Publications by authors named "Prasad G Iyer"

162 Publications

Spray cryotherapy prevents need for palliative stenting in patients with esophageal cancer-associated dysphagia.

Dis Esophagus 2021 Jul 27. Epub 2021 Jul 27.

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

Background: Dysphagia is the most common symptom in advanced esophageal cancer patients. Esophageal stent placement (SP) is a common palliation method but can be associated with significant morbidity. Limited data exist regarding the ability of spray cryotherapy (SC) prolong time to SP.

Methods: A Mayo Clinic (Rochester, MN) patient database was reviewed for cases with a SC indication of esophageal cancer palliation from 2007-2019. Procedures were performed using a liquid nitrogen SC system to apply 2-5 separate 20 second freeze and 60 second thaw cycles based on tumor characteristics. Primary outcome was time to subsequent palliative SP.

Results: Of 56 patients (71.4% male, mean age 77.8 ± 10.2 years) who underwent a total of 199 SC sessions (mean 3.6 ± 2.7, range 1-12 per patient), 41 had adenocarcinoma and 15 squamous cell carcinoma (SCC). Overall, 13 patients underwent subsequent SP within a mean duration of 15.7 ± 11.0 months over a mean follow-up duration of 25.6 ± 29.4 months. Treatment did produce stenosis in 16 patients, who required dilation within a mean period of 193.1 ± 294.1 days; notably, 10 patients had a history of preceding malignant strictures requiring dilation. Two patients experienced bleeding requiring transfusion, whereas 1 experienced perforation at the start of SC. Prior chemotherapy and/or radiation was not associated with developing an SC-related complication (risk ratio (RR) 1.5; 95% CI 0.6-3.7, P > 0.4).

Conclusions: SC appears to be an effective and safe modality to palliate esophageal cancer in appropriate candidates. Majority of patients who undergo SC avoid the need for future SP. If patients eventually require SP, they are able to, on average, defer stenting for >1 year from SC initiation.
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http://dx.doi.org/10.1093/dote/doab051DOI Listing
July 2021

Prediction of progression in Barrett's esophagus: does inflammation hold the key?

Authors:
Prasad G Iyer

Endoscopy 2021 Aug 27;53(8):782-783. Epub 2021 Jul 27.

Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, United States.

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http://dx.doi.org/10.1055/a-1381-7899DOI Listing
August 2021

Outcomes of endoscopic ultrasound and endoscopic resection of gastrointestinal subepithelial lesions: a single-center retrospective cohort study.

Ann Gastroenterol 2021 Jul-Aug;34(4):516-520. Epub 2021 Apr 2.

Division of Gastroenterology and Hepatology (Ariosto H. Hernandez-Lara, Ana Garcia Garcia de Paredes, Louis M. Wong Kee Song, Michael J. Levy, Ferga C. Gleeson, Amrit K. Kamboj, Barham K. Abu-Dayyeh, Vinay Chandrasekhara, Prasad G. Iyer, Andrew C. Storm, Elizabeth Rajan).

Background: Endoscopic resection (ER) is an emerging therapeutic alternative for subepithelial gastrointestinal lesions (SELs). We aimed to determine whether size, layer of origin, and histology based on endoscopic ultrasound (EUS) and EUS-guided sampling (EUS-GS) influenced the outcomes and selection of patients for ER.

Methods: We performed a retrospective review of patients who underwent EUS, EUS-GS and resection of SELs from 2012-2019. Two pathologists reviewed the histology and layer of origin of all resected specimens, serving as the criterion for EUS accuracy.

Results: Seventy-three patients were included, of whom 59 (81%) were gastric SELs. Per EUS, median lesion size was 21 mm (interquartile range 15-32), and 63 (86%) originated from the 4th layer. The overall accuracy of EUS and EUS-GS in predicting the layer of origin and histology was 88% (95% confidence interval [CI] 77-94%) and 96% (95%CI 87-98%), respectively. Based on EUS, 18 (25%) patients were referred for ER, 5 (7%) to laparoscopic-endoscopic cooperative surgery, and 50 (68%) to surgery. Size >20 mm was associated with the type of resection approach (P=0.005), while layer of origin and histology were not (P=0.06 and P=0.09, respectively). When SELs were inaccurately classified (n=4) there were no adverse events or revision of the resection approach.

