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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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). DISCUSSION: EsoCheck/EsoGuard demonstrated high sensitivity and specificity in detecting BE and BE-related neoplasia.

Rates of Recurrent Intestinal Metaplasia and Dysplasia After Successful Endoscopic Therapy of Barrett's Neoplasia by Endoscopic Mucosal Resection vs Endoscopic Submucosal Dissection and Ablation: A Large North American Multicenter Cohort.

INTRODUCTION: Endoscopic eradication therapy (EET) combining endoscopic resection (ER) with endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) followed by ablation is the standard of care for the treatment of dysplastic Barrett's esophagus (BE). We have previously shown comparable rates of complete remission of intestinal metaplasia (CRIM) with both approaches. However, data comparing recurrence after CRIM are lacking. We compared rates of recurrence after CRIM with both techniques in a multicenter cohort. METHODS: Patients undergoing EET achieving CRIM at 3 academic institutions were included. Demographic and clinical data were abstracted. Outcomes included rates and predictors of any BE and dysplastic BE recurrence in the 2 groups. Cox-proportional hazards models and inverse probability treatment weighting (IPTW) analysis were used for analysis. RESULTS: A total of 621 patients (514 EMR and 107 ESD) achieving CRIM were included in the recurrence analysis. The incidence of any BE (15.7, 5.7 per 100 patient-years) and dysplastic BE recurrence (7.3, 5.3 per 100 patient-years) were comparable in the EMR and ESD groups, respectively. On multivariable analyses, the chances of BE recurrence were not influenced by ER technique (hazard ratio 0.87; 95% confidence interval 0.51-1.49; P = 0.62), which was also confirmed by IPTW analysis (ESD vs EMR: hazard ratio 0.98; 95% confidence interval 0.56-1.73; P = 0.94). BE length, lesion size, and history of cigarette smoking were independent predictors of BE recurrence. DISCUSSION: Patients with BE dysplasia/neoplasia achieving CRIM, initially treated with EMR/ablation, had comparable recurrence rates to ESD/ablation. Randomized trials are needed to confirm these outcomes between the 2 ER techniques.

Reduced risk of de novo Barrett esophagus after bariatric surgery: a national database study.

BACKGROUND: Bariatric surgery is an effective treatment for obesity and may decrease the morbidity and mortality of obesity-associated cancers. OBJECTIVE: We investigated the risk of a new diagnosis of Barrett esophagus (BE) following bariatric surgery compared to screening colonoscopy controls. SETTING: Large national database including patients who received care in inpatient, outpatient, and specialty care services. METHODS: A national healthcare database (TriNetX, LLC) was used for this analysis. Cases included adults (aged ≥18 yr) who had undergone either sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Controls included adults undergoing screening colonoscopy and an esophagoduodenoscopy on the same day and had never undergone bariatric surgery. Cases and controls were propensity-matched for confounders. The risk of de novo diagnosis of BE at least 1 year after bariatric surgery was compared between cases and controls. Secondary analyses examined the effect of bariatric surgery on metabolic outcomes such as weight loss and body mass index (BMI). The risk of de novo diagnosis of BE in SG was compared with RYGB. Odds ratios (OR) and 95% CI were used to report on these associations. RESULTS: In the propensity-matched analysis, patients who had undergone a bariatric surgical procedure showed a significantly reduced risk of de novo BE when compared with screening colonoscopy controls (.67 [.48, .94]). There was substantial reduction in weight and BMI in the bariatric surgery group when compared with baseline. There was no significant difference in de novo BE diagnosis between the propensity-matched SG and RYGB groups (.77 [.5, 1.2]). CONCLUSION: Patients who underwent bariatric surgery (RYGB or SG) had a lower risk of being diagnosed with BE compared with screening colonoscopy controls who did not receive bariatric surgery. This effect appears to be largely mediated by reduction in weight and BMI.

Prevalence and Predictors of Barrett's Esophagus After Negative Initial Endoscopy: Analysis From Two National Databases.

