Barrett's Dysplasia Research Articles

Barrett's esophagus: best practices for treatment and post-treatment surveillance.

Barrett's esophagus (BE) is a premalignant condition that increases the risk of esophageal adenocarcinoma (EAC). Significantly more common in the Western world, risk factors include increased age, male sex, white race, gastro-esophageal reflux disease (GERD), central obesity, and cigarette smoking. The rates of progression to cancer depend on the grade of Barrett's dysplasia. Screening for BE is recommended in patients with GERD and additional risk factors. Endoscopic surveillance of patients with BE likely improves overall outcomes. Advanced endoscopic imaging can help increase the efficiency of current endoscopic surveillance. Endoscopic therapy is safe and effective for the treatment of dysplastic BE and intramucosal EAC, but ongoing surveillance following treatment is necessary. This review will cover screening, surveillance, advanced imaging, chemoprevention, endoscopic treatment, and post-treatment surveillance of BE.

TGR5 expression in benign, preneoplastic and neoplastic lesions of Barrett's esophagus: Case series and findings.

AIMTo examined the bile acid receptor TGR5 expression in squamous mucosa, Barrett’s mucosa, dysplasia and esophageal adenocarcinoma (EA).METHODSSlides were stained with TGR5 antibody. The staining intensity was scored as 1+, 2+ and 3+. The extent of staining (percentage of cells staining) was scored as follows: 1+, 1%-10%, 2+, 11%-50%, 3+, 51%-100%. A combined score of intensity and extent was calculated and categorized as negative, weak, moderate and strong staining. TGR5 mRNA was measured by real time PCR.RESULTSWe found that levels of TGR5 mRNA were significantly increased in Barrett’s dysplastic cell line CP-D and EA cell line SK-GT-4, when compared with Barrett’s cell line CP-A. Moderate to strong TGR5 staining was significantly higher in high-grade dysplasia and EA cases than in Barrett’s esophagus (BE) or in low-grade dysplasia. Moderate to strong staining was slightly higher in low-grade dysplasia than in BE mucosa, but there is no statistical significance. TGR5 staining had no significant difference between high-grade dysplasia and EA. In addition, TGR5 staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis.CONCLUSIONWe conclude that TGR5 immunostaining was much stronger in high-grade dysplasia and EA than in BE mucosa or low-grade dysplasia and that its staining intensity was not associated with the clinical stage, the pathological stage and the status of lymph node metastasis. TGR5 might be a potential marker for the progression from BE to high-grade dysplasia and EA.

Role of endoscopy in early oesophageal cancer.

Incidence of oesophageal adenocarcinoma has increased exponentially in the West over the past few decades. Following detection of advanced cancers, 5-year survival rates remain bleak, making identification of early neoplasia, which has a better outcome, important. Detection of subtle oesophageal lesions during endoscopy can be challenging, and advanced imaging techniques might improve their detection. High-definition endoscopy has become a standard in most endoscopy centres, and this technology probably provides better delineation of mucosal features than standard-definition endoscopy. Various image enhancement techniques are now available with the development of new electronics and software systems. Image enhancement with chromoendoscopy using dyes has been a cost-effective option for many years, yet these techniques have been replaced in some contexts by electronic chromoendoscopy, which can be used with the press of a button. However, Lugol's chromoendoscopy remains the gold standard to identify squamous dysplasia. Identification and characterization of subtle neoplastic lesions could help to target biopsies and perform endoscopic resection for better local staging and definitive therapy. In vivo histology with techniques such as confocal endomicroscopy could make endotherapy feasible within a shorter timescale than when relying on histology on tissue samples. Once early neoplasia is identified, treatments include endoscopic resection, endoscopic submucosal dissection or various ablative techniques. Endotherapy has the advantage of being a less invasive technique than oesophagectomy, and is associated with lower mortality and morbidity. Endoscopic ablation therapies have evolved over the past few years, with radiofrequency ablation showing the best results in terms of success rates and complications in Barrett dysplasia.

PGI20 - Cost-Effectiveness of Endoscopic Treatment with Radiofrequency Ablation for Patients with Barrett's Esophagus and High Or Low Grade Dysplasia in Spain

PGI20 - Cost-Effectiveness of Endoscopic Treatment with Radiofrequency Ablation for Patients with Barrett's Esophagus and High Or Low Grade Dysplasia in Spain

Oesophageal biopsies are insufficient to predict final histology after endoscopic resection in early Barrett's neoplasia.

