Short-segment Barrett's Esophagus Research Articles

Multicenter, Prospective Trial of Nonendoscopic Biomarker-Driven Detection of Barrett's Esophagus and Esophageal Adenocarcinoma.

Preliminary data suggest that an encapsulated balloon (EsoCheck), coupled with a 2 methylated DNA biomarker panel (EsoGuard), detects Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) with high accuracy. The initial assay requires sample freezing upon collection. The purpose of this study was to assess a next-generation EsoCheck sampling device and EsoGuard assay in a much-enlarged multicenter study clinically enhanced by using a Clinical Laboratory Improvement Amendments of 1988-compliant assay and samples maintained at room temperature. Cases with nondysplastic BE (NDBE), dysplastic BE (indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia), EAC, junctional adenocarcinoma, plus endoscopy controls without esophageal intestinal metaplasia, were prospectively enrolled. Medical assistants at 6 institutions delivered the encapsulated balloon per orally with inflation in the stomach. The inflated balloon sampled the distal 5 cm of the esophagus and then was deflated and retracted into the capsule, preventing sample contamination. EsoGuard bisulfite sequencing assayed levels of methylated vimentin and methylated cyclin A1. A total of 243 evaluable patients-88 cases (median age 68 years, 78% men, 92% White) and 155 controls (median age 57 years, 41% men, 88% White)-underwent adequate EsoCheck sampling. The mean procedural time was approximately 3 minutes. Cases included 31 with NDBE, 16 with indefinite for dysplasia/low-grade dysplasia, 23 with high-grade dysplasia, and 18 with EAC/junctional adenocarcinoma. Thirty-seven NDBE and dysplastic BE cases (53%) were short-segment BE (<3 cm). Overall sensitivity was 85% (95% confidence interval 0.78-0.93) and specificity was 85% (95% confidence interval 0.79-0.90). Sensitivity for NDBE was 84%. EsoCheck/EsoGuard detected 100% of cancers (n = 18). EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

Adjunctive Use of WATS-3D in Symptomatic GERD Patients Increases Detection of Barrett's Esophagus and Dysplasia.

Patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy for Barrett's esophagus (BE) frequently demonstrate columnar-lined epithelium (CLE), with forceps biopsies (FB) failing to yield intestinal metaplasia (IM). Repeat endoscopy is often necessary. Assess the yield of IM leading to a diagnosis of BE by the addition of Wide-Area Trans-epithelial Sampling (WATS-3D) to FB in the screening of GERD patients. We performed a prospective registry study of GERD patients undergoing screening upper endoscopy. Patients had both WATS-3D and FB. Patients were classified by their Z line appearance: regular, irregular (<1 cm CLE), possible short-segment BE (1-<3cm), and possible long-segment BE (≥3cm). Demographics, IM yield, and dysplasia yield were calculated. Adjunctive yield was defined as cases identified by WATS-3D not detected by FB, divided by cases detected by FB. Clinicians were asked if WATS-3D results impacted patient management. Of 23,933 patients, 6,829(28.5%) met endoscopic criteria for BE. Of these, 2,878(42.1%) had IM identified by either FB or WATS-3D. Among patients fulfilling endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5%, and absolute yield was 18.1%. 1,317 patients (19.3%) who fulfilled endoscopic BE criteria had IM detected solely by WATS-3D. Of 240 patients with dysplasia, 107(44.6%) were found solely by WATS-3D. Among patients with positive WATS-3D but negative FB, the care plan changed in 90.7%. The addition of WATS-3D to FB in GERD patients being screened for BE resulted in confirmation of BE in an additional 1/5 th of patients. Furthermore, dysplasia diagnoses approximately doubled.

Development of an Artificial Intelligence Diagnostic System Using Linked Color Imaging for Barrett's Esophagus.

Background: Barrett's esophagus and esophageal adenocarcinoma cases are increasing as gastroesophageal reflux disease increases. Using artificial intelligence (AI) and linked color imaging (LCI), our aim was to establish a method of diagnosis for short-segment Barrett's esophagus (SSBE). Methods: We retrospectively selected 624 consecutive patients in total at our hospital, treated between May 2017 and March 2020, who experienced an esophagogastroduodenoscopy with white light imaging (WLI) and LCI. Images were randomly chosen as data for learning from WLI: 542 (SSBE+/- 348/194) of 696 (SSBE+/- 444/252); and LCI: 643 (SSBE+/- 446/197) of 805 (SSBE+/- 543/262). Using a Vision Transformer (Vit-B/16-384) to diagnose SSBE, we established two AI systems for WLI and LCI. Finally, 126 WLI (SSBE+/- 77/49) and 137 LCI (SSBE+/- 81/56) images were used for verification purposes. The accuracy of six endoscopists in making diagnoses was compared to that of AI. Results: Study participants were 68.2 ± 12.3 years, M/F 330/294, SSBE+/- 409/215. The accuracy/sensitivity/specificity (%) of AI were 84.1/89.6/75.5 for WLI and 90.5/90.1/91.1/for LCI, and those of experts and trainees were 88.6/88.7/88.4, 85.7/87.0/83.7 for WLI and 93.4/92.6/94.6, 84.7/88.1/79.8 for LCI, respectively. Conclusions: Using AI to diagnose SSBE was similar in accuracy to using a specialist. Our finding may aid the diagnosis of SSBE in the clinic.

