James F. Brown

The COVID-19 pandemic has had a profound impact on provision of endoscopy services globally as staff and real estate were repurposed. As we begin to recover from the pandemic, a cohesive international approach is needed, and guidance on how to resume endoscopy services safely to avoid unintended harm from diagnostic delays. The aim of these guidelines is to provide consensus recommendations that clinicians can use to facilitate the swift and safe resumption of endoscopy services. An evidence-based literature review was carried out on the various strategies used globally to manage endoscopy during the COVID-19 pandemic and control infection. A modified Delphi process involving international endoscopy experts was used to agree on the consensus statements. A threshold of 80% agreement was used to establish consensus for each statement. 27 of 30 statements achieved consensus after two rounds of voting by 34 experts. The statements were categorised as pre-endoscopy, during endoscopy and postendoscopy addressing relevant areas of practice, such as screening, personal protective equipment, appropriate environments for endoscopy and infection control precautions, particularly in areas of high disease prevalence. Recommendations for testing of patients and for healthcare workers, appropriate locations of donning and doffing areas and social distancing measures before endoscopy are unique and not dealt with by any other guidelines. This international consensus using a modified Delphi method to produce a series of best practice recommendations to aid the safe resumption of endoscopy services globally in the era of COVID-19.

Background Studies examining the impact of training modules on characterization of diminutive colonic polyps (DCP) show varying results. Aim We aimed to assess the impact of a novel web-based training module on the accuracy of in vivo characterization of DCPs using different imaging modalities. Differences between groups with varying degrees of endoscopic experience were also assessed. Methods In total, 90 images of 30 DCPs viewed with high definition white light (HDWL), i-Scan, and indigo carmine chromoendoscopy were included in an online test module. Testing was undertaken before and after completing a novel web-based in vivo characterization training module. In total, 21 subjects (medical students (MS), gastroenterology trainees (GT), and gastroenterology consultants (GC)) undertook the tests and training module. Results No statistically significant difference in overall accuracy was found between the three groups either pre- (MS 59.1 %, GR 65.7 %, GC 62.4 %, P = ns for all three comparisons) or post-training (MS 69.2 %, GR 71.1 %, GC 71.3 %, P = ns for all three comparisons). Accuracy improved significantly for all three groups post-training (P < 0.001) as did interobserver agreement. No significant differences in accuracy between modalities were found pre-training (HDWL 64.8 %, i-Scan 60.0 %, chromoendoscopy 62.2 %, P = ns). Post-training accuracy with HDWL and chromoendoscopy was better than with i-Scan (HDWL 72.9 % vs i-Scan 65.1 %, P = 0.002; i-Scan 65.1 % vs chromoendoscopy 73.7 %, P < 0.001). The proportion of high confidence predictions increased from 25.7 % to 41.5 %, with a high confidence prediction accuracy of 81.7 %. Conclusions Skills for in vivo characterization of DCPs are not acquired through endoscopic experience alone. A novel web-based training intervention results in modest improvements in accuracy with further improvements likely to require more prolonged training.

Gastrointestinal (GI) motility disorders such as irritable bowel syndrome (IBS) can occur when coordinated smooth muscle contractility is disrupted. Potassium (K⁺) channels regulate GI smooth muscle tone and are key to GI tract relaxation, but their molecular and functional phenotypes are poorly described. Here we define the expression and functional roles of mechano-gated K_2P channels in mouse ileum and colon. Expression and distribution of the K_2P channel family were investigated using quantitative RT-PCR (qPCR), immunohistochemistry and confocal microscopy. The contribution of mechano-gated K_2P channels to mouse intestinal muscle tension was studied pharmacologically using organ bath. Multiple K_2P gene transcripts were detected in mouse ileum and colon whole tissue preparations. Immunohistochemistry confirmed TREK-1 expression was smooth muscle specific in both ileum and colon, whereas TREK-2 and TRAAK channels were detected in enteric neurons but not smooth muscle. In organ bath, mechano-gated K_2P channel activators (Riluzole, BL-1249, flufenamic acid, and cinnamyl 1-3,4-dihydroxy-alpha-cyanocinnamate) induced relaxation of KCl and CCh pre-contracted ileum and colon tissues and reduced the amplitude of spontaneous contractions. These data reveal the specific expression of mechano-gated K_2P channels in mouse ileum and colon tissues and highlight TREK-1, a smooth muscle specific K_2P channel in GI tract, as a potential therapeutic target for combating motility pathologies arising from hyper-contractility.

