American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the management of chronic pancreatitis: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the role of endoscopy in the management of chronic pancreatitis (CP). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses effectiveness of endoscopic therapies for the management of pain in CP, including celiac plexus block, endoscopic management of pancreatic duct (PD) stones and strictures, and adverse events such as benign biliary strictures (BBSs) and pseudocysts. In patients with painful CP and an obstructed PD, the ASGE suggests surgical evaluation in patients without contraindication to surgery before initiation of endoscopic management. In patients who have contraindications to surgery or who prefer a less-invasive approach, the ASGE suggests an endoscopic approach as the initial treatment over surgery, if complete ductal clearance is likely. When a decision is made to proceed with a celiac plexus block, the ASGE suggests an EUS-guided approach over a percutaneous approach. The ASGE suggests indications for when to consider ERCP alone or with pancreatoscopy and extracorporeal shock wave lithotripsy alone or followed by ERCP for treating obstructing PD stones based on size, location, and radiopacity. For the initial management of PD strictures, the ASGE suggests using a single plastic stent of the largest caliber that is feasible. For symptomatic BBSs caused by CP, the ASGE suggests the use of covered metal stents over multiple plastic stents. For symptomatic pseudocysts, the ASGE suggests endoscopic therapy over surgery. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

TEMPORARY REMOVAL: American Society for Gastrointestinal Endoscopy guideline on the role of therapeutic EUS in the management of biliary tract disorders: summary and recommendations.

The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

International consensus on the management of large (≥20 mm) colorectal laterally spreading tumors: World Endoscopy Organization Delphi study.

OBJECTIVES: There have been significant advances in the management of large (≥20 mm) laterally spreading tumors (LSTs) or nonpedunculated colorectal polyps; however, there is a lack of clear consensus on the management of these lesions with significant geographic variability especially between Eastern and Western paradigms. We aimed to provide an international consensus to better guide management and attempt to homogenize practices. METHODS: Two experts in interventional endoscopy spearheaded an evidence-based Delphi study on behalf of the World Endoscopy Organization Colorectal Cancer Screening Committee. A steering committee comprising six members devised 51 statements, and 43 experts from 18 countries on six continents participated in a three-round voting process. The Grading of Recommendations, Assessment, Development and Evaluations tool was used to assess evidence quality and recommendation strength. Consensus was defined as ≥80% agreement (strongly agree or agree) on a 5-point Likert scale. RESULTS: Forty-two statements reached consensus after three rounds of voting. Recommendations included: three statements on training and competency; 10 statements on preresection evaluation, including optical diagnosis, classification, and staging of LSTs; 14 statements on endoscopic resection indications and technique, including statements on en bloc and piecemeal resection decision-making; seven statements on postresection evaluation; and eight statements on postresection care. CONCLUSIONS: An international expert consensus based on the current available evidence has been developed to guide the evaluation, resection, and follow-up of LSTs. This may provide guiding principles for the global management of these lesions and standardize current practices.

GAN Inversion for Data Augmentation to Improve Colonoscopy Lesion Classification.

A major challenge in applying deep learning to medical imaging is the paucity of annotated data. This study explores the use of synthetic images for data augmentation to address the challenge of limited annotated data in colonoscopy lesion classification. We demonstrate that synthetic colonoscopy images generated by Generative Adversarial Network (GAN) inversion can be used as training data to improve polyp classification performance by deep learning models. We invert pairs of images with the same label to a semantically rich and disentangled latent space and manipulate latent representations to produce new synthetic images. These synthetic images maintain the same label as the input pairs. We perform image modality translation (style transfer) between white light and narrow-band imaging (NBI). We also generate realistic synthetic lesion images by interpolating between original training images to increase the variety of lesion shapes in the training dataset. Our experiments show that GAN inversion can produce multiple colonoscopy data augmentations that improve the downstream polyp classification performance by 2.7% in F1-score and 4.9% in sensitivity over other methods, including state-of-the-art data augmentation. Testing on unseen out-of-domain data also showcased an improvement of 2.9% in F1-score and 2.7% in sensitivity. This approach outperforms other colonoscopy data augmentation techniques and does not require re-training multiple generative models. It also effectively uses information from diverse public datasets, even those not specifically designed for the targeted downstream task, resulting in strong domain generalizability. Project code and model: https://github.com/DurrLab/GAN-Inversion.