Algorithm Training and Testing for a Nonendoscopic Barrett’s Esophagus Detection Test in Prospective Multicenter Cohorts

Endoscopic Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) detection is invasive and expensive. Nonendoscopic BE/EAC detection tools are guideline-endorsed alternatives. We previously described a 5-methylated DNA marker (MDM) panel assayed on encapsulated sponge cell collection device (CCD) specimens. We aimed to train a new algorithm using a 3-MDM panel and test its performance in an independent cohort. Algorithm training and test samples were from 2 prospective multicenter cohorts. All BE cases had esophageal intestinal metaplasia (with or without dysplasia/EAC); control subjects had no endoscopic evidence of BE. The CCD procedure was followed by endoscopy. From CCD cell lysates, DNA was extracted, bisulfite treated, and MDMs were blindly assayed. The algorithm was set and locked using cross-validated logistic regression (training set) and its performance was assessed in an independent test set. Training (N= 352) and test (N= 125) set clinical characteristics were comparable. The final panel included 3 MDMs (NDRG4, VAV3, ZNF682). Overall sensitivity was 82% (95% CI, 68%-94%) at 90% (79%-98%) specificity and 88% (78%-94%) sensitivity at 84% (70%-93%) specificity in training and test sets, respectively. Sensitivity was 90% and 68% for all long- and short-segment BE, respectively. Sensitivity for BE with high-grade dysplasia and EAC was 100% in training and test sets. Overall sensitivity for nondysplastic BE was 82%. Areas under the receiver operating characteristic curves for BE detection were 0.92 and 0.94 in the training and test sets, respectively. A locked 3-MDM panel algorithm for BE/EAC detection using a nonendoscopic CCD demonstrated excellent sensitivity for high-risk BE cases in independent validation samples. (Clinical trials.gov: NCT02560623, NCT03060642.).

A219 EARLY CANADIAN EXPERIENCE WITH BALLOON CRYOTHERAPY FOR BARRETT’S ESOPHAGUS

Abstract Background Balloon Cryotherapy (bCr) is a novel endoscopic treatment modality for Barrett’s esophagus (BE) associated dysplasia. Cryotherapy offers an additional approach, particularly in cases refractory to or with an anatomical impediment to radiofrequency ablation (RFA), currently first line in endoscopic eradiation therapy (EET). The use of bCr is new in Canada and it was introduced in Alberta in February 2023. Aims To present the early experience of bCr use for BE from a provincial Canadian cohort. Methods An Alberta health technology assessment approved bCr, which was then incorporated into the provincial BE treatment algorithm. Indications for bCr include: 1) RFA-refractory, 2) anatomical impediment to RFA, 3) need for concomitant biopsy/EMR, and 4) pain with RFA. All patients who underwent bCr for BE in Alberta from February to September 2023 at two tertiary care centers were included. Data on demographics, BE lesion characteristics, prior BE treatments, and bCr use are presented. Results During the 8-month period, 22 patients underwent a total of 32 bCr treatments. The median age was 68, with 77% of patients being male. At baseline, 81% had long-segment BE (≥3 cm), with a median maximal BE length of 7cm. The majority had baseline histology of high-grade dysplasia (HGD) (n=11, 50%), followed by low-grade dysplasia (LGD) (n=5, 22%), T1a (n=4, 18%), T1b (n=1, 4.5%), and intestinal metaplasia (IM) (n=1, 4.5%). All patients had previously received EET, with 77% undergoing a combination of EMR, RFA, APC, and/or ESD. Most had received RFA (n=18, 81%, median sessions=5) and EMR (n=13, 59%, median sessions=2). Some had prior APC (n=10, 45%, median sessions=1) and one had ESD. Prior to bCr, most patients had converted to short-segment (ampersand:003C3cm) BE (n=16, 72%), and histology was predominately IM (31%), followed by visible BE though no biopsy (27%), HGD (22%), T1a (13%), and LGD (4.5%). The primary indication for bCr was RFA-refractory BE (n=17, 77%), followed by anatomical impediment to RFA (n=4, 18%), and concomitant EMR (n=1, 4%). No procedures were aborted due to technical difficulties and there were no major adverse events such as perforation, bleeding, or pain requiring hospitalization. Among those with follow-up after a bCr session (n=19, 59%), one reported pain, two reported self-limited dysphagia, and one had a stricture requiring dilation. Of the 7 patients with post-bCr endoscopy, all had no dysplasia on the first set of biopsies (no IM, n=4; IM, n=2; indefinite for dysplasia, n=1). Conclusions Our early experience with bCr demonstrates there is a need for additional EET for BE. Cryotherapy, in accordance with gastroenterology society guidelines, is a promising next step in the BE algorithm. In our provincial cohort, bCr has shown technical success, and preliminary data suggests that it is safe and effective in ablating resistant BE segments. Funding Agencies None

Association between hiatal hernia and Barrett's esophagus: an updated meta-analysis with trial sequential analysis.

