Establishment of Standards for the Referral of Large Non-Pedunculated Colorectal Polyps: An International Expert Consensus Using a Modified Delphi Process.

BACKGROUND AND AIMS: Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large non-pedunculated colorectal polyps are often referred to expert centres for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of our study was to establish minimum expected standards for the referral of LNPCP for potential ER. METHODS: A Delphi methodology was employed to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and three rounds of surveys were conducted to achieve consensus, with quantitative and qualitative data analysed for each round. RESULTS: A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographics, relevant medications, lesion factors, photodocumentation and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements ranged from 7.04 to 9.29 out of 10, with high percentages of experts considering most statements as a very high priority. Subgroup analysis by continent revealed some variations in consensus rates among experts from different regions. CONCLUSION: The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.

The Toronto Upper Gastrointestinal Cleaning Score: a prospective validation study.

BACKGROUND : Assessment of mucosal visualization during esophagogastroduodenoscopy (EGD) can be improved with a standardized scoring system. To address this need, we created the Toronto Upper Gastrointestinal Cleaning Score (TUGCS). METHODS : We developed the TUGCS using Delphi methodology, whereby an international group of endoscopy experts iteratively rated their agreement with proposed TUGCS items and anchors on a 5-point Likert scale. After each Delphi round, we analyzed responses and refined the TUGCS using an 80 % agreement threshold for consensus. We used the intraclass correlation coefficient (ICC) to assess inter-rater and test-retest reliability. We assessed internal consistency with Cronbach's alpha and item-total and inter-item correlations with Pearson's correlation coefficient. We compared TUGCS ratings with an independent endoscopist's global rating of mucosal visualization using Spearman's ρ. RESULTS : We achieved consensus with 14 invited participants after three Delphi rounds. Inter-rater reliability was high at 0.79 (95 %CI 0.64-0.88). Test-retest reliability was excellent at 0.83 (95 %CI 0.77-0.87). Cronbach's α was 0.81, item-total correlation range was 0.52-0.70, and inter-item correlation range was 0.38-0.74. There was a positive correlation between TUGCS ratings and a global rating of visualization (r = 0.41, P = 0.002). TUGCS ratings for EGDs with global ratings of excellent were significantly higher than those for EGDs with global ratings of fair (P = 0.01). CONCLUSION : The TUGCS had strong evidence of validity in the clinical setting. The international group of assessors, broad variety of EGD indications, and minimal assessor training improves the potential for dissemination.

Clinical and pathological predictors of failure of endoscopic therapy for Barrett's related high-grade dysplasia and early esophageal adenocarcinoma.

BACKGROUND AND AIMS: Multimodal endoscopic treatment for Barrett's esophagus (BE) related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) is safe and effective. However, there is a paucity of data to predict the response to endoscopic treatment. This study aimed to identify predictors of failure to achieve complete eradication of neoplasia (CE-N) and complete eradication of intestinal metaplasia (CE-IM). METHODS: We performed a retrospective analysis of prospectively collected data of all HGD/EAC cases treated endoscopically at a tertiary referral center. Only patients with confirmed HGD/EAC from initial endoscopic mucosal resection (EMR) were included. Potential predictive variables including clinical characteristics, endoscopic features, and index histologic parameters of the EMR specimens were evaluated using multivariate Cox regression. RESULTS: A total of 457 patients were diagnosed with HGD/EAC by initial EMR from January 2008 to January 2019. Of these, 366 patients who underwent subsequent endoscopic treatment with or without RFA were included. Cumulative incidence rates at 3 years for CE-N and CE-IM were 91.4% (95% CI 87.8-94.2%) and 66.8% (95% CI 61.2-72.3%), respectively during a median follow-up period of 35 months. BE segment of 3-10 cm (HR 0.45; 95% CI 0.36-0.57) and > 10 cm (HR 0.25; 95% CI 0.15-0.40) were independent clinical predictors associated with failure to achieve CE-N. With respect to CE-IM, increasing age (HR 0.88; 95% CI 0.78-1.00) was another predictor along with BE segment of 3-10 cm (HR 0.37; 95% CI 0.28-0.49) and > 10 cm (HR 0.15; 95% CI 0.07-0.30). Lymphovascular invasion increased the risk of CE-N and CE-IM failure in EAC cases. CONCLUSION: Failure to achieve CE-N and CE-IM is associated with long-segment BE and other clinical variables. Patients with these predictors should be considered for a more intensive endoscopic treatment approach at expert centers.

