Search

The incidence of esophageal adenocarcinoma (EA) has drastically increased in the United States since 1970s for unclear reasons. We hypothesized that the widespread usage of antibiotics has increased the procarcinogenic potential of the orodigestive microbiota along the sequence of gastroesophageal reflux (GR), Barrett's esophagus (BE) and EA phenotypes. This case control study included normal controls (NC) and three disease phenotypes GR, BE and EA. Microbiota in the mouth, esophagus, and stomach, and rectum were analyzed using 16S rRNA gene sequencing. Overall, we discovered 44 significant pairwise differences in abundance of microbial taxa between the four phenotypes, with 12 differences in the mouth, 21 in the esophagus, two in the stomach, and nine in the rectum. Along the GR→BE→EA sequence, oral and esophageal microbiota were more diversified, the dominant genus Streptococcus was progressively depleted while six other genera Atopobium, Actinomyces, Veillonella, Ralstonia, Burkholderia and Lautropia progressively enriched. In NC, Streptococcus appeared to control populations of other genera in the foregut via numerous negative and positive connections, while in disease states, the rich network was markedly simplified. Inferred gene functional content showed a progressive enrichment through the stages of EA development in genes encoding antibiotic resistance, ligands of Toll-like and NOD-like receptors, nitrate-nitrite-nitric oxide pathway and acetaldehyde metabolism. The orodigestive microbiota is in a progressive dysbiotic state along the GR-BE-EA sequence. The increasing dysbiosis and antibiotic and procarcinogenic genes in the disease states warrants further study to define their roles in EA pathogenesis., (© 2022 UICC.)

Background & Aims: Endoscopic intervention or pharmacologic inhibition of cyclooxygenase might be used to prevent progression of Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC). We investigated whether patients with BE prefer endoscopic therapy or chemoprevention of EAC., Methods: Eighty-one subjects with nondysplastic BE were given a survey that described 2 scenarios. The survey explained that treatment A (ablation), endoscopy, reduced lifetime risk of EAC by 50%, with 5% risk for esophageal stricture, whereas treatment B (aspirin) reduced lifetime risk of EAC by 50% and the risk of heart attack by 30%, yet increased the risk for ulcer by 75%. Subjects indicated their willingness to undergo either treatment A and/or treatment B if endoscopic surveillance were required every 3-5 years, every 10 years, or were not required. Visual aids were included to represent risk and benefit percentages., Results: When surveillance was required every 3-5 years, more subjects were willing to undergo treatment A than treatment B (78%, 63 of 81 vs 53%, 43 of 81; P < .01). There were no differences in age, sex, education level, or history of cancer, heart disease, or ulcer between patients willing to undergo treatment A and those willing to undergo treatment B. Altering the frequency of surveillance did not affect patients' willingness to undergo either treatment., Conclusions: In a simulated scenario, patients with BE preferred endoscopic intervention over chemoprevention for EAC. Further investigation of the shared decision-making process regarding preventive strategies for patients with BE may be warranted., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Endoscopic therapy has emerged as an alternative to surgical esophagectomy for the management of Barrett's esophagus (BE)-associated neoplasia. Accurate pretreatment staging is essential to ensure an appropriate choice of therapy and optimal long-term outcomes. This study aimed to assess the frequency with which expert histopathologic review of biopsies combined with endoscopic mucosal resection (EMR) would alter the pretreatment diagnosis of BE-associated neoplasia., Methods: Patients referred to the Vanderbilt Barrett's Esophagus Endoscopic Treatment Program (V-BEET) were retrospectively identified. Demographic, histopathologic, and endoscopic data were extracted from the medical record., Results: For this study, 29 subjects referred for endoscopic staging of BE fulfilled the entry criteria. The referral diagnosis was low-grade dysplasia (LGD) in 3 % (1/29), high-grade dysplasia (HGD) in 62 % (18/29), intramucosal adenocarcinoma (T1a) adenocarcinoma in 17 % (5/29), and invasive adenocarcinoma in 17 % (5/29) of the subjects. Expert histopathologic review of available referral biopsy specimens altered the diagnosis in 33 % (5/15) of the cases. Further diagnostic staging with EMR showed BE without dysplasia in 10 % (3/29), LGD in 14 % (4/29), HGD in 34 % (10/29), T1a adenocarcinoma in 28 % (8/29), and invasive adenocarcinoma in 14 % (4/29) of the patients. The combination of expert histopathologic review and EMR altered the initial diagnosis for 55 % (16/29) of the subjects, with 56 % (9/16) upstaged to more advanced disease and 44 % (7/16) downstaged to less advanced disease., Conclusions: The practice of combined expert histopathologic review and EMR alters the pretreatment diagnosis for the majority of patients with BE-associated neoplasia. Caution is advised for those embarking on endoscopic or surgical treatment for BE-associated neoplasia in the absence of these staging methods.