Barrett's esophagus (BE) is a precursor of esophageal adenocarcinoma. It is critical to recognize the risk factors associated with BE. The present meta-analysis aims to systematically estimate the association of hiatal hernia with the risk of BE. A meta-analysis with trial sequential analysis. The PubMed, EMBASE, and Cochrane Library databases were searched. The pooled odds ratios (ORs) and adjusted ORs (aORs) with their 95% confidence intervals (CIs) were calculated for the combined estimation of unadjusted data and data adjusted for confounders, respectively. Heterogeneity was quantified using the Cochrane Q test and I² statistics. Subgroup, meta-regression, and leave-one-out sensitivity analyses were employed to explore the sources of heterogeneity. Forty-seven studies with 131,517 participants were included. Based on the unadjusted data from 47 studies, hiatal hernia was significantly associated with an increased risk of any length BE (OR = 3.91, 95% CI = 3.31-4.62, p < 0.001). The heterogeneity was significant (I² = 77%; p < 0.001) and the definition of controls (p = 0.014) might be a potential contributor to heterogeneity. Based on the adjusted data from 14 studies, this positive association remained (aOR = 3.26, 95% CI = 2.44-4.35, p < 0.001). The heterogeneity was also significant (I² = 65%; p < 0.001). Meta-analysis of seven studies demonstrated that hiatal hernia was significantly associated with an increased risk of long-segment BE (LSBE) (OR = 10.01, 95% CI = 4.16-24.06, p < 0.001). The heterogeneity was significant (I² = 78%; p < 0.001). Meta-analysis of seven studies also demonstrated that hiatal hernia was significantly associated with an increased risk of short-segment BE (OR = 2.76, 95% CI = 2.05-3.71, p < 0.001). The heterogeneity was not significant (I² = 30%; p = 0.201). Hiatal hernia should be a significant risk factor for BE, especially LSBE. PROSPERO registration number CRD42022367376.

295. RELATIONSHIP BETWEEN ABDOMINAL FAT DISTRIBUTION AND PROGRESSION OF BARRETT’S ESOPHAGUS TO ADENOCARCINOMA

Abstract Background Obesity was known to be a risk factor of the incidence of Barrett’s esophagus (BE) and Barrett’s esophageal adenocarcinoma (BEA). Especially excessive visceral fat has recently reported to promote some cancers, including BEA. This study aimed to clarify the impact of abdominal fat distribution on the progression of BE to adenocarcinoma in long-segment BE (LSBE) and short-segment BE (SSBE). Methods Study 1: We retrospectively reviewed the 124 patients with pathologically defined superficial BEA who underwent endoscopic resection, including 4 endoscopic mucosal resection (EMR) and 85 endoscopic submucosal dissection (ESD), or surgical operation (35 esophagectomy) in our institution between January 2004 and December 2018. 124 BEA cases included 34 LSBE (length ≥ 3 cm) cases and 90 SSBE (length ≥ 1 and &amp;lt; 3 cm) cases. Using computed tomography volumetry, we measured areas of visceral (VFA) and subcutaneous (SFA) fat at the level of the umbilicus, and calculated the VFA/SFA ratio in each patient, defining high-VFA/SFA ratio (≧1.0) and low-VFA/SFA ratio (&amp;lt;1.0). VFA/SFA ratio were compared and analyzed between BEA with LSBE group and BEA with SSBE group. Study2: We divided 62 patients who had LSBE into two groups based on prognosis of BEA; BEA with LSBE (34 patients) and non-BEA with LSBE group (18 patients). Abovementioned parameters were compared and analyzed between these two groups. Study3: Abovementioned parameters were compared and analyzed between BEA with SSBE (90 cases) and non-BEA with SSBE group (100 controls). Results study1: High VS ratio were seen in 22 (64.7%) patients among BEA with LSBE group and 34 (37.8%) patients among BEA with SSBE group, which is statistically significant (p = 0.0072). Study2: High VS ratio were seen in 6 (33.3%) patients among non-BEA with LSBE group. This result was statistically significant compared to BEA with LSBE group (0.038). Study3: In non-BEA with SSBE, 32 patients (32.0%) had High VS ratio, showing no significant difference compared to BEA with SSBE. Conclusion High VFA/SFA ratio was significantly associated with progression of long-segment Barrett’s esophagus to esophageal adenocarcinoma.