Clinical characteristics may distinguish patients with esophageal adenocarcinoma arising from long- versus short-segment Barrett's esophagus.

BACKGROUND AND AIMS: Patients with long-segment Barrett's esophagus (LSBE; ≧3 cm) have higher risk of developing esophageal adenocarcinoma (EAC) than those with short-segment Barrett's esophagus (SSBE; <3 cm). However, it is unclear whether patients developing EAC from LSBE or SSBE differ significantly according to baseline clinical characteristics. METHODS: We conducted a retrospective analysis of a prospectively maintained database comprising consecutive patients with early EAC treated by endoscopic mucosal resection at a single, tertiary-referral center. Information regarding baseline clinical characteristics were determined. Univariate and multivariate logistic regression were performed to identify factors that differed significantly between patients with EAC arising from SSBE and LSBE. RESULTS: A total of 145 LSBE EAC and 179 SSBE EAC cases were identified. The LSBE EAC patients had a stronger association with having a hiatal hernia compared to the SSBE EAC patients. In contrast, inverse associations were observed in LSBE EAC patients with statin use and smoking pack-years relative to SSBE EAC patients. CONCLUSIONS: Patients who developed EAC on a background of LSBE were more likely to have a hiatus hernia compared to patients with SSBE EAC, who were more likely to have higher smoking pack-years and higher rates of statin use.

Endoscopic treatment of Barrett's esophagus: What can we learn from the Western perspective?

The incidence of Barrett's esophagus (BE)-related neoplasia in Western countries has increased in the past several decades and, even in Eastern countries, it appears to be increasing. Endoscopic therapies are the first-line treatment for BE-related neoplasia; however, there is still no standardized treatment strategy. Most of the data have been published from Western countries where the ultimate goal of treatment is complete eradication of BE mucosa removing subtle synchronous lesions and preventing metachronous neoplasia. A multimodality approach that combines endoscopic resection and radiofrequency ablation (RFA) has been widely accepted in the West. In contrast, the lack of access to RFA treatment in the East has meant that endoscopic resection is the only feasible option. There is a wide divergence in treatment strategies for BE-related neoplasia between the East and the West. It is very important to consider these basic differences in the context of the currently available evidence to date. Therefore, the purpose of this article is to review the recent literature and to provide an overview of the endoscopic treatment options for BE.

Increased Intestinal Permeability in Relatives of Patients With Crohn's Disease Is Not Associated With Small Bowel Ulcerations.

BACKGROUND & AIMS: Many first-degree relatives of patients with Crohn's disease (CD) have increased intestinal permeability. Video capsule endoscopy (VCE) is the most sensitive imaging test to identify small bowel mucosal lesions that could indicate subclinical CD. We aimed to estimate the association of increased intestinal permeability with small bowel ulcerations detectable by VCE in healthy first-degree relatives of patients with CD. METHODS: We conducted a cross-sectional study of 223 healthy, asymptomatic first-degree relatives of patients with CD (parents, siblings, and children; 9-45 years old) enrolled at the University of Alberta between 2009 and 2012. Patients were given the lactulose and mannitol test to measure small bowel permeability; we used high-performance liquid chromatography to measure concentrations of lactulose and mannitol in urine samples (increased permeability defined as a ratio of lactulose/mannitol 0.025 or greater). Patients with increased permeability (n = 39) and randomly selected subjects with normal permeability (n = 59) were then examined by VCE for signs of small bowel inflammation and subclinical CD. The prevalence of small bowel lesions was compared among groups. We performed logistic regression analyses to estimate odds ratios for the association of small bowel ulcerations with intestinal permeability. RESULTS: Among 223 first-degree relatives of patients with CD, 30% were found to have increased intestinal permeability; VCE examination found 24% of subjects to have 3 or more small bowel ulcers. Three or more small bowel ulcers were detected in 28% of patients with increased intestinal permeability and 20% of patients with normal intestinal permeability (P = .37). The adjusted odds ratio for the association of 3 or more small bowel ulcers with increased intestinal permeability was 1.5 (95% confidence interval, 0.6-3.8; P = .46). CONCLUSIONS: Thirty percent of healthy, asymptomatic first-degree relatives of patients with CD have increased intestinal permeability. However, a strong association of small bowel ulceration seen on VCE with increased intestinal permeability was not observed.

