Summary of recommendations
For explanation of levels of evidence and grades for recommendations, see Levels of evidence and grades for recommendations below. You may also like to refer to the Appendix - Guideline Development Process
Barrett's Oesophagus and Mucosal Neoplasia
|Globally, the prevalence of Barrett’s Oesophagus is generally low (<5%) and only in selected groups such as those with gastro-oesophageal reflux disease is it substantially higher (>15%). Prevalence also varies significantly by different ethnicities (e.g., Asians <1% prevalence) and by gender (i.e. more common in males).|
| Clinical assessment of a person’s future risk of Barrett’s Oesophagus should consider:
• Person’s sex
• History of gastro-oesophageal acid reflux
• Waist-hip ratio or other measures of central adiposity
• Smoking history
• Family history of oesophageal adenocarcinoma and/or Barrett's Oesophagus
What are the risk factors for progression from non-dysplastic BO to high-grade dysplasia or adenocarcinoma?
| A clinical assessment of a patient’s future risk of high-grade dysplasia or adenocarcinoma in the setting of non-dysplastic Barrett’s Oesophagus should consider their:
|There is no evidence to support general population screening for Barrett’s Oesophagus.|
|In the absence of Randomised Controlled Trial evidence of effectiveness, screening for Barrett’s Oesophagus would be most cost-effective if limited to 50-year old men with gastro-oesophageal reflux disease.|
|Biopsies assessing for intestinal metaplasia (columnar epithelium with goblet cells) should be performed when any length of salmon pink mucosa is seen extending above the gastro-oesophageal junction into the tubular oesophagus for a confirmed diagnosis of Barrett’s Oesophagus.|
|The presence of Barrett’s Oesophagus should be described using the Prague C & M Criteria.|
|The current practice of random four-quadrant biopsies at 2cm intervals remains the mainstay for tissue sampling until stronger evidence emerges for various advancements in endoscope technology and chromoendoscopy.||B|
|Focal abnormalities such as ulcerated or nodular lesions can be specifically targeted with biopsies and labelled prior to random biopsies from the rest of the mucosa as minor biopsy-related bleeding is common and may impair endoscopic views.|
|Technological advancements in chromoendoscopy, digital enhancements and enhanced-magnification can currently complement rather than replace random four-quadrant biopsies at 2cm intervals. Biopsies obtained every 2cm to be placed into separate jars which are labelled according to the distance from the incisors, while biopsies from the gastro-oesophageal junction and cardia can also be specifically labelled as such.|
| Definition of Barrett’s Oesophagus
To identify patients at increased risk of neoplastic progression, Barrett’s Oesophagus is defined as metaplastic columnar mucosa in the oesophagus, with intestinal metaplasia proven histologically.
|There is insufficient evidence to recommend the use of acid suppressive therapy for the regression of Barrett’s Oesophagus.||B|
|Insufficient evidence exists to routinely recommend anti-reflux surgery for the regression of Barrett’s Oesophagus.||C|
|Acid suppressive therapy and anti-reflux surgery can be used to control symptoms and heal reflux oesophagitis in patients with Barrett’s Oesophagus. There is insufficient evidence to recommend high dose (twice daily) acid suppressive therapy when symptom control or mucosal healing is achieved with standard dosing.|
|Ablation of Barrett’s Oesophagus should remain limited to individuals with high grade dysplasia in Barrett’s Oesophagus who are at imminent risk of developing oesophageal adenocarcinoma.||B|
|The treatment of gastro-oesophageal reflux with either proton pump inhibitors or antireflux surgery has not been shown to influence progression to oesophageal adenocarcinoma.|
|There is currently no good evidence supporting the use of COX inhibitors for prevention of oesophageal adenocarcinoma.|
|Symptomatic patients with Barrett’s Oesophagus should be treated with Proton Pump Inhibitor therapy (PPI), with the dose titrated to control symptoms.||C|
|Long term outcome studies do not yet support ablation in patients without dysplasia.||B|
Surveillance and Follow-up
|In the absence of any randomised trial evidence, the frequency of surveillance endoscopy in Barrett’s Oesophagus can be guided by currently available practice guidelines.|
|It is advisable to undertake endoscopic surveillance in suitable patients with Barrett’s Oesophagus. The frequency of surveillance is based on the presence or absence of dysplasia on previous Seattle protocol biopsies and length of Barrett’s Oesophagus.|
|A diagnosis of dysplasia (indefinite, low and high grade) should be confirmed by a second pathologist, ideally an expert gastrointestinal pathologist.|
