Publications by authors named "David A Katzka"

230 Publications

Disparate Health Care in Barrett's Esophagus: The First Step Is Awareness.

Authors:
David A Katzka

Am J Gastroenterol 2021 06;116(6):1182-1183

Mayo Clinic, Rochester, Minnesota.

Abstract: Disparities in medical treatment related to differences in race, gender, and creed are present in all fields of practice. This a complex issue requires multiple perspectives to gain advancements in patient care. This editorial examines the recently published article uses the GI Quality Improving Consortium to investigate disparities in adherence to quality indicators in Barrett's esophagus.
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http://dx.doi.org/10.14309/ajg.0000000000001262DOI Listing
June 2021

Presentation of the Julius M. Friedenwald Medal to Michael Camilleri, MD, AGAF.

Gastroenterology 2021 Jun;160(7):2563-2571

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

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http://dx.doi.org/10.1053/j.gastro.2021.04.039DOI Listing
June 2021

The Volume-Outcome Effect Calls for Centralization of Care in Esophageal Adenocarcinoma: Results From a Large National Cancer Registry.

Am J Gastroenterol 2021 04;116(4):811-815

1Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado; 2Adult and Child Center for Health Outcomes Research, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; 3Division of Surgical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; 4Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA; 5Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA; 6Department of Population and Data Sciences, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA; 7Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA; 8Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Rochester, Minnesota, USA.

Introduction: Using the National Cancer Database, we assessed the relationship between facility overall esophageal adenocarcinoma (EAC) case volume and survival.

Methods: We categorized facilities into volume quintiles based on annual EAC patient volume and performed a multivariable Cox proportional hazards regression between facility patient volume and survival.

Results: In a cohort of 116,675 patients, facilities with higher vs lower (≥25 vs 1-4 cases) annual EAC patient volume demonstrated improved survival (adjusted hazard ratio: 0.80. 95% confidence interval: 0.70-0.91).

Discussion: This robust volume-outcome effect calls for centralization of care for EAC patients at high annual case volume facilities.
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http://dx.doi.org/10.14309/ajg.0000000000001046DOI Listing
April 2021

Effects of Central Obesity on Esophageal Epithelial Barrier Function.

Am J Gastroenterol 2021 Apr 22. Epub 2021 Apr 22.

1Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA; 2Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA; 3Division of Gastroenterology, Billings Clinic, Billings, Montana, 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
April 2021

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

Ann Intern Med 2021 May 4. 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
May 2021

Magnitude and Time-Trend Analysis of Post-Endoscopy Esophageal Adenocarcinoma: A Systematic Review and Meta-analysis.

Clin Gastroenterol Hepatol 2021 Apr 23. Epub 2021 Apr 23.

Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Electronic address:

Background & Aims: Identification of postendoscopy esophageal adenocarcinoma (PEEC) among Barrett's esophagus (BE) patients presents an opportunity to improve survival of esophageal adenocarcinoma (EAC). We aimed to estimate the proportion of PEEC within the first year after BE diagnosis.

Methods: Multiple databases (Medline, Embase, Scopus, and Cochrane databases) were searched until September 2020 for original studies with at least 1-year follow-up evaluation that reported EAC and/or high-grade dysplasia (HGD) in the first year after index endoscopy in nondysplastic BE, low-grade dysplasia, or indefinite dysplasia. The proportions of PEEC defined using EAC alone and EAC+HGD were calculated by dividing EAC or EAC+HGD in the first year over the total number of EAC or EAC+HGD, respectively.

Results: We included 52 studies with 145,726 patients and a median follow-up period of 4.8 years. The proportion of PEEC (EAC) was 21% (95% CI, 13-31) and PEEC (EAC+HGD) was 26% (95% CI, 19-34). Among studies with nondysplastic BE only, the PEEC (EAC) proportion was 17% (95% CI, 11-23) and PEEC (EAC+HGD) was 14% (95% CI, 8-19). Among studies with 5 or more years of follow-up evaluation, the PEEC (EAC) proportion was 10% and PEEC (EAC+HGD) was 19%. Meta-regression analysis showed a strong inverse relationship between PEEC and incident EAC (P < .001). The PEEC (EAC) proportion increased from 5% in studies published before 2000 to 30% after 2015. Substantial heterogeneity was observed for most analyses.