BACKGROUND & AIMS: Guidelines suggest a single screening esophagogastroduodenoscopy (EGD) in patients with multiple risk factors for Barrett's esophagus (BE). We aimed to determine BE prevalence and predictors on repeat EGD after a negative initial EGD, using 2 large national databases (GI Quality Improvement Consortium [GIQuIC] and TriNetX). METHODS: Patients who underwent at least 2 EGDs were included and those with BE or esophageal adenocarcinoma detected at initial EGD were excluded. Patient demographics and prevalence of BE on repeat EGD were collected. Multivariate logistic regression was performed to assess for independent risk factors for BE detected on the repeat EGD. RESULTS: In 214,318 and 153,445 patients undergoing at least 2 EGDs over a median follow-up of 28-35 months, the prevalence of BE on repeat EGD was 1.7% in GIQuIC and 3.4% in TriNetX, respectively (26%-45% of baseline BE prevalence). Most (89%) patients had nondysplastic BE. The prevalence of BE remained stable over time (from 1 to >5 years from negative initial EGD) but increased with increasing number of risk factors. BE prevalence in a high-risk population (gastroesophageal reflux disease plus ≥1 risk factor for BE) was 3%-4%. CONCLUSIONS: In this study of >350,000 patients, rates of BE on repeat EGD ranged from 1.7%-3.4%, and were higher in those with multiple risk factors. Most were likely missed at initial evaluation, underscoring the importance of a high-quality initial endoscopic examination. Although routine repeat endoscopic BE screening after a negative initial examination is not recommended, repeat screening may be considered in carefully selected patients with gastroesophageal reflux disease and ≥2 risk factors for BE, potentially using nonendoscopic tools.

Endoscopic submucosal dissection with versus without traction for pathologically staged T1B esophageal cancer: a multicenter retrospective study.

BACKGROUND AND AIMS: Positive vertical margins (VMs) are common after endoscopic submucosal dissection (ESD) of T1b esophageal cancer (EC) and are associated with an increased risk of recurrence. Traction during ESD provides better exposure of the submucosa and may allow deeper dissection, potentially reducing the risk of positive VMs. We conducted a retrospective multicenter study to compare the proportion of resections with positive VMs in ESD performed with versus without traction in pathologically staged T1b EC. METHODS: Patients who underwent ESD revealing T1b EC (squamous or adenocarcinoma) at 10 academic tertiary referral centers in the United States (n = 9) and Brazil (n = 1) were included. Demographic and clinical data were abstracted. ESD using either traction techniques (tunneling, pocket) or traction devices (clip line, traction wire) were classified as ESD with traction (Tr-ESD) and those without were classified as conventional ESD without traction. The primary outcome was a negative VM. Multivariable logistic regression was used to assess associations with negative VMs. RESULTS: A total of 166 patients with pathologically staged T1b EC underwent Tr-ESD (n = 63; 38%) or conventional ESD without traction (n = 103; 62%). Baseline factors were comparable between both groups. On multivariable analysis, Tr-ESD was found to be independently associated with negative VMs (odds ratio, 2.25; 95% confidence interval, 1.06-4.91; P = .037) and R0 resection (odds ratio, 2.83; 95% confidence interval, 1.33-6.23; P = .008). CONCLUSION: Tr-ESD seems to be associated with higher odds of negative VMs than ESD without traction for pathologically staged T1b EC, and future well-conducted prospective studies are warranted to establish the findings of the current study.

Patients With Esophageal Adenocarcinoma With Prior Gastroesophageal Reflux Disease Symptoms Are Similar to Those Without Gastroesophageal Reflux Disease: A Cross-Sectional Study.

