Advanced endoscopic imaging for detection of Barrett's esophagus.

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC), and is caused by chronic gastroesophageal reflux. BE can progress over time from metaplasia to dysplasia, and eventually to EAC. EAC is associated with a poor prognosis, often due to advanced disease at the time of diagnosis. However, if BE is diagnosed early, pharmacologic and endoscopic treatments can prevent progression to EAC. The current standard of care for BE surveillance utilizes the Seattle protocol. Unfortunately, a sizable proportion of early EAC and BE-related high-grade dysplasia (HGD) are missed due to poor adherence to the Seattle protocol and sampling errors. New modalities using artificial intelligence (AI) have been proposed to improve the detection of early EAC and BE-related HGD. This review will focus on AI technology and its application to various endoscopic modalities such as high-definition white light endoscopy, narrow-band imaging, and volumetric laser endomicroscopy.

Rio de Janeiro Global Consensus on Landmarks, Definitions, and Classifications in Barrett's Esophagus: World Endoscopy Organization Delphi Study.

BACKGROUND & AIMS: Despite the significant advances made in the diagnosis and treatment of Barrett's esophagus (BE), there is still a need for standardized definitions, appropriate recognition of endoscopic landmarks, and consistent use of classification systems. Current controversies in basic definitions of BE and the relative lack of anatomic knowledge are significant barriers to uniform documentation. We aimed to provide consensus-driven recommendations for uniform reporting and global application. METHODS: The World Endoscopy Organization Barrett's Esophagus Committee appointed leaders to develop an evidence-based Delphi study. A working group of 6 members identified and formulated 23 statements, and 30 internationally recognized experts from 18 countries participated in 3 rounds of voting. We defined consensus as agreement by ≥80% of experts for each statement and used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the quality of evidence and the strength of recommendations. RESULTS: After 3 rounds of voting, experts achieved consensus on 6 endoscopic landmarks (palisade vessels, gastroesophageal junction, squamocolumnar junction, lesion location, extraluminal compressions, and quadrant orientation), 13 definitions (BE, hiatus hernia, squamous islands, columnar islands, Barrett's endoscopic therapy, endoscopic resection, endoscopic ablation, systematic inspection, complete eradication of intestinal metaplasia, complete eradication of dysplasia, residual disease, recurrent disease, and failure of endoscopic therapy), and 4 classification systems (Prague, Los Angeles, Paris, and Barrett's International NBI Group). In round 1, 18 statements (78%) reached consensus, with 12 (67%) receiving strong agreement from more than half of the experts. In round 2, 4 of the remaining statements (80%) reached consensus, with 1 statement receiving strong agreement from 50% of the experts. In the third round, a consensus was reached on the remaining statement. CONCLUSIONS: We developed evidence-based, consensus-driven statements on endoscopic landmarks, definitions, and classifications of BE. These recommendations may facilitate global uniform reporting in BE.

Measuring the Submucosal Depth of Invasion in Endoscopic Mucosal Resections for Barrett-associated Adenocarcinoma: Practical Issues and Relevance for the Decision for Esophagectomy.

CONTEXT.­: Endoscopic mucosal resection (EMR) has made it possible for Barrett esophagus patients with superficial cancers to be treated without esophagectomy. Recent guidelines recommend measuring depth of invasion (DOI) in submucosal cancers based on reports that in low-risk cancers, submucosal invasion 500 µm or less is associated with low nodal metastasis rates. However, pathologists face challenges in reproducibly measuring DOI. OBJECTIVE.­: To determine how often DOI measurements could impact treatment and to evaluate reproducibility in measuring submucosal DOI in EMR specimens. DESIGN.­: Consecutive adenocarcinoma EMR cases were identified, including cases of "low histologic risk" submucosal cancer, as follows: those with negative deep margins, no high-grade histology (G3), and no lymphovascular invasion. Submucosal DOI was measured by 7 pathologists according to guidelines. RESULTS.­: Of 213 cancer EMR cases, 46 were submucosa invasive and 6 cases were low histologic risk submucosal cancers for which measurement could impact decision-making. Of these low histologic risk cases, 3 were categorized as superficial, indicating that measurement would be a clinically actionable decision point in only 1.4% of adenocarcinoma EMRs. Interobserver agreement for in-depth categorization between 7 pathologists was moderate (κ = 0.42), and the range of measurements spanned the 500-µm relevant threshold in 40 of 55 measured samples (72.7%). CONCLUSIONS.­: While therapeutic decisions would rarely have depended on DOI measurements alone in our cohort, interobserver variability raises concerns about their use as a sole factor on which to offer patients conservative therapy. Responsibly reporting and clinically using submucosal DOI measurements will require practical experience troubleshooting common histologic artifacts, as well as multidisciplinary awareness of the impact of variable specimen-handling practices.