Efficacy of single-incision needle-knife biopsy for sampling subepithelial lesions.

Background and study aims Single-incision needle-knife (SINK) biopsy is a diagnostic method for acquiring tissue samples for subepithelial lesions (SELs). A single linear incision is made in the overlying mucosa and tissue samples are obtained by passing conventional biopsy forceps through the opening and deep into the lesion. The aim of this study was to describe the efficacy and safety of this technique. Patients and methods Consecutive patients who underwent SINK biopsy for an upper gastrointestinal SEL between October 2013 and September 2015 were retrospectively reviewed. Results Forty-nine patients underwent 50 SINK biopsies. Sufficient sampling for a definite pathologic diagnosis was obtained in 42 (86 %) cases, with 91 % (40/44) having sufficient sample to perform immunohistochemistry when deemed clinically relevant. Of the 26 patients with prior non-diagnostic biopsies or FNA, a specific diagnosis was obtained in 85 % (22/26). There were no significant adverse events. Conclusions SINK biopsy is a safe and feasible strategy for obtaining a definitive tissue diagnosis with immunohistochemistry for SELs.

Magnetic imaging-assisted colonoscopy vs conventional colonoscopy: a randomized controlled trial.

AIM: To compare magnetic imaging-assisted colonoscopy (MIC) with conventional colonoscopy (CC). METHODS: Magnetic imaging technology provides a computer-generated image of the shape and position of the colonoscope onto a monitor to give visual guidance to the endoscopist. It is designed to improve colonoscopy performance and tolerability for patients by enabling visualization of loop formation and endoscope position. Recently, a new version of MIC technology was developed for which there are limited data.To evaluate this latest generation of MIC among experienced rather than inexperienced or trainee endoscopists, a prospective randomized trial was performed using only gastroenterologists with therapeutic endoscopy training. Consecutive patients undergoing elective outpatient colonoscopy were randomized to MIC or CC, with patients blinded to their group assignment. Endoscopic procedural metrics and quantities of conscious sedation medications were recorded during the procedures. The procedure was classified as "usual" or "difficult" by the endoscopist at the conclusion of each case based on the need for adjunctive maneuvers to facilitate endoscope advancement. After more than one hour post-procedure, patients completed a 10 cm visual analogue pain scale to reflect the degree of discomfort experienced during their colonoscopy. The primary outcome was patient comfort expressed by the visual analogue pain score. Secondary outcomes consisted of endoscopic procedural metrics as well as a sedation score derived from standardized dose increments of the conscious sedation medications. RESULTS: Two hundred fifty-three patients were randomized and underwent MIC or CC between September 2011 and October 2012. The groups were similar in terms of the indications for colonoscopy and patient characteristics. There were no differences in cecal intubation rates (100% vs 99%), insertion distance-to-cecum (82 cm vs 83 cm), time-to-cecum (6.5 min vs 7.2 min), or polyp detection rate (47% vs 52%) between the MIC and CC groups. The primary outcome of mean pain score (1.0 vs 0.9 out of 10, P = 0.41) did not differ between MIC and CC groups, nor did the mean sedation score (8.2 vs 8.5, P = 0.34). Within the subgroup of cases considered more challenging or difficult, time-to-cecum was significantly faster with MIC compared to CC, 10.1 min vs 13.4 min respectively (P = 0.01). Sensitivity analyses confirmed a similar pattern of overall findings when each endoscopist was considered separately, demonstrating that the mean results for the entire group were not unduly influenced by outlier results from any one endoscopist. CONCLUSION: Although the latest version of MIC resulted in faster times-to-cecum within a subgroup of more challenging cases, overall it was no better than CC in terms of patient comfort, sedation requirements and endoscopic procedural metrics, when performed in experienced hands.

Endoscopic ultrasound in the diagnosis and treatment of pancreatic disease.

Endoscopic ultrasound (EUS) is an important part of modern gastrointestinal endoscopy and now has an integral role in the diagnostic evaluation of pancreatic diseases. Furthermore, as EUS technology has advanced, it has increasingly become a therapeutic procedure, and the prospect of multiple applications of interventional EUS for the pancreas is truly on the near horizon. However, this review focuses on the established diagnostic and therapeutic roles of EUS that are used in current clinical practice. In particular, the diagnostic evaluation of acute pancreatitis, chronic pancreatitis, cystic pancreatic lesions and solid masses of the pancreas are discussed. The newer enhanced imaging modalities of elastography and contrast enhancement are evaluated in this context. The main therapeutic aspects of pancreatic EUS are then considered, namely celiac plexus block and celiac plexus neurolysis for pain control in chronic pancreatitis and pancreas cancer, and EUS-guided drainage of pancreatic fluid collections.

Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation.

AIM: To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission. METHODS: Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI) < 150] during follow-up visits based on physician global assessments. A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI > 220) and a therapeutic intervention with CD medication(s), or a hospitalization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n = 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5) polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group. RESULTS: Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked difference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years ± 0.6 years, while those still in remission were at the time of this study, 8.1 years ± 2.6 years post-discontinuation of infliximab, P < 0.001. The 8 patients who had lost remission after discontinuing infliximab had a mean number of 5 infusions (range 3-7), with a mean treatment time of 7.2 mo (range 1.5 mo-15 mo). The mean duration of time from the last infusion of infliximab to the time of loss of remission was 382 d (range 20 d-701 d). The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions (range 3-12), with a mean treatment duration of 12 mo (range 3.6 mo-32 mo) (P = 0.45 relative to those who lost remission). CONCLUSION: There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sustained remission and which will relapse rapidly after stopping infliximab.

Hyperamylasemia and pancreatitis following spiral enteroscopy.

BACKGROUND: Acute pancreatitis is a significant potential complication with double-balloon enteroscopy. Hyperamylasemia is frequently observed after both double-balloon enteroscopy and single-balloon enteroscopy but often without associated pancreatitis. Whether the same phenomenon occurs with spiral enteroscopy is currently unknown. AIMS: To determine the incidence of pancreatitis and hyperamylasemia following spiral enteroscopy. METHODS: A prospective cohort study of consecutive patients undergoing proximal spiral enteroscopy was conducted. Serum amylase levels were measured immediately before and following the procedure, combined with observation for clinical signs of pancreatitis. RESULTS: A total of 32 patients underwent proximal spiral enteroscopy, with a mean total procedure time of 51 min (range 30 min to 100 min) and mean depth of insertion of 240 cm (range 50 cm to 350 cm). The diagnostic yield was 50%, with 31% of all procedures being therapeutic. While no patients exhibited signs that raised suspicion of pancreatitis, hyperamylasemia was common (20%). Hyperamylasemia was not significantly associated with procedure duration or depth of insertion but was linked to patients with Peutz-Jeghers syndrome and with the use of propofol sedation, suggesting that it may be more common in difficult cases. CONCLUSIONS: Postprocedural hyperamylasemia occurred frequently with proximal spiral enteroscopy, while no associated pancreatitis was observed. This finding suggests that hyperamylasemia may not necessarily reflect pancreatic injury nor portend a risk for pancreatitis.

Canadian Digestive Health Foundation Public Impact Series 5: Pancreatitis in Canada. Incidence, prevalence, and direct and indirect economic impact.

The Canadian Digestive Health Foundation initiated a scientific program to assess the incidence, prevalence, mortality and economic impact of digestive disorders across Canada in 2009. The current article presents the updated findings from the study concerning pancreatitis.

Abnormal intestinal permeability in Crohn's disease pathogenesis.

Increased small intestinal permeability is a longstanding observation in both Crohn's disease patients and in their healthy, asymptomatic first-degree relatives. However, the significance of this compromised gut barrier function and its place in the pathogenesis of the disease remains poorly understood. The association between abnormal small intestinal permeability and a specific mutation in the NOD2 gene, which functions to modulate both innate and adaptive immune responses to intestinal bacteria, suggests a common, genetically determined pathway by which an abnormal gut barrier could result in chronic intestinal inflammation. Furthermore, rodent colitis models show that gut barrier defects precede the development of inflammatory changes. However, it remains possible that abnormal permeability is simply a consequence of mucosal inflammation. Further insight into whether abnormal barrier function is the cause or consequence of chronic intestinal inflammation will be crucial to understanding the role of intestinal permeability in the pathogenesis of Crohn's disease.

Small bowel endoscopy for obscure GI bleeding.

Advancements in small bowel endoscopy have revolutionized the investigation and management of obscure GI bleeding. Capsule endoscopy and double balloon endoscopy, followed more recently by single balloon endoscopy and spiral enteroscopy, have progressed into established technologies that have now become integrated within clinical practice. As such, small bowel endoscopy research has matured to focus less on immediate endoscopic findings and ever increasingly on important clinical outcomes with long-term follow-up. The purpose of this paper is to review the role of small bowel endoscopy in obscure GI bleeding, while providing insights that may help guide clinicians in their decision-making.