Conclusions: PEEC accounts for a high proportion of HGD/EACs and is proportional to reduction in incident EAC. Using best endoscopic techniques now and performing future research on improving neoplasia detection through implementation of quality measures and educational tools is needed to reduce PEEC.
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http://dx.doi.org/10.1016/j.cgh.2021.04.032DOI Listing
April 2021

Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial.

Clin Gastroenterol Hepatol 2021 Apr 19. Epub 2021 Apr 19.

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.

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the U.S. Food and Drug Administration.

Methods: In this double-blind, placebo-controlled, phase 3 trial, patients 11-55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (≤6 eosinophils/high-power field) or dysphagia symptom responders (≥30% reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined.

Results: Overall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received ≥1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.1% vs 1.0%; Δ52% [95% confidence interval (CI), 43.3%-59.1%]; P < .001) or symptom response (52.6% vs 39.1%; Δ13% [95% CI, 1.6%-24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, -13.0 (SEM 1.2) vs -9.1 (SEM 1.5) (Δ-3.9 ]95% CI, -7.1 to -0.8]; P = .015); EREFS, -4.0 (SEM 0.3) vs -2.2 (SEM 0.4) (Δ-1.8 [95% CI, -2.6 to -1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity.

Conclusions: In patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated. ClinicalTrials.gov number: NCT02605837.
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http://dx.doi.org/10.1016/j.cgh.2021.04.022DOI Listing
April 2021

In Memoriam-Donald O. Castell, MD.

Gastroenterology 2021 May 2;160(6):1905-1907. Epub 2021 Apr 2.

Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1053/j.gastro.2021.04.002DOI Listing
May 2021

Defining the Long-Term Clinical Course and Need for Repeat Dilation for Patients With Schatzki Rings.

Clin Gastroenterol Hepatol 2021 Apr 1. Epub 2021 Apr 1.

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

Schatzki rings (SRs) are a well-known cause of intermittent solid-food dysphagia. Although some patients sustain improvement after 1 endoscopic dilation, others require repeated dilations for recurrent symptoms. SRs are believed to be distinct from strictures caused by gastroesophageal reflux disease. SRs are sharply localized lesions with clearly defined margins, whereas peptic strictures have a more gradual transition between normal and abnormal esophagus to produce a funnel-shaped narrowing. Consequently, it has been assumed that repeat dilation is less common in SRs dissimilar from medically untreated peptic strictures. The study aim was to identify clinical and radiologic predictors for repeated esophageal dilations in patients with SRs and to assess if peptic stricture-like characteristics of rings correspond to need for repeat dilation.
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http://dx.doi.org/10.1016/j.cgh.2021.03.040DOI Listing
April 2021

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

Am J Gastroenterol 2021 Mar 10. Epub 2021 Mar 10.

Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA; Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA; Department of Pathology, 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
March 2021

Development of quality indicators for the diagnosis and management of achalasia.

Neurogastroenterol Motil 2021 Mar 15:e14118. Epub 2021 Mar 15.

Division of Gastroenterology, Duke University School of Medicine, Durham, North Carolina, USA.

Background: The management of achalasia has improved due to diagnostic and therapeutic innovations. However, variability in care delivery remains and no established measures defining quality of care for this population exist. We aimed to use formal methodology to establish quality indicators for achalasia patients.

Methods: Quality indicator concepts were identified from the literature, consensus guidelines and clinical experts. Using RAND/University of California, Los Angeles (UCLA) Appropriateness Method, experts in achalasia independently ranked proposed concepts in a two-round modified Delphi process based on 1) importance, 2) scientific acceptability, 3) usability, and 4) feasibility. Highly valid measures required strict agreement (≧ 80% of panelists) in the range of 7-9 for across all four categories.

Key Results: There were 17 experts who rated 26 proposed quality indicator topics. In round one, 2 (8%) quality measures were rated valid. In round two, 19 measures were modified based on panel suggestions, and experts rated 10 (53%) of these measures as valid, resulting in a total of 12 quality indicators. Two measures pertained to patient education and five to diagnosis, including discussing treatment options with risk and benefits and using the most recent version of the Chicago Classification to define achalasia phenotypes, respectively. Other indicators pertained to treatment options, such as the use of botulinum toxin for those not considered surgical candidates and management of reflux following achalasia treatment.