|Patients with one or more modifiable risk factors for progression to oesophageal adenocarcinoma (such as smoking) should be encouraged to make lifestyle changes.||D|
|Patients with Barrett's Oesophagus length equal to or greater than 3cm may have more frequent surveillance than those less than 3cm.|
|Patients with one or more modifiable risk factors for progression from Barrett's Oesophagus to oesophageal adenocarcinoma (such as smoking or obesity) should be encouraged to make lifestyle changes.||D|
|Patients with evidence of “regression” of Barrett's Oesophagus i.e. reduced Barrett's Oesophagus length or absence of intestinal metaplasia, can still continue surveillance.|
|Patients with significant co-morbidities, or those whom are unable to tolerate procedural intervention for dysplasia/oesphageal adenocarcinoma may be considered to be discharged from surveillance.|
Barrett's Oesophagus and Neoplasia
Definition and Diagnosis
|Endoscopic resection is the most accurate staging modality for early oesophageal adenocarcinoma for suitable lesions and where appropriate expertise is available.||D|
|Endoscopic ultrasound can be used prior to endoscopic resection for the identification of deeply invasive adenocarcinoma (≥T2) and locoregional lymph node metastasis, particularly for lesions with ulcerated or depressed morphology.||D|
|FDG-PET or PET/CT is not routinely indicated in staging early oesophageal adenocarcinoma. It is best used for the staging of distant metastases or in cases of suspected more advanced local disease.||D|
|Insufficient evidence exists to recommend evaluation of AG2 expression as a protein biomarker in fresh tissue to aid in the diagnosis of Barrett's Oesophagus.||D|
|Insufficient evidence exists to recommend cytokeratin staining to aid in the diagnosis of Barrett's Oesophagus.||D|
|Insufficient evidence exists to recommend magnifying endoscopy to aid in the diagnosis of Barrett's Oesophagus.||D|
|Insufficient evidence exists to recommend the implementation of immunohistochemistry biomarkers to aid in the diagnosis of Barrett's Oesophagus.||D|
|Insufficient evidence exists to recommend mucin (MUC) expression immunostaining in formalin-fixed, paraffin-embedded tissue to aid in the diagnosis of Barrett's Oesophagus.||D|
|Insufficient high quality evidence exists to recommend the non-endoscopic capsule sponge device coupled with immunohistochemistry for trefoil factor 3 (TFF3) to replace the current clinical standard for the diagnosis of Barrett's Oesophagus.||C|
|Insufficient evidence exists to recommend the implementation of serum G17 for the diagnosis of Barret's Oesophagus.||D|
Low grade dysplasia
|The diagnosis of low grade dysplasia should be confirmed by a second pathologist, ideally an expert gastrointestinal pathologist.||C|
|In patients with confirmed low grade dysplasia, it is advised to perform rigorous high definition endoscopy or refer to an expert centre for assessment.||C|
|In patients with confirmed low grade dysplasia, intensified endoscopic surveillance is required. Endoscopic ablation may be considered especially where low grade dysplasia is definite, multifocal and present on more than one occasion. This decision needs to be individualised, based on discussion of risk and benefits with the patient.||B|
High grade dysplasia and early cancer
|The confirmation of high grade dysplasia should act as a trigger for definitive treatment.|
|Endoscopic mucosal resection should be considered for patients with intramucosal adenocarcinoma or high grade dysplasia and visible/nodular lesions.||D|
|Radiofrequency ablation should be considered for patients with high grade dysplasia and flat segments of Barrett's. Radiofrequency ablation may be the preferred treatment strategy over endoscopic mucosal resection for patients with long segments Barrett's Oesophagus or circumferential Barrett's due to a lower rate of stricture formation.||B|
|It is advisable to refer patients with Barrett’s Oesophagus and dysplasia or early oesophageal adenocarcinoma to tertiary referral centres for management.|
After successful endoscopic treatment for BO neoplasia, how frequently should patients undergo endoscopy?
|All lesions and visible abnormalities should be staged by focal endoscopic resection.||D|
| Patients with T1a on endoscopic work-up should be offered endoscopic resection as a less morbid and potentially equally effective treatment option in comparison to oesophagectomy.
Selected patients with T1b early oesophageal adenocarcinoma may be offered endoscopic resection if oesophagectomy is not indicated.
|If endoscopic resection of early oesophageal adenocarincoma is planned, endoscopic mucosal resection is appropriate in most cases.||C|
| Following resection of early oesophageal adenocarcinoma the remaining Barrett’s mucosa should be eradicated.
Following resection of early oesophageal adenocarcinoma, Barrett’s eradication options include complete Barrett’s endoscopic resection, radiofrequency ablation, cryotherapy and argon plasma coagulation.