341. THE PREDICTION STRATEGY OF SUBMUCOSAL INVASION IN SUPERFICIAL BARRETT’S ADENOCARCINOMA BY THE COMBINATION OF HISTOLOGY IN BIOPSY AND MAGNIFYING ENDOSCOPY

Abstract Background Endoscopically predicting the depth of invasion of superficial Barrett’s esophageal adenocarcinoma (s-BEA) is important for choosing an appropriate treatment. This study aimed to evaluate the endoscopic and histopathological characteristics to diagnose s-BEA with submucosal invasion. Methods We retrospectively reviewed 105 tumors from 97 patients endoscopically and pathologically diagnosed with s-BEA in short-segment Barrett’s esophagus (SSBE) (60 lesions in 60 patients) and long-segment Barrett’s esophagus (LSBE) (45 lesions in 37 patients). One hundred five s-BEA lesions were classified into 60 intramucosal (pT1a) tumors and 45 submucosal (pT1b) tumors. Clinicopathological and endoscopic characteristics, including the histology in the biopsy specimens, were analyzed with comparison in pT1a vs pT1b tumors. The histology in the biopsy specimens was classified into two types such as the presence or absence of poorly differentiated component (PDC). Risk factors for submucosal invasion identified using univariate analysis were entered into a multivariate logistic regression analysis. Subsequently, the findings of magnifying endoscopy with narrow-band imaging (ME-NBI) were assessed to determine whether the poorly differentiated component (PDC) in the resected specimens can be identified or not. Results pT1b tumors showed significantly higher frequency than pT1a tumors in the following features: PDC in the biopsy specimens (21/45, 46.7%; vs 1/60, 1.7%; OR = 24.8), complex macroscopic type (33/45, 73.3%; vs 15/60, 25.0%; OR = 4.47), and tumor diameter &amp;gt; 20 mm (31/45, 68.9%; vs 13/60, 21.7%; OR = 4.40). In 87 tumors which were able to be evaluated for endoscopic findings with ME-NBI, 9 out of 11 tumors with corkscrew pattern or wavy micro-vessels showed PDC in the resected specimens. The sensitivity, specificity, and positive predicted value of these irregular vessels for predicting PDC in the resected specimens were 40.9%, 96.9%, and 81.8%, respectively. Conclusion PDC in the biopsy specimens, tumor diameter &amp;gt; 20 mm, and complex macroscopic type were independent predictors for submucosal invasion of BEA. The presence of PDC in the biopsy specimens was an especially useful predictor of T1b cancer with the highest odds. Further, ME-NBI can be useful to diagnose the presence of PDC in BEA.

Intestinal metaplasia in follow-up endoscopies among Asian patients with short-segment Barrett's esophagus: Regression, sampling error, and associated factors

The percentage of and factors associated with the regression of Barrett's esophagus (BE) or its characteristic intestinal metaplasia (IM) remain unclear, and conflicting results have been reported because of diverse regression and sampling error definitions. Thus, we investigated the rates of IM regression, sampling error, and associated factors. Forty-two patients with proven short-segment BE with IM who underwent two follow-up endoscopies with biopsies of Barrett's mucosa were retrospectively analyzed. Additional Alcian blue and MUC2 staining were done on the biopsy specimens without IM in hematoxylin-eosin staining. Only patients with negative hematoxylin-eosin, Alcian blue, and MUC2 staining for IM in both follow-up endoscopies were considered to have true regression. When all three stains were negative for IM in the first, but positive in the second follow-up endoscopy, we considered IM persisting and declared sampling error. Among the 18 patients without IM at the first follow-up endoscopy, only five (11.9%) were judged to have true regression. Prolonged proton-pump inhibitor use was significantly associated with regression. Limited experience of the endoscopist, and insufficient biopsy number were significantly related to sampling error. Receiver operating characteristic (ROC) curve analysis showed the best cut-off value of the biopsy number/maximal-length (cm) ratio to predict sampling error was 2.25. In our patients with short-segment BE, 11.9% experienced regression of IM. Prolonged proton-pump inhibitors treatment was associated with regression. An insufficient biopsy number was related to a missed IM, which may be eliminated by maintaining biopsy number/maximal-length (cm) ratio ≥2.25.

Editorial introductions.