Conclusions & Inferences: Using a robust methodology, achalasia quality indicators were identified, which can form the basis for establishing quality gaps and generating fully specified quality measures.
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http://dx.doi.org/10.1111/nmo.14118DOI Listing
March 2021

Characterization of Prevalent, Post-Endoscopy, and Incident Esophageal Cancer in the United States: A Large Retrospective Cohort Study.

Clin Gastroenterol Hepatol 2021 Feb 5. Epub 2021 Feb 5.

Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado. Electronic address:

Background & Aims: Efforts to assess and improve the effectiveness of Barrett's esophagus (BE) screening and surveillance are ongoing in the United States. Currently, there are limited population-based data in the United States to guide these efforts.

Methods: We performed a retrospective cohort study using data from large commercial and Medicare Advantage health plans in the United States from 2004 - 2019. We identified individuals with BE and analyzed the proportion who developed EAC. EACs were classified as prevalent EAC (diagnosed within 30 days of index endoscopy), post-endoscopy esophageal adenocarcinoma (PEEC, diagnosed 30 - 365 days after index endoscopy), and incident EAC (diagnosed 365 days or more after index endoscopy). Using this cohort, we performed a nested case-control study to identify factors associated with prevalent EAC at BE diagnosis and study healthcare utilization prior to BE diagnosis.

Results: We identified 50,817 individuals with incident BE. Of the 366 who developed EAC, 67.2%, 13.7%, and 19.1% were diagnosed with prevalent EAC, PEEC, and incident EAC respectively. Factors positively associated with prevalent EAC versus BE without prevalent EAC included male sex, dysphagia, weight loss, and Charlson-Deyo comorbidity score. In those with prevalent EAC, most patients with dysphagia or weight loss had their symptoms first recorded within three months of EAC diagnosis. Healthcare utilization rates were similar between those with and without prevalent EAC.

Conclusions: Two-thirds of EACs among individuals with BE are diagnosed at the time of BE diagnosis. Additionally, PEEC accounts for 14% of these EACs. These results may guide future research studies that investigate novel BE diagnostic strategies that reduce the morbidity and mortality of EAC.
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http://dx.doi.org/10.1016/j.cgh.2021.02.005DOI Listing
February 2021

The risk of neoplasia in patients with Barrett's esophagus indefinite for dysplasia: a multicenter cohort study.

Gastrointest Endosc 2021 Feb 4. Epub 2021 Feb 4.

MRC Cancer Unit, University of Cambridge, Cambridge, United Kingdom.

Background And Aims: Current understanding of the risk of neoplastic progression in patients with Barrett's esophagus with indefinite dysplasia (BE-IND) stems from small retrospective and pathology registry studies. In this multicenter cohort study, we aimed to determine the incidence and prevalence of neoplasia in BE-IND.

Methods: Patients with confirmed BE-IND from 2 academic centers were included if they had no previous evidence of dysplasia and underwent endoscopic follow-up (FU) of ≥1 year. The rate of progression to neoplasia was calculated and categorized as prevalent (progression within 1 year of FU) and incident (progression after 1 year of FU). Multivariable regression adjusted for relevant clinical features was performed to identify risk factors for progression.

Results: Four hundred sixty-five patients diagnosed with BE-IND were identified between 1997 and 2017, of which 223 (48.0%) were excluded. Of the remaining 242 patients, 184 (76.0%) had no evidence of dysplasia during FU. In 23 patients (9.5%), prevalent neoplasia occurred (20 low-grade dysplasia [LGD], 2 high-grade dysplasia [HGD], 1 intramucosal cancer [IMC]), whereas 35 patients (14.5%) developed incident neoplasia (27 LGD, 5 HGD, 3 IMC), after a median 1.5 years (interquartile range, 0.6-3.2 years). The incidence rates of any neoplasia and HGD/IMC were 3.2 and 0.6 cases/100 patient-years, respectively. BE length correlated with an increased risk of prevalent (odds ratio, 1.18 per 1 cm; 95% confidence interval, 1.02-1.38; P = .033) and incident neoplasia (odds ratio, 1.02; 95% confidence interval, 1.00-1.03; P = .016).