Conclusions: EUS plays an important role in the outcome of resection approach for SELs, with size significantly influencing the selection for ER. In patients undergoing ER, no revised resections were needed when EUS was inaccurate.
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http://dx.doi.org/10.20524/aog.2021.0621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276353PMC
April 2021

Systematic review with meta-analysis: neoplasia detection rate and post-endoscopy Barrett's neoplasia in Barrett's oesophagus.

Aliment Pharmacol Ther 2021 Jul 18. Epub 2021 Jul 18.

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

Background: Neoplasia detection rate, the proportion of Barrett's oesophagus patients with high-grade dysplasia or oesophageal adenocarcinoma detected at index surveillance endoscopy has been proposed as a quality metric. However, the correlation between neoplasia detection rate and a clinically relevant outcome like post-endoscopy Barrett's neoplasia remains unknown. Post-endoscopy Barrett's neoplasia refers to the rate of high-grade dysplasia or oesophageal adenocarcinoma on repeat endoscopy within one year of an index screening examination revealing non-dysplastic Barrett's oesophagus or low-grade dysplasia.

Aim: To assess correlation between neoplasia detection rate and post-endoscopy Barrett's neoplasia.

Methods: We performed a systematic search of multiple databases from date of inception to June 2021 to identify cohort studies reporting both neoplasia detection rate and post-endoscopy Barrett's neoplasia. Data from each study were pooled using a random effects model, and their correlation assessed using meta-regression. Heterogeneity was assessed and a priori planned subgroup analyses were conducted.

Results: Ten studies with 27 894 patients with Barrett's oesophagus were included. The pooled neoplasia detection rate and post-endoscopy Barrett's neoplasia were 5.0% (95% CI: 3.4%-7.1%, I  = 97%) and 19.6% (95% CI: 10.1%-34.7%, I  = 96%), respectively. Meta-regression revealed a statistically significant inverse relationship between the two variables (coefficient -3.50, 95% CI: -4.63 to -2.37, P < 0.01). With every 1% increase of neoplasia detection rate, post-endoscopy Barrett's neoplasia decreased by 3.50%. Heterogeneity was high despite adjusting for study quality and performing several subgroup analyses.

Conclusion: We observed a statistically significant inverse correlation between neoplasia detection rate and post-endoscopy Barrett's neoplasia. Additional studies are needed to further validate this correlation.
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http://dx.doi.org/10.1111/apt.16531DOI Listing
July 2021

Comparative Cost Effectiveness of Reflux-Based and Reflux-Independent Strategies for Barrett's Esophagus Screening.

Am J Gastroenterol 2021 Jun 9. Epub 2021 Jun 9.

Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: Minimally invasive tests for Barrett's esophagus (BE) detection have raised the prospect of broader nonreflux-based testing. Cost-effectiveness studies have largely studied men aged 50 years with chronic gastroesophageal reflux disease (GERD) symptoms. We evaluated the comparative cost effectiveness of BE screening tests in GERD-based and GERD-independent testing scenarios.

Methods: Markov modeling was performed in 3 scenarios in 50 years old individuals: (i) White men with chronic GERD (GERD-based); (ii) GERD-independent (all races, men and women), BE prevalence 1.6%; and (iii) GERD-independent, BE prevalence 5%. The simulation compared multiple screening strategies with no screening: sedated endoscopy (sEGD), transnasal endoscopy, swallowable esophageal cell collection devices with biomarkers, and exhaled volatile organic compounds. A hypothetical cohort of 500,000 individuals followed for 40 years using a willingness to pay threshold of $100,000 per quality-adjusted life year (QALY) was simulated. Incremental cost-effectiveness ratios (ICERs) comparing each strategy with no screening and comparing screening strategies with each other were calculated.

Results: In both GERD-independent scenarios, most non-sEGD BE screening tests were cost effective. Swallowable esophageal cell collection devices with biomarkers were cost effective (<$35,000/QALY) and were the optimal screening tests in all scenarios. Exhaled volatile organic compounds had the highest ICERs in all scenarios. ICERs were low (<$25,000/QALY) for all tests in the GERD-based scenario, and all non-sEGD tests dominated no screening. ICERs were sensitive to BE prevalence and test costs.

Discussion: Minimally invasive nonendoscopic tests may make GERD-independent BE screening cost effective. Participation rates for these strategies need to be studied.
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http://dx.doi.org/10.14309/ajg.0000000000001336DOI Listing
June 2021

Managing Recurrences Following Endoscopic Therapy for Barrett Esophagus.

