AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia.

BACKGROUND & AIMS: Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS: The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS: This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

Intensifying supportive care is associated with improved survival in gastric cancer patients with malignant ascites.

BACKGROUND: Gastric cancer patients with malignant ascites often have poor functional status and malnutrition that preclude receipt of systemic therapies. Thus, these patients have a very poor prognosis. Beginning in 2019, our multidisciplinary gastric cancer disease-oriented team implemented a more aggressive supportive care plan for gastric cancer patients with malignant ascites. The initiative included measures such as supplemental enteral nutrition, ascites drainage, and initiation of chemotherapy on an inpatient basis. We compared outcomes for gastric cancer patients who presented with synchronous malignant ascites treated before and after the implementation of the care plan. METHODS: We performed a retrospective review of our institutional database to identify patients diagnosed with gastric adenocarcinoma and synchronous malignant ascites between 2010 and 2022. We compared overall survival (OS) between patients diagnosed from 2010 to 2018, which will be referred to as the historical control era and patients diagnosed from 2019 to 2022, which will be called the aggressive supportive care era. RESULTS: Fifty-four patients were included in our analysis; 31 patients were treated in the historical control time frame, and 23 patients were treated during the aggressive supportive care era. Demographic, clinical, and pathologic characteristics were similar between groups. 3% of historical controls received supplemental tube feeds at diagnosis as compared to 30% of the aggressive supportive care cohort (p < 0.01). 3% of historical controls received their first cycle of chemotherapy in the inpatient setting versus 39% of patients treated during the aggressive supportive care era (p < 0.01). The median number of chemotherapy cycles received was 5 among historical controls and 9.5 among aggressive supportive care era patients (p = 0.02). There was no difference in the number of days spent as an inpatient between the two groups. The median OS for historical control patients was 5.4 months as compared with 10.4 months for patients treated during aggressive supportive care era (p = 0.04). CONCLUSIONS: Gastric cancer patients with synchronous malignant ascites treated during a timeframe when our multidisciplinary team implemented more aggressive supportive care measures had improved OS as compared with historic controls. Our results suggest that aggressive supportive measures for these patients with highly challenging clinical issues and poor prognosis can prolong survival. Specifically, initiation of chemotherapy in the inpatient setting and supplemental nutrition should be considered for patients at high risk for treatment intolerance.

A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

High Proportions of Newly Detected Visible Lesions and Pathology Grade Change Among Patients with Barrett's Esophagus Referred to Expert Centers.

BACKGROUND AND AIMS: Endoscopic eradication therapy for Barrett's esophagus (BE)-related neoplasia is increasingly being performed at tertiary and community centers. While it has been suggested that these patients should be evaluated at expert centers, the impact of this practice has not been evaluated. We aimed to assess the impact of referral of BE-related neoplasia patients to expert centers by assessing the proportion of patients with change in pathological diagnosis and visible lesions detected. METHODS: Multiple databases were searched until December 2021 for studies of patients with BE referred from the community to expert center. The proportions of pathology grade change and newly detected visible lesions at expert centers were pooled using a random-effects model. Subgroup analyses were performed based on baseline histology and other relevant factors. RESULTS: Twelve studies were included (1630 patients). The pooled proportion of pathology grade change after expert pathologist review was 47% (95% CI 34-59%) overall and 46% (95% CI 31-62%) among patients with baseline low-grade dysplasia. When upper endoscopy was repeated at an expert center, the pooled proportion of pathology grade change was still high 47% (95% 26-69%) overall and 40% (95% CI 34-45%) among patients with baseline LGD. The pooled proportion of newly detected visible lesions was 45% (95% CI 28-63%) and among patients referred with LGD was 27% (95% CI 22-32%). CONCLUSION: An alarmingly high proportion of newly detected visible lesions and pathology grade change were found when patients were referred to expert centers supporting the need for centralized care for BE-related neoplasia patients.