Small bowel enteroscopy.

Over the past decade, the advent of capsule endoscopy and balloon-assisted enteroscopy has revolutionized the approach to small intestinal diseases. The small bowel is no longer out of reach, and has fallen within the diagnostic and therapeutic realm of the gastrointestinal endoscopist. Double-balloon enteroscopy was the first type of balloon-assisted endoscopy and is the method for which there are the most data. Single-balloon enteroscopy has since been introduced as an alternative balloon-assisted method, followed more recently by the development of spiral overtube-assisted enteroscopy. The purpose of the present article is to review these methods of small bowel enteroscopy and to discuss the latest developments. While the investigation of small bowel diseases cannot be addressed without considering the central role of capsule endoscopy, a detailed assessment is beyond the scope of the present article, and capsule endoscopy will only be discussed as it pertains to enteroscopy.

Double balloon enteroscopy and capsule endoscopy for obscure gastrointestinal bleeding: an updated meta-analysis.

BACKGROUND AND AIM: Uncertainty remains about the best test to evaluate patients with obscure gastrointestinal bleeding (OGIB). Previous meta-analyses demonstrated similar diagnostic yields with capsule endoscopy (CE) and double balloon enteroscopy (DBE) but relied primarily on data from abstracts and were not limited to bleeding patients. Many studies have since been published. Therefore, we performed a new meta-analysis comparing CE and DBE focused specifically on OGIB. METHODS: A comprehensive literature search was performed of comparative studies using both CE and DBE in patients with OGIB. Data were extracted and analyzed to determine the weighted pooled diagnostic yields of each method and the odds ratio for the successful localization of a bleeding source. RESULTS: Ten eligible studies were identified. The pooled diagnostic yield for CE was 62% (95% confidence interval [CI] 47.3-76.1) and for DBE was 56% (95% CI 48.9-62.1), with an odds ratio for CE compared with DBE of 1.39 (95% CI 0.88-2.20; P = 0.16). Subgroup analysis demonstrated the yield for DBE performed after a previously positive CE was 75.0% (95% CI 60.1-90.0), with the odds ratio for successful diagnosis with DBE after a positive CE compared with DBE in all patients of 1.79 (95% CI 1.09-2.96; P = 0.02). In contrast, the yield for DBE after a previously negative CE was only 27.5% (95% CI 16.7-37.8). CONCLUSIONS: Capsule endoscopy and double balloon enteroscopy provide similar diagnostic yields in patients with OGIB. However, the diagnostic yield of DBE is significantly higher when performed in patients with a positive CE.

Retrograde double balloon enteroscopy: comparing performance of solely retrograde versus combined same-day anterograde and retrograde procedure.

OBJECTIVE: Retrograde double balloon enteroscopy (DBE) is important for evaluating the distal small bowel, but it is more challenging compared to the oral route. Optimizing small bowel insertion may enhance the diagnostic utility of the examination. We sought to determine if insertion depths achieved with retrograde DBE when performed as an isolated procedure differed significantly from when performed immediately following anterograde DBE. MATERIAL AND METHODS: A retrospective analysis was conducted of all retrograde DBE procedures performed at our center with comparisons made between "distal-only" DBE without preceding anterograde DBE and "combined" DBE after a prior same-day anterograde DBE. RESULTS: Two hundred ninety retrograde DBE procedures were performed in 264 patients over 5 years. Success of terminal ileal intubation exceeded 95%. The mean insertion depth into the distal small bowel differed significantly with 112 cm (95% CI 95-129) in the "distal-only" group and 92 cm (95% CI 85-98) in the "combined" group (p = 0.01), with a trend toward a corresponding increased diagnostic yield of 48% versus 37%, respectively (p = 0.15). Multivariate regression analysis identified both insertion route strategy (distal-only > combined; p = 0.01) and type of DBE endoscope (diagnostic > therapeutic; p = 0.02) as significant predictors of retrograde insertion depth. CONCLUSIONS: The insertion depth of retrograde DBE is significantly greater when carried out as a separate distal procedure and not in combination with a preceding anterograde DBE, and when performed using a diagnostic as opposed to the therapeutic DBE endoscope. This increased retrograde depth of insertion may be associated with an increased diagnostic yield.