Following resection of early oesophageal adenocarcinoma the patient should undergo regular and careful surveillance examinations.
|Ablative therapies should not be used as primary endoscopic therapy for early oesophageal adenocarcinoma.||C|
|Endoscopic resection of early oesophageal adenocarcinoma should be performed in referral centres that have integrated expertise in endoscopy, imaging, surgery, and histopathology.|
|Careful and dedicated interrogation of all Barrett’s mucosa is advised.|
What endoscopic surveillance protocol should be followed for patients with BO and high grade dysplasia?
|Surveillance is generally not indicated for patients with high grade dysplasia, and therapeutic intervention must be considered instead.|
|Targeted biopsies of visible lesions plus quadrantic biopsies every 1cm throughout the segment of Barrett’s mucosa should be taken.|
|High resolution endoscopes should be used, with optional use of virtual chromoendoscopy such as narrow band imaging (NBI).|
|If endoscopic surveillance is performed, intervals of three months may be appropriate.|
How effective is endoscopic management compared with surgical management for high grade dysplasia in patients with BO?
|It is recommended that patients with high grade dysplasia in Barrett’s Oesophagus be managed in centres with high volume experience of the condition. The treatment and follow-up should occur in those specialist centres.||C|
| Patients with high grade dysplasia in Barrett's Oesophagus can be discussed at a multidisciplinary team meeting at a specialist centre.
Endoscopic treatment will be the first line treatment option for the majority of patients with high grade dysplasia in Barrett's Oesophagus. There will be a group of patients for whom endoscopic treatment is not appropriate or successful and will be best treated with surgery in a specialist centre.
Levels of evidence and grades for recommendations
The following table provides a list of the evidence-based recommendations detailed in the content of each topic question. The table below provides details on the highest level of evidence identified to support each recommendation (I-IV). The Summary of Recommendations table includes the grade for each recommendation (A-D). The key references that underpin the recommendation are provided in the last column. Individual levels of evidence can be found in the Evidence Summaries for each recommendation in each question.
Each recommendation was assigned a grade by the expert working group taking into account the volume, consistency, generalisability, applicability and clinical impact of the body of evidence supporting each recommendation. When no Level I or II evidence was available and in some areas, in particular where there was insufficient evidence in the literature to make a specific evidence-based recommendation, but also strong and unanimous expert opinion amongst the working group members about both the advisability of making a clinically relevant statement and its content, recommended best practice points were generated. Thus, the practice points relate to the evidence in each question, but are more expert opinion-based than evidence-based. These can be identified throughout the guidelines with the following: Practice point (PP).
|Grade of recommendation||Description|
|A||Body of evidence can be trusted to guide practice|
|B||Body of evidence can be trusted to guide practice in most situations|
|C||Body of evidence provides some support for recommendation(s) but care should be taken in its application|
|D||Body of evidence is weak and recommendation must be applied with caution|
|Where no good-quality evidence is available but there is consensus among Guideline committee members, consensus-based guidance points are given, these are called "Practice points"|
Adapted from: National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Canberra: NHMRC; 2009. (https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf)
Level of evidence was assigned according to the following criteria from the NHMRC Evidence Hierarchy:
|I||A systematic review of level II studies||A systematic review of level II studies||A systematic review of level II studies||A systematic review of level II studies||A systematic review of level II studies|
|II||A randomised controlled trial||A study of test accuracy with: an independent, blinded comparison with a valid reference standard, among consecutive patients with a defined clinical presentation||A prospective cohort study||A prospective cohort study||A randomised controlled trial|
|III-1||A pseudo-randomised controlled trial (i.e. alternate allocation or some other method)||A study of test accuracy with: an independent, blinded comparison with a valid reference standard, among non-consecutive patients with a defined clinical presentation||All or none||All or none||A pseudo-randomised controlled trial (i.e. alternate allocation or some other method)|
|III-2|| A comparative study with concurrent controls:
||A comparison with reference standard that does not meet the criteria required for Level II and III-1 evidence||Analysis of prognostic factors amongst untreated control patients in a randomised controlled trial||A retrospective cohort study|| A comparative study with concurrent controls:
|III-3|| A comparative study without concurrent controls:
||Diagnostic case-control study||A retrospective cohort study||A case-control study|| A comparative study without concurrent controls:
|IV||Case series with either post-test or pre-test/post-test outcomes||Study of diagnostic yield (no reference standard)||Case series, or cohort study of patients at different stages of disease||A cross-sectional study||Case series|
Source: National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for developers of guidelines. Canberra: NHMRC; 2009. (https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf)
- National Health and Medical Research Council. NHMRC levels of evidence and grades for recommendations for guideline developers. Canberra: National Health and Medical Research Council; 2009 Available from: https://www.nhmrc.gov.au/_files_nhmrc/file/guidelines/developers/nhmrc_levels_grades_evidence_120423.pdf.