Prateek Sharma

Long-term follow-up of Barrett's high-grade dysplasia

OBJECTIVE:The management of Barretts high-grade dysplasia (HGD) remains controversial. The aims of this study were to evaluate prospectively the outcome of unifocal HGD (uHGD) in patients with Barretts esophagus, and to determine demographic and endoscopic features predictive of progression to multifocal HGD (mHGD) and/or adenocarcinoma.METHODS:Consecutive Barretts patients in whom uHGD was found at initial endoscopy or during surveillance underwent intensification of medical treatment and repeat endoscopy. The study endpoint was progression to mHGD or adenocarcinoma or HGD in conjunction with a dysplasia-associated lesion or mass (DALM). HGD diagnosis was confirmed by a second, blinded pathologist.RESULTS:A total of 15 Barretts patients with uHGD met inclusion criteria and have been prospectively followed for a mean ± SD of 36.8 ± 23.2 months. All were white and male, with a mean age ± SD of 61.4 ± 14.9 yr. Barretts length varied from 1 to 13 cm (mean, ± SD, 6.8 ± 4 cm). Overall, eight (53.3%) uHGD progressed: four of 15 (26.7%) to frank cancer between 17 and 35 months of follow-up, two of 15 (13.3%) to mHGD with DALM in conjunction with one or more foci of possible intramucosal cancer after 12–91 months of follow-up, one of 15 (6.7%) to mHGD with a focus of possible intramucosal cancer after 14 months, and one of 15 (6.7%) to mHGD after 29 months. Seven of 15 (46.7%) uHGD have regressed, five to no dysplasia and two to LGD, over the course of follow-up ranging from 24 to 73 months (mean ± SD, 43.3 ± 19.9). All three patients with short-segment Barretts esophagus with uHGD regressed. Fishers exact test revealed that Barretts length ≥3 cm and presence of hiatal hernia approached significance (p < 0.08) in predicting uHGD progression to mHGD/DALM/cancer. However, use of the log-rank test to account for differences in length of follow-up show no significance for hiatal hernia or Barretts length.CONCLUSIONS:Barretts uHGD has a high risk for progressing to mHGD or cancer. Justification of an observational approach to uHGD should be discouraged. Markers of uHGD progression, as well as regression, are needed.

p53 protein overexpression in low grade dysplasia (LGD) in barrett’s esophagus: Immunohistochemical marker predictive of progression ☆

OBJECTIVES:The presence of low grade dysplasia (LGD) within Barretts esophagus (BE) has a multitude of ramifications. Identification of markers that could risk stratify LGD would be of great clinical benefit. We aimed to prospectively evaluate the prognosis of the immunohistochemical overexpression of p53 protein in BE colocalized to LGD.METHODS:Consecutive BE patients in whom LGD was found had a repeat esophagogastroduodenoscopy within 8–12 wk per an ongoing prospective study. At each esophagogastroduodenoscopy, a therapeutic scope was used in conjunction with the Seattle Biopsy Protocol. Patients were observed until development of multifocal high grade dysplasia (mHGD), presence of an HGD dysplasia-associated lesion or mass (DALM) lesion, or frank adenocarcinoma. p53 protein overexpression was determined by computerized immunoquantitation using image analysis software on step serial-sectioned specimens of BE segment(s) harboring LGD. Kaplan-Meier survival curves were made on the ability of p53 staining colocalized to areas of LGD to predict progression to mHGD, HGD DALM, or cancer during prospective follow-up.RESULTS:Forty-eight BE patients with LGD were observed for a mean of 41.2 ± 22.5 months. During this period, five of 48 patients progressed to mHGD with a focus in which intramucosal cancer could not be excluded (one), mHGD/DALM with one or more foci in which intramucosal cancer could not be excluded (two), cancer (one), or mHGD (one). Twelve had persistent LGD and 31 had regressed to no dysplasia. p53 staining was positive and colocalized to areas of LGD in 4/31 of patients that regressed, 3/12 that persisted, and 3/5 that progressed. Kaplan-Meier curves differed significantly between p53 positive and negative patients for outcome defined as progression of LGD.CONCLUSIONS:p53 colocalization with LGD at index LGD diagnosis is a risk factor for progression of LGD. This can potentially be used to risk stratify BE LGD patients in terms of surveillance intervals or enrollment into secondary prevention studies.

Diagnosis and Management of Barrett’s Esophagus: What’s Next?

The past decade has led to marked improvements in our understanding regarding the pathogenesis and risk of progression of Barretts esophagus (BE), enhanced imaging technology to improve dysplasia detection, and the development and refinement of endoscopic techniques, such as mucosal ablation and endoscopic mucosal resection(EMR), to eradicate BE. However, many questions remain including identifying which, if any, candidates are most appropriate for screening for BE; how to improve current surveillance protocols; predicting which patients with BE will develop neoplastic progression; identifying the most appropriate candidates for endoscopic eradication therapy; developing algorithms for appropriate management posteradication; and understanding the potential role of chemoprophylaxis. This article describes potential future advances regarding screening, surveillance, risk stratification, endoscopic eradication therapies, and chemoprevention and provides a potential future management strategy for patients with BE.

Multipolar Electrocoagulation (MPEC): An Early, Widely Available Technique

Multipolar electrocoagulation (MPEC) ablation is a simple-to-use, familiar, widely available, inexpensive, and safe option for the endoscopic treatment of Barrett’s epithelium. While its use has primarily been tested in non-dysplastic Barrett’s epithelium, it may also be of value in non-nodular low-grade and high-grade dysplasia. It can achieve endoscopic and histologic ablation in at least 70–80% of the treated patients, with successful ablation typically achieved within three to four ablation procedures. Head-to-head comparisons with other thermal ablative techniques such as APC show the two techniques to be similar, although a non-statistically significant trend to improved efficacy was seen favoring MPEC. Successful acid suppression appears to be helpful in achieving effective ablation with this technique. Future studies comparing this technique with alternative ablation modalities, assessing its durability and the need for continued surveillance in successfully ablated patients, and evaluating whether ablation reduces the risk of subsequently developing adenocarcinoma are needed. Given these uncertainties, its use at present may best be limited to ablating residual short/limited areas of non-nodular Barrett’s esophagus with high-grade dysplasia or early cancer.