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Background and Aims We previously identified a 5 methylated DNA marker (MDM) panel for the detection of nonendoscopic Barrett’s esophagus (BE). In this study, we aimed to recalibrate the performance of the 5 MDM panel using a simplified assay in a training cohort, validate the panel in an independent test cohort, and explore the accuracy of an MDM panel with only 3 markers. Methods Participants were recruited from 3 medical centers. The sponge on a string device (EsophaCap; CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and control subjects. A 5 MDM panel was blindly assayed using a simplified assay. Random forest modeling analysis was performed, in silico cross-validated in the training set, and then locked down, before test set analysis. Results The training set had 199 patients: 110 BE cases and 89 control subjects, and the test set had 89 patients: 60 BE cases and 29 control subjects. Sensitivity of the 5 MDM panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under the receiver operating characteristic curves were .96 and .97 in the training and test sets, respectively. Model accuracy was not influenced by age, sex, or smoking history. Multiple 3 MDM panels achieved similar accuracy. Conclusions A 5 MDM panel for BE is highly accurate in training and test sets in a blinded multisite case-control analysis using a simplified assay. This panel may be reduced to only 3 MDMs in the future. (Clinical trial registration number: NCT 02560623.)

Photodynamic priming (PDP), a collateral effect of photodynamic therapy, can transiently alter the tumor microenvironment (TME) beyond the cytotoxic zone. Studies have demonstrated that PDP increases tumor permeability and modulates immune-stimulatory effects by inducing immunogenic cell death, via the release of damage-associated molecular patterns and tumor-associated antigens. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest of cancers with a stubborn immunosuppressive TME and a dense stroma, representing a challenge for current molecular targeted therapies often involving macromolecules. We, therefore, tested the hypothesis that PDP’s TME modulation will enable targeted therapy and result in immune stimulation. Using triple-receptor-targeted photoimmuno-nanoconjugate (TR-PINs)-mediated PDP, targeting epidermal growth factor receptor, transferrin receptor, and human epidermal growth factor receptor 2 we show light dose-dependent TR-PINs mediated cytotoxicity in human PDAC cells (MIA PaCa-2), co-cultured with human pancreatic cancer-associated fibroblasts (PCAFs) in spheroids. Furthermore, TR-PINs induced the expression of heat shock proteins (Hsp60, Hsp70), Calreticulin, and high mobility group box 1 in a light dose and time-dependent manner. TR-PINs-mediated T cell activation was observed in co-cultures of immune cells with the MIA PaCa-2-PCAF spheroids. Both CD4+ T and CD8+ T cells showed light dose and time-dependant antitumor reactivity by upregulating degranulation marker CD107a and interferon-gamma post-PDP. Substantial tumor cell death in immune cell-spheroid co-cultures by day 3 shows the augmentation by antitumor T cell activation and their ability to recognize tumors for a light dose-dependent kill. These data confirm enhanced destruction of heterogeneous pancreatic spheroids mediated by PDP-induced phototoxicity, TME modulation and increased immunogenicity with targeted nanoconstructs.

Background and study aims Endoscopic submucosal dissection (ESD) is technically challenging, difficult to learn, and carries a substantial risk of perforation, all of which remain significant barriers to its adoptability. We aimed to determine whether use of a novel scissor-type knife improved efficacy and safety among novice performers of ESD.Materials and methods Following a brief didactic session on ESD, participants performed ESD of two lesions (2 cm diameter) in an ex vivo porcine gastric model. One resection was performed with a conventional knife and the other with the scissor knife (order of knife randomized). We recorded procedure time, successful en bloc resection, and adverse events (including full-thickness perforation and muscle injury) for each dissection. Participants completed a post-study survey.Results 10 endoscopists (8 trainees, 2 staff) considered novices in ESD participated. Compared with the conventional knife, use of the scissor knife was associated with a significantly shorter time to completion of submucosal dissection (mean 6.2 [SD 5.6] vs. 15.6 [SD 15.6] minutes; P = 0.04) and total procedure time was not significantly different (22.1 [SD 13.3] vs. 24.9 [SD 26.5] minutes; P = 0.65). Scissor knife use was also associated with a significantly lower proportion of perforation and/or muscle injury (10.0 % vs. 70.0 %; P Conclusions Among novices performing ESD on an ex vivo animal model, use of a scissor knife was associated with a significantly lower proportion of adverse events without prolonging procedure time. Scissor-type knives may improve ESD safety, at least among novices.

Background and Aims Locally advanced pancreatic cancer (LAPC) often causes obstruction. Verteporfin photodynamic therapy (PDT) can feasibly “debulk” the tumor more safely than noncurative surgery and has multiple advantages over older PDT agents. We aimed to assess the feasibility of EUS-guided verteporfin PDT in ablating nonresectable LAPC. Methods Adults with LAPC with adequate biliary drainage were prospectively enrolled. Exclusion criteria were significant metastatic disease burden, disease involving >50% duodenal or major artery circumference, and recent treatment with curative intent. CT was obtained between days –28 to 0. On day 0, verteporfin .4 mg/kg was infused 60 to 90 minutes before EUS, during which a diffuser was positioned in the tumor and delivered light at 50 J/cm for 333 seconds. CT was obtained on day 2, with adverse event monitoring occurring on days 1, 2, and 14. The primary outcome was presence of necrosis. Results Of 8 patients (62.5% men, mean age 65 ± 7.9 years) included in the study, 5 were staged at T3, 2 at T2, and 1 at T1. Most (n = 4) had primary lesions in the pancreatic head. Mean pretrial tumor diameter was 33.3 ± 13.4 mm. On day 2 CT, 5 lesions demonstrated a zone of necrosis measuring a mean diameter of 15.7 ± 5.5 mm; 3 cases did not develop necrosis. No adverse events were noted during the procedure or postprocedure observation period (days 1-3), and no changes in patient-reported outcomes were noted. Conclusions In this pilot study, EUS-guided verteporfin PDT is feasible and shows promise as a minimally invasive ablative therapy for LAPC in select patients. Tumor necrosis is visible within 48 hours after treatment. Patient enrollment and data collection are ongoing. (Clinical trial registration number: NCT03033225.)

