Comparison of endoscopic mucosal resection versus endoscopic submucosal dissection for Barrett's neoplasia and esophageal adenocarcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are both accepted resection strategies for Barrett's esophagus-related neoplasia and esophageal adenocarcinoma (EAC). However, a lack of consensus exists regarding which technique offers superior outcomes. This study aims to systematically review the evidence comparing EMR versus ESD in treating Barrett's neoplasia and EAC. METHODS: We searched 3 databases (Embase, MEDLINE, Cochrane Central) through October 2023. We included studies comparing the efficacy of EMR and ESD for Barrett's neoplasia and EAC. Primary outcomes include en bloc, R0, and curative resection; complete remission of dysplasia (CRD), and local recurrence. Secondary outcomes encompass adverse events. RESULTS: Our search identified 905 records. Eleven studies were included in the final analyses. Data showed significantly higher en bloc resection rates with ESD (odds ratio [OR], 31.53; 95% confidence interval [CI], 10.02-99.19; P < .01; 7 studies). R0 resection rates were significantly higher with ESD (OR, 5.92; 95% CI, 2.75-12.77; P < .01; 8 studies). Curative resection rates tended to be higher with ESD (OR, 3.49; 95% CI, 0.86-14.14; P = .080; 4 studies). There was no significant difference in CRD rates (OR, 0.92; 95% CI, 0.37-2.26; P = .86; 3 studies). Local recurrence rates tended to be lower with ESD (OR, 0.35; 95% CI, 0.11-1.04; P = .058; 10 studies). As for adverse events, there was no significant difference in bleeding, perforation, and postoperative stricture rates. CONCLUSIONS: This systematic review and meta-analysis demonstrates that ESD achieves higher en bloc, R0, and curative resection rates, with a tendency toward lower recurrence rates. These results suggest that ESD may be a more effective option for managing Barrett's neoplasia and EAC. (International Prospective Register of Systematic Reviews [PROSPERO] registration number: CRD42023426486.).

Establishment of standards for the referral of large nonpedunculated 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 nonpedunculated colorectal polyps are often referred to expert centers 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 this study was to establish minimum expected standards for the referral of large nonpedunculated colonic polyps for potential endoscopic resection. METHODS: A Delphi method was used 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 3 rounds of surveys were conducted to achieve consensus. Quantitative and qualitative data were analyzed 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 demographic characteristics, 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, which were scored on a scale of 1 to 10, ranged from 7.04 to 9.29, with high percentages of experts considering most statements as a very high priority. Subgroup analysis according to continent revealed some variations in consensus rates among experts from different regions. CONCLUSIONS: 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.

Recurrence following successful eradication of neoplasia with endoscopic mucosal resection compared with endoscopic submucosal dissection in Barrett's esophagus: a retrospective comparison.

BACKGROUND: Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are effective treatments for Barrett's neoplasia. However, little is known about recurrence rates following these techniques. We compared long-term neoplasia recurrence rates following EMR and ESD. METHODS: This study included patients with Barrett's neoplasia (high grade dysplasia/adenocarcinoma) treated between July 2019 and December 2023 at a tertiary referral center in Canada. Outcomes were residual neoplasia at first follow-up, complete remission of neoplasia (CRN), and neoplasia recurrence following CRN. RESULTS: 157 patients were included (87 EMR, 70 ESD). Compared with EMR, the ESD group had larger lesions (median 2 vs. 3 cm, P<0.05), more adenocarcinoma (85.1% vs. 94.3%, P = 0.07), and deeper submucosal invasion (T1a: 71.6% vs. 75.8%; T1b-SM1: 25.7% vs. 6.1%; T1b≥SM2: 2.7% vs. 18.2%; P<0.05). Among 124 patients with follow-up (71 EMR, 53 ESD), 84.9% of ESD-treated patients had curative resections (i.e. R0 resection with low risk for lymph node metastasis), whereas 94.4% of EMR-treated patients had deep margin R0 resection of low risk lesions. At first follow-up, residual neoplasia (14.1% vs. 11.3%) and CRN (97.2% vs. 100%) were similar in the EMR and ESD groups, but neoplasia recurrence following CRN was significantly higher with EMR (13% vs. 1.9%, P<0.05), with cumulative probability of recurrence at 3 years of 18.3% vs. 4.2%, respectively. CONCLUSIONS: Neoplasia recurrence following CRN was significantly higher following EMR compared with ESD, suggesting that ESD may be superior to EMR in preventing neoplasia recurrence in Barrett's esophagus.

