Unlocking quality in endoscopic mucosal resection.

A review of the development of the key performance metrics of endoscopic mucosal resection (EMR), learning from the experience of the establishment of widespread colonoscopy quality measurements. Potential future performance markers for both colonoscopy and EMR are also evaluated to ensure continued high quality performance is maintained with a focus service framework and predictors of patient outcome.

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.

Endoscopy training through the COVID-19 pandemic: maintaining procedural volumes and key performance standards.

Objective: Endoscopy departments have experienced considerable challenges in the provision of endoscopy services since the start of the COVID-19 pandemic. Several studies have reported a reduction of procedures performed by trainee endoscopists during the pandemic. The aim of this study was to assess the impact on colonoscopy training and quality in an academic centre throughout successive waves of the pandemic. Methods: This was a single-centre, retrospective, observational study comparing colonoscopies performed at a tertiary endoscopy centre in Ireland at different stages of the pandemic with those performed during a similar time frame prepandemic. Data were collected using electronic patient records. Primary outcomes were procedure volumes, adenoma detection rate and mean adenoma per procedure. Results: In the prepandemic period, 798 colonoscopies were performed. During the same period in 2020, 172 colonoscopies were performed. In 2021, during the third wave of the pandemic, 538 colonoscopies were performed. Percentages of colonoscopies performed by trainees were 46.0% (n=367) in 2019, 25.6% (n=44) in 2020 and 45.2% (n=243) in 2021. Adenoma detection rate was 21.3% in 2019, 38.6% in 2020 and 23.9% in 2021. Mean adenoma per procedure was 0.45 in 2019, 0.86 in 2020 and 0.49 in 2021. Caecal intubation rate was 90.74% in 2019, 90.9% in 2020 and 95.88% in 2021. Conclusion: The COVID-19 pandemic initially had a negative impact on overall colonoscopy volumes and training. Despite a reduction in procedural volume, key performance standards were maintained by trainees. Maintenance of hands-on training is essential to allow trainees achieve and retain competency in endoscopy.

ERCP and SARS-COV-2: an urgent procedure that should be immune.

BACKGROUND: Radical changes to clinical and endoscopy practice have been rapidly introduced following the spread of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Urgent endoscopies are, however, intended to proceed as normal with additional personal protective procedures. A perceived reduction in hospital attendances may suggest a number of urgently indicated endoscopic retrograde cholangio-pancreatographies (ERCPs) are being missed. Objectives and Methods: A review of all ERCPs carried out in a large tertiary referral endoscopy unit under healthcare restrictions was compared to the same time period in previous years. The intention was to determine if ERCPs are proceeding as normal or if there is a difference in referral characteristics. RESULTS: Under service restrictions (13 March to the end of April 2020), 55 ERCPs were performed compared with 87 ERCPs in 2019. Similar numbers to 2019 were also recorded in the preceding years. One case of coronavirus disease 2019 (COVID-19) was reported in a patient in the days following ERCP, with no cases notified among staff related to endoscopy. CONCLUSIONS: A reduction in ERCP referrals raises concern that a cohort of patients with significant biliary disease remain undetected. Whether this results in later, and more severe, presentation remains to be seen but a potential surge in such cases could significantly burden all future endoscopy planning services.

Barrett's Registry Collaboration of academic centers in Ireland reveals high progression rate of low-grade dysplasia and low risk from nondysplastic Barrett's esophagus: report of the RIBBON network.

