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Background and Aims Inflammatory Bowel Disease colitis-associated dysplasia is managed with either enhanced surveillance and endoscopic resection or prophylactic surgery. The rate of progression to cancer after a dysplasia diagnosis remains uncertain in many cases and patients have high thresholds for accepting proctocolectomy. Individualised discussion of management options is encouraged to take place between patients and their multidisciplinary teams for best outcomes. We aimed to develop a toolkit to support a structured, multidisciplinary and shared decision-making approach to discussions about dysplasia management options between clinicians and their patients. Methods Evidence from systematic literature reviews, mixed-methods studies conducted with key stakeholders and decision-making expert recommendations were consolidated to draft consensus statements by the DECIDE steering group. These were then subjected to an international, multidisciplinary modified electronic Delphi process until an a priori threshold of 80% agreement was achieved to establish consensus for each statement. Results 31 members (15 gastroenterologists, 14 colorectal surgeons and two nurse specialists) from 9 countries formed the Delphi panel. We present the 18 consensus statements generated after two iterative rounds of anonymous voting. Conclusions By consolidating evidence for best practice using literature review, key stakeholder and decision-making expert consultation we have developed international consensus recommendations to support healthcare professionals counselling patients on the management of high cancer risk colitis-associated dysplasia. The final toolkit includes clinician and patient decision aids to facilitate shared decision-making.

The naked mole rat (NMR), Heterocephalus glaber, the longest-living rodent1, provides a unique opportunity to explore how evolution has shaped adult stem cell (ASC) activity with increasing lifespan. Using cumulative BrdU labelling and a quantitative imaging approach to track intestinal ASCs (Lgr5+) in NMRs over time in their native in vivo state, we show adaptations to living in near-anaerobic2, food-deprived3 subterranean environment, has necessitated an expanded pool of Lgr5+ cells, which exhibit slower division rates compared to short-lived mice, but have similar turnover as humans. Unlike human LGR5+ cells at the crypt base (LGR5+CBC) that slow down their division rates by entering quiescence(G0) 4, NMR Lgr5+CBC cells in both the small intestine and the colon transit slowly through the active cell cycle (G1 to M) by prolonging arrest at G1 and/or G2. The inverse correlation between ASC division rates and lifespan appears to be specific to Lgr5+CBC/LGR5+CBC cells as this relationship is not seen for cells outside the crypt base. Our data provide an explanation for the observed anticorrelation between somatic mutation rates and longevity in mammals5, with ASC lineages in longer-lived organisms turning over slowly to possibly mitigate ASC exhaustion and reduce mutation rates for long-term tissue maintenance. Finally, we also observe an expanded pool of differentiated cells in NMRs that confer enhanced protection and function to the intestinal mucosa which is able to detect any chemical imbalance in the luminal environment efficiently, triggering a robust anti-proliferative, pro-apoptotic response within the stem cell zone.

ObjectiveEndoscopic resection (ER) often involves referral to tertiary centres with high volume practices. Lesions can be subject to prior manipulation and mischaracterisation of features required for accurate planning, leading to prolonged or cancelled procedures. As potential solutions, repeating diagnostic procedures is burdensome for services and patients, while even enriched written reports and still images provide insufficient information to plan ER. This project sought to determine the frequency and implications of polyp mischaracterisation and whether the use of telestration might prevent it.Design/methodA retrospective data analysis of ER referrals to four tertiary centres was conducted for the period July–December 2019. Prospective telestration with a novel digital platform was then performed between centres to achieve consensus on polyp features and ER planning.Results163 lesions (163 patients; mean age 67.9±12.2 y; F=62) referred from regional hospitals, were included. Lesion site was mismatched in 11 (6.7%). Size was not mentioned in the referral in 27/163 (16.6%) and incorrect in 81/136 (51.5%), more commonly underestimated by the referring centre (ConclusionsPolyp mischaracterisation is a frequent feature of ER referrals, but could be corrected by the use of telestration between centres. Our study involved expert-to-expert consensus, so extending to ‘real-world’ referring centres would offer additional learning for a digital pathway.

Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Conclusion Our study indicates that ESG is highly cost effective versus LM alone for the treatment of adults with class II obesity in England. Background Endoscopic sleeve gastroplasty (ESG) is a minimally invasive procedure that has been demonstrated in the MERIT randomised, controlled trial to result in substantial and durable additional weight loss in adults with obesity compared with lifestyle modification (LM) alone. We sought to conduct the first cost-effectiveness of ESG versus LM alone in adults with class II obesity (BMI 35.0-39.9 kg/m2) from a national healthcare system perspective in England based on results from this study. Methods A 6-state Markov model was developed comprising 5 BMI-based health states and an absorbing death state. Baseline characteristics, utilities, and transition probabilities were informed by patient-level data from the subset of patients with class II obesity in MERIT. Adverse events (AEs) were based on the MERIT safety population. Mortality was estimated by applying BMI-specific hazard ratios from the published literature to UK general population mortality rates. Utilities for the healthy weight and overweight health states were informed from the literature; disutility associated with increasing BMI in the class I-III obesity health states was estimated using MERIT utility data. Disutility due to AEs and the prevalence of obesity-related comorbidities were based on the literature. Costs included intervention costs, AE costs, and comorbidity costs. Results ESG resulted in higher overall costs than LM alone but led to an increase in quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) for ESG vs LM alone was £2453/QALY gained. ESG was consistently cost effective across a wide range of sensitivity analyses, with no ICER estimate exceeding £10 000/QALY gained. In probabilistic sensitivity analysis, the mean ICER was £2502/QALY gained and ESG remained cost effective in 98.25% of iterations at a willingness-to-pay threshold of £20 000/QALY.