Authors:
Prasad G Iyer

Gastroenterol Hepatol (N Y) 2020 May;16(5):262-264

Professor of Medicine Division of Gastroenterology and Hepatology Mayo Clinic Rochester, Minnesota.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132635PMC
May 2020

Response.

Gastrointest Endosc 2021 06;93(6):1434-1435

Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

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http://dx.doi.org/10.1016/j.gie.2021.01.022DOI Listing
June 2021

Effects of Central Obesity on Esophageal Epithelial Barrier Function.

Am J Gastroenterol 2021 Jul;116(7):1537-1541

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

Introduction: We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER).

Methods: Thirty-eight participants were divided into 4 groups: Obesity-/GER-, Obesity+/GER-, Obesity-/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured.

Results: The Obesity+/GER- group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity-/GER + and Obesity+/GER+ patients.

Discussion: Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.
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http://dx.doi.org/10.14309/ajg.0000000000001196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243777PMC
July 2021

Nonendoscopic Detection of Barrett Esophagus and Esophageal Adenocarcinoma: Recent Advances and Implications.

Ann Intern Med 2021 Jul 4;174(7):1006-1007. Epub 2021 May 4.

Mayo Clinic, Rochester, Minnesota (P.G.I., D.A.K.).

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http://dx.doi.org/10.7326/M20-7164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292209PMC
July 2021

Validation of a methylated DNA marker panel for the nonendoscopic detection of Barrett's esophagus in a multisite case-control study.

Gastrointest Endosc 2021 Apr 20. Epub 2021 Apr 20.

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

Background And Aims: We previously identified a 5 methylated DNA marker (MDM) panel for the detection of nonendoscopic Barrett's esophagus (BE). In this study, we aimed to recalibrate the performance of the 5 MDM panel using a simplified assay in a training cohort, validate the panel in an independent test cohort, and explore the accuracy of an MDM panel with only 3 markers.

Methods: Participants were recruited from 3 medical centers. The sponge on a string device (EsophaCap; CapNostics, Concord, NC, USA) was swallowed and withdrawn, followed by endoscopy, in BE cases and control subjects. A 5 MDM panel was blindly assayed using a simplified assay. Random forest modeling analysis was performed, in silico cross-validated in the training set, and then locked down, before test set analysis.

Results: The training set had 199 patients: 110 BE cases and 89 control subjects, and the test set had 89 patients: 60 BE cases and 29 control subjects. Sensitivity of the 5 MDM panel for BE diagnosis was 93% at 90% specificity in the training set and 93% at 93% specificity in the test set. Areas under the receiver operating characteristic curves were .96 and .97 in the training and test sets, respectively. Model accuracy was not influenced by age, sex, or smoking history. Multiple 3 MDM panels achieved similar accuracy.

Conclusions: A 5 MDM panel for BE is highly accurate in training and test sets in a blinded multisite case-control analysis using a simplified assay. This panel may be reduced to only 3 MDMs in the future. (Clinical trial registration number: NCT02560623.).
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http://dx.doi.org/10.1016/j.gie.2021.03.937DOI Listing
April 2021

What is the optimal surveillance strategy for non-dysplastic Barrett's esophagus?

Curr Treat Options Gastroenterol 2020 Sep 25;18(3):369-383. Epub 2020 Jun 25.

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

Purpose Of Review: There is conflicting data on the effectiveness of the currently recommended endoscopic surveillance strategy in non-dysplastic BE patients. We reviewed the literature to evaluate the (cost) effectiveness of the current surveillance strategy. We also reviewed critical strategies and new technologies which could improve dysplasia detection.

Recent Findings: Adherence to the current EGD surveillance guidelines is suboptimal with high rates of missed dysplasia/EAC. The influence of surveillance on EAC mortality appears modest. Careful cleansing, inspection and sampling of the BE mucosa using high resolution while light and (electronic) chromoendoscopy is critical. Newer sampling techniques coupled with computer aided diagnosis and emerging imaging technologies have shown promise in improving dysplasia detection. Personalized surveillance with risk stratification based on risk factors for progression may be on the horizon.

Summary: Current BE surveillance strategy will likely be further refined and optimized by emerging new technologies in tissue sampling, advanced imaging and risk stratification.
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http://dx.doi.org/10.1007/s11938-020-00297-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963123PMC
September 2020

Esophageal Epidermoid Metaplasia: Clinical Characteristics and Risk of Esophageal Squamous Neoplasia.