Barrett's esophagus (BE) is the main pathological precursor of esophageal adenocarcinoma (EAC). Progression to high-grade dysplasia (HGD) or EAC from nondysplastic BE (NDBE), low-grade dysplasia (LGD) and indefinite for dysplasia (IND) varies widely between population-based studies and specialized centers for many reasons, principally the rigor of the biopsy protocol and the accuracy of pathologic definition. In the Republic of Ireland, a multicenter prospective registry and bioresource (RIBBON) was established in 2011 involving six academic medical centers, and this paper represents the first report from this network. A detailed clinical, endoscopic and pathologic database registered 3,557 patients. BE was defined strictly by both endoscopic evidence of Barrett's epithelium and the presence of specialized intestinal metaplasia (SIM). A prospective web-based database was used to gather information with initial and follow-up data abstracted by a data manager at each site. A total of 2,244 patients, 1,925 with no dysplasia, were included with complete follow-up. The median age at diagnosis was 60.5 with a 2.1:1 male to female ratio and a median follow-up time of 2.7 years (IQR 1.19-4.04), and 6609.25 person years. In this time period, 125 (5.57%) progressed to HGD/EAC, with 74 (3.3%) after 1 year of follow-up and 38 (1.69%) developed EAC, with 20 (0.89%) beyond 1 year. The overall incidence of HGD/EAC was 1.89% per year; 1.16% if the first year is excluded. The risk of progression to EAC alone overall was 0.57% per year, 0.31% excluding the first year, and 0.21% in the 1,925 patients who had SIM alone at diagnosis. Low-grade dysplasia (LGD) progressed to HGD/EAC in 31% of patients, a progression rate of 12.96% per year, 6.71% with the first year excluded. In a national collaboration of academic centers in Ireland, the progression rate for NDBE was similar to recent population studies. Almost one in two who progressed was evident within 1 year. Crucially, LGD diagnosed and confirmed by specialist gastrointestinal pathologists represents truly high-risk disease, highlighting the importance of expertise in diagnosis and management, and providing indirect support for ablative therapies in this context.

Golimumab effectiveness and safety in clinical practice for moderately active ulcerative colitis.

BACKGROUND AND AIMS: Golimumab (GLB) is an antitumour necrosis factor-α (anti-TNF) therapy that has shown efficacy as induction and maintenance therapy for ulcerative colitis (UC). We aimed to describe the outcome of GLB therapy for UC in a real-world clinical practice. PATIENTS AND METHODS: Consecutive patients receiving GLB for UC in six Irish Academic Medical Centres were identified. The primary study endpoint was the 6-month corticosteroid-free remission rate. The secondary endpoints included the 3-month clinical response, time free of GLB discontinuation and adverse events. RESULTS: Seventy-two patients were identified [57% men; median (range) age of 41.4 years (20.3-76.8); disease duration 6.6 years (0-29.9); follow-up 8.7 months (0.4-39.2)]. Sixty-four percent of patients were anti-TNF naive. The 3-month clinical response and the 6-month corticosteroid-free remission rates were 55 and 39%, respectively. Forty-four percent of patients discontinued GLB during the follow-up, median (95% confidence interval) time to GLB discontinuation 18.7 months (9.2-28.1). A C-reactive protein more than 5 mg/l at baseline was associated with failure to achieve 6-month corticosteroid-free remission and a shorter time to GLB discontinuation, odds ratio 0.2 (0.1-0.7), P=0.008, and hazard ratio (95% confidence interval) 2.8 (1.3-5.7), P=0.007, respectively. Adverse events occurred in 7% of patients (n=5), all of which were minor and self-limiting. CONCLUSION: These real-world clinical data suggest that GLB is an effective and safe therapy for a UC cohort with significant previous anti-TNF exposure. An elevated baseline C-reactive protein, likely reflective of increased inflammatory burden, is associated with a reduced likelihood of a successful outcome of GLB therapy.

Protocol for a multicentred randomised controlled trial investigating the use of personalised golimumab dosing tailored to inflammatory load in ulcerative colitis: the GOAL-ARC study (GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis) led by the INITIAtive group (NCT 0268772).

INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), often leading to an impaired quality of life in affected patients. Current treatment modalities include antitumour necrosis factor (anti-TNF) monoclonal antibodies (mABs) including infliximab, adalimumab and golimumab (GLM). Several recent retrospective and prospective studies have demonstrated that fixed dosing schedules of anti-TNF agents often fails to consistently achieve adequate circulating therapeutic drug levels (DL) with consequent risk of immunogenicity treatment failure and potential risk of hospitalisation and colectomy in patients with UC.The design of GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis aims to address the impact of dose escalation of GLM immediately following induction and during the subsequent maintenance phase in response to suboptimal DL or persisting inflammatory burden as represented by raised faecal calprotectin (FCP). AIM: The primary aim of the study is to ascertain if monitoring of FCP and DL of GLM to guide dose optimisation (during maintenance) improves rates of patient continuous clinical response and reduces disease activity in UC. METHODS AND ANALYSIS: A randomised, multicentred two-arm trial studying the effect of dose optimisation of GLM based on FCP and DL versus treatment as per SMPC. Eligible patients will be randomised in a 1:1 ratio to 1 of 2 treatment groups and shall be treated over a period of 46 weeks. ETHICS AND DISSEMINATION: The study protocol was approved by the Research Ethics committee of St. Vincent's University Hospital. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. TRIAL REGISTRATION NUMBERS: EudraCT number: 2015-004724-62; Clinicaltrials.gov Identifier: NCT0268772; Pre-results.

High-risk family colorectal cancer screening service in Ireland: Critical review of clinical outcomes.

BACKGROUND: We present the 15-year experience of a family colorectal cancer screening service in Ireland with emphasis on real life experience and outcomes. METHODS: Questionnaires were used to assess family cancer history and assign patients to risk categories; 'Moderate Risk', HNPCC, (suspected) genetic syndrome (non-HNPCC), 'Low Risk'. Screening was by full colonoscopy. We report neoplastic yield, examining effect of risk category, age, gender, and index colonoscopy findings. RESULTS: Between 1998 and 2013, 2242 individuals were referred; 57.3% female, 42.7% male, median age 46 years (range9-85yrs). Median follow up time was 7.9yrs (range 0.5-15.3yrs). Follow up data after exclusion (non-compliance, known CRC) was available in 1496 (66.7%): 'Moderate risk' 785 (52.5%), HNPCC 256 (17.1%), (suspected) genetic syndrome (non-HNPCC) 85 (5.7%), 'Low Risk' 370 (24.7%). Screening was performed in 1025(68.5%) patients; colonoscopy data available for 993 (96.9%); total 1914 colonoscopies. At index colonoscopy, 178 (18.0%) patients had adenomas; 56 (5.5%) advanced adenoma. During the entire study period, 240 (24.2%) had an adenoma; 69 (7.0%) advanced adenoma. Cancers were diagnosed on screening in 2 patients. Older age and male gender were associated with higher adenoma detection rate; p<0.001, p=0.01, respectively. Risk category did not affect adenoma yield. Adenoma and advanced adenoma detection at index colonoscopy were associated with detection of same at follow up screening; p<0.001. CONCLUSION: Male gender and age (>50) were the core identifiable risk factors for neoplasia at screening colonoscopy in this family screening setting. Our results would support less intensive surveillance in younger patients (<50), particularly where index colonoscopy is normal.

Endoscopic pneumatic dilation versus botulinum toxin injection in the management of primary achalasia.