Limitations of Heartburn and Other Societies' Criteria in Barrett's Screening for Detecting De Novo Esophageal Adenocarcinoma.

BACKGROUND & AIMS: Despite extensive Barrett's esophagus (BE) screening efforts, most patients with esophageal adenocarcinoma (EAC) present de novo. It is unclear how much of this problem is the result of insensitivity or poor applications of current screening guidelines. We aimed to evaluate the sensitivity of guidelines by determining the proportion of prevalent EAC cases that meet the American College of Gastroenterology (ACG) or the British Society of Gastroenterology (BSG) guidelines for BE screening and determine whether changes to criteria would enhance detection. METHODS: A retrospective single-center cohort from the United States (n = 663) and a prospective multicenter cohort from the United Kingdom (n = 645) were collected and analyzed independently. Screening eligibility was determined as patients with chronic reflux and at least 2 or more risk factors as defined by the guidelines. We calculated the proportion of screening-eligible patients and then compared BE/EAC risk factors between screening-eligible and screening-ineligible patients using the chi-squared or Student t test as appropriate. RESULTS: In the Mayo clinic cohort there were 54.9% EAC cases and in the UK cohort there were 38.9% EAC cases that were not identified by ACG or BSG screening criteria, respectively. Among patients who did not meet the screening criteria, lack of heartburn was observed in 86.5% in the Mayo clinic cohort and in 61.4% in the UK cohort. Other risk factors that were lacking included obesity (defined as a body mass index of ≥30 kg/m2) and family history of EAC. Eliminating chronic reflux from the ACG/BSG criteria improved eligibility for screening from 45.1% to 81.3% (P < .001) in the Mayo Clinic cohort and from 61.1% (n = 394) to 81.5% (n = 526; P < .001) in the UK cohort. However, reflux may be difficult to ascertain from the history, and by including proton pump inhibitor use status in addition to the BSG criteria, screening eligibility improved by 10.0% in the UK cohort (n = 459; P < .001). CONCLUSIONS: ACG/BSG BE screening guidelines have limited our ability to detect prevalent EAC. An optimized approach to identifying the individuals most suitable for EAC screening needs to be implemented, particularly one that does not rely on chronic reflux symptoms.

Magnitude and Time-Trend Analysis of Postendoscopy Esophageal Adenocarcinoma: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Identification of postendoscopy esophageal adenocarcinoma (PEEC) among Barrett's esophagus (BE) patients presents an opportunity to improve survival of esophageal adenocarcinoma (EAC). We aimed to estimate the proportion of PEEC within the first year after BE diagnosis. METHODS: Multiple databases (Medline, Embase, Scopus, and Cochrane databases) were searched until September 2020 for original studies with at least 1-year follow-up evaluation that reported EAC and/or high-grade dysplasia (HGD) in the first year after index endoscopy in nondysplastic BE, low-grade dysplasia, or indefinite dysplasia. The proportions of PEEC defined using EAC alone and EAC+HGD were calculated by dividing EAC or EAC+HGD in the first year over the total number of EAC or EAC+HGD, respectively. RESULTS: We included 52 studies with 145,726 patients and a median follow-up period of 4.8 years. The proportion of PEEC (EAC) was 21% (95% CI, 13-31) and PEEC (EAC+HGD) was 26% (95% CI, 19-34). Among studies with nondysplastic BE only, the PEEC (EAC) proportion was 17% (95% CI, 11-23) and PEEC (EAC+HGD) was 14% (95% CI, 8-19). Among studies with 5 or more years of follow-up evaluation, the PEEC (EAC) proportion was 10% and PEEC (EAC+HGD) was 19%. Meta-regression analysis showed a strong inverse relationship between PEEC and incident EAC (P < .001). The PEEC (EAC) proportion increased from 5% in studies published before 2000 to 30% after 2015. Substantial heterogeneity was observed for most analyses. CONCLUSIONS: PEEC accounts for a high proportion of HGD/EACs and is proportional to reduction in incident EAC. Using best endoscopic techniques now and performing future research on improving neoplasia detection through implementation of quality measures and educational tools is needed to reduce PEEC.