Can optical evaluation distinguish between T1a and T1b esophageal adenocarcinoma: an international expert interobserver agreement study.

BACKGROUND: Piecemeal endoscopic mucosal resection (EMR) is an acceptable technique for T1a esophageal adenocarcinoma, but en bloc R0 excision is advocated for T1b disease as it may offer a potential cure and mitigate recurrence. Thus, distinguishing between T1a and T1b disease is imperative under current treatment paradigms. We investigated whether expert Barrett's endoscopists could make this distinction based on optical evaluation. METHODS: Endoscopic images of histologically confirmed high grade dysplasia (HGD), T1a, and T1b disease (20 sets for each) were compiled from consecutive patients at a single institution. Each set contained four images including an overview, a close-up in high definition white light, a near-focus magnification image, and a narrow-band image. Experts predicted the histology for each set. RESULTS: 19 experts from 8 countries (Australia, USA, Italy, Netherlands, Germany, Canada, Belgium, and Portugal) participated. The majority had been practicing for > 20 years, with a median (interquartile range) annual case volume of 50 (18-75) for Barrett's EMR and 25 (10-45) for Barrett's endoscopic submucosal dissection. Esophageal adenocarcinoma (T1a/b) could be distinguished from HGD with a pooled sensitivity of 89.1 % (95 %CI 84.7-93.4). T1b adenocarcinoma could be predicted with a pooled sensitivity of 43.8 % (95 %CI 29.9-57.7). Fleiss' kappa was 0.421 (95 %CI 0.399-0.442; P < 0.001), indicating fair-to-moderate agreement. CONCLUSIONS: Expert Barrett's endoscopists could reliably differentiate T1a/T1b esophageal adenocarcinoma from HGD. Despite fair-to-moderate agreement for T staging, T1b disease could not be reliably distinguished from T1a disease. This may impact clinical decision making and selection of endoscopic techniques.

Efficacy of endoscopic interventions versus surgery for pain management in patients with chronic calcific pancreatitis: a systematic review and meta-analysis.

INTRODUCTION: Chronic calcific pancreatitis (CCP) is a debilitating inflammatory condition characterized by the accumulation of calcific deposits in the pancreatic tissue, leading to chronic abdominal pain and functional insufficiencies. This study aims to systematically review and meta-analyse comparative studies assessing the efficacy of endotherapy versus surgery in managing CCP-related pain. METHODS: MEDLINE, EMBASE, and Cochrane library (CENTRAL and CDSR), from inception to October 2023, were searched. The inclusion criteria encompassed randomized controlled trials (RCTs) and non-randomized controlled trials (NRS), and cohort studies comparing endoscopic interventions to surgery for pain management in patients with CCP. Pain relief, procedural technical success, and procedural-related complications were the outcomes of interest. Two review authors (CN, KK) independently assessed study eligibility criteria and performed data extraction. Using a random-effects model, pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. The level of certainty of the evidence was assessed using the GRADE approach. RESULTS: Five studies were included. For the outcome of pain relief, a meta-analysis of five studies (3 RCTs and 2 cohort studies) demonstrated a significant therapeutic effect in favour of surgery with an OR of 2.36 (95% CI: 1.12 to 5.00, I2 = 41.70), with moderate level of certainty of evidence. In the analysis of five studies (3 RCTs, 1 NRS and 2 cohort studies), procedural technical success was comparable between the two groups (OR of 3.02, 95% CI: 0.47 to 19.59, I2 = 79.27%) as were adverse events (OR 1.31, 95% CI: 0.47 to 3.70, I2 = 50.93%). CONCLUSION: In conclusion, this systematic review and meta-analysis suggest that surgery may be more effective in relieving pain in patients with CCP compared to endoscopic interventions. Disease stage may be important to determine the appropriateness of each procedure. PROSPERO (CRD42023476153).

Association of gastric myotomy length in peroral endoscopic myotomy (POEM) with gastro-esophageal junction distensibility measured by Endoluminal Functional Lumen Imaging Probe (EndoFLIP).

BACKGROUND: Endoluminal Functional Lumen Imaging Probe (EndoFLIP) is a device that measures gastro-esophageal junction (GEJ) distensibility. However, it is not demonstrated that GEJ distensibility increases proportionally with varying gastric myotomy length in peroral endoscopic myotomy (POEM). This study aimed to investigate the association between gastric myotomy length in POEM and intraoperative EndoFLIP findings. METHODS: This single-center, retrospective cohort study included patients who underwent POEM with intraoperative EndoFLIP from December 2019 to January 2023. Using EndoFLIP, minimal balloon diameter and its distensibility index (DI) were measured pre- and post-myotomy. Primary and secondary outcomes were the post-myotomy EndoFLIP findings at 30 ml and 40 ml volume fills. RESULTS: The study included 44 patients (mean age 53.1 years, 50% female). Chicago classification included achalasia type I (39%), II (41%), III (9%), hypercontractile esophagus (2%), and EGJOO (9%). The mean esophageal myotomy length was 7.5 ± 2.2 cm and gastric myotomy was 2.1 ± 0.6 cm. Simple linear regression analyses indicated that for each 1 cm increase in gastric myotomy length, the DI at 30 ml volume fill was estimated to increase by 2.0 mm2/mmHg (p < 0.05, R2 = 0.41), the minimal diameter at 30 ml volume fill was estimated to increase by 2.4 mm (p < 0.05, R2 = 0.48), and the minimal diameter at 40 ml volume fill was estimated to increase by 1.3 mm (p < 0.05, R2 = 0.09). CONCLUSIONS: This study demonstrates a significant linear relationship between gastric myotomy length and GEJ distensibility measured by EndoFLIP during POEM. These findings may be useful in clinical practice by enabling EndoFLIP to help calibrate a desired gastric myotomy length to achieve optimal DI and minimal diameter.

Outpatient flexible endoscopic diverticulotomy for the management of Zenker's diverticulum: a retrospective analysis of a large single-center cohort.

BACKGROUNDS AND AIMS: Flexible endoscopic Zenker's diverticulotomy (EZD) is well established as a safe and effective technique. Because of rare but concerning adverse events, most centers admit patients for observation and barium swallow study. Our center routinely performs EZD as a day procedure, discharging appropriate patients on the same day after clinical review. This study evaluates outcomes of this cohort compared with previously published studies where patients are admitted for observation. METHODS: A retrospective analysis was performed of EZD procedures done at our center using a flexible endoscope and, in most cases, a diverticulotomy overtube with patients under moderate sedation or general anesthesia. Patients were observed for 2 hours and discharged if no clinical concerns were found. Patient comorbidities, American Society of Anesthesiologists physical status, and endoscopic adverse events were recorded against the American Society for Gastrointestinal Endoscopy severity grading system. RESULTS: Two hundred forty EZD procedures were performed between January 2015 and February 2021. Eleven (4.6%) intraprocedural adverse events occurred: 4 perforations, 4 bleeds, and 1 each postprocedural pain, delirium, and vomiting, respectively. All were recognized within the 2-hour observation period and were managed conservatively, except 1 patient who required surgery. Six patients (2.5%) presented with delayed adverse events: 2 bleeds, 2 perforations, and 2 postprocedural pain. All patients recovered uneventfully with supportive care. CONCLUSIONS: All significant adverse events requiring endoscopic or surgical intervention were identified before discharge. Delayed adverse events occurred in 2.5% of cases, all of which were managed supportively. Our data are comparable with published cohorts of admitted patients, demonstrating that appropriately selected patients may be managed as outpatients while maintaining similar safety outcomes.

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.

Predictors of recurrence of dysplasia or cancer in patients with dysplastic Barrett's esophagus following complete eradication of dysplasia: a single-center retrospective cohort study.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) for Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) are considered effective treatments for eradication of BE. Little is known about the impact of achieving complete eradication of intestinal metaplasia (CE-IM) following the complete eradication of neoplasia (CE-N), specifically if CE-IM reduces the risk of recurrent dysplasia. METHODS: Retrospective cohort study of consecutive patients with BE and HGD or intramucosal cancer (IMC)-treated endoscopically at a tertiary referral center between 2001 and 2019. Association between CE-IM and recurrent dysplasia after CE-N was evaluated. RESULTS: A total of 433 patients treated with EMR and/or RFA were included. Of these, 381 (88%) achieved CE-N, of which 345 (80%) had adequate follow-up for inclusion in the analysis. A total of 266 (77%) patients achieved CE-IM; with a median follow-up since initial treatment for HGD/IMC of 45.9 months (IQR 25.9, 93.1); 20 patients (5.8%) had recurrent dysplasia after achieving CE-N. Kaplan Meier survival curves revealed that time free of recurrence in those who achieved CE-IM was significantly higher (p = 0.002). In the multivariable analysis, CE-IM was associated with a significant lower hazard of recurrence (HR 0.2, 95% CI 0.1, 0.6), whereas the number of endoscopic treatments to achieve CE-N was associated with a significant higher hazard of recurrence (HR 1.1, 95% CI 1.0, 1.2). CONCLUSION: Achieving CE-IM following CE-N reduces the risk of recurrent dysplasia and should be considered a treatment target among patients with BE undergoing endoscopic therapies for HGD or EAC.