Endoscopic resection (ER) with or without ablation is the first choice treatment for early Barrett's neoplasia. Adequate staging is important to assure a good oncological outcome. The purpose of this study was to investigate the diagnostic accuracy of pre-operative biopsies in patients who undergo ER for high-grade dysplasia (HGD) or early adenocarcinoma (EAC) in Barrett's oesophagus (BE) and the cardia. Between November 2005-May 2012, 142 ERs performed in 137 patients were obtained. Worst pre-ER and ER histology were compared. Upgrading/downgrading was defined as any more/less severe histological grading on the ER specimen. The accuracy of pre-ER biopsies in predicting final histology was 61%. ER changed the pre-treatment diagnosis in 55 of the 142 procedures (39%) with downgrading in 23 cases (16%) and upgrading from HGD to T1a or T1b in 32 cases (23%). In the majority of upgraded cases, a visible lesion according to the Paris classification could be detected (26/32, 81%). The diagnostic accuracy of oesophageal biopsies alone in predicting final pathology in Barrett's dysplasia is only 61%. The majority of upgraded lesions are detectable. When ablative therapy is considered in HGD Barrett's dysplasia a meticulous inspection for and removal of all small visible lesions is mandatory.

Enfermedades esofágicas: enfermedad por reflujo gastroesofágico, Barrett, acalasia y esofagitis eosinofílica

The most interesting conclusions and/or advances presented at Digestive Disease Week 2016 were the following: a) gastroesophageal reflux disease: proton pump inhibitor-refractory reflux disease is frequently associated with poor treatment adherence, psychiatric comorbidities and functional gastrointestinal disorders. These possible entities should be investigated in all cases of proton pump inhibitor-refractory reflux disease; b) Barrett's oesophagus: the efficacy of screening remains unclear; however, new minimally-invasive techniques such as the cytosponge allow more effective detection, both of Barrett's oesophagus and Barrett's oesophagus-associated dysplasia or neoplasia; c) achalasia: evidence indicates that peroral endoscopic myotomy is as effective as surgery and is a safer alternative; d) eosinophilic oesophagitis: high-dose proton pump inhibitors are required to rule out proton pump inhibitor-responsive eosinophilic oesophagitis; montelukast is not clearly effective in the treatment of eosinophilic oesophagitis, although moderate efficacy cannot be ruled out.

Complex Esophageal Reconstruction Procedures Have Acceptable Outcomes Compared With Routine Esophagectomy

Complex esophageal reconstruction (CER) is defined as restoring esophageal continuity in a previously operated field, using a nongastric conduit, or after esophageal diversion. This study compares the outcomes of CER with non-CER (NCER), which uses an undisturbed stomach for reconstruction. This single-institution retrospective cohort study compares 75 CERs with 75 NCERs from 1995 to 2014 that were matched for cancer versus benign disease. Distributions of demographic characteristics, comorbidities, and complications were compared between CER and NCER. Odds of mortality at 30 and 90 days were calculated with logistic regression. Overall survival was illustrated with Kaplan-Meier method and Cox proportional hazards regression. Although patients were similar in age, sex, and preoperative comorbidities, more non-white patients underwent CER (p= 0.04). Most NCER patients had adenocarcinoma (44%) or Barrett's high-grade dysplasia (39%); most CER patients had other benign disease (44%) or squamous cell carcinoma (24%, p < 0.01). CER had statistically significantly higher rates of reoperation, pneumonia, infection, and gastrointestinal complications, and longer median length of stay than NCER. Odds of mortality for CER and NCER at 30 days (odds ratio [OR] 1.0, 95% CI: 0.1 to 16.3), 90 days (OR 2.6, 95% CI: 0.5 to 13.9) and overall (adjusted hazard ratio 1.56, 95% CI: 0.9 to 2.7) were not statistically significantly different. Compared with NCER, CER patients had higher rates of return to the operating room, more postoperative infections and gastrointestinal complications, and longer length of stay. However, 30-day, 90-day, and overall survival were similar. CER should be offered to patients with acceptable risks and anticipated long-term survival.

