Abstract
Background
The initial results from ablation therapy for metaplastic/dysplastic Barrett’s esophagus (BE) are promising, but the results of extended follow-up evaluation are seldom reported.
Methods
Neodymium:yttrium–aluminum-garnet laser ablation and successful antireflux surgery for 18 patients with metaplastic BE primarily resulted in the total histologic eradication of BE in 15 patients (83%). After antireflux surgery, the healing of gastroesophageal reflux disease (GERD) was objectively verified in all the patients. At late follow-up evaluation, endoscopy, conventional histology, molecular oxidative stress analyses in comparison with normal control conditions (8-hydroxydeoxyguanosine [8-OHdG], superoxide dismutase [SOD], glutathione [GSH], myeloperoxydase [MP]), and immunohistochemistry (p53, and Cdx2, caudal-related homeobox gene 2, marking intestinal differentiation) of the neosquamous epithelium were performed.
Results
At the end of the follow-up period (range, 3–15 years; mean, 8 years), intestinal metaplasia without dysplasia was detected histologically in eight patients (44%). Six patients had macroscopic BE (mean length, 3.5 cm; range 1–10 cm). The neosquamous epithelium was histologically normal, with no underlying columnar tissue. The fundoplication was endoscopically normal in 14 patients (82%). The 8-OHdG level was higher in the neosquamous epithelium than in the control conditions in the distal esophagus (4.3 vs. 0.52; P = 0.0002) and the proximal esophagus (1.8 vs. 0.95; P = 0.006). Likewise, SOD activity was higher in the neosquamous epithelium (0.38 vs. 0.12; P = 0.0005), whereas MP activity and GSH levels remained normal. Three patients showed slight nuclear p53 expression (typical in normal inflammatory reactions), whereas Cdx2 positivity was confined to one case with recurrent intestinal metaplasia.
Conclusions
The neosquamous mucosa, generated by the ablation of BE and the treatment of GERD with fundoplication, was stable during long-term follow-up evaluation in two-thirds of the patients with initial eradication. It had normal p53 expression and no Cdx2 protein expression. The oxidative stress of the neosquamous esophagus remained high, although the clinical significance of this is unclear.
Similar content being viewed by others
References
Spechler SJ, Lee E, Ahnen D, Goyal RK, Hirano I, Ramirez F, Raufman JP, Sampliner R, Schnell T, Sontag S, Vlahcevic ZR, Young R, Williford W (2001) Long-term outcome of medical and surgical therapies for gastroesophageal reflux disease: follow-up of a randomized controlled trial. J Am Med Assoc 285:2331–2338
Kauttu TM, Rantanen TK, Sihvo EI, Rasanen JV, Puolakkainen P, Salo JA (2011) Esophageal adenocarcinoma arising after antireflux surgery: a population-based analysis. Eur J Cardiothorac Surg 40:1450–1454
Parrilla P, Martinez de Haro LF, Ortiz A, Munitiz V, Molina J, Bermejo J, Canteras M (2003) Long-term results of a randomized prospective study comparing medical and surgical treatment of Barrett’s esophagus. Ann Surg 237:291–298
Bowers SP, Mattar SG, Waring PJ, Galloway K, Nasir A, Pascal R, Hunter JG (2003) KTP laser ablation of Barrett’s esophagus after antireflux surgery results in long-term loss of intestinal metaplasia: potassium–titanyl-phosphate. Surg Endosc 17:49–54
Ferraris R, Fracchia M, Foti M, Sidoli L, Taraglio S, Vigano L, Giaccone C, Rebecchi F, Meineri G, Senore C, Pera A (2007) Barrett’s oesophagus: long-term follow-up after complete ablation with argon plasma coagulation and the factors that determine its recurrence. Aliment Pharmacol Ther 25:835–840
Garewal H, Ramsey L, Sharma P, Kraus K, Sampliner R, Fass R (1999) Biomarker studies in reversed Barrett’s esophagus. Am J Gastroenterol 94:2829–2833
Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M (2006) Free radicals, metals, and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160:1–40
Olyaee M, Sontag S, Salman W, Schnell T, Mobarhan S, Eiznhamer D, Keshavarzian A (1995) Mucosal reactive oxygen species production in oesophagitis and Barrett’s oesophagus. Gut 37:168–173
Rasanen JV, Sihvo EI, Ahotupa MO, Farkkila MA, Salo JA (2007) The expression of 8-hydroxydeoxyguanosine in oesophageal tissues and tumours. Eur J Surg Oncol 33:1164–1168
Sihvo EI, Salminen JT, Rantanen TK, Ramo OJ, Ahotupa M, Farkkila M, Auvinen MI, Salo JA (2002) Oxidative stress has a role in malignant transformation in Barrett’s oesophagus. Int J Cancer 102:551–555
Rantanen TK, Rasanen JV, Sihvo EI, Ahotupa MO, Farkkila MA, Salo JA (2006) The impact of antireflux surgery on oxidative stress of esophageal mucosa caused by gastroesophageal reflux disease: 4-yr follow-up study. Am J Gastroenterol 101:222–228