Gastrointestinal (GI) motility disorders such as irritable bowel syndrome (IBS) can occur when coordinated smooth muscle contractile activity is disrupted, and little is known about the molecular identity of the potassium (K ⁺ ) channels that promote GI tract relaxation. Thus, elucidating the expression and function of the potassium channels could reveal novel therapeutic targets to treat spasmodic gut disorders. Here we utilise quantitative RT‐PCR (qPCR), organ bath pharmacology and immunohistochemistry to determine the expression and contribution of K _2P channel subtypes in regulating mouse intestinal motility. For isolated organ bath pharmacology, distal ileum and colon segments (2–3cm) were dissected from adult C57BL/6 mice, mounted on an aerator and suspended from a force transducer in an organ bath containing Krebs solution at 32°C. Tension generated from longitudinal muscle contraction was recorded using LabChart® software (AD Instruments). The effects of a variety mechano‐gated K _2P channel activators were assessed on sub‐threshold 10 μM carbachol (CCh) or 60 mM KCl pre‐contracted tissue. Data are displayed as mean ± SEM ( n = 6, unless stated) and statistical analysis performed by t‐test with significance at p < 0.05. Immunohistochemistry and confocal microscopy was performed on perfusion‐fixed (1% PFA) whole‐mount preparations of the mouse distal ileum and colon. We first performed a qPCR analysis for 14 K _2P channel genes on independent ileum and colon sections from 3 animals. KCNK1 (TWIK‐1) and KCNK5 (TASK‐2) showed the greatest relative expression both in ileum and colon, with KCNK2 (TREK‐1) also prominent in ileum but not colon. Given the pause pharmacology for TWIK‐1 and TASK‐2, and previous research highlighting TREK‐1 functionality in colon (1) we pursued the expression pattern and functional role of mechano‐gated K _2P channels in gut. 100 μM riluzole caused a significant relaxation in CCh pre‐contracted muscle tension in both ileum (37.1 ± 3.9 %, n = 14, p n = 11, p =0.0023). Relaxation induced by 60 μM BL‐1249 and the structurally related fluflenamic acid (100 μM) differed between ileum and colon; 93.1 ± 1.2 % vs 56.1 ± 4.2 % ( p p = 0.0108) respectively. Immunoreactivity for the TREK‐1 channel was widely distributed across both circular smooth muscle and longitudinal smooth muscle in ileum and colon. Immunoreactivity for the TREK‐2 channel was located on neurons of both the myenteric and submucosal plexuses in ileum and colon, and was associated with NOS, Chat and calretinin‐immunopositive myenteric plexus neurons. TRAAK channel immunoreactivity was evident on NOS, Chat and calretinin‐immunopositive neurons located in both myenteric and submucosal plexus neurons in ileum and colon. These data reveal the molecular and functional diversity of the mechano‐gated K _2P channels within the mouse GI tract and highlight the K _2P channels as potential therapeutic targets for treating GI motility disorders.

Background and study aims Acetic acid chromoendoscopy (AAC) enhances the ability to correctly identify Barrett’s neoplasia, and is increasingly used by both expert and nonexpert endoscopists. Despite its increasing use, there is no validated training strategy to achieve competence. The aims of our study were to develop a validated training tool in AAC-assisted lesion recognition, to assess endoscopists’ baseline knowledge of AAC-assisted lesion recognition, and to evaluate the efficacy and impact of this training tool. Methods A validated assessment of 40 images and 20 videos was developed. A total of 13 endoscopists with experience of Barrett’s endoscopy but no formal training in AAC were recruited to the study. Participants underwent: baseline assessment 1, online training, assessment 2, interactive seminar, assessment 3. Results Baseline assessment demonstrated a sensitivity of 83 % and a negative predictive value (NPV) of 83 %. The online training intervention significantly improved sensitivity to 95 % and NPV to 94 % (P < 0.01). Further improvement was seen after a 1-day interactive seminar including live cases, with sensitivity increasing to 98 % and NPV to 97 %. Conclusions The data demonstrate the need for training in AAC-assisted lesion recognition as baseline performance, even by Barrett’s experts, was poor. The online training and testing tool for AAC for Barrett’s neoplasia was successfully developed and validated. The training intervention improved performance of endoscopists to meet ASGE PIVI standards. The training tool increases the endoscopist’s degree of confidence in the use of AAC. The training tool also leads to shift in attitudes of endoscopists from Seattle protocol towards AAC-guided biopsy protocol for Barrett’s surveillance.

Background and study aims: Mucosal views can be impaired by residual bubbles and mucus during gastroscopy. This study aimed to determine whether a pre-gastroscopy drink containing simethicone and N-acetylcysteine improves mucosal visualisation. Patients and methods: We conducted a randomized controlled trial recruiting 126 subjects undergoing routine gastroscopy. Subjects were randomized 1:1:1 to receive: A—pre-procedure drink of water, simethicone and N-acetylcysteine (NAC); B—water alone; or C—no preparation. Study endoscopists were blinded to group allocation. Digital images were taken at 4 locations (lower esophagus/upper gastric body/antrum/fundus), and rated for mucosal visibility (MV) using a 4-point scale (1 = best, 4 = worst) by 4 separate experienced endoscopists. The primary outcome measure was mean mucosal visibility score (MVS). Secondary outcome measures were procedure duration and volume of fluid flush required to achieve adequate mucosal views. Results: Mean MVS for Group A was significantly better than for Group B (1.35 vs 2.11, P < 0.001) and Group C (1.35 vs 2.21, P < 0.001). Mean flush volume required to achieve adequate mucosal views was significantly lower in Group A than Group B (2.0 mL vs 31.5 mL, P = 0.001) and Group C (2.0 mL vs 39.2 mL P < 0.001). Procedure duration did not differ significantly between any of the 3 groups. MV scores at each of the 4 locations demonstrated significantly better mucosal visibility in Group A compared to Group B and Group C (P < 0.0025 for all comparisons). Conclusions: A pre-procedure drink containing simethicone and NAC significantly improves mucosal visibility during gastroscopy and reduces the need for flushes during the procedure. Effectiveness in the lower esophagus demonstrates potential benefit in Barrett’s oesophagus surveillance gastroscopy.

