Treatment of Barrett's oesophagus

One of the two main types of oesophageal (gullet) cancer, oesophageal adenocarcinoma, is rapidly increasing in incidence in the western world. The prognosis for patients treated for oesophageal adenocarcinoma is appalling with fewer than 15% of individuals surviving beyond five years. Barrett’s oesophagus has been identified as the pre-cancerous stage of adenocarcinoma. It is recognised that Barrett's oesophagus develops as a complication of acid and bile reflux which commonly, but not inevitably, leads to heartburn symptoms. In response to these injurious agents, the normal squamous lining of the oesophagus is replaced by a columnar lining resembling the lining of the intestine. This intestinal subtype has the highest risk of malignancy and the term Barrett's oesophagus is used only for this subtype in many areas of the world, and in most research publications. Barrett's oesophagus can gradually progress to adenocarcinoma through a series of stages called dysplasia which can be identified in biopsies examined under the microscope.

As outcomes after treatment of adenocarcinoma are so poor, there has been increasing interest in treatments for Barrett's oesophagus. The aim of these treatments is to eradicate the Barrett's oesophagus lining or associated dysplasia with the aim of reducing the risk of cancer developing. This systematic review has shown that acid suppression therapies (surgery or drugs) have little or no significant effect on reversing Barrett's oesophagus but anti-reflux surgery appears to reduce dysplasia and protects against the development of dysplasia. A number of endoscopic therapies have also been developed over recent years. Argon plasma coagulation, which burns away the Barrett's oesophagus segment, and photodynamic therapy, which uses light to activate an injected drug, have both been shown to be successful at eradicating Barrett’s and dysplasia. However, small areas of Barrett's oesophagus buried under the newly formed squamous oesophagus remain a concern. A relatively new technique using radiofrequency waves, called radio frequency ablation appears successful at eradicating Barrett's with fewer side effects. There are currently very few randomised controlled trials to help clinicians and patients decide on the best treatment options in the long as well as the short-term. Overall, radiofrequency ablation appears to be the most successful therapy to date for patients with early cancer or severe (high-grade) dysplasia in Barrett's oesophagus. Significantly more work is needed in this area to guide routine clinical practice for this common condition.

Authors' conclusions: 

Despite their failure to eradicate Barrett's oesophagus, the role of medical and surgical interventions to reduce the troubling symptoms and sequelae of GORD is not questioned. Whether therapies for GORD reduce the cancer risk is not yet known. Ablative therapies have an increasing role in the management of dysplasia within Barrett's and current data would favour the use of radiofrequency ablation compared with photodynamic therapy. Radiofrequency ablation has been shown to yield significantly fewer complications than photodynamic therapy and is very efficacious at eradicating both dysplasia and Barrett's itself. However, long-term follow-up data are still needed before radiofrequency ablation can be used in routine clinical care without the need for very careful post-treatment surveillance. More clinical trial data and in particular randomised controlled trials are required to assess whether or not the cancer risk is reduced in routine clinical practice.

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Background: 

Treatments for Barrett's oesophagus, the precursor lesion of adenocarcinoma, are available but whether these therapies effectively prevent the development of adenocarcinoma, and in some cases eradicate the Barrett's oesophagus segment, remains unclear.

Objectives: 

To summarise, quantify and compare the efficacy of pharmacological, surgical and endoscopic treatments for the eradication of dysplastic and non-dysplastic Barrett's oesophagus and prevention of these states from progression to adenocarcinoma.

Search strategy: 

We searched CENTRAL (The Cochrane Library 2004, issue 4), MEDLINE (1966 to June 2008) and EMBASE (1980 to June 2008).

Selection criteria: 

Randomised controlled trials (RCTs) comparing medical, endoscopic or non-resectional surgical treatments for Barrett's oesophagus. The primary outcome measures were complete eradication of Barrett's and dysplasia at 12 months, and reduction in the number of patients progressing to cancer at five years or latest time point.

Data collection and analysis: 

Three authors independently extracted data and assessed the quality of the trials included in the analysis.

Main results: 

Sixteen studies, including 1074 patients, were included. The mean number of participants in the studies was small (n = 49; range 8 to 208). Most studies did not report on the primary outcomes. Medical and surgical interventions to reduce symptoms and sequelae of gastro-oesophageal reflux disease (GORD) did not induce significant eradication of Barrett's oesophagus or dysplasia. Endoscopic therapies (photodynamic therapy (PDT with aminolevulinic acid or porfimer sodium), argon plasma coagulation (APC) and radiofrequency ablation (RFA)) all induced regression of Barrett's oesophagus and dysplasia. The data for photodynamic therapy were heterogeneous with a mean eradication rate of 51% for Barrett's oesophagus and between 56% and 100% for dysplasia, depending on the treatment regimens. The variation in photodynamic therapy eradication rates for dysplasia was dependent on the drug, source and dose of light. Radiofrequency ablation resulted in eradication rates of 77% and 86% for Barrett's oesophagus and dysplasia, while those rates were 2% and 21% in the sham treatment group respectively. Endoscopic treatments were generally well tolerated, however all were associated with some buried glands, particularly following argon plasma coagulation and photodynamic therapy, as well as photosensitivity and strictures induced by porfimer sodium based photodynamic therapy in particular.

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