Publications by authors named "Charles J Lightdale"

122 Publications

Turning a Spotlight on Gastric Cancer.

Gastrointest Endosc Clin N Am 2021 Jul;31(3):xiii-xiv

Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2021.04.003DOI Listing
July 2021

Randomized Controlled Trial of the Gastrin/CCK Receptor Antagonist Netazepide in Patients with Barrett's Esophagus.

Cancer Prev Res (Phila) 2021 Jun 29;14(6):675-682. Epub 2021 Mar 29.

Department of Medicine, Columbia University Irving Medical Center, New York, New York.

Hypergastrinemia has been associated with high-grade dysplasia and adenocarcinoma in patients with Barrett's esophagus, and experimental studies suggest proinflammatory and proneoplastic effects of gastrin on Barrett's esophagus. This is of potential concern, as patients with Barrett's esophagus are treated with medications that suppress gastric acid production, resulting in increased physiologic levels of gastrin. We aimed to determine whether treatment with the novel gastrin/CCK receptor antagonist netazepide reduces expression of markers associated with inflammation and neoplasia in Barrett's esophagus. This was a randomized, double-blind, placebo-controlled trial of netazepide in patients with Barrett's esophagus without dysplasia. Subjects were treated for 12 weeks, with endoscopic assessment at baseline and at end of treatment. The primary outcome was within-individual change in cellular proliferation as assessed by Ki67. Secondary analyses included changes in gene expression, assessed by RNA-sequencing, and safety and tolerability. A total of 20 subjects completed the study and were included in the analyses. There was no difference between arms in mean change in cellular proliferation (netazepide: +35.6 Ki67+ cells/mm, SD 620.7; placebo: +307.8 Ki67+ cells/mm, SD 640.3; = 0.35). Netazepide treatment resulted in increased expression of genes related to gastric phenotype () and certain cancer-associated markers (), and decreased expression of intestinal markers , and No serious adverse events related to study drug occurred. The gastrin/CCK receptor antagonist netazepide did not reduce cellular proliferation in patients with nondysplastic Barrett's esophagus. Further research should focus on the biological effects of gastrin in Barrett's esophagus. Treatment of patients with Barrett's esophagus with a gastrin/CCK receptor antagonist did not have obvious chemopreventive effects.
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http://dx.doi.org/10.1158/1940-6207.CAPR-21-0050DOI Listing
June 2021

Video Capsule Endoscopy: Safe, Effective, Evolving, Here to Stay.

Gastrointest Endosc Clin N Am 2021 Apr 8;31(2):xiii-xiv. Epub 2021 Feb 8.

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2021.01.003DOI Listing
April 2021

Barrett's Esophagus: Current Management and New Approaches.

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

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2020.09.008DOI Listing
January 2021

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

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

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

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

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

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

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

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

Endoscopes and Antibiotic-Resistant Bacteria: Controlling the Risk.

Gastrointest Endosc Clin N Am 2020 Oct 29;30(4):xiii-xiv. Epub 2020 Jul 29.

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2020.07.001DOI Listing
October 2020

Prospective development and validation of a volumetric laser endomicroscopy computer algorithm for detection of Barrett's neoplasia.

Gastrointest Endosc 2021 04 29;93(4):871-879. Epub 2020 Jul 29.

Department of Gastroenterology and Hepatology, Amsterdam UMC, location AMC, Amsterdam, the Netherlands.

Background And Aims: Volumetric laser endomicroscopy (VLE) is an advanced imaging modality used to detect Barrett's esophagus (BE) dysplasia. However, real-time interpretation of VLE scans is complex and time-consuming. Computer-aided detection (CAD) may help in the process of VLE image interpretation. Our aim was to train and validate a CAD algorithm for VLE-based detection of BE neoplasia.

Methods: The multicenter, VLE PREDICT study, prospectively enrolled 47 patients with BE. In total, 229 nondysplastic BE and 89 neoplastic (high-grade dysplasia/esophageal adenocarcinoma) targets were laser marked under VLE guidance and subsequently underwent a biopsy for histologic diagnosis. Deep convolutional neural networks were used to construct a CAD algorithm for differentiation between nondysplastic and neoplastic BE tissue. The CAD algorithm was trained on a set consisting of the first 22 patients (134 nondysplastic BE and 38 neoplastic targets) and validated on a separate test set from patients 23 to 47 (95 nondysplastic BE and 51 neoplastic targets). The performance of the algorithm was benchmarked against the performance of 10 VLE experts.

