Top

Current Treatment Options in Gastroenterology

Published in:

01-03-2019 | Barrett Esophagus | Esophagus (PG Iyer, Section Editor)

Predictors of Progression in Barrett’s Esophagus

Authors: Subhankar Chakraborty, MBBS, PhD, Prasad G. Iyer, MD, MSc

Published in: Current Treatment Options in Gastroenterology | Issue 1/2019

Abstract

Purpose of review

To review recently published data on factors that predict the risk of progression of Barrett’s esophagus (BE) to high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC).

Recent findings

Computer models have been developed that could help predict the risk of progression with greater accuracy. The progression of BE score (PIB) is one such model based on clinical and endoscopic features, while a second uses automated image analysis of formalin-fixed and paraffin-embedded tissues looking for morphologic features and immunostaining patterns for molecular markers. Panels of genes such as those regulated by Myc and hypermethylated genes have been recently described.

Summary

EAC remains a cancer with a poor 5-year survival of less than 20%. Screening for BE, the only known precursor of EAC is recommended only in high-risk individuals. Clinical, endoscopic, and molecular predictors of progression have been identified but require validation. These tools could in turn help focus screening and surveillance efforts to reduce mortality from EAC.

Nguyen T, Thrift AP, Yu X, Duan Z, El-Serag HB. The annual risk of esophageal adenocarcinoma does not decrease over time in patients with Barrett's esophagus. Am J Gastroenterol. 2017;112(7):1049–55. https://doi.org/10.1038/ajg.2017.18.CrossRefPubMed

Codipilly DC, Chandar AK, Singh S, Wani S, Shaheen NJ, Inadomi JM, et al. The effect of endoscopic surveillance in patients with Barrett’s esophagus: a systematic review and meta-analysis. Gastroenterology. 2018;154(8):2068–86 e5. https://doi.org/10.1053/j.gastro.2018.02.022.CrossRefPubMedPubMedCentral

Visrodia K, Singh S, Krishnamoorthi R, Ahlquist DA, Wang KK, Iyer PG, et al. Magnitude of missed esophageal adenocarcinoma after Barrett’s esophagus diagnosis: a systematic review and meta-analysis. Gastroenterology. 2016;150(3):599–607 e7; quiz e14–5. https://doi.org/10.1053/j.gastro.2015.11.040.

Gaddam S, Singh M, Balasubramanian G, Thota P, Gupta N, Wani S, et al. Persistence of nondysplastic Barrett’s esophagus identifies patients at lower risk for esophageal adenocarcinoma: results from a large multicenter cohort. Gastroenterology. 2013;145(3):548–53 e1. https://doi.org/10.1053/j.gastro.2013.05.040.CrossRefPubMed

Singh S, Manickam P, Amin AV, Samala N, Schouten LJ, Iyer PG, et al. Incidence of esophageal adenocarcinoma in Barrett’s esophagus with low-grade dysplasia: a systematic review and meta-analysis. Gastrointest Endosc. 2014;79(6):897–909 e4; quiz 83 e1, 83 e3. https://doi.org/10.1016/j.gie.2014.01.009.

Inadomi JM, Sampliner R, Lagergren J, Lieberman D, Fendrick AM, Vakil N. Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis. Ann Intern Med. 2003;138(3):176–86.CrossRefPubMed

Singh S, Sharma AN, Murad MH, Buttar NS, El-Serag HB, Katzka DA, et al. Central adiposity is associated with increased risk of esophageal inflammation, metaplasia, and adenocarcinoma: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2013;11(11):1399–412 e7. https://doi.org/10.1016/j.cgh.2013.05.009.CrossRef

Krishnamoorthi R, Borah B, Heien H, Das A, Chak A, Iyer PG. Rates and predictors of progression to esophageal carcinoma in a large population-based Barrett’s esophagus cohort. Gastrointest Endosc. 2016;84(1):40–6 e7. https://doi.org/10.1016/j.gie.2015.12.036S0016-.CrossRefPubMedPubMedCentral

•• Krishnamoorthi R, Singh S, Ragunathan K, Visrodia K, Wang KK, Katzka DA, et al. Factors associated with progression of Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol. 2018;16(7):1046–55 e8. https://doi.org/10.1016/j.cgh.2017.11.044. A recent systemic review and meta-analysis that found that age, male gender, smoking and increasing length of BE segment increase while use of PPIs and statins lower the risk of BE progression.CrossRefPubMed

10.

