Publications by authors named "Nicholas J Shaheen"

332 Publications

Gender and Nationality Trends in Manuscripts Published in Prominent Gastroenterology Journals Between 1997 and 2017.

Dig Dis Sci 2021 May 18. Epub 2021 May 18.

Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA.

Background: Gender disparities remain in the field of gastroenterology (GI) despite the decreasing gender gap in the medical field overall. We sought to examine primary and last female authorship as a marker of academic opportunity and advancement to assess the proportion of women publishing in GI over 20 years (1997-2017).

Methods: In this observational study, we assessed the gender and nationality of primary and last authors of original research manuscripts in three GI journals (Gastroenterology, Gut, and American Journal of Gastroenterology) across a 20-year period in 5-year intervals (in 1997, 2002, 2007, and 2012). We used a validated gender-determining algorithm, genderize.io, to classify gender. Our primary outcome was the proportion of female primary and last authors, with secondary measures assessing trends in gender and nationality.

Results: Through the Genderize.io gender database, we were able to identify the gender for 3,673 (95.9%) of primary author names and 3,504 (95.4%) of last author names in the 3,615 manuscripts evaluated. Overall, there was a significant increase in female primary authors over time, from 18.1% in 1997 to 42.6% in 2017, a 6.0% increase per 5-year period (95% CI 4.8-7.2%). A similar trend was found for female last authors, however, at a slower rate, from 8.3% in 1997 to 24.7% in 2017, a 3.5% increase per 5 years (95% CI 2.5-4.4%). These trends were noted cumulatively, and in each journal individually. Manuscripts with a female last author were more likely to demonstrate a female primary author.

Conclusion: Female authorship in high-impact gastroenterology journals has increased over time. Last authorship has lagged primary authorship in female representation and has increased more slowly over time. Interventions to reduce gender disparity in GI research should focus on the transition from first to last authorship.
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http://dx.doi.org/10.1007/s10620-021-07021-2DOI Listing
May 2021

Racial Disparities in Adherence to Quality Indicators in Barrett's Esophagus: An Analysis Using the GIQuIC National Benchmarking Registry.

Am J Gastroenterol 2021 06;116(6):1201-1210

University of Colorado School of Medicine, Division of Gastroenterology and Hepatology, Anschutz Medical Campus, Aurora, Colorado, USA.

Introduction: Racial disparities in outcomes in esophageal adenocarcinoma are well established. Using a nationwide registry, we aimed to compare clinical and endoscopic characteristics of blacks and whites with Barrett's esophagus (BE) and adherence to defined quality indicators.

Methods: We analyzed data from the Gastrointestinal Quality Improvement Consortium Registry between January 2012 and December 2019. Patients who underwent esophagogastroduodenoscopy with an indication of BE screening or surveillance, or an endoscopic finding of BE, were included. Adherence to recommended endoscopic surveillance intervals of 3-5 years for nondysplastic BE and adherence to Seattle biopsy protocol were assessed. Multivariate logistic regression was conducted to assess variables associated with adherence.

Results: A total of 100,848 esophagogastroduodenoscopies in 84,789 patients met inclusion criteria (blacks-3,957 and whites-96,891). Blacks were less likely to have histologically confirmed BE (34.3% vs 51.7%, P < 0.01), had shorter BE lengths (1.61 vs 2.35 cm, P < 0.01), and were less likely to have any dysplasia (4.3% vs 7.1%, P < 0.01). Although whites were predominantly male (62.2%), about half of blacks with BE were female (53.0%). Blacks with nondysplastic BE were less likely to be recommended appropriate surveillance intervals (OR 0.78; 95% CI 0.68-0.89). Adherence rates to the Seattle protocol were modestly higher among blacks overall (OR 1.12, 95% CI 1.04-1.20), although significantly lower among blacks with BE segments >6 cm.

Discussion: The use of sex as a risk factor for BE screening may be inappropriate among blacks. Fewer blacks were recommended appropriate surveillance intervals, and blacks with longer segment BE were less likely to undergo Seattle biopsy protocol.
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http://dx.doi.org/10.14309/ajg.0000000000001230DOI Listing
June 2021

Age of diagnosis in familial Barrett's associated neoplasia.

Fam Cancer 2021 Mar 11. Epub 2021 Mar 11.

Case Western Reserve University School of Medicine, Cleveland, OH, USA.

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.
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http://dx.doi.org/10.1007/s10689-021-00239-zDOI Listing
March 2021

Utility and Cost-Effectiveness of a Nonendoscopic Approach to Barrett's Esophagus Surveillance After Endoscopic Therapy.

Clin Gastroenterol Hepatol 2021 Feb 10. Epub 2021 Feb 10.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

Background & Aims: A non-endoscopic approach to Barrett's esophagus (BE) surveillance after radiofrequency ablation (RFA) would offer a less invasive method for monitoring. We assessed the test characteristics and cost-effectiveness of the Cytosponge (Medtronic, Minneapolis, MN) in post-RFA patients.

Methods: We performed a multicenter study of dysplastic BE patients after at least one round of RFA. A positive Cytosponge before endoscopy was defined as intestinal metaplasia (IM) on cytological assessment and/or TFF3 immunohistochemistry. Sensitivity, specificity, and receiver operator characteristic (ROC) curves were calculated. Multivariable regression was used to estimate the odds of a positive Cytosponge in BE. A microsimulation cost-effectiveness model was performed to assess outcomes of various surveillance strategies: endoscopy-only, Cytosponge-only, and alternating endoscopy/Cytosponge.