The utility of P53 immunohistochemistry in the diagnosis of Barrett's oesophagus with indefinite for dysplasia.

AIMS: Barrett's oesophagus with indefinite for dysplasia (BE-IND) is a subjective diagnosis with a low interobserver agreement (IOA) among pathologists and uncertain clinical implications. This study aimed to assess the utility of p53 immunohistochemistry (p53-IHC) in assessing BE-IND specimens. METHODS AND RESULTS: Archive endoscopic biopsies with a BE-IND diagnosis from two academic centres were analysed. First, haematoxylin and eosin-stained slides (H&E) were reviewed by four expert gastrointestinal (GI) pathologists allocated into two groups (A and B). After a washout period of at least 8 weeks, H&E slides were reassessed side-to-side with p53-IHC available. We compared the rate of changed diagnosis and the IOA for all BE grades before and after p53-IHC. We included 216 BE-IND specimens from 185 patients, 44.0 and 32.9% of which were confirmed after H&E slide revision by groups A and B, respectively. More than half the cases were reclassified to a non-dysplastic BE (NDBE), while 5.6% of cases in group A and 7.4% in group B were reclassified to definite dysplasia. The IOA for NDBE, BE-IND, low-grade dysplasia (LGD) and high-grade dysplasia (HGD)/intramucosal cancer (IMC) was 0.31, 0.21, -0.03 and -0.02, respectively. Use of p53-IHC led to a >40% reduction in BE-IND diagnoses (P < 0.001) and increased IOA for all BE grades [κ = 0.46 (NDBE), 0.26 (BE-IND), 0.49 (LGD), 0.35 (HGD/IMC)]. An aberrant p53-IHC pattern significantly increased the likelihood of reclassifying BE-IND to definite dysplasia (odds ratio = 44.3, 95% confidence interval = 18.8-113.0). CONCLUSION: P53-IHC reduces the rate of BE-IND diagnoses and improves the IOA among pathologists when reporting BE with equivocal epithelial changes.

Esophageal adenocarcinoma phenotypes and risk factors.

PURPOSE OF REVIEW: The incidence of esophageal adenocarcinoma (EAC) has increased significantly over the last several decades. The majority of EAC patients present without a prior history of Barrett's esophagus (BE). As a result, endoscopic surveillance has made a suboptimal impact on EAC survival. These concerns raise serious question whether the time has come to take a different direction. The aim of this article is to review evolving evidence of EAC phenotypes and risk factors. RECENT FINDINGS: A recent study has identified two phenotypes of EAC based on the presence or absence of intestinal metaplasia (IM) in the background of the tumor (BE/IM and non-BE/IM). The study found that one-half of patients with EAC have the non-BE/IM phenotype, which is associated with more aggressive behavior and worse survival. A retrospective review demonstrates that the proportion of the two phenotypes has been stable over the last decades. Similarly, the increasing incidence of EAC cannot be explained by an increased frequency of new, unique risk factors but rather by a higher prevalence of already known risk factors. Emerging data also demonstrates that, whereas reflux symptoms are an unreliable feature for screening regardless of phenotype, the absence of reflux symptoms is more common for the non-BE/IM. Differences in the degree of genomic methylation and immune response might explain the two phenotypes at a genomic level. SUMMARY: EAC phenotypes have implications for tumor behavior and phenotypic differences might underlie our suboptimal screening efforts. Future screening efforts should not uniformly rely on reflux symptoms as a prerequisite for screening and should consider alternatives to the current screening strategy.

