Barrett's oesophagus

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Endoscopic appearances of Barrett's oesophagus. The islands of paler tissue are the remnant 'native' squamous cells, while the 'velvety' columnar tissue has a similar appearance, as you would expect, as the stomach mucosa (the stomach folds of the proximal stomach are just visible).

Barrett's oesophagus is a term used to describe the presence of columnar epithelium in the lower oesophagus, usually as a result of metaplasia. There is ambiguity both in the historical definition and in the modern day definition of Barrett's oesophagus (see section on terminology below). For this reason some prefer the term columnar-lined oesophagus (CLO) to the eponymous label.

In essence, the normal squamous epithelium in the area is replaced by encroachment of columnar epithelium, of which there are 3 types: intestinal, gastric (fundal) and (oesphago-gastric) junctional columnar cells. Only intestinal metaplasia carries a significant risk of malignant progression. It is induced by chronic reflux.

It gives a characteristic appearance on endoscopy and diagnosis can be confirmed with biopsy. Barrett's oesophagus gives an increased risk of dysplasia and oesophageal cancer. The relative risk risk is estimated at x30-x50 and the absolute risk ~0.5% annually. However, a recent Danish study suggests the annual risk is closer to 0.12%.[1] The literature needs to be interpreted in the context that as of 2013 there is no consensus as to the histology of the condition internationally.




Described by Norman Ruppert Barrett, thoracic surgeon.[2]

The label is source of confusion as one of the two cases that Norman Barrett described in 1950 was a congenitally short oesophagus such that the gastric mucosa was pulled up into the thorax. The second was a case of congenital heterotopic gastric mucosa in the oesophagus with ulceration.[2] The association with reflux disease was described a few years later. Indeed, Barrett's original paper supported the idea that columnar epithelium was explained by a tubular stomach being pulled up into the thorax, but his views changed in 1957.[3] His 1957 paper, however, did not state that the columnar epithelium could be of the intestinal-type, nor did it specify the extent required to qualify for the condition he was describing.

The situation was clarified somewhat by a paper in 1976 describing the three possible types of columnar epithelium: fundal, junctional and intestinal.[4] When to apply the label of Barrett's oesophagus remained confusing as biopsies from the oesophago-gastric junction or cardia of stomach would result in false-positive columnar epithelium, an easy mistake to make in patients with hiatus herniae or where the oesophago-gastric junction was uneven or unclear due to oesophagitis.

The diagnosis was clear enough in segments of metaplasia long enough to obviously be in the oesophagus, but for shorter segments there was no agreed cut-off. For research purposes, some investigators applied arbitrary minimum lengths, ranging from 2 to 5cm, to avoid the false-positives described. These varying length criteria were adopted by some clinicians who disregarded shorter segments of columnar epithelium. As the main concern with Barrett's oesophagus was the risk of adenocarcinoma, this had the effect of excluding shorter lesions that still carried a risk of dysplasia and malignant progression.[5][6] Columnar epithelium of the fundal and junctional type were also found in resected oesophageal tumours, demonstrating non-intestinal type columnar epithelium could still represent a risk for malignancy, though some have argued that this represented intestinal-type epithelium that had lost goblet cells.

Definitions and Diagnostic Criteria

LogoKeyPointsBox.pngThe presence of goblet cells in the columnar epithelium is a diagnostic criterion in the USA but not UK

There is general agreement that endoscopic appearences should be corroborated by histological analysis. However, the UK[7] and American[8] definitons differ in that histological confirmation of intestinal-type epithelium is a sine qua non. The BSG guidelines do not not insist on intestinal metaplasia on the rationale that intestinal metaplasia may be patchy and therefore prone to sampling errors. Intestinal metaplasia is thought to be present in endoscopically visible columnar-lined if sufficient biopsies are taken over time. Therefore, the combination of endoscopy and histology is important as neither is sufficient on their own; endoscopic appearences suggestive of Barrett's may harbour metaplasia of the fundal-type on histological analysis which is at low risk, while, conversely, normal-looking oesophagus may sometimes harbour microsopic intestinal metaplasia, which may be regarded as physiological.[9]

QuotationMarkLeft.png An appropriate definition of “Barrett’s oesophagus” (more appropriately referred to as columnar-lined oesophagus [CLO]) is an oesophagus in which any portion of the normal squamous lining has been replaced by a metaplastic columnar epithelium which is visible macroscopically. In order to make a positive diagnosis of “Barrett’s oesophagus”, a segment of columnar metaplasia of any length must be visible endoscopically above the oesophago-gastric junction and confirmed or corroborated histologically.[7] QuotationMarkRight.png

In the BSG 2013 guidelines, diagnosis of Barrett's still does not required the presence of intestinal metaplasia, but its repeated absence in short segment disease lowers the risk of progression to a level that discharge from surveillance can be considered; if 2 or more endoscopic assesssments with histology show Barrett's oesophagus <3cm and showing only gastric metaplasia, no further follow-up may be required.