INTRODUCTION: Minimally invasive tests for Barrett's esophagus (BE) detection have raised the prospect of broader nonreflux-based testing. Cost-effectiveness studies have largely studied men aged 50 years with chronic gastroesophageal reflux disease (GERD) symptoms. We evaluated the comparative cost effectiveness of BE screening tests in GERD-based and GERD-independent testing scenarios. METHODS: Markov modeling was performed in 3 scenarios in 50 years old individuals: (i) White men with chronic GERD (GERD-based); (ii) GERD-independent (all races, men and women), BE prevalence 1.6%; and (iii) GERD-independent, BE prevalence 5%. The simulation compared multiple screening strategies with no screening: sedated endoscopy (sEGD), transnasal endoscopy, swallowable esophageal cell collection devices with biomarkers, and exhaled volatile organic compounds. A hypothetical cohort of 500,000 individuals followed for 40 years using a willingness to pay threshold of $100,000 per quality-adjusted life year (QALY) was simulated. Incremental cost-effectiveness ratios (ICERs) comparing each strategy with no screening and comparing screening strategies with each other were calculated. RESULTS: In both GERD-independent scenarios, most non-sEGD BE screening tests were cost effective. Swallowable esophageal cell collection devices with biomarkers were cost effective (

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 submucosal dissection (ESD) is used for treating early luminal GI cancers. ESD is the standard of care in Asia, where it results in multiday admissions for observation. The goal of our study was to evaluate the safety and feasibility of same-day discharge (SDD) after ESD.This is a retrospective cohort study of adults who underwent similar esophageal ESD with a Clutch Cutter device (DP2618DT; Fujifilm) at the Mayo Clinic (Rochester, Minn, USA) from 2017 to 2019 with a single endoscopist. The primary end point was postprocedural adverse events within 7 days of ESD.Of 96 patients (75% male, mean age, 70 ± 10.3 years) undergoing a total of 140 ESDs, 85 were SDD versus 55 admissions. Of the 55 admits, 53 were discharged within 24 hours, whereas 2 were admitted for 2 to 3 days for reasons unrelated to the ESD procedure. Admissions were more likely to have a history of antiplatelet/anticoagulant use (56.4% vs 34.1%; P = .01) and higher mean American Society of Anesthesiologists (ASA) score (3.2 vs 2.9; P = .007). Admissions had larger resections (28.6 vs 20.1 mm; P .0001) with longer procedural durations (103.4 vs 62 minutes; P .0001). Among SDDs, no intraprocedural or postprocedural adverse events were seen. Among admissions, 1 (1.8% vs 0%; P = .39) experienced intraprocedural bleeding requiring endoscopic intervention, 1 required transfusion before discharge within 24 hours of ESD (1.8% vs 0%; P = .39), and 1 required rehospitalization and endoscopic intervention within 7 days to address an active bleed along the resection margin (1.8% vs 0%; P = .39).SDD after esophageal ESD is safe and feasible. An experienced endoscopist can determine if SDD can be considered in patients with ASA physical classification status ≤2 who undergo resections off antiplatelet/anticoagulant therapy and do not experience intraprocedural adverse events.

Background Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett’s esophagus (BE). Interpretation of a 6-cm long, circumferential VLE “full scan” may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE). Methods 29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as “neoplastic” or “NDBE.” If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence. Results VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % – 79 %) of neoplastic VLE videos. In 54 % (range 27 % – 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % – 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %). Conclusions Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.

Background:Esophageal adenocarcinoma is a lethal cancer with rising incidence. There are limited data in younger (Methods:We queried the Surveillance, Epidemiology, and End Results 9 database to identify patients with esophageal adenocarcinoma between 1975 and 2015. Patients were stratified into three age strata: Results:Esophageal adenocarcinoma incidence has increased in patients Conclusions:Young-onset esophageal adenocarcinoma, while uncommon, is rising in incidence. Concerningly, the proportion of advanced disease continues to increase. Young-onset esophageal adenocarcinoma also presents at more advanced stages, resulting in poorer esophageal adenocarcinoma–free survival.Impact:Patients with esophageal adenocarcinoma younger than 50 years present at more advanced stages with higher esophageal adenocarcinoma–specific mortality compared with older peers. Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated.

Background Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used in Barrett's esophagus (BE) surveillance. VLE interpretation relies on identification of specific features associated with BE dysplasia and can be enhanced by intelligent real-time image segmentation (IRIS). The diagnostic performance of established VLE interpretation systems has not been validated. This study uses a dataset of histology-matched regions of interest (ROI) to determine the diagnostic performance of VLE with and without IRIS enhancement. Methods VLE scans with ROIs laser-marked for targeted biopsy and matching histopathology were performed in patients undergoing BE surveillance. ROIs were rated independently for BE dysplasia by 3 blinded VLE experts using established VLE interpretation systems. Following a washout period, ROIs were rated using IRIS adapted to the VLE interpretation systems. Inter-rater agreement, diagnostic performance, and optimal diagnostic thresholds were calculated for each scoring system. Results A total of 71 laser-marked ROIs from 44 patients (mean age: 68 years) and BE length of 5 cm were included. About 45.1% of ROIs contained dysplasia. Inter-rater agreement was uniformly very good or excellent and only the surface intensity scoring agreement was enhanced by IRIS. The scoring systems’ AUC ranged from 0.59 to 0.74 and 0.60 to 0.75 for VLE with and without IRIS, respectively. When diagnostic thresholds of the existing scoring systems were optimized, the adjusted AUC ranged from 0.70 to 0.78. Conclusions This is the first study to validate and optimize the diagnostic performance of established VLE interpretation systems for BE dysplasia. IRIS image enhancement adapted to these interpretation systems demonstrated similar diagnostic performance.

