Low-grade Dysplasia In Barrett's Esophagus Research Articles

Treatment of Barrett's esophagus with low-grade dysplasia using Hibrid-APC

Introduction: Barrett's esophagus (BE) with low-grade dysplasia represents a risk of progression towards esophageal adenocarcinoma. Hybrid-APC turns out to be an effective, safe, easy to use and relatively low-cost technique to stop this progression. Aims: to describe the therapeutic response of Hybrid-APC in patients with low-grade dysplasia in Barrett's esophagus. Method: an observational, descriptive investigation of a series of cases was carried out at the National Center for Minimal Access Surgery between December 2018 and December 2020. Twenty patients with BE histologically classified with low-grade dysplasia were included. Ablation with Hybrid APC was applied, and endoscopy was performed three and six months after the end of the treatment. The therapeutic response was evaluated through histological remission and the presence of complications. The information was processed in the statistical program SPSS, version 21. Results: mean age 50.5 (range 27-81 years). 55% (11) are male. Eighty-five percent were asymptomatic and 90% had circumferential BE. 55% (11) required a HybridAPC session. With an average of 1.4 sessions, macroscopic and histological remission without dysplasia was achieved at three and six months in 90% (18/20) and 92.8% (13/14) of the patients respectively, without witnessing complications. Conclusions: endoscopic treatment with the Hybrid-APC has a good therapeutic response, with a good histological remission and without complications, in patients with low-grade dysplasia in BE.

Endoscopic therapy for confirmed low-grade dysplasia in Barrett's esophagus.

Barrett's esophagus (BE) is a premalignant condition characterized by replacement of the esophageal lining with metastatic columnar epithelium. To date, the management in case of confirmed low-grade dysplasia (LGD) remains controversial. In this article we summarize the available endoscopic options and their results in terms of efficacy and safety in the treatment of confirmed LGD in BE.

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

Clinical significance and management of Barrett's esophagus with epithelial changes indefinite for dysplasia.

Barrett's esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND.

Su1474 Safety and Efficacy of Endoscopic Spray Cryotherapy for Barrett's Dysplasia: Results of the National Cryospray Registry

Safety and Efficacy of Endoscopic Spray Cryotherapy for Barrett’s Dysplasia: Results of the National Cryospray Registry Shireen Ghorbani*, Franklin Tsai, Bruce D. Greenwald, Sunguk Jang, John A. Dumot, Matthew Mckinley, Nicholas J. Shaheen, Fadlallah Habr, Walter Coyle Division of Gastroenterology and Hepatology, Scripps Green Hospital, La Jolla, CA; Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD; Division of Gastroenterology, Cleveland Clinic, Cleveland, OH; Division of Gastroenterology, University Hospitals Case Medical Center, Cleveland, OH; Division of Gastroenterology, Prohealth Syosset Hospital, Lake Success, NY; Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC; Division of Gastroenterology, University Medicine Foundation, Providence, RI Background: Endoscopic spray cryotherapy has been shown to be efficacious in eradicating high-grade dysplasia (HGD) in Barrett esophagus (BE) in multiple retrospective series. However, large prospective series evaluating the safety and efficacy of cryotherapy for Barrett’s dysplasia, particularly low grade dysplasia (LGD), have been lacking. Methods: A multicenter, prospective open-label registry study including subjects with BE and HGD or LGD. Primary outcomes were complete eradication of dysplasia and complete eradication of all intestinal metaplasia. Results: One hundred thirty-four subjects (mean age 67 years, 86% male) with Barrett’s dysplasia (29% LGD, 71% HGD; 37% SSBE, 63% LSBE; mean length 4.2 cm) underwent 464 treatments (mean 3.5 sessions per subject). There were no esophageal perforations, reports of severe pain, or related deaths. Strictures developed in 3 subjects, 2 of which required dilation. One subject was hospitalized for post cryotherapy bleeding in the setting of NSAID use requiring endoscopic hemostasis clip placement. Thirty-four percent of subjects reported mild to moderate post procedure symptoms. For subjects with LGD (mean length 5 cm), 26 (67%) had completed all planned cryotherapy treatments (mean 2.6 sessions) and were included in the efficacy analysis. Twenty-three subjects (88%) had complete eradication of all dysplasia and 16 (62%) had complete eradication of all intestinal metaplasia. For subjects with HGD (mean length 3.9 cm), 82 (86%) had completed all planned cryotherapy treatments (mean 3.5 sessions) and were included in the efficacy analysis. Seventy-five subjects (91%) had complete eradication of HGD, 69 (84%) had complete eradication of all dysplasia and 56 (68%) had complete eradication of all intestinal metaplasia. Conclusions: In the largest prospective cohort to date, short-term data suggest that endoscopic spray cryotherapy is a safe and highly effective modality for eradication of Barrett’s with LGD or HGD.