The American definition requires:[8][10]

  1. Cephalad displacement of the squamocolumnar junction on endoscopy
    • The Z line intersection of the squamous epithelium of the tubular oesophagus and the gastric columnar epithelium is displaced either in a circumferential fashion or has tongues of columnar epithelium
  2. Intestinalised epithelium or epithelium containing goblet cells in a biopsy of the tubular oesophagus


BSG 2013

The categories are simplified compared to the 2005 guidelines, but presumes it is seen endoscopically and supports the use of the Prague notation for describing the extent:[11]

  • Barrett's oesophagus with gastric metaplasia (+/- dysplasia +/- grade of dysplasia)
  • Barrett's oesophagus with intestinal metaplasia (+/- dysplasia +/- grade of dysplasia)
  • No evidence of Barrett's oesophagus

BSG 2005

The BSG 2005 guidelines recommend 4 categories for histological reporting:[7]

  1. Biopsies diagnostic for columnar-lined oesophagus
    • Used when native oesophageal tissue is seen adjacent to metaplastic glandular tissue.
  2. Biopsies corroborative of an endoscopic diagnosis of columnar-lined oesophagus
    • Intestinal metaplastic glandular mucosa is seen, characterised by goblet cells, but could represent intestinal metaplasia within the cardia of the stomach or in a hiatus hernia.
  3. Biopsies in keeping with, but not specific for columnar-lined oesophagus
    • Used when gastric-type mucosa seen, but without intestinal metaplasia. Could represent columnar-lined oesophagus, but biopsies could have come from the OG junction or stomach.
  4. Biopsies without evidence of columnar-lined oesophagus
    • Oesophageal-type squamous mucosa with no evidence of glandular epithelium.

Alcian Blue & PAS staining can be used to aid identification of goblet cells which tend to stain blue with Alcian Blue.


This is important to help determine resource effectiveness of various screening strategies. In western populations at death: about 350/100,000. Swedish prevalance is 1.6%. However the elderly may have prevalences as high as 25%, but it must be remembered the strong association with hiatus hernias and their size as well as with symptoms of GORD, although GORD does not predict Barrett's well.

Age, sex and ethnic associations exist such as white elderly men seem most at risk. Obesity is associated while chronic smoking and alcohol abuse are weakly associated. No definite protective effect of NSAIDs has been demonstrated even though there is a negative association[10].


Management is aimed at controlling the primary reflux, especially of gastric acid, although this often does not reverse the metaplasia. Surveillance endoscopy can detect early dysplasia. If dysplasia is severe, the traditional treatment has been prophylatic oesophagectomy, a major operation with many potential complications, including death, but this has been largely been replaced by less drastic methods of controlling dysplasia, typically some form of endoscopic ablative treatment.

Photodynamic Therapy

Photodynamic therapy appears to be at least as effective as surgery.[12][13]

May be associated with stricturing and therefore now losing favour.

Radiofrequency Ablation

Resolution of dysplasia in 77.4% of patients versus 2.3% in placebo in a randomised, controlled trial of a total of 127 patients.[14]

One proprietary system of delivering this is called Halo® system.

Endoscopic Mucosal Resection


As only a small proportion of patients with Barret's oesophagus will actually develop severe dysplasia or early oesophageal cancer, it is not clear which patients should be screened and whether screening affects eventual outcome.

Surveillance typically involves quadrantic biopsies every 1-2cm of Barrett's oesophagus, the so-called Seattle protocol.[15][16] Not all studies show superiority of this approach compared to less intensive protocols.[17] However, the Seattle protocol is recommended by the BSG 2013 guidelines.[11]

There is not sufficient evidence that newer endoscopic technologies such as narrow-band imaging and chromoendoscopy offer improved detection of dysplasia over conventional white-light endoscopy, particularly if careful high-resolution white-light endoscopy is used (evidence reviewed in BSG guidelines[11]).

In the 2005 BSG guidelines, the most effective and cost-effective surveillance interval was put forward as two years, but acknowledged that there was a lack of good quality evidence to support screening, a finding highlighted in 2006 Health Technology Assessment report[18]. This reports that in most cases, screening does more harm than good and suggesting that it is unlikely that surveillance will be cost effective.

The 2013 BSG guidelines note that newer data suggests a lower risk of malignant conversion than previously thought,[1] reducing the benefit of surveillance. A more individualised approach to the screening interval is recommended based on the length of Barrett's oesophagus and type of metaplasia, taking into account the patient's wishes and overall fitness. Barrett's oesophagus >3cm should be surveyed every 2-3 years, whereas if the maximum length is <3cm and shows only gastric metaplasia on 2 occasions, discharge from follow-up may be considered.