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.

The clinical application of photodynamic therapy (PDT) for gastrointestinal (GI) neoplastic lesions has been developed with appreciation for the great efforts and kind support of Dr. Tom Dougherty and his followers' contributions. There are several published studies on clinical PDT in the field of GI oncology. Esophageal cancer was one of the first clinical indications for PDT that was approved as an endoscopic procedure in both the United States and Japan. PDT was initially used as a palliative local treatment for patients with obstructive esophageal cancer. PDT is also indicated for eradicative therapy for dysplastic Barret's esophagus, which is the precursor state of esophageal adenocarcinoma, with the support of level one evidence. In Japan, PDT was approved as a curative treatment for superficial esophageal carcinoma lesions, which are difficult to treat with endoscopic resection. Further, PDT using second-generation photosensitizers is approved for early local failure after radiotherapy, for which treatment with other modalities is difficult. PDT has also been assessed in other GI cancers, including gastric cancer, biliary cancer and pancreatic cancer. In this review, we overview the history and state of PDT for GI cancer.

Summary Introduction Esophageal adenocarcinoma (EAC) is an aggressive cancer, associated with reflux esophagitis and intestinal metaplasia (IM). One underlying biological mechanism, which possibly drives the development of EAC, is the dysregulated expression of Bone Morphogenetic Proteins (BMPs). Aim To investigate if local delivery of Noggin, a BMP antagonist, reduced EAC. Methods After obtaining proof of principal on local delivery of a Noggin/Sucralfate substance, a randomized controlled trial to test the effects of Noggin on EAC development was performed in a surgical rat model. In the model, an esophago-jejunostomy leads to development of reflux-esophagitis, IM and eventually EAC. Rats were treated by Noggin/Sucralfate or Sucralfate alone. Treatment was administered from 26 to 29 weeks after the operation. Results Of the 112 operated rats, 52 survived beyond 26 weeks. Finally, 25 rats treated with Noggin/Sucralfate and 21 with Sucralfate, were evaluated. At the end, 39 (85%) of the animals had IM while 28 (61%) developed cancer. There were significantly more cancers in the Noggin/Sucralfate arm (50%) versus the Sucralfate group (73%) (Chi square, P Conclusion In this study, we demonstrated that inhibition of BMPs by Noggin reduced development of EAC in a surgical esophagitis-IM-EAC rat model. In future, effective targeting of the BMP pathway with selective BMP-inhibitors could become an important asset to improve EAC patient outcome.

Simple Summary Surgical resection is currently the only potentially curative option for patients with pancreatic adenocarcinoma (PDAC). However, 80% of patients are ineligible for surgery due to the presence of invasive disease or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents a promising approach to improving long-term survival. We investiaged the efficacy of a photodynamic therapy (PDT) based treatment regimen at preventing the spread and reducing the burden of metastases in animal models of PDAC. We demonstrate that PDT in combination with the first-line chemotherapeutic nab-paclitaxel dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that PDT-based treatment regimens may enable reclassification of patients with previously inoperable disease as surgical candidates. Abstract Despite substantial drug development efforts, pancreatic adenocarcinoma (PDAC) remains a difficult disease to treat, and surgical resection is the only potentially curative option. Unfortunately, 80% of patients are ineligible for surgery due to the presence of invasive disease and/or distant metastases at the time of diagnosis. Treatment strategies geared towards reclassifying these patients as surgical candidates by reducing metastatic burden represents the most promising approach to improve long-term survival. We describe a photodynamic therapy (PDT) based approach that, in combination with the first-line chemotherapeutic nab-paclitaxel, effectively addresses distant metastases in three separate orthotopic PDAC models in immunodeficient mice. In addition to effectively controlling local tumor growth, PDT plus nab-paclitaxel primes the tumor to elicit systemic effects and reduce or abrogate metastases. This combination dramatically inhibits (up to 100%) the eventual development of metastases in models of early stage PDAC, and completely eliminates metastasis in 55% of animals with already established distant disease in late-stage models. Our findings suggest that this light activation process initiates local biological and/or physiological changes within the tumor microenvironment that can be leveraged to treat both localized and distant disease, and potentially reclassify patients with previously inoperable disease as surgical candidates.

Goals To develop an encounter decision aid [Barrett's esophagus Choice (BE-Choice)] for patients and clinicians to engage in shared decision making (SDM) for management of BE with low-grade dysplasia (BE-LGD) and assess its impact on patient-important outcomes. Background Currently, there are 2 strategies for management of BE-LGD-endoscopic surveillance and ablation. SDM can help patients decide on their preferred management option. Study Phase-I: Patients and clinicians were engaged in a user-centered design approach to develop BE-Choice. Phase-I included review of evidence on BE-LGD management, observation of usual care (UC), creation, field-testing, and iterative development of BE-Choice in clinical settings. Phase-II: Impact of BE-Choice on patient-important outcomes (patient knowledge, decisional conflict, and patient involvement in decision making) was assessed using a controlled before-after study design (UC vs. BE-Choice). Results Phase-I: Initial prototype was designed with observation of 8 clinical encounters. With field-testing, 3 successive iterations were made before finalizing BE-Choice. BE-Choice was paper based and fulfilled the qualifying criteria of International patient decision aid standards. Phase II: 29 patients were enrolled, 8 to UC and 21 to BE-Choice. Compared with UC, use of BE-Choice improved patient knowledge (90.4% vs. 70.5%; P=0.03), decisional comfort (89.6 vs. 71.9; P=0.01), and patient involvement (OPTION score: 27.1 vs. 19.2; P=0.01). Conclusions BE-Choice is a feasible and effective decision aid to promote SDM in the management of BE-LGD. On pilot testing, BE-Choice had promising impact on patient-important outcomes. A larger multicenter trial is needed to confirm our results and promote widespread use of BE-Choice.

