-related and screening-related beliefs and emotions are associated with non-participation in FIT (-based screening). Research is warranted to explore if these negative beliefs and emotions are modifiable and, if so, whether this would improve screening uptake. The association between the influence of a partner and screening participation present a challenge around improving uptake among those not in co-habiting relationships.

Risk of Progression of Gastric Intestinal Metaplasia Is Significantly Greater When Detected in Both Antrum and Body.

BACKGROUND: Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide. GC is usually preceded by a cascade of well-defined precursor lesions, set in place by an environmental trigger (H. pylori) including intestinal metaplasia (GIM) and dysplasia. AIMS: To investigate the rates of progression of GIM to dysplasia and GC in a region of low gastric cancer incidence. METHODS: We identified all patients diagnosed with GIM between January 1, 2008, and June 30, 2012. Any repeat upper endoscopy more than 1 year after index diagnosis and before December 31, 2018, was considered follow-up. Carcinomas the bulk of which were macroscopically located below the OGJ were considered primary gastric cancer. RESULTS: Progression to more advanced lesions was observed in six patients (0.6%). Four patients (three male) developed GC at median age 74 years (SD 6). Two patients progressed to dysplasia (one male) at median age 71 years (SD 4). Patients with GIM in both gastric antrum and body were significantly more likely to progress than those with GIM in only one location (3.1% vs. 0.4%) (p value 0.017). Fifty-eight patients who had H. pylori eradicated were followed up. No progression to dysplasia or GC was noted in this group, with 28 patients having persistent GIM at follow-up. CONCLUSION: Patients with GIM in both antrum and body had a significantly increased risk of progression and warrant close attention. This is comparable to routinely followed premalignant conditions such as Barrett's esophagus and Colonic Polyps, and appropriate surveillance protocols should be followed in this group.

Genomic profiling of intestinal T-cell receptor repertoires in inflammatory bowel disease.

Growing evidence shows that inflammatory bowel disease (IBD) results from dysregulation of immune responses to gut microbes. T-cell receptors (TCRs) expressed on the T-cell surface play critical roles in discriminating pathogens from commensal intestinal microorganisms at the front line of the adaptive immune system. The breakdown of this interaction may trigger persistent inflammatory responses to gut bacteria, resulting in IBD. Taking advantage of high-throughput sequencing, we developed an integrated approach to dissect the intestinal TCR repertoires underlying IBD by collecting peripheral blood and inflamed intestine from the same set of 11 IBD cases. The intestinal TCR repertoires show lower clonotype diversity (p < 0.05) and stronger clonal expansion (p < 0.02) than those in the blood. This pattern becomes more profound in TCRs unique to the inflamed tissue compared with shared TCRs. Our approach further identified the increased usage of TRAV12-3 (false discovery rate, FDR < 5%), which biases its choices of J genes towards the reduction of TRAJ37 and TRAJ43 usage (FDR < 20%) in the inflamed intestine. Our genomic profiling suggests that this selective bias of V and J gene usage may lead to a loss of diversity in the intestinal TCR repertoires and result in mucosal inflammation in IBD.

Imaging alternatives to colonoscopy: CT colonography and colon capsule. European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline - Update 2020.

1: ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia.Strong recommendation, high quality evidence.ESGE/ESGAR do not recommend barium enema in this setting.Strong recommendation, high quality evidence. 2: ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. The timing depends on an interdisciplinary decision including endoscopic and radiological factors.Strong recommendation, low quality evidence.ESGE/ESGAR suggests that, in centers with expertise in and availability of colon capsule endoscopy (CCE), CCE preferably the same or the next day may be considered if colonoscopy is incomplete.Weak recommendation, low quality evidence. 3: When colonoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with alarm symptoms.Strong recommendation, high quality evidence.Because of lack of direct evidence, ESGE/ESGAR do not recommend CCE in this situation.Very low quality evidence.ESGE/ESGAR recommend CTC as an acceptable alternative to colonoscopy for patients with non-alarm symptoms.Strong recommendation, high quality evidence.In centers with availability, ESGE/ESGAR suggests that CCE may be considered in patients with non-alarm symptoms.Weak recommendation, low quality evidence. 4: Where there is no organized fecal immunochemical test (FIT)-based population colorectal screening program, ESGE/ESGAR recommend CTC as an option for colorectal cancer screening, providing the screenee is adequately informed about test characteristics, benefits, and risks, and depending on local service- and patient-related factors.Strong recommendation, high quality evidence.ESGE/ESGAR do not suggest CCE as a first-line screening test for colorectal cancer.Weak recommendation, low quality evidence. 5: ESGE/ESGAR recommend CTC in the case of a positive fecal occult blood test (FOBT) or FIT with incomplete or unfeasible colonoscopy, within organized population screening programs.Strong recommendation, moderate quality evidence.ESGE/ESGAR also suggest the use of CCE in this setting based on availability.Weak recommendation, moderate quality evidence. 6: ESGE/ESGAR suggest CTC with intravenous contrast medium injection for surveillance after curative-intent resection of colorectal cancer only in patients in whom colonoscopy is contraindicated or unfeasibleWeak recommendation, low quality evidence.There is insufficient evidence to recommend CCE in this setting.Very low quality evidence. 7: ESGE/ESGAR suggest CTC in patients with high risk polyps undergoing surveillance after polypectomy only when colonoscopy is unfeasible.Weak recommendation, low quality evidence.There is insufficient evidence to recommend CCE in post-polypectomy surveillance.Very low quality evidence. 8: ESGE/ESGAR recommend against CTC in patients with acute colonic inflammation and in those who have recently undergone colorectal surgery, pending a multidisciplinary evaluation.Strong recommendation, low quality evidence. 9: ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp ≥ 6 mm detected at CTC or CCE.Follow-up CTC may be clinically considered for 6 - 9-mm CTC-detected lesions if patients do not undergo polypectomy because of patient choice, comorbidity, and/or low risk profile for advanced neoplasia.Strong recommendation, moderate quality evidence.