Endoscopic submucosal dissection for colorectal lesions: outcomes from a United States experience.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is commonly used in Asia for resection of large non-pedunculated colorectal polyps (LNPCPs) and early (T1) colorectal cancers. It allows for en bloc removal and is often curative. We describe outcomes of colorectal ESD from a United States (US) academic medical center and compare this to international experiences. METHODS: Retrospective review was performed of colonic lesions referred to the University of Chicago Medical Center for ESD from 2012 to 2020. Clinical and procedural data were collected. RESULTS: The study included 78 lesions with mean size of 29.7 mm (range 10-100 mm). The overall en bloc resection rate was 73.1% (n = 57). Between the first and second half of the study, it improved from 61.5 to 84.6% (p = 0.02). Histology showed adenocarcinoma in fifteen lesions (19.2%). Of all neoplastic lesions (n = 68), resection with negative margins (R0) was achieved in 54 cases (79.4%). Adverse events occurred in 9 cases (11.5%), but most (n = 6, 66.7%) were successfully treated endoscopically. Follow-up endoscopy was performed in 46 patients (59.0%) at a mean interval of 6.8 months (SD ± 5.0 months) with two case of recurrent lesion (4.3%). CONCLUSIONS: This study shows successful colorectal ESD outcomes at a US tertiary center. The en bloc resection rate was lower than other cohorts, but a learning curve was demonstrated. The R0 resection, lesion recurrence, and adverse event rates were similar to other non-Asian experiences, but not as favorable as in Asia [Fuccio et al. in Gastrointest Endosc 86:74-86.e17, 2017]. Increased ESD training in the US can help optimize utilization and outcomes.

External validation of blue light imaging (BLI) criteria for the optical characterization of colorectal polyps by endoscopy experts.

BACKGROUND AND AIM: Recently, the BLI Adenoma Serrated International Classification (BASIC) system was developed by European experts to differentiate colorectal polyps. Our aim was to validate the BASIC classification system among the US-based endoscopy experts. METHODS: Participants utilized a web-based interactive learning system where the group was asked to characterize polyps using the BASIC criteria: polyp surface (presence of mucus, regular/irregular and [pseudo]depressed), pit appearance (featureless, round/non-round with/without dark spots; homogeneous/heterogeneous distribution with/without focal loss), and vessels (present/absent, lacy, peri-cryptal, irregular). The final testing consisted of reviewing BLI images/videos to determine whether the criteria accurately predicted the histology results. Confidence in adenoma identification (rated "1" to "5") and agreement in polyp (adenoma vs non-adenoma) identification and characterization per BASIC criteria were derived. Strength of interobserver agreement with kappa (k) value was reported for adenoma identification. RESULTS: Ten endoscopy experts from the United States identified conventional adenoma (vs non-adenoma) with 94.4% accuracy, 95.0% sensitivity, 93.8% specificity, 93.8% positive predictive value, and 94.9% negative predictive value using BASIC criteria. Overall strength of interobserver agreement was high: kappa 0.89 (0.82-0.96). Agreement for the individual criteria was as follows: surface mucus (93.8%), regularity (65.6%), type of pit (40.6%), pit visibility (66.9%), pit distribution (57%), vessel visibility (73%), and being lacy (46%) and peri-cryptal (61%). The confidence in diagnosis was rated at high ≥4 in 67% of the cases. CONCLUSIONS: A group of US-based endoscopy experts have validated a simple and easily reproducible BLI classification system to characterize colorectal polyps with >90% accuracy and a high level of interobserver agreement.

Endoscopic resection is more effective than biopsy or EUS to detect residual rectal neuroendocrine tumor.