Impact of trimodality sampling on detection of malignant biliary strictures compared with patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: Malignant biliary strictures can be difficult to diagnose, with up to 20% considered indeterminate after initial tissue sampling. This study aimed to determine the performance characteristics of transpapillary biopsy sampling (TPB) and fluorescence in situ hybridization (FISH) in isolation or in combination with standard brush cytology (BC) in patients who received trimodality sampling for biliary strictures. METHODS: This single-center retrospective cohort study included patients with biliary strictures undergoing ERCP with trimodality sampling between September 2014 and April 2019. Performance characteristics for each diagnostic test alone and in combination were calculated. RESULTS: Two hundred four patients underwent trimodality biliary sampling, including 104 (51.0%) with malignancy. The diagnostic sensitivity for malignancy with BC (17.3%) significantly improved with dual modality (BC+FISH, 58.7%; BC+TPB, 40.4%) or trimodality sampling (68.3%; P < .001 for all comparisons). Trimodality sampling improved diagnostic sensitivity for malignancy compared with BC+FISH (P = .002) and BC+TPB (P < .001). There was no statistically significant difference in the sensitivity of trimodality sampling in detecting cholangiocarcinoma (79.7%) compared with pancreatic cancer (62.5%; P = .1). Among 57 patients with primary sclerosing cholangitis (PSC), the sensitivity of detecting biliary malignancy (n = 20) was 20% for BC and significantly improved with the addition of FISH (80%; P < .001) but not with TPB (35.0%; P = .25). Trimodality sampling did not further improve diagnostic sensitivity (85%) over BC+FISH (80%) for malignancy in the setting of PSC (P = 1). CONCLUSIONS: Trimodality sampling improves the diagnostic sensitivity for the detection of malignant biliary strictures with no significant difference in sensitivity for cholangiocarcinoma compared with pancreatic cancer. However, in patients with PSC, trimodality sampling was not superior to BC+FISH.

Utilisation of artificial intelligence for the development of an EUS-convolutional neural network model trained to enhance the diagnosis of autoimmune pancreatitis.

OBJECTIVE: The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time. DESIGN: A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC. RESULTS: From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP). CONCLUSION: The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.

Risk Factor Profiles Can Distinguish Esophageal Adenocarcinoma From Barrett's Esophagus.

INTRODUCTION: It is assumed that screening risk factors for Barrett's esophagus (BE) and prevalent esophageal adenocarcinoma (EAC) are the same. METHODS: A matched case-control study comparing risk factors between EAC and BE was performed. RESULTS: In 1,356 patients (678 with EAC and 678 with BE), heartburn (52.7%), diabetes, hyperlipidemia, hypertension, nonalcoholic steatohepatitis, and metabolic syndrome were less common in EAC (52.7, 29.2, 45.7, 48.2, 12, and 28.5%, resp.) compared with BE (84.5, 37.6, 82.2, 64.6, 18.4, and 44.1%, P < 0.01). Mean alanine aminotransferase and HgA1c levels were also significantly lower in EAC compared with BE. DISCUSSION: Optimal strategies for screening for prevalent EAC may be different than that for BE.

The risk of neoplasia in patients with Barrett's esophagus indefinite for dysplasia: a multicenter cohort study.

BACKGROUND AND AIMS: Current understanding of the risk of neoplastic progression in patients with Barrett's esophagus with indefinite dysplasia (BE-IND) stems from small retrospective and pathology registry studies. In this multicenter cohort study, we aimed to determine the incidence and prevalence of neoplasia in BE-IND. METHODS: Patients with confirmed BE-IND from 2 academic centers were included if they had no previous evidence of dysplasia and underwent endoscopic follow-up (FU) of ≥1 year. The rate of progression to neoplasia was calculated and categorized as prevalent (progression within 1 year of FU) and incident (progression after 1 year of FU). Multivariable regression adjusted for relevant clinical features was performed to identify risk factors for progression. RESULTS: Four hundred sixty-five patients diagnosed with BE-IND were identified between 1997 and 2017, of which 223 (48.0%) were excluded. Of the remaining 242 patients, 184 (76.0%) had no evidence of dysplasia during FU. In 23 patients (9.5%), prevalent neoplasia occurred (20 low-grade dysplasia [LGD], 2 high-grade dysplasia [HGD], 1 intramucosal cancer [IMC]), whereas 35 patients (14.5%) developed incident neoplasia (27 LGD, 5 HGD, 3 IMC), after a median 1.5 years (interquartile range, 0.6-3.2 years). The incidence rates of any neoplasia and HGD/IMC were 3.2 and 0.6 cases/100 patient-years, respectively. BE length correlated with an increased risk of prevalent (odds ratio, 1.18 per 1 cm; 95% confidence interval, 1.02-1.38; P = .033) and incident neoplasia (odds ratio, 1.02; 95% confidence interval, 1.00-1.03; P = .016). CONCLUSION: Patients with BE-IND should be closely monitored, because nearly a quarter harbor or will shortly develop dysplasia. BE length is a clinical predictor of neoplastic progression; however, more-accurate molecular biomarkers for risk stratification are warranted.