BACKGROUND AND AIMS: Multiband mucosectomy (MBM) is a widely used technique for the treatment of Barrett's esophagus (BE). However, large multicenter studies enabling a generalizable estimation of the risk of serious adverse events, such as perforation and postprocedural bleeding, are lacking. The aim of this study was to estimate the rate of, and risk factors for, serious adverse events associated with MBM. METHODS: In this retrospective analysis, consecutive patients who underwent MBM for treatment of BE in 14 tertiary referral centers in Europe, the United States, Canada, and Australia were included. Primary outcomes were perforation and postprocedural bleeding rate. Potential risk factors were identified by logistic regression. RESULTS: Between 2001 and 2016, a total of 3827 MBM procedures were performed in 2447 patients (84% male, mean age 66 years, median BE length C2M4). Perforation occurred in 17 procedures (0.4%; 95% confidence interval [CI], 0.3-0.7), of which 15 could be treated endoscopically or conservatively. Female gender was an independent risk factor for perforation (odds ratio [OR], 2.77; 95% CI, 1.02-7.57; P = .05). Postprocedural bleeding occurred after 35 procedures (0.9%; 95% CI, 0.6-1.3). The number of resections (OR, 1.15; 95% CI, 1.06-1.25; P < .001) was significantly associated with postprocedural bleeding. CONCLUSION: The results of this study show that MBM for BE is safe with a low risk of serious adverse events. In addition, most of the adverse events could be managed endoscopically or conservatively. The number of resections was an independent risk factor for postprocedural bleeding. ispartof: GASTROINTESTINAL ENDOSCOPY vol:92 issue:2 pages:259-+ ispartof: location:United States status: published

Background Pre-operative staging of pancreatic adenocarcinoma guides clinical decision making. Limited data indicate that metastasis to celiac ganglia (CG) correlates with poor prognosis. We investigated feasibility and safety of endoscopic ultrasound fine needle aspiration (EUS-FNA) detection of CG metastasis and its impact upon tumor stage, resectability, and survival in pancreatic ductal adenocarcinoma (PDAC). Patients We reviewed our prospectively maintained EUS and cytopathology databases to identify patients with FNA proven CG metastasis in patients with PDAC from 2004 to 2017. Clinical demographics, EUS, CT, MRI, cytopathology, cancer stage, and resectability data were analyzed. Survival of PDAC patients with CG metastasis was compared to the expected survival of PDAC patients of similar stage as reported by the United States National Cancer Database. Results Twenty-one patients with PDAC [median age 73 (IQR63-78); 14 (67%) female)], had CG metastasis confirmed by cytopathologic assessment. CG metastasis resulted in tumor upstaging relative to other EUS findings and cross sectional imaging findings in 12 (57%) and 15 (71%) patients, and converted cancers from resectable to unresectable relative to EUS and cross sectional imaging in 7 (37%) and 7 (37%) patients, respectively. In patients with PDAC, the survival of patients with CG metastasis was not significantly different from the overall survival (hazard ratio 0.71; 95% confidence interval 0.44, 1.13; p = 0.15). Conclusions EUS-FNA may safely identify CG metastases. While CG metastasis upstaged and altered the resectability status among this cohort of patients with PDAC, the survival data with regard to PDAC suggest that this may be misguided.

Goals To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. Background Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review. Study NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. "Progressors" were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression. Results In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis. Conclusions In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.

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. Eliminating chronic reflux from the ACG/BSG criteria improved eligibility for screening from 45.1% to 81.3% (P 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.

Background and Aims Strong evidence supports the use of radiofrequency ablation (RFA) in the management of dysplastic/neoplastic Barrett’s esophagus (BE). Recently, the efficacy of the cryoballoon ablation (CBA) system was demonstrated in multicenter cohort studies. We aimed to assess the comparative effectiveness and safety of these 2 ablation modalities for endoscopic eradication therapy (EET) in a cohort study. Methods Data were abstracted on patients with dysplastic BE or intramucosal carcinoma undergoing EET using RFA or CBA as the primary ablation modality at 2 referral centers. The primary outcome was the rate of complete remission intestinal metaplasia (CRIM). Secondary outcomes were rates of complete remission of dysplasia (CRD) and adverse events. Cox proportional hazards models and propensity scored–matched analyses were conducted to compare outcomes. Results Three hundred eleven patients (CBA, 85 patients; RFA, 226 patients) with a median follow-up of 1.5 years (interquartile range, .8, 2.5) in the RFA group and 2.0 years (interquartile range, 1.3, 2.5) in the CBA group were studied. On multivariable analyses, the chances of reaching CRD and CRIM were not influenced by ablation modality. Propensity score–matched analysis revealed a comparable chance of achieving CRIM (CBA vs RFA: hazard ratio, 1.24; 95% confidence interval, .79-1.96; P = .35) and CRD (CBA vs RFA: hazard ratio, 1.19; 95% confidence interval, .82-1.73; P = .36). The CBA group had a higher stricture rate compared with the RFA group (10.4% vs 4.4%, P = .04). Conclusions Histologic outcomes of EET using CBA and RFA for dysplastic BE appear to be comparable. A randomized trial is needed to definitively compare outcomes between these 2 modalities.

