What are the endoscopic features of neoplasia (dysplasia and early cancer) within a BO segment?

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What are the endoscopic features of neoplasia (dysplasia and early cancer) within a BO segment?

Introduction

Dysplasia and early cancer in Barrett’s Oesophagus (BO) can be inconspicuous. This is the premise behind the present recommended strategy of performing random four quadrant biopsies in every two centimetres of the BO segment. This approach has been frequently described as ‘’hit and miss’’ and is fraught with problems such as adherence where only 41-56% of endoscopist follow the recommended guideline.[1][2] Newer endoscopic imaging modalities have been proposed to improve the detection of dysplasia. Numerous studies have been performed on chromoendoscopy techniques (Methylene Blue, Indigo Carmine and Acetic Acid), electronic image enhancement technologies (Narrow Band Imaging, I Scan, Fujinon Intelligent Chromo Endoscopy) and high magnification platforms (Confocal Endomicroscopy, Endocytoscopy). Although promising, the data appears to have been limited mostly to tertiary referral and research centres with experience and interest in endoscopic imaging. There is lack of information if these methods can ultimately impact patient management. At the present moment, high resolution white light endoscopy (HR-WLE) remains the gold standard in evaluating patients with BO although the modalities described above can be used in addition to HR-WLE to improve characterisation of lesions.[3] Thus, it is important to understand the gross morphological features of dysplasia and early cancer and if available, apply some of the more advanced imaging methods.


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How should surveillance be performed?

For purposes of standardisation, the Prague’s C & M criteria has been proposed. The criteria includes the assessment of the circumferential (C) and maximum (M) extent of the endoscopically visualised BO segment, as well as endoscopic landmarks, such as the upper end of the gastric folds[4] (see also What is the endoscopic definition of BO and how is it described?). These findings have been validated in two large studies to date and has been found to be not only practical but reproducible.[5][6] It also enables accurate identification of a lesion on repeat endoscopy for endoscopic resection especially if biopsies which have been performed previously on an inconspicuous area reveal dysplasia or early cancer.

Dysplasia in BO can be patchy.[7] Thus examination of any patient with BO should be meticulous. Debris and mucous should be washed off. If there is extensive peristalsis, antispasmodic agents can be used. A recent study from Kansas described spending longer times inspecting the BO segment (1cm/minute) which led to a significant increase in the yield of detecting dysplastic lesions.[8]


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Gross features of dysplasia and early cancer which should be looked for

There is some evidence that cancer preferentially occurs in the distal Barrett's segment. A study of 213 patients with esophageal adenocarcinoma reported that in over 80% of cases, the tumor was located at the distal margin of the columnar-lined segment.[9] It is also important to pay special attention to the two to five o’clock position in patients with shorter segments of BO (<5cm) as there is evidence that these areas could harbor more dysplasia.[10] It may be worthwhile to retroflex the endoscope in a hiatal hernia segment and carefully examine this area.

All ulcers in BO should be monitored closely for carcinoma. In a large case series that reported endoscopic characteristics of mucosal cancers, depressed or excavated lesions were found in 49 of 349 patients (14%).[11] Biopsies should always be taken in depressed regions and if negative; repeated after a course of proton pump inhibitor therapy.

Visible lumps or nodules consisting of high grade dysplasia (HGD) suggest a more advanced lesion where more sinister pathology may be present. Studies have shown that endoscopic resection of visible lumps or nodules consisting of HGD in biopsies result in an upgrade to a final diagnosis of cancer in almost 40% of cases.[12][13] In a surgical series of esophagectomies performed for presumed HGD in biopsies, coexisting cancer was found in 78% of patients with a visible lesion compared to 32% without a visible lesion (p = 0.019).[14] The importance of careful examination for synchronous and more advanced pathology cannot be underestimated.


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Interrogating suspicious areas

Suspicious lesions visualised on ‘white light overview’ can be interrogated further with any of the enhanced imaging techniques described above. Digital or optical magnification endoscopes have been utilised using Methylene Blue (MB), Acetic Acid (AA) or Narrow Band Imaging (NBI). A meta-analysis by Ngamruengphong et al of 450 patients with BO in nine studies concluded that MB chromoendoscopy was comparable and not superior to conventional four-quadrant random biopsies.[15] AA and NBI appear to be more promising. Areas harboring dysplasia or early cancer appear to lose the aceto-whitening reaction when AA is used.[16][17] With NBI and magnification, an irregular microvasculature and/or microstructure can be visualised in areas harbouring dysplasia or cancer.[18][19][20][21] A few studies have looked at even higher levels of magnification (>450X) using Confocal Endomicroscopy[22][23][24][25][26] or Endocytoscopy[27][28] where histology can be visualised in real time. Irregularity of the cellular structure remains the key feature in differentiating dysplastic from non dysplastic tissue.