Background: Accurate endoscopic detection and staging are critical for appropriate management of Barrett's esophagus (BE)-associated neoplasia. Prior investigation has demonstrated that the distribution of endoscopically detectable early neoplasia is not uniform but instead favors specific directional distributions within a short BE segment; however, it is unknown whether the directional distribution of neoplasia differs with increasing distance from the gastroesophageal junction, including in patients with long-segment BE., Objective: To identify whether directional distribution of BE-associated neoplasia is influenced by distance from the gastroesophageal junction., Design: Retrospective cohort study., Setting: Tertiary-care referral center., Patients: Patients with either short-segment or long-segment BE undergoing EMR., Intervention: EMR., Main Outcome Measurements: Directional distribution of BE-associated neoplasia stratified by distance from gastroesophageal junction., Results: EMR was performed on 60 lesions meeting study criteria during the specified time period. Pathology demonstrated low-grade dysplasia in 22% (13/60), high-grade dysplasia in 38% (23/60), intramucosal (T1a) adenocarcinoma in 23% (14/60), and invasive (≥ T1b) adenocarcinoma in 17% (10/60). Directional distribution of lesions was not uniform (P < .001), with 62% of lesions (37/60) located between the 1 o'clock and 5 o'clock positions. When circular statistics methodology was used, there was no difference in the directional distribution of neoplastic lesions located within 3 cm of the gastroesophageal junction compared with ≥ 3 cm from the gastroesophageal junction., Limitations: Single-center study may limit external validity., Conclusion: The directional distribution of neoplastic foci within a BE segment is not influenced by distance of the lesion from the gastroesophageal junction. Mucosa between the 1 o'clock and 5 o'clock locations merits careful attention and endoscopic inspection in individuals with both short-segment BE and long-segment BE., (Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Buried Barrett's, or subsquamous intestinal metaplasia (SSIM), is defined as the presence of metaplastic, columnar tissue beneath overlying squamous epithelium. Therefore, SSIM cannot be detected by endoscopic visual examination alone; it is detectable only by tissue biopsy. SSIM can develop in patients with Barrett's esophagus (BE) after chronic pharmacologic suppression of gastric acid; it has been identified before and after endoscopic ablative therapies in cohort studies. It is important to determine the malignant potential of SSIM and the effects of endoscopic therapy for BE on development of SSIM; answers to these questions could affect long-term endoscopic surveillance and ablation strategies for patients with BE., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Few options exist for patients with localized esophageal cancer ineligible for conventional therapies. Endoscopic spray cryotherapy with low-pressure liquid nitrogen has demonstrated efficacy in this setting in early studies., Objective: To assess the safety and efficacy of cryotherapy in esophageal carcinoma., Design: Multicenter, retrospective cohort study., Setting: Ten academic and community medical centers between 2006 and 2009., Patients: Subjects with esophageal carcinoma in whom conventional therapy failed and those who refused or were ineligible for conventional therapy., Interventions: Cryotherapy with follow-up biopsies. Treatment was complete when tumor eradication was confirmed by biopsy or when treatment was halted because of tumor progression, patient preference, or comorbid condition., Main Outcome Measurements: Complete eradication of luminal cancer and adverse events., Results: Seventy-nine subjects (median age 76 years, 81% male, 94% with adenocarcinoma) were treated. Tumor stage included T1-60, T2-16, and T3/4-3. Mean tumor length was 4.0 cm (range 1-15 cm). Previous treatment including endoscopic resection, photodynamic therapy, esophagectomy, chemotherapy, and radiation therapy failed in 53 subjects (67%). Forty-nine completed treatment. Complete response of intraluminal disease was seen in 31 of 49 subjects (61.2%), including 18 of 24 (75%) with mucosal cancer. Mean (standard deviation) length of follow-up after treatment was 10.6 (8.4) months overall and 11.5 (2.8) months for T1 disease. No serious adverse events were reported. Benign stricture developed in 10 (13%), with esophageal narrowing from previous endoscopic resection, radiotherapy, or photodynamic therapy noted in 9 of 10 subjects., Limitations: Retrospective study design, short follow-up., Conclusions: Spray cryotherapy is safe and well tolerated for esophageal cancer. Short-term results suggest that it is effective in those who could not receive conventional treatment, especially for those with mucosal cancer., (Copyright 2010 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background: Photodynamic therapy (PDT) has been used extensively for endoscopic ablation of Barrett's esophagus with high-grade dysplasia (HGD) or intramucosal carcinoma., Objective: To identify patient variables that influence the likelihood of response to PDT., Design: A retrospective cohort study., Setting: Tertiary-referral center., Patients: A total of 116 patients with Barrett's esophagus and with HGD, intramucosal carcinoma, or T1 cancer., Interventions: PDT with porfimer sodium., Main Outcome Measurements: (1) Ablation of HGD and/or intramucosal carcinoma and (2) eradication of all Barrett's epithelium., Results: Of the patients, 51% underwent treatment for HGD and 49% of patients had intramucosal carcinoma or T1 cancer. At 12-month follow-up, ablation of HGD and/or cancer was observed in 70% of patients, and ablation of all Barrett's epithelium was observed in 39%. In multivariate analysis, the pretreatment length of Barrett's esophagus was inversely correlated with successful ablation of all Barrett's epithelium. Patients with Barrett's esophagus length more than 3 cm were less likely to experience complete ablation compared with patients with Barrett's esophagus length 3 cm or less (odds ratio [OR] 0.15 [95% CI, 0.04-0.50]). Patients with intramucosal carcinoma were not significantly less likely to experience elimination of HGD and/or cancer (OR 0.77 [95% CI, 0.30-2.00]) or ablation of all Barrett's epithelium (OR 0.82 [95% CI, 0.32-2.07]) compared with patients with HGD alone., Limitations: Retrospective study, limited sample size without a control group for comparison., Conclusions: PDT of Barrett's esophagus with HGD, intramucosal carcinoma, or T1 cancer can result in ablation of dysplasia and/or eradication of all Barrett's epithelium. Factors associated with the likelihood of response include length of Barrett's esophagus. The presence of intramucosal carcinoma or T1 cancer was not associated with higher likelihood of treatment failure.