Results: Of 234 patients, Cytosponge adequately sampled the distal esophagus in 175 (75%). Of the 142 with both endoscopic and histologic data, 19 (13%) had residual/recurrent BE. For detecting any residual Barrett's, Cytosponge had a sensitivity of 74%, specificity of 85%, accuracy of 84%, and ROC curve showed an area under the curve of 0.74. The adjusted odds of a positive Cytosponge in BE were 17.1 (95% CI, 5.2-55.9). Cytosponge-only surveillance dominated all the surveillance strategies, being both less costly and more effective. Cytosponge-only surveillance required <1/4 the endoscopies, resulting in only 0.69 additional EAC cases/1000 patients, and no increase in EAC deaths when compared to currently-practiced endoscopy-only surveillance.

Conclusions: A positive Cytosponge test was strongly associated with residual BE after ablation. While the assay needs further refinement in this context, it could serve as a cost-effective surveillance examination.
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http://dx.doi.org/10.1016/j.cgh.2021.02.013DOI Listing
February 2021

Acceptability and Adequacy of a Non-endoscopic Cell Collection Device for Diagnosis of Barrett's Esophagus: Lessons Learned.

Dig Dis Sci 2021 Feb 3. Epub 2021 Feb 3.

Gastrointestinal Associates, Knoxville, TN, USA.

Background: Endoscopic screening for Barrett's esophagus (BE) is common, costly, and underperformed in at-risk people. A non-endoscopic cell collection device can be used to collect esophageal cells, enabling BE screening.

Aims: This study assessed the acceptability and adequacy of a commercial non-endoscopic cell collection device in a US population.

Methods: Six sites enrolled patients with confirmed BE or heartburn/regurgitation for ≥ 6 months. Patients underwent administration of the device, consisting of a sponge encapsulated in a capsule. The capsule dwelled in the stomach for 7.5 min and was retracted via an attached suture. An adequate sample was ≥ 1 columnar cell by H&E staining. Sample quality was rated using a 0-5 scale, with 0 = no columnar cells and 5 = plentiful groups. Trefoil Factor 3 (TFF3) staining was performed. Accuracy was assessed using esophagogastroduodenoscopy (EGD)/biopsy as the gold standard.

Results: Of 191 patients, 99.5% successfully swallowed the device. Overall sample adequacy was 91% (171/188), with 84% (158/188) high quality. The detachment rate was 2/190 (1%). Overall sensitivity, specificity, and accuracy of the assay with TFF3 staining were 76%, 77%, and 76%. Sensitivity, specificity, and accuracy for ≥ 3 cm BE were 86%, 77%, and 82%. Asked if willing to repeat the procedure, 93% would, and 65% indicated a preference for the device over EGD.

Conclusions: This study demonstrated a high rate of sample adequacy and promising acceptability of this non-endoscopic sampling device in a US population. Diagnostic characteristics suggest that non-endoscopic assessment of BE deserves further development as an alternative to endoscopy.
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http://dx.doi.org/10.1007/s10620-021-06833-6DOI Listing
February 2021

Massively Parallel Sequencing of Esophageal Brushings Enables an Aneuploidy-Based Classification of Patients With Barrett's Esophagus.

Gastroenterology 2021 May 22;160(6):2043-2054.e2. Epub 2021 Jan 22.

Department of Medicine, Case Western Reserve University, Cleveland, Ohio; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio; Seidman Cancer Center, University Hospitals Cleveland Medical Center, Cleveland, Ohio. Electronic address:

Background & Aims: Aneuploidy has been proposed as a tool to assess progression in patients with Barrett's esophagus (BE), but has heretofore required multiple biopsies. We assessed whether a single esophageal brushing that widely sampled the esophagus could be combined with massively parallel sequencing to characterize aneuploidy and identify patients with disease progression to dysplasia or cancer.

Methods: Esophageal brushings were obtained from patients without BE, with non-dysplastic BE (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), or adenocarcinoma (EAC). To assess aneuploidy, we used RealSeqS, a technique that uses a single primer pair to interrogate ∼350,000 genome-spanning regions and identify specific chromosome arm alterations. A classifier to distinguish NDBE from EAC was trained on results from 79 patients. An independent validation cohort of 268 subjects was used to test the classifier at distinguishing patients at successive phases of BE progression.

Results: Aneuploidy progression was associated with gains of 1q, 12p, and 20q and losses on 9p and 17p. The entire chromosome 8q was often gained in NDBE, whereas focal gain of 8q24 was identified only when there was dysplasia. Among validation subjects, a classifier incorporating these features with a global measure of aneuploidy scored positive in 96% of EAC, 68% of HGD, but only 7% of NDBE.

Conclusions: RealSeqS analysis of esophageal brushings provides a practical and sensitive method to determine aneuploidy in BE patients. It identifies specific chromosome changes that occur early in NDBE and others that occur late and mark progression to dysplasia. The clinical implications of this approach can now be tested in prospective trials.
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http://dx.doi.org/10.1053/j.gastro.2021.01.209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141353PMC
May 2021

Generic Measures of Quality of Life Are Not Correlated with Disease Activity in Eosinophilic Esophagitis.