Background Dysphagia is the most common symptom in advanced esophageal cancer patients. Esophageal stent placement (SP) is a common palliation method but can be associated with significant morbidity. Limited data exist regarding the ability of spray cryotherapy (SC) prolong time to SP. Methods A Mayo Clinic (Rochester, MN) patient database was reviewed for cases with a SC indication of esophageal cancer palliation from 2007–2019. Procedures were performed using a liquid nitrogen SC system to apply 2–5 separate 20 second freeze and 60 second thaw cycles based on tumor characteristics. Primary outcome was time to subsequent palliative SP. Results Of 56 patients (71.4% male, mean age 77.8 ± 10.2 years) who underwent a total of 199 SC sessions (mean 3.6 ± 2.7, range 1–12 per patient), 41 had adenocarcinoma and 15 squamous cell carcinoma (SCC). Overall, 13 patients underwent subsequent SP within a mean duration of 15.7 ± 11.0 months over a mean follow-up duration of 25.6 ± 29.4 months. Treatment did produce stenosis in 16 patients, who required dilation within a mean period of 193.1 ± 294.1 days; notably, 10 patients had a history of preceding malignant strictures requiring dilation. Two patients experienced bleeding requiring transfusion, whereas 1 experienced perforation at the start of SC. Prior chemotherapy and/or radiation was not associated with developing an SC-related complication (risk ratio (RR) 1.5; 95% CI 0.6–3.7, P > 0.4). Conclusions SC appears to be an effective and safe modality to palliate esophageal cancer in appropriate candidates. Majority of patients who undergo SC avoid the need for future SP. If patients eventually require SP, they are able to, on average, defer stenting for >1 year from SC initiation.

Photodynamic therapy (PDT) offers localized focal ablation in unresectable pancreatic tumors while tissues surrounding the treatment volume experience a lower light dose, termed photodynamic priming (PDP). While PDP does not cause tissue damage, it has been demonstrated to promote vascular permeability, improve drug delivery, alleviate tumor cell density, and reduce desmoplasia and the resultant internal pressure in pre-clinical evaluation. Preclinical data supports PDP as a neoadjuvant therapy beneficial to subsequent chemotherapy or immunotherapy, yet it is challenging to quantify PDP effects in clinical treatment without additional imaging and testing. This study investigated the potential of radiomic analysis using CT scans acquired before and after PDT to identify areas experiencing PDT-induced necrosis as well as quantify PDP effects in the surrounding tissues. A total of 235 CT tumor slices from seven patients undergoing PDT for pancreatic tumors were examined. Radiomic features assessed included intensity metrics (CT number in Hounsfield Units) and texture analysis using several gray-level co-occurrence matrix (GLCM) parameters. Pre-treatment scans of tumor areas that resulted in PDT-induced necrosis showed statistically significant differences in intensity and texture-based features that could be used to predict the regions that did respond (paired t-test, response versus no response, p p

Complex chromosomal alterations are a hallmark of advanced cancers but rarely seen in normal tissue. The progression of precancerous lesions to malignancy is often accompanied by increasing complexity of chromosomal alterations that can drive their transformation through focal oncogenic amplifications. However, the etiology and evolution dynamics of these alterations are poorly understood. Here we study chromosomal copy-number evolution in the progression of Barrett’s esophagus (BE) to esophageal adenocarcinoma (EAC) by multi-regional whole-genome sequencing analysis of BE samples with dysplasia and microscopic EAC foci. Through haplotype-specific copy-number analysis of BE genome evolution, we identified distinct patterns of episodic copy-number evolution consistent with the outcomes of abnormal mitosis and dicentric chromosome breakage. While abnormal mitosis, including whole-genome duplication, accounts for most chromosome or arm-level copy-number changes, segmental copy-number alterations display signatures of multi-generational evolution of unstable dicentric chromosomes. Continuous evolution of dicentric chromosomes through breakage-fusion-bridge cycles and chromothripsis rapidly increases genomic complexity and diversity among BE cells, culminating in the generation of distinct focal amplifications. These mutational processes enable multiple subclones within small dysplastic areas to undergo parallel transformation to cancer following acquisition of distinct oncogenic amplifications. Our results demonstrate how chromosomal instability drives clonal diversification in precancer evolution and promotes tumorigenesis in primary human samples.

The feasibility of ultrahigh-resolution OCT capsule endoscopy working at 800 nm was demonstrated by imaging ex vivo freshly resected human esophageal tissues, and its performance was compared with conventional volumetric laser endomicroscopy (VLE) working at 1300 nm. The results showed that the ultrahigh-resolution capsule can identify histology-confirmed diagnostic features with much finer details and contrast, particularly in mucosal layers, and demonstrated its promising potential of differentiating pathological changes in earlier stages.

The recent report from the highly regarded interventional endoscopy group in Hamburg suggests that endoscopic submucosal dissection (ESD) can lead to dissemination of oesophageal adenocarcinoma (Ehlken H et al , Gut 2021, PMID: 33441377). This study reported the rapid recurrence of two cases of submucosal Barrett’s oesophagus (BO)-related adenocarcinoma treated with near-circumferential and circumferential ESD. The cancers had extensive recurrence at the base of the resection penetrating into the muscularis propria and even more alarming lymph node metastasis. The authors sequenced the tumours to demonstrate that the recurrences were similar to the primary tumour. They then performed additional studies to demonstrate that the endoscope might be the cause of seeding. The authors found that there was opportunity for seeding to occur through contaminated endoscopic biopsy channels by demonstrating malignant cytology could be found in the biopsy channels of 5/5 patients biopsied with advanced cancers by forceps. It should be noted that trying to culture biopsy samples from BO biopsies is quite difficult, and tumour implantation is not a trivial biological event to achieve. Downstream tumour implantation (ie, in the stomach or duodenum) from an ESD for oesophageal cancer has not been reported to our knowledge. Furthermore, steroids that had been used after ESD procedures to prevent strictures were identified as one mechanism to potentially aid recurrence as the addition of steroids to oesophageal adenocarcinoma line cultures induced proliferation. Despite this evidence, the clinical literature does not support dissemination of cancer …