Tu1139 Volumetric Laser Endomicroscopy Improves Detection of Persistent or Recurrent Barrett's Esophagus, Dysplasia and Neoplasia Following Endoscopic Treatment

Tu1139 Volumetric Laser Endomicroscopy Improves Detection of Persistent or Recurrent Barrett's Esophagus, Dysplasia and Neoplasia Following Endoscopic Treatment

Tu1169 Safety and Efficacy of Endoscopic Mucosal Resection Before RFA for Barrett's Dysplasia: Meta-Analysis

Tu1169 Safety and Efficacy of Endoscopic Mucosal Resection Before RFA for Barrett's Dysplasia: Meta-Analysis

57 Significant Reduction in the Disease Progression in Barrett's Esophagus Low-Grade Dysplasia Patients Treated With Endoscopic Eradiation Therapy Compared With Surveillance Endoscopy: A Systematic Review and Meta-Analysis

57 Significant Reduction in the Disease Progression in Barrett's Esophagus Low-Grade Dysplasia Patients Treated With Endoscopic Eradiation Therapy Compared With Surveillance Endoscopy: A Systematic Review and Meta-Analysis

59 Long-Term Durability of Liquid Nitrogen Spray Cryotherapy in Barrett's Esophagus-Associated High Grade Dysplasia: 5-Year Follow Up

59 Long-Term Durability of Liquid Nitrogen Spray Cryotherapy in Barrett's Esophagus-Associated High Grade Dysplasia: 5-Year Follow Up

Combining endoscopic submucosal dissection and endoscopic mucosal resection to treat neoplasia in Barrett's esophagus.

Piecemeal endoscopic mucosal resection (EMR) is the standard treatment of nodular Barrett's esophagus dysplasia and T1a cancer. Piecemeal resection may be incomplete and makes precise histologic assessment difficult. Endoscopic submucosal dissection (ESD) is a technique that enables en-bloc resection but has not gained widespread acceptance due to its technical difficulty, risk and long procedure time. We developed a protocol consisting of a combination of a limited ESD with supplementary EMR in the same session if necessary, designed to increase en-bloc resection of the most worrisome neoplastic area while maximizing the rate of complete resection of dysplasia. Records of consecutive patients referred for treatment during a 2-year period were reviewed. Eleven patients were treated: two with ESD and nine with combined ESD/EMR. Eight patients had mucosal lesions; three patients had submucosally invasive cancer and were referred to surgery. Five of the 8 mucosal lesions were removed en-bloc by ESD with dysplasia-free margins. Two patients with T1a cancer had low-grade dysplasia in the ESD margins and removal of all dysplasia on EMR. One patient with T1a cancer had high-grade dysplasia in the ESD margins and on EMR. He required a second endoscopy to remove residual neoplasia. There were no adverse events. The mean procedure time was 66.4±15.1min. Combining a limited ESD with EMR in the same session enables efficient treatment of visible dysplastic lesions in Barrett's esophagus.

Safety and efficacy of endoscopic spray cryotherapy for Barrett's dysplasia: results of the National Cryospray Registry.

Retrospective series have shown the efficacy of endoscopic spray cryotherapy in eradicating high-grade dysplasia (HGD) in Barrett's esophagus (BE); however, prospective data are lacking, and efficacy for low-grade dysplasia (LGD) is unclear. The aim of this study was to assess the efficacy and safety of spray cryotherapy in patients with LGD or HGD. A multicenter, prospective open-label registry enrolled patients with dysplastic BE. Spray cryotherapy was performed every 2-3 months until there was no endoscopic evidence of BE and no histological evidence of dysplasia, followed by surveillance endoscopies up to 2 years. Primary outcome measures were complete eradication of dysplasia (CE-D) and complete eradication of all intestinal metaplasia (CE-IM). Ninety-six subjects with Barrett's dysplasia (67% HGD; 65% long-segment BE; mean length 4.5 cm) underwent 321 treatments (mean 3.3 per subject). Mean age was 67 years, 83% were male. Eighty patients (83%) completed treatment with follow-up endoscopy (mean duration 21 months). In patients with LGD, rate of CE-D was 91% (21/23) and rate of CE-IM was 61% (14/23). In HGD, CE-D rate was 81% (46/57) and CE-IM was 65% (37/57). In patients with short-segment BE (SSBE) with any dysplasia, CE-D was achieved in 97% (30/31) and CE-IM in 77% (24/31). There were no esophageal perforations or related deaths. One subject developed a stricture, which did not require dilation. One patient was hospitalized for bleeding in the setting of non-steroidal anti-inflammatory drug use. In the largest prospective cohort to date, data suggest endoscopic spray cryotherapy is a safe and effective modality for eradication of BE with LGD or HGD, particularly with SSBE.