BACKGROUND: Achalasia is an oesophageal motility disorder, of unknown cause, which results in increased lower oesophageal sphincter (LOS) tone and symptoms of difficulty swallowing. Treatments are aimed at reducing the LOS tone. Current endoscopic therapeutic options include pneumatic dilation (PD) or botulinum toxin (BTX) injection. OBJECTIVES: To undertake a systematic review comparing the efficacy and safety of two endoscopic treatments, PD and intrasphincteric BTX injection, in the treatment of oesophageal achalasia. SEARCH METHODS: Trials were initially identified by searching MEDLINE (1966 to August 2008), EMBASE (1980 to September 2008), ISI Web of Science (1955 to September 2008), The Cochrane Library Issue 3, 2008.  Searches in all databases were conducted in October 2005 and updated in September 2008 and April 2014. The Cochrane highly sensitive search strategy for identifying randomised trials in MEDLINE, sensitivity maximising version in the Ovid format, was combined with specific search terms to identify randomised controlled trials in MEDLINE. The MEDLINE search strategy was adapted for use in the other databases that were searched. SELECTION CRITERIA: Randomised controlled trials comparing PD to BTX injection in individuals with primary achalasia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study quality assessment and data extraction. MAIN RESULTS: Seven studies involving 178 participants were included. Two studies were excluded from the meta-analysis of remission rates on the basis of clinical heterogeneity of the initial endoscopic protocols. There was no significant difference between PD or BTX treatment in remission within four weeks of the initial intervention; with a risk ratio of remission of 1.11 (95% CI 0.97 to 1.27). There was also no significant difference in the mean oesophageal pressures between the treatment groups; with a weighted mean difference for PD of -0.77 (95% CI -2.44 to 0.91, P = 0.37). Data on remission rates following the initial endoscopic treatment were available for three studies at six months and four studies at 12 months. At six months 46 of 57 PD participants were in remission compared to 29 of 56 in the BTX group, giving a risk ratio of 1.57 (95% CI 1.19 to 2.08, P = 0.0015); whilst at 12 months 55 of 75 PD participants were in remission compared to 27 of 72 BTX participants, with a risk ratio of 1.88 (95% CI 1.35 to 2.61, P = 0.0002). No serious adverse outcomes occurred in participants receiving BTX, whilst PD was complicated by perforation in three cases. AUTHORS' CONCLUSIONS: The results of this meta-analysis suggest that PD is the more effective endoscopic treatment in the long term (greater than six months) for patients with achalasia.

Inter-endoscopist agreement in diagnosis of Barrett's oesophagus.

OBJECTIVE: To assess how interpretation of abnormalities at the oesophago-gastric junction (OGJ) when making a diagnosis of Barrett's oesophagus (BO) varies between endoscopists and to examine the impact of the endoscopy experience on these decisions. DESIGN/SETTING: Members of the Irish Society of Gastroenterology who regularly perform gastroscopy were invited to participate in a web based image assessment study. INTERVENTIONS: Questions were posed to ascertain level of endoscopy experience, and participants were asked to indicate the presence or absence of BO in 12 endoscopic images of the OGJ. OUTCOME MEASURES: Primary outcome was overall level of agreement in responses and relationship to endoscopy experience. RESULTS: The responses of 65 clinicians regularly performing gastroscopy were analysed. In 3/12 images, showing typical long segment BO, there was a strong consensus on the endoscopic diagnosis (>95% agreement). However, agreement was fair to poor (κ for multiple raters, 0.31) on the presence or absence of short BO segments at endoscopy. Minimal differences were observed between experienced endoscopists (individuals with >10 years' endoscopy experience) and less experienced counterparts in the threshold for BO diagnosis. Inter-endoscopist agreement overall was not significantly better within the more experienced group. CONCLUSION: The study demonstrates low interobserver agreement in endoscopic diagnosis of (short segment) BO, even among experienced endoscopists. Given the costs associated with endoscopic surveillance of BO, prompt efforts to promote consensus diagnosis and improve agreement are required as an important quality improvement measure in this area.

Multispectral scanning during endoscopy guides biopsy of dysplasia in Barrett's esophagus.

Esophageal cancer is increasing in frequency in the United States faster than any other cancer. Barrett's esophagus, an otherwise benign complication of esophageal reflux, affects approximately three million Americans and precedes almost all cases of esophageal cancer. If detected as high-grade dysplasia (HGD), most esophageal cancers can be prevented. Standard-of-care screening for dysplasia uses visual endoscopy and a prescribed pattern of biopsy. This procedure, in which a tiny fraction of the affected tissue is selected for pathological examination, has a low probability of detection because dysplasia is highly focal and visually indistinguishable. We developed a system called endoscopic polarized scanning spectroscopy (EPSS), which performs rapid optical scanning and multispectral imaging of the entire esophageal surface and provides diagnoses in near real time. By detecting and mapping suspicious sites, guided biopsy of invisible, precancerous dysplasia becomes practicable. Here we report the development of EPSS and its application in several clinical cases, one of which merits special consideration.

Do the benefits of metal stents justify the costs? A systematic review and meta-analysis of trials comparing endoscopic stents for malignant biliary obstruction.

BACKGROUND: A variety of stent designs has been studied for endoscopic stenting of the bile duct in patients with malignant biliary obstruction. Although metal stents are associated with longer patency, their costs are significantly higher than plastic stents. AIMS: To compare clinical outcome and cost-effectiveness of endoscopic metal and plastic stents for malignant biliary obstruction by a systematic review and meta-analysis of all randomized controlled trials in this area. METHODS: We conducted searches to identify all randomized controlled trials in any language from 1966 to 2006 using electronic databases and hand-searching of conference abstracts. Meta-analysis was performed with RevMan software [Review Manager (RevMan) version 4.2 for Windows. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2003]. RESULTS: Seven randomized controlled trials were identified that met the inclusion criteria, and 724 participants were randomized to either metal or plastic endoscopic stents. No significant difference between the two stent types in terms of technical success, therapeutic success, 30-day mortality or complications was observed. Metal stents were associated with a significantly less relative risk (RR) of stent occlusion at 4 months than plastic stents [RR, 0.44; 95% confidence interval (CI) 0.3, 0.63; P<0.01]. The overall risk of recurrent biliary obstruction was also significantly lower in patients treated with metal stents (RR, 0.52; 95% confidence interval 0.39, 0.69; P<0.01). The median incremental cost-effectiveness ratio of metal stents was $1820 per endoscopic retrograde cholangiopancreatography prevented. CONCLUSION: Endoscopic metal stents for malignant biliary obstruction are associated with significantly higher patency rates than plastic stents as early as 4 months after insertion. Metal stents will be cost-effective if the unit cost of additional endoscopic retrograde cholangiopancreatographies per patient exceeds $1820.

Malignant distal biliary obstruction: a systematic review and meta-analysis of endoscopic and surgical bypass results.

BACKGROUND: Surgical bypass and endoscopic stents are available for palliative bypass of malignant distal biliary obstruction. AIM: Comparison of reported outcomes in randomized controlled trials (RCTs) which included surgery, endoscopic plastic stents or endoscopic metal stents in palliative relief of malignant distal biliary obstruction. METHODS: Systematic review and meta-analysis of published literature and conference proceedings review to June 2006. RESULTS: We found 24 studies, containing 2436 patients, which met our inclusion criteria. Endoscopic stenting with plastic stents (three studies) is associated with a lower risk of complications (RR 0.60, 95% CI 0.45-0.81), but a higher risk of recurrent biliary obstruction (RR 18.59, 95% CI 5.33 -64.86) than traditional surgical bypass. Self-expanding metal stents (seven studies) are associated with a significantly reduced risk of recurrent biliary obstruction at 4 months (RR 0.44, 95% CI 0.3, 0.63), or prior to death or end of study (RR 0.52, 95% CI 0.39-0.69), but are not superior to plastic stents in terms of technical success, therapeutic success, mortality or complications. Cost-effectiveness outcomes were not suitable for meta-analysis. No other plastic stent designs have been demonstrated to be superior to polyethylene stents (12 studies). CONCLUSIONS: Endoscopic metal stents are the intervention of choice in patients with malignant distal biliary obstruction, producing similar outcomes to plastic stents, but with improved patency rates.