Background & Aims Tethered capsule endomicroscopy (TCE) involves swallowing a small tethered pill that implements optical coherence tomography (OCT) imaging, procuring high resolution images of the whole esophagus. Here, we demonstrate and evaluate the feasibility and safety of TCE and a portable OCT imaging system in patients with Barrett’s esophagus (BE) in a multi-center (5-site) clinical study. Methods Untreated patients with BE as per endoscopic biopsy diagnosis were eligible to participate in the study. TCE procedures were performed in unsedated patients by either doctors or nurses. After the capsule was swallowed, the device continuously obtained 10-μm-resolution cross-sectional images as it traversed the esophagus. Following imaging, the device was withdrawn through mouth, and disinfected for subsequent reuse. BE lengths were compared to endoscopy findings when available. OCT-TCE images were compared to volumetric laser endomicroscopy (VLE) images from a patient who had undergone VLE on the same day as TCE. Results 147 patients with BE were enrolled across all sites. 116 swallowed the capsule (79%), 95/114 (83.3%) men and 21/33 (63.6%) women (P = .01). High-quality OCT images were obtained in 104/111 swallowers (93.7%) who completed the procedure. The average imaging duration was 5.55 ± 1.92 minutes. The mean length of esophagus imaged per patient was 21.69 ± 5.90 cm. A blinded comparison of maximum extent of BE measured by OCT-TCE and EGD showed a strong correlation (r = 0.77-0.79). OCT-TCE images were of similar quality to those obtained by OCT-VLE. Conclusions The capabilities of TCE to be used across multiple sites, be administered to unsedated patients by either physicians or nurses who are not expert in OCT-TCE, and to rapidly and safely evaluate the microscopic structure of the esophagus make it an emerging tool for screening and surveillance of BE patients. Clinical trial registry website and trial number: NCT02994693 and NCT03459339.

Introduction Esophageal epidermoid metaplasia (EEM) is a rare disease. Methods Patients with EEM diagnosed between 2014 and 2020 were reviewed. Results Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy. Discussion EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.

Receptor heterogeneity in cancer is a major limitation of molecular targeting for cancer therapeutics. Single-receptor-targeted treatment exerts selection pressures that result in treatment escape for low-receptor-expressing tumor subpopulations. To overcome this potential for heterogeneity-driven resistance to molecular targeted photodynamic therapy (PDT), we present for the first time a triple-receptor-targeted photoimmuno-nanoconjugate (TR-PIN) platform. TR-PIN functionalization with cetuximab, holo-transferrin, and trastuzumab conferred specificity for epidermal growth factor receptor (EGFR), transferrin receptor (TfR), and human epidermal growth factor receptor 2 (HER-2), respectively. The TR-PINs exhibited up to a 24-fold improvement in cancer cell binding compared with EGFR-specific cetuximab-targeted PINs (Cet-PINs) in low-EGFR-expressing cell lines. Photodestruction using TR-PINs was significantly higher than the monotargeted Cet-PINs in heterocellular 3D in vitro models of heterogeneous pancreatic ductal adenocarcinoma (PDAC, MIA PaCa-2 cells) and heterogeneous head and neck squamous cell carcinoma (HNSCC, SCC9 cells) containing low-EGFR-expressing T47D (high TfR) or SKOV-3 (high HER-2) cells. Through their capacity for multiple tumor target recognition, TR-PINs can serve as a unique and amenable platform for the effective photodynamic eradication of diverse tumor subpopulations in heterogeneous cancers to mitigate escape for more complete and durable treatment responses.

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.

Introduction Nonendoscopic Barrett's esophagus (BE) screening may help improve esophageal adenocarcinoma outcomes. We previously demonstrated promising accuracy of methylated DNA markers (MDMs) for the nonendoscopic diagnosis of BE using samples obtained from a capsule sponge-on-string (SOS) device. We aimed to assess the accuracy of these MDMs in an independent cohort using a commercial grade assay. Methods BE cases had ≥ 1 cm of circumferential BE with intestinal metaplasia; controls had no endoscopic evidence of BE. The SOS device was withdrawn 8 minutes after swallowing, followed by endoscopy (the criterion standard). Highest performing MDMs from a previous study were blindly assessed on extracted bisulfite-converted DNA by target enrichment long-probe quantitative amplified signal (TELQAS) assays. Optimal MDM combinations were selected and analyzed using random forest modeling with in silico cross-validation. Results Of 295 patients consented, 268 (91%) swallowed the SOS device; 112 cases and 89 controls met the pre-established inclusion criteria. The median BE length was 6 cm (interquartile range 4-9), and 50% had no dysplasia. The cross-validated sensitivity and specificity of a 5 MDM random forest model were 92% (95% confidence interval 85%-96%) and 94% (95% confidence interval 87%-98%), respectively. Model performance was not affected by age, gender, or smoking history but was influenced by the BE segment length. SOS administration was well tolerated (median [interquartile range] tolerability 2 [0, 4] on 10 scale grading), and 95% preferred SOS over endoscopy. Discussion Using a minimally invasive molecular approach, MDMs assayed from SOS samples show promise as a safe and accurate nonendoscopic test for BE prediction.

Esophageal adenocarcinoma (EAC) develops as a consequence of gastroesophageal reflux disease and Barrett’s esophagus (BE). While combination therapy with chemotherapy or concurrent chemoradiotherapy followed by esophagectomy improves survival in more advanced tumors, the optimal treatment strategy for early-stage EAC is undefined. Endoscopic eradication therapy, consisting of endoscopic resection and mucosal ablation, has revolutionized therapy for superficial (T1a) EAC in BE and allows for esophageal preservation in appropriate patients at low risk for lymph node metastasis (LNM). This review critically examines the literature regarding evaluation, treatment, and outcomes in patients with T1 EAC. The literature was queried via the PubMed database to include articles published between 1990 and 2017. Search terms were generated from the key statements “Endoscopic eradication therapy results in equivalent overall survival when compared to esophagectomy for clinical T1aN0 EAC” and “Esophagectomy provides better overall survival than endoscopic eradication therapy for cT1b EAC”. Abstracts were reviewed and included according to predefined selection and exclusion criteria, and were then assessed according to the GRADE system. In patients with T1aN0 EAC, overall survival with endoscopic eradication therapy is equal to esophagectomy. Given the substantial risk of LNM in patients with submucosal (T1b) EAC, esophagectomy remains the standard of care for surgical candidates. In the case of inoperability or low-risk lesions, endoscopic resection may be considered adequate therapy. Chemotherapy and radiation can be offered as primary therapy for non-surgical candidates with lesions not amenable to endoscopic therapy, but does not have a clear role in the adjuvant setting after either endoscopic or surgical resection.