Conclusion: Patients with BE-IND should be closely monitored, because nearly a quarter harbor or will shortly develop dysplasia. BE length is a clinical predictor of neoplastic progression; however, more-accurate molecular biomarkers for risk stratification are warranted.
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http://dx.doi.org/10.1016/j.gie.2021.01.042DOI Listing
February 2021

Editorial: penetration of food protein through the oesophageal mucosa - is this where EoE starts? Authors' reply.

Aliment Pharmacol Ther 2021 02;53(3):449

Department of Pediatrics and Medicine, Mayo Clinic, Rochester, MN, USA.

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http://dx.doi.org/10.1111/apt.16223DOI Listing
February 2021

Esophageal motility disorders on high-resolution manometry: Chicago classification version 4.0.

Neurogastroenterol Motil 2021 01;33(1):e14058

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.

Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.
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http://dx.doi.org/10.1111/nmo.14058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034247PMC
January 2021

Same-day opioid administration in opiate naïve patients is not associated with opioid-induced esophageal dysfunction (OIED).

Neurogastroenterol Motil 2021 05 22;33(5):e14059. Epub 2020 Dec 22.

Department of Gastroenterology, Hepatology Mayo Clinic, Rochester, MN, USA.

Background: Opioid-induced esophageal dysfunction (OIED) is a recognized complication of chronic opioid use. However, the impact of acute opioid administration on esophageal motility remains unclear.

Methods: Opioid naïve patients with high-resolution manometry (HRM) <480 min following esophagogastroduodenoscopy (EGD) (opioid-HRM) and a control group with HRM <36 h prior to EGD between January 1, 2016, and November 10, 2018, from a single institution were identified. EGDs were performed exclusively with versed and fentanyl.

Key Results: One hundred and seventy-four patients were identified, with 83 (47.7%) opioid-HRM and 91 (52.3%) controls. Mean time from EGD to HRM was 229 (78-435) min. Baseline clinical features and HRM indications were similar between opioid-HRM and controls. Chicago classification v3.0 defined HRM findings were similar between groups. Major motility disorders as defined by the Chicago classification v3.0 occurred at a similar frequency among opioid-HRM and controls (27.7% vs. 36.3%, p = 0.23). Mean distal contractile integrity (DCI) was higher in opioid-HRM (1939.3 ± 1318.9 vs. 1792.2 ± 2062.3 mmHg∙cm∙s, p = 0.043), but maximum DCI, distal latency, and integrated relaxation pressure did not differ between groups. Subgroup analysis assessing time and dose dependency did not identify differences in individual manometric parameters and Chicago classification v3.0 diagnosis between patients with HRM <240 min after EGD, >240 min after EGD, ≥125 mcg of IV fentanyl, <125 mcg IV fentanyl and controls.

Conclusions And Inferences: Same-day acute opioid administration did not affect HRM findings in opioid naïve patients. Studies assessing the pathophysiology of and duration-dependent relationship with opioids in OIED are needed.
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http://dx.doi.org/10.1111/nmo.14059DOI Listing
May 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

Ectopic Esophageal Sebaceous Glands.

Clin Gastroenterol Hepatol 2020 Dec 3. Epub 2020 Dec 3.

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

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http://dx.doi.org/10.1016/j.cgh.2020.11.034DOI Listing
December 2020

Mucosal penetration and clearance of gluten and milk antigens in eosinophilic oesophagitis.

Aliment Pharmacol Ther 2021 02 2;53(3):410-417. Epub 2020 Dec 2.

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

Background: The Th2 allergic pathway in eosinophilic oesophagitis (EoE) responds to food antigen exposure.

Aim: To compare the presence and temporal pattern of food antigen penetration in oesophageal mucosa in active and inactive EoE and controls METHODS: Thirty-two patients with EoE (20 active) and 10 controls were asked to eliminate all wheat and/or dairy 12, 24, 48, 72 or 96 hours before endoscopy. Immunostaining on endoscopic biopsies was performed for gliadin, casein and whey.