Background & Aims: Patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma are at risk of progression to invasive carcinoma. Both esophagectomy and endoscopic ablation are treatment options. The aim of this study was to identify predictors of surgical versus endoscopic therapy at a tertiary center., Methods: An institutional database identified patients with Barrett's esophagus between 2003 and 2007. Demographic data and International Classification of Diseases-9th revision codes for esophagectomy, endoscopic ablation, as well as selected medical comorbidities were retrieved. Individual endoscopy, surgical, and pathology reports were reviewed., Results: Among 2107 individuals with Barrett's esophagus, 79 underwent esophagectomy and 80 underwent endoscopic ablation. The mean age was 63.1 +/- 10.6 years in the surgical group and 69.7 +/- 9.4 years in the ablation group (P < .0001). Among high-grade dysplasia/intramucosal carcinoma patients, 9 of 76 (12%) first seen by a gastroenterologist underwent esophagectomy, whereas 18 of 21 (86%) first seen by a surgeon underwent esophagectomy. In a logistic regression model, factors associated independently with esophagectomy were as follows: patient age of 60 or younger (odds ratio [OR], 4.95; 95% confidence interval [CI], 1.65-14.9), cancer stage T1sm or greater (OR, 16.0; 95% CI, 5.60-45.6), and initial consultation performed by a surgeon (vs gastroenterologist) (OR, 35.1; 95% CI, 9.58-129)., Conclusions: Patient age and cancer stage predict treatment modality for Barrett's esophagus with neoplasia. Treatment choice is influenced further by whether the initial evaluation is performed by a gastroenterologist or a surgeon.

Objectives: Although evidence suggests that aspirin and celecoxib may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE), these drugs can also cause harmful side effects. Our aim was to determine and characterize preferences for these two drugs in patients with BE., Methods: Preferences data were collected from recruited BE patients using a customized questionnaire, which incorporated standard risk communication techniques. Summary profiles outlined the benefits and harms of celecoxib and aspirin presented anonymously. Both drugs were portrayed as reducing the risk of EAC and increasing the risk of GI events. However, celecoxib increased the risk of myocardial infarction (MI) while aspirin reduced the risk. Factors influencing patient acceptance of each drug were analyzed., Results: One hundred of 109 (92%) subjects completed the study. Under base case conditions, 15% stated that they would take celecoxib and 76% aspirin (P < 0.0001). Patients identified the greater risk of MI as the primary reason for their unwillingness to take celecoxib and the lower risk of EAC for aspirin. Even in scenarios in which the benefits of celecoxib were improved and the harms reduced, a majority continued to find it unacceptable., Conclusions: A majority of those surveyed stated that they would take aspirin but would not take celecoxib. Most patients are interested in EAC chemoprevention, but the amount of protection and the side effect profile of a drug determine its acceptability. These data can inform physicians regarding the tradeoffs patients are willing to consider for chemoprevention.

Background: Optical coherence tomography (OCT) is a cross-sectional, high-resolution imaging modality that has been shown to accurately differentiate esophageal specialized intestinal metaplasia (SIM) from gastric cardia at the squamocolumnar junction (SCJ) and diagnose high-grade dysplasia and intramucosal carcinoma in patients with SIM. The clinical utility of OCT has been limited, however, by its inability to acquire images over large areas., Objective: The aim of this study was to use recently developed high-speed OCT technology, termed optical frequency domain imaging (OFDI), and a new balloon-centering catheter (2.5 cm diameter) to demonstrate the feasibility of large area, comprehensive optical microscopy of the entire distal esophagus (approximately 6.0 cm) in patients., Design: A pilot feasibility study., Setting: Massachusetts General Hospital., Patients: Twelve patients undergoing routine EGD., Results: Comprehensive microscopy of the distal esophagus was successfully performed in 10 patients with the OFDI system and balloon catheter. There were no complications resulting from the imaging procedure. Volumetric data sets were acquired in less than 2 minutes. OFDI images at the SCJ showed a variety of microscopic features that were consistent with histopathologic findings, including squamous mucosa, cardia, SIM with and without dysplasia, and esophageal erosion., Limitations: Inability to obtain direct correlation of OFDI data and histopathologic diagnoses., Conclusions: Comprehensive volumetric microscopy of the human distal esophagus was successfully demonstrated with OFDI and a balloon-centering catheter, providing a wealth of detailed information about the structure of the esophageal wall. This technique will support future studies to compare OFDI image information with histopathologic diagnoses.