Current Opinion in Gastroenterology was launched in 1985. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of gastroenterology is divided into 12 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Matthew A. CiorbaMatthew A. CiorbaDr Matthew Ciorba is a gastroenterologist and biomedical researcher dedicated to advancing care in the Inflammatory Bowel Diseases (IBD) and Colon Cancer. His clinical expertise is in caring for patients with Crohn's and ulcerative colitis and preventing colon cancer. He is Director of the IBD Center at Washington University, USA, and leads one of the largest clinical teams in the USA dedicated to providing comprehensive and cutting-edge clinical care to more than 8000 patients affected by IBD. His basic-translational research program is dedicated to defining pathways and mechanisms of intestinal inflammation and the transition to colon cancer. His lab has developed methods to study intestinal organoids and tumoroids to facilitate studies of the epithelial response to inflammation, injury and repair. His lab investigations have spawned four ground-breaking Bench-to-Bedside clinical trials addressing unmet patient needs in colitis, enteritis and rectal cancer using probiotics, novel immunotherapies and manipulating bile acids. In addition to his own lab, Dr Ciorba is also Director of IBD Research at Washington University and use this platform to foster collaborative discovery between the world-class scientific investigators and the robust IBD clinical program. Finally, he is deeply committed to training the next generation of medical investigators who will advance discovery and treatment of digestive diseases. Supporting this mission, he serves as Associate Director of the GI Fellowship's T32 Research Training grant and serves on several training grant review committees for several organizations including the CCF, AGA and NIH. Stuart J. SpechlerStuart J. SpechlerStuart Jon Spechler, MD is Chief of the Division of Gastroenterology and Co-Director of the Center for Esophageal Diseases at Baylor University Medical Center at Dallas, as well as the Co-Director of the Center for Esophageal Research at the Baylor Scott and White Research Institute. Prior to joining Baylor University Medical Center in January 2017, Dr Spechler was the Chief of the Division of Gastroenterology for the VA North Texas Healthcare System, Professor of Medicine, and holder of the Berta M. and Cecil O. Patterson Chair in Gastroenterology at the University of Texas Southwestern Medical Center, and he had been the Director of the Center for Swallowing Disorders at the Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts. Dr Spechler's research has focused primarily on disorders of the esophagus, especially GERD and its complications, and eosinophilic esophagitis. He has chaired three VA Cooperative Studies on medical and surgical treatments for gastroesophageal reflux disease. He described the condition known as “short-segment Barrett's esophagus” in 1994. Dr. Spechler has published more than 300 scientific reports, editorials, review articles, and book chapters on esophageal disorders. He is best known for his work in the areas of GERD, Barrett's esophagus, and eosinophilic esophagitis. Dr Spechler has served on the editorial boards of numerous journals including Gastroenterology, Gut, Alimentary Pharmacology and Therapeutics, Digestive Diseases and Sciences and Diseases of the Esophagus, and he has served as Chair of the Gastroenterology Teaching Project and the Esophago-Gastro-Duodenal Section of the American Gastroenterological Association.

Comparison of Texture and Color Enhancement Imaging with White Light Imaging in 52 Patients with Short-Segment Barrett's Esophagus.

BACKGROUND Texture and color enhancement imaging (TXI), a new type of image-enhanced endoscopy, may improve the detection of gastrointestinal lesions. Barrett's esophagus (BE) requires an accurate diagnosis since it may undergo neoplastic transformation. We aimed to evaluate the usefulness of TXI compared with white light imaging (WLI) in BE. MATERIAL AND METHODS In this prospective study at a single hospital from February 2021 to February 2022, we enrolled 52 consecutive patients with BE. Endoscopic images of BE using WLI, TXI mode 1 (TXI-1), TXI mode 2 (TXI-2), and narrow-band imaging (NBI) were compared by 10 endoscopists (5 experts and 5 trainees). Endoscopists scored visibility for the images as follows: 5 (improved), 4 (somewhat improved), 3 (equivalent), 2 (somewhat decreased), and 1 (decreased). Total visibility scores for all 10 endoscopists, and subgroups composed of the 5 expert endoscopists and the 5 trainee endoscopists, were evaluated. Main-group (10 endoscopists) scores of ≥40, 21-39, and ≤20, and subgroup (5 endoscopists) scores of ≥20, 11-19, and ≤10, were considered "improved", "equivalent", and "decreased", respectively. Inter-rater reliability (intra-class correlation coefficient [ICC]) was calculated and images were objectively assessed based on L*a*b* color values and color differences (ΔE*). RESULTS All 52 cases were diagnosed as short-segment BE (SSBE). TXI-1/TXI-2 improved visibility compared with WLI was: 78.8%/32.7% for all endoscopists; 82.7%/40.4% for trainees; and 76.9%/34.6% for experts. NBI did not improve visibility. The ICC for TXI-1 and TXI-2 compared with WLI was "excellent" for all endoscopists. The ΔE* between esophageal and Barrett's mucosae, and between Barrett's and gastric mucosae, was higher for TXI-1 than for WLI (P<0.01, P<0.05, respectively). CONCLUSIONS TXI, especially TXI-1, improves the endoscopic diagnosis of SSBE compared with WLI, regardless of the endoscopist's skill.

Comprehensive DNA methylation profiling of Barrett's esophagus and esophageal adenocarcinoma in Japanese patients.

