Diagnosis of Columnar Metaplasia of the Esophageal Mucosa in Patients with Complicated Gastroesophageal Reflux Disease

Aim: to improve methods of diagnostics of esophageal mucosal forms of metaplasia and dysplasia in patients with complicated forms of gastroesophageal reflux disease (GERD) using multidisciplinary approach.

Material and methods. Overall, 131 patients aged 18 to 84 years (mean age — 55.8 ± 16.7 years) with confirmed diagnosis of GERD complicated by development of metaplasia of mucosa of distal esophagus were included in retroand prospective study. At the prehospital stage the patients' complaints were estimated, anamnesis was taken. At the first stage of the diagnostic program all patients underwent detailed esophagogastroduodenoscopy in high resolution with white light. The region of esophageal mucosa with signs of metaplasia and determination of its prevalence was examined and evaluated with special attention. Ultrashort segment was revealed in 26 patients, short segment — in 47 patients, long segment of mucosal metaplasia was revealed in 58 patients. Then to reveal the signs of dysplasia we used specifying endoscopic methods: the structure of pitted and microvascular pattern was estimated in narrow spectral mode using BING classification system. If an irregular type of metaplasized epithelium structure was detected in the process of BING assessment, the areas suspicious for dysplasia were marked, followed by aim forceps biopsy from them. The next stage was staining of the metaplasized segment with 1.5 % ethanic acid solution — acetowhitening. PREDICT classification system was used to evaluate the stained mucosal sections with metaplasia. Targeted forceps biopsy was performed from the altered areas that most quickly lost their coloring. The final stage of the diagnostic program in all patients was a forceps biopsy of the mucosa of the metaplasic segment according to the Seattle protocol, which requires increasing the number of fragments as the metaplasic segment lengthens in a “blind” biopsy. The biopsy material was stained with hematoxylin and eosin, and periodic acid Schiff reaction was performed in combination with alcyanine blue according to the standard technique.

Results. Endoscopic examination in white light and evaluation of metaplasia extent revealed ultrashort segment (<1 cm) in 26/131 (19.9 %) patients; short segment (1–3 cm) — in 47/131 (35.9 %); long segment (> 3 cm) — in 58/131 (44.3 %) patients. Among the diagnostic techniques used, the BING and PREDICT classifications had the highest accuracy, sensitivity, and specificity (accuracy — 88.9 and 95.3 %, sensitivity — 90.5 and 91.3 %, and specificity — 86.7 and 100 %, respectively), which significantly exceeded the Seattle protocol also used in this work. The results showed a low level of specificity (31.2 %), accuracy (54.5 %), and sensitivity (76.8 %) of the Seattle protocol. The use of BING and PREDICT classifications provided marking of compromised zones, allowing targeted histological sampling.

Conclusions. The original study demonstrated the greatest sensitivity, specificity, and accuracy of PREDICT and BING methods in the diagnosis of metaplasia with signs of dysplasia in patients with complicated GERD. It is also important that the use of BING and PREDICT classification systems allows to reduce the number of biopsy samples in comparison with their unreasonably large number according to the Seattle protocol, thereby reducing mucosal and submucosal trauma of the esophagus and the risk of complications.

1. Shaheen N.J., Falk G.V., Ayer P.G., Gerson L.B.; American College of Gastroenterology. ACG clinical guide: Diagnosis and treatment of Barrett's esophagus. Am J Gastroenterol. 2016;111(1):30–50. DOI: 10.1038/ajg.2015.322

2. Wani S., Falk G.W., Post J., Yerian L., Hall M., Wang A., et al. Risk factors for progression of low-grade dysplasia in patients with Barrett’s esophagus. Gastroenterology. 2011;141(4):1179–86. DOI: 10.1053/j.gastro.2011.06.055

3. Rex D.K., Cummings O.W., Shaw M., Cumings M.D., Wong R.K., Vasudeva R.S., et al. Screening for Barrett's esophagus in colonoscopy patients with and without heartburn. Gastroenterology. 2003;125(6):1670–7. DOI: 10.1053/j.gastro.2003.09.030

4. Duits L.C., Phoa K.N., Curvers W.L., Kate F.J.W.T, Meijer G.A., Seldenrijk C.A., et al. Barrett’s oesophagus patients with low-grade dysplasia can be accurately risk-stratified after histological review by an expert pathology panel. Gut. 2015;64(5):700–6. DOI: 10.1136/gutjnl-2014-307278

5. Sharma P. Clinical practice. Barrett's esophagus. N Eng J Med. 2009;361(26):2548–56. DOI: 10.1056/NEJMcp0902173

6. Rastogi A., Puli S., El-Serag H.B., Bansal A., Wani S., Sharma P. Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: Meta-analysis. Gastrointest Endosc. 2008;67(3):394–8. DOI: 10.1016/j.gie.2007.07.019

7. Wang K.K., Sampliner R.E.; 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;103(3):788–97. DOI: 10.1111/j.1572-0241.2008.01835.x

8. Fitzgerald R.C., di Pietro M., Ragunath K., Ang Y., Jin-Yong Kang J., Watson P., et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus. Gut. 2014;63(1):7–42. DOI: 10.1136/gutjnl-2013-305372