Dig Dis Sci 2021 Jan 25. Epub 2021 Jan 25.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, CB#7080, Bioinformatics Building, 130 Mason Farm Rd. UNC-CH, Chapel Hill, NC, 27599-7080, USA.

Background: The relationship between histologic disease activity in eosinophilic esophagitis (EoE) and generic measures of quality of life (QoL) is unclear.

Aims: To determine differences in QoL in adults with EoE based on histologic activity and assess changes in QoL over time.

Methods: We performed an analysis of prospectively collected data from patients in the University of North Carolina EoE Registry. Patients were categorized with histologically active (≥ 15 eosinophils per high-power field [eos/hpf]) or inactive (< 15 eos/hpf) disease. Dysphagia severity was measured with a Likert scale. QoL was measured with 36-Item Short Form (SF-36), compared between active and inactive groups, and assessed longitudinally.

Results: Of 147 EoE cases, those with inactive disease (n = 56) reported less dysphagia severity (3.2 vs. 1.9; p = 0.003) and had lower endoscopic severity (3.8 vs. 1.0; p < 0.001) than those with active disease (n = 91). While SF-36 scores did not differ between active and inactive status, lower mental component scores (MCS) were seen in patients treated with empiric dietary elimination (44.9 vs. 50.8; p = 0.005). Dysphagia severity was negatively correlated with both physical component score (PCS) (r = -0.33; p < 0.001) and MCS (r = -0.18; p = 0.03). Despite more cases achieving histologic response over time, SF-36 scores did not improve on either raw or adjusted analyses.

Conclusion: QoL measured by SF-36 in EoE was similar regardless of histologic disease activity and was in the range of population averages. General QoL metrics like the SF-36 do not appear to have substantial utility in EoE.
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http://dx.doi.org/10.1007/s10620-020-06719-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310530PMC
January 2021

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Carcinogenesis 2021 04;42(3):369-377

Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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http://dx.doi.org/10.1093/carcin/bgaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052954PMC
April 2021

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

Am J Gastroenterol 2020 11;115(11):1879-1890

Division of Gastroenterology, University of North Carolina, Chapel Hill, North Carolina, USA.

Introduction: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE.

Methods: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1-6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year.

Results: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR.

Discussion: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).
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http://dx.doi.org/10.14309/ajg.0000000000000822DOI Listing
November 2020

An Analysis of the GIQuIC Nationwide Quality Registry Reveals Unnecessary Surveillance Endoscopies in Patients With Normal and Irregular Z-Lines.

Am J Gastroenterol 2020 11;115(11):1869-1878

University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Introduction: Population-based estimates of adherence to Barrett's esophagus (BE) guidelines are not available. Using a national registry, we assessed surveillance intervals for patients with normal and irregular Z-lines based on the presence or absence of intestinal metaplasia (IM) and among patients with suspected or confirmed BE.

Methods: We analyzed data from the GI Quality Improvement Consortium Registry. Endoscopy data, including procedure indication, demographics, endoscopy and histology findings, and recommendations for further endoscopy, were assessed from January 2013 through December 2019. Patients with an indication of BE screening or surveillance or an endoscopic finding of BE were included. Biopsy and surveillance practices were assessed based on the length of columnar epithelium (0 cm, <1 cm, 1-3 cm, and >3 cm) and diagnosis based on histology findings.

Results: A total of 1,907,801 endoscopies were assessed; 135,704 endoscopies (7.1%) performed in 114,894 patients met the inclusion criteria (men 61.4%, Whites 91%, and mean age of 61.7 years [SD 12.5]). Among patients with normal Z-lines, surveillance endoscopy was recommended for 81% of patients with IM and 20% of individuals without IM. Among patients with irregular Z-lines, surveillance endoscopy was recommended for 81% with IM and 24% without IM. Approximately 30% of patients with confirmed nondysplastic BE (lengths 1-3 and >3 cm) had recommended surveillance intervals of <3 years.

Discussion: An analysis of data from a nationwide quality registry demonstrated that patients without BE are receiving recommendations for surveillance endoscopies and many patients with nondysplastic BE are reexamined too soon.
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http://dx.doi.org/10.14309/ajg.0000000000000960DOI Listing
November 2020

Clinical features and time trends associated with an endoscopically normal esophagus in active eosinophilic esophagitis.

Endoscopy 2020 Oct 6. Epub 2020 Oct 6.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.

Background: A proportion of patients with active eosinophilic esophagitis (EoE) have a normal-appearing esophagus on esophagogastroduodenoscopy (EGD). We aimed to determine the associations between the baseline clinical features and the endoscopically normal esophagus in EoE, as well as time trends in reporting.

Methods: In this retrospective study of active EoE cases from 2002 - 2018, patients with and without esophageal endoscopic abnormalities were compared. Multivariable logistic regression identified the independent predictors of a normal EGD. The proportion of patients with a normal EGD was determined per year, and before and after the introduction of the first EoE guidelines and the EoE Endoscopic Reference Score (EREFS).