Results: Using the training set to construct the algorithm resulted in an accuracy of 92%, sensitivity of 95%, and specificity of 92%. When performance was assessed on the test set, accuracy, sensitivity, and specificity were 85%, 91%, and 82%, respectively. The algorithm outperformed all 10 VLE experts, who demonstrated an overall accuracy of 77%, sensitivity of 70%, and specificity of 81%.

Conclusions: We developed, validated, and benchmarked a VLE CAD algorithm for detection of BE neoplasia using prospectively collected and biopsy-correlated VLE targets. The algorithm detected neoplasia with high accuracy and outperformed 10 VLE experts. (The Netherlands National Trials Registry (NTR) number: NTR 6728.).
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http://dx.doi.org/10.1016/j.gie.2020.07.052DOI Listing
April 2021

Expert assessment on volumetric laser endomicroscopy full scans in Barrett's esophagus patients with or without high grade dysplasia or early cancer.

Endoscopy 2021 Mar 8;53(3):218-225. Epub 2020 Jun 8.

Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.

Background:  Volumetric laser endomicroscopy (VLE) allows for near-microscopic imaging of the superficial esophageal wall and may improve detection of early neoplasia in Barrett's esophagus (BE). Interpretation of a 6-cm long, circumferential VLE "full scan" may however be challenging for endoscopists. We aimed to evaluate the accuracy of VLE experts in correctly diagnosing VLE full scans of early neoplasia and non-dysplastic BE (NDBE).

Methods:  29 VLE full scan videos (15 neoplastic and 14 NDBE) were randomly evaluated by 12 VLE experts using a web-based module. Experts were blinded to the endoscopic BE images and histology. The 15 neoplastic cases contained a subtle endoscopically visible lesion, which on endoscopic resection showed high grade dysplasia or cancer. NDBE cases had no visible lesions and an absence of dysplasia in all biopsies. VLE videos were first scored as "neoplastic" or "NDBE." If neoplastic, assessors located the area most suspicious for neoplasia. Primary outcome was the performance of VLE experts in differentiating between non-dysplastic and neoplastic full scan videos, calculated by accuracy, sensitivity, and specificity. Secondary outcomes included correct location of neoplasia, interobserver agreement, and level of confidence.

Results:  VLE experts correctly labelled 73 % (95 % confidence interval [CI] 67 % - 79 %) of neoplastic VLE videos. In 54 % (range 27 % - 66 %) both neoplastic diagnosis and lesion location were correct. NDBE videos were consistent with endoscopic biopsies in 52 % (95 %CI 46 % - 57 %). Interobserver agreement was fair (kappa 0.28). High level of confidence was associated with a higher rate of correct neoplastic diagnosis (81 %) and lesion location (73 %).

Conclusions:  Identification of subtle neoplastic lesions in VLE full scans by experts was disappointing. Future studies should focus on improving methodologies for reviewing full scans, development of refined VLE criteria for neoplasia, and computer-aided diagnosis of VLE scans.
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http://dx.doi.org/10.1055/a-1194-0397DOI Listing
March 2021

Colorectal Cancer Screening: Where We Are and Moving Forward.

Gastrointest Endosc Clin N Am 2020 Jul 15;30(3):xiii-xiv. Epub 2020 Apr 15.

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7158773PMC
July 2020

Notch Signaling Mediates Differentiation in Barrett's Esophagus and Promotes Progression to Adenocarcinoma.

Gastroenterology 2020 08 20;159(2):575-590. Epub 2020 Apr 20.

Department of Medicine, Columbia University Irving Medical Center, New York, New York; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York.

Background & Aims: Studies are needed to determine the mechanism by which Barrett's esophagus (BE) progresses to esophageal adenocarcinoma (EAC). Notch signaling maintains stem cells in the gastrointestinal tract and is dysregulated during carcinogenesis. We explored the relationship between Notch signaling and goblet cell maturation, a feature of BE, during EAC pathogenesis.