Minimally invasive methods have been described to detect Barrett’s esophagus (BE), but are limited by subjectivity and suboptimal accuracy. We identified methylated DNA markers (MDMs) for BE in tissue and assessed their accuracy on whole esophagus brushings and capsule sponge samples. Step 1: Unbiased whole methylome sequencing was performed on DNA from BE and normal squamous esophagus (SE) tissue. Discriminant MDM candidates were validated on an independent patient cohort (62 BE cases, 30 controls) by quantitative methylation specific PCR (qMSP). Step 2: Selected MDMs were further evaluated on whole esophageal brushings (49 BE cases, 36 controls). 35 previously sequenced esophageal adenocarcinoma (EAC) MDMs were also evaluated. Step 3: 20 BE cases and 20 controls were randomized to swallow capsules sponges (25 mm, 10 pores or 20 pores per inch (ppi)) followed endoscopy. DNA yield, tolerability, and mucosal injury were compared. Best MDM assays were performed on this cohort. Step 1: 19 MDMs with areas under the ROC curve (AUCs) >0.85 were carried forward. Step 2: On whole esophageal brushings, 80% of individual MDM candidates showed high accuracy for BE (AUCs 0.84–0.94). Step 3: The capsule sponge was swallowed and withdrawn in 98% of subjects. Tolerability was superior with the 10 ppi sponge with minimal mucosal injury and abundant DNA yield. A 2-marker panel (VAV3 + ZNF682) yielded excellent BE discrimination (AUC = 1). Identified MDMs discriminate BE with high accuracy. BE detection appears safe and feasible with a capsule sponge. Corroboration in larger studies is warranted. ClinicalTrials.gov number NCT02560623.

Endoscopic eradication therapy (EET) is highly effective in treating dysplastic Barrett's esophagus (BE). Current surveillance intervals after complete remission of intestinal metaplasia (CRIM) are based on expert opinion. We performed a meta-analysis to compare BE detection in the first year to the subsequent ones METHODS: We searched MEDLINE, EMBASE, Scopus and Cochrane Central Register of Controlled Trials through 1 August 2017 for studies reporting IM and neoplasia detection after CRIM. Pooled incidence rate (IR) of IM detection was calculated for each year after CRIM. We compared IM, dysplasia, and high grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) detection in the first year after CRIM to the years after.Twenty two studies were included involving 1973 patients with follow-up of 5176 patient-years. IM detection IR per patient-year in the 1st year was 12% (95% CI: 8-17%), in the 2nd year 7% (95% CI: 4-11%), and in the 3rd year 3% (95% CI: 1-7%). IM detection rate in the first year was significantly higher compared to the years after (relative risk (RR) 1.8 (95% CI: 1.29-2.49)). Dysplasia detection IR in the first year after achieving CRIM was 3% per patient-year (95% CI: 2-5%). Dysplasia detection IR after the first year was 1% (95% CI: 1-2%) and significantly higher in the first year compared to the years after (RR: 1.92 (95% CI: 1.32-2.8). HGD/EAC detection was 1 %/patient-year (95% CI: 0-2%) in the first year after CRIM compared to 0%/patient-year (95% CI: 0-1%) in subsequent years. HGD/EAC IR was higher in the first year (RR: 1.58 (95% CI: 0.94-2.65)).Neoplasia detection after successful treatment of BE appears more common within the first year of surveillance. This appears to be due to incompletely treated prevalent rather than recurrent disease. More intensive surveillance in the first year following CRIM is warranted.

The management of Barrett's esophagus and early esophageal adenocarcinoma has shifted away from esophagectomy and toward endoscopic techniques, including endoscopic resection and ablative therapies. The most commonly used ablative therapies are radiofrequency ablation and cryotherapy. Radiofrequency ablation has risen to the top of the management algorithm due to its favorable safety profile and established track record of efficacy in patients with dysplastic Barrett's. Cryotherapy offers early promise as an alternatively safe and effective ablative modality. We review radiofrequency ablation and cryotherapy techniques, and updated data regarding their efficacy and safety as well as their roles in the management of Barrett's esophagus.

BACKGROUND AND AIM Volumetric laser endomicroscopy (VLE) is used to identify Barrett's esophagus (BE) dysplasia. Selection of a dysplastic region of interest (ROI) can be challenging due to feature variability across a large amount of data. The degree of agreement among VLE users in selecting a ROI has not been studied. METHODS High-definition videos that divided a VLE scan from 18 patients with biopsy-proven BE dysplasia into 1-cm segments were reviewed using a four-quadrant grid superimposed for systematic interpretation. VLE scans were selected based on image quality and appropriate visualization of BE epithelium. Four experienced VLE users rated each quadrant as dysplastic or non-dysplastic. For quadrants rated as dysplastic, reviewers selected a single timeframe with representative features. A high-degree of agreement among reviewers was defined as ≥75% agreement on the quadrant diagnosis and ≥50% agreement on selected timeframe (±2 s). RESULTS Thirty-one videos, each 32 s in length, comprising 124 quadrants were reviewed. There was high-agreement among reviewers in 99 (80%) quadrants, of which 68 (69%) were rated as dysplastic. Compared with quadrants rated as non-dysplastic, ROIs of quadrants rated as dysplastic contained a higher number of epithelial glands (12.7 vs 1.2, P

Although esophageal adenocarcinoma is an uncommon cancer, it is often fatal unless found at an early disease stage. Screening to discover early stage disease for its only known precursor, Barrett esophagus, is currently the only solution to improve survival. Multiple strategies have been suggested for screening including identification of a higher risk population using epidemiological factors such as sex, age, symptoms of reflux, and presence of central obesity. In addition, new nonendoscopic methods of screening have been created including sponges, balloons, breath tests, and tests on various bodily fluids. All of these new developments were created in order to improve the efficacy and cost-effectiveness of screening. New technologies may allow for a low-cost, noninvasive screening technology that is highly acceptable to healthy patients at risk for esophageal cancer.

Background and Aims Seattle protocol forceps biopsies (FB) are currently recommended for surveillance in Barrett’s esophagus (BE) but limited by sampling error and lack of adherence. Wide-area transepithelial sampling with 3D analysis (WATS-3D) is reported to increase BE dysplasia detection. We assessed the incremental yield and clinical significance of WATS-3D for dysplasia detection over FB in a systematic review and meta-analysis. Methods We queried major scientific databases for studies using WATS-3D and FB from 2000-2020. Primary outcome was the incremental yield of WATS-3D detected dysplasia (defined as a composite of indefinite for dysplasia [IND], low- and high-grade dysplasia [LGD, HGD] and esophageal adenocarcinoma [EAC]) over FB. Secondary outcomes were incremental yields of HGD/EAC, and rate of reconfirmation of WATS-3D dysplasia on subsequent FB. Results Meta-analysis of 7 eligible studies demonstrated that FB diagnosed dysplasia in 15.9% of cases, whereas incremental yield with WATS-3D was 7.2% (95% CI, 3.9%-11.5%; I2=92.1%). Meta-analysis of 6 studies demonstrated that FB diagnosed HGD/EAC in 2.3% of patients, whereas incremental yield with WATS-3D was 2.1% (95% CI, 0.4%-5.3%; I2=92.7%). Notably, WATS-3D was negative in 62.5% of cases where FB identified dysplasia. Two studies reported reconfirmation of WATS-3D dysplasia with FB histology in only 20 patients. Conclusion WATS-3D increases dysplasia detection, however, the clinical significance of this increased dysplasia detection remains uncertain. Data from endoscopic follow up to ascertain FB histology in patients with dysplasia based solely on WATS-3D are needed to determine the optimal clinical application and significance of WATS only dysplasia.

BACKGROUND AND AIMS: Endoscopic resection (ER) is an important component of the endoscopic treatment of Barrett’s Esophagus (BE) with dysplasia and intramucosal adenocarcinoma (IMC). ER can be performed by cap assisted endoscopic mucosal resection (cEMR) or endoscopic submucosal dissection (ESD). We compared the histological outcomes of ESD versus cEMR, followed by ablation. METHODS: We queried a prospectively maintained database of all patients undergoing cEMR and ESD followed by ablation at our institution from January 2006 to March 2020 and abstracted relevant demographic and clinical data. Our primary outcomes included the rate of complete remission of dysplasia (CRD): absence of dysplasia on surveillance histology and complete remission of intestinal metaplasia (CRIM): absence of intestinal metaplasia. Our secondary outcome included complication rates. RESULTS: We included 537 patients in the study: 456 who underwent cEMR and 81 who underwent ESD. The cumulative probabilities of CRD at 2 years were 75.8% and 85.6% in the cEMR and ESD groups (p< 0.01). Independent predictors of CRD were: ESD (HR: 2.38; p0.05). The only independent predictor of CRIM was a shorter BE segment (HR: 1.16; p < 0.01). CONCLUSIONS: BE patients with dysplasia or IMC undergoing ESD reach CRD at higher rates than those treated with cEMR, though CRIM rates at two years and complication rates were similar between the two groups.

Background and Aims Wide-area transepithelial sampling (WATS) with computer-assisted 3-dimensional analysis is a sampling technique that combines abrasive brushing of the Barrett's esophagus (BE) mucosa followed by neural network analysis to highlight abnormal-appearing cells. Methods We performed a randomized trial of referred BE patients undergoing surveillance at 16 medical centers. Subjects received either biopsy sampling followed by WATS or WATS followed by biopsy sampling. The primary outcome was rate of detection of high-grade dysplasia/esophageal adenocarcinoma (HGD/EAC) using WATS in conjunction with biopsy sampling compared with biopsy sampling alone using standard histopathologic criteria. Secondary aims included evaluating neoplasia detection rates based on the procedure order (WATS vs biopsy sampling first), of each procedure separately, and the additional time required for WATS. Results One hundred sixty patients (mean age, 63.4 years; 76% men; 95% white) completed the trial. The median circumferential and maximal BE extents were 1.0 cm (interquartile range: .0-5.0) and 4.0 cm (interquartile range, 2.0-8.0), respectively. The diagnostic yield for biopsy sampling alone was as follows: HGD/EAC, 7 (4.4%); low-grade dysplasia (LGD), 28 (17.5%); nondysplastic BE (NDBE), 106 (66.25%); and no BE, 19 (11.9%). The addition of WATS to biopsy sampling yielded an additional 23 cases of HGD/EAC (absolute increase, 14.4%; 95% confidence interval, 7.5%-21.2%). Among these 23 patients, 11 were classified by biopsy sampling as NDBE and 12 as LGD/indefinite for dysplasia (IND); 14 received biopsy sampling first and 9 WATS first (not significant) and most (n = 21; 91.7%) had a prior dysplasia history. WATS added an average of 4.5 minutes to the procedure. Conclusion Results of this multicenter, prospective, randomized trial demonstrate that the use of WATS in a referral BE population increases the detection of HGD/EAC. (Clinical trial registration number: NCT03008980.)