Sa1251 Volumetric Laser Endomicroscopy Increases Detection of Persistent or Recurrent Barrett's Esophagus and Dysplasia in the Absence of Findings on White Light Endoscopy

Sa1251 Volumetric Laser Endomicroscopy Increases Detection of Persistent or Recurrent Barrett's Esophagus and Dysplasia in the Absence of Findings on White Light Endoscopy

Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett's esophagus, dysplasia and adenocarcinoma

BackgroundToll-like receptors (TLRs) recognize microbial and endogenous ligands and have already shown to play a role in esophageal cancer. In this study, we evaluated especially TLRs that sense bacterial cell wall components in Barrett's esophagus, dysplasia and esophageal adenocarcinoma.MethodsTLRs 1, 2, 4 and 6 were stained immunohistochemically and assessed in esophageal specimens from patients with esophageal dysplasia (n = 30) or adenocarcinoma (n = 99). Structures and lesions were evaluated including normal esophagus (n = 88), gastric (n = 67) or intestinal metaplasia (n = 51) without dysplasia, and low-grade (n = 42) or high-grade dysplasia (n = 37), and esophageal adenocarcinoma (n = 99).ResultsWe found TLR1, TLR2, TLR4 and TLR6 expression in all lesions. TLR expression increased in Barrett's mucosa and dysplasia. There was profound increase of TLR expression from gastric- to intestinal-type columnar epithelium. In cancers, high nuclear and cytoplasmic staining of TLR4 associated with metastatic disease and poor prognosis.ConclusionsTLR1, TLR2, TLR4 and TLR6 are upregulated during malignant changes of esophageal columnar epithelium. Increased TLR4 expression associates with advanced stage and poor prognosis in esophageal adenocarcinoma.

Functional outcome after Ivor Lewis esophagectomy for cancer.

Little is known on functional outcome after Ivor Lewis esophagectomy (ILE) with intrathoracic anastomosis. Patients who underwent ILE were identified from a prospective database. Clinicopathological data were retrieved and compared with functional outcome data based on patient self-assessment by a standard questionnaire. Predictive factors for selected functional complaints were identified with logistic regression analyses. Three hundred and twenty-two patients (80.4% male, mean age 62 years) were studied. Indications for surgery were adenocarcinoma (62.4%), squamous cell carcinoma (28%), and HG Barrett dysplasia (7%). Preoperative chemoradiation (CRT) was administered to 42.5% of patients. Anastomotic leakage occurred in 5.6% and was associated with higher age and diabetes mellitus. Functional symptoms identified were reflux (39%), delayed gastric emptying (37%), dumping (21.4%), and anastomotic stenosis (16%). In the multivariate models, anastomotic stenosis was associated with smaller stapler diameter and presence of esophagitis. Postoperative reflux was associated with higher BMI, whereas dumping was predicted by female gender and age. The quality of life questionnaires revealed a good general health status in 82% of the patients. Functional complaints after ILE consist of reflux, delayed gastric emptying, dumping, and dysphagia, and are affected by age, gender, BMI, diabetes mellitus, and stapler diameter.

Institutional Experience in Diagnostic Usability of Volumetric Laser Endo-Microscopy in Barrettʼs Esophagus

Introduction: Barrett's Esophagus (BE) is a well-known precursor lesion to Esophageal Adenocarcinoma. Random four-quadrant biopsies every 1-2 cm (the Seattle Biopsy Protocol) in addition to aggressive sampling of any mucosal abnormality has been recommended; however, there is controversy about the intense biopsy sampling protocol in detecting the incidental Barrett's dysplasia and cancer. Volumetric laser endomicroscopy (VLE) is a novel second-generation optical coherence tomography imaging procedure that elicits volumetric cross-sectional and longitudinal images over six cm of the esophagus with resolution less than ten microns Methods: A prospective enrollment of patients with known BE at our institution was conducted from September 2014-Febuary 2015. Patients were undergoing surveillance and/or therapeutic endoscopic procedures along with VLE. Patients of age 18 and above with history of BE were included. Based on VLE findings; lesions with high-risk features were identified and targeted biopsies were taken. Seattle protocol biopsies, which is the standard of care, were also taken in four quadrants every 1 cm for surveillance. Biopsies were evaluated by two-blinded pathologists. Results: Fifty-two patients with known BE were included in the analysis. There were no adverse events associated with the use of VLE. Mean age was 66 +/- 10 years with 71% males (n=37). Out of 52 patients, 41(79 %) underwent prior radio frequency ablations and/or endoscopic mucosal resections. Seattle protocol biopsies were performed in all 52 cases and additional targeted biopsies were performed in 46 cases as prompted by findings seen on VLE. Out of 52 cases, 21 were found to have BE on histopathology. VLE scans were abnormal in 19 out of 21 patients giving the sensitivity of 91% and NPV of 75%. One patient with BE had normal HD-WLE but abnormal features were detected on VLE scan. The two patients missed on VLE scanning had small foci of non-dysplastic BE at the gastro-esophageal junction and these were appreciated as small islands on HD-WLE. All the cases of BE were detected with combination HD-WLE and VLE. Conclusion: VLE is a reliable clinical modality which can be used for detection of BE. When used in conjunction with HD-WLE, the diagnostic yield is favorable and can decrease the miss rate of BE. Our study demonstrated excellent sensitivity and NPV. We believe there is a learning curve and further experience will only improve the diagnostic yield.