Methods: We measured goblet cell density and levels of Notch messenger RNAs in BE tissues from 164 patients, with and without dysplasia or EAC, enrolled in a multicenter study. We analyzed the effects of conditional expression of an activated form of NOTCH2 (pL2.Lgr5.N2IC), conditional deletion of NOTCH2 (pL2.Lgr5.N2fl/fl), or loss of nuclear factor κB (NF-κB) (pL2.Lgr5.p65fl/fl), in Lgr5 (progenitor) cells in L2-IL1B mice (which overexpress interleukin 1 beta in esophagus and squamous forestomach and are used as a model of BE). We collected esophageal and stomach tissues and performed histology, immunohistochemistry, flow cytometry, transcriptome, and real-time polymerase chain reaction analyses. Cardia and forestomach tissues from mice were cultured as organoids and incubated with inhibitors of Notch or NF-kB.

Results: Progression of BE to EAC was associated with a significant reduction in goblet cell density comparing nondysplastic regions of tissues from patients; there was an inverse correlation between goblet cell density and levels of NOTCH3 and JAG2 messenger RNA. In mice, expression of the activated intracellular form of NOTCH2 in Lgr5 cells reduced goblet-like cell maturation, increased crypt fission, and accelerated the development of tumors in the squamocolumnar junction. Mice with deletion of NOTCH2 from Lgr5 cells had increased maturation of goblet-like cells, reduced crypt fission, and developed fewer tumors. Esophageal tissues from in pL2.Lgr5.N2IC mice had increased levels of RelA (which encodes the p65 unit of NF-κB) compared to tissues from L2-IL1B mice, and we found evidence of increased NF-κB activity in Lgr5 cells. Esophageal tissues from pL2.Lgr5.p65fl/fl mice had lower inflammation and metaplasia scores than pL2.Lgr5.N2IC mice. In organoids derived from pL2-IL1B mice, the NF-κB inhibitor JSH-23 reduced cell survival and proliferation.

Conclusions: Notch signaling contributes to activation of NF-κB and regulates differentiation of gastric cardia progenitor cells in a mouse model of BE. In human esophageal tissues, progression of BE to EAC was associated with reduced goblet cell density and increased levels of Notch expression. Strategies to block this pathway might be developed to prevent EAC in patients with BE.
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http://dx.doi.org/10.1053/j.gastro.2020.04.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484392PMC
August 2020

Gastroesophageal Reflux Disease: Changing the Conversation.

Gastrointest Endosc Clin N Am 2020 Apr 17;30(2):xi-xii. Epub 2020 Feb 17.

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2020.02.001DOI Listing
April 2020

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

Gastrointest Endosc 2020 07 15;92(1):31-39.e1. Epub 2020 Jan 15.

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

Background And Aims: The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival.

Methods: Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival.

Results: One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival.

Conclusions: In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.
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http://dx.doi.org/10.1016/j.gie.2020.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321863PMC
July 2020

Closure Power: Advances in Endoscopic Clipping and Sewing.

Gastrointest Endosc Clin N Am 2020 Jan 25;30(1):xiii-xiv. Epub 2019 Oct 25.

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2019.10.002DOI Listing
January 2020

Alterations to the Esophageal Microbiome Associated with Progression from Barrett's Esophagus to Esophageal Adenocarcinoma.

Cancer Epidemiol Biomarkers Prev 2019 10 29;28(10):1687-1693. Epub 2019 Aug 29.

Department of Medicine, Columbia University Irving Medical Center, New York, New York.

Background: The incidence of esophageal adenocarcinoma has risen dramatically over the past half century, and the underlying reasons are incompletely understood. Broad shifts to the upper gastrointestinal microbiome may be partly responsible. The goal of this study was to describe alterations in the esophageal microbiome that occur with progression from Barrett's esophagus to esophageal adenocarcinoma.

Methods: A case-control study was performed of patients with and without Barrett's esophagus who were scheduled to undergo upper endoscopy. Demographic, clinical, and dietary intake data were collected, and esophageal brushings were collected during the endoscopy. 16S rRNA gene sequencing was performed to characterize the microbiome.