Am J Gastroenterol 2021 Jul;116(7):1533-1536

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

Introduction: Esophageal epidermoid metaplasia (EEM) is a rare disease.

Methods: Patients with EEM diagnosed between 2014 and 2020 were reviewed.

Results: Forty EEM cases were identified. EEM occurred in 9 (23%) patients before, concordant, or after esophageal squamous cell carcinoma (ESCC). EEM was associated with previous esophageal lichen planus in 5 patients, Barrett's esophagus 7, and esophageal adenocarcinoma 1. EEM was focal in 28 (70%) or diffuse in 12 (30%) and not detected in 45% on recent previous endoscopy.

Discussion: EEM is a premalignant underrecognized condition associated with multiple conditions. Close follow-up or endoscopic treatment may be warranted because of its ESCC association.
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http://dx.doi.org/10.14309/ajg.0000000000001225DOI Listing
July 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

AGA Clinical Practice Update on the Management of Refractory Helicobacter pylori Infection: Expert Review.

Gastroenterology 2021 Apr 29;160(5):1831-1841. Epub 2021 Jan 29.

Division of Gastroenterology, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

The purpose of this CPU Expert Review is to provide clinicians with guidance on the management of Helicobacter pylori after an initial attempt at eradication therapy fails, including best practice advice on specific regimen selection, and consideration of patient and systems factors that contribute to treatment efficacy. This Expert Review is not a formal systematic review, but is based upon a review of the literature to provide practical advice. No formal rating of the strength or quality of the evidence was carried out. Accordingly, a combination of available evidence and consensus-based expert opinion were used to develop these best practice advice statements.
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http://dx.doi.org/10.1053/j.gastro.2020.11.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281326PMC
April 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

Response.

Gastrointest Endosc 2021 01;93(1):283-284

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

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http://dx.doi.org/10.1016/j.gie.2020.09.015DOI Listing
January 2021

Epidemiology and Outcomes of Young-Onset Esophageal Adenocarcinoma: An Analysis from a Population-Based Database.

Cancer Epidemiol Biomarkers Prev 2021 01 11;30(1):142-149. Epub 2020 Dec 11.

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

Background: Esophageal adenocarcinoma is a lethal cancer with rising incidence. There are limited data in younger (<50 years) patients with esophageal adenocarcinoma. We aimed to assess time trends in the incidence and outcomes of "young-onset" esophageal adenocarcinoma using a population-based database.

Methods: We queried the Surveillance, Epidemiology, and End Results 9 database to identify patients with esophageal adenocarcinoma between 1975 and 2015. Patients were stratified into three age strata: <50, 50 to 69, and ≥70 years. Staging was stratified as localized, regional, and distant. Trends in incidence, disease stage, and survival were assessed in three periods (1975-89, 1990-99, and 2000-2015). Univariate and multivariate models were created to identify predictors of mortality.

Results: Esophageal adenocarcinoma incidence has increased in patients <50 years of age, with an annual percentage change of 2.9% (95% confidence interval, 1.4%-4.4%) from 1975 to 2015. Young-onset esophageal adenocarcinoma presented at more advanced stages (regional + distant) compared with older patients (84.9% vs. 67.3%; < 0.01), with increasing proportion of advanced stages over the study period. These patients also experienced poorer 5-year esophageal adenocarcinoma-free survival compared with older patients (22.9%% vs. 29.6%; < 0.01), although this finding was attenuated on stage-stratified analysis.

Conclusions: Young-onset esophageal adenocarcinoma, while uncommon, is rising in incidence. Concerningly, the proportion of advanced disease continues to increase. Young-onset esophageal adenocarcinoma also presents at more advanced stages, resulting in poorer esophageal adenocarcinoma-free survival.

Impact: Patients with esophageal adenocarcinoma younger than 50 years present at more advanced stages with higher esophageal adenocarcinoma-specific mortality compared with older peers. Current diagnostic and management strategies for young-onset esophageal adenocarcinoma may need to be reevaluated.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855414PMC
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

Comparative Outcomes of Cap Assisted Endoscopic Resection and Endoscopic Submucosal Dissection in Dysplastic Barrett's Esophagus.

Clin Gastroenterol Hepatol 2020 Nov 18. Epub 2020 Nov 18.

Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Rochester, Minnesota. Electronic address:

Background & Aims: Endoscopic resection is an important component of the endoscopic treatment of Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma. Endoscopic resection can be performed by cap-assisted endoscopic mucosal resection (cEMR) or endoscopic submucosal dissection (ESD). We compared the histologic outcomes of ESD vs cEMR, followed by ablation.

Methods: We queried a prospectively maintained database of all patients undergoing cEMR and ESD followed by ablation at our institution from January 2006 to March 2020 and abstracted relevant demographic and clinical data. Our primary outcomes included the rate of complete remission of dysplasia (CRD): absence of dysplasia on surveillance histology, and complete remission of intestinal metaplasia (CRIM): absence of intestinal metaplasia. Our secondary outcome included complication rates.

Results: We included 537 patients in the study: 456 underwent cEMR and 81 underwent ESD. The cumulative probabilities of CRD at 2 years were 75.8% and 85.6% in the cEMR and ESD groups, respectively (P < .01). Independent predictors of CRD were as follows: ESD (hazard ratio [HR], 2.38; P < .01) and shorter BE segment length (HR, 1.11; P < .01). The cumulative probabilities of CRIM at 2 years were 59.3% and 50.6% in the cEMR and ESD groups, respectively (P > .05). The only independent predictor of CRIM was a shorter BE segment (HR, 1.16; P < .01).

Conclusions: BE patients with dysplasia or intramucosal adenocarcinoma undergoing ESD reach CRD at higher rates than those treated with cEMR, although CRIM rates at 2 years and complication rates were similar between the 2 groups.
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http://dx.doi.org/10.1016/j.cgh.2020.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128933PMC
November 2020

Endoscopic Screening for Barrett's Esophagus and Esophageal Adenocarcinoma: Rationale, Candidates, and Challenges.

Gastrointest Endosc Clin N Am 2021 Jan 21;31(1):27-41. Epub 2020 Oct 21.

Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, USA. Electronic address:

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), a cancer with increasing incidence and poor survival. Risk of EAC in patients with BE is higher compared with the general population. Endoscopic screening for BE is performed to identify patients earlier in the metaplasia-dysplasia-carcinoma sequence from BE to EAC to enable eradication therapy. BE screening should be considered in individuals with multiple risk factors for BE and EAC. Challenges to BE screening include the absence of a cost-effective, widely applicable minimally invasive screening tool, gastroesophageal reflux disease centric screening recommendations, and limitations of current endoscopic surveillance practice.
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http://dx.doi.org/10.1016/j.giec.2020.08.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127641PMC
January 2021

Gastroesophageal Reflux Disease and Barrett Esophagus in the Elderly.

Clin Geriatr Med 2021 02 29;37(1):17-29. Epub 2020 Oct 29.

Barrett's Esophagus Unit, Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SouthWest, Rochester, MN 55905, USA.

As our population continues to age, the early diagnosis and optimal management of patients with gastroesophageal reflux disease becomes paramount. Maintaining a low threshold for evaluating atypical symptoms in this population is key to improving outcomes. Should patients develop complications including severe esophagitis, peptic stricture, or Barrett esophagus, then a discussion of medical, endoscopic, and surgical treatments that accounts for patient's comorbidities and survival is important. Advances in screening, surveillance, and endoscopic treatment of Barrett esophagus have allowed us to dispel concerns of futility and treat a larger subset of the at-risk population.
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http://dx.doi.org/10.1016/j.cger.2020.08.003DOI Listing
February 2021

Clinical significance of recurrent gastroesophageal junction intestinal metaplasia after endoscopic eradication of Barrett's esophagus.

Gastrointest Endosc 2021 06 2;93(6):1250-1257.e3. Epub 2020 Nov 2.

Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA. Electronic address:

Background And Aims: After endoscopic eradication of Barrett's esophagus (BE), recurrence of intestinal metaplasia at the gastroesophageal junction (GEJIM) is common. The clinical significance of this finding is unclear. We assessed whether recurrent GEJIM is associated with increased risk of subsequent dysplasia and whether endoscopic treatment lowers this risk.

Methods: A retrospective, multicenter, cohort study was performed of treated BE patients who achieved complete eradication of intestinal metaplasia (IM). Postablation follow-up was performed at standard intervals. Recurrent GEJIM was defined as nondysplastic IM on gastroesophageal junction biopsy specimens without endoscopic evidence of BE. Patients were categorized as "never-GEJIM," "GEJIM-observed," or "GEJIM-treated." Endoscopic treatment for recurrent GEJIM was at the endoscopists' discretion. The primary outcome was dysplasia recurrence. Analyses were performed using log-rank tests and Cox proportional hazards modeling.