Predictors for lymph node metastasis and survival of patients with T1b esophageal adenocarcinoma treated with surgery and endoscopic therapy: an analysis of the Surveillance, Epidemiology, and End Results database.

BACKGROUND AND AIMS: Limited data exist regarding the long-term outcomes of endoscopic therapy (ET) with or without chemoradiation therapy (CRT) for T1b esophageal adenocarcinoma (EAC). Our aim was to identify the risk factors for lymph node metastasis (LNM) in T1b EAC and assess how the chosen treatment modality affects overall survival (OS) and cancer-specific survival (CSS). METHODS: We analyzed patients with histologically confirmed T1b EAC diagnosed between 2004 and 2018 using the Surveillance, Epidemiology, and End Results database. Focusing on T1bN0M0 staging, the patients were divided into 2 groups (ET [n = 174] and surgery [n = 769]), and OS and CSS rates were calculated. RESULTS: Of 1418 patients with T1b EAC, 228 cases (16.1%) exhibited LNM at diagnosis. Notable risk factors for LNM included poorly differentiated tumor and lesion size ≥20 mm. For T1bN0M0 cases, ET was commonly performed from 2009 to 2018 (odds ratio [OR], 4.3), especially for patients aged ≥65 years (OR, 3.1) with tumor size <20 mm (OR, 2.3). During the median 50 months of follow-up, age ≥65 years (hazard ratio [HR], 1.9), ET (HR, 1.5), and CRT (HR, 1.4) were associated with poorer OS. Factors linked to decreased CSS were age ≥65 years (subhazard ratio [SHR], 1.6), poorly differentiated tumors (SHR, 1.5), and CRT (SHR, 1.5). CONCLUSIONS: In T1b EAC, tumor size ≥20 mm and poor differentiation are notable risk factors for LNM. ET exhibited comparable CSS outcomes to surgery for carefully selected T1bN0M0 lesions. CRT did not provide additional survival benefit for these lesions; however, large-scale studies are required to validate this finding.

A computer-aided polyp detection system in screening and surveillance colonoscopy: an international, multicentre, randomised, tandem trial.

BACKGROUND: Studies on the effect of computer-aided detection (CAD) in a daily clinical screening and surveillance colonoscopy population practice are scarce. The aim of this study was to evaluate a novel CAD system in a screening and surveillance colonoscopy population. METHODS: This multicentre, randomised, controlled trial was done in ten hospitals in Europe, the USA, and Israel by 31 endoscopists. Patients referred for non-immunochemical faecal occult blood test (iFOBT) screening or surveillance colonoscopy were included. Patients were randomomly assigned to CAD-assisted colonoscopy or conventional colonoscopy; a subset was further randomly assigned to undergo tandem colonoscopy: CAD followed by conventional colonoscopy or conventional colonoscopy followed by CAD. Primary objectives included adenoma per colonoscopy (APC) and adenoma per extraction (APE). Secondary objectives included adenoma miss rate (AMR) in the tandem colonoscopies. The study was registered at ClinicalTrials.gov, NCT04640792. FINDINGS: A total of 916 patients were included in the modified intention-to-treat analysis: 449 in the CAD group and 467 in the conventional colonoscopy group. APC was higher with CAD compared with conventional colonoscopy (0·70 vs 0·51, p=0·015; 314 adenomas per 449 colonoscopies vs 238 adenomas per 467 colonoscopies; poisson effect ratio 1·372 [95% CI 1·068-1·769]), while showing non-inferiority of APE compared with conventional colonoscopy (0·59 vs 0·66; p<0·001 for non-inferiority; 314 of 536 extractions vs 238 of 360 extractions). AMR in the 127 (61 with CAD first, 66 with conventional colonoscopy first) patients completing tandem colonoscopy was 19% (11 of 59 detected during the second pass) in the CAD first group and 36% (16 of 45 detected during the second pass) in the conventional colonoscopy first group (p=0·024). INTERPRETATION: CAD increased adenoma detection in non-iFOBT screening and surveillance colonoscopies and reduced adenoma miss rates compared with conventional colonoscopy, without an increase in the resection of non-adenomatous lesions. FUNDING: Magentiq Eye.

Clinical outcomes of endoscopic submucosal dissection for superficial esophageal neoplasia in close proximity to esophageal varices: a multicenter international experience.