It is, however, not yet clear at this stage whether these modalities can replace biopsies. Some of them are expensive, time consuming, technically difficult and requires additional knowledge in interpreting images. Given its high negative predictive value, there could be a role where normal areas which do not harbour any dysplasia (based on various criteria advocated by various investigators) could be ‘left alone’ and simply not sampled.[29][30][31] Only abnormal or suspicious areas should be subjected to biopsies or resection. This practice could potentially lead to a paradigm shift of how patients are surveyed presently and warrants further assessment.

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Conclusion

Given the inconspicuous nature of dysplasia in BO, meticulous inspection and attention to subtle endoscopic anomalies using the best available equipment and endoscopes are warranted. At the present moment, after careful interrogation of the BO mucosa; random four quadrant biopsies according to the Seattle protocol should be undertaken (see also What is the histological definition and grading of dysplasia in patients with BO? and What are the histological features of early adenocarcinoma of the oesophagus?).

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References

  1. Mandal A, Playford RJ, Wicks AC. Current practice in surveillance strategy for patients with Barrett's oesophagus in the UK. Aliment Pharmacol Ther 2003 May 15;17(10):1319-24 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12755845.
  2. Abrams JA, Kapel RC, Lindberg GM, Saboorian MH, Genta RM, Neugut AI, et al. Adherence to biopsy guidelines for Barrett's esophagus surveillance in the community setting in the United States. Clin Gastroenterol Hepatol 2009 Jul;7(7):736-42; quiz 710 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19268726.
  3. Bennett C, Vakil N, Bergman J, Harrison R, Odze R, Vieth M, et al. Consensus statements for management of Barrett's dysplasia and early-stage esophageal adenocarcinoma, based on a Delphi process. Gastroenterology 2012 Aug 1;143(2):336-46 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22537613.
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  5. Chang CY, Lee YC, Lee CT, Tu CH, Hwang JC, Chiang H, et al. The application of Prague C and M criteria in the diagnosis of Barrett's esophagus in an ethnic Chinese population. Am J Gastroenterol 2009 Jan;104(1):13-20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19098843.
  6. Lee YC, Cook MB, Bhatia S, Chow WH, El-Omar EM, Goto H, et al. Interobserver reliability in the endoscopic diagnosis and grading of Barrett's esophagus: an Asian multinational study. Endoscopy 2010 Sep;42(9):699-704 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20806154.
  7. Cameron AJ, Carpenter HA. Barrett's esophagus, high-grade dysplasia, and early adenocarcinoma: a pathological study. Am J Gastroenterol 1997 Apr;92(4):586-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9128304.
  8. Gupta N, Gaddam S, Wani SB, Bansal A, Rastogi A, Sharma P. Longer inspection time is associated with increased detection of high-grade dysplasia and esophageal adenocarcinoma in Barrett's esophagus. Gastrointest Endosc 2012 Sep;76(3):531-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22732877.
  9. Theisen J, Stein HJ, Feith M, Kauer WK, Dittler HJ, Pirchi D, et al. Preferred location for the development of esophageal adenocarcinoma within a segment of intestinal metaplasia. Surg Endosc 2006 Feb;20(2):235-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16391958.
  10. Kariyawasam VC, Bourke MJ, Hourigan LF, Lim G, Moss A, Williams SJ, et al. Circumferential location predicts the risk of high-grade dysplasia and early adenocarcinoma in short-segment Barrett's esophagus. Gastrointest Endosc 2012 May;75(5):938-44 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22381529.
  11. Pech O, Behrens A, May A, Nachbar L, Gossner L, Rabenstein T, et al. Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus. Gut 2008 Sep;57(9):1200-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18460553.
  12. Pech O, Gossner L, Manner H, May A, Rabenstein T, Behrens A, et al. Prospective evaluation of the macroscopic types and location of early Barrett's neoplasia in 380 lesions. Endoscopy 2007 Jul;39(7):588-93 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17611912.
  13. Peters FP, Brakenhoff KP, Curvers WL, Rosmolen WD, Fockens P, ten Kate FJ, et al. Histologic evaluation of resection specimens obtained at 293 endoscopic resections in Barrett's esophagus. Gastrointest Endosc 2008 Apr;67(4):604-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18155214.
  14. Tharavej C, Hagen JA, Peters JH, Portale G, Lipham J, DeMeester SR, et al. Predictive factors of coexisting cancer in Barrett's high-grade dysplasia. Surg Endosc 2006 Mar;20(3):439-43 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16437272.