Molecular mechanisms of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remain unclear in Japanese patients. Japanese EACs frequently have underlying short length BE: short-segment BE(SSBE), for which, neoplastic potential remains unclear. We performed comprehensive methylation profiling of EAC and BE in Japanese patients, mostly comprised with SSBE. Using three different groups of biopsies obtained from non-neoplastic BE from patients without cancer (n = 50; N group), with EAC (n = 27; ADJ group) and EAC (n = 22; T group), methylation statuses of nine candidate genes (N33, DPYS, SLC16A12, CDH13, IGF2, MLF1, MYOD1, PRDM5, and P2RX7) were examined by the bisulfite pyrosequencing. Reduced representation bisulfite sequencingwas performed to characterize the genome-wide methylation status in 32 samples (12 from N, 12 ADJ, and 8 from T groups). In the candidate approach, methylation levels of N33, DPYS, and SLC16A12 were higher in ADJ and T groups compared to that in N group. The ADJ group was an independent factor for higher DNA methylation in non-neoplastic BE. The genome-wide approach demonstrated an increase of hypermethylation from ADJ to T groups relative to N group near the transcription start sites. Among gene groups hypermethylated in ADJ and T groups (n = 645) and T group alone (n = 1438), 1/4 and 1/3 were overlapped with downregulated genes in the microarray data set, respectively. Accelerated DNA methylation is observed in EAC and underlying BE in Japanese patients, mostly comprised with SSBE, highlighting the potential impact of methylation in early carcinogenesis.

Esophageal Hypocontractile Disorders and Hiatal Hernia Size Are Predictors for Long Segment Barrett’s Esophagus

Presently, there is paucity of information about clinical predictors, especially esophageal motor abnormalities, for long segment Barrett's esophagus (LSBE) as compared with short segment Barrett's esophagus (SSBE). The aims of this study are to compare the frequency of esophageal function abnormalities between patients with LSBE and those with SSBE and to determine their clinical predictors. This was a multicenter cohort study that included all patients with a diagnosis of BE who underwent high-resolution esophageal manometry. Motility disorders were categorized as hypercontractile disorders or hypocontractile disorders and their frequency was compared between patients with LSBE and those with SSBE. Multivariable logistic regression modeling was used to calculate the odds of being diagnosed with LSBE relative to SSBE for demographics, comorbidities, medication use, endoscopic findings, and the type of motility disorders. A total of 148 patients with BE were identified, of which 89 (60.1%) had SSBE and 59 (39.9%) LSBE. Patients with LSBE had a significantly larger hiatal hernia and higher likelihood of erosive esophagitis than patients with SSBE (P = 0.002). Patients with LSBE had a significantly lower mean LES resting pressure, distal contractile integral, distal latency, and significantly higher failed swallows and hypocontractile motility disorders than those with SSBE (P < 0.05). Hiatal hernia and hypocontractile motility disorder increased the odds of LSBE by 38.0% and 242.0%, as opposed to SSBE. The presence of a hypocontractile motility disorder increased the risk for LSBE. Furthermore, the risk for LSBE was directly associated with the length of the hiatal hernia.

S432 Fifty Percent Increase in Low-Grade Dysplasia Detection Using Probe-Based Confocal Endomicroscopy in a Metropolitan Veteran Cohort Undergoing Short Segment Barrett’s Esophagus Surveillance

Introduction: Seattle protocol (SP) is the standard method to biopsy Barrett’s esophagus. However, SP may miss dysplasia in all types of BE. Few studies have focused on pCLE in the diagnosis of dysplasia in short segment Barrett’s esophagus (SSBE). The primary aim of our study was to determine if pCLE was more effective in diagnosing dysplastic mucosa in patients undergoing surveillance endoscopy in SSBE. Methods: Patients undergoing surveillance endoscopy and diagnosed with SSBE between January 1, 2018 and January 1, 2021 at the VA Loma Linda Healthcare System (VALLHCS) were included. Patients who underwent pCLE were compared to those undergoing SP. Esophagogastroduodenoscopy (EGD) was performed using a high definition diagnostic upper endoscope (Olympus, Center Valley PA). All patients in both pCLE and SP group underwent high-definition white light examination (HD-WLE). All pCLE examinations were performed by two gastroenterologists (C.S.J.and N.S.) using GastroFlex UHD Confocal Miniprobe (Cellvizio, Mauna Kea Technologies). Age, sex, number of EGDs prior to a diagnosis of dysplasia, hiatal hernia length and pCLE findings were assessed. SSBE was defined using Prague criteria, circumference (C) ≤ 2cm and maximal length of Barrett's segment (M) ≤ 3cm. Two pathologists reviewed all biopsies with a diagnosis of dysplasia. Continuous variables were compared using a Fisher’s exact test with p≤0.05 as statistically significant. This study was approved by the institutional review board for VALLHCS. Results: Sixty-seven patients were identified as having SSBE. Sixteen patients underwent pCLE-targeted biopsies while 51 underwent SP. The mean age of the pCLE group was 64 years and 65.9 years for those who underwent SP. There was no difference in age, BMI, smoking status, statin, H2 blocker or PPI use in patients who underwent pCLE-targeted biopsies versus those who underwent SP. Low-grade dysplasia was detected in 17 patients (25.3%). Of these 17 patients, 11 were detected with pCLE, and 6 were detected with SP. The use of pCLE was significantly associated with detection of low-grade dysplasia (11/16, 68.7%) compared to (6/51, 11.7%) with a p-value of < 0.001. Conclusion: In a primarily male metropolitan veteran population, pCLE may be helpful in identifying low grade dysplasia in patients with SSBE. SP biopsy techniques may miss LGD during SSBE surveillance.