Application of artificial intelligence using a novel EUS-based convolutional neural network model to identify and distinguish benign and malignant hepatic masses.

BACKGROUND AND AIMS: Detection and characterization of focal liver lesions (FLLs) is key for optimizing treatment for patients who may have a primary hepatic cancer or metastatic disease to the liver. This is the first study to develop an EUS-based convolutional neural network (CNN) model for the purpose of identifying and classifying FLLs. METHODS: A prospective EUS database comprising cases of FLLs visualized and sampled via EUS was reviewed. Relevant still images and videos of liver parenchyma and FLLs were extracted. Patient data were then randomly distributed for the purpose of CNN model training and testing. Once a final model was created, occlusion heatmap analysis was performed to assess the ability of the EUS-CNN model to autonomously identify FLLs. The performance of the EUS-CNN for differentiating benign and malignant FLLs was also analyzed. RESULTS: A total of 210,685 unique EUS images from 256 patients were used to train, validate, and test the CNN model. Occlusion heatmap analyses demonstrated that the EUS-CNN model was successful in autonomously locating FLLs in 92.0% of EUS video assets. When evaluating any random still image extracted from videos or physician-captured images, the CNN model was 90% sensitive and 71% specific (area under the receiver operating characteristic [AUROC], 0.861) for classifying malignant FLLs. When evaluating full-length video assets, the EUS-CNN model was 100% sensitive and 80% specific (AUROC, 0.904) for classifying malignant FLLs. CONCLUSIONS: This study demonstrated the capability of an EUS-CNN model to autonomously identify FLLs and to accurately classify them as either malignant or benign lesions.

Comparison of Phenotypes and Risk Factors for Esophageal Adenocarcinoma at Present vs Prior Decades.

BACKGROUND & AIMS: The incidence of esophageal adenocarcinoma (EAC) has increased over the past decades. It is unclear if this increase is the result of a new cancer phenotype or an increase in risk factors for EAC. We aimed to compare risk factors, the proportions of intestinal and nonintestinal phenotypes of EAC, and survival times of patients during the 2009 to 2012 time period vs the 1996 to 1997 time period. METHODS: We performed a retrospective single-center cohort study of 829 patients with EAC from the time periods of 1996 to 1997 and 2009 to 2012. Baseline characteristics were compared using χ2 analysis for categoric variables and the Student t test for continuous variables. The Cox proportional hazards model was used to compare 5-year survival. RESULTS: We included 149 patients from the 1996 to 1997 time period and 680 patients from the 2009 to 2012 time period. There was no significant difference between the cohorts in terms of age at cancer presentation, sex, or history of smoking (P > .05). Gastroesophageal reflux symptoms were absent in almost half of the patients from each time period (P = .46). Intestinal metaplasia was identified in esophageal tumor tissues from 48.3% of patients with EAC in the 1996 to 1997 time period and in 49.9% of patients in the 2009 to 2012 time period (P = .45). Patients from each time period presented with similar-stage cancer (P = .25), most at stage III (43% in the 1996-1997 period and 37.8% in the 2009-2012 period). Having EAC during the period of 1996 to1997 was associated with an increased risk of death (hazard ratio, 1.6; 95% CI, 1.3-2.0; P = .001), compared with the 2009 to 2012 time period, in a univariate model (adjusted hazard ratio, 1.7; 95% CI, 1.4-2.1; P < .001) after we controlled for sex, age at diagnosis, tumor stage, and presence of intestinal metaplasia. CONCLUSIONS: In a comparison of patients with EAC from the time periods of 1996 to 1997 vs 2009 to 2012, we found similar and persistent proportions of tumor phenotypes, characterized by a lack of intestinal metaplasia or heartburn symptoms. The lack of symptoms could contribute to our continued inability to identify incident cancers and/or improve patient survival.

