Skip to main content
SpringerLink
Log in

Long-Term Follow-up of Barrett’s Epithelium: Medical Versus Antireflux Surgical Therapy

  • 2011 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Barrett’s esophagus (BE) is the most serious complication of GERD. In BE patients, this observational study compares the effects of antireflux surgery versus antisecretory medical therapy.

Methods

Overall, 89 BE patients (long BE = 45; short BE = 44) were considered: 45 patients underwent antireflux surgery and 44 underwent medical therapy. At both initial and follow-up endoscopy, symptoms were assessed using a detailed questionnaire; BE phenotypic changes [intestinal metaplasia (IM) presence/type, Cdx2 expression] were assessed by histology (H&E), histochemistry (HID), and immunohistochemistry. Surgical failures were defined as follows: (1) abnormal 24-h pH monitoring results after surgery, (2) endoscopically evident recurrent esophagitis, and (3) recurrent hiatal hernia or slipped fundoplication on endoscopy or barium swallow.

Results

Reversion of IM was observed in 12/44 SSBE and 0/45 LSBE patients (p < 0.01). Reversion was more frequently observed after effective antireflux surgery than after medical treatment (p = 0.04). In patients with no further evidence of IM after therapy, Cdx2 expression was also absent (p = 0.02). The extent of IM was reduced, and the IM phenotype improved in SSBE patients after surgery.

Conclusions

Patients with short BE (but not those with long BE) may benefit from surgically reducing the esophagus’ exposure to GE reflux; among these patients, successful surgery carries a higher IM reversion rate than medical treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Falk GW. Barrett’s esophagus. Gastroenterology 2002; 122:1569–91

    Article  PubMed  Google Scholar 

  2. DeMeester SR, DeMeester TR. Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy. Ann Surg 2000; 231:300–32

    Article  Google Scholar 

  3. Cameron AJ, Carpenter HA. Barrett’s esophagus, high grade dysplasia and early adenocarcinoma: a pathological study. Am J Gastroenterol 1997; 92:586–591

    PubMed  CAS  Google Scholar 

  4. Clark GW, Ireland AP, Peters H, Chandrasoma P, DeMeester TR, Bremner CG. Short Segment Barrett’s Esophagus: a prevalent complication of gastroesophageal reflux disease with malignant potential. J Gastrointest Surg 1997; 1: 113–122

    Article  PubMed  CAS  Google Scholar 

  5. Csendes A, Smok G, Quiroz J et al. Clinical, endoscopic and functional studies in 408 patients with Barrett’s esophagus, compared to 174 cases of intestinal metaplasia of the cardia Am J Gastroenterol 2002; 97: 554–560

    Article  PubMed  Google Scholar 

  6. Mueller J, Werner M, Stolte M. Barrett’s esophagus: histopathological definitions and criteria. World J Surg 2004; 28: 148–154

    Article  PubMed  Google Scholar 

  7. Groisman GM, Amar M, Meir A. Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett’s) metaplasia. Mod Pathol 2004; 17: 1282–88

    Article  PubMed  CAS  Google Scholar 

  8. Zaninotto G, Rizzetto C. Surgical options and outcomes in Barrett’s esophagus Curr Opin Gastroenterol. 2007; 23: 452–5.

    Article  PubMed  Google Scholar 

  9. Jamieson JR, Stein HJ, DeMeester TR et al. Ambulatory 24-h esophageal pH monitoring: normal values, optimal thresholds, specificity, sensitivity and reproducibility. Am J Gastroenterol 1992; 87: 104–11

    Google Scholar 

  10. Passaretti S, Zaninotto G, Di Martino N, Leo P, Costantini M, Baldi F. Standards for oesophageal manometry. A position statement from the Gruppo Italiano di Studio per la Motilita’ dell’Apparato Digerente. Dig Liv Dis 2000; 32: 46–55

    Article  CAS  Google Scholar 

  11. Sampliner RE, Fennerty B., Garewal HS. Reversal of Barrett’s esophagus with acid suppression and multipolar electrocoagulation: preliminary results. Gastrointest Endosc. 1996; 44 532–5

    Article  PubMed  CAS  Google Scholar 

  12. Lundell LR, Dent J, Bennett JR, et al. Endoscopic assessment of esophagitis: clinical and functional correlates and further validation of the Los Angeles classification. Gut 1999; 45:172–80

    Article  PubMed  CAS  Google Scholar 

  13. Jass J, Filipe MN. A variant of intestinal metaplasia associated with gastric carcinoma. A histochemical study. Histopathology 1979; 3: 191–9