Background Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are established techniques for treatment of superficial gastrointestinal neoplasia. Limitations of EMR are low en bloc resection rates for larger lesions, resulting in frequent recurrences. Major disadvantages of ESD are technical difficulty and long procedure times. We evaluated technical feasibility and safety of newly designed devices for en bloc resection of lesions measuring 20–40 mm in a technique called endoscopic submucosal resection (ESR). Methods This case series included 93 lesions from different locations (11 stomach, 25 colon, 57 rectum) with a median size of 29 mm (range 10–70). ESR was performed using two novel instruments for circumferential mucosal incision and deep submucosal resection, respectively. Results Resection by ESR was feasible in all cases. En bloc and R0 rates were insufficient when ESR was attempted without prior circumferential mucosal incision, but were 70 % and 63 %, respectively, when mucosal incision was done before application of the submucosal resection device. We observed three complications (two delayed bleedings, one microperforation) but no cases of emergency surgery or 30-day mortality. Conclusions Results demonstrated feasibility and excellent safety of ESR using two novel devices for en bloc resection of early gastrointestinal neoplasia. The technique offered relative technical ease and high efficacy.

Background and Aims There are no agreed-on endoscopic signs for the diagnosis of villous atrophy (VA) in celiac disease (CD), necessitating biopsy sampling for diagnosis. Here we evaluated the role of near-focus narrow-band imaging (NF-NBI) for the assessment of villous architecture in suspected CD with the development and further validation of a novel NF-NBI classification. Methods Patients with a clinical indication for duodenal biopsy sampling were prospectively recruited. Six paired NF white-light endoscopy (NF-WLE) and NF-NBI images with matched duodenal biopsy sampling including the bulb were obtained from each patient. Histopathology grading used the Marsh-Oberhuber classification. A modified Delphi process was performed on 498 images and video recordings by 3 endoscopists to define NF-NBI classifiers, resulting in a 3-descriptor classification: villous shape, vascularity, and crypt phenotype. Thirteen blinded endoscopists (5 expert, 8 nonexpert) then undertook a short training module on the proposed classification and evaluated paired NF-WLE–NF-NBI images. Results One hundred consecutive patients were enrolled (97 completed the study; 66 women; mean age, 51.2 ± 17.3 years). Thirteen endoscopists evaluated 50 paired NF-WLE and NF-NBI images each (24 biopsy-proven VAs). Interobserver agreement among all validators for the diagnosis of villous morphology using the NF-NBI classification was substantial (κ = .71) and moderate (κ = .46) with NF-WLE. Substantial agreement was observed between all 3 NF-NBI classification descriptors and histology (weighted κ = 0.72-.75) compared with NF-WLE to histology (κ = .34). A higher degree of confidence using NF-NBI was observed when assessing the duodenal bulb. Conclusions We developed and validated a novel NF-NBI classification to reliably diagnose VA in suspected CD. There was utility for expert and nonexpert endoscopists alike, using readily available equipment and requiring minimal training. (Clinical trial registration number: NCT04349904.)

Background Optical diagnosis of colorectal polyps remains challenging. Image-enhancement techniques such as narrow-band imaging and blue-light imaging (BLI) can improve optical diagnosis. We developed and prospectively validated a computer-aided diagnosis system (CADx) using high-definition white-light (HDWL) and BLI images, and compared the system with the optical diagnosis of expert and novice endoscopists. Methods CADx characterized colorectal polyps by exploiting artificial neural networks. Six experts and 13 novices optically diagnosed 60 colorectal polyps based on intuition. After 4 weeks, the same set of images was permuted and optically diagnosed using the BLI Adenoma Serrated International Classification (BASIC). Results CADx had a diagnostic accuracy of 88.3 % using HDWL images and 86.7 % using BLI images. The overall diagnostic accuracy combining HDWL and BLI (multimodal imaging) was 95.0 %, which was significantly higher than that of experts (81.7 %, P = 0.03) and novices (66.7 %, P Conclusion CADx had a significantly higher diagnostic accuracy than experts and novices for the optical diagnosis of colorectal polyps. Multimodal imaging, incorporating both HDWL and BLI, improved the diagnostic accuracy of CADx. BASIC did not increase the diagnostic accuracy of endoscopists compared with intuitive optical diagnosis.

Background and Aims EMR of large (≥2 cm) nonpedunculated colorectal polyps (LNPCPs) is associated with high rates of recurrent/residual adenoma, possibly because of microadenoma left at the margin of resection. Data supporting this mechanism are required. We aimed to determine the incidence of residual microadenoma at the defect margin and base after EMR. Methods We performed a retrospective observational study of patients undergoing EMR of large LNPCPs with the lateral defect margin further resected using the EndoRotor device (Interscope Medical, Inc, Worcester, Mass, USA) after confirming no visible residual adenomatous tissue. Aspects of the defect base were also resected in selected patients. Patients underwent surveillance at 3 to 6 months. Results Resection of the normal defect margin was performed in 41 patients and of aspects of the base in 21 patients. Mean lesion size was 43.0 mm (range, 20-130). Microscopic residual lesion was detected in the margin of apparently normal mucosa in 8 cases (19%). In 7 cases this was an adenoma, and in 1 case a serrated lesion was found at the margin of a resected tubular adenoma. Microscopic residual lesion was detected at the base in 5 of 21 cases. Residual/recurrent adenoma was detected in 2 patients. Neither had residual microadenoma at the lateral margin or base detected after the primary resection. Conclusions Microscopic residual adenoma after wide-field EMR was detected in 19% of cases at the apparently normal defect margin and at the resection base in 5 of 21 cases. This study confirms the presence of residual microadenoma after resection of LNPCPs, providing evidence for the mechanism of recurrence.

The difficulty of life scale (DLS) instrument is used to measure specific life problems in patients with ulcerative colitis (UC). Importantly, health care providers should consider the characteristics of the country in which they support patients with UC. This cross-cultural comparison study investigated DLS among patients with UC in Japan and the United Kingdom (UK). Outpatients attending one hospital in London and one in Osaka were included. We collected patient information using the DLS questionnaire, which comprises 18 items in three domains. Mean differences between Japan and the UK were compared for the total score and each domain of the DLS. Variables with P.05 in univariate analysis were entered into a multiple regression model. We included 142 patients from Japan and 100 patients from the UK in the analysis. Univariate results showed that UK patients had more difficulties than Japanese patients in all three domains. Multivariate results showed that only "decline of vitality or vigor" showed significantly lower difficulty scores in Japanese patients. Having four or more bowel movements per day, visible bleeding, and being a homemaker or unemployed were significantly associated with greater difficulty according to the DLS total score. The level of daily life difficulties assessed using the DLS was greater among patients in the UK than among Japanese patients. This comparative study between patients with UC in Japan and the UK demonstrated certain country-related features for domain 3, "decline of vitality or vigor," of the DLS. The reasons why UK patients felt greater decline in vitality or vigor may be that these patients may have symptoms other than bowel symptoms; also, Japanese patients are more hesitant to express discomfort. The findings of this study might lead to a better understanding of culturally sensitive perceptions of daily life difficulties in UC.