INTRODUCTION: A substantial proportion of patients with esophageal adenocarcinoma (EAC) do not report gastroesophageal reflux disease (GERD) symptoms. This study aimed to compare the risk factor profiles and cancer stage at presentation of patients with EAC with and without prior GERD. METHODS: In this retrospective cross-sectional study, patients with EAC were divided into 2 cohorts: (i) EAC with prior GERD: patients who reported typical GERD symptoms (heartburn or regurgitation) ≥1 year before cancer diagnosis and (ii) EAC without prior GERD: patients who did not report prior GERD symptoms or reported symptoms within 1 year of their cancer diagnosis. Baseline demographics, risk factors, and cancer stage at presentation were compared between the 2 cohorts. In addition, the distribution of patients based on numbers of BE/EAC-associated risk factors (1, 2, 3, 4, and 5 or more) was examined in the symptomatic and asymptomatic cohorts. RESULTS: Over 13 years, 388 patients with EAC with prior GERD and 245 patients with EAC without prior GERD were recruited. Both groups had similar baseline demographics and risk factors, but patients with EAC with prior GERD were more likely to have a history of BE. Asymptomatic patients had more advanced disease. Patients with 3 or more BE/EAC-related risk factors formed the largest proportion of patients in both the symptomatic and asymptomatic cohorts. DISCUSSION: Patients with EAC with and without prior GERD symptoms are phenotypically similar, suggesting that BE screening efforts to prevent or detect early EAC should not be restricted to just those with GERD.

NON-ENDOSCOPIC ESOPHAGEAL SAMPLING DEVICE AND BIOMARKER PANEL FOR DETECTION OF BARRETT'S ESOPHAGUS (BE) AND ESOPHAGEAL ADENOCARCINOMA (EAC).

BACKGROUND: We previously reported an encapsulated balloon (EsoCheck TM , EC), which selectively samples the distal esophagus, that coupled with a two methylated DNA biomarker panel (EsoGuard TM , EG), detected Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), with a sensitivity and specificity of 90.3% and 91.7%, respectively. This previous study utilized frozen EC samples. AIM: To assess a next generation EC sampling device and EG assay that utilizes a room temperature sample preservative to enable office-based testing. METHODS: Cases with nondysplastic (ND) and dysplastic (indefinite=IND, low grade dysplasia = LGD, high grade dysplasia = HGD) BE, EAC, junctional adenocarcinoma (JAC) and controls with no intestinal metaplasia (IM) were included. Nurses or physician assistants at six institutions, who were trained in EC administration, delivered the encapsulated balloon per orally and inflated it in the stomach. The inflated balloon was pulled back to sample 5 cm of the distal esophagus, then deflated and retracted into the EC capsule to prevent sample contamination from proximal esophagus. Nextgen EG sequencing assays performed on bisulfite-treated DNA extracted from EC samples determined levels of methylated Vimentin (mVIM) and methylated Cyclin A1 (mCCNA1) in a CLIA-certified laboratory, blinded to patients' phenotypes. RESULTS: 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 EC sampling. Mean time for EC sampling was just over 3 minutes. The cases included 31 NDBE, 16 IND/LGD, 23 HGD, and 18 EAC/JAC. Thirty-seven (53%) of the non-dysplastic and dysplastic BE cases were short-segment BE (SSBE; < 3 cm). Overall sensitivity for detecting all cases was 85% (95% CI= 0.78-0.93) and specificity was 85% (95% CI=0.79-0.90). Sensitivity for NDBE was 84% (n=37). The EC/EG test detected 100% of cancers. CONCLUSION: The next-generation EC/EG technology has been both successfully updated to incorporate a room temperature sample collection preservative and successfully implemented in a CLIA certified laboratory. When performed by trained personnel, EC/EG detects non-dysplastic BE, dysplastic BE, and cancer with high sensitivity and specificity, replicating the operating characteristics of the initial pilot study of this technology. Future applications utilizing EC/EG to screen broader populations at risk for developing cancer are proposed. SIGNIFICANCE: This multi-center study demonstrates the successful performance of a commercially available clinically implementable non-endoscopic screening test for BE in the U.S., as recommended in the most recent ACG Guideline and AGA Clinical Update. It transitions and validates a prior academic laboratory-based study of frozen research samples over to a CLIA laboratory, one that also integrates a clinically practical room temperature method for sample acquisition and storage, enabling office-based screening.

Surveillance in Barrett's Esophagus: Challenges, Progress, and Possibilities.