BACKGROUND : There are limited data on the feasibility of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) located at or adjacent to esophageal varices. We aimed to evaluate the outcomes of ESD in these patients. METHODS: This multicenter retrospective study included cirrhotic patients with a history of esophageal varices with SEN located at or adjacent to the esophageal varices who underwent ESD. RESULTS: 23 patients with SEN (median lesion size 30 mm; 16 squamous cell neoplasia and seven Barrett's esophagus-related neoplasia) were included. The majority were Child-Pugh B (57 %) and had small esophageal varices (87 %). En bloc, R0, and curative resections were achieved in 22 (96 %), 21 (91 %), and 19 (83 %) of patients, respectively. Severe intraprocedural bleeding (n = 1) and delayed bleeding (n = 1) were successfully treated endoscopically. No delayed perforation, hepatic decompensation, or deaths were observed. During a median (interquartile range) follow-up of 36 (22-55) months, one case of local recurrence occurred after noncurative resection. CONCLUSION: ESD is feasible and effective for SEN located at or adjacent to esophageal varices in cirrhotic patients. Albeit, the majority of the esophageal varices in our study were small in size, when expertise is available, ESD should be considered as a viable option for such patients.

A Tale of 2 Tics: Endoscopic Treatment of Perforated Periampullary Diverticulum Within a Giant Duodenal Diverticulum.

Periampullary diverticulum presenting with severe complications, such as perforations, is associated with high morbidity and mortality. Traditionally, only surgical or conservative management has been warranted. In this case, we present a 76-year-old woman with a spontaneously perforated periampullary diverticulum, located within a larger duodenal diverticulum, who achieved complete recovery with endoscopic closure after an initial unsuccessful attempt at surgical management. This case report highlights the role of endoscopy in the treatment of complicated diverticulum perforation.

Incidence and risk factors for recurrence of ampullary adenomas after endoscopic papillectomy: Comparative analysis of familial adenomatous polyposis and sporadic ampullary adenomas in an international multicenter cohort.

OBJECTIVES: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA. METHODS: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease. RESULTS: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence. CONCLUSION: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients.

Through-the-scope suture closure of nonampullary duodenal endoscopic mucosal resection defects: a retrospective multicenter cohort study.

BACKGROUND: Delayed bleeding is among the most common adverse events associated with endoscopic mucosal resection (EMR) of nonampullary duodenal polyps. We evaluated the rate of delayed bleeding and complete defect closure using a novel through-the-scope (TTS) suturing system for the closure of duodenal EMR defects. METHODS: We reviewed the electronic medical records of patients who underwent EMR for nonampullary duodenal polyps of ≥ 10 mm and prophylactic defect closure with TTS suturing between March 2021 and May 2022 at centers in the USA. We evaluated the rates of delayed bleeding and complete defect closure. RESULTS: 36 nonconsecutive patients (61 % women; mean [SD] age, 65 [12] years) underwent EMR of ≥ 10-mm duodenal polyps followed by attempted defect closure with TTS suturing. The mean (SD) lesion size was 29 (19) mm, defect size was 37 (25) mm; eight polyps (22 %) involved > 50 % of the lumen circumference. Complete closure was achieved in all cases (78 % with TTS suturing alone), using a median of one TTS suturing kit. There were no cases of delayed bleeding and no adverse events attributed to application of the TTS suturing device. CONCLUSION: Prophylactic closure of nonampullary duodenal EMR defects using TTS suturing resulted in a high rate of complete closure and no delayed bleeding events.

Incidence, severity, and mortality of post-ERCP pancreatitis: an updated systematic review and meta-analysis of 145 randomized controlled trials.

BACKGROUND AND AIMS: The incidence, severity, and mortality of post-ERCP pancreatitis (PEP) largely remain unknown with changing trends in ERCP use, indication, and techniques. We sought to determine the incidence, severity, and mortality of PEP in consecutive and high-risk patients based on a systemic review and meta-analysis of patients in placebo and no-stent arms of randomized control trials (RCTs). METHODS: The MEDLINE, Embase, and Cochrane databases were searched from the inception of each database to June 2022 to identify full-text RCTs evaluating PEP prophylaxes. The incidence, severity, and mortality of PEP from the placebo or no-stent arms of RCTs were recorded for consecutive and high-risk patients. A random-effects meta-analysis for a proportions model was used to calculate PEP incidence, severity, and mortality. RESULTS: One hundred forty-five RCTs were found with 19,038 patients in the placebo or no-stent arms. The overall cumulative incidence of PEP was 10.2% (95% confidence interval [CI], 9.3-11.3), predominantly among the academic centers conducting such RCTs. The cumulative incidences of severe PEP and mortality were .5% (95% CI, .3-.7) and .2% (95% CI, .08-.3), respectively, across 91 RCTs with 14,441 patients. The cumulative incidences of PEP and severe PEP were 14.1% (95% CI, 11.5-17.2) and .8% (95% CI, .4-1.6), respectively, with a mortality rate of .2% (95% CI, 0-.3) across 35 RCTs with 3733 patients at high risk of PEP. The overall trend for the incidence of PEP among patients randomized to placebo or no-stent arms of RCTs has remained unchanged from 1977 to 2022 (P = .48). CONCLUSIONS: The overall incidence of PEP is 10.2% but is 14.1% among high-risk patients based on this systematic review of placebo or no-stent arms of 145 RCTs; this rate has not changed between 1977 and 2022. Severe PEP and mortality from PEP are relatively uncommon.

