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Long-Term Follow-Up of Malignancy Biomarkers in Patients With Barrett's Esophagus Undergoing Medical or Surgical Treatment

de Haro, Luisa F. Martinez MD, PhD*; Ortiz, Angeles MD, PhD*; Parrilla, Pascual MD, PhD*; Munitiz, Vicente MD, PhD*; Martinez, Carlos M. PhD; Revilla, Beatriz PhD; de Angulo, David Ruiz MD*; Bermejo, Juan MD; Yélamos, Jose PhD§; Molina, Joaquin MD

doi: 10.1097/SLA.0b013e31824e6c6a
Original Articles

Objective: This study aims to compare some validated biomarkers of malignancy (Ki-67, p53, and apoptosis) between 2 groups of patients with Barrett's esophagus (BE) undergoing randomly medical or surgical treatment.

Background: The treatment of choice to prevent the malignant progression of BE remains controversial. Translational studies using biomarkers associated with the metaplasia-tumor pathway could be useful to provide some information in