Endoscopic surveillance of Barrett's esophagus, aiming to detect prevalent dysplasia and adenocarcinoma, followed by effective endoscopic treatment, is an integral part of the esophageal adenocarcinoma prevention paradigm. However, several limitations, such as the subtle appearance of dysplasia, sampling error (inherent in current surveillance protocols), and noncompliance with surveillance recommendations, lead to missed dysplasia and neoplasia, reducing the effectiveness of surveillance as currently practiced. Careful endoscopic assessment with high-resolution white-light endoscopy, dye-based or electronic chromoendoscopy, and comprehensive sampling of the BE mucosa, remains the cornerstone of endoscopic surveillance. Emerging innovations in this area span the gamut of more efficient sampling methods, advanced imaging tools, artificial intelligence, and molecular marker-powered approaches as adjuncts, to identify prevalent and predict incident dysplasia or adenocarcinoma. Development and implementation of validated quality indicators will allow additional advancement of this critical field. These approaches will hopefully enable efficient and effective cancer prevention and treatment.

Role of through-the-scope catheter-based EUS in inflammatory bowel disease diagnosis and activity assessment.

BACKGROUND AND AIMS: Distinguishing Crohn's disease (CD) from ulcerative colitis (UC) may be difficult when the disease is limited to the colon. Transmural healing is an important adjunctive measure of inflammatory bowel disease activity. The aim of this study was to examine the role of EUS in differentiating CD versus UC and evaluating transmural disease activity. METHODS: This prospective cohort study enrolled 20 patients with CD (10 active [aCD], 10 inactive), 20 patients with UC (10 active [aUC], 10 inactive), and 20 control subjects who underwent colonoscopy from 2019 to 2021 at a tertiary care center. Measurements of bowel wall layer thickness from the rectum and cecum were obtained using a through-the-scope US catheter (UM-3R-3; Olympus, Center Valley, Penn, USA) at the time of colonoscopy. RESULTS: Compared with control subjects, patients with aCD had thicker rectal submucosa and total wall layer (submucosa median, 1.80 mm [interquartile range {IQR}, 1.40-2.00] vs .60 mm [IQR, .40-.70]; total wall median, 3.70 mm [IQR, 3.52-4.62] vs 2.10 mm [IQR, 1.70-2.40], respectively; P < .01). Similar significant findings were observed for the cecal wall layers. Compared with control subjects, patients with aUC had thicker rectal mucosa and total wall but not submucosa or muscularis propria layers (mucosa median, 1.35 mm [IQR, 1.12-1.47] vs .60 mm [IQR, .57-.70]; total wall median, 3.45 mm [IQR, 2.85-3.75] vs 2.10 mm [IQR, 1.70-2.40], respectively; P < .01). Patients with aCD compared with those with aUC had a significantly thicker rectal submucosa layer (median, 1.80 mm [IQR, 1.40-2.00] vs .55 mm [IQR, .40-.75], respectively, P < .01). Cutoff values of 1.1 mm for rectal submucosa in CD (sensitivity, 1.0; specificity, 1.0) and 1.1 mm for rectal mucosa in UC (sensitivity, .8; specificity, .9) were found to differentiate active from inactive disease. CONCLUSIONS: EUS measurements of colon wall layers can help diagnose aCD versus aUC and assess transmural disease activity. (Clinical trial registration number: NCT03863886.).

Evidence-Based Cognitive Endoscopy Simulators: Do They Exist? A Systematic Search and Evaluation of Existing Platforms.

BACKGROUND: The development of guidelines by gastroenterology societies increasingly stresses evidence-based endoscopic practice. AIMS: We performed a systematic assessment to determine whether endoscopic video teaching platforms incorporate evidence-based educational strategies and methods in order to disseminate guideline-based endoscopic management strategies. METHODS: Platforms with a video component were systematically identified using the Google search engine, Apple and Android application stores, and searching four major gastroenterology society websites and three known platforms, to identify all relevant platforms. Two video samples from each teaching platform were reviewed independently by two authors and assessed for use of a priori defined principles of evidence-based medicine, as determined by consensus agreement and for the use of simulation. RESULTS: Fourteen platforms were included in the final analysis, and two videos from each were analyzed. One of the 14 platforms used simulation and incorporated evidence-based medicine principles consistently. Nine of the 14 platforms were not transparent in regard to citation. None of the platforms consistently cited the certainty of evidence or explained how evidence was selected. CONCLUSIONS: Education of guideline-based endoscopic management strategies using principles of evidence-based medicine is under-utilized in endoscopic videos. In addition, the use of cognitive simulation is absent in this arena. There is a paucity of evidence-based cognitive endoscopy simulators designed for fellows that incorporate systematic evaluation, and efforts should be made to create this platform.