Comparison of endoscopic treatment modalities for Barrett’s neoplasia

There are few data comparing endoscopic treatment outcomes for Barrett's esophagus (BE). To compare treatment outcomes in BE patients treated with radiofrequency ablation (RFA), RFA after EMR, and porfimer sodium photodynamic therapy (Ps-PDT). Retrospective, observational study. Single tertiary center between 2001 and2013. A total of 342 BE patients treated with RFA (n= 119), EMR+RFA (n= 98), and Ps-PDT (n= 125). Rates of complete remission of intestinal metaplasia (CRIM), BE recurrence, and adverse events. Baseline BE high-grade dysplasia (HGD) and adenocarcinoma were more common in the Ps-PDT group (89%) compared with the EMR-RFA (70%) and RFA (37%) groups. At a median follow-up of 14.2 months, 173 patients (50.6%) achieved CRIM. CRIM was significantly more common in Ps-PDT patients compared with RFA (P< .001) and EMR-RFA (P< .001) patients on multivariable analysis. In patients who achieved CRIM, the rates of subsequent BE recurrence were relatively similar among the 3 groups. Although the rates of bleeding were similar, strictures were less common in RFA patients (2.4%) compared with EMR-RFA (13.3%, P= .001) and Ps-PDT (10.4%, P=.043) patients. This study of endoscopic treatment for Barrett's dysplasia and neoplasia found that complete remission was achieved more often and more rapidly after Ps-PDT with similar disease recurrence rates compared with EMR or RFA. Adverse events were more common after EMR and Ps-PDT. Further studies are required to determine which ablation and resection techniques are ideally suited for each BE patient.

Overdiagnosis of high-grade dysplasia in Barrett's esophagus: a multicenter, international study

Numerous histological mimics of high-grade dysplasia in Barrett's esophagus predispose to overdiagnosis and potential serious mismanagement, including unnecessary esophagectomy. This study investigates the prevalence and sources of this problem. Biopsies from 485 patients diagnosed with Barrett's high-grade dysplasia were screened for a multi-institutional, international Barrett's endoscopic ablation trial. Screening included review of the original diagnostic slides and an additional protocol endoscopy with an extensive biopsy sampling. Observer variability by the study pathologists was assessed through two blinded diagnostic rounds on 437 biopsies from 26 random study endoscopies. Study diagnostic reassessments revealed significantly lower rates of high-grade dysplasia. Only 248 patients (51%) were confirmed to have high-grade dysplasia. The remaining patients had inflamed gastric cardia without Barrett's (n=18; 7%), Barrett's without dysplasia (n=35; 15%), indefinite change (n=61; 26%), low-grade dysplasia (n=79; 33%), adenocarcinoma (n=43; 18%), and other (n=1; <1%), yielding an alarming total of 194 or 40% of patients who were overdiagnosed with Barrett's high-grade dysplasia. Study pathologists achieved a high-level agreement (90% three-way inter-observer agreement per biopsy, Kappa value 0.77) for high-grade dysplasia. Confounding factors promoting overdiagnosis included Barrett's inflammatory atypia (n=182), atypia limited to the basal metaplastic glands (n=147), imprecise criteria for low grade neoplasia (n=102), tangential sectioning artifact (n=59), and reactive gastric cardiac mucosa (n=38). A total of 194 patients (40%) were overdiagnosed with Barrett's high-grade dysplasia, as affirmed by the extensive screening process and high-level study pathologist agreement. The multiple diagnostic pitfalls uncovered should help raise pathologists' awareness of this problem and improve diagnostic accuracy.

Tu1561 Oral Corticosteroids May Decrease Esophageal Stricturing Associated With Extensive Mucosal Resection for Barrett's Dysplasia

Endoscopic mucosal resection (EMR) for the treatment of Barrett's esophagus (BE) dysplasia, has been associated with esophageal stricturing (up to 40%), especially when the resections are extensive. The dilations required as treatment are time-consuming, expensive and not risk-free. Additionally, the associated scarring, may limit future endoscopic treatments. Recent data from circumferential endoscopic submucosal dissection for esophageal squamous carcinoma, suggest a stricture-prevention role of oral steroids in this context.