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;11(8):934–43. https://doi.org/10.1016/j.cgh.2013.02.017.CrossRefPubMedPubMedCentral

11.

Di Caro S, Cheung WH, Fini L, Keane MG, Theis B, Haidry R, et al. Role of body composition and metabolic profile in Barrett’s oesophagus and progression to cancer. Eur J Gastroenterol Hepatol. 2016;28(3):251–60. https://doi.org/10.1097/MEG.0000000000000536.CrossRefPubMedPubMedCentral

12.

Andrici J, Cox MR, Eslick GD. Cigarette smoking and the risk of Barrett’s esophagus: a systematic review and meta-analysis. J Gastroenterol Hepatol. 2013;28(8):1258–73. https://doi.org/10.1111/jgh.12230.CrossRefPubMed

13.

Cook MB, Kamangar F, Whiteman DC, Freedman ND, Gammon MD, Bernstein L, et al. Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the international BEACON consortium. J Natl Cancer Inst. 2010;102(17):1344–53. https://doi.org/10.1093/jnci/djq289.CrossRefPubMedPubMedCentral

14.

Chak A, Buttar NS, Foster NR, Seisler DK, Marcon NE, Schoen R, et al. Metformin does not reduce markers of cell proliferation in esophageal tissues of patients with Barrett’s esophagus. Clin Gastroenterol Hepatol. 2015;13(4):665–72 e1-4. https://doi.org/10.1016/j.cgh.2014.08.040.CrossRefPubMed

15.

Agrawal S, Patel P, Agrawal A, Makhijani N, Markert R, Deidrich W. Metformin use and the risk of esophageal cancer in Barrett esophagus. South Med J. 2014;107(12):774–9. https://doi.org/10.14423/SMJ.0000000000000212.CrossRefPubMed

16.

Lou Z, Xing H, Li D. Alcohol consumption and the neoplastic progression in Barrett's esophagus: a systematic review and meta-analysis. PLoS One. 2014;9(10):e105612. https://doi.org/10.1371/journal.pone.0105612.CrossRefPubMedPubMedCentral

17.

Hamade N, Vennelaganti S, Parasa S, Vennalaganti P, Gaddam S, Spaander MCW, et al. Lower annual rate of progression of short-segment vs long-segment Barrett’s esophagus to esophageal adenocarcinoma. Clin Gastroenterol Hepatol. 2018. https://doi.org/10.1016/j.cgh.2018.07.008.

18.

Krishnamoorthi R, Lewis JT, Krishna M, Crews NJ, Johnson ML, Dierkhising RA, et al. Predictors of progression in Barrett’s esophagus with low-grade dysplasia: results from a multicenter prospective BE registry. Am J Gastroenterol. 2017;112(6):867–73. https://doi.org/10.1038/ajg.2017.84.CrossRefPubMed

19.

Gregson EM, Bornschein J, Fitzgerald RC. Genetic progression of Barrett’s oesophagus to oesophageal adenocarcinoma. Br J Cancer. 2016;115(4):403–10. https://doi.org/10.1038/bjc.2016.219.CrossRefPubMedPubMedCentral

20.

Findlay JM, Middleton MR, Tomlinson I. Genetic biomarkers of Barrett’s esophagus susceptibility and progression to dysplasia and cancer: a systematic review and meta-analysis. Dig Dis Sci. 2016;61(1):25–38. https://doi.org/10.1007/s10620-015-3884-5.CrossRefPubMed

21.

Desai TK, Samala N. The incidence of esophageal adenocarcinoma among patients with nondysplastic Barrett’s esophagus has been overestimated. Clin Gastroenterol Hepatol. 2011;9(4):363–4; author reply 4-5. https://doi.org/10.1016/j.cgh.2010.11.009.

22.

Krishnamoorthi R, Ramos GP, Crews N, Johnson M, Dierkhising R, Shi Q, et al. Persistence of nondysplastic Barrett’s esophagus is not protective against progression to adenocarcinoma. Clin Gastroenterol Hepatol. 2017;15(6):950–2. https://doi.org/10.1016/j.cgh.2017.02.019.CrossRefPubMed

23.

Horvath B, Singh P, Xie H, Thota PN, Allende DS, Pai RK, et al. Risk for esophageal neoplasia in Barrett’s esophagus patients with mucosal changes indefinite for dysplasia. J Gastroenterol Hepatol. 2015;30(2):262–7. https://doi.org/10.1111/jgh.12696.CrossRefPubMed

24.

Kestens C, Leenders M, Offerhaus GJ, van Baal JW, Siersema PD. Risk of neoplastic progression in Barrett’s esophagus diagnosed as indefinite for dysplasia: a nationwide cohort study. Endoscopy. 2015;47(5):409–14. https://doi.org/10.1055/s-0034-1391091.CrossRefPubMed

25.

Curvers WL, ten Kate FJ, Krishnadath KK, Visser M, Elzer B, Baak LC, et al. Low-grade dysplasia in Barrett's esophagus: overdiagnosed and underestimated. Am J Gastroenterol. 2010;105(7):1523–30. https://doi.org/10.1038/ajg.2010.171.CrossRefPubMed

26.

Whitson MJ, Falk GW. Predictors of progression to high-grade dysplasia or adenocarcinoma in Barrett’s esophagus. Gastroenterol Clin N Am. 2015;44(2):299–315. https://doi.org/10.1016/j.gtc.2015.02.005.CrossRef

27.

Rubenstein JH, Waljee AK, Dwamena B, Bergman J, Vieth M, Wani S. Yield of higher-grade neoplasia in Barrett’s esophagus with low-grade dysplasia is double in the first year following diagnosis. Clin Gastroenterol Hepatol. 2018;16(9):1529–30. https://doi.org/10.1016/j.cgh.2018.01.002.CrossRefPubMedPubMedCentral

28.

Wani S, Qumseya B, Sultan S, Agrawal D, Chandrasekhara V, Harnke B, et al. Endoscopic eradication therapy for patients with Barrett’s esophagus-associated dysplasia and intramucosal cancer. Gastrointest Endosc. 2018;87(4):907–31 e9. https://doi.org/10.1016/j.gie.2017.10.011.CrossRefPubMed

29.

Galipeau PC, Li X, Blount PL, Maley CC, Sanchez CA, Odze RD, et al. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med. 2007;4(2):e67. https://doi.org/10.1371/journal.pmed.0040067.CrossRefPubMedPubMedCentral

30.

Davelaar AL, Calpe S, Lau L, Timmer MR, Visser M, Ten Kate FJ, et al. Aberrant TP53 detected by combining immunohistochemistry and DNA-FISH improves Barrett's esophagus progression prediction: a prospective follow-up study. Genes Chromosom Cancer. 2015;54(2):82–90. https://doi.org/10.1002/gcc.22220.CrossRefPubMed

31.

Kastelein F, Biermann K, Steyerberg EW, Verheij J, Kalisvaart M, Looijenga LH, et al. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett’s oesophagus. Gut. 2013;62(12):1676–83. https://doi.org/10.1136/gutjnl-2012-303594.CrossRefPubMed

32.

Weston AP, Banerjee SK, Sharma P, Tran TM, Richards R, Cherian R. p53 protein overexpression in low grade dysplasia (LGD) in Barrett’s esophagus: immunohistochemical marker predictive of progression. Am J Gastroenterol. 2001;96(5):1355–62. https://doi.org/10.1111/j.1572-0241.2001.03851.x.CrossRefPubMed

33.

Keswani RN, Noffsinger A, Waxman I, Bissonnette M. Clinical use of p53 in Barrett’s esophagus. Cancer Epidemiol Biomark Prev. 2006;15(7):1243–9. https://doi.org/10.1158/1055-9965.EPI-06-0010.CrossRef

34.

Janmaat VT, van Olphen SH, Biermann KE, Looijenga LHJ, Bruno MB, Spaander MCW. Use of immunohistochemical biomarkers as independent predictor of neoplastic progression in Barrett’s oesophagus surveillance: a systematic review and meta-analysis. PLoS One. 2017;12(10):e0186305. https://doi.org/10.1371/journal.pone.0186305PONE-D-17-.CrossRefPubMedPubMedCentral

35.

Bird-Lieberman EL, Neves AA, Lao-Sirieix P, O'Donovan M, Novelli M, Lovat LB, et al. Molecular imaging using fluorescent lectins permits rapid endoscopic identification of dysplasia in Barrett’s esophagus. Nat Med. 2012;18(2):315–21. https://doi.org/10.1038/nm.2616.CrossRefPubMed

36.

Alvi MA, Liu X, O'Donovan M, Newton R, Wernisch L, Shannon NB, et al. DNA methylation as an adjunct to histopathology to detect prevalent, inconspicuous dysplasia and early-stage neoplasia in Barrett’s esophagus. Clin Cancer Res. 2013;19(4):878–88. https://doi.org/10.1158/1078-0432.CCR-12-2880.CrossRefPubMed

37.

Jin Z, Cheng Y, Gu W, Zheng Y, Sato F, Mori Y, et al. A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus. Cancer Res. 2009;69(10):4112–5. https://doi.org/10.1158/0008-5472.CAN-09-0028.CrossRefPubMedPubMedCentral

38.

Timmer MR, Martinez P, Lau CT, Westra WM, Calpe S, Rygiel AM, et al. Derivation of genetic biomarkers for cancer risk stratification in Barrett’s oesophagus: a prospective cohort study. Gut. 2016;65(10):1602–10. https://doi.org/10.1136/gutjnl-2015-309642.CrossRefPubMed

39.

•• Parasa S, Vennalaganti S, Gaddam S, Vennalaganti P, Young P, Gupta N, et al. Development and validation of a model to determine risk of progression of Barrett’s esophagus to neoplasia. Gastroenterology. 2018;154(5):1282–9 e2. https://doi.org/10.1053/j.gastro.2017.12.009. This study describes a new score based on computer modeling based on clinical, endoscopic features and degree of dysplasia to predict progression of BE to HGD/EAC.CrossRefPubMed

40.

•• Critchley-Thorne RJ, Davison JM, Prichard JW, Reese LM, Zhang Y, Repa K, et al. A tissue systems pathology test detects abnormalities associated with prevalent high- grade dysplasia and esophageal cancer in Barrett’s esophagus. Cancer Epidemiol Biomark Prev. 2017;26(2):240–8. https://doi.org/10.1158/1055-9965.EPI-16-0640. This study describes a computer model using automated analysis of tissue morphology and staining for molecular markers to stratify risk of progression in BE.CrossRef

Title: Predictors of Progression in Barrett’s Esophagus
Authors: Subhankar Chakraborty, MBBS, PhD
Prasad G. Iyer, MD, MSc
Publication date: 01-03-2019
Publisher: Springer US
Keyword: Barrett Esophagus
Published in: Current Treatment Options in Gastroenterology / Issue 1/2019
Print ISSN: 1092-8472
Electronic ISSN: 1534-309X
DOI: https://doi.org/10.1007/s11938-019-00214-9

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Predictors of Progression in Barrett’s Esophagus

Abstract

Purpose of review

Recent findings

Summary

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose of review

Recent findings

Summary

Please log in to get access to this content

Other articles of this Issue 1/2019

Optical Diagnosis of Colorectal Polyps: Recent Developments

Colorectal Cancer in Young Adults

Advances in the Diagnosis and Treatment of GERD: New Tricks for an Old Disease

Endoscopic Retrograde Cholangiopancreatography in Pediatric Populations

New Advances in the Treatment of Acute Pancreatitis

Challenges in Endoscopic Therapy of Dysplastic Barrett’s Esophagus

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page