Results: Of 878 EoE patients, 101 (11.5 %) had an endoscopically normal esophagus; they were younger (8.3 vs. 25.4 years), had shorter median symptom duration before diagnosis (2.8 vs. 5.0 years), were less likely to have dysphagia (40 % vs. 76 %) or food impaction (8 % vs. 33 %), and more likely to have abdominal pain (37 % vs. 19 %) ( < 0.01 for all). On multivariable logistic regression, independent predictors of a normal esophagus were younger age (odds ratio [OR] 0.96, 95 % confidence interval [CI] 0.94 - 0.98), abdominal pain (OR 2.03, 95 %CI 1.13 - 3.67), and lack of dysphagia (OR 0.49, 95 %CI 0.26 - 0.93). The proportion of patients with a normal esophagus decreased from 21 % before the first EoE guidelines to 7 % ( < 0.01) after introduction of the EREFS.

Conclusions: An endoscopically normal esophagus is seen in ~10 % of active EoE patients and should not preclude biopsies; younger age, abdominal pain, and lack of dysphagia are independent predictors. The proportion of normal EGDs decreased over time, suggesting improved recognition of endoscopic findings.
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http://dx.doi.org/10.1055/a-1284-5891DOI Listing
October 2020

Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.

Gastroenterology 2020 12 9;159(6):2065-2076.e1. Epub 2020 Sep 9.

Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.

Background & Aims: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored.

Methods: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits.

Results: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, P = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, P = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals.

Conclusions: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.
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http://dx.doi.org/10.1053/j.gastro.2020.08.052DOI Listing
December 2020

Measuring Quality in Barrett's Endoscopy.

Clin Gastroenterol Hepatol 2021 May 3;19(5):889-891. Epub 2020 Sep 3.

Center for Esophageal Diseases and Swallowing and, Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.

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http://dx.doi.org/10.1016/j.cgh.2020.09.007DOI Listing
May 2021

Efficacy, pharmacokinetics and neurocognitive performance of dual, NRTI-sparing antiretroviral therapy in acute HIV-infection.

AIDS 2020 11;34(13):1923-1931

Department of Medicine, University of North Carolina at Chapel Hill (UNC) School of Medicine.

Objectives: The aim of this study was to evaluate penetration of antiretrovirals into compartments and efficacy of a dual, NRTI-sparing regimen in acute HIV infection (AHI).

Design: Single-arm, open-label pilot study of participants with AHI initiating ritonavir-boosted darunavir 800 mg once daily and etravirine 400 mg once daily or 200 mg twice daily within 30 days of AHI diagnosis.

Methods: Efficacy was defined as HIV RNA less than 200 copies/ml by week 24. Optional sub-studies included pharmacokinetics analysis from genital fluids (weeks 0-4, 12, 48), cerebrospinal fluid (CSF) (weeks 2-4, 24 and 48) and endoscopic biopsies (weeks 4-12 and 36-48). Neuropsychological performance was assessed at weeks 0, 24 and 48.

Results: Fifteen AHI participants were enrolled. Twelve (80%) participants achieved HIV RNA less than 200 copies/ml by week 24. Among 12 participants retained through week 48, nine (75%) remained suppressed to less than 50 copies/ml. The median time from ART initiation to suppression less than 200 and less than 50 copies/ml was 59 and 86 days, respectively. The penetration ratios for etravirine and darunavir in gut associated lymphoid tissue were 19.2 and 3.05, respectively. Most AHI participants achieving viral suppression experienced neurocognitive improvement. Of the three participants without overall improvement in neurocognitive functioning as measured by impairment ratings (more than two tests below 1 SD), two had virologic failure.

Conclusion: NRTI-sparing ART started during AHI resulted in rapid viral suppression similar to NRTI-based regimens. More novel and compact two-drug treatments for AHI should be considered. Early institution of ART during AHI appears to improve overall neurocognitive function and may reduce the risk of subsequent neurocognitive impairment. CLINICALTRIALS.GOV:: NCT00855413.
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http://dx.doi.org/10.1097/QAD.0000000000002652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541775PMC
November 2020

New data on an old weapon: is argon plasma coagulation adequate treatment for dysplastic Barrett's esophagus?

Endoscopy 2021 02 30;53(2):133-135. Epub 2020 Jul 30.

Center for Esophageal Diseases and Swallowing, and Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States.

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http://dx.doi.org/10.1055/a-1230-5610DOI Listing
February 2021

Reviving Routine Gastrointestinal Endoscopy in the COVID-19 Era.

Am J Gastroenterol 2020 09;115(9):1376-1379

Department of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.

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http://dx.doi.org/10.14309/ajg.0000000000000790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396215PMC
September 2020

ENDOSCOPIC TREATMENT OF ESOPHAGEAL NEOPLASIA: A DECADE OF EVOLUTION.

Trans Am Clin Climatol Assoc 2020 ;131:297-314

CHAPEL HILL, NORTH CAROLINA.

Traditional therapy for early esophageal neoplasia has been esophagectomy. In the past decade, the approach to these conditions has rapidly evolved, such that endoscopic therapy has become the primary modality to treat patients with esophageal dysplasia and superficial carcinoma. A variety of modalities are available, including thermal methods, such as radiofrequency ablation and argon plasma coagulation; cryotherapy, including spray liquid nitrogen cryotherapy and balloon-based nitrous oxide cryotherapy; and tissue resection methods, such as endoscopic mucosal resection and endoscopic submucosal dissection. Level 1 evidence substantiates that patients treated with these therapies have a low risk of developing invasive cancer. These treatments demonstrate an excellent safety profile. Future work in this area will define the best modalities of treatment, assess the utility of endoscopic therapy in combination with radiation therapy and chemotherapy, and improve current screening regimens to allow earlier detection of neoplasia.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358467PMC
March 2021

A Model Using Clinical and Endoscopic Characteristics Identifies Patients at Risk for Eosinophilic Esophagitis According to Updated Diagnostic Guidelines.

