Are there groups of patients with BO that can be discharged from surveillance?

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Are there groups of patients with BO that can be discharged from surveillance?

Introduction

The aim of surveillance in non-dysplastic Barrett's Oesophagus (BO) is to detect evidence of the progression to cancer to provide intervention that is curative. If there is a subgroup of cases which progress to cancer at a low or negligible rate, then these cases may be effectively discharged from surveillance as no benefit for the surveillance would exist. Similarly, if a subgroup of cases is unlikely to benefit from intervention, then these cases may also be discharged from surveillance. The majority of studies that investigate factors in the progression to oesophageal adenocarcinoma (OAC) concentrate on risk factors that increase the progression rate, rather than protective factors that may reduce or normalise this rate (see also What are the risk factors for progression from non-dysplastic BO to high grade dysplasia and adenocarcinoma?). In addition, there are no randomised studies and no long term data reporting outcomes of surveillance of patients in low risk groups, or groups where surveillance was ceased. However, on extrapolation from available data, a number of recommendations may still be made based on observations from these studies.

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What are the endoscopic and/or histological factors of non-dysplastic BO patients that may lead to discharge from surveillance?

Shorter segments of BO and the absence of dysplasia have been shown to have lower rates of progression to cancer than longer BO length and the presence of dysplasia. Short segment BO, defined as biopsy proven BO of less than 3cm length from the gastro-oesophageal junction (GOJ), has been observed to have a lower incidence of progression to OAC of 0.19% per year (compared with 0.33% per year overall).[1][2] Histological evidence of intestinal metaplasia in cases with normal appearing GOJ has been reported (termed “cardiac intestinal metaplasia”). This has been observed in a number of studies to have a low or negligible rate of progression to dysplasia and/or cancer.[3][4][5]

A further subgroup of patients may have a columnar lined oesophagus (CLO) with histological evidence of gastric differentiation, but without evidence of intestinal differentiation i.e. do not have identified goblet cells at histology. These are defined as “gastric metaplasia”. At this stage, it is still unclear whether patients with evidence of gastric metaplasia are a further subgroup of patients with a defined risk of OAC, and international guidelines differ in their advice. The British Society of Gastroenterology (BSG) guidelines include these within the spectrum of BO based on studies which show that there is malignant potential with similar observed rates.[6] Furthermore, subsequent sampling in these patients has been shown to result in observed intestinal metaplasia, as reported in a prospective study by Gatenby et al.[7] Hence, continued surveillance is recommended in BSG guidelines for these patients, particularly if the observed segment is ≥1cm. However, the American Gastroenterology Association (AGA) guidelines exclude these cases as it is felt that these do not represent true intestinal differentiation,[8] and recent studies support a low malignant potential if this is observed.[9] At this stage, patients with CLO may be recommended surveillance using similar protocols if the length of CLO is greater than 3cm. If the length is less than 3cm, then patients may be discharged from surveillance if certain criteria are met (see section below, What is the suggested surveillance protocol that may lead to discharge from surveillance?).

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What are the patient factors of non-dysplastic BO patients that may lead to discharge from surveillance?

At this stage, there is a lack of strong evidence about factors that may reduce the incidence of progression from BO to OAC. There are number of factors which have been independently associated with lower progression rates to OAC, including female gender,[9][10] never smokers,[11] and normal body mass index.[12] These factors alone are not sufficient to recommend complete discharge from surveillance, but lifestyle changes may be recommended to reduce risk of progression. There are number of studies which show a benefit for chemo-preventative medications such as anti-inflammatories,[13] acid suppressive medications,[14] and statins,[15] which are hypothesised to reduce factors which may drive malignancy. A randomised study is currently being conducted studying the role of anti-inflammatories and proton pump inhibitors in the progression to OAC.[16] However, further study is required to determine if the reported risk reduction of these medications will be significant enough to recommend discharge for surveillance.

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What is the suggested surveillance protocol that may lead to discharge from surveillance?

To summarise the current international guidelines regarding patients with non-dysplastic BO, the AGA does not recommend surveillance for patients with CLO without intestinal metaplasia regardless of length. The BSG recommends no surveillance if the observed CLO (without intestinal metaplasia) is less than 1cm, and those 1cm or greater may continue surveillance using the same protocol as intestinal metaplasia. As there is no high level evidence to support either position, clinicians should be guided by their index of suspicion regarding the appropriate surveillance for these patients. These international guidelines (i.e. BSG and AGA) imply that if intestinal metaplasia or dysplasia is observed, then surveillance should continue indefinitely (see also How frequently should patients with BO undergo endoscopy?, What is the appropriate management of low grade dysplasia in patients with BO? and What are the goals of treatment of high grade dysplasia in patients with BO?).

There are currently no guidelines that outline management if there is observed “regression” of BO length or the observation of gastric metaplasia in the setting of a previous diagnosis of intestinal metaplasia. Due to (a) inter-observer variation during endoscopy, (b) possible sampling error and (c) no observed reduction in the rate of progression to OAC, normal endoscopic surveillance should continue if “regression” of BO is suspected (see also Are there any medical or surgical interventions that cause regression of BO?).

In addition, there are no guidelines as to what age and after how many years that surveillance may cease. It may be considered that if other co-morbidities significantly reduce the expected life expectancy, or if there is likely to be significant morbidity associated with procedural intervention for dysplasia/OAC, then these patients may be discharged from surveillance.