Safety and histologic outcomes of endoscopic submucosal dissection with a novel articulating knife for esophageal neoplasia.

BACKGROUND AND AIMS: Treatment of large esophageal neoplasia is gradually evolving from piecemeal to en bloc resections. Endoscopic submucosal dissection (ESD) is known to achieve more complete resections than piecemeal EMR for large lesions, yet it remains underused in the West because of technical and safety concerns with traditional electrosurgical knives. We aimed to evaluate a novel endoscopic articulating knife used with ESD (ESD-AR) to determine its safety and efficacy for large esophageal neoplasms in comparison with EMR. METHODS: We retrospectively studied clinically indicated cases of ESD-AR and EMR for esophageal lesions that were 15 mm or greater. All EMR cases had at least 3 simultaneous EMRs to adequately compare resection area. Rates of perforation, GI bleeding, technical performance, and pre- and postendoscopic resection diagnoses were evaluated. RESULTS: Seventy-two ESD-AR and 72 widespread EMR cases were evaluated for Barrett's esophagus (56%), adenocarcinoma (36%), squamous nodularity (2%), and squamous cell carcinoma (6%). There were no statistical differences in age, sex, Barrett's esophagus length, and lesion or resection size between the 2 groups. No perforations occurred. Two adverse events were recorded with ESD-AR and none with EMR (3% vs 0%, P = .50); these were associated with anticoagulation use (P = .04) and greater resection area (P = .02). There were more upgraded diagnoses post-ESD versus EMR (27% vs 12%, P = .05). CONCLUSIONS: ESD-AR by an experienced endoscopist has a comparable safety profile with widespread EMR for large esophageal neoplasia and may have advantages for diagnostic staging.

Cholangioscopy Biopsies Improve Detection of Cholangiocarcinoma When Combined with Cytology and FISH, but Not in Patients with PSC.

BACKGROUND AND AIMS: Single-operator cholangioscopy (SOC) has been suggested to be a cost-effective strategy for the detection of cholangiocarcinoma (CCA). The aim of this study is to compare the performance characteristics of SOC-guided biopsies and transpapillary biopsies with standard sampling techniques for the detection of CCA. METHODS: A retrospective cohort study of patients undergoing SOC between 1/2007 and 10/2018 at a single academic center was performed. Demographic, procedural, and outcomes data were recorded and analyzed using STATA 14.0. Sensitivity comparison between diagnostic tests was performed using exact McNemar test exclusively among patients with CCA. Two-sided p value < 0.05 was considered statistically significant. RESULTS: Ninety-two patients were included; 36 (39.1%) with primary sclerosing cholangitis (PSC), 41 (44.6%) with CCA, and median follow-up was 15.1 months. In the overall cohort, brush cytology demonstrated a sensitivity of 44.7% and increased with the addition of FISH (56.8%; p = 0.12), FISH with SOC-guided biopsy (71.4%; p = 0.03), and FISH with transpapillary biopsy (64.5%; p = 0.01). However, in patients with PSC, there was no significant improvement in sensitivity with the addition of SOC-guided biopsy or transpapillary biopsy in addition to FISH when compared to brush cytology. There was no difference in the rates of overall adverse events (14% vs. 23.2%; p = 0.27) or infection (3% vs. 4%; p = 0.83) in patients with and without PSC. CONCLUSIONS: SOC-guided and transpapillary biopsies improve sensitivity for the detection of cholangiocarcinoma in combination with other ERCP-based techniques compared to brush cytology alone. However, while safe, these modalities do not significantly improve the sensitivity for the detection of malignancy in PSC patients.