    Article  PubMed  CAS  Google Scholar 

  14. Phillips RW, Frierson HF, Mosakuk A. Cdx2 as a marker of epithelial differentiation in the esophagus. Am J Surg Pathol 2003; 27: 1442 1447

    Article  PubMed  Google Scholar 

  15. Rugge M, Correa P, Dixon MF, et al. Gastric dysplasia: the Padova International classification. Am J Surg Path 2000; 24:167–76

    Article  PubMed  CAS  Google Scholar 

  16. Kaur BS, Ouatu-lascar R, Omary MB et al. Bile salts induce or blunt cell proliferation in Barrett’s esophagus in an acid-dependent fashion. Am J Physiol 2000; 278:G1000-9

    CAS  Google Scholar 

  17. Ingravallo G, Dall’Olmo L, Segat D et al. Cdx2 Hox gene product in a rat model of esophageal cancer. J Experim & Clin Canc Res 2009; 29: 108–14

    Article  Google Scholar 

  18. Fassan M, Volinia S, Palatini J et al. MicroRNA expression profiling in human Barrett’s carcinogenesis. Int J Cancer. 2010 Dec 2. [Epub ahead of print].

  19. Rugge M, Fassan M, Zaninotto G, et al Aurora kinase A in Barrett’s carcinogenesis. Hum Pathol. 2010 Oct;41(10):1380–6. Epub 2010 Jul 24.

    Article  PubMed  CAS  Google Scholar 

  20. Bowers SP, Mattur SO, Smith CD, et al. Clinical and histologic follow-up after antireflux surgery for Barrett’s esophagus. J Gastrointest Surg 2002; 6: 532–39

    Article  PubMed  Google Scholar 

  21. Gurski RR, Peters JH, Hagenn JA et al Barrett’s esophagus can and does regress after antireflux surgery: a study of prevalence and predictive factors. J Am Coll Surg 2003; 196:706–13

    Article  PubMed  Google Scholar 

  22. Oelschager BK, Barreca M, Chang L, Oleynikov D, Pellegrini CA. Clinical and pathologic response of Barrett’s esophagus after antireflux surgery. Ann Surg 2003; 238:458–66

    Google Scholar 

  23. O’Riordan JM, Byrne PJ, Ravi N, Keeling PW, Reynolds JV. Long-term clinical and pathologic response after antireflux surgery. Am J Surg 2004; 188:27–33

    Article  PubMed  Google Scholar 

  24. Zaninotto G, Cassaro M, Pennelli G, Battaglia G, et al. Barrett’s epithelium after antireflux surgery. J Gastrointest Surg 2005; 9: 1253–1261

    Article  PubMed  Google Scholar 

  25. Biertho L, Dallemagne B, Dewandre J-M et al. Laparoscopic treatment of Barrett’s esophagus: long-term results. Surg Endosc 2007; 21:11–5

    Article  PubMed  CAS  Google Scholar 

  26. Csendes A, Braghetto I, Burdiles P et al. Late results of the surgical treatment of 125 patients with short-segment Barrett Esophagus. Arch Surg 2009; 144: 921–27

    Article  PubMed  Google Scholar 

  27. Dikman R, Kim JL, Camargo L et al. Correlation of gastroesophageal reflux disease symptoms characteristics with long-segment Barrett’s esophagus. Dis Esophagus 2006; 19:360–5

    Article  Google Scholar 

  28. Zentilin P, Reglioni S, Savarino V. Pathophysiological characteristics of long- and short-segment Barrett’s esophagus. Scand J Gastroenterol 2003; (S 38) 239: 40–43

    Google Scholar 

  29. Zaninotto G, Portale G, Parenti A et al. Role of acid and bile reflux in development of specialized intestinal metaplasia in distal esophagus. Digest Liver Dis 2002; 34:251–7

    Article  CAS  Google Scholar 

  30. Pfaffenbach B, Hullerum J, Orth et al. Bile and acid reflux in long and short segment Barrett’s esophagus and in reflux disease. Z Gastroenterol 2000; 38:565–70

    Article  PubMed  CAS  Google Scholar 

  31. Horwhat JD, Baroni D, Maydonovitch C et al. Normalization of intestinal metaplasia in the esophagus and esophagogastric junction: incidence and clinical data Am J Gastroenterol 2007; 192: 497–506

    Article  Google Scholar 

  32. Souza RF, Krishnan K, Spechler J. Acid, bile and Cdx: the ABC of making Barrett’s metaplasia. Am J Physiol Gastrointest Liver Physiol 2008; 295:211–18