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.

Development of significant disease in a cohort of patients with non-specific enteritis on capsule endoscopy: clinical suspicion and a high base line Lewis score are predictive of Crohn's disease.

BACKGROUND: As with isolated ileitis the findings of nonspecific small bowel enteritis (NSE) on capsule endoscopy (CE) poses a clinical challenge. There is lack of available evidence to help clinicians to predict significant disease and long-term prognosis. AIM: To define the natural history of NSE in an Irish cohort. METHODS: Patients with a finding of NSE were identified from a database. Subsequent investigations, treatments and diagnosis were recorded. Patients were grouped based on ultimate diagnosis: Crohn's disease (CD), Irritable bowel syndrome (IBS), NSAIDs enteritis (NSAIDs), persistent NSE and no significant disease (NAD). RESULTS: 88 patients, 46 (52%) male, mean age 52 ± 17.8 years were included with a mean follow up of 23 ± months. The ultimate diagnoses were NAD = 43 (49%), CD = 17 (19%), IBS = 14 (16%), NSAIDs = 12 (14%) and persistent NSE = 2 (2%). Significantly, more patients diagnosed with CD on follow up were referred with suspected CD. CD = 14/17 (82%) vs 13/57 (23%), p < 0.001. While a diagnosis of CD was associated with a positive baseline Lewis score (> 135); 11/17 (65%) CD versus 16/ 71 (23%). Female gender was associated with an ultimate diagnosis of IBS (OR 5, p < 0.02). Older age was associated with NSAIDs enteritis, while more subjects without significant gastrointestinal disease were anemic on presentation. CONCLUSION: The majority (49%) of NSE patients do not develop significant small bowel disease. CD occurred in 19% of NSE patients on follow up. Clinical suspicion and capsule severity are predictive of Crohn's disease on initial CE.

Strictureplasty versus bowel resection for the surgical management of fibrostenotic Crohn's disease: a systematic review and meta-analysis.

BACKGROUND: Strictureplasty (SPX) conserves bowel length and minimizes the risk of developing short bowel syndrome in patients undergoing surgery for Crohn's disease (CD). However, SPX may be associated with a higher risk of recurrence compared with bowel resection (BR). AIM: We sought to compare morbidity and recurrence following SPX and BR in patients with fibrostenotic CD. METHODS: A systematic review was performed according to PRISMA and MOOSE guidelines. Observational studies that compared outcomes of CD patients undergoing either SPX or BR were identified. Log hazard ratios (InHR) for recurrence-free survival (RFS) and their standard errors were calculated from Kaplan-Meier plots or Cox regression models and pooled using the inverse variance method. Dichotomous variables were pooled as odds ratios (OR) using the Mantel-Haenszel method. Continuous variables were pooled as weighted mean differences. RESULTS: Twelve studies of 1026 CD patients (SPX n = 444, 43.27%; BR with or without SPX n = 582, 56.72%) were eligible for inclusion. There was an increased likelihood of disease recurrence with SPX than with BR (OR 1.61; 95% CI, 1.03, 2.52; p = 0.04; I2 = 0%). Patients who had a SPX alone had a significantly reduced RFS than those who underwent BR (HR 1.47; 95% CI, 1.08, 2.01; p = 0.02; I2 = 0%). There was no difference in morbidity between the groups (OR 0.58; 95% CI, 0.26, 1.28; p = 0.18; I2 = 0%). CONCLUSION: SPX should only be performed in those patients with Crohn's strictures that are at high risk for short bowel syndrome and intestinal failure; otherwise, BR is the favored surgical technique for the management of fibrostenotic CD.