GI endoscopy is highly resource-intensive with a significant contribution to greenhouse gas (GHG) emissions and waste generation. Sustainable endoscopy in the context of climate change is now the focus of mainstream discussions between endoscopy providers, units and professional societies. In addition to broader global challenges, there are some specific measures relevant to endoscopy units and their practices, which could significantly reduce environmental impact. Awareness of these issues and guidance on practical interventions to mitigate the carbon footprint of GI endoscopy are lacking. In this consensus, we discuss practical measures to reduce the impact of endoscopy on the environment applicable to endoscopy units and practitioners. Adoption of these measures will facilitate and promote new practices and the evolution of a more sustainable specialty.

Background and Aim: Upper gastrointestinal tumors account for 5% of upper gastrointestinal bleeds. These patients are challenging to treat due to the diffuse nature of the neoplastic bleeding lesions, high rebleeding rates, and significant transfusion requirements. TC-325 (Cook Medical, North Carolina, USA) is a hemostatic powder for gastrointestinal bleeding. The aim of this study was to examine the outcomes of upper gastrointestinal bleeds secondary to tumors treated with Hemospray therapy. Methods: Data were prospectively collected on the use of Hemospray from 17 centers. Hemospray was used during emergency endoscopy for upper gastrointestinal bleeds secondary to tumors at the discretion of the endoscopist as a monotherapy, dual therapy with standard hemostatic techniques, or rescue therapy. Results: One hundred and five patients with upper gastrointestinal bleeds secondary to tumors were recruited. The median Blatchford score at baseline was 10 (interquartile range [IQR], 7–12). The median Rockall score was 8 (IQR, 7–9). Immediate hemostasis was achieved in 102/105 (97%) patients, 15% of patients had a 30-day rebleed, 20% of patients died within 30 days (all-cause mortality). There was a significant improvement in transfusion requirements following treatment (P

Climate change has been described as ‘the biggest global health threat of the 21st century’.1 Medical professionals have a vital role in mitigating the impact of healthcare systems on the environment and protecting vulnerable people through the development of sustainable clinical practices. We have previously written about how gastroenterologists must act now to change our endoscopy practice and make it more aligned with core principles of environmentally sustainable healthcare. But it is clear there is a significant lack of evidence to accurately define the scope of the environmental impact of gastroenterology services, or models of best practice to shape policy and move the field in a new direction. This article aims to provide a framework for us to design and implement quality improvement projects (QIPs) in gastroenterology as a strategy to deliver a more sustainable future in line with the National Health Service (NHS) Net Zero targets.2 Mortimer et al have described the key principles required,3 4 and we aim to apply these to a gastroenterology context and specifically endoscopy services. The value of a healthcare intervention relates to the outcomes delivered against its cost, and the benchmark for cost-effectiveness set by the National Institute for Health and Care Excellence is £20–30 000 per quality-adjusted life year gained.5 However, economists interested in sustainability recognise that costs also need to recognise the social and environmental impact of what is consumed: the so-called ‘triple bottom line’.6 Value can thus be presented using this schematic formula as described by Mortimer et al 3: Value=outcomes for patients and populations/environmental+social+financial impacts. Considered in this way, every healthcare intervention has not only financial implications, but also a social cost on the patient and their family/carers, and environmental implications from resource use and carbon footprint, against which the clinical benefit needs …

Each year, over 18 million endoscopy procedures are performed in the United States (US) alone. Endoscopy is the third highest generator of waste in healthcare, a sector with significant contributions to carbon emissions worldwide. Endoscopy carries a substantial carbon footprint owing to its resource-heavy decontamination processes, complex waste streams, high throughput caseloads and its heavy reliance on single-use, nonrecyclable consumables. In this review, we aim to identify sources of waste within endoscopy, provide a framework approach for measuring the carbon footprint, and propose actionable steps that can be delivered to mitigate endoscopy's carbon footprint. Based on operational energy usage and plastic waste from endoscopic procedures alone, we estimate the carbon footprint of endoscopy in the United States at 85,768 metric tons of CO2 emissions annually, equivalent to more than 9 million gallons of gasoline consumed, 94 million pounds of coal burned and 212 million miles driven in average nonelectric car. Sequestering these CO2 emissions would require an additional 112,000 acres of new forests per year. Urgent action is therefore needed within endoscopy units. Units should start by embracing the 3R's of sustainability—“Reduce, Reuse, Recycle.” Patient and administrative pathways in endoscopy should be process mapped to identify opportunities for sustainability interventions at each step. Finally, we propose a taxonomy of sustainability interventions where a pragmatic “Review, Research, and Reinvent” approach can be applied at all levels, ranging from the individual to international societies, to minimize the carbon footprint of endoscopy.

Histological remission is evolving as an important treatment target in UC. We aimed to develop a simple histological index, aligned to endoscopy, correlated with clinical outcomes, and suited to apply to an artificial intelligence (AI) system to evaluate inflammatory activity.MethodsUsing a set of 614 biopsies from 307 patients with UC enrolled into a prospective multicentre study, we developed the Paddington International virtual ChromoendoScopy ScOre (PICaSSO) Histologic Remission Index (PHRI). Agreement with multiple other histological indices and validation for inter-reader reproducibility were assessed. Finally, to implement PHRI into a computer-aided diagnosis system, we trained and tested a novel deep learning strategy based on a CNN architecture to detect neutrophils, calculate PHRI and identify active from quiescent UC using a subset of 138 biopsies.ResultsPHRI is strongly correlated with endoscopic scores (Mayo Endoscopic Score and UC Endoscopic Index of Severity and PICaSSO) and with clinical outcomes (hospitalisation, colectomy and initiation or changes in medical therapy due to UC flare-up). A PHRI score of 1 could accurately stratify patients’ risk of adverse outcomes (hospitalisation, colectomy and treatment optimisation due to flare-up) within 12 months. Our inter-reader agreement was high (intraclass correlation 0.84). Our preliminary AI algorithm differentiated active from quiescent UC with 78% sensitivity, 91.7% specificity and 86% accuracy.ConclusionsPHRI is a simple histological index in UC, and it exhibits the highest correlation with endoscopic activity and clinical outcomes. A PHRI-based AI system was accurate in predicting histological remission.

Background: A treat-to-target strategy, in which strictly defined treatment targets facilitate decision making in clinical practice, is advocated as an optimised management approach for some chronic disorders. The aim of the STARDUST trial was to assess whether a treat-to-target strategy with early endoscopy, regular biomarker and clinical symptom monitoring, and dose intensification for persistent inflammatory activity, was more successful in achieving endoscopic improvement at week 48 than a clinically driven maintenance strategy in patients with moderate-to-severe active Crohn's disease receiving ustekinumab. Methods: This open-label, multicentre, randomised phase 3b trial included adults with active, moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220–450 and Simple Endoscopic Score in Crohn's Disease [SES-CD] ≥3) for whom conventional therapy or one biologic therapy, or both, had failed. Patients received intravenous ustekinumab approximating 6 mg/kg at baseline and subcutaneous ustekinumab 90 mg at week 8. At week 16, patients with a CDAI improvement of 70 or more points from baseline were randomly assigned (1:1) to receive standard-of-care or treat-to-target maintenance treatment through week 48. Randomisation was balanced by using randomly permuted blocks and was stratified by biologic history status and baseline SES-CD score. All patients who signed informed consent, who were not screening failures, and who received at least one dose of study treatment were included in week 16 analyses. All patients included in week 16 analyses and randomly assigned to one of the maintenance treatment regimens were included in the week 48 efficacy and safety analyses (ie, on an intention-to-treat basis). Patients assigned to the treat-to-target arm received ustekinumab every 12 weeks or every 8 weeks based on SES-CD improvement from baseline and could escalate to every 4 weeks through week 48 if prespecified targets were missed. Patients assigned to the standard-of-care arm received ustekinumab every 12 weeks or every 8 weeks; those receiving treatment every 12 weeks could escalate per European labelling. The primary efficacy endpoint was endoscopic response at week 48 (SES-CD score ≥50% decrease from baseline), analysed by non-responder imputation. This trial is registered at ClinicalTrials.gov, NCT03107793, and is active but not recruiting. Findings: 498 patients received standard induction treatment, of whom 440 were randomly assigned to the treat-to-target group (n=219) or the standard-of-care group (n=221). At week 48, there was no significant difference in endoscopic response (83 [38%] of 219 patients vs 66 [30%] of 221 patients; p=0·087), endoscopic remission (25 [11%] vs 32 [15%]; p=0·334), mucosal healing (31 [14%] vs 37 [17%]; p=0·449), and clinical remission (135 [62%] vs 154 [70%]; p=0·072) between the two groups; clinical response was significantly lower in the treat-to-target group than in the standard-of-care group (149 [68%] vs 172 [78%]; p=0·020). Other endoscopic, clinical, and biomarker outcomes were generally not significantly different between groups. The most commonly reported treatment-emergent adverse events were nasopharyngitis (29 [13%] of 219 patients in the treat-to-target group vs 29 [13%] of 221 patients in the standard-of-care group), abdominal pain (23 [11%] vs 19 [9%]), arthralgia (24 [11%] vs 19 [9%]), and headache (24 [11%] vs 21 [10%]). Interpretation: Timely escalation of ustekinumab therapy for patients with Crohn's disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. Future studies need to confirm if some subgroups of patient might benefit from a treat-to-target strategy with ustekinumab. Funding: Janssen-Cilag.

ObjectiveThe COVID-19 pandemic has placed increased strain on healthcare systems worldwide with enormous reorganisation undertaken to support ‘COVID-centric’ services. Non-COVID-19 admissions reduced secondary to public health measures to halt viral transmission. We aimed to understand the impact of the response to COVID-19 on the outcomes of upper gastrointestinal (UGI) bleeds.Design/methodsA retrospective observational multicentre study comparing outcomes following endoscopy for UGI bleeds from 24 March 2020 to 20 April 2020 to the corresponding dates in 2019. The primary outcome was in-hospital survival at 30 days with secondary outcomes of major rebleeding within 30 days postprocedure and intervention at the time of endoscopy.Results224 endoscopies for 203 patients with UGI bleeds were included within this study. 19 patients were diagnosed with COVID-19. There was a 44.4% reduction in the number of procedures performed between 2019 and 2020. Endoscopies performed for UGI bleeds in the COVID-19 era were associated with an adjusted reduced 30-day survival (OR 0.25, 95% CI 0.08–0.67). There was no increased risk of major rebleeding or interventions during this era. Patients with COVID-19 did not have reduced survival or increased complication rates.ConclusionEndoscopy for UGI bleeds in the COVID-19 era is associated with reduced survival. No clear cause has been identified but we suspect that this is a secondary effect of the response to the COVID-19 pandemic. Urgent work is required to encourage the public to seek medical help if required and to optimise patient pathways to ensure that the best possible care is provided.

Background Vitamin D deficiency has been implicated in the pathogenesis of inflammatory bowel disease. Emerging literature suggests that optimization of vitamin D levels may be associated with improvements in disease activity and quality of life. We conducted a meta-analysis exploring the effect of vitamin D on serum 25-hydroxyvitamin D (s-25[OH]D) levels, clinical improvement, and biomarkers. Methods MEDLINE, EMBASE, the Cochrane Library, and sources for grey literature were searched from inception until September 2019. The primary outcome was s-25(OH)D mean differences. Heterogeneity was assessed using the χ 2 test and the I2 statistic. Review Manager software v. 5.3 was used. Results Twelve randomized controlled trials (n = 611) and 4 observational studies (n = 359) were included in the meta-analysis. On average, in the randomized controlled trials, vitamin D supplementation increased s-25(OH)D levels by 15.50 ng/mL (95% confidence interval [CI], 11.08-19.92, P ≤ 0.00001, I2 = 90%) and in observational studies they increased by 18.39 ng/mL (95% CI, 8.91-27.88, P = 0.0001, I2 = 82%). Subgroup analyses between vitamin D and placebo groups revealed that vitamin D increased s-25(OH)D by 14.85 ng/mL (95% CI, 9.96-19.73, P ≤ 0.00001, I2 = 90%) and when high doses of vitamin D were compared with low doses, high doses increased s-25(OH)D by 18.27 ng/mL (95% CI, 5.44-31.10, P = 0.005, I2 = 90%). The Harvey Bradshaw Index improved by –1.47 points (95% CI, –2.47 to –0.47, P = 0.004, I2 = 0%) and the high-sensitivity C-reactive protein decreased by –1.58 mg/L (95% CI, –2.95 to –0.21, P = 0.02, I2 = 0%). Conclusions Vitamin D supplementation in patients with IBD and vitamin D deficiency is effective at correcting vitamin D levels and is associated with improvement in clinical and biochemical disease activity scores.