Clin Gastroenterol Hepatol 2020 Jul 4. Epub 2020 Jul 4.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address:

Background And Aims: Updated diagnostic guidelines for eosinophilic esophagitis (EoE) have eliminated the requirement for a proton pump inhibitor (PPI) trial, but there are no models to identify patients with EoE based on these new criteria. We aimed to develop a predictive model for diagnosis of EoE based on the updated EoE diagnostic guidelines.

Methods: We performed a secondary analysis of a prospective study of adult patients referred for outpatient esophagogastroduodenoscopy at University of North Carolina who had symptoms of esophageal dysfunction; patients with prevalent EoE were excluded. We analyzed data from 206 EoE cases (mean age 40.1, 62.6% male, 93.2% white) and 306 controls (mean age 52.3, 37.9% male, 79.7% white). We built predictive models for case-control status, using clinical, endoscopic, and histologic features, and defining EoE by either the new or historical definition of PPI non-response. Model discrimination was assessed by the area under the receiver-operator characteristic curve (AUC).

Results: Before endoscopy, younger age, male sex, history of atopic condition or food allergy, and dysphagia identified patients with EoE with an AUC of 0.83. When we included endoscopy findings suggestive of EoE, the model identified patients with EoE with an AUC of 0.92; this increased to 0.99 when histology was included.

Conclusion: We developed a model to identify patients with EoE, without a trial of PPIs, based on updated diagnostic guidelines. Clinical features and endoscopic findings identified patients with EoE with an AUC of 0.92-even without histologic data and in the absence of dysphagia. This model can be used to select patients with upper gastrointestinal symptoms but without dysphagia for early diagnostic endoscopy. The model can also be used to identify cases of EoE when eosinophil counts are greater than 15 in biopsies but other causes of esophageal eosinophilia cannot necessarily be excluded.
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http://dx.doi.org/10.1016/j.cgh.2020.06.068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779708PMC
July 2020

State of Evidence in Minimally Invasive Management of Gastroesophageal Reflux: Findings of a Scoping Review.

Gastroenterology 2020 10 1;159(4):1504-1525. Epub 2020 Jul 1.

Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California.

Backgrounds & Aims: Endoscopic management of gastroesophageal reflux disease (GERD) is being employed increasingly. The aim of this scoping review was to assess the volume of available evidence on the benefits of endoscopic and minimally invasive surgical therapies for GERD.

Methods: criteria were used to perform an extensive literature search of data regarding the reported benefit of endoscopic therapies in GERD. Randomized controlled studies were utilized when available; however, data from observational studies were also reviewed.

Results: A formal review of evidence was performed in 22 studies. Inclusion and exclusion criteria and study duration were noted and tabulated. Assessment of outcomes was based on symptoms and objective criteria reported by investigators. Reported outcomes for the interventions were tabulated under the heading of subjective (symptom scores, quality of life metrics, and change in proton pump inhibitor use) and objective metrics (pH parameters, endoscopic signs, and lower esophageal sphincter pressure changes). Adverse events were noted and tabulated. The majority of studies showed symptomatic and objective improvement of GERD with the device therapies. Adverse events were minimal. However, normalization of acid exposure occurred in about 50% of patients and, for some modalities, long-term durability is uncertain.

Conclusions: This scoping review revealed that the endoluminal and minimally invasive surgical devices for GERD therapy are a promising alternative to proton pump inhibitor therapy. Their place in the treatment algorithm for GERD will be better defined when important clinical parameters, especially durability of effect, are better understood.
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http://dx.doi.org/10.1053/j.gastro.2020.05.097DOI Listing
October 2020

Overutilization of Endoscopic Surveillance in Barrett's Esophagus: The Perils of Too Much of a Good Thing.

Am J Gastroenterol 2020 07;115(7):1019-1021

Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

A cost-utility analysis in the current issue of AJG examines the ramifications of the overuse of surveillance endoscopy in Barrett's esophagus (BE). This study suggests that excess surveillance is expensive, increasing costs by 50% or more, with only nominal increases in quality-adjusted life expectancy. This study joins a growing literature of cost-utility analyses that suggest that more is not likely better when it comes to surveillance endoscopy. Given the plentiful literature showing overutilization of surveillance endoscopy in BE, the authors argue for a focus on the quality of endoscopy rather than increased frequency of surveillance to improve returns on our healthcare investment.
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http://dx.doi.org/10.14309/ajg.0000000000000650DOI Listing
July 2020

Persistent indefinite for dysplasia in Barrett's esophagus is a risk factor for dysplastic progression to low-grade dysplasia.

Dis Esophagus 2020 Sep;33(9)

Division of Gastroenterology, University of Minnesota, Minneapolis, MN, USA.