Results: Six hundred thirty-three patients were analyzed; median follow-up was 47 months (interquartile range, 24-69). Most patients (81%) had high-grade dysplasia or intramucosal adenocarcinoma before treatment. Dysplasia recurrence was 2.2% per year. GEJIM-observed patients had the lowest rate of recurrence (.6%/y) followed by GEJIM-treated (2.2%/y) and never-GEJIM (2.6%/y) (log-rank P = .07). In multivariate analyses, compared with never-GEJIM, the risk of dysplasia recurrence was significantly lower in GEJIM-observed patients (adjusted hazard ratio, .19; 95% confidence interval, .05-.81) and not different in GEJIM-treated patients (adjusted hazard ratio, .81; 95% confidence interval, .39-1.67). Older age and longer initial BE length were independently associated with recurrence.

Conclusions: Recurrent GEJIM after endoscopic eradication of BE was not associated with an increased risk of subsequent dysplasia. Future studies are warranted to determine if observation is appropriate for this finding.
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http://dx.doi.org/10.1016/j.gie.2020.10.027DOI Listing
June 2021

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

Am J Gastroenterol 2021 01;116(1):198-201

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

Introduction: It is assumed that screening risk factors for Barrett's esophagus (BE) and prevalent esophageal adenocarcinoma (EAC) are the same.

Methods: A matched case-control study comparing risk factors between EAC and BE was performed.

Results: In 1,356 patients (678 with EAC and 678 with BE), heartburn (52.7%), diabetes, hyperlipidemia, hypertension, nonalcoholic steatohepatitis, and metabolic syndrome were less common in EAC (52.7, 29.2, 45.7, 48.2, 12, and 28.5%, resp.) compared with BE (84.5, 37.6, 82.2, 64.6, 18.4, and 44.1%, P < 0.01). Mean alanine aminotransferase and HgA1c levels were also significantly lower in EAC compared with BE.

Discussion: Optimal strategies for screening for prevalent EAC may be different than that for BE.
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http://dx.doi.org/10.14309/ajg.0000000000001001DOI Listing
January 2021

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

Gut 2021 Jul 7;70(7):1335-1344. Epub 2020 Oct 7.

Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA

Objective: The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time.

Design: A database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC.

Results: From 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP).

Conclusion: The developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.
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http://dx.doi.org/10.1136/gutjnl-2020-322821DOI Listing
July 2021

Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study.

Cancer Epidemiol Biomarkers Prev 2020 12 18;29(12):2642-2650. Epub 2020 Sep 18.

Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.

Background: Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices.

Methods: MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons.

Results: Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia ( < 0.004).

Conclusions: MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results.

Impact: MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710574PMC
December 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

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

Gastrointest Endosc 2021 05 28;93(5):1121-1130.e1. Epub 2020 Aug 28.

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

Background And Aims: Detection and characterization of focal liver lesions (FLLs) is key for optimizing treatment for patients who may have a primary hepatic cancer or metastatic disease to the liver. This is the first study to develop an EUS-based convolutional neural network (CNN) model for the purpose of identifying and classifying FLLs.

Methods: A prospective EUS database comprising cases of FLLs visualized and sampled via EUS was reviewed. Relevant still images and videos of liver parenchyma and FLLs were extracted. Patient data were then randomly distributed for the purpose of CNN model training and testing. Once a final model was created, occlusion heatmap analysis was performed to assess the ability of the EUS-CNN model to autonomously identify FLLs. The performance of the EUS-CNN for differentiating benign and malignant FLLs was also analyzed.

Results: A total of 210,685 unique EUS images from 256 patients were used to train, validate, and test the CNN model. Occlusion heatmap analyses demonstrated that the EUS-CNN model was successful in autonomously locating FLLs in 92.0% of EUS video assets. When evaluating any random still image extracted from videos or physician-captured images, the CNN model was 90% sensitive and 71% specific (area under the receiver operating characteristic [AUROC], 0.861) for classifying malignant FLLs. When evaluating full-length video assets, the EUS-CNN model was 100% sensitive and 80% specific (AUROC, 0.904) for classifying malignant FLLs.

