Report from STS Workforce on Evidence Based SurgeryThe Society of Thoracic Surgeons Practice Guideline Series: Guidelines for the Management of Barrett's Esophagus With High-Grade Dysplasia
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
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A rigorous biopsy protocol must be maintained throughout surveillance. (Level B Evidence)
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Histological evaluation of high-grade dysplasia should be undertaken by two pathologists experienced in interpreting esophageal metaplasia and dysplasia. (Level C Evidence)
Class IIa
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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
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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)
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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
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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
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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
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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)
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Esophagectomy for Barrett's esophagus with HGD is reasonable and can be performed safely, with an operative mortality approaching 1%. (Level B Evidence)
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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
References (77)
- et al.
Barrett's esophagus: development of dysplasia and adenocarcinoma
Gastroenterology
(1989) - et al.
Jumbo biopsy forceps protocol still misses unsuspected cancer in Barrett's esophagus with high-grade dysplasia
Gastrointest Endosc
(1999) - et al.
Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation
Hum Pathol
(2001) - et al.
Extent of high-grade dysplasia in Barrett's esophagus correlates with risk of adenocarcinoma
Gastroenterology
(2001) - et al.
An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus
Gastroenterology
(1993) - et al.
Long-term nonsurgical management of Barrett's esophagus with high-grade dysplasia
Gastroenterology
(2001) - et al.
Long-term follow-up of Barrett's high-grade dysplasia
Am J Gastroenterol
(2000) - et al.
Combined endoscopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett's esophagus
Gastrointest Endos
(2001) - et al.
Optimizing endoscopic biopsy detection of early cancers in Barrett's high-grade dysplasia
Am J Gastroenterol
(2000) - et al.
Observer variation in the diagnosis of dysplasia in Barrett's esophagus
Hum Pathol
(1988)
Flow-cytometric and histological progression to malignancy in Barrett's esophagus: prospective endoscopic surveillance of a cohort
Gastroenterology
Predictors of progression to cancer in Barrett's esophagus: baseline histology and flow cytometry identify low- and high-risk patient subsets
Am J Gastroenterol
Predictors of progression in Barrett's esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression
Am J Gastroenterol
Computerized morphometry as an aid in determining the grade of dysplasia and progression to adenocarcinoma in Barrett's esophagus
Lab Invest
p53 protein overexpression in low grade dysplasia (LGD) in Barrett's esophagus: immunohistochemical marker predictive of progression
Am J Gastroenterol
Barrett's esophagus: photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa, and treatment of superficial esophageal cancer
Gastrointest Endosc
Photodynamic therapy for Barrett's esophagus: follow-up in 100 patients
Gastrointest Endosc
Photodynamic ablation of high-grade dysplasia and early cancer in Barrett's esophagus by means of 5-aminolevulinic acid
Gastroenterology
Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia
Gastrointest Endos
Initial results using low-dose photodynamic therapy in the treatment of Barrett's esophagus
Gastrointest Endosc
Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial
Gastrointest Endosc
Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett's high-grade dysplasia
Gastrointest Endosc
Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett's esophagus
Gastroenterology
Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett's esophagus: 1-year follow-up of 100 patients
Gastrointest Endosc
Circumferential ablation of Barrett's esophagus that contains high-grade dysplasia: a U.S. Multicenter Registry
Gastrointest Endosc
Clinical biology and surgical therapy of intramucosal adenocarcinoma of the esophagus
J Am Coll Surg
Curative endoscopic resection of early esophageal adenocarcinomas (Barrett's cancer)
Gastrointest Endosc
Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett's esophagus
Gastroenterology
Endoscopic biopsy can detect high-grade dysplasia or early adenocarcinoma in Barrett's esophagus without grossly recognizable neoplastic lesions
Gastroenterology
Circumferential EMR and complete removal of Barrett's epithelium: a new approach to management of Barrett's esophagus containing high-grade intraepithelial neoplasia and intramucosal carcinoma
Gastrointest Endosc
Dysplasia and cancer in a large multicenter cohort of patients with Barrett's esophagus
Clin Gastroenterol Hepatol
Management of high-grade dysplasia in patients with Barrett's esophagus
Clin Gastroenterol Hepatol
Surgical treatment of esophageal high-grade dysplasia
Ann Thorac Surg
Long-term outcome of esophagectomy for high-grade dysplasia or cancer found during surveillance for Barrett's esophagus
J Gastrointest Surg
Outcomes after esophagectomy: a ten-year prospective cohort
Ann Thorac Surg
Impact of hospital volume on clinical and economic outcomes for esophagectomy
Ann Thorac Surg
Transthoracic esophagectomy: a safe approach to carcinoma of the esophagus
Ann Thorac Surg
Esophagectomy—it's not just about mortality anymore: standardized perioperative clinical pathways improve outcomes in patients with esophageal cancer
J Gastrointest Surg
Cited by (42)
Esophageal Procedures
2021, Cohen's Comprehensive Thoracic AnesthesiaEndoscopic Management of High-Grade Dysplasia and Superficial Esophageal Carcinoma
2019, Shackelford's Surgery of the Alimentary Tract: 2 Volume SetManagement of Barrett's high-grade dysplasia: Initial results from a population-based national audit
2016, Gastrointestinal EndoscopyEliminating a Need for Esophagectomy: Endoscopic Treatment of Barrett Esophagus With Early Esophageal Neoplasia
2014, Seminars in Thoracic and Cardiovascular SurgeryCitation Excerpt :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.
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).