Endoscopic management versus transanal surgery for early primary or early locally recurrent rectal neoplasms-a systematic review and meta-analysis.

BACKGROUND: Both endoscopic techniques and transanal surgery are viable options that allow organ preservation for early rectal neoplasms. Whilst endoscopic approaches are less invasive and carry less morbidity, it is unclear whether they are as oncologically effective. AIM: To compare endoscopic techniques with transanal surgery in the management of early rectal neoplasms. METHODS: A systematic literature search was performed for randomised and observational studies comparing these techniques. The pre-specified main outcomes measured were en bloc and R0 resection rates and recurrence. Pair-wise meta-analysis was performed. RESULTS: This review included 1044 patients. Transanal surgery had increased R0 resection rates (odds ratio (OR) 2.66; 95% CI 1.64; 4.31; p < 0.001) versus endoscopic management. The latter was associated with higher rates of incomplete resection (OR 2.25; 95% CI 1.14, 4.46; p = 0.02) and further intervention (OR 1.78; 95% CI 1.09, 2.88; p = 0.02). There was no difference in the rates of late recurrence (OR 1.01; 95% CI 0.53, 1.91; p = 0.99) or further major surgery (OR 0.87; 95% CI 0.39, 1.94; p = 0.73) between the groups. Endoscopic treatment was associated with a shorter operating time (weighted mean difference (WMD) - 12.08; 95% CI - 18.97, - 5.19; p < 0.001) and LOS (WMD - 1.94; 95% CI - 2.43, - 1.44; p < 0.001), as well as lower rates of urinary retention post-operatively (OR 0.12; 95% CI 0.02, 0.63; p = 0.01). CONCLUSION: Endoscopic techniques should be favoured in the setting of benign early rectal neoplasms given their decreased morbidity and increased cost-effectiveness. However, where malignancy is suspected transanal surgery should be the preferred option given the superior R0 resection rate.

Meta-analysis of early bowel resection versus initial medical therapy in patient's with ileocolonic Crohn's disease.

BACKGROUND: Early bowel resection (EBR) in ileocolonic Crohn's disease (CD) may be associated with more durable remission compared with initial medical therapy (IMT) even when biologic therapy is included. AIM: To compare the efficacy of EBR versus IMT for ileocolonic CD METHODS: A systematic search was performed to identify studies that compared EBR (performed < 1 year from initial diagnosis) or IMT for the management of ileocolonic CD. Log hazard ratios (InHR) for relapse-free survival (RFS) and their standard errors were calculated from Kaplan-Meier plots and pooled using the inverse-variance method. Dichotomous variables were pooled as odds ratios (OR). Quality assessment of the included studies was performed using the Newcastle-Ottawa (NOS) and Jadad scales. RESULTS: A total of 7 studies with 1863 CD patients (EBR n = 581, 31.2%; IMT n = 1282, 68.8%) were eligible for inclusion. There was a moderate-to-high risk of bias. The median NOS was 8 (range 7-9). There was a reduced likelihood of overall (OR, 0.53; 95% confidence interval (95% CI), 0.34, 0.83; p = 0.005) and surgical (OR, 0.47; 95% CI, 0.24, 0.91; p = 0.03) relapse with EBR. There was also a less requirement for maintenance biologic therapy (OR, 0.24; 95% CI, 0.14, 0.42; p < 0.0001). Patients who underwent EBR had a significantly improved RFS than those who underwent IMT (HR, 0.62; 95% CI, 0.52, 0.73; p < 0.001). There was no difference in morbidity (OR, 1.67; 95% CI, 0.44, 6.36; p = 0.45) between the groups. CONCLUSION: EBR may be associated with less relapse and need for maintenance biologic therapy than IMT. 'Upfront' or early resection may represent a reasonable and cost-effective alternative to biologic therapy, especially in biologic-resistant subpopulations.

Helicobacter pylori resistance to current therapies.

PURPOSE OF REVIEW: Helicobacter pylori eradication rates have fallen in recent years, mainly because of the emergence of antibiotic-resistant infections. Indeed the WHO has recently designated clarithromycin-resistant H. pylori infection a high priority for antibiotic resistance research and development. This review aims to discuss the most up-to-date information on the methods to detect H. pylori antibiotic resistance, the recent data on resistance rates, and the most appropriate treatment strategies to overcome antibiotic resistance. RECENT FINDINGS: There has been active research into the development and assessment of genotypic diagnostic assays for both the invasive and noninvasive detection of antibiotic-resistant infection. There are regional variations in the prevalence of H. pylori antibiotic resistance. Primary resistance rates in general are on the rise and high rates of clarithromycin resistance (>15%) have been reported in many parts of the world. SUMMARY: Optimizing antimicrobial susceptibility testing by both invasive and noninvasive means is crucial to accurately evaluate resistance rates for the optimization of both regional and personalized H. pylori treatment strategies.