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, SS Giovanni e Paolo Hospital, ULSS 12, Venice, Italy

    Giovanni Zaninotto

  2. Department of Surgical and Gastroenterological Sciences, Surgical Unit—Clinica Chirurgica I—and Gastroenterology Unit “R. Farini”, Padua, Italy

    Renato Salvador, Fabio Farinati, Chiara Tieppo, Nicola Passuello, Lisa Zanatta, Mario Costantini, Claudia Mescoli, Alberto Ruol & Ermanno Ancona

  3. Department of Diagnostic Medical Sciences & Special Therapies—Pathology & Cytopathology Unit School of Medicine, University of Padova, Padua, Italy

    Paola Parente, Matteo Fassan & Massimo Rugge

  4. Surgical Oncology, Istituto Oncologico Veneto, IOV-IRCCS, Padua, Italy

    Francesco Cavallin & Giorgio Battaglia

  5. U.O.C. Chirurgia Generale, Ospedale SS Giovanni e Paolo, ULSS 12, Castello 5777, Venice, Italy

    Giovanni Zaninotto

Authors
  1. Giovanni Zaninotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paola Parente
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renato Salvador
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fabio Farinati
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chiara Tieppo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nicola Passuello
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lisa Zanatta
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Matteo Fassan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Francesco Cavallin
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Mario Costantini
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Claudia Mescoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Giorgio Battaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Alberto Ruol
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ermanno Ancona
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Massimo Rugge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Zaninotto.

Additional information

Discussant

Dr. George Triadafilopoulos (Mountain View, CA):

Significance

This is a cohort, parallel-group study that assessed the influence of fundoplication versus medical therapy on clinical and endoscopic findings and Cdx2 protein expression in patients with nondysplastic Barrett’s esophagus. It is a large-scale effort with an impressive collection of clinical, physiologic, and biological data over a mean period of 3 years, and it was conducted at a center of excellence in esophageal surgery.

Brief critique

It is not a prospective randomized trial; hence, the two groups were not directly comparable. As an example, the age of the surgical group was younger, potentially favorably influencing outcome. The mean duration—3 years—is relatively short, since possible late failures of surgical therapy were not accounted for. The medically treated group was not optimized for pH control; patients were treated for symptoms only. We know that up to 50% of Barrett’s esophagus patients maintain abnormal acid exposure even on twice daily PPI, while >90% of patients after fundoplication normalize acid exposure.

Questions

Is regression (16–47%) a reasonable endpoint in Barrett’s esophagus? Or should we be aiming for complete elimination of metaplasia and Cdx2 expression?

What were the dysplasia rates in the two groups? One would imagine that dysplasia or neoplasia would be more important markers of disease behavior.

Today that we have safe and effective methods for Barrett’s esophagus ablation (such as HALO), wouldn’t it be reasonable to conduct a prospective, randomized trial of medical versus surgical therapy in ablated patients aiming at prevention of dysplasia or complete ablation and lack of Cdx2 expression?

Closing Discussant

Dr. Renato Salvador: Thank you very much for your comments. We acknowledge that this study is not a randomized trial but compares two large cohorts of Barrett’s patients from a single institution, receiving different treatments. On the other hand, our results could stimulate the organization of a multicenter RCT and we strongly feel that this kind of study is largely due. The most relevant outcome of the present study is that, when acid suppression is achieved, intestinal metaplasia, which is the main feature of BE, may regress in a substantial number of patients either with PPI treatment or antireflux surgery, but this regression is observed only in patients with short-segment Barrett’s esophagus. Further, IM regression is three times more frequent in patients who received antireflux surgery. Is 50% regression a good end point in an era when radiofrequency may ablate completely all metaplastic tissue? The answer to this relevant question could be that by aggressively treating, with medical or surgical acid suppression, patients with short-segment BE, who represent two third of the BE population, we can reserve ablative therapy for the minority of patients with long-segments BE, who are probably at more risk of adenocarcinoma. As far as the second question is concerned, we had only one patient with low-grade dysplasia in a long BE segment. The patient was treated by antireflux surgery, and LG dysplasia was still evident at follow-up. We totally agree that a trial on medical versus surgical therapy in patients with long-segment BE should be designed in the next future.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zaninotto, G., Parente, P., Salvador, R. et al. Long-Term Follow-up of Barrett’s Epithelium: Medical Versus Antireflux Surgical Therapy. J Gastrointest Surg 16, 7–15 (2012). https://doi.org/10.1007/s11605-011-1739-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-011-1739-8

Keywords

Search

Navigation