Patients with Barrett's esophagus (BE) are at increased risk of esophageal adenocarcinoma (EAC). The risk is largely based on the degree of dysplasia. Dysplasia cannot always be differentiated from inflammatory changes, and therefore may be classified as indefinite for dysplasia (IND). The risk of progressive dysplasia in patients with IND is unclear. Our aim is to characterize the risk of progression in US veterans with BE-IND. We performed a single-center retrospective cohort study of patients with BE-IND between 2006 and 2016. All IND was diagnosed by consensus conference with an expert gastrointestinal (GI) pathologist or review by an expert GI pathologist and persistence was defined as IND present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of high-grade dysplasia (HGD)/EAC. Secondary outcomes included any progression including incident low-grade dysplasia (LGD), any prevalent dysplasia and risk factors for dysplastic progression, namely persistent IND. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Among 107 patients with BE-IND, there were no incident cases of HGD/EAC. Twenty patients (18.7%) developed incident LGD during a median follow-up of 2.39 years (interquartile range, 1.13-5.17). The annual rate of progression to LGD was 5.95 per 100 patient-years (95% CI, 3.73-9.02). Prevalent dysplasia was common (9.3%). Eight patients had prevalent LGD, one patient had prevalent HGD and one patient had prevalent EAC. Twenty-eight patients (30.1%) were found to have persistent IND. Among those with persistent IND, 10 (36%) patients progressed to LGD (none to HGD/EAC). The progression rate to LGD for patients with persistent IND was 7.86 (95% CI, 3.99-14.02) cases per 100 patient-years versus 4.78 (95% CI, 2.48-8.52) for nonpersistent IND (P = 0.036). The odds ratio for progression to LGD in persistent IND was 3.06 (95% CI, 1.08-8.64). In multivariate analysis adjusting for age, smoking history, presence of hiatal hernia and BMI > 30, persistent IND remained significant (OR 3.23; 95% CI, 1.04-9.98). Regression to nondysplastic BE was very common. Seventy-one (61%) patients developed complete and sustained regression of all dysplastic changes at last follow-up. Persistent IND, present in one-third of patients with IND, is an independent risk factor for progression to LGD. Although no patients in this cohort developed HGD/EAC, prevalent dysplasia was common (9.3%). Taken together, patients with IND should receive close surveillance for both prevalent and incident dysplasia especially if IND is persistent.
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http://dx.doi.org/10.1093/dote/doaa015DOI Listing
September 2020

Radiofrequency Ablation of Barrett's Esophagus: Have We Gone Too Far, or Not Far Enough?

Curr Gastroenterol Rep 2020 May 7;22(6):29. Epub 2020 May 7.

Department of Medicine, Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Purpose Of Review: Barrett's esophagus (BE) is a premalignant condition of the esophagus associated with an increased risk for esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) is a safe and effective first-line treatment for dysplastic BE and early stage EAC. This report reviews clinically relevant evidence published over the last 3 years regarding RFA for BE.

Recent Findings: Our use of this technology has simultaneously gone too far, in that many patients who may not derive a benefit from these treatments are receiving them, and not far enough, in that many patients who would be eligible for ablative therapy never undergo screening exams to assess them for dysplastic BE, or do not have endoscopic therapy considered part of the treatment of superficial invasive cancer. Research to better identify patients with BE, risk stratify those patients, improve the quality of RFA treatment, and inform surveillance practices has the potential to optimize the benefit of RFA, and minimize the harms, costs, and risks.
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http://dx.doi.org/10.1007/s11894-020-00766-2DOI Listing
May 2020

Practice patterns and adherence to clinical guidelines for diagnosis and management of eosinophilic esophagitis among gastroenterologists.

Dis Esophagus 2020 May 7. Epub 2020 May 7.

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Real-world practice patterns of eosinophilic esophagitis (EoE) among gastroenterologists are not well-described. The aim is to describe practice patterns of EoE diagnosis and management and assess concordance with consensus guidelines. We conducted a cross-sectional online survey of gastroenterologists in the USA using Qualtrics, which was dispersed through the North Carolina Society of Gastroenterology (NCSG) and the American College of Gastroenterology member listservs. A similar survey was sent to NCSG members in 2010 and responses were compared in a subanalysis. Of 240 respondents, 37% (n = 80) worked in an academic setting versus 63% (n = 138) community practice setting. Providers saw a median of 18 (interquartile range 2-100) EoE patients annually and 24% (n = 52) were 'very familiar' with EoE guidelines. A proton-pump inhibitor (PPI) trial was required by 37% of providers prior to EoE diagnosis. In total, 60% used a ≥15 eosinophils per high-power field cut point for diagnosis and 62% biopsied from the proximal and distal esophagus on initial exam. Only 12% (n = 28) followed EoE diagnosis guidelines. For first-line treatment, 7% used dietary therapy, 32% topical steroids, and 61% used PPIs; 67% used fluticasone as first-line steroid; 41% used maintenance steroid treatment in responders. In the NCSG cohort, a higher proportion in 2017 followed guideline diagnosis recommendations compared with 2010 (14% vs. 3%; P = 0.03) and a higher proportion used dietary therapy as first-line treatment (13% vs. 3%; P = 0.046). There is variability in EoE practice patterns for EoE management, with management differing markedly from consensus guidelines. Further education and guideline dissemination are needed to standardize practice.
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http://dx.doi.org/10.1093/dote/doaa025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350163PMC
May 2020

Utility of major basic protein, eotaxin-3, and mast cell tryptase staining for prediction of response to topical steroid treatment in eosinophilic esophagitis: analysis of a randomized, double-blind, double dummy clinical trial.