Results: A total of 45 patients were enrolled and included in the analyses [16 controls; 14 Barrett's esophagus without dysplasia (NDBE); 6 low-grade dysplasia (LGD); 5 high-grade dysplasia (HGD); and 4 esophageal adenocarcinoma]. There was no difference in alpha diversity between non-Barrett's esophagus and Barrett's esophagus, but there was evidence of decreased diversity in patients with esophageal adenocarcinoma as assessed by Simpson index. There was an apparent shift in composition at the transition from LGD to HGD, and patients with HGD and esophageal adenocarcinoma had decreased Firmicutes and increased Proteobacteria. In addition, patients with HGD or esophageal adenocarcinoma had increased and and reduced . In the study population, patients taking proton pump inhibitors had increased and decreased Gram-negative bacteria overall.

Conclusions: Shifts in the Barrett's esophagus-associated microbiome were observed in patients with HGD and esophageal adenocarcinoma, with increases in certain potentially pathogenic bacteria.

Impact: The microbiome may play a role in esophageal carcinogenesis.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774849PMC
October 2019

Colonoscopic Polypectomy: Improved and New Methods.

Gastrointest Endosc Clin N Am 2019 Oct 5;29(4):xiii-xiv. Epub 2019 Jul 5.

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2019.06.008DOI Listing
October 2019

How I do a diagnostic EUS.

Gastrointest Endosc 2019 10 15;90(4):543-545. Epub 2019 Jul 15.

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

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http://dx.doi.org/10.1016/j.gie.2019.04.235DOI Listing
October 2019

How I do a diagnostic EUS.

Endoscopy 2019 10 15;51(10):973-975. Epub 2019 Jul 15.

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

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http://dx.doi.org/10.1055/a-0959-1513DOI Listing
October 2019

Use of the Electronic Health Record to Target Patients for Non-endoscopic Barrett's Esophagus Screening.

Dig Dis Sci 2019 Dec 4;64(12):3463-3470. Epub 2019 Jul 4.

Division of Digestive and Liver Diseases, Columbia University Medical Center, 630 W 168th Street, P&S 3-401, New York, NY, 10032, USA.

Background: Clinical prediction models targeting patients for Barrett's esophagus (BE) screening include data obtained by interview, questionnaire, and body measurements. A tool based on electronic health records (EHR) data could reduce cost and enhance usability, particularly if combined with non-endoscopic BE screening methods.

Aims: To determine whether EHR-based data can identify BE patients.

Methods: We performed a retrospective review of patients ages 50-75 who underwent a first-time esophagogastroduodenoscopy. Data extracted from the EHR included demographics and BE risk factors. Endoscopy and pathology reports were reviewed for histologically confirmed BE. Screening criteria modified from clinical guidelines were assessed for association with BE. Subsequently, a score based on multivariate logistic regression was developed and assessed for its ability to identify BE subjects.

Results: A total of 2931 patients were assessed, and BE was found in 1.9%. Subjects who met screening criteria were more likely to have BE (3.3% vs. 1.1%, p = 0.001), and the criteria predicted BE with an AUROC of 0.65 (95% CI 0.59-0.71). A score based on logistic regression modeling included gastroesophageal reflux disease, sex, body mass index, and ever-smoker status and identified BE subjects with an AUROC of 0.71 (95% CI 0.64-0.77). Both prediction tools produced higher AUROCs in women than in men.

Conclusions: EHR-based BE risk prediction tools identify BE patients with fair accuracy. While these tools may improve the efficiency of patient targeting for BE screening in the primary care setting, challenges remain to identify high-risk patients for non-invasive BE screening in clinical practice.
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http://dx.doi.org/10.1007/s10620-019-05707-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191846PMC
December 2019

Management of Inflammatory Bowel Disease: Progress and Promise.

Gastrointest Endosc Clin N Am 2019 Jul;29(3):xiii-xiv

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2019.03.003DOI Listing
July 2019

High-resolution genomic alterations in Barrett's metaplasia of patients who progress to esophageal dysplasia and adenocarcinoma.

Int J Cancer 2019 11 2;145(10):2754-2766. Epub 2019 May 2.

Department of Pathology and Cell Biology, Columbia University Irving Medical Center (CUIMC), New York, NY.

