Report from STS Workforce on Evidence Based Surgery
The Society of Thoracic Surgeons Practice Guideline Series: Guidelines for the Management of Barrett's Esophagus With High-Grade Dysplasia

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The management of Barrett's esophagus with high-grade dysplasia is controversial. The standard of care has traditionally been esophagectomy. However, a number of treatment options aimed at esophageal preservation are increasingly being utilized by many centers. These esophageal-sparing approaches include endoscopic surveillance, mucosal ablation, and endoscopic mucosal resection. In this guideline we review the best evidence supporting these commonly used strategies for high-grade dysplasia to better define management and guide future investigation.

Section snippets

Methods

Initially the Medline, Cochrane Library, and the Trip databases were searched for the terms Barrett's or high-grade dysplasia, or both, or surgery, photodynamic therapy and radiofrequency ablation, or a combination of these. The timeframe was not restricted. The Trip database returned two references. The Cochrane Library, which was restricted to randomized controlled trials, returned 91 of which 35 were initially considered relevant. The Medline PubMed returned 64 references of which four were

Recommendations

Class I

  • A rigorous biopsy protocol must be maintained throughout surveillance. (Level B Evidence)

  • Histological evaluation of high-grade dysplasia should be undertaken by two pathologists experienced in interpreting esophageal metaplasia and dysplasia. (Level C Evidence)

Class IIa

  • It is reasonable to limit endoscopic surveillance of high-grade dysplasia to high-volume centers with specific expertise in the management of Barrett's esophagus and preferably performed in the context of a clinical trial.

Patient Selection for Surveillance

Assumptions that must be made to justify surveillance are: (1) HGD is an entity distinct and distinguishable from intramucosal carcinoma, (2) HGD does not invariably progress to carcinoma, (3) if there is progression, it can be reliably detected at an early, curable stage, and (4) patients undergoing surveillance are reliable for follow-up and are candidates for further therapy if progression is diagnosed.

Progression of metaplasia through dysplasia to adenocarcinoma is a widely accepted theory

Biopsy Protocol

There are no randomized trials comparing methods of biopsy. The Seattle Protocol (biopsies with jumbo forceps in four quadrants, along every centimeter of metaplastic epithelium with extra biopsies taken from suspicious areas) is advocated by some. Reid and colleagues [17] argued that cancer can be detected at an early stage of invasion and that rigorous biopsy protocols can distinguish patients with HGD from those with invasive disease. In their case-series, 48 cancers were detected in 45

Pathologist Interpretation of High-Grade Dysplasia

Histologic criteria for dysplasia were described in 1988 by Reid and colleagues [21]. Despite these criteria being accepted nearly 20 years ago, significant interobserver variability still exists among pathologists experienced in gastrointestinal dysplasia [22]. The key factor in determining whether a patient is a reasonable candidate for surveillance is the differentiation between HGD and intramucosal cancer, a task described by an expert in Barrett's dysplasia as “difficult at best” [10].

Recommendations

Class IIa

  • Photodynamic therapy (PDT) should be considered for eradication of high-grade dysplasia (HGD) in patients at high risk for undergoing esophagectomy and for those refusing esophagectomy. (Level B Evidence)

  • It is reasonable to use photodynamic therapy (PDT) to ablate residual intestinal metaplasia after endoscopic mucosal resection (EMR) of a small intramucosal carcinoma in high-risk patients. (Level B Evidence)

Class IIb

  • Radiofrequency ablation (RFA) may be considered to treat patients

Photodynamic Therapy for High-Grade Dysplasia

Photodynamic therapy involves the systemic administration of a photosensitizer (usually a porphyrin derivative or precursor) that selectively accumulates in neoplastic esophageal mucosal cells. Endoscopic delivery of low-energy, non-thermal laser light at a specific wavelength activates the chemical, leading to singlet oxygen formation and the destruction of these cells. Photodynamic therapy balances depth and completeness of mucosal ablation against the development of complications, most

Radiofrequency Ablation for HGD

Radiofrequency ablation using the HALO360 System (BarrX Medical Inc, Sunnyvale, CA) has been recently introduced into clinical practice. This uses a balloon-based array to deliver a high-power, ultra-short burst of ablative energy to the abnormal esophageal epithelium. This system appears to be safe and effective for Barrett's, and clinical trials are currently underway for HGD. No phase III data are currently available, and most data are currently in abstract form.

A two-phase prospective,

Recommendation

Class IIa

  • It is reasonable to use endoscopic mucosal resection (EMR) to excise discrete esophageal mucosal nodules that are small, flat, or polypoid in nature, and not invading deeper than the submucosa. Due to the frequent multi-focality of Barrett's, a concomitant mucosal ablative procedure is frequently required to assure complete eradication of disease. (Level B Evidence)

Endoscopic mucosal resection has been used to excise discrete mucosal nodules in the setting of Barrett's esophagus with

Recommendations

Class IIa

  • It is reasonable to use esophagectomy to eliminate high-grade dysplasia and any associated cancer. The majority of cancers found incidentally in patients with HGD are cured by esophagectomy. (Level B Evidence)

  • Esophagectomy for Barrett's esophagus with HGD is reasonable and can be performed safely, with an operative mortality approaching 1%. (Level B Evidence)

  • It is beneficial to perform esophagectomies for high-grade dysplasia in high-volume centers and by surgical teams with specific

Esophageal Cancer Prevention and Cure

Perhaps best considered in the context of prophylaxis of cancer, esophagectomy for HGD is effective and reasonable. The incidence of adenocarcinoma in all patients with Barrett's esophagus ranges from 0.2% to 2% per year, with a 0.5% annual incidence being the best supported [58, 59]. However, when HGD is present, 25% to 75% of patients will have concomitant unsuspected invasive cancer (Table 1), with recent trends favoring incidences more towards the lower end of this range. Because molecular

Morbidity and Mortality of Esophagectomy Specifically for HGD

A common argument against esophagectomy for HGD is that it is associated with excessive morbidity and mortality. However, historical claims of 50% morbidity and 10% mortality [65] are controverted by the results of many retrospective modern series particularly for HGD.

Most studies describe outcomes after esophagectomy principally for cancer, not HGD. This is an important distinction, because the majority of cancers tend to be more locally advanced and patients more debilitated preoperatively,

Quality of Life After Esophagectomy

Longitudinal studies have demonstrated that the quality of life after esophagectomy is good to excellent. As expected, there is a prolonged adjustment period, and the quality of life of patients immediately after esophagectomy seems to be worse than comparable controls for the first 9 months after the operation [71]. In addition, patients learn to tolerate episodic reflux and intermittent diarrhea and dumping [39, 63]. Despite these concerns, by 5 years, esophagectomy patients equal or exceed

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      An extensive literature regarding the safety and efficacy of endoscopic ablation and resection in the management of BE with HGD has evolved. As a result, gastroenterological and surgical societies in the United States, as well as the National Comprehensive Cancer Network, have recommended endoscopic therapies as the treatments of choice for HGD, relegating esophagectomy to a minority of cases.8-11 Our experience is consistent with such recommendations; esophagectomy has disappeared as a treatment for HGD in our institution since 2008.

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    This paper was written by members of The Society of Thoracic Surgeons Treatment Options for High-Grade Dysplasia of the Esophagus Guideline Task Force whose names appear in the author line.

    For the full text of The Society of Thoracic Surgeons (STS) Guideline on the Management of Barrett's Esophagus With High-Grade Dysplasia, as well as other titles in The STS Practice Guideline Series, visit http://www.sts.org/sections/aboutthesociety/practiceguidelines at the official STS website (www.sts.org).

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