Novel through-the-scope suture closure of colonic EMR defects (with video).

BACKGROUND AND AIMS: Large colon polyps removed by EMR can be complicated by delayed bleeding. Prophylactic defect clip closure can reduce post-EMR bleeding. Larger defects can be challenging to close using through-the-scope clips (TTSCs), and proximal defects are difficult to reach using over-the-scope techniques. A novel, through-the-scope suturing (TTSS) device allows direct closure of mucosal defects without scope withdrawal. The goal of this study was to evaluate the rate of delayed bleeding after the closure of large colon polyp EMR sites with TTSS. METHODS: A multicenter retrospective cohort study was performed involving 13 centers. All defect closure by TTSS after EMR of colon polyps ≥2 cm from January 2021 to February 2022 were included. The primary outcome was rate of delayed bleeding. RESULTS: A total of 94 patients (52% female; mean age, 65 years) underwent EMR of predominantly right-sided (n = 62 [66%]) colon polyps (median size, 35 mm; interquartile range, 30-40 mm) followed by defect closure with TTSS during the study period. All defects were successfully closed with TTSS alone (n = 62 [66%]) or with TTSS and TTSCs (n = 32 [34%]), using a median of 1 (interquartile range, 1-1) TTSS system. Delayed bleeding occurred in 3 patients (3.2%), with 2 requiring repeated endoscopic evaluation/treatment (moderate). CONCLUSION: TTSS alone or with TTSCs was effective in achieving complete closure of all post-EMR defects, despite a large lesion size. After TTSS closure with or without adjunctive devices, delayed bleeding was seen in 3.2% of cases. Further prospective studies are needed to validate these findings before wider adoption of TTSS for large polypectomy closure.

Safety and feasibility of same-day discharge after endoscopic submucosal dissection: a Western multicenter prospective cohort study.

BACKGROUND AND AIMS: Recent Western studies support the safety and efficacy of endoscopic submucosal dissection (ESD) for lesions throughout the GI tract. Although admission for observation after ESD is standard in Asia, a more selective approach may optimize resource utilization. We aimed to evaluate the safety and feasibility of same-day discharge (SDD) after ESD and factors associated with admission. METHODS: This was a post hoc analysis of a multicenter, prospective cohort of patients undergoing ESD (2016-2021). The primary end points were safety of SDD and factors associated with post-ESD admission. RESULTS: Of 831 patients (median age, 67 years; 57% male) undergoing 831 ESDs (240 performed in the esophagus, 126 in the stomach, and 465 in the colorectum; median lesion size, 44 mm), 588 (71%) were SDD versus 243 (29%) admissions. Delayed bleeding and perforation occurred in 12 (2%) and 4 (.7%) of SDD patients, respectively; only 1 (.2%) required surgery. Of the 243 admissions, 223 (92%) were discharged after ≤24 hours of observation. Interestingly, larger lesion size (>44 mm) was not associated with higher admission rate (odds ratio [OR], .5; 95% confidence interval [CI], .3-.8; P = .001). Lesions in the upper GI tract versus colon (OR, 1.7; 95% CI, 1.1-2.6; P = .01), invasive cancer (OR, 1.9; 95% CI, 1.2-3.1; P = .01), and adverse events (OR, 2.7; 95% CI, 1.5-4.8; P = .001) were independent factors for admission. Admissions were more likely performed by endoscopists with ESD volume <50 cases (OR, 2.1; 95% CI, 1.3-3.3; P = .001) with procedure time >75 minutes (OR, 13.5; 95% CI, 8.5-21.3; P < .0001). CONCLUSIONS: SDD after ESD can be safe and feasible. Patients with invasive cancer, lesions in the upper GI tract, longer procedure times, or procedures performed by low-volume ESD endoscopists are more likely to be admitted postprocedure. Risk stratification of patients for SDD after ESD should help optimize resource utilization and enhance ESD uptake in the West. (Clinical trial registration number: NCT02989818.).

A novel through-the-scope helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: a multicenter study.

BACKGROUND: Complete closure of large mucosal defects following colorectal endoscopic submucosal dissection (ESD) with through-the-scope (TTS) clips is oftentimes not possible. We aimed to report our early experience of using a novel TTS suturing system for the closure of large mucosal defects after colorectal ESD. METHODS: We performed a retrospective multicenter cohort study of consecutive patients who underwent attempted prophylactic defect closure using the TTS suturing system after colorectal ESD. The primary outcome was technical success in achieving complete defect closure, defined as a < 5 mm residual mucosal defect in the closure line using TTS suturing, with or without adjuvant TTS clips. RESULTS: 82 patients with a median defect size of 30 (interquartile range 25-40) mm were included. Technical success was achieved in 92.7 % (n = 76): TTS suturing only in 44 patients (53.7 %) and a combination of TTS suturing to approximate the widest segment followed by complete closure with TTS clips in 32 (39.0 %). Incomplete/partial closure, failure of appropriate TTS suture deployment, and the need for over-the-scope salvage closure methods were observed in 7.3 % (n = 6). One intraprocedural bleed, one delayed bleed, and three intraprocedural perforations were observed. There were no adverse events related to placement of the TTS suture. CONCLUSION: The TTS suture system is an effective and safe tool for the closure of large mucosal defects after colorectal ESD and is an alternative when complete closure with TTS clips alone is not possible.

Endoscopic Submucosal Dissection in the Stomach and Duodenum: Techniques, Indications, and Outcomes.

Gastric endoscopic submucosal dissection (ESD) is established for management of early gastric cancer (EGC). Diagnosis of EGC relies on adequate endoscopic assessment involving lesion size, histopathology, presence of ulceration, and depth of invasion. Absolute indications for endoscopic resection of EGC are if patients are presumed to have a less than 1% risk of lymph node metasta endoscopic submucosal dissectionsis, and long-term outcomes are similar to those with surgical gastrectomy. Duodenal ESD is more technically difficult and requires expertise in ESD in other locations.

Generation and multiomic profiling of a TP53/CDKN2A double-knockout gastroesophageal junction organoid model.

Inactivation of the tumor suppressor genes tumor protein p53 (TP53) and cyclin-dependent kinase inhibitor 2A (CDKN2A) occurs early during gastroesophageal junction (GEJ) tumorigenesis. However, because of a paucity of GEJ-specific disease models, cancer-promoting consequences of TP53 and CDKN2A inactivation at the GEJ have not been characterized. Here, we report the development of a wild-type primary human GEJ organoid model and a CRISPR-edited transformed GEJ organoid model. CRISPR-Cas9-mediated TP53 and CDKN2A knockout (TP53/CDKN2AKO) in GEJ organoids induced morphologic dysplasia and proneoplastic features in vitro and tumor formation in vivo. Lipidomic profiling identified several platelet-activating factors (PTAFs) among the most up-regulated lipids in CRISPR-edited organoids. PTAF/PTAF receptor (PTAFR) abrogation by siRNA knockdown or a pharmacologic inhibitor (WEB2086) reduced proliferation and other proneoplastic features of TP53/CDKN2AKO GEJ organoids in vitro and tumor formation in vivo. In addition, murine xenografts of Eso26, an established human esophageal adenocarcinoma cell line, were suppressed by WEB2086. Mechanistically, TP53/CDKN2A dual inactivation disrupted both the transcriptome and the DNA methylome, likely mediated by key transcription factors, particularly forkhead box M1 (FOXM1). FOXM1 activated PTAFR transcription by binding to the PTAFR promoter, further amplifying the PTAF-PTAFR pathway. Together, these studies established a robust model system for investigating early GEJ neoplastic events, identified crucial metabolic and epigenomic changes occurring during GEJ model tumorigenesis, and revealed a potential cancer therapeutic strategy. This work provides insights into proneoplastic mechanisms associated with TP53/CDKN2A inactivation in early GEJ neoplasia, which may facilitate early diagnosis and prevention of GEJ neoplasms.