Background and study aims Rectal neuroendocrine tumors (NETs) are often discovered incidentally and may be misidentified as adenomatous polyps. This can result in a partial resection at the index procedure, and lesions are often referred for staging or evaluation for residual disease at the resection site. The aim of this study was to identify the ideal method to confirm complete excision of small rectal NETs. Patients and methods Data from patients with a previously resected rectal NET referred for follow-up endoscopy or endoscopic ultrasound (EUS) were retrospectively reviewed. Univariate analysis was performed on categorical data using the Chi-squared test. Results Forty-nine patients with rectal NETs were identified by pathology specimens. Of those, 39 underwent follow-up endoscopy or EUS and were included. Baseline characteristics included gender (71 % F, 29 % M), age (57.2 ±â€Š13.4 yrs) lesion size (7.3 ±â€Š4.2 mm) and location. The prior resection site was identified in 37/39 patients who underwent tissue sampling. Residual NET was found histologically in 14/37 lesions. All residual disease was found during salvage endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) and 43 % had a normal-appearing scar. Every patient undergoing EUS had an unremarkable exam. Initial cold biopsy polypectomy ( P  = 0.006), visible lesions ( P  = 0.001) and EMR/ESD of the prior resection site ( P  = 0.01) correlated with residual NET. Conclusions Localized rectal NETs may be incompletely removed with standard polypectomy. If an advanced resection is not performed initially, repeat endoscopy with salvage EMR or ESD of the scar should be considered. For small rectal NETs, biopsy may miss residual disease when there is no visible lesion and EUS appears to have no benefit.

Histologic changes caused by injection of a novel submucosal lifting agent for endoscopic resection in GI lesions.

BACKGROUND AND AIMS: ORISE Gel is a recently introduced, U.S. Food and Drug Administration-approved submucosal lifting agent used in endoscopic resection of GI lesions. Histologically evident gel deposits in resected specimens may pose a potential diagnostic pitfall. To aid in recognition of this procedure-related artifact, we report the largest histologic series of ORISE Gel in endoscopic and surgical resection specimens to date. METHODS: Fifty-eight EMR/endoscopic submucosal dissection (ESD) specimens with ORISE Gel injection and 5 interval surgical resection specimens with previous ORISE Gel injection were included. Patient demographics and endoscopy reports were obtained. Histologic slides from all cases were reviewed. Histochemical stains were performed on select cases. RESULTS: Fifty-one EMR and 7 ESD specimens were identified. In 51 of 58 (88%) endoscopic resection specimens, amorphous, pale blue-gray, finely granular material was evident in the submucosa, as well as focally within the mucosa in 4 cases. Most cases showed homogeneous near-complete filling of the submucosa with this material, whereas a few demonstrated areas of condensation and retraction. Mucicarmine and periodic acid-Schiff stains were negative for mucin. Interval surgical resection specimens revealed extensive deposition of dense, eosinophilic material with associated multinucleated giant cells in the submucosa in all cases, with transmural extension in 3 cases. CONCLUSION: ORISE Gel injection during endoscopic resection of GI lesions results in deposition of amorphous, blue-gray material seen in histologic sections, whereas interval surgical resection specimens demonstrate dense, eosinophilic material with an associated giant cell reaction. Awareness of these artifacts will help avoid misinterpretation of their presence as pathologic findings.

Multifocal Cryoballoon Ablation for Eradication of Barrett's Esophagus-Related Neoplasia: A Prospective Multicenter Clinical Trial.

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1-6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).

Endoscopic ultrasound acquired portal venous circulating tumor cells predict progression free survival and overall survival in patients with pancreaticobiliary cancers.

BACKGROUND AND AIMS: Despite recent advances, patients with pancreaticobiliary cancers have a poor prognosis. We previously demonstrated the efficacy of endoscopic ultrasound (EUS) guided acquisition of portal vein (PV) blood for enumeration of circulating tumor cells (CTCs). The aim of this study was to assess PV-CTCs as potential biomarkers for the assessment of progression-free (PFS) and overall survival (OS) in patients with pancreaticobiliary cancers. METHODS: 17 patients with biopsy-proven pancreaticobiliary malignancy were enrolled. CTCs were enumerated from both peripheral and PV blood. All patients were followed until death. PFS and OS were evaluated with the log-rank test and summarized with the use of Kaplan-Meier methods. Unadjusted and adjusted Cox-proportional hazards models were fitted to study the relationship between PV-CTCs and PFS and OS. RESULTS: After 3.5 years of follow-up, all patients had expired. PV-CTCs were detected in all patients (median PV-CTCs 62.0/7.5 mL (interquartile range [IQR] 17-132). The mean PFS in patients with PV-CTCs <185/7.5 mL was significantly longer than patients with PV-CTCs ≥185/7.5 mL (43.3 weeks vs. 12.8 weeks, log-rank p = 0.002). The mean OS in patients with PV-CTCs <185/7.5 mL was significantly longer than patients with PV-CTCs ≥185/7.5 mL (75.8 weeks vs. 29.5 weeks, log-rank p = 0.021). In an adjusted Cox-proportional hazards model, PV-CTCs were significant predictors of both PFS and OS (HR 1.004, p = 0.037; HR 1.004, p = 0.044 respectively). CONCLUSION: In this pilot and feasibility study, EUS-acquired PV-CTCs predicted PFS and OS. Our findings suggest that PV-CTCs can help provide important prognostic data for both providers and patients.