9. Takubo K., Aida J., Naomoto Y., Sawabe M., Arai T., Shiraishi H., et al. Cardiac rather than intestinal type background in endoscopic resection specimens of minute Barrett adenocarcinoma. Hum Pathol. 2009;40(1):65–74. DOI: 10.1016/j.humpath.2008.06.008

10. Emura F., Chandrasekar V.T., Hassan C., Armstrong D., Messmann H., Arantes V., et al. Rio de Janeiro Global Consensus on landmarks, definitions, and classifications in Barrett’s esophagus: World Endoscopy Organization Delphi Study. Gastroenterology. 2022;163(1):84–96.е2. DOI: 10.1053/j.gastro.2022.03.022

11. Lavery D.L., Martinez P., Gay L.J., Cereser B., Novelli M.R., Rodriguez-Justo M., et al. Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett’s oesophagus. Gut. 2016;65(6):907–13. DOI: 10.1136/gutjnl-2015-310748

12. Levine D.S., Haggitt R.C., Blount P.L., Rabinovitch P.S., Rusch V.W., Reid B.J. An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett’s esophagus. Gastroenterology. 1993;105(1):40–50. DOI: 10.1016/0016-5085(93)90008-z

13. Kariv R., Plesec T.P., Goldblum J.R., Bronner M., Oldenburgh M., Rice T.W., et al. The Seattle protocol does not more reliably predict the detection of cancer at the time of esophagectomy than a less intensive surveillance protocol. Clin Gastroenterol Hepatol. 2009;7(6):653–8. DOI: 10.1016/j.cgh.2008.11.024

14. Sharma P., McQuaid K., Dent J., Fennerty B.M., Sampliner R., Spechler S., et al. A critical review of the diagnosis and management of Barrett’s esophagus: The AGA Chicago workshop. Gastroenterology. 2004;127(1):310–30. DOI: 10.1053/j.gastro.2004.04.010

15. Abrams J., Kapel R., Lindberg G., Saboorian M., Genta R., Neugut A., et al. Adherence to biopsy guidelines for Barrett’s esophagus surveillance in the community setting in the United States. Clin Gastroenterol Hepatol. 2009;7(7):736-742. DOI: 10.1016/j.cgh.2008.12.027

16. Visrodia K., Singh S., Krishnamoorthi R., Ahlquist D.A., Wang K.K., Iyer P.G., et al. Magnitude of missed esophageal adenocarcinoma after Barrett’s esophagus diagnosis: A systematic review and meta-analysis. Gastroenterology. 2016;150(3):599–607. DOI: 10.1053/j.gastro.2015.11.040

17. Sharma P., Bergman J.J., Goda K., Kato M., Messmann H., Alsop B.R., et al. Development and validation of a classification system for detecting esophageal dysplasia and adenocarcinoma in Barrett's esophagus using narrow-band imaging. Gastroenterology. 2016;150(3):591–8. DOI: 10.1053/j.gastro.2015.11.037

18. Kandiah K., Chedgy F.J.Q., Subramaniam S., Longcroft-Wheaton G., Bassett P., Repici A., et al. International development and validation of a classification system for the identification of Barrett's neoplasia using acetic acid chromoendoscopy: The Portsmouth acetic acid classification (PREDICT). Gut. 2018;67(12):2085–91. DOI: 10.1136/gutjnl-2017-314512

19. Belova G.V., Rudenko O.S. Endoscopic anatomy of esophageal-gastric junction was normal, when hiatus hernias and cylindricity metaplasia of esophageal mucosa. Eksperimental'naya i klinicheskaya gastroenterologiya. 2017;144(8):52–4. (In Russ.).

20. Sharma P., Dent J., Armstrong D., Bergman J.G.H.M., Gossner L., Hoshihara Y., et al. The development and validation of an endoscopic grading system for Barrett’s esophagus: The Prague C&M criteria. Gastroenterology. 2006;131(5):1392–9. DOI: 10.1053/j.gastro.2006.08.032

21. Inoue H., Fujiyoshi Y., Abad M.R.A., Rodriguez de Santiago E., Sumi K., Iwaya Y., et al. A novel endoscopic assessment of the gastroesophageal junction for the prediction of gastroesophageal reflux disease: A pilot study. Endosc Int Open. 2019;7(11):E1468–73. DOI: 10.1055/a0990-9737

22. Inoue H., Shimamura Y., Rodriguez de Santiago E., Kobayashi Y., Ominami M., Fujiyoshi Y., et al. Diagnostic performance of the endoscopic pressure study integrated system (EPSIS): A novel diagnostic tool for gastroesophageal reflux disease. Endoscopy. 2019;51(8):759–62. DOI: 10.1055/a-0938-2777

23. Weusten B., Bisschops R., Coron E., Ribeiro M., Dumonceau J.M., Esteban L.M., et al. Endoscopic management of Barrett’s esophagus: European Society of Gastrointestinal Endoscopy (ESGE) position statement. Endoscopy. 2017;49(2):191–8. DOI: 10.1055/s-0042-122140

24. Ivashkin V.T., Mayev I.V., Trukhmanov A.S., Baranskaya Ye.K., Dronova О.B., Zayratyants О.V., et al. Diagnostics and treatment of gastroesophageal reflux disease: Clinical guidelines of the Russian Gastroenterological Association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2017;27(4):75–95. (In Russ.). DOI: 10.22416/1382-4376-2017-27-4-75-95