Low-Grade Dysplasia in Barrett's Esophagus: Overdiagnosed and Underestimated

Published data on the natural history of low-grade dysplasia (LGD) in Barrett's esophagus (BE) are inconsistent and difficult to interpret. We investigated the natural history of LGD in a large community-based cohort of BE patients after reviewing the original histological diagnosis by an expert panel of pathologists. Histopathology reports of all patients diagnosed with LGD between 2000 and 2006 in six non-university hospitals were reviewed by two expert pathologists. This panel diagnosis was subsequently compared with the histological outcome during prospective endoscopic follow-up. A diagnosis of LGD was made in 147 patients. After pathology review, 85% of the patients were downstaged to non-dysplastic BE (NDBE) or to indefinite for dysplasia. In only 15% of the patients was the initial diagnosis LGD. Endoscopic follow-up was carried out in 83.6% of patients, with a mean follow-up of 51.1 months. For patients with a consensus diagnosis of LGD, the cumulative risk of progressing to high-grade dysplasia or carcinoma (HGD or Ca) was 85.0% in 109.1 months compared with 4.6% in 107.4 months for patients downstaged to NDBE (P<0.0001). The incidence rate of HGD or Ca was 13.4% per patient per year for patients in whom the diagnosis of LGD was confirmed. For patients downstaged to NDBE, the corresponding incidence rate was 0.49%. LGD in BE is an overdiagnosed and yet underestimated entity in general practice. Patients diagnosed with LGD should undergo an expert pathology review to purify this group. In case the diagnosis of LGD is confirmed, patients should undergo strict endoscopic follow-up or should be considered for endoscopic ablation therapy.

Anti-phosphorylated histone H3 expression in Barrett's esophagus, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

The high interobserver variability in grading dysplasia in Barrett's esophagus demands a biomarker that can be applied in routine surgical pathology practice. Immunohistochemistry for phosphorylated histone H3 is a reliable marker of identifying mitotic figures and has not been evaluated in Barrett's esophagus-associated neoplastic lesions. We retrospectively studied the expression of phosphorylated histone H3 in 88 endoscopic biopsy samples of Barrett's esophagus without dysplasia (n=19), indefinite for dysplasia (n=11), low-grade dysplasia (n=27), high-grade dysplasia (n=19), or adenocarcinoma (n=12) from a sample of 54 patients. The samples were included after consensus diagnosis of two gastrointestinal pathologists on the hematoxylin–eosin (HE)-stained sections. Anti-phosphorylated histone H3-labeled mitotic figures were counted per 10 consecutive high-power fields (HPFs) in three distinct regions: surface epithelium, upper 2/3, and lower 1/3 of the crypts. Anti-phosphorylated histone H3-labeled mitotic counts for the three compartments of the crypts and the total scores for Barrett's esophagus, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma were compared using the Mann–Whitney U test. For each compartment, the number of anti-phosphorylated histone H3-positive nuclei was higher in low-grade dysplasia than in Barrett's esophagus without dysplasia or indefinite for dysplasia (P<0.001), but no difference was found between Barrett's esophagus without dysplasia and indefinite for dysplasia. High-grade dysplasia biopsies had significantly more anti-phosphorylated histone H3-labeled mitotic figures in the surface epithelium than the low-grade dysplasia (P<0.001). Adenocarcinoma had higher anti-phosphorylated histone H3-labeled mitotic figures than the high-grade dysplasia (P<0.001). Our data support the previous findings of expansion of the proliferative zone and importance of surface mitotic figure in the progression of Barrett's esophagus—low-grade dysplasia–high-grade dysplasia. In addition, phosphorylated histone H3 is a potential supportive marker to histology in differentiating low-grade dysplasia from indefinite for dysplasia and high-grade dysplasia from adenocarcinoma in the mucosal biopsy samples.