Results: Gluten, casein and whey were detected by positive staining in 17/32 (53.1%), 21/32 (65.6%), and 30/32 (92.0%) of patients, respectively. In active vs inactive EoE, 70.0% vs 25.0% (P < 0.05), 80.0% vs 41.5%, and 90.0% vs 90.9% patients had detectable gliadin, casein and whey, respectively. Casein and whey (20.0% and 100%, respectively) but not gliadin, were present in controls. The gliadin staining density was greater in active compared to inactive disease at ≤ 24 vs >24 hours after exposure (P = 0.05) but no differences were detected when comparing active and inactive patients for casein and whey. There was greater staining density for whey than casein for all patients at ≤24 hours (mean 2.14 ± 0.91 and 1.07 ± 1.33, P = 0.02). In active EoE, IgG4 was present in 14/20 compared to one inactive patient.

Conclusion: The oesophageal epithelium is selectively permeable and has relatively long dwell times for food antigens known to trigger EoE. The precise mechanism of antigen-specific mucosal entry and the factors that determine the induction or effector trigger of the Th2 pathway activation merit further study.
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http://dx.doi.org/10.1111/apt.16180DOI Listing
February 2021

Advances in the diagnosis and management of gastroesophageal reflux disease.

BMJ 2020 11 23;371:m3786. Epub 2020 Nov 23.

Northwestern University, Feinberg School of Medicine, Department of Medicine, Chicago, IL USA

Gastroesophageal reflux disease (GERD) is a multifaceted disorder encompassing a family of syndromes attributable to, or exacerbated by, gastroesophageal reflux that impart morbidity, mainly through troublesome symptoms. Major GERD phenotypes are non-erosive reflux disease, GERD hypersensitivity, low or high grade esophagitis, Barrett's esophagus, reflux chest pain, laryngopharyngeal reflux, and regurgitation dominant reflux. GERD is common throughout the world, and its epidemiology is linked to the Western lifestyle, obesity, and the demise of Because of its prevalence and chronicity, GERD is a substantial economic burden measured in physician visits, diagnostics, cancer surveillance protocols, and therapeutics. An individual with typical symptoms has a fivefold risk of developing esophageal adenocarcinoma, but mortality from GERD is otherwise rare. The principles of management are to provide symptomatic relief and to minimize potential health risks through some combination of lifestyle modifications, diagnostic testing, pharmaceuticals (mainly to suppress or counteract gastric acid secretion), and surgery. However, it is usually a chronic recurring condition and management needs to be personalized to each case. While escalating proton pump inhibitor therapy may be pertinent to healing high grade esophagitis, its applicability to other GERD phenotypes wherein the modulating effects of anxiety, motility, hypersensitivity, and non-esophageal factors may dominate is highly questionable.
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http://dx.doi.org/10.1136/bmj.m3786DOI Listing
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

Verrucous esophageal carcinoma is a unique indolent subtype of squamous cell carcinoma: a systematic review and individual patient regression analysis.

J Gastroenterol 2021 Jan 20;56(1):12-24. Epub 2020 Oct 20.

Assistant in Medicine, Instructor in Medicine, Harvard Medical School, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, GRJ 825D, Boston, MA, 02114, USA.

Background And Aims: Verrucous esophageal carcinoma (VEC) is a rare malignancy that presents a diagnostic challenge. We aim to characterize the clinical and genomic features, tumor behavior, and treatment outcomes of VEC to guide clinical practice.

Methods: We performed a systematic review of the literature and identified additional cases from Massachusetts General Hospital records and The Cancer Genome Atlas (TCGA). We obtained individual VEC patient data and analyzed publicly available clinicogenomic data from TCGA. We performed a regression analysis comparing cases of VEC to esophageal squamous cell carcinoma (ESCC) to identify factors influencing survival.

Results: A total of 135 patients were reported in 82 publications, and four unpublished cases from Massachusetts General Hospital (median age 65 years, 69% males, 48% smokers, 33% consumed alcohol). Symptoms were present at diagnosis in 95% of patients, most commonly dysphagia and weight loss. Median symptom onset to diagnosis time was 11.5 months with frequent misdiagnosis as Candida esophagitis. Among VEC cases with pathologic staging, lymph node metastases were rare (5%) compared to ESCC (40%). VEC was genomically characterized by enrichment of SMARCA4 missense mutations and a lack of pathogenic TP53 mutations. Despite its diagnostic elusiveness, in a multivariate regression analysis, VEC was detected at earlier stages (p =  < 0.001) compared to ESCC, and advanced stage was the only significant factor affecting survival (p = 0.013).