488. RADIOFREQUENCY ABLATION OF LOW-GRADE DYSPLASIA IS COST-EFFECTIVE FOR PATIENTS WITH LONG-SEGMENT BARRETT'S OESOPHAGUS

Abstract Barrett’s oesophagus is a precursor to oesophageal adenocarcinoma (OAC), which can be lethal if found at late stages. Stages of Barrett's oesophagus are generally divided into non-dysplasia or dysplasia. There is little doubt that patients with high-grade dysplasia require endoscopic intervention, usually with ablative techniques. Endoscopic treatment of low-grade dysplasia (LGD) has been more controversial, however. Our main aim was to improve cost-effectiveness of LGD ablation using length of Barrett's oesophagus to select high-risk individuals. A cost-utility analysis was undertaken using a Markov cohort model, which simulated progression and regression of non-dysplastic Barrett’s oesophagus (NDBE) to EAC (cycle length of 6 months, time horizon of 35 years). Health states included: NDBE, regression of metaplasia, low-grade dysplasia (LGD), high-grade dysplasia (HGD), EAC, and death. Cost pertaining to investigations and treatments were sourced from local health network. Quality-adjusted life-year (QALY) data were taken from literature values. Initial estimates of transition probabilities between health states were derived from literature and calibrated to lifetime risk of HGD and OAC using standardised methodology. One-way and probabilistic sensitivity analysis were conducted. Several strategies (39 total) were tested in this cost-utility analysis and were broadly divided into selective (length-based) or non-selective LGD ablation. In addition to LGD ablation, surveillance intervals for NDBE were altered to improve cost-effectiveness. In non-selective group of strategies, only 1 was found to be cost-effective, whereas 24 of 28 length-based LGD ablation strategies were found to be cost-effective (at a willingness to pay threshold of AU$50,000/QALY). Probabilistic analysis (1000 simulations) showed that exclusion of individuals with short segment Barrett's oesophagus (SSBE) from surveillance with ablation of LGD in long-segment Barrett's oesophagus (LSBE) was the most cost-effective strategy (AU$33,031/QALY). Patients with long-segment Barrett's oesophagus are at significantly higher risk of progression to adenocarcinoma. Results of this study indicate reducing endoscopic surveillance for SSBE with routine surveillance for LSBE with ablation of LGD when detected is cost-effective in 100% of the simulations. Several studies in recent years have shown similar results. Thus ablation of LGD in Barrett's oesophagus requires serious consideration, especially for high-risk individuals.

Clinical Endoscopic and Histologic Findings of a Long-Term Follow-Up (10.7 Years) After Roux-en-Y Laparoscopic Gastric Bypass: a Prospective Study.

Bariatric surgery, with laparoscopic Roux-en-Y gastric bypass (LYGB), is one of the most effective treatments for long-term weight loss. However, there are few publications concerning endoscopic evaluations at late control. The purpose was to evaluate the macroscopic and histological findings at the distal esophagus, gastric pouch, jejunal limb and the evolution of Barrett's esophagus (BE) in the long term. Cohort of 110 patients with obesity underwent LYGB in a university hospital. Several clinical, endoscopic and histological evaluations were performed after surgery. Exclusion criteria were previous bariatric procedure, hiatal hernia > 4cm, BE with histological dysplasia and body mass index (BMI) > 50kg/m2. Average age was 38.7 ± 9years with 70% females. BMI averaged 39.6 ± 6kg/m2. Follow-up was 10.7 ± 2years, and 18 patients (16.4%) were lost. The total weight loss was 23.4 ± 7kg. Erosive esophagitis, present in 33% of patients, decreased to 5%. After surgery, intestinal metaplasia regressed to cardial mucosa in 5 of 8 patients. One patient developed a short-segment BE. The level of control to gastroesophageal reflux disease (GERD) symptom control was 87% to responders (Visick I-II) and 13% to non-responders (Visick III-IV). An increase in dilated cardia type III was observed (p < 0.001). The length of the gastric pouch increased significantly after surgery (p < 0.001). Anastomotic ulcers healed at 6months with proton pump inhibitor (PPI) use, without recurrence. LYGB is a very effective surgical procedure to control symptoms of GERD and/or endoscopic erosive esophagitis. Besides, regression of Barrett's mucosa to carditis occurred in 62%.