AMACR Immunostaining is Useful in Detecting Dysplastic Epithelium in Barrett's Esophagus, Ulcerative Colitis, and Crohn's Disease

Alpha-methylacyl-CoA racemase (AMACR) catalyzes the racemization of alpha-methyl, branched carboxylic coenzyme A thioesters, and is overexpressed in a variety of neoplasms, such as prostate and colon cancer. The aim of this study was to evaluate AMACR expression in the metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus (BE), ulcerative colitis (UC), and Crohn's disease (CD) and to determine whether its expression can be used to detect dysplastic epithelium in these conditions. One hundred thirty-four routinely processed biopsy and/or resection specimens from 134 patients with BE [M/F ratio: 5.7, mean age: 67 y (36 negative (intestinal metaplasia only), 14 indefinite for dysplasia (IND), 16 low-grade dysplasia (LGD), 32 high-grade dysplasia (HGD), and 36 invasive adenocarcinoma (ACA)] and 74 specimens from 74 patients with inflammatory bowel disease (IBD) [56 with ulcerative colitis, 18 with Crohn's disease, M/F ratio: 1.8, mean age: 55 y (17 negative, 7 IND, 26 LGD, 10 HGD, and 14 ACA)] were immunostained with a monoclonal AMACR antibody (p504S). The degree of cytoplasmic staining in all cases was evaluated in a blinded fashion according to the following grading system: 0, negative (0% cells positive); 1+, 1% to 10% cells positive; 2+, 10% to 50% cells positive; or 3+, >50% cells positive. In patients with BE, AMACR was not expressed in any negative foci (0%) but was significantly increased (P<0.0001) in foci of LGD (38%), HGD (81%), and ACA (72%). Three of 14 (21%) IND foci from 3 BE patients were only focally positive (grade 1: 7%, 2: 14%). However, 1 of these 3 patients had follow-up information available and had developed ACA subsequently. Similarly, in patients with IBD, AMACR was not expressed in any foci considered negative for dysplasia, but was significantly increased (P<0.0001) in foci of LGD (96%), HGD (80%), and ACA (71%). Only 1/7 (14%) IND focus from 1 patient was focally positive (grade 1). The sensitivity for the detection of LGD and HGD in BE and IBD was 38% and 81%, and 96% and 80%, respectively, for the 2 types of disorders. The specificity was 100% for both BE and IBD. AMACR is involved in the neoplastic progression in BE and IBD. The high degree of specificity of AMACR for dysplasia/carcinoma in BE and IBD suggests that it may be useful to detect neoplastic epithelium in these conditions.

Endoscopic mucosal resection of large hyperplastic polyps in 3 patients with Barrett’s esophagus

To report the endoscopic treatment of large hyperplastic polyps of the esophagus and esophago-gastric junction (EGJ) associated with Barrett's esophagus (BE) with low-grade dysplasia (LGD), by endoscopic mucosal resection (EMR). Cap fitted EMR (EMR-C) was performed in 3 patients with hyperplastic-inflammatory polyps (HIPs) and BE. The polyps were successfully removed in the 3 patients. In two patients, with short segment BE (SSBE) (<= 3 cm), the metaplastic tissue was completely excised. A 2 cm circumferential EMR was performed in one patient with a polyp involving the whole EGJ. A simultaneous EMR-C of a BE-associated polypoid dysplastic lesion measuring 1 cm multiply 10 cm, was also carried out. In the two patients, histologic assessment detected LGD in BE. No complications occurred. Complete neosquamous re-epithelialization occurred in the two patients with SSBE. An esophageal recurrence occurred in the remaining one and was successfully retreated by EMR. EMR-C appears to be a safe and effective method for treating benign esophageal mucosal lesions, allowing also the complete removal of SSBE.

Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma

Endoglin (CD105), a member of transforming growth factor beta1 receptor complex, has been shown to be a more useful marker to identify tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor (VEGF) expression as possible prognostic markers in esophageal adenocarcinoma. Surgical specimens from 75 patients with esophageal adenocarcinoma treated with esophagectomy were immunostained for endoglin, CD31, and VEGF. We also included 10 cases of Barrett's esophagus with high-grade dysplasia and 10 cases with Barrett's esophagus low-grade dysplasia. Positively stained microvessels (MVs) were counted in hot spots at magnification of x400. Results were expressed as the highest number of MV identified. For VEGF, intensity of staining was scored on 3-tiered scale. Endoglin demonstrated significantly more vessels than the CD31 (mean, 28.9 +/- 13.2 versus 19.0 +/- 9.4, P < .001). Both endoglin and CD31 MV counts showed significant correlation with stage of the disease (r = 0.59, P < .001; r = 0.52, P < .001, respectively) and patient survival (log rank P < .01). Only endoglin MV count was significantly correlated with the presence of angiolymphatic invasion (r = 0.34, P < .05) and lymph node (LN) metastases (r = 0.48, P < .001). Univariate analysis showed that endoglin MV count is an independent prognostic factor. Endoglin showed a significant increase in MV count in Barrett's esophagus with high-grade dysplasia when compared with Barrett's esophagus low-grade dysplasia (P < .01), whereas CD31 did not show any significant difference. VEGF was expressed in 48 (64%) of 75 cases of adenocarcinoma and was significantly correlated with angiolymphatic invasion, LN metastases, and survival. In conclusion, endoglin is a specific and sensitive marker for tumor angiogenesis. Endoglin staining also showed prognostic significance with positive correlation with the presence of angiolymphatic invasion, LN metastases, tumor stage, and survival.

P53 expression in low grade dysplasia in Barrett's esophagus: correlation with interobserver agreement and disease progression.

The frequency of progression from low grade dysplasia (LGD) to high grade dysplasia/carcinoma (HGD/ CA) in Barrett's esophagus (BE) varies among studies. Current assessment is made more difficult because of pathologists' interobserver variability in diagnosing LGD. We recently conducted an interobserver study on LGD and reported a positive correlation between the extent of agreement among GI pathologists and progression of LGD. In the current study, we analyzed the immunohistochemical staining for p53 in patients diagnosed with LGD with known clinical outcome and interobserver agreement data. Fixed, paraffin-embedded endoscopic biopsy specimens from 16 patients diagnosed with LGD in BE were immunostained for p53 (DO-7, Dako, Carpinteria, CA). Hematoxylin and eosin-stained and immunostained sections were examined in tandem to determine whether the LGD areas in question stained for p53. The p53 immunoreactivity was correlated with clinical progression and with the interobserver agreement among three GI pathologists. The overall mean follow-up was 23 months (range 2-84 months). LGD areas in seven of eight patients (88%) who progressed to HGD/CA stained positively for p53 compared to only two of eight nonprogressors (25%). A correlation with clinical progression was seen for p53 positivity (p = 0.017; log-rank test), and for either p53 positivity or complete agreement among three GI pathologists on LGD diagnosis (p = 0.014; log-rank test). The p53 staining demonstrated 88% sensitivity and 75% specificity for progression of LGD to HGD/CA. Adding complete interobserver agreement on LGD among three experienced GI pathologists to p53 positivity resulted in improved sensitivity with no change in specificity (100% and 75%, respectively). In conjunction with histological evaluation by GI pathologists for a diagnosis of LGD, immunohistochemical staining for p53 can be used as an adjunctive test, as it correlated with progression to HGD/CA in this series.