Dissection-enabled scaffold-assisted resection (DeSCAR): a novel technique for resection of residual or non-lifting gastrointestinal neoplasia of the colon, expanded experience and follow-up.

Background and study aims Colonic lesions may not be amenable to conventional endoscopic mucosal resection (EMR) due to previous manipulation, submucosal invasion, or lesion flatness. In 2018, we described Dissection-enabled Scaffold Assisted Resection (DeSCAR) to be safe for the endoscopic resection of non-lifting or residual colonic lesions 1 In this study, we expand our original cohort to describe our expanded experience with patients undergoing DeSCAR and assess the efficacy, safety, and feasibility of DeSCAR for endoscopic resection of non-lifting or residual colonic lesions. Patients and methods We retrospectively reviewed 57 patients from 2015-2019 who underwent DeSCAR for colonic lesions with incomplete lifting and/or previous manipulation. Cases were reviewed for location, prior manipulation, rates of successful resection, adverse events, and endoscopic follow up to assess for residual lesions. Results Fifty-seven lesions underwent DeSCAR. Of the patients, 51 % were female, and average patient age was 69 years. Lesions were located in the cecum (n = 16), right colon (n = 27), left colon (n = 10), and rectum (n = 4). Average lesion size was 27.7 mm. Previous manipulation occurred in 54 cases (72 % biopsy, 44 % resection attempt, 18 % intralesional tattoo). The technical success rate for resection of non-lifting lesions was 98 %. There were two delayed bleeding episodes (one required endoscopic intervention) and one small perforation (managed by endoscopic hemoclip closure). Endoscopic follow up was available in 31 patients (54 %) with no residual adenoma in 28 patients (90 % of those surveilled). Conclusions Our expanded experience with DeSCAR demonstrates high safety, feasibility, and effectiveness for the endoscopic management of non-lifting or residual colonic lesions.

EUS-Guided Portal Venous Sampling of Circulating Tumor Cells.

PURPOSE OF REVIEW: Although liquid biopsies hold significant promise in the management of patients with cancer, peripheral blood analyses remain dependent on the degree of tumor burden with prohibitively low yields until the cancer is widely metastatic. Multiple lines of evidence support a dynamic, spatiotemporal localization of circulating tumor cells (CTCs) supporting specific targeting of vascular compartments, such as the portal vein. This review discusses the literature evaluating the possibility of portal venous blood as a new, potentially higher yield liquid biopsy and the current devices and techniques for endoscopic ultrasound (EUS)-guided portal venous sampling for CTC detection. RECENT FINDINGS: Two recent studies in pancreatic cancer have demonstrated that portal venous blood can be safely sampled via EUS and consistently yields significantly higher CTC counts compared with matched peripheral blood. EUS-acquired samples can be used for molecular testing, clinical prognostication, and drug sensitivity analyses. Portal venous CTCs are identified in higher quantity relative to peripheral blood and can be safely obtained via EUS. Further studies are required to demonstrate the clinical utility of EUS-guided portal venous tumor material enrichment and analysis; however, obtaining EUS-guided "liquid biopsies" appears to merit significant consideration for procedural adoption.

Changes in tumor vascularity depicted by contrast-enhanced EUS as a predictor of prognosis and treatment efficacy in patients with unresectable pancreatic cancer (PEACE): A study protocol.

Patients with unresectable pancreatic cancer have a poor prognosis. The analysis of prognostic factors before treatment may be helpful in determining the best therapeutic strategies. The aim of the PEACE study is to assess the vascularity of pancreatic malignant tumors using contrast-enhanced harmonic EUS (CEH-EUS) and to clarify the prognostic value of tumor vascularity in patients with locally advanced and metastatic pancreatic cancer. Hereby, we present the protocol of a prospective, nonrandomized, single-arm, multicenter study aiming to assess changes in tumor vascularity using CEH-EUS before and 2 months after treatment initiation in patients with unresectable, locally advanced/metastatic pancreatic cancer and to examine the correlation between vascular changes and treatment response, progression-free survival, and overall survival.