The main risk factor for esophageal dysplasia and adenocarcinoma (DAC) is Barrett's esophagus (BE), characterized by intestinal metaplasia. The critical genomic mechanisms that lead to progression of nondysplastic BE to DAC remain poorly understood and require analyses of longitudinal patient cohorts and high-resolution assays. We tested BE tissues from 74 patients, including 42 nonprogressors from two separate groups of 21 patients each and 32 progressors (16 in a longitudinal cohort before DAC/preprogression-BE and 16 with temporally concurrent but spatially separate DAC/concurrent-BE). We interrogated genome-wide somatic copy number alterations (SCNAs) at the exon level with high-resolution SNP arrays in DNA from formalin-fixed samples histologically confirmed as nondysplastic BE. The most frequent abnormalities were SCNAs involving FHIT exon 5, CDKN2A/B or both in 88% longitudinal BE progressors to DAC vs. 24% in both nonprogressor groups (p = 0.0004). Deletions in other genomic regions were found in 56% of preprogression-BE but only in one nonprogressor-BE (p = 0.0004). SCNAs involving FHIT exon 5 and CDKN2A/B were also frequently detected in BE temporally concurrent with DAC. TP53 losses were detected in concurrent-BE but not earlier in preprogression-BE tissues of patients who developed DAC. CDKN2A/p16 immunohistochemistry showed significant loss of expression in BE of progressors vs. nonprogressors, supporting the genomic data. Our data suggest a role for CDKN2A/B and FHIT in early progression of BE to dysplasia and adenocarcinoma that warrants future mechanistic research. Alterations in CDKN2A/B and FHIT by high-resolution assays may serve as biomarkers of increased risk of progression to DAC when detected in BE tissues.
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http://dx.doi.org/10.1002/ijc.32351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6750991PMC
November 2019

Shorter time to achieve endoscopic eradication is not associated with improved long-term outcomes in Barrett's esophagus.

Dis Esophagus 2019 Aug;32(8)

Department of Medicine, Columbia University Medical Center, New York, USA.

Quality indicators have been proposed for endoscopic eradication therapy of Barrett's esophagus (BE). One such measure suggests that complete eradication of intestinal metaplasia (CE-IM) should be achieved within 18 months of starting treatment. The aim of this study was to assess whether achievement of CE-IM within 18 months is associated with improved long-term clinical outcomes. This was a retrospective cohort study of BE patients who underwent endoscopic eradication. Time to CE-IM was recorded and categorized as ≤ or > 18 months. The main outcome measures were recurrence of IM and of dysplasia after CE-IM, defined as a single endoscopy without endoscopic evidence of BE or histologic evidence of intestinal metaplasia. Recurrence was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards modeling. A total of 290 patients were included in the analyses. The baseline histology was high-grade dysplasia or intramucosal carcinoma in 74.2% of patients. CE-IM was achieved in 85.5% of patients, and 54.1% of the cohort achieved CE-IM within 18 months. Achieving CE-IM within 18 months was not associated with reduced risk of recurrence of IM or dysplasia in both unadjusted and adjusted analyses. In this cohort, older age and increased BE length were associated with IM recurrence, and increased hiatal hernia size was associated with dysplasia recurrence. Compared to longer times, achieving CE-IM within 18 months was not associated with a reduced risk of recurrence of IM or dysplasia. Alternative evidence-based quality metrics for endoscopic eradication therapy should be identified.
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http://dx.doi.org/10.1093/dote/doz026DOI Listing
August 2019

The Endoscopic Hepatologist: Not an Oxymoron.

Gastrointest Endosc Clin N Am 2019 04;29(2):xiii-xiv

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2019.02.002DOI Listing
April 2019

Cystic fibrosis is associated with an increased risk of Barrett's esophagus.

J Cyst Fibros 2019 05 23;18(3):425-429. Epub 2018 Nov 23.

Division of Digestive & Liver Diseases, Columbia University Medical Center, New York, NY, USA.

Background: Cystic fibrosis (CF) patients have increased risks of gastrointestinal cancers, including esophageal adenocarcinoma. Gastroesophageal reflux disease (GERD) is highly prevalent in CF and manifests at early ages. CF patients may be at increased risk for long-term sequelae of chronic GERD, including Barrett's esophagus (BE). We aimed to assess whether patients with CF have an increased risk of BE or related neoplasia.