The Ephrin B2 Receptor Tyrosine Kinase Is a Regulator of Proto-oncogene MYC and Molecular Programs Central to Barrett's Neoplasia.

BACKGROUND & AIMS: Mechanisms contributing to the onset and progression of Barrett's (BE)-associated esophageal adenocarcinoma (EAC) remain elusive. Here, we interrogated the major signaling pathways deregulated early in the development of Barrett's neoplasia. METHODS: Whole-transcriptome RNA sequencing analysis was performed in primary BE, EAC, normal esophageal squamous, and gastric biopsy tissues (n = 89). Select pathway components were confirmed by quantitative polymerase chain reaction in an independent cohort of premalignant and malignant biopsy tissues (n = 885). Functional impact of selected pathway was interrogated using transcriptomic, proteomic, and pharmacogenetic analyses in mammalian esophageal organotypic and patient-derived BE/EAC cell line models, in vitro and/or in vivo. RESULTS: The vast majority of primary BE/EAC tissues and cell line models showed hyperactivation of EphB2 signaling. Transcriptomic/proteomic analyses identified EphB2 as an endogenous binding partner of MYC binding protein 2, and an upstream regulator of c-MYC. Knockdown of EphB2 significantly impeded the viability/proliferation of EAC and BE cells in vitro/in vivo. Activation of EphB2 in normal esophageal squamous 3-dimensional organotypes disrupted epithelial maturation and promoted columnar differentiation programs, notably including MYC. EphB2 and MYC showed selective induction in esophageal submucosal glands with acinar ductal metaplasia, and in a porcine model of BE-like esophageal submucosal gland spheroids. Clinically approved inhibitors of MEK, a protein kinase that regulates MYC, effectively suppressed EAC tumor growth in vivo. CONCLUSIONS: The EphB2 signaling is frequently hyperactivated across the BE-EAC continuum. EphB2 is an upstream regulator of MYC, and activation of EphB2-MYC axis likely precedes BE development. Targeting EphB2/MYC could be a promising therapeutic strategy for this often refractory and aggressive cancer.

Novel DNA Methylation Biomarker Panel for Detection of Esophageal Adenocarcinoma and High-Grade Dysplasia.

PURPOSE: Current endoscopy-based screening and surveillance programs have not been proven effective at decreasing esophageal adenocarcinoma (EAC) mortality, creating an unmet need for effective molecular tests for early detection of this highly lethal cancer. We conducted a genome-wide methylation screen to identify novel methylation markers that distinguish EAC and high-grade dysplasia (HGD) from normal squamous epithelium (SQ) or nondysplastic Barrett's esophagus (NDBE). EXPERIMENTAL DESIGN: DNA methylation profiling of samples from SQ, NDBE, HGD, and EAC was performed using HM450 methylation arrays (Illumina) and reduced-representation bisulfate sequencing. Ultrasensitive methylation-specific droplet digital PCR and next-generation sequencing (NGS)-based bisulfite-sequencing assays were developed to detect the methylation level of candidate CpGs in independent esophageal biopsy and endoscopic brushing samples. RESULTS: Five candidate methylation markers were significantly hypermethylated in HGD/EAC samples compared with SQ or NDBE (P < 0.01) in both esophageal biopsy and endoscopic brushing samples. In an independent set of brushing samples used to construct biomarker panels, a four-marker panel (model 1) demonstrated sensitivity of 85.0% and 90.8% for HGD and EACs respectively, with 84.2% and 97.9% specificity for NDBE and SQ respectively. In a validation set of brushing samples, the panel achieved sensitivity of 80% and 82.5% for HGD and EAC respectively, at specificity of 67.6% and 96.3% for NDBE and SQ samples. CONCLUSIONS: A novel DNA methylation marker panel differentiates HGD/EAC from SQ/NDBE. DNA-methylation-based molecular assays hold promise for the detection of HGD/EAC using esophageal brushing samples.