Conclusions: VEC is a rare, clinically and genomically distinct subtype of ESCC. Recognition and diagnosis of this lesion may allow the pursuit of curative and less morbid treatment strategies.
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http://dx.doi.org/10.1007/s00535-020-01736-1DOI Listing
January 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

Effects of Diaphragmatic Breathing on the Pathophysiology and Treatment of Upright Gastroesophageal Reflux: A Randomized Controlled Trial.

Am J Gastroenterol 2021 01;116(1):86-94

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

Introduction: Uncontrolled results suggest that diaphragmatic breathing (DB) is effective in gastroesophageal reflux disease (GERD) but the mechanism of action and rigor of proof is lacking. This study aimed to determine the effects of DB on reflux, lower esophageal sphincter (LES), and gastric pressures in patients with upright GERD and controls.

Methods: Adult patients with pH proven upright GERD were studied. During a high-resolution impedance manometry, study patients received a standardized pH neutral refluxogenic meal followed by LES challenge maneuvers (Valsalva and abdominal hollowing) while randomized to DB or sham. After that, patients underwent 48 hours of pH-impedance monitoring, with 50% randomization to postprandial DB during the second day.

Results: On examining 23 patients and 10 controls, postprandial gastric pressure was found to be significantly higher in patients compared with that in controls (12 vs 7 mm Hg, P = 0.018). Valsalva maneuver produced reflux in 65.2% of patients compared with 44.4% of controls (P = 0.035). LES increased during the inspiratory portion of DB (42.2 vs 23.1 mm Hg, P < 0.001) in patients and healthy persons. Postprandial DB reduced the number of postprandial reflux events in patients (0.36 vs 2.60, P < 0.001) and healthy subjects (0.00 vs 1.75, P < 0.001) compared with observation. During 48-hour ambulatory study, DB reduced the reflux episodes on day 2 compared with observation on day 1 in both the patient and control groups (P = 0.049). In patients, comparing DB with sham, total acid exposure on day 2 was not different (10.2 ± 7.9 vs 9.4 ± 6.2, P = 0.804). In patients randomized to DB, esophageal acid exposure in a 2-hour window after the standardized meal on day 1 vs day 2 reduced from 11.8% ±6.4 to 5.2% ± 5.1, P = 0.015.

Discussion: In patients with upright GERD, DB reduces the number of postprandial reflux events pressure by increasing the difference between LES and gastric pressure. These data further encourage studying DB as therapy for GERD.
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http://dx.doi.org/10.14309/ajg.0000000000000913DOI Listing
January 2021

Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse.

Dig Dis Sci 2020 Sep 29. Epub 2020 Sep 29.

Department of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, SW, Rochester, MN, 55905, USA.

Background: Identification of clinical predictors of response to first-line therapies for EoE is needed to guide initial medical management.

Study Design: A retrospective analysis of patients diagnosed with EoE from 2011 to 2018 was conducted. Clinical and diagnostic variables including demographics, endoscopic, and esophagram findings were compared between PPI responders and PPI nonresponders. All patients underwent a standard 8-week twice-daily PPI trial, with PPI responsiveness defined as < 15 eos/hpf on repeat EGD. Univariate and multivariable analyses were conducted to identify risk factors for nonresponse, and ROC curves were created to identify cutoff values.

Results: A total of 223 EoE patients (135 male, median age 39 (29-51)) were identified, with PPI nonresponse (PPI-NR) in 71% of patients. PPI-NR was seen in all 10 patients with failure of scope passage, with an OR of 9.06 by univariate analysis (P = 0.1485). In a multivariable model, age per 10 years (OR 0.71; P = 0.007), BMI per 1 kg/m (OR 0.94; P = 0.03), and peripheral eosinophil count per 100 per mm (OR 1.37; P = 0.003) were independent risk factors. Dichotomization to maximize sensitivity and specificity identified age ≤ 36 years old, BMI ≤ 25.2 kg/m, and peripheral eos > 460 per mm as predictive thresholds for PPI-NR. The probability of PPI-NR was 72.4-84.5% with 1 risk factor, 87.9-93.8% with 2 risk factors, and 97.2% with all 3 risk factors.