Dis Esophagus 2020 Jun;33(6)

Center for Esophageal Diseases and Swallowing, and Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

Inflammatory factors in eosinophilic esophagitis (EoE), including major basic protein (MBP), eotaxin-3 (EOT3) and mast cell tryptase (TRP), may predict treatment response to topical corticosteroids (tCS). We aimed to determine whether baseline levels of these markers predict response to tCS for EoE. To do this, we analyzed data from a randomized trial comparing two topical steroids for treatment of newly diagnosed EoE (NCT02019758). A pretreatment esophageal biopsy was stained for MBP, EOT3, and TRP to quantify tissue biomarker levels (cells/mm2). Levels were compared between histologic responders (<15 eos/hpf) and nonresponders (the primary outcome), and endoscopic responders (EREFS<2) and nonresponders. Complete histologic response (<1 eos/hpf) was also assessed, and area under the receiver operator characteristic curve (AUC) was calculated. We also evaluated whether baseline staining predicted symptom relapse in the trial's off-treatment observation phase. Baseline samples were evaluable in 110/111 subjects who completed the randomized trial. MBP levels were higher in nonresponders (n = 36) than responders (704 vs. 373 cells/mm2; P = 0.007), but EOT3 and TRP levels were not statistically different. The combination of all three stains had an AUC of 0.66 to predict response. For complete histologic response, baseline TRP levels were higher in nonresponders (n = 69) than responders (370 vs. 268 mast cells/mm2; P = 0.01), with an AUC of 0.65. The AUC for endoscopic response was 0.68. Baseline staining did not predict symptom recurrence after remission. Pretreatment MBP, EOT3, and TRP levels were not strongly or consistently associated with histologic or endoscopic response to topical steroids. While elevated TRP levels may be associated with nonresponse compared with complete response, the magnitude and predictive utilities were modest. Novel methods for predicting steroid response are still required.
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http://dx.doi.org/10.1093/dote/doaa003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273184PMC
June 2020

Reduced Esophageal Contractility Is Associated with Dysplasia Progression in Barrett's Esophagus: A Multicenter Cohort Study.

Dig Dis Sci 2020 12 5;65(12):3631-3638. Epub 2020 Feb 5.

Division of Gastroenterology and Hepatology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.

Background: The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) continues to rise, and risk stratification of patients with BE is needed. Impaired esophageal motility is associated with gastroesophageal reflux disease; however, whether esophageal dysmotility is a risk factor for dysplasia progression in BE is incompletely understood. This study aimed to characterize esophageal motility patterns in patients with BE and identify physiologic factors associated with dysplasia progression in BE.

Methods: This multicenter retrospective study assessed data from adult patients with histologically confirmed BE who underwent high-resolution esophageal manometry from 1/2014 to 1/2018 at four tertiary care centers. Longitudinal data were collected when available among patients with non-dysplastic BE (NDBE) and separated as: no dysplastic progression or positive dysplastic progression. Multivariable logistic regression assessed for independent predictors of dysplasia progression.

Results: Among 193 patients, histology at index endoscopy identified 152 (79%) NDBE, 23 (12%) low-grade dysplasia, 14 (7%) high-grade dysplasia, and 4 (2%) EAC. Ninety-eight (51%) had abnormal esophageal motor function on manometry. Longitudinal data were available for 84 of 152 patients with initial NDBE. Twelve (14%) exhibited dysplastic progression to low-grade (6) or high-grade (6) dysplasia. Mean esophageal distal contractile integral was lower for patients that progressed [455 mmHg s cm (SD 515)] compared with patients who did not progress [987 mmHg s cm (SD 953); aOR 1.21 (95% CI 1.01, 1.44)].

Conclusion: In this retrospective study of 193 BE patients, the majority exhibited abnormal esophageal motor function. Reduced esophageal contractility was independently associated with dysplastic progression in BE. Characterizing esophageal physiology in BE may help to risk stratify patients.
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http://dx.doi.org/10.1007/s10620-020-06098-5DOI Listing
December 2020

Development of a Preliminary Question Prompt List as a Communication Tool for Adults With Gastroesophageal Reflux Disease: A Modified Delphi Study.

J Clin Gastroenterol 2020 Nov/Dec;54(10):857-863

Stanford Esophageal Multidimensional Program in Innovation and Research Excellence (SEMPIRE), Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford.

Background: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, encouraging patients to ask questions to facilitate their consultation with their physician.

Aim: The aim of this study was to develop a QPL specific to adults with gastroesophageal reflux disease (GERD), created by esophageal experts.

Methods: The QPL content (78 questions) was derived through a modified Delphi method consisting of 2 rounds. In round 1, 18 esophageal experts provided 5 answers to the prompt "What you wish your patients would ask" and "What questions do patients often not ask, that I wish they would ask?" In round 2, the experts rated each question on a 5-point Likert scale, and responses rated as "essential" or "important," determined by an a priori threshold of ≥4.0, were accepted for the QPL.