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival.

PURPOSE: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies. METHODS: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I v higher-stage). Overall survival was determined using the Kaplan-Meier method. RESULTS: Of 1,461 high-risk individuals enrolled into CAPS5, 48.5% had a pathogenic variant in a PDAC-susceptibility gene. Ten patients were diagnosed with PDAC, one of whom was diagnosed with metastatic PDAC 4 years after dropping out of surveillance. Of the remaining nine, seven (77.8%) had a stage I PDAC (by surgical pathology) detected during surveillance; one had stage II, and one had stage III disease. Seven of these nine patients with PDAC were alive after a median follow-up of 2.6 years. Eight additional patients underwent surgical resection for worrisome lesions; three had high-grade and five had low-grade dysplasia in their resected specimens. In the entire CAPS cohort (CAPS1-5 studies, 1,731 patients), 26 PDAC cases have been diagnosed, 19 within surveillance, 57.9% of whom had stage I and 5.2% had stage IV disease. By contrast, six of the seven PDACs (85.7%) detected outside surveillance were stage IV. Five-year survival to date of the patients with a screen-detected PDAC is 73.3%, and median overall survival is 9.8 years, compared with 1.5 years for patients diagnosed with PDAC outside surveillance (hazard ratio [95% CI]; 0.13 [0.03 to 0.50], P = .003). CONCLUSION: Most pancreatic cancers diagnosed within the CAPS high-risk cohort in the recent years have had stage I disease with long-term survival.

Sex differences in esophageal cancer overall and by histological subtype.

Esophageal cancer is the seventh most common type of cancer in the world, the sixth leading cause of cancer-related death and its incidence is expected to rise 140% in the world in a period of 10 years until 2025. The overall incidence is higher in males, while data about prognosis and survival are not well established yet. The goal of this study was to carry out a comprehensive analysis of differences between sexes and other covariates in patients diagnosed with primary esophageal cancer. Data from 2005 to 2020 were obtained from the University Hospitals (UH) Seidman Cancer Center and from 2005 to 2018 from SEER. Patients were categorized according to histological subtype and divided according to sex. Pearson Chi-square test was used to compare variables of interest by sex and the influence of sex on survival was assessed by Kaplan Meier, log rank tests and Cox proportional hazards regression models. A total of 1205 patients were used for analysis. Sex differences in all types were found for age at diagnosis, histology, smoking status and prescriptions of NSAIDs and in SCC for age at diagnosis and alcoholism. Survival analysis didn't showed differences between males and females on univariable and multivariable models. Males have a higher incidence of Esophageal Cancer and its two main subtypes but none of the comprehensive set of variables analyzed showed to be strongly or unique correlated with this sex difference in incidence nor are they associated with a sex difference in survival.

Outcomes for endoscopic submucosal dissection of pathologically staged T1b esophageal cancer: a multicenter study.

BACKGROUND AND AIMS: The outcomes of endoscopic submucosal dissection (ESD) for T1b esophageal cancer (EC) and its recurrence rates remain unclear in the West. Using a multicenter cohort, we evaluated technical outcomes and recurrence rates of ESD in the treatment of pathologically staged T1b EC. METHODS: We included patients who underwent ESD of T1b EC at 7 academic tertiary referral centers in the United States (n = 6) and Brazil (n = 1). We analyzed demographic, procedural, and histopathologic characteristics and follow-up data. Time-to-event analysis was performed to evaluate recurrence rates. RESULTS: Sixty-six patients with pathologically staged T1b EC after ESD were included in the study. A preprocedure staging EUS was available in 54 patients and was Tis/T1a in 27 patients (50%) and T1b in 27 patients (50%). En-bloc resection rate was 92.4% (61/66) and R0 resection rate was 54.5% (36/66). Forty-nine of 66 patients (74.2%) did not undergo surgery immediately after resection and went on to surveillance. Ten patients had ESD resection within the curative criteria, and no recurrences were seen in a 13-month (range, 3-18.5) follow-up period in these patients. Ten of 39 patients (25.6%) with noncurative resections had residual/recurrent disease. Of the 10 patients with noncurative resection, local recurrence alone was seen in 5 patients (12.8%) and metastatic recurrence in 5 patients (12.8%). On univariate analysis, R1 resection had a higher risk of recurrent disease (hazard ratio, 6.25; 95% confidence interval, 1.29-30.36; P = .023). CONCLUSIONS: EUS staging of T1b EC has poor accuracy, and a staging ESD should be considered in these patients. ESD R0 resection rates were low in T1b EC, and R1 resection was associated with recurrent disease. Patients with noncurative ESD resection of T1b EC who cannot undergo surgery should be surveyed closely, because recurrent disease was seen in 25% of these patients.