EUS-guided portal vein sampling.

EUS provides real-time images of the intramural gastrointestinal tract and adjacent structures that otherwise would not be visible. Given the anatomic proximity to the bowel, accurate identification of the major abdominal vasculature, such as the portal vein, serves as a useful landmark tool for identifying anatomy and staging of malignancies. Recently, increased reports have centered on the utility of EUS-guided vascular access of the portal vein for diagnostic and therapeutic interventions. Pilot and feasibility studies in human patients utilizing EUS-guided portal vein access for circulating tumor cell enumeration and portal pressure gradient monitoring suggest that sampling the portal vein under EUS guidance is safe and effective. This review discusses the rationale and technical aspects of EUS-guided portal vein sampling for diagnostic purposes in gastrointestinal cancer. Understanding the technical aspects of EUS-guided portal vein sampling will be critical to standardizing the procedure, developing new vascular access technologies, and increasing the safety profile.

Dissection-enabled scaffold-assisted resection (DeSCAR): a novel technique for resection of residual or non-lifting GI neoplasia of the colon (with video).

BACKGROUND AND AIMS: As a result of previous manipulation or submucosal invasion, GI lesions referred for EMR frequently have flat areas of visible tissue that cannot be snared. Current methods for treating residual tissue may lead to incomplete eradication or not allow complete tissue sampling for histologic evaluation. Our aim is to describe dissection-enabled scaffold-assisted resection (DeSCAR), a new technique combining circumferential ESD with EMR for removal of superficial non-lifting or residual "islands" with suspected submucosal involvement/fibrosis. METHODS: From 2015 to 2017, lesions referred for EMR were retrospectively reviewed. Cases were identified where lifting and/or snaring of the lesion was incomplete and the DeSCAR technique was undertaken. Cases were reviewed for location, previous manipulation, rates of successful hybrid resection, and adverse events. RESULTS: Twenty-nine lesions underwent DeSCAR because of non-lifting or residual "islands" of tissue. Fifty-two percent of the patients were male and 48% were female; average age was 66 years (standard deviation ±9.9 years). Lesions were located in the cecum (n = 10), right side of the colon (n = 12), left side of the colon (n = 4), and rectum (n = 3). Average size was 31 mm (standard deviation ±20.6 mm). Previous manipulation had occurred in 28 of 29 cases (83% biopsy, 34% resection attempt, 52% tattoo). The technical success rate for resection of non-lifting lesions was 100%. There was one episode of delayed bleeding but no other adverse events. CONCLUSIONS: DeSCAR is a feasible and safe alternative to argon plasma coagulation and avulsion for the endoscopic management of non-lifting or residual GI lesions, providing en bloc resection of tissue for histologic review. Further studies are needed to demonstrate long-term eradication and for comparison with other methods.

EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-Summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop.

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic EUS. The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

Use of volumetric laser endomicroscopy for dysplasia detection at the gastroesophageal junction and gastric cardia.

AIM: To determine specific volumetric laser endomicroscopy (VLE) imaging features associated with neoplasia at the gastroesophageal junction (GEJ) and gastric cardia. METHODS: During esophagogastroduodenoscopy for patients with known or suspected Barrett's esophagus, VLE was performed before biopsies were taken at endoscopists' discretion. The gastric cardia was examined on VLE scan from the GEJ (marked by top of gastric folds) to 1 cm distal from the GEJ. The NinePoints VLE console was used to analyze scan segments for characteristics previously found to correlate with normal or abnormal mucosa. Glands were counted individually. Imaging features identified on VLE scan were correlated with biopsy results from the GEJ and cardia region. RESULTS: This study included 34 cases. Features characteristic of the gastric cardia (gastric rugae, gastric pit architecture, poor penetration) were observed in all (100%) scans. Loss of classic gastric pit architecture was common and there was no difference between those with neoplasia and without (100% vs 74%, P = NS). The abnormal VLE feature of irregular surface was more often seen in patients with neoplasia than those without (100% vs 18%, P < 0.0001), as was heterogeneous scattering (86% vs 41%, P < 0.005) and presence of anomalous glands (100% vs 59%, P < 0.05). The number of anomalous glands did not differ between individual histologic subgroups (ANOVA, P = NS). CONCLUSION: The transition from esophagus to gastric cardia is reliably identified on VLE. Histologically abnormal cardia mucosa produces abnormal VLE features. Optical coherence tomography algorithms can be expanded for use at the GEJ/cardia.