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.

Risk factors for serious adverse events associated with multiband mucosectomy in Barrett's esophagus: an international multicenter analysis of 3827 endoscopic resection procedures.

BACKGROUND AND AIMS: Multiband mucosectomy (MBM) is a widely used technique for the treatment of Barrett's esophagus (BE). However, large multicenter studies enabling a generalizable estimation of the risk of serious adverse events, such as perforation and postprocedural bleeding, are lacking. The aim of this study was to estimate the rate of, and risk factors for, serious adverse events associated with MBM. METHODS: In this retrospective analysis, consecutive patients who underwent MBM for treatment of BE in 14 tertiary referral centers in Europe, the United States, Canada, and Australia were included. Primary outcomes were perforation and postprocedural bleeding rate. Potential risk factors were identified by logistic regression. RESULTS: Between 2001 and 2016, a total of 3827 MBM procedures were performed in 2447 patients (84% male, mean age 66 years, median BE length C2M4). Perforation occurred in 17 procedures (0.4%; 95% confidence interval [CI], 0.3-0.7), of which 15 could be treated endoscopically or conservatively. Female gender was an independent risk factor for perforation (odds ratio [OR], 2.77; 95% CI, 1.02-7.57; P = .05). Postprocedural bleeding occurred after 35 procedures (0.9%; 95% CI, 0.6-1.3). The number of resections (OR, 1.15; 95% CI, 1.06-1.25; P < .001) was significantly associated with postprocedural bleeding. CONCLUSION: The results of this study show that MBM for BE is safe with a low risk of serious adverse events. In addition, most of the adverse events could be managed endoscopically or conservatively. The number of resections was an independent risk factor for postprocedural bleeding.

Clinical Practice Guidelines for the Use of Video Capsule Endoscopy.

BACKGROUND & AIMS: Video capsule endoscopy (CE) provides a noninvasive option to assess the small intestine, but its use with respect to endoscopic procedures and cross-sectional imaging varies widely. The aim of this consensus was to provide guidance on the appropriate use of CE in clinical practice. METHODS: A systematic literature search identified studies on the use of CE in patients with Crohn's disease, celiac disease, gastrointestinal bleeding, and anemia. The quality of evidence and strength of recommendations were rated using the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. RESULTS: The consensus includes 21 statements focused on the use of small-bowel CE and colon capsule endoscopy. CE was recommended for patients with suspected, known, or relapsed Crohn's disease when ileocolonoscopy and imaging studies were negative if it was imperative to know whether active Crohn's disease was present in the small bowel. It was not recommended in patients with chronic abdominal pain or diarrhea, in whom there was no evidence of abnormal biomarkers typically associated with Crohn's disease. CE was recommended to assess patients with celiac disease who have unexplained symptoms despite appropriate treatment, but not to make the diagnosis. In patients with overt gastrointestinal bleeding, and negative findings on esophagogastroduodenoscopy and colonoscopy, CE should be performed as soon as possible. CE was recommended only in selected patients with unexplained, mild, chronic iron-deficiency anemia. CE was suggested for surveillance in patients with polyposis syndromes or other small-bowel cancers, who required small-bowel studies. Colon capsule endoscopy should not be substituted routinely for colonoscopy. Patients should be made aware of the potential risks of CE including a failed procedure, capsule retention, or a missed lesion. Finally, standardized criteria for training and reporting in CE should be defined. CONCLUSIONS: CE generally should be considered a complementary test in patients with gastrointestinal bleeding, Crohn's disease, or celiac disease, who have had negative or inconclusive endoscopic or imaging studies.

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.