Prediction of neoplastic progression in Barrett's esophagus using nanoscale nuclear architecture mapping: a pilot study.

BACKGROUND AND AIMS: Nanoscale nuclear architecture mapping (nanoNAM), an optical coherence tomography-derived approach, is capable of detecting with nanoscale sensitivity structural alterations in the chromatin of epithelial cell nuclei at risk for malignant transformation. Because these alterations predate the development of dysplasia, we aimed to use nanoNAM to identify patients with Barrett's esophagus (BE) who might progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS: This is a nested case-control study of 46 BE patients, of which 21 progressed to HGD/EAC over 3.7 ± 2.37 years (cases/progressors) and 25 patients who did not progress over 6.3 ± 3.1 years (control subjects/nonprogressors). The archived formalin-fixed paraffin-embedded tissue blocks collected as part of standard clinical care at the index endoscopy were used. nanoNAM imaging was performed on a 5-µm formalin-fixed paraffin-embedded section, and each nucleus was mapped to a 3-dimensional (3D) depth-resolved optical path difference (drOPD) nuclear representation, quantifying nanoscale-sensitive alterations in the 3D nuclear architecture of the cell. Using 3D-drOPD representation of each nucleus, we computed 12 patient-level nanoNAM features summarizing the alterations in intrinsic nuclear architecture. A risk prediction model was built incorporating nanoNAM features and clinical features. RESULTS: A statistically significant differential shift was observed in the drOPD cumulative distributions between progressors and nonprogressors. Of the 12 nanoNAM features, 6 (mean-maximum, mean-mean, mean-median, entropy-median, entropy-entropy, entropy-skewness) showed a statistically significant difference between cases and control subjects. NanoNAM features based prediction model identified progression in independent validation sets, with an area under the receiver operating characteristic curve of 80.8% ± .35% (mean ± standard error), with an increase to 82.54% ± .46% when combined with length of the BE segment. CONCLUSIONS: NanoNAM can serve as an adjunct to histopathologic evaluation of BE patients and aid in risk stratification.

Age of diagnosis in familial Barrett's associated neoplasia.

The identification of hereditary cancer genes for esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), may prove critical for the development of novel prevention and treatment strategies. Specifically, efforts for detecting BE and EAC susceptibility genes have focused on families with three or more affected members, since these individuals have an earlier age onset compared to non-familial individuals. Given that the use of BE may overestimate the likelihood of disease heritability, we evaluated the age of diagnosis in kindreds with a restricted definition including only confirmed high-grade dysplasia (HGD) or EAC. The Familial Barrett's Esophagus Consortium database was used to identify individuals with HGD and EAC. These individuals were subsequently split into three kindred groups: non-familial-a single affected family member, duplex-two affected family members, and multiplex-three or more affected family members. Age of cancer diagnosis and other risk factors were compared between individuals in these groups. The study included 441 non-familial, 46 duplex, and 13 multiplex individuals. There was a statistically significant difference for age of diagnosis for individuals in the multiplex families compared to the non-familial and duplex families (56.0 versus 64.3, 63.5; p = 0.049). There was no significant difference between demographic factors and other cancer risk factors between family types. The results of this study support a genetic basis for familial Barrett's associated neoplasia and evaluation of the genetic susceptibility to this disease should continue to focus on families with multiple (three or more) affected members.