The enteric nervous system (ENS) provides the intrinsic neural control of the gastrointestinal tract (GIT) and regulates virtually all GI functions. Altered neuronal activity within the ENS underlies various GI disorders with stress being a key contributing factor. Thus, elucidating the expression and function of the neurotransmitter systems, which determine neuronal excitability within the ENS, such as the GABA-GABA_A receptor (GABA_AR) system, could reveal novel therapeutic targets for such GI disorders. Molecular and functionally diverse GABA_ARs modulate rapid GABAergic-mediated regulation of neuronal excitability throughout the nervous system. However, the cellular and subcellular GABA_AR subunit expression patterns within neurochemically defined cellular circuits of the mouse ENS, together with the functional contribution of GABA_AR subtypes to GI contractility remains to be determined. Immunohistochemical analyses revealed that immunoreactivity for the GABA_AR gamma (γ) 2 and alphas (α) 1, 2, 3 subunits was located on somatodendritic surfaces of neurochemically distinct myenteric plexus neurons, while being on axonal compartments of submucosal plexus neurons. In contrast, immunoreactivity for the α4–5 subunits was only detected in myenteric plexus neurons. Furthermore, α-γ2 subunit immunoreactivity was located on non-neuronal interstitial cells of Cajal. In organ bath studies, GABA_AR subtype-specific ligands had contrasting effects on the force and frequency of spontaneous colonic longitudinal smooth muscle contractions. Finally, enhancement of γ2-GABA_AR function with alprazolam reversed the stress-induced increase in the force of spontaneous colonic contractions. The study demonstrates the molecular and functional diversity of the GABA_AR system within the mouse colon providing a framework for developing GABA_AR-based therapeutics in GI disorders.

The polyunsaturated fatty acids (PUFA) arachidonic acid (AA, n-6) and eicosapentaenoic acid (EPA, n-3) are precursors of eicosanoids and other lipid mediators which have critical roles in inflammation. The mediators formed from the different PUFA have different potencies. We hypothesised that metabolic changes associated with colonic mucosal inflammation would modify the bioavailability of the eicosanoid precursors AA and EPA. Colonic mucosa biopsies were obtained from patients with ulcerative colitis and from matched controls. Inflammation was graded endoscopically and histologically. Esterified and non-esterified fatty acids were determined within the biopsies using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, respectively. Biopsy samples were collected from 69 UC patients (54 providing both inflamed and non-inflamed mucosa) and 69 controls. Inflamed mucosa had higher AA (p<0.001) and lower EPA (p<0.010) contents and a higher AA:EPA ratio (p<0.001). Inflamed mucosa also had higher docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) and lower linoleic acid (LA) and α-linolenic acid (α-LNA) contents (all p<0.001), compared to non-inflamed and controls. There were significant correlations between severity of inflammation and contents of AA, DPA and DHA (positive correlations) and of LA, α-LNA and EPA (negative correlations). Higher AA, AA:EPA ratio, DPA and DHA and lower LA, α-LNA and EPA are seen in inflamed mucosa in UC and correlate with severity of inflammation. This suggests an alteration in fatty acid metabolism in the inflamed gut mucosa, which may offer novel targets for intervention and should be considered if nutritional strategies are used.

Background: There is growing evidence that indigo carmine chromoendoscopy is effective for the in vivo diagnosis of colonic polyps. However, the impact of colonoscope resolution on diagnostic accuracy has not been investigated.Objective: We aimed to compare the effectiveness of in vivo diagnosis of small colonic polyps using indigo carmine dye spray with standard‐definition and high‐definition colonoscopes.Methods: Procedures were performed using Fujinon colonoscopes and EPX 4400 processor. Fujinon standard‐definition (SD) and high‐definition (HD) colonoscopes were used, with the endoscopist blinded to colonoscope definition. Polyps <10 mm were assessed using 0.2% indigo carmine dye spray, with the predicted diagnosis recorded. In each case the kind of colonoscope (SD or HD) was recorded. Polyps were removed and sent for histological analysis, with the pathologist blinded to the diagnosis made by the endoscopist. The predicted diagnosis was compared with the true histology to calculate the accuracy, sensitivity and specificity of in vivo assessment using either SD or HD scopes.Results: In total 237 polyps <10 mm in size were examined. There was no statistically significant difference for any of the measured parameters between SD and HD assessments, with an accuracy, sensitivity and specificity of 89%, 91% and 87% with SD colonoscopes and 92%, 96% and 84% with HD colonoscopes.Conclusions: The accuracy of in vivo assessment of small colonic polyps with indigo carmine dye spray is excellent with standard‐definition colonoscopes and is not improved with high‐definition colonoscopes.