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Evidence summary and recommendations

Evidence summary Level References
Short segment BO (<3cm) has a lower rate of progression to oesophageal adenocarcinoma, but not low enough to recommend discharge from surveillance. III-2 [1], [2]
Cardiac intestinal metaplasia (intestinal metaplasia without endoscopic evidence of Barrett's Oesophagus) has a low or negligible rate of progression to dysplasia/oesophageal adenocarcinoma. IV [3], [4], [5]
Patients with evidence of columnar lined oesophagus (i.e. gastric metaplasia without intestinal metaplasia) may be considered to have surveillance, particularly if subsequent intestinal metaplasia is identified. III-2 [6], [7]
There is lack of strong evidence for factors that may reduce incidence enough to consider discharge from surveillance, although studies are in progress which may yield risk reducing modifiers. II, III-2, III-3 [11], [12], [13], [15]
Evidence-based recommendationQuestion mark transparent.png Grade
For patients with < 1cm of columnar lined oesophagus that do not have evidence of intestinal metaplasia or dysplasia on Seattle protocol biopsy of the segment, endoscopic surveillance is not recommended
C
The given value was not understood.


Evidence-based recommendationQuestion mark transparent.png Grade
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



Practice pointQuestion mark transparent.png

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.


Practice pointQuestion mark transparent.png

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.

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References

  1. 1.0 1.1 Desai TK, Krishnan K, Samala N, Singh J, Cluley J, Perla S, et al. The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett's oesophagus: a meta-analysis. Gut 2012 Jul;61(7):970-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21997553.
  2. 2.0 2.1 Thomas T, Abrams KR, De Caestecker JS, Robinson RJ. Meta analysis: Cancer risk in Barrett's oesophagus. Aliment Pharmacol Ther 2007 Dec;26(11-12):1465-77 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17900269.
  3. 3.0 3.1 Sharma P, Weston AP, Morales T, Topalovski M, Mayo MS, Sampliner RE. Relative risk of dysplasia for patients with intestinal metaplasia in the distal oesophagus and in the gastric cardia. Gut 2000 Jan;46(1):9-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10601047.
  4. 4.0 4.1 Horwhat JD, Baroni D, Maydonovitch C, Osgard E, Ormseth E, Rueda-Pedraza E, et al. Normalization of intestinal metaplasia in the esophagus and esophagogastric junction: incidence and clinical data. Am J Gastroenterol 2007 Mar;102(3):497-506 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17156135.
  5. 5.0 5.1 Chang Y, Liu B, Liu GS, Wang T, Gong J. Short-segment Barrett's esophagus and cardia intestinal metaplasia: A comparative analysis. World J Gastroenterol 2010 Dec 28;16(48):6151-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21182233.
  6. 6.0 6.1 Kelty CJ, Gough MD, Van Wyk Q, Stephenson TJ, Ackroyd R. Barrett's oesophagus: intestinal metaplasia is not essential for cancer risk. Scand J Gastroenterol 2007 Nov;42(11):1271-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17852872.
  7. 7.0 7.1 Gatenby PA, Ramus JR, Caygill CP, Shepherd NA, Watson A. Relevance of the detection of intestinal metaplasia in non-dysplastic columnar-lined oesophagus. Scand J Gastroenterol 2008;43(5):524-30 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18415743.
  8. Wang KK, Sampliner RE, Practice Parameters Committee of the American College of Gastroenterology. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus. Am J Gastroenterol 2008 Mar;103(3):788-97 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18341497.
  9. 9.0 9.1 Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, et al. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst 2011 Jul 6;103(13):1049-57 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21680910.
  10. de Jonge PJ, van Blankenstein M, Looman CW, Casparie MK, Meijer GA, Kuipers EJ. Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study. Gut 2010 Aug;59(8):1030-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20639249.
  11. 11.0 11.1 Coleman HG, Bhat S, Johnston BT, McManus D, Gavin AT, Murray LJ. Tobacco smoking increases the risk of high-grade dysplasia and cancer among patients with Barrett's esophagus. Gastroenterology 2012 Feb;142(2):233-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22062359.
  12. 12.0 12.1 Duggan C, Onstad L, Hardikar S, Blount PL, Reid BJ, Vaughan TL. Association between markers of obesity and progression from Barrett's esophagus to esophageal adenocarcinoma. Clin Gastroenterol Hepatol 2013 Aug 1;11(8):934-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23466711.
  13. 13.0 13.1 Kastelein F, Spaander MC, Biermann K, Steyerberg EW, Kuipers EJ, Bruno MJ, et al. Nonsteroidal anti-inflammatory drugs and statins have chemopreventative effects in patients with Barrett's esophagus. Gastroenterology 2011 Dec;141(6):2000-8; quiz e13-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21878200.
  14. Singh S, Garg SK, Singh PP, Iyer PG, El-Serag HB. Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis. Gut 2013 Nov 12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/24221456.
  15. 15.0 15.1 Singh S, Singh AG, Singh PP, Murad MH, Iyer PG. Statins Are Associated with Reduced Risk of Esophageal Cancer, Particularly in Patients with Barrett's Esophagus: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2013 Jan 25 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23357487.
  16. Jankowski J, Sharma P. Review article: approaches to Barrett's oesophagus treatment-the role of proton pump inhibitors and other interventions. Aliment Pharmacol Ther 2004 Feb;19 Suppl 1:54-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/14725580.

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Appendices


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