The BOSS trial may answer the value of endoscopic surveillance.


  1. a b Hvid-Jensen F, Pedersen L, Drewes AM, Sørensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett's esophagus. The New England journal of medicine. 2011 Oct 13; 365(15):1375-83.(Link to article – subscription may be required.)
  2. a b BARRETT NR. Chronic peptic ulcer of the oesophagus and 'oesophagitis'. The British journal of surgery. 1950 Oct; 38(150):175-82.
  3. BARRETT NR. The lower esophagus lined by columnar epithelium. Surgery. 1957 Jun; 41(6):881-94.
  4. Paull A, Trier JS, Dalton MD, Camp RC, Loeb P, Goyal RK. The histologic spectrum of Barrett's esophagus. The New England journal of medicine. 1976 Aug 26; 295(9):476-80.
  5. Clark GW, Smyrk TC, Burdiles P, Hoeft SF, Peters JH, Kiyabu M, Hinder RA, Bremner CG, DeMeester TR. Is Barrett's metaplasia the source of adenocarcinomas of the cardia? Archives of surgery (Chicago, Ill. : 1960). 1994 Jun; 129(6):609-14.
  6. Cameron AJ, Lomboy CT, Pera M, Carpenter HA. Adenocarcinoma of the esophagogastric junction and Barrett's esophagus. Gastroenterology. 1995 Nov; 109(5):1541-6.
  7. a b c Barrett’s columnar-lined oesophagus British Society of Gastroenterology, 2005
  8. a b Wang KK, Sampliner RE. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. The American journal of gastroenterology. 2008 Mar; 103(3):788-97.(Link to article – subscription may be required.)
  9. Trudgill NJ, Suvarna SK, Kapur KC, Riley SA. Intestinal metaplasia at the squamocolumnar junction in patients attending for diagnostic gastroscopy. Gut. 1997 Nov; 41(5):585-9.
  10. a b Shaheen NJ, Richter JE. Barrett's oesophagus. Lancet. 2009 Mar 7; 373(9666):850-61.(Link to article – subscription may be required.)
  11. a b c Fitzgerald RC, di Pietro M, Ragunath K, Ang Y, Kang JY, Watson P, Trudgill N, Patel P, Kaye PV, Sanders S, O'Donovan M, Bird-Lieberman E, Bhandari P, Jankowski JA, Attwood S, Parsons SL, Loft D, Lagergren J, Moayyedi P, Lyratzopoulos G, de Caestecker J. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut. 2014 Jan; 63(1):7-42.(Link to article – subscription may be required.)
  12. Pech O, Gossner L, May A, Rabenstein T, Vieth M, Stolte M, Berres M, Ell C. Long-term results of photodynamic therapy with 5-aminolevulinic acid for superficial Barrett's cancer and high-grade intraepithelial neoplasia. Gastrointestinal endoscopy. 2005 Jul; 62(1):24-30.
  13. Prasad GA, Wang KK, Buttar NS, Wongkeesong LM, Krishnadath KK, Nichols FC, Lutzke LS, Borkenhagen LS. Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett's esophagus. Gastroenterology. 2007 Apr; 132(4):1226-33.(Link to article – subscription may be required.)
  14. Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, Galanko JA, Bronner MP, Goldblum JR, Bennett AE, Jobe BA, Eisen GM, Fennerty MB, Hunter JG, Fleischer DE, Sharma VK, Hawes RH, Hoffman BJ, Rothstein RI, Gordon SR, Mashimo H, Chang KJ, Muthusamy VR, Edmundowicz SA, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Falk GW, Kimmey MB, Madanick RD, Chak A, Lightdale CJ. Radiofrequency Ablation in Barrett's Esophagus with Dysplasia. The New England journal of medicine. 2009 May 28; 360(22):2277-88.(Link to article – subscription may be required.)
  15. Levine DS, Haggitt RC, Blount PL, Rabinovitch PS, Rusch VW, Reid BJ. An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus. Gastroenterology. 1993 Jul; 105(1):40-50.
  16. Levine DS, Blount PL, Rudolph RE, Reid BJ. Safety of a systematic endoscopic biopsy protocol in patients with Barrett's esophagus. The American journal of gastroenterology. 2000 May; 95(5):1152-7.(Link to article – subscription may be required.)
  17. Kariv R, Plesec TP, Goldblum JR, Bronner M, Oldenburgh M, Rice TW, Falk GW. The Seattle protocol does not more reliably predict the detection of cancer at the time of esophagectomy than a less intensive surveillance protocol. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2009 Jun; 7(6):653-8; quiz 606.(Link to article – subscription may be required.)
  18. Surveillance of Barrett’s oesophagus: exploring the uncertainty through systematic review, expert workshop and economic modelling Health Technology Assessment, 2006