Conclusions: This study demonstrated the capability of an EUS-CNN model to autonomously identify FLLs and to accurately classify them as either malignant or benign lesions.
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http://dx.doi.org/10.1016/j.gie.2020.08.024DOI Listing
May 2021

Outcomes of radiofrequency ablation by manual versus self-sizing circumferential balloon catheters for the treatment of dysplastic Barrett's esophagus: a multicenter comparative cohort study.

Gastrointest Endosc 2021 04 31;93(4):880-887.e1. Epub 2020 Jul 31.

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

Background And Aims: Radiofrequency ablation (RFA) is the preferred ablative modality for treating dysplastic Barrett's esophagus. The recently introduced self-sizing circumferential ablation catheter eliminates the need for a sizing balloon. Although it enhances efficiency, outcomes have not been compared with the previous manual-sizing catheter. We evaluated the comparative safety and efficacy of these 2 ablation systems in a large, multicenter cohort.

Methods: Patients undergoing RFA at 3 tertiary care centers from 2005 to 2018 were included. Circumferential RFA was performed in a standard fashion, followed by focal RFA as needed. Outcomes were compared between the self-sizing and manual-sizing groups. The primary outcome was the rate of adverse events, including strictures, perforation, and bleeding. Secondary outcomes were procedure time and treatment efficacy, as assessed by rates and time to complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM).

Results: Three hundred eighteen patients were included, 90 (28.3%) treated with the self-sizing catheter and 228 (71.7%) with the manual-sizing catheter. Twenty-one patients (6.6%) developed strictures (8 [8.9%] in the self-sizing group and 13 [5.7%] in the manual-sizing group, P = .32). Of the self-sizing strictures, 75% occurred at the 12J dose before widespread adoption of the current 10J treatment standard. One patient developed bleeding, and no perforations were encountered. Procedure time was significantly shorter in the self-sizing group. No significant differences were observed in rates of and time to CE-D and CE-IM.

Conclusions: These findings suggest that both systems are comparable in safety and efficacy. The use of the self-sizing system may enhance the efficiency of RFA for treating dysplastic Barrett's esophagus.
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http://dx.doi.org/10.1016/j.gie.2020.07.056DOI Listing
April 2021

Neoplasia Detection Rate in Barrett's Esophagus and Its Impact on Missed Dysplasia: Results from a Large Population-Based Database.

Clin Gastroenterol Hepatol 2021 May 21;19(5):922-929.e1. Epub 2020 Jul 21.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Background & Aims: It is a challenge to detect dysplasia in Barrett's esophagus (BE) and esophageal adenocarcinomas (EACs) are missed in 25%-33% of cases. The neoplasia detection rate (NDR), defined as the rate of high-grade dysplasia (HGD) or EAC detection during initial surveillance endoscopy, has been proposed as a quality metric for endoscopic evaluation of patients with BE. However, current estimates are from referral center cohorts, which might overestimate NDR. Effects on rates of missed dysplasia are also unknown. We analyzed data from a large cohort of patients with BE to estimate the NDR and factors associated with it, and assess the effects of the NDR on the rate of missed dysplasia.

Methods: We analyzed data from 1066 patients in the Rochester Epidemiology Project-linked medical record system, a population-based cohort of patients with BE (confirmed by review of the endoscopic and histologic reports) from 11 southeastern Minnesota counties from 1991 through 2019. Biopsies reported to contain dysplasia were confirmed by expert gastrointestinal pathologists. The NDR was calculated as the rate of HGD or EAC detected by histologic analyses of biopsies collected during the first surveillance endoscopy. Patients without HGD or EAC at their initial endoscopy (n = 391) underwent repeat endoscopy within 12 months; HGD or EAC detected at the repeat endoscopy were considered to be missed on index endoscopy. Factors associated with NDR and missed dysplasia were identified using univariate and multivariate logistic regression models.

Results: The NDR was 4.9% (95% CI, 3.8-6.4); 3.1% of patients had HGD, 1.8% had EAC, and 10.6% had low-grade dysplasia. Factors associated with higher rates of detection of neoplasia included older age, male sex, smoking, increasing length of BE, and surveillance endoscopies by gastroenterologists. This NDR was associated with a substantially lower rate of missed dysplasia (13%).

Conclusions: In an analysis of 1066 patients with BE in a population-based cohort, we found a lower NDR and lower rate of missed dysplasia than previously reported. NDR may have value as a quality metric in BE surveillance if validated in other cohorts.
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http://dx.doi.org/10.1016/j.cgh.2020.07.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854811PMC
May 2021
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