Dvorak K, Payne CM, Chavarria M, Ramsey L, Dvorakova B, Bernstein H, Holubec H, Sampliner RE, Guy N, Condon A, Bernstein C, Green SB, Prasad A, Garewal HS (2007) Bile acids in combination with low pH induce oxidative stress and oxidative DNA damage: relevance to the pathogenesis of Barrett’s oesophagus. Gut 56:763–771
Prasad GA, Bansal A, Sharma P, Wang KK (2010) Predictors of progression in Barrett’s esophagus: current knowledge and future directions. Am J Gastroenterol 105:1490–1502
Moons LM, Bax DA, Kuipers EJ, Van Dekken H, Haringsma J, Van Vliet AH, Siersema PD, Kusters JG (2004) The homeodomain protein CDX2 is an early marker of Barrett’s oesophagus. J Clin Pathol 57:1063–1068
Salo JA, Salminen JT, Kiviluoto TA, Nemlander AT, Ramo OJ, Farkkila MA, Kivilaakso EO, Mattila SP (1998) Treatment of Barrett’s esophagus by endoscopic laser ablation and antireflux surgery. Ann Surg 227:40–44
Laihia JK, Jansen CT, Ahotupa M (1993) Lucigenin and linoleate enhanced chemiluminescent assay for superoxide dismutase activity. Free Radic Biol Med 14:457–461
Saville B (1958) A scheme for the colorimetric determination of microgram amounts of thiols. Analyst 83:670–672
Suzuki K, Ota H, Sasagawa S, Sakatani T, Fujikura T (1983) Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Anal Biochem 132:345–352
Rantanen TK, Salminen JT, Makinen JE, Sipponen PI, Kiviluoto TA, Salo JA (2001) Clinical significance of esophageal histologic findings after antireflux surgery. Arch Surg 136:733–736
Bright T, Watson DI, Tam W, Game PA, Astill D, Ackroyd R, Wijnhoven BP, Devitt PG, Schoeman MN (2007) Randomized trial of argon plasma coagulation versus endoscopic surveillance for barrett esophagus after antireflux surgery: late results. Ann Surg 246:1016–1020
Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, Galanko JA, Bronner MP, Goldblum JR, Bennett AE, Jobe BA, Eisen GM, Fennerty MB, Hunter JG, Fleischer DE, Sharma VK, Hawes RH, Hoffman BJ, Rothstein RI, Gordon SR, Mashimo H, Chang KJ, Muthusamy VR, Edmundowicz SA, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Falk GW, Kimmey MB, Madanick RD, Chak A, Lightdale CJ (2009) Radiofrequency ablation in Barrett’s esophagus with dysplasia. N Engl J Med 360:2277–2288
Ortiz A, Martinez de Haro LF, Parrilla P, Morales G, Molina J, Bermejo J, Liron R, Aguilar J (1996) Conservative treatment versus antireflux surgery in Barrett’s oesophagus: long-term results of a prospective study. Br J Surg 83:274–278
Rossi M, Barreca M, de Bortoli N, Renzi C, Santi S, Gennai A, Bellini M, Costa F, Conio M, Marchi S (2006) Efficacy of Nissen fundoplication versus medical therapy in the regression of low-grade dysplasia in patients with Barrett esophagus: a prospective study. Ann Surg 243:58–63
Jimenez P, Piazuelo E, Sanchez MT, Ortego J, Soteras F, Lanas A (2005) Free radicals and antioxidant systems in reflux esophagitis and Barrett’s esophagus. World J Gastroenterol 11:2697–2703
Huo X, Zhang HY, Zhang XI, Lynch JP, Strauch ED, Wang JY, Melton SD, Genta RM, Wang DH, Spechler SJ, Souza RF (2010) Acid and bile salt-induced CDX2 expression differs in esophageal squamous cells from patients with and without Barrett’s esophagus. Gastroenterology 139:194–203
Lopes CV, Pereira-Lima J, Hartmann AA (2005) p53 Immunohistochemical expression in Barrett’s esophagus before and after endoscopic ablation by argon plasma coagulation. Scand J Gastroenterol 40:259–263
Pouw RE, Gondrie JJ, Rygiel AM, Sondermeijer CM, ten Kate FJ, Odze RD, Vieth M, Krishnadath KK, Bergman JJ (2009) Properties of the neosquamous epithelium after radiofrequency ablation of Barrett’s esophagus containing neoplasia. Am J Gastroenterol 104:1366–1373
Acknowledgments
The authors thank Professor Markku Ahotupa of Turku University for carrying out the oxidative stress analyses, Dr. Tarja Peräkylä of the Helsinki University Central Hospital for her assistance in biopsy sampling, and Mrs. Yvonne Sundström for her skillful technical and secretarial assistance. The study was supported by the Helsinki University Central Hospital Research Funds (EVO) and the Sigrid Jusélius Foundation.
Disclosures
Tuuli Kauttu, Jari Räsänen, Leena Krogerus, Eero Sihvo, Pauli Puolakkainen, and Jarmo A. Salo have no conflicts of interest or financial ties to disclose.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kauttu, T., Räsänen, J., Krogerus, L. et al. Long-term results of ablation with antireflux surgery for Barrett’s esophagus: a clinical and molecular biologic study. Surg Endosc 26, 1892–1897 (2012). https://doi.org/10.1007/s00464-011-2121-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00464-011-2121-3