The COVID-19 pandemic is putting unprecedented pressures on healthcare systems globally. Early insights have been made possible by rapid sharing of data from China and Italy. In the UK, we have rapidly mobilised inflammatory bowel disease (IBD) centres in order that preparations can be made to protect our patients and the clinical services they rely on. This is a novel coronavirus; much is unknown as to how it will affect people with IBD. We also lack information about the impact of different immunosuppressive medications. To address this uncertainty, the British Society of Gastroenterology (BSG) COVID-19 IBD Working Group has used the best available data and expert opinion to generate a risk grid that groups patients into highest, moderate and lowest risk categories. This grid allows patients to be instructed to follow the UK government’s advice for shielding, stringent and standard advice regarding social distancing, respectively. Further considerations are given to service provision, medical and surgical therapy, endoscopy, imaging and clinical trials.

Objective Enteroendocrine cells (EECs) survey the gut luminal environment and coordinate hormonal, immune and neuronal responses to it. They exhibit well-characterised physiological roles ranging from the control of local gut function to whole body metabolism, but little is known regarding the regulatory networks controlling their differentiation, especially in the human gut. The small molecule isoxazole-9 (ISX-9) has been shown to stimulate neuronal and pancreatic beta-cell differentiation, both closely related to EEC differentiation. Our aim was to use ISX-9 as a tool to explore EEC differentiation. Methods We investigated the effects of ISX-9 on EEC differentiation in mouse and human intestinal organoids, using real-time quantitative polymerase chain reaction (RT-qPCR), fluorescent-activated cell sorting, immunostaining and single-cell RNA sequencing. Results ISX-9 increased the number of neurogenin3-RFP (Ngn3)-positive endocrine progenitor cells and upregulated NeuroD1 and Pax4, transcription factors that play roles in mouse EEC specification. Single-cell analysis showed induction of Pax4 expression in a developmentally late Ngn3+ population of cells and potentiation of genes associated with progenitors biased toward serotonin-producing enterochromaffin (EC) cells. Further, we observed enrichment of organoids with functional EC cells that was partly dependent on stimulation of calcium signalling in a population of cells residing outside the crypt base. Inducible Pax4 overexpression, in ileal organoids, uncovered its importance as a component of early human endocrine specification and highlighted the potential existence of two major endocrine lineages, the early appearing enterochromaffin lineage and the later developing peptidergic lineage which contains classical gut hormone cell types. Conclusion Our data provide proof-of-concept for the controlled manipulation of specific endocrine lineages with small molecules, whilst also shedding new light on human EEC differentiation and its similarity to the mouse. Given their diverse roles, understanding endocrine lineage plasticity and its control could have multiple therapeutic implications., Graphical abstract Image 1, Highlights • ISX-9 promotes flux through the Ngn3 lineage and enriches it with enterochromaffin cells. • ISX-9 engages an enterochromaffin biased transcriptional programme in endocrine fated cells. • Enterochromaffin bias is partly dependent on calcium signalling in progenitor cells. • ISX-9 reveals conserved gut endocrine specification between mouse and human. • Pax4 overexpression in human ileum organoids mimics the effects of ISX-9 on EC bias.

Background There is a trend toward organ conservation in the management of rectal tumors. However, there is no consensus on standardized investigations to guide treatment. Objective We report the value of multimodal endoscopic assessment (white light, magnification chromoendoscopy and narrow band imaging, selected colonoscopic ultrasound) for rectal early neoplastic tumors to inform treatment decisions. Design This was a retrospective study. Setting The study was conducted in a tertiary referral unit for interventional endoscopy and early colorectal cancer. Patients A total of 296 patients referred with rectal early neoplastic tumors were assessed using standardized multimodal endoscopic assessment and classified according to risk of harboring invasive cancer. Main outcome measures Sensitivity, specificity, positive and negative predictive values of multimodal endoscopic assessment, and previous biopsy to predict invasive cancer were calculated and treatment outcomes reported. Results After multimodal endoscopic assessment, lesions were classified as invasive cancer, at least deep submucosal invasion (n = 65); invasive cancer, superficial submucosal invasion or high risk of covert cancer (n = 119); or low risk of covert cancer (n = 112). Sensitivity, specificity, positive predictive values, and negative predictive values of multimodal endoscopic assessment for diagnosing invasive cancer, deep submucosal invasion, were 77%, 98%, 93%, and 93%. The combined classification of all lesions with invasive cancer or high risk of covert cancer had a negative predictive value of 96% for invasive cancer on final histopathology. Sensitivity of previous biopsy was 37%. A total of 47 patients underwent radical surgery and 33 transanal endoscopic microsurgery. No patients without invasive cancer were subjected to radical surgery; 222 patients initially underwent endoscopic resection. Of the 203 without deep submucosal invasion, 95% avoided surgery and were free from recurrence at last follow-up. Limitations This was a retrospective study from a tertiary referral unit. Conclusions Standardized multimodal endoscopic assessment guides rational treatment decisions for rectal tumors resulting in organ-conserving treatment for all patients without deep submucosal invasive cancer. See Video Abstract at http://links.lww.com/DCR/B133. LA EVALUACION ENDOSCOPICA MULTIMODAL COMO GUIA DE DECISIONES EN EL TRATAMIENTO DE TUMORES RECTALES NEOPLASICOS PRECOCES: La tendencia actual es la preservacion del organo en el manejo de los tumores de rectao. Sin embargo, no hay consenso sobre las investigaciones estandar para guiar dicho tratamiento.Presentamos los valores de la evaluacion endoscopica multimodal (luz blanca, cromoendoscopia de aumento, imagen de banda estrecha y ecografia colonoscopica seleccionada) para tumores rectales neoplasicos tempranos y asi notificar las decisiones sobre el tratamiento.Estudio retrospectivo.El estudio se realizo en una unidad de referencia terciaria para endoscopia intervencionista y cancer colorrectal temprano.Se evaluaron 296 pacientes referidos con tumores neoplasicos precoces de recto mediante una evaluacion endoscopica multimodal estandarizada y se clasificaron de acuerdo al riesgo de albergar un cancer invasivo.Se calcularon la sensibilidad, la especificidad, los valores predictivos positivos y negativos de la evaluacion endoscopica multimodal y la biopsia previa para predecir el cancer invasivo y se notificaron los resultados para el tratamiento.Despues de la evaluacion endoscopica multimodal, las lesiones se clasificaron como: cancer invasive (al menos invasion submucosa profunda n = 65); cancer invasive (invasion submucosa superficial o alto riesgo de cancer encubierto n = 119) y finalmente aquellos de bajo riesgo de cancer encubierto (n = 112). La sensibilidad, la especificidad, los valores predictivos positivos y negativos de la evaluacion endoscopica multimodal para el diagnostico de cancer invasivo, la invasion submucosa profunda fueron 77%, 98%, 93% y 93% respectivamente. La clasificacion combinada de todas las lesiones con cancer invasivo o de alto riesgo de cancer encubierto tuvo un VPN del 96% para el cancer invasivo en la histopatologia final. La sensibilidad fue de 37% en todas las biopsias previas. 47 pacientes fueron sometidos a cirugia radical, 33 por microcirugia endoscopica transanal. Ningun paciente sin cancer invasivo fue sometido a cirugia radical. Inicialmente, 222 pacientes fueron sometidos a reseccion endoscopica. De los 203 sin invasion submucosa profunda, el 95% evito la cirugia y no tuvieron recurrencia en el ultimo seguimiento.Estudio retrospectivo de una unidad de referencia terciaria.La evaluacion endoscopica multimodal estandarizada guia las decisiones racionales de tratamiento para los tumores rectales que resultan en un tratamiento conservador de organos para todos los pacientes sin cancer invasivo submucoso profundo. Consulte Video Resumen en http://links.lww.com/DCR/B133.

INTRODUCTION: With increasing advances in minimally invasive endoscopic therapies and endoscopic resection techniques for luminal disease, there is an increased risk of post-procedure bleeding. This can contribute to significant burden on patient’s quality of life and health resources when reintervention is required. Hemospray (Cook Medical, North Carolina, USA) is a novel haemostatic powder licensed for gastrointestinal bleeding. The aim of this single-arm, prospective, non-randomised multicentre international study is to look at outcomes in patients with upper gastrointestinal bleeds following elective endoscopic therapy treated with Hemospray to achieve haemostasis. METHODS: Data was prospectively collected on the use of Hemospray from 16 centres (January 2016–November 2019). Hemospray was used during the presence of progressive intraprocedural bleeding post-endoscopic therapy as a monotherapy, dual therapy with standard haemostatic techniques or rescue therapy once standard methods had failed. Haemostasis was defined as the cessation of bleeding within 5 min of the application of Hemospray. Re-bleeding was defined as a sustained drop in haemoglobin (>2 g/l), haematemesis or melaena with haemodynamic instability after the index endoscopy. RESULTS: A total of 73 patients were analysed with bleeding post-endoscopic therapy. The median Blatchford score at baseline was five (interquartile range 0–9). The median Rockall score was six (interquartile range 5–7). Immediate haemostasis following the application of Hemospray was achieved in 73/73 (100%) of patients. Two out of 57 (4%) had a re-bleed post-Hemospray, one was following oesophageal endoscopic mucosal resection and the other post-duodenal endoscopic mucosal resection. Both patients had a repeat endoscopy and therapy within 24 h. Re-bleeding data was missing for 16 patients, and mortality data was missing for 14 patients. There were no adverse events recorded in association with the use of Hemospray. CONCLUSION: Hemospray is safe and effective in achieving immediate haemostasis following uncontrolled and progressive intraprocedural blood loss post-endoscopic therapy, with a low re-bleed rate.

ObjectiveFaecal calprotectin (fCAL) is an established marker of intestinal inflammation in inflammatory bowel disease (IBD). Disproportionally high fCAL levels, for the severity of intestinal inflammation, have been previously observed in primary sclerosing cholangitis associated IBD (PSC-IBD). The aim of this study was to test the hypothesis that fCAL is a marker of biliary injury in PSC-IBD.MethodsWe used two cohorts: (1) post hoc analysis of a colonoscopic surveillance study allowing correlation of fCAL to endoscopic severity as measured by the ulcerative colitis endoscopic index of severity (UCEIS) in PSC-IBD (n=20) and ulcerative colitis (UC, n=20) and (2) prospective recruitment of patients attending for endoscopic retrograde cholangiopancreatography allowed the correlation of fCAL to biliary calprotectin (n=8).ResultsA strong correlation was seen between fCAL and UCEIS in UC (r=0.821, 95% CI (0.585 to 0.929), pConclusionfCAL is a surrogate marker for biliary inflammation in PSC-IBD.Trial registration numberNCT02543021.

Climate change and the destruction of ecosystems by human activities are among the greatest challenges of the 21st century and require urgent action. Health care activities significantly contribute to the emission of greenhouse gases and waste production, with gastrointestinal (GI) endoscopy being one of the largest contributors. This Position Statement aims to raise awareness of the ecological footprint of GI endoscopy and provides guidance to reduce its environmental impact. The European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) outline suggestions and recommendations for health care providers, patients, governments, and industry. Main statements 1 GI endoscopy is a resource-intensive activity with a significant yet poorly assessed environmental impact. 2 ESGE-ESGENA recommend adopting immediate actions to reduce the environmental impact of GI endoscopy. 3 ESGE-ESGENA recommend adherence to guidelines and implementation of audit strategies on the appropriateness of GI endoscopy to avoid the environmental impact of unnecessary procedures. 4 ESGE-ESGENA recommend the embedding of reduce, reuse, and recycle programs in the GI endoscopy unit. 5 ESGE-ESGENA suggest that there is an urgent need to reassess and reduce the environmental and economic impact of single-use GI endoscopic devices. 6 ESGE-ESGENA suggest against routine use of single-use GI endoscopes. However, their use could be considered in highly selected patients on a case-by-case basis. 7 ESGE-ESGENA recommend inclusion of sustainability in the training curricula of GI endoscopy and as a quality domain. 8 ESGE-ESGENA recommend conducting high quality research to quantify and minimize the environmental impact of GI endoscopy. 9 ESGE-ESGENA recommend that GI endoscopy companies assess, disclose, and audit the environmental impact of their value chain. 10 ESGE-ESGENA recommend that GI endoscopy should become a net-zero greenhouse gas emissions practice by 2050.

Aki Kawakami,1,2 Makoto Tanaka,2 Lee Meng Choong,1 Reiko Kunisaki,3 Shin Maeda,4 Ingvar Bjarnason,1 Bu’Hussain Hayee1 1Department of Gastroenterology, King’s College Hospital, London, UK; 2Department of Critical and Invasive-Palliative Care Nursing, Graduate School of Health Care Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Japan; 3Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Yokohama, Japan; 4Department of Gastroenterology, Yokohama City University Graduate School of Medicine, Yokohama, JapanCorrespondence: Makoto Tanaka, Department of Critical and Invasive-Palliative Care Nursing, Graduate School of Health Care Sciences, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan, Tel +81-3-5803-4507, Fax +81-3-5803-4507, Email tanaka.cc@tmd.ac.jpPurpose: Non-adherence to medication was reported by 28% of Japanese patients with ulcerative colitis, but in the United Kingdom, patients with inflammatory bowel disease have lower medication adherence, which increases clinical relapse risk. The objective of this study was to compare medication adherence among patients with ulcerative colitis in Japan with previously reported results and patients in the United Kingdom.Patients and Methods: This cross-cultural comparison study investigated medication adherence among 100 ulcerative colitis patients in the United Kingdom and 432 ulcerative colitis patients in Japan. Adherence was assessed using The Morisky Medication Adherence Scale-8 questionnaire. Patient clinical features were collected from medical records and the questionnaire. Distribution of responses for each item, questionnaire total score, difference in ratio for each item between Japanese and UK patients, and difference in percentage of low/medium/high adherence between Japanese and UK patients were compared.Results: The proportion of low/medium or high adherence was significantly different between countries (42.6% and 7.4% [Japan] vs 24.0% and 76.0% [United Kingdom]; p< 0.01). Significantly more Japanese patients reported taking medication correctly the day before the questionnaire compared with UK patients.Conclusion: UK patients were more likely to not take medication when they felt their symptoms were under control compared with Japanese patients. UK patients perceived it was more difficult to remember to take the medication than Japanese patients. This study highlights culturally sensitive medication-taking behaviors in Japanese and UK patients with ulcerative colitis.Keywords: cross-cultural comparison, self-management, race, inflammatory bowel disease

Infection prevention and control (IPC) measures put in place during the first phases of the COVID-19 pandemic were effective in reducing endoscopy-related transmission while allowing recovery of activity. In late 2020 a novel, more infectious, SARS-CoV-2 variant (VOC 202012/01) was associated with a second ’surge' or acceleration phase in the UK. We sought to measure whether pre-existing IPC guidance would be sufficient to prevent transmission in this scenario. Prospective data were collected from eight UK centres for n=2440 procedures. Pre-endoscopy, nine (0.37%) asymptomatic patients were positive for SARS-CoV-2 by nasopharyngeal swab (NPS) testing and their procedures deferred. Post endoscopy, 30 (1.27%) developed symptoms suspicious for COVID-19, with 15 (0.65%) testing positive on NPS. Three (0.12%) cases were attributed to potential transmission from endoscopy attendance. All 15 patients recovered fully requiring only community treatment. Although we report cases potentially transmitted by endoscopy attendance in this latest study, the risk of COVID-19 transmission following outpatient endoscopy remains very low. Thus, IPC measures developed in earlier pandemic phases appear robust, but our data emphasise the need for vigilance and strict adherence to these measures in order to optimally protect both patients and staff. The effects of the COVID-19 pandemic continue to extend beyond direct care of affected patients,1 particularly impacting outpatient diagnostics including GI endoscopy. Considerable concerns remain around the potential impact on detection of, and survival from, significant disease such as cancer.2 3 In mid-2020, a pandemic deceleration phase4 in the UK led to a period of intense ‘restart and recovery’ activity in endoscopy to mitigate the effects of delayed or cancelled procedures. This was supported by professional society guidance on the development of ‘COVID-minimised’ or ‘green’ pathways with NPS testing of patients before their attendance for the procedure.5–7 Activity was limited by the impact on endoscopy staff …

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the efficacy and safety of a 6‐thioguanine nucleotide (6‐TGN) metabolite‐based dosing strategy for maintenance of remission using azathioprine or mercaptopurine in Crohn's disease and ulcerative colitis.

Background and study aims Scoring endoscopic disease activity in colitis represents a complex task for artificial intelligence (AI), but is seen as a worthwhile goal for clinical and research use cases. To date, development attempts have relied on large datasets, achieving reasonable results when comparing normal to active inflammation, but not when generating subscores for the Mayo Endoscopic Score (MES) or ulcerative colitis endoscopic index of severity (UCEIS). Patients and methods Using a multi-task learning framework, with frame-by-frame analysis, we developed a machine-learning algorithm (MLA) for UCEIS trained on just 38,124 frames (73 patients with biopsy-proven ulcerative colitis). Scores generated by the MLA were compared to consensus scores from three independent human reviewers. Results Accuracy and agreement (kappa) were calculated for the following differentiation tasks: (1) normal mucosa vs active inflammation (UCEIS 0 vs ≥ 1; accuracy 0.90, κ = 0.90); (2) mild inflammation vs moderate-severe (UCEIS 0–3 vs ≥ 4; accuracy 0.98, κ = 0.96); (3) generating total UCEIS score (κ = 0.92). Agreement for UCEIS subdomains was also high (κ = 0.80, 0.83 and 0.88 for vascular pattern, bleeding and erosions respectively). Conclusions We have demonstrated that, using modified data science techniques and a relatively smaller datasets, it is possible to achieve high levels of accuracy and agreement with human reviewers (in some cases near-perfect), for AI in colitis scoring. Further work will focus on refining this technique, but we hope that it can be used in other tasks to facilitate faster development.