Conclusions: Young age, reduced BMI, elevated peripheral eosinophil count, and likely inability to pass an endoscope predict lack of response to PPIs in patients with EoE.
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http://dx.doi.org/10.1007/s10620-020-06633-4DOI Listing
September 2020

Effectiveness and Safety of High- vs Low-Dose Swallowed Topical Steroids for Maintenance Treatment of Eosinophilic Esophagitis: A Multicenter Observational Study.

Clin Gastroenterol Hepatol 2020 Aug 13. Epub 2020 Aug 13.

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

Background & Aims: Data evaluating efficacy of different doses of swallowed topical corticosteroids (STC) in the long-term management of eosinophilic esophagitis (EoE) are lacking. We assessed long-term effectiveness and safety of different STC doses for adults with EoE after achievement of histological remission.

Methods: We performed a retrospective multicenter study at five EoE referral centers (US and Switzerland). We analyzed data on 82 patients with EoE in histological remission and ongoing STC treatment with therapeutic adherence of ≥75% (58 males; mean age at diagnosis, 37.2±14.4 years). Patients were followed for a median of 2.2 years (interquartile range [IQR], 1.0-3.8 years). We collected data from 217 follow-up endoscopy visits. The primary endpoint was time to histological relapse.

Results: Histological relapse occurred in 67% of patients. Relapse rates were comparable in patients taking low dose (≤0.5 mg per day, n = 58) and high dose STC (>0.5 mg per day, n = 24) with 72 vs 54% (ns). However, histological relapse occurred significantly earlier with low dose STC (1.0 vs 1.8 years, P = .030). There was no difference regarding rates of and time to stricture formation for low vs high dose STC. Esophageal candidiasis was observed in 6% of patients (5% for low dose, 8% for high dose, ns). No dysplasia or mucosal atrophy was detected.

Conclusion: Histological relapse frequently occurs in EoE despite ongoing STC treatment regardless of STC doses. However, relapse develops later in patients on high dose STC without an increase in side-effects. Doses higher than 0.5 mg/day may be considered for EoE maintenance treatment, but advantage over lower doses appears to be small.
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http://dx.doi.org/10.1016/j.cgh.2020.08.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108396PMC
August 2020

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

Achalasia: When a Simple Disease Becomes Complex.

Gastroenterology 2020 09 18;159(3):821-824. Epub 2020 Jul 18.

Division of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland; and Digestive Function: Basel, Laboratory and Clinic for Motility Disorders and Functional Gastrointestinal Diseases, Centre for integrative Gastroenterology, Klinik Arlesheim, Arlesheim, Switzerland. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.07.028DOI Listing
September 2020

AGA Clinical Practice Update on Reducing Rates of Post-Endoscopy Esophageal Adenocarcinoma: Commentary.

Gastroenterology 2020 10 14;159(4):1533-1537. Epub 2020 Jul 14.

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

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http://dx.doi.org/10.1053/j.gastro.2020.06.089DOI Listing
October 2020

Food-induced immediate response of the esophagus-A newly identified syndrome in patients with eosinophilic esophagitis.

Allergy 2021 01 19;76(1):339-347. Epub 2020 Aug 19.

Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.

Background: Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as "food-induced immediate response of the esophagus" (FIRE), observed in EoE patients.

Methods: Food-induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE.

Results: Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P < .01) and in those with high allergic comorbidity. Food-induced immediate response of the esophagus symptoms included narrowing, burning, choking, and pressure in the esophagus appearing within 5 minutes of ingesting a provoking food that lasted less than 2 hours. Symptom severity rated a median 7 points on a visual analogue scale from 1 to 10. Fresh fruits/vegetables and wine were the most frequent triggers. Endoscopic food removal was significantly more commonly reported in male patients with vs without FIRE (44.3% vs 27.6%; P = .03).

Conclusions: Food-induced immediate response of the esophagus is a novel syndrome frequently reported in EoE patients, characterized by an intense, unpleasant/painful sensation occurring rapidly and reproducibly in 40% of surveyed EoE patients after esophageal contact with specific foods.
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http://dx.doi.org/10.1111/all.14495DOI Listing
January 2021