Methods: A matched cohort study was performed of adults with and without CF who had undergone upper endoscopy. Non-CF patients were matched in a 4:1 ratio by age, sex, year of exam, and endoscopist. Odds ratios were calculated for the association between CF and BE or related neoplasia, and multivariable logistic regression modeling was performed to adjust for matching variables and additional potential confounders.

Results: 122 CF patients underwent endoscopy, and 488 matched controls were identified. Seven (5.7%) CF patients had BE or related neoplasia, including one GE junction adenocarcinoma. Mean age of affected CF patients was 36.0, and 85.7% had a prior solid organ transplant. The odds of BE was significantly increased in CF patients (OR 2.91, 95% CI 1.08-7.81). The risk remained significantly increased in a multivariable model including matching variables (OR 3.32, 95% CI 1.19-9.22) and in a parsimonious model (OR 2.99, 95% CI 1.06-8.42).

Conclusions: Adults with CF have a 3-fold increased risk of BE or related neoplasia and appears to develop at younger ages. Consideration should be given to screening for BE in select CF patients, especially those who have undergone solid organ transplantation.
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http://dx.doi.org/10.1016/j.jcf.2018.11.005DOI Listing
May 2019

Gastroparesis: New Approaches in Management.

Gastrointest Endosc Clin N Am 2019 01;29(1):xiii-xiv

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2018.09.002DOI Listing
January 2019

Increasing Dietary Fiber Intake Is Associated with a Distinct Esophageal Microbiome.

Clin Transl Gastroenterol 2018 10 25;9(10):199. Epub 2018 Oct 25.

Department of Medicine, Columbia University Medical Center, New York, NY, USA.

Introduction: There is increasing evidence that the microbiome contributes to esophageal disease. Diet, especially fiber and fat intake, is a known potent modifier of the colonic microbiome, but its impact on the esophageal microbiome is not well described. We hypothesized that dietary fiber and fat intake would be associated with a distinct esophageal microbiome.

Methods: We collected esophageal samples from 47 ambulatory patients scheduled to undergo endoscopy who completed a validated food frequency questionnaire quantifying dietary fiber and fat intake. Using 16S high-throughput sequencing, we determined composition of the esophageal microbiome and predicted functional capacity of microbiota based on fiber and fat intake.

Results: Among all samples, the most abundant phyla were Firmicutes (54.0%), Proteobacteria (19.0%), Bacteroidetes (17.0%), Actinobacteria (5.2%), and Fusobacteria (4.3%). Increasing fiber intake was significantly associated with increasing relative abundance of Firmicutes (p = 0.04) and decreasing relative abundance of Gram-negative bacteria overall (p = 0.03). Low fiber intake was associated with increased relative abundance of several Gram-negative bacteria, including Prevotella, Neisseria, and Eikenella. Several predicted metabolic pathways differed between highest and lowest quartile of fiber intake. Fat intake was associated with altered relative abundance of few taxa, with no alterations at the phylum level and no changes in microbiome functional composition.

Conclusions: Dietary fiber, but not fat, intake was associated with a distinct esophageal microbiome. Diet should be considered an important modifier of the esophageal microbiome in future studies. Studies are also needed to elucidate how the effects of dietary fiber on the esophageal microbiome may contribute to esophageal disease.
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http://dx.doi.org/10.1038/s41424-018-0067-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200756PMC
October 2018

Management of Benign Pancreatic Diseases.

Gastrointest Endosc Clin N Am 2018 10;28(4):xiii-xiv

Department of Medicine, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA. Electronic address:

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http://dx.doi.org/10.1016/j.giec.2018.08.001DOI Listing
October 2018

WATS for Barrett's surveillance.

Gastrointest Endosc 2018 07;88(1):201-202

Gastroenterology, Columbia University School of Medicine, New York, New York, USA.

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http://dx.doi.org/10.1016/j.gie.2018.01.038DOI Listing
July 2018

A simpler way to do radiofrequency ablation for Barrett's oesophagus.

Lancet Gastroenterol Hepatol 2018 08 20;3(8):525-526. Epub 2018 Jun 20.

Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, 10032 NY, USA. Electronic address:

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http://dx.doi.org/10.1016/S2468-1253(18)30174-2DOI Listing
August 2018