Results: Twelve esophageal experts participated. Of 143 questions from round 1, 110 (76.9%) were accepted for inclusion in the QPL, meeting a median value of ≥4.0, and, subsequently, it reduced to 78, minimizing redundancy. Median values ranged between 4.0 and 5.0, with the highest agreement median (5.0) for questions asking dosing and timing of proton pump inhibitor therapy, and surveillance in Barrett's. Questions were categorized into the following categories: "What does this illness mean," "lifestyle modifications," "general treatment," "treatment with proton pump inhibitors," "What I should expect for my future," and "Barrett's." The largest number of questions covered lifestyle modifications (21.8%), with the highest agreement median (5.0) for "How helpful are lifestyle modifications in GERD?"

Conclusions: A preliminary GERD-specific QPL, the first of its kind, was developed by esophageal experts. Modification after more patient consultation and feedback is planned in subsequent versions to create a GERD-QPL for eventual use in clinical gastroenterology.
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http://dx.doi.org/10.1097/MCG.0000000000001300DOI Listing
June 2021

Approach to the Post-Ablation Barrett's Esophagus Patient.

Am J Gastroenterol 2020 06;115(6):823-831

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Because of the rising incidence and lethality of esophageal adenocarcinoma, Barrett's esophagus (BE) is an increasingly important premalignant target for cancer prevention. BE-associated neoplasia can be safely and effectively treated with endoscopic eradication therapy (EET), incorporating tissue resection and ablation. Because EET has proliferated, managing patients after complete eradication of intestinal metaplasia has taken on increasing importance. Recurrence after complete eradication of intestinal metaplasia occurs in 8%-10% of the patients yearly, and the incidence may remain constant over time. Most recurrences occur at the gastroesophageal junction, whereas those in the tubular esophagus are endoscopically visible and distally located. A simplified biopsy protocol limited to the distal aspect of the BE segment, in addition to gastroesophageal junction sampling, may enhance efficiency and cost without significantly reducing recurrence detection. Similarly, research suggests that current surveillance intervals may be excessively frequent, failing to reflect the cancer risk reduction of EET. If validated, longer surveillance intervals could reduce the burden of resource-intensive endoscopic surveillance. Several important questions in post-EET management remain unanswered, including surveillance duration, the significance of gastric cardia intestinal metaplasia, and the role of advanced imaging and nonendoscopic sampling techniques in detecting recurrence. These merit further research to enhance quality of care and promote a more evidence-based approach.
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http://dx.doi.org/10.14309/ajg.0000000000000514DOI Listing
June 2020

Risk of Cancer in Patients With Barrett Esophagus.

Gastroenterol Hepatol (N Y) 2019 Dec;15(12):688-690

Bozymski-Heizer Distinguished Professor of Medicine Chief, Division of Gastroenterology & Hepatology University of North Carolina School of Medicine Chapel Hill, North Carolina.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935029PMC
December 2019

Distal esophagus is the most commonly involved site for strictures in patients with eosinophilic esophagitis.

Dis Esophagus 2020 Mar;33(2)

Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

While strictures are common in eosinophilic esophagitis (EoE), there are few data on stricture distribution and characteristics. Our primary aim was to characterize strictures by location in the esophagus in EoE and associated clinical, endoscopic, and histologic features. This was a retrospective study from the UNC EoE Clinicopathologic Database of subjects with esophageal strictures or narrowing from 2002 to 2017. Strictures were categorized as distal esophagus/gastroesophageal junction, mid-esophagus, proximal esophagus, or diffusely narrowed. Stricture location was assessed and compared with clinical, endoscopic, and histologic features, and also with treatment response to diet or topical steroids. Efficacy of combination therapy with dilation and intralesional steroid injection was assessed in a sub-group of patients with strictures. Of 776 EoE cases, 219 (28%) had strictures, 45% of which were distal, 30% were proximal, 5% were mid-esophageal, and 20% had diffuse narrowing. Those with mid-esophageal strictures were younger (P = 0.02) and had shorter symptom duration (P < 0.01). Those with diffuse esophageal narrowing were more likely to be women (57%) and have abdominal pain (25%). There was no association between other clinical, endoscopic, and histologic findings and treatment response based on stricture location. Fourteen patients (8%) received intralesional triamcinolone injection and subsequently achieved a higher mean dilation diameter after injection (13.7 vs. 15.5 mm; P < 0.01). In conclusion, almost half of strictures in EoE patients were in the distal esophagus. Therefore, EoE should be a diagnostic consideration in patients with focal distal strictures and not presumed to be secondary to gastroesophageal reflux disease.
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http://dx.doi.org/10.1093/dote/doz088DOI Listing
March 2020

Association Between Levels of Sex Hormones and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.

Clin Gastroenterol Hepatol 2020 11 19;18(12):2701-2709.e3. Epub 2019 Nov 19.

Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; School of Cancer and Pharmaceutical Sciences, King's College London, London, United Kingdom.

Background & Aims: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones are associated with risk of EAC or Barrett's esophagus (BE).

Methods: We conducted a Mendelian randomization analysis using data from patients with EAC (n = 2488) or BE (n = 3247) and control participants (n = 2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single-nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs.

Results: Higher genetically predicted levels of follicle-stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01-1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per SD increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index.

Conclusions: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle-stimulating and luteinizing hormones and risk of BE and EAC.
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http://dx.doi.org/10.1016/j.cgh.2019.11.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7580878PMC
November 2020
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