Clinicopathological Characteristics of Superficial Barrett's Adenocarcinoma in a Japanese Population: A Retrospective, Multicenter Study.

Objective Although Barrett's adenocarcinoma (BA) remains a minor disease in Japan, its incidence has been gradually increasing. We analyzed the characteristics of BA in Japanese populations. Methods We retrospectively reviewed medical records and analyzed the clinicopathological differences between short-segment Barrett's esophagus (SSBE) and long-segment Barrett's esophagus (LSBE), as well as metastasis. Local recurrence and metachronous lesions were analyzed only in patients who underwent endoscopic resection (ER). Patients Consecutive patients who had pathological T1 BAs resected by ER or surgery from January 2003 to December 2017. Results A total of 168 patients were analyzed, including 139 with SSBE and 29 with LSBE. In total, 67% of the SSBE lesions and 32% of the LSBE lesions were located between 0 and 3 o'clock (p=0.0014). No patients who achieved pathological margin-free resection (pR0) and 17% of patients who did not achieve pR0 experienced local recurrence (p=0.0131). None of the patients without lymphovascular involvement, a poorly differentiated component, lesion size of ＞30 mm, and submucosal invasion of ＞500 μm experienced metastasis. The 5-year cumulative incidence rate of metachronous BA after ER was 0% in patients with SSBE and 40% in patients with LSBE (p=0.0005). Conclusion Superficial BA was likely to be detected at the right anterior wall of SSBE in the Japanese population. The risk for metachronous BA after ER was high in Japanese patients with LSBE, as in Western patients.

Diagnosis and Management of Barrett's Esophagus: An Updated ACG Guideline.

Barrett's esophagus (BE) is a common condition associated with chronic gastroesophageal reflux disease. BE is the only known precursor to esophageal adenocarcinoma, a highly lethal cancer with an increasing incidence over the last 5 decades. These revised guidelines implement Grading of Recommendations, Assessment, Development, and Evaluation methodology to propose recommendations for the definition and diagnosis of BE, screening for BE and esophageal adenocarcinoma, surveillance of patients with known BE, and the medical and endoscopic treatment of BE and its associated early neoplasia. Important changes since the previous iteration of this guideline include a broadening of acceptable screening modalities for BE to include nonendoscopic methods, liberalized intervals for surveillance of short-segment BE, and volume criteria for endoscopic therapy centers for BE. We recommend endoscopic eradication therapy for patients with BE and high-grade dysplasia and those with BE and low-grade dysplasia. We propose structured surveillance intervals for patients with dysplastic BE after successful ablation based on the baseline degree of dysplasia. We could not make recommendations regarding chemoprevention or use of biomarkers in routine practice due to insufficient data.

Clinical adverse events and device failures for the Barrx™ radiofrequency ablation catheter system: a MAUDE database analysis.

BackgroundThe Barrx™ radiofrequency ablation (RFA) catheter system comes in several different variations and sizes and is widely used for the eradication of Barrett’s esophagus (BE). The Barrx™ 360 and 360 Express system is used to perform circumferential RFA, while the Barrx™ focal catheter system is used for secondary focal RFA or primary treatment of short-segment BE. We aimed to investigate the number and type of complications and device failures associated with the Barrx™ RFA catheter system.MethodWe analyzed post-marketing surveillance data from the Food and Drug Administration’s Manufacturer and User Facility Device Experience (MAUDE) database from August 2011 to August 2021.ResultsDuring the study period, 148 unique reports detailing 78 device issues and 87 patient-related adverse events were identified. The most reported adverse events for patients were stenosis secondary to treatment (n=15, 17.24%), mucosal laceration of the esophagus (n=13, 14.94%), chest pain (n=10, 11.49%), and odynophagia/dysphagia (n=7, 8.05%). The most common device complication was failure of the device to deploy when activated (n=10, 13.82%). Other device malfunctions included material deformation/distortion (n=7, 8.97%), catheter breakage (n=6, 7.69%), connection problems between the generator cable and RFA device (n=6, 7.69%), and failure of the balloon to properly inflate (n=5, 6.41%).ConclusionFindings from the MAUDE database highlight patient and device complications that endoscopists should be aware of prior to RFA of BE with the Barrx™ RFA catheter system.

Helicobacter pylori infection is associated with reduced risk of Barrett\u2019s esophagus: a meta-analysis and systematic review

BackgroundHelicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett’s esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship.MethodsWe reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies.Results46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51–0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15–0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82–1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25–0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78–1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54–0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43–1.78; P = 0.73).ConclusionsHp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection.