Complete polypectomy and early detection and management of residual disease to reduce the risk of interval colorectal cancers.

Advances in colorectal polyp detection and resection methods aim to reduce interval cancer rates. Complete polypectomy is essential to reduce the risk of early recurrence and the development of interval cancers. To achieve this, polyps must first be correctly identified and then completely excised. This article reviews current adenoma detection methods in use and the management of residual disease.

Treatment of Helicobacter pylori infection in 2018.

Treatment options for the eradication of Helicobacter pylori continue to evolve. There have been many guidelines for H. pylori treatment published, which may lead to some confusion. However, most are in agreement with the most recent iteration of the Maastricht treatment guidelines. Triple therapy is still the most frequently used treatment, especially in areas of low clarithromycin resistance. Its best results are achieved when taken for a minimum of 10 days and with high-dose acid suppression. Quadruple therapy is gaining in popularity particularly in areas with increasing resistance to standard triple therapy. Whether three antibiotics, or bismuth and two antibiotics are used, excellent eradication rates are achieved, albeit with increased side effects. Levofloxacin second-line therapy is widely used; however bismuth, when available, is an increasingly successful option. Sequential therapy is challenging in terms of compliance and is no longer recommended. This past year witnessed a notable increase in the number of studies based on antimicrobial susceptibility testing and tailored eradication therapy, reflecting the role of culture-guided treatment, which may well represent the future of H. pylori treatment and prevent the inappropriate use of antibiotics.

Rates and outcomes of testing for lynch syndrome in a national colorectal cancer screening programme.

BACKGROUND: Lynch Syndrome (LS), the most common cause of hereditary colorectal cancer (CRC), is characterised by pathogenic variants in mismatch repair (MMR) genes. Universal testing of all CRCs for LS can increase detection. Rates and outcomes of testing in Ireland's national CRC screening programme have not been examined previously. METHODS: CRCs diagnosed at two screening sites between 2015 and 2020 were identified. Patient records were used to determine if CRCs had been tested for MMR deficiency and if detected, what downstream testing to rule out LS or genetic testing to confirm LS was undertaken. RESULTS: Over five years, 206 CRCs were diagnosed. Testing for LS was carried out for 100% of CRCs at site A and 69% of CRCs at site B. Of CRCs tested for LS, 14 (8%) were MMR deficient. After downstream testing for BRAF mutation or hypermethylation of MLH1, three CRCs were identified as potentially LS-related. Of these two individuals declined genetic testing and one was lost to follow-up. CONCLUSIONS: By 2020 both sites had implemented universal testing of all CRCs for LS. A small number of individuals were identified as being eligible for genetic testing for LS, however those offered declined testing and one individual was lost to follow up. This highlights the importance of universal testing and the need for referral pathways to ensure all appropriate individuals are referred onwards to genetic services.

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.

Mucosal Healing in Crohn's Disease: Bull's Eye or Bust? "The Pro Position".

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. SUMMARY: Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. KEY MESSAGES: Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.

Impact of photodocumentation of caecal intubation on colonoscopy outcomes.

OBJECTIVES: The European and American colonoscopy guidelines recommend mandatory photodocumentation of caecal intubation to allow retrospective analysis and improve outcomes. We aim to demonstrate whether photodocumentation of caecal intubation improves colonoscopy outcomes. METHODS: We extracted images and procedural data from 317 consecutive colonoscopies. Images were anonymised and reviewed by four expert reviewers who scored their certainty that caecal intubation was achieved. Statistical analysis correlated adequately and inadequately photodocumented cases with polyp detection rate (PDR) and adenoma detection rate (ADR). RESULTS: The patients' mean age was 59.4 years and 52% were male. Eighty-one percent were performed by consultant endoscopists and 19% by specialist registrar. Sixty-five percent of these procedures were performed by gastroenterologists and 35% by surgical endoscopists. Fifty-three percent were deemed to have adequately demonstrated photographic evidence of caecal intubation. Statistical analysis comparing adequately and inadequately photodocumented cases: the PDR of procedures with confirmed caecal intubation was greater than procedures without photographic evidence (40% vs 34%). Similarly, the ADR of photographically confirmed cases was greater than that of inadequately photodocumented cases (25% vs 18%). The number of images taken per procedure positively correlated with photographic documentation of caecal intubation. CONCLUSION: While failing to reach statistical significance, there was a nominal difference in ADR and PDR demonstrated between the two groups, and with predominantly positive confidence intervals, this might suggest that a larger sample size could result in significance in favour of photodocumentation of caecal intubation. Future studies would be warranted. However, endoscopists that take more images were more likely to have proven caecal intubation.

Is Endoscopic Band Ligation a Superior Treatment Modality for Gastric Antral Vascular Ectasia Compared to Argon Plasma Coagulation?

BACKGROUND/AIMS: Gastric antral vascular ectasia (GAVE) is a rare acquired vascular lesion of the gastric antrum. The most frequent presentation of GAVE is iron deficiency anemia. Endoscopic therapy is the mainstay of treatment. However, there is no consensus regarding the optimal treatment modality. METHODS: A retrospective cohort study was performed on patients with GAVE, including patients receiving endoscopic therapy. Treatment was with either argon plasma coagulation (APC) or endoscopic band ligation (EBL). Basic demographic data, indication for index procedure, number of sessions, and pre- and post-hemoglobin levels were collected. The aim of the study was to compare outcomes across the two treatment modalities. RESULTS: One hundred and seventeen diagnoses of GAVE were made. Sixty-two patients (53%) required endoscopic treatment for symptomatic GAVE (female, n=38, 61%; mean age of 74.4 years). Two hundred and eighteen procedures were performed during the study period. APC was performed (n=161, 74%) more frequently than EBL (n=57, 26%). Patients treated with APC at index required a median 5 subsequent therapeutic interventions (APC or EBL), while those treated with EBL at index required a further 2.9 treatments (EBL only) (p<0.05). CONCLUSION: APC was the most common treatment modality employed. We demonstrate an increasing incidence of EBL. Patients treated with EBL at index treatment required fewer subsequent treatment sessions and had a greater mean rise in hemoglobin. This suggests a more effective endoscopic response with EBL.

Coeliac disease enteropathy and symptoms may be aggravated by angiotensin receptor blockers in patients on a gluten-free diet.

BACKGROUND: Angiotensin receptor blocker-associated enteropathy (ARB-e) is an increasingly recognised clinical entity with symptoms and histological findings identical to coeliac disease (CD). There is evidence to suggest immune-mediated mucosal injury in ARB-e with a high prevalence of DQ2/DQ8; however, as IgA anti-tissue transglutaminase (anti-TTG) is usually negative, an insult other than TTG-mediated injury is suspected. The impact of ARBs on disease activity in patients with CD is not known. OBJECTIVE: To assess the effect of ARB exposure on patients with established CD. METHODS: A patient record search of 1142 individual patients attending a dedicated coeliac clinic from 2010 to the present identified 59 patients treated with ARB. Those with CD confirmed by serology (TTG + ve/EMA + ve) and histopathology (Marsh criteria) were included (n = 40, 0.52%). Data collected included disease duration, compliance with gluten-free diet (GFD), reported symptoms (diarrhoea, weight loss and abdominal pain), surrogate markers of absorption (Vitamin D, Iron, Calcium and Haemoglobin), in addition to anti-TTG titre and histological grade at last follow up. Patients were age and sex-matched in a 1:2 ratio with CD patients not taking ARBs (controls), with comparable rates of disease duration and compliance with GFD. RESULTS: The ARB and control groups were matched in terms of age (mean 66.2 years) and gender (female 63%). Strict compliance with GFD was reported in 55% and 56%, respectively. Persistent symptoms were reported in 10/40 (25%) of the ARB group compared with 7/82 (9%) of controls (p = 0.0181). There were lower rates of mucosal healing (Marsh grade 0) in the ARB group (36% n = 11) compared to controls (55%, n = 33). There was no significant difference in anti-TTG titres. Surrogate markers of absorption were comparable across the groups, except for Vitamin D which was lower in those taking olmesartan (p = 0.0015). CONCLUSIONS: ARBs may aggravate the enteropathy and lead to increased symptoms in patients with bone fide diagnosed CD following a GFD.

Review Article: vaccination for patients with inflammatory bowel disease during the COVID-19 pandemic.

BACKGROUND: Poor immune responses are frequently observed in patients with inflammatory bowel disease (IBD) receiving established vaccines; risk factors include immunosuppressants and active disease. AIMS: To summarise available information regarding immune responses achieved in patients with IBD receiving established vaccines. Using this information, to identify risk factors in the IBD population related to poor vaccine-induced immunity that may be applicable to vaccines against COVID-19. METHODS: We undertook a literature review on immunity to currently recommended vaccines for patients with IBD and to COVID-19 vaccines and summarised the relevant literature. RESULTS: Patients with IBD have reduced immune responses following vaccination compared to the general population. Factors including the use of immunomodulators and anti-TNF agents reduce response rates. Patients with IBD should be vaccinated against COVID-19 at the earliest opportunity as recommended by International Advisory Committees, and vaccination should not be deferred because a patient is receiving immune-modifying therapies. Antibody titres to COVID-19 vaccines appear to be reduced in patients receiving anti-TNF therapy, especially in combination with immunomodulators after one vaccination. Therefore, we should optimise any established risk factors that could impact response to vaccination in patients with IBD before vaccination. CONCLUSIONS: Ideally, patients with IBD should be vaccinated at the earliest opportunity against COVID-19. Patients should be in remission and, if possible, have their corticosteroid dose minimised before vaccination. Further research is required to determine the impact of different biologics on vaccine response to COVID-19 and the potential for booster vaccines or heterologous prime-boost vaccinations in the IBD population.

Dye-based chromoendoscopy following polypectomy reduces incomplete polyp resection.

Background and study aims The completeness of a polyp resection is an important determinant of quality in colonoscopy, and may reduce incidence of interval cancers. Incomplete resection rates (IRR) vary widely and range from 6.5 % to 22.7 %. Residual disease is more likely with larger polyps, for sessile serrated adenomas, and with more proximal lesions. Chromoendoscopy is increasingly employed in lesion detection. The aims of this study were to assess local IRR, and to determine whether chromoendoscopy could correctly identify residual disease post polypectomy. Patients and methods This was a prospective study examining post polypectomy sites. Chromoendoscopy (0.13 % indigo carmine) was applied to resection bases to identify residual disease. Targeted base biopsies were taken from identified residual disease (positive group) or random base biopsies were taken when a clear base was visualised (negative group). Overall rates of incomplete resection were documented. Reported rates post chromoendoscopy and actual histological rates were documented and compared. Results A total of 102 polyps were identified for inclusion, of which 15 % (n = 16) were excluded. Resection quality was evaluated in 86 polyps of 61 patients (female n = 33 54 %; mean Age 62.3 years). Polyps were mainly removed by cold snare (n = 71, 82.5 %). Most polyps (n = 58, 67 %) measured between 5 to 10 mm. Polyps were largely located in the right colon (n = 57, 66 %). Overall histological residual disease occurred in 17 /86 (19.6 %). Chromoendoscopy correctly identified residual disease in 13 of 17 bases (76.5 %). Only four of /86 (4.6 %) of polyp bases were missclassified post-chromoendoscopy (odds ratio 0.284 (95 % CI 0.0857-0.9409), P  = 0.03). Conclusion Indigo carmine chromoendoscopy improves early detection of residual disease post polypectomy, reducing incomplete resection rates.

Lower gastrointestinal symptoms and symptoms-based triaging systems are poor predictors of clinical significant disease on colonoscopy.

Introduction: Lower gastrointestinal symptoms (LGS) are a common cause of referral to the gastroenterology service. International guidelines are available to prioritise referrals. Some studies have reported that symptoms alone are a poor marker of clinically significant disease (CSD) but symptoms remain the main way to prioritise referrals in routine clinical practice. Aims/background: To correlate LGS with colonoscopy findings in an unselected patient cohort and to investigate whether using National Institute for Health and Care Excellence (NICE) guidelines improve risk stratification. Method: Colonoscopy data over a 2-year period were obtained from our endoscopy database. Only patients with assessment of symptoms as their primary indication for colonoscopy were included. Patient records were retrospectively reviewed. Exclusion criteria: known inflammatory bowel disease (IBD), familial cancer syndromes, polyp and colorectal cancer (CRC) surveillance, and prior colonoscopy within 5 years. Demographics, symptoms and colonoscopy findings were recorded and analysed. Results: 1116 cases were reviewed; 493 (44%) males, age 54.3 years (16-91). CSD occurred in only 162 (14.5%); CRC 19 (1.7%), high-risk adenoma 40 (3.6%), inflammation 97 (8.7%) (IBD 65 (5.8%), microscopic colitis 9 (0.8%) and indeterminate-inflammation 23 (2%)), angiodysplasia 6 (0.5%). Diarrhoea gave the highest diagnostic yield for CSD of 5.3% (OR 3.15, 95% CI 2.2 to 4.7, p<0.001), followed by PR bleeding, 2.9% (OR 1.9, 95% CI 1.24 to 2.9, p=0.003). Weight loss gave the lowest diagnostic yield of 0.4%; (OR 0.79, 95% CI 0.28 to 2.24, p=0.65). 592 (53%) and 517 (46%) fitted the NICE guidelines for CRC and IBD, respectively. Using NICE positivity improved detection but overall yield remained low 3% vs 0.4% (OR 7.71, 95% CI 1.77 to 33.56, p=0.0064) for CRC, and 9% vs 2.8% (OR 3.5, 95% CI 1.99 to 6.17, p<0.0001) for IBD. Conclusions: The overall prevalence of CSD in our unselected symptomatic patients is low (14.5%). A holistic approach including combining symptoms and demographics with novel tools including stool biomarkers and minimally invasive colonoscopy alternatives should be applied to avoid unnecessary colonoscopy.

The burden of digestive disease across Europe: Facts and policies.

The past decade has witnessed a significant increase in the incidence of GI diseases across Europe. There are clear differences in outcomes for patients in Europe based on geographical and economic differences, and there is a worrying inequality in the provision of healthcare across the continent. Recent demographic studies have highlighted the heavy burden of GI disease across Europe. There is increasing demand for endoscopic procedures which are becoming increasingly more complex and demand further expertise and training. A co-ordinated and cohesive approach to research, specialist training and healthcare funding is required to overcome these inequalities.

Validation of the 'United Registries for Clinical Assessment and Research' [UR-CARE], a European Online Registry for Clinical Care and Research in Inflammatory Bowel Disease.

BACKGROUND: The 'United Registries for Clinical Assessment and Research' [UR-CARE] database is an initiative of the European Crohn's and Colitis Organisation [ECCO] to facilitate daily patient care and research studies in inflammatory bowel disease [IBD]. Herein, we sought to validate the database by using fictional case histories of patients with IBD that were to be entered by observers of varying experience in IBD. METHODS: Nineteen observers entered five patient case histories into the database. After 6 weeks, all observers entered the same case histories again. For each case history, 20 key variables were selected to calculate the accuracy for each observer. We assumed that the database was such that ≥ 90% of the entered data would be correct. The overall proportion of correctly entered data was calculated using a beta-binomial regression model to account for inter-observer variation and compared to the expected level of validity. Re-test reliability was assessed using McNemar's test. RESULTS: For all case histories, the overall proportion of correctly entered items and their confidence intervals included the target of 90% (Case 1: 92% [88-94%]; Case 2: 87% [83-91%]; Case 3: 93% [90-95%]; Case 4: 97% [94-99%]; Case 5: 91% [87-93%]). These numbers did not differ significantly from those found 6 weeks later [NcNemar's test p > 0.05]. CONCLUSION: The UR-CARE database appears to be feasible, valid and reliable as a tool and easy to use regardless of prior user experience and level of clinical IBD experience. UR-CARE has the potential to enhance future European collaborations regarding clinical research in IBD.