As the incidence of inflammatory bowel disease (IBD) rises and the global population ages, the number of older people living with these conditions will inevitably increase. The challenges posed by comorbid conditions, polypharmacy, the unintended consequences of long-term treatment and the real but often underestimated mismatch between chronological and biological ages underpin management. Significantly, there may be differences in disease characteristics, presentation and management of an older patient with IBD, together with other unique challenges. Importantly, clinical trials often exclude older patients, so treatment decisions are frequently pragmatic, extrapolated from a number of sources of evidence and perhaps primarily dictated by concerns around adverse effects. This review aimed to discuss the epidemiology, clinical features and considerations with management in older patients with IBD.

Background and aim Acute gastrointestinal bleeding carries poor outcomes unless prompt endoscopic hemostasis is achieved. Mortality in these patients remains significant. Hemospray is a novel intervention that creates a mechanical barrier over bleeding sites. We report the largest dataset of patient outcomes after treatment with Hemospray from an international multicenter registry. Patients and methods Prospective data (Jan 2016-May 2018) from 12 centers across Europe were collected. Immediate hemostasis was defined as endoscopic cessation of bleeding within 5 min after application of Hemospray. Rebleeding was defined as subsequent drop in hemoglobin, hematemesis, persistent melena with hemodynamic compromise post-therapy. Results Three hundred and fourteen cases were recruited worldwide (231 males, 83 females). Median pretreatment Blatchford score was 11 (IQR: 8-14) and median complete Rockall score (RS) was 7 (IQR: 6-8) for all patients. Peptic ulcer disease (PUD) was the most common pathology (167/314 = 53%) and Forrest Ib the most common bleed type in PUD (100/167 = 60%). 281 patients (89.5%) achieved immediate hemostasis after successful endoscopic therapy with Hemospray. Rebleeding occurred in 29 (10.3%) of the 281 patients who achieved immediate hemostasis. Seven-day and 30-day all-cause mortality were 11.5% (36/314) and 20.1% (63/314), respectively (lower than the predicted rates as per the RS). Similar hemostasis rates were noted in the Hemospray monotherapy (92.4%), combination therapy (88.7%) and rescue therapy (85.5%) groups. Conclusions These data show high rates of immediate hemostasis overall and in all subgroups. Rebleeding and mortality rates were in keeping/lower than predicted rates.

The latest state of the art technological innovations have led to a palpable progression in endoscopic imaging and may facilitate standardisation of practice. One of the most rapidly evolving modalities is artificial intelligence with recent studies providing real-time diagnoses and encouraging results in the first randomised trials to conventional endoscopic imaging. Advances in functional hypoxia imaging offer novel opportunities to be used to detect neoplasia and the assessment of colitis. Three-dimensional volumetric imaging provides spatial information and has shown promise in the increased detection of small polyps. Studies to date of self-propelling colonoscopes demonstrate an increased caecal intubation rate and possibly offer patients a more comfortable procedure. Further development in robotic technology has introduced ex vivo automated locomotor upper gastrointestinal and small bowel capsule devices. Eye-tracking has the potential to revolutionise endoscopic training through the identification of differences in experts and non-expert endoscopist as trainable parameters. In this review, we discuss the latest innovations of all these technologies and provide perspective into the exciting future of diagnostic luminal endoscopy.

BACKGROUND: People with cystic fibrosis (CF) report a variety of gastrointestinal (GI) symptoms, independent of pancreatic enzyme insufficiency (PEI), reminiscent of other chronic GI disorders. There are currently no accepted or validated assessment tools and neither the range, frequency nor severity of GI symptoms has been systematically described in CF. We present results of a cross-sectional study using established tools and compare them to current measures of quality of life (QOL). METHODS: Consecutive patients attending specialist CF appointments were asked to complete questionnaires including the GI Symptom Rating Scale (GSRS); Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) and Cystic Fibrosis Questionnaire (CFQ-R). Questionnaire terminology was altered to replace references to ‘IBS’ with ‘GI symptoms’. RESULTS: In total, 107 patients were recruited (mean age, 27.8 ± 9.6 years; 60 female), and 94 (88%) had PEI. Body mass index was 22.1 ± 3.6 kg/m(2), forced expiratory volume in one second was 59 + 27.7% predicted. Fifty-three (49.5%) were p.Phe508del homozygous. Overall 69/107 (65%) reported significant GI symptoms independent of PEI or adherence to pancreatic enzyme replacement therapy (PERT), with the four most frequent being attributable to the lower GI tract: bloating/distension, flatulence, abdominal pain and borborygmi (gurgling). There was no numerical correlation between any CFQ-R domain (particularly Digestion domain) and GSRS or SSS. CONCLUSION: This is the first systematic study measuring GI symptoms in CF using validated GI tools. Symptoms are not related to PERT or genotype and appear to be captured well by the GSRS. Further research will study longitudinal changes with treatment, and therapeutic trials in CF may use these tools to demonstrate a positive impact on ‘non-respiratory’ symptoms and QOL.

Background: The duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months. Methods: International multicentre, open-label study. Patients (BMI 24-40) with T2D (HbA1c 59-86 mmol/mol (7.5%-10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction. Results: Forty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (-10±2 mmol/mol (-0.9%±0.2%), p, SCOPUS: ar.j, info:eu-repo/semantics/published

Almost any colorectal superficial neoplastic lesion can be treated by endoscopic resection (ER) but very little is known about outcomes of ER leaving circumferential or near-circumferential mucosal defects. We report the outcomes of ER leaving ≥ 75% circumferential mucosal defects performed in a western expert centre. Five hundred eighty-seven ERs of large colorectal lesions ≥ 20 mm were grouped according to the extent of the mucosal defect and comparisons made between those with