An innovative technique using a percutaneously placed guidewire allows for higher success rate for ERCP compared to balloon enteroscopy assistance in Roux-en-Y gastric bypass anatomy.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in Roux-en-Y gastric bypass (RYGB). Current approaches either have high failure rate, are resource intensive, or invasive. OBJECTIVE: To describe successful adoption of an old technique for performance of ERCP in patients with RYGB anatomy employing enteroscopy with the assistance of a percutaneously placed guidewire, which facilitates both reaching and cannulating the major papilla. METHOD: A retrospective cohort study in a tertiary-care center. We included patients with RYGB from 2015 to 2017 who underwent ERCP. We compared success rate and adverse events between rendezvous guidewire-assisted (RGA) and balloon-assisted enteroscopy (BAE) ERCP techniques. RESULTS: Thirty patients with RYGB underwent 62 ERCPs. The mean age was 62.2 ± 11 years with female predominance 83.3%. The procedures were performed using BAE 43/62 (69.3%), RGA 13/62 (21%), gastrostomy tube 5/62 (8.1%), and colonoscope 1/62 (1.6%). In patients with a native papilla (n = 37 ERCPs), clinical success rate with BAE was 36.8% compared to 100% with RGA (P < 0.001). There was no significant difference in bleeding (P = 0.17), post-ERCP pancreatitis (P = 0.4), or luminal perforation (P = not estimated) between the two techniques in native papilla. The mean procedure time with the RGA was significantly shorter than successful BAE with mean difference: 33 min (95% CI 8-57 min, P = 0.01). Twenty-five ERCPs were performed in eight patients with non-native papilla. BAE success rate in non-native papilla was 95.8%. The mean procedure time of the BAE in non-native papilla was 111 ± 60 min. Native papillae were associated with a significantly higher BAE failure rate compared to non-native papillae (OR: 12; 95% CI 1.44-99.7, P = 0.02). CONCLUSION: In patients with RYGB, RGA appears to be highly successful and safe in achieving clinical success for patients with native papilla as compared to BAE.

Surgical outcomes of ERCP-guided transpapillary gallbladder drainage versus percutaneous cholecystostomy as bridging therapies for acute cholecystitis followed by interval cholecystectomy.

BACKGROUND: Select patients with acute cholecystitis (AC) are not candidates for index cholecystectomy. We compared the influence of ERCP-guided transpapillary gallbladder drainage (ERGD) versus percutaneous cholecystostomy (PC) on delayed cholecystectomy outcomes. METHODS: Consecutive patients undergoing ERGD or PC for AC from January 2007 to October 2018 were included. Primary outcome was the rate of conversion to open cholecystectomy and perioperative complications in groups. RESULTS: The study included 52 patients with ERGD and 140 with PC prior to cholecystectomy (median 68 days [IQR: 47-105.5]). Technical success was higher in the PC group (100% vs 91%; P = 0.0004). There was a nonsignificant trend to lower postoperative complications with ERGD (30.7% vs 43.5%; P = 0.07). No difference in conversion to open cholecystectomy OR: 1.5 (95% CI: 0.68-3.65; P = 0.28) or severity of complications (Clavien-Dindo grade >2) OR: 0.60, (95% CI: 0.19-1.87; P = 0.38) was noted between the ERGD and PC groups. PC was associated with higher rates of unplanned repeat intervention (16.4% vs 7.7%; P = 0.02). CONCLUSION: ERGD is suitable for patients with AC who is candidates for delayed cholecystectomy and should be considered for gallbladder drainage in patients with concomitant choledocholithiasis or cholangitis who require ERCP.