What are the goals of treatment of high grade dysplasia in patients with BO?
What are the goals of treatment of high grade dysplasia in patients with BO?
There is no high level research evidence which directly answers this question. Therefore, the following is based on the evidence regarding various management strategies used in high grade dysplasia (HGD) and the risk of continued surveillance with no intervention.
There is a histologic progression from non-dysplastic Barrett’s metaplasia to low grade dysplasia, high grade dysplasia, intramucosal cancer and invasive malignancy. Due to the rich lymphatic supply to the oesophagus, even early invasive malignancy has a significant chance of metastasis. For this reason, as well as the possibility of sampling error, high grade dysplasia has traditionally been the trigger for therapeutic intervention in Barrett’s Oesophagus. Furthermore, the risk of progression to adenocarcinoma appears to accelerate with increasing dysplastic change (see also What is the appropriate management of low grade dysplasia in patients with BO? and What endoscopic surveillance protocol should be followed for patients with BO and high grade dysplasia?).
High grade dysplasia is prone to both over and under-staging. Therefore, given the importance of this diagnosis, the first goal of managing the patient with HGD is to confirm the diagnosis.
Confirmation of HGD diagnosis
Histologic Confirmation (overstaging)
The intra-observer agreement for dysplasia staging of BO is poor. This is particularly so in the presence of reflux oesophagitis, where inflammatory atypia may be misinterpreted as HGD (ie: overstaging). Even amongst gastrointestinal pathologists inter-observer error for grading dysplasia is only moderate, with a kappa 0.43. It is therefore recommended that all BO specimens reported as HGD should be accompanied by a corroborating opinion by a second histopathologist.
Endoscopic Confirmation (understaging)
Surgical literature suggests that a significant proportion of patients operated on for “HGD” in fact had adenocarcinoma in the excised specimen. In the older surgical literature this was up to 20-40% but in a more recent study only 5% of those operated on for "HGD" had submucosal invasive disease at resection. It is, therefore, important to be as careful as possible in assessing the other mucosa for irregularities or nodules which may suggest more advanced disease. This should be done at the time of the index procedure. However, if the endoscopic appearance is not concerning, and the histological diagnosis of HGD is received subsequently, then it is suggested to repeat the endoscopy for further careful endoscopic assessment and biopsy. This detailed review of the patient’s Barrett’s segment may include the use of imaging enhancement techniques and should include biopsy strategy according to the Seattle protocol. It may be reasonable to consider referring patients to a centre with expertise in the management of Barrett’s Oesophagus for this detailed endoscopic review. Furthermore, any suspicious areas (irregularities, nodules or ulcerations) should be removed by endoscopic mucosal resection in order to permit full histologic assessment prior to determining management and particularly prior to undergoing ablative therapy (which does not afford further histologic review).
Goals of treatment
Once the severity of neoplastic progression has been confirmed as being HGD (as far as practicable), the goal of treatment is to prevent the progression to malignancy through the removal of dysplastic tissue. More specifically the goals of treatment are:
- The removal of all dysplastic tissue
- The removal of all Barrett’s metaplasia if possible
- Preservation of normal swallowing/nutrition
- Minimisation of morbidity due to the eradication technique
- Confirmation of the diagnosis of HGD (ie: exclusion of malignancy) through examination of resected tissue (endoscopically or surgically), where possible
- Continued follow up in patients who have had endoscopic therapy
There is no management strategy which perfectly fulfils all these criteria. There continues to be debate as to the most appropriate management of good surgical candidates.
Endoscopic mucosal resection may be used in four settings:
- as definitive treatment to remove all Barrett’s in patients with short segment disease,
- to allow adequate histologic staging of nodular lesions (ie: acting as a "big biopsy"),
- to remove nodular lesions prior to confluent ablative therapy (eg: radiofrequency ablation which has a limited depth of approximately 500µm), or
- to remove suspicious lesions in poor health status patients as definitive therapy.
Confluent ablative therapies include photodynamic therapy (PDT), radiofrequency ablation (RFA), argon plasma coagulation and cryotherapy. In 2013 RFA has largely replaced PDT as the standard ablative treatment for high grade dysplasia. The primary aim of treatment is to remove all Barrett’s tissue. With RFA, eradication of dysplasia is achieved in 86% of patients. Eradication of all Barrett’s tissue is more difficult, achieved in 77% of patients. Of those patients undergoing successful eradication of all Barrett’s tissue, 5-25% will have recurrence of Barrett’s Oesophagus at 12 month follow-up. Therefore, even in cases where all Barrett’s appears to have been eliminated, both by endoscopic visualisation as well as Seattle protocol biopsies of the neosquamous segment there is a need for continued long-term surveillance.
Surgical resection has the advantage of certainty – cancer can be excluded with certainty and the Barrett’s segment is completely removed. This comes at a significant burden of morbidity (up to 40% in expert centres) and mortality (approximately 2.5% in experienced centres), but is still an option which should be discussed, particularly in the setting of relatively young patients.
Evidence summary and recommendations
The confirmation of high grade dysplasia should act as a trigger for definitive treatment.
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