  15. Ngamruengphong S, Sharma VK, Das A. Diagnostic yield of methylene blue chromoendoscopy for detecting specialized intestinal metaplasia and dysplasia in Barrett's esophagus: a meta-analysis. Gastrointest Endosc 2009 May;69(6):1021-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19215918.
  16. Fortun PJ, Anagnostopoulos GK, Kaye P, James M, Foley S, Samuel S, et al. Acetic acid-enhanced magnification endoscopy in the diagnosis of specialized intestinal metaplasia, dysplasia and early cancer in Barrett's oesophagus. Aliment Pharmacol Ther 2006 Mar 15;23(6):735-42 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16556175.
  17. Longcroft-Wheaton G, Duku M, Mead R, Poller D, Bhandari P. Acetic acid spray is an effective tool for the endoscopic detection of neoplasia in patients with Barrett's esophagus. Clin Gastroenterol Hepatol 2010 Oct;8(10):843-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20601133.
  18. Wolfsen HC, Crook JE, Krishna M, Achem SR, Devault KR, Bouras EP, et al. Prospective, controlled tandem endoscopy study of narrow band imaging for dysplasia detection in Barrett's Esophagus. Gastroenterology 2008 Jul;135(1):24-31 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18442484.
  19. Kara MA, Ennahachi M, Fockens P, ten Kate FJ, Bergman JJ. Detection and classification of the mucosal and vascular patterns (mucosal morphology) in Barrett's esophagus by using narrow band imaging. Gastrointest Endosc 2006 Aug;64(2):155-66 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16860062.
  20. Sharma P, Bansal A, Mathur S, Wani S, Cherian R, McGregor D, et al. The utility of a novel narrow band imaging endoscopy system in patients with Barrett's esophagus. Gastrointest Endosc 2006 Aug;64(2):167-75 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16860063.
  21. Singh R, Anagnostopoulos GK, Yao K, Karageorgiou H, Fortun PJ, Shonde A, et al. Narrow-band imaging with magnification in Barrett's esophagus: validation of a simplified grading system of mucosal morphology patterns against histology. Endoscopy 2008 Jun;40(6):457-63 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18459090.
  22. Kiesslich R, Gossner L, Goetz M, Dahlmann A, Vieth M, Stolte M, et al. In vivo histology of Barrett's esophagus and associated neoplasia by confocal laser endomicroscopy. Clin Gastroenterol Hepatol 2006 Aug;4(8):979-87 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16843068.
  23. Dunbar KB, Okolo P 3rd, Montgomery E, Canto MI. Confocal laser endomicroscopy in Barrett's esophagus and endoscopically inapparent Barrett's neoplasia: a prospective, randomized, double-blind, controlled, crossover trial. Gastrointest Endosc 2009 Oct;70(4):645-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19559419.
  24. Leung KK, Maru D, Abraham S, Hofstetter WL, Mehran R, Anandasabapathy S. Optical EMR: confocal endomicroscopy-targeted EMR of focal high-grade dysplasia in Barrett's esophagus. Gastrointest Endosc 2009 Jan;69(1):170-2 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18582880.
  25. Pohl H, Rösch T, Vieth M, Koch M, Becker V, Anders M, et al. Miniprobe confocal laser microscopy for the detection of invisible neoplasia in patients with Barrett's oesophagus. Gut 2008 Dec;57(12):1648-53 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18755886.
  26. Bajbouj M, Vieth M, Rösch T, Miehlke S, Becker V, Anders M, et al. Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrett's esophagus. Endoscopy 2010 Jun;42(6):435-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20506064.
  27. Pohl H, Koch M, Khalifa A, Papanikolaou IS, Scheiner K, Wiedenmann B, et al. Evaluation of endocytoscopy in the surveillance of patients with Barrett's esophagus. Endoscopy 2007 Jun;39(6):492-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17554642.
  28. Singh R, Chen Yi Mei SL, Tam W, Raju D, Ruszkiewicz A. Real-time histology with the endocytoscope. World J Gastroenterol 2010 Oct 28;16(40):5016-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20976836.
  29. Sharma P, Hawes RH, Bansal A, Gupta N, Curvers W, Rastogi A, et al. Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett's oesophagus: a prospective, international, randomised controlled trial. Gut 2013 Jan;62(1):15-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22315471.
  30. Jayasekera C, Taylor AC, Desmond PV, Macrae F, Williams R. Added value of narrow band imaging and confocal laser endomicroscopy in detecting Barrett's esophagus neoplasia. Endoscopy 2012 Dec;44(12):1089-95 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23188660.
  31. Singh R, Shahzad MA, Tam W, Goda K, Yu LH, Fujishiro M, et al. Preliminary feasibility study using a novel narrow-band imaging system with dual focus magnification capability in Barrett's esophagus: Is the time ripe to abandon random biopsies? Dig Endosc 2013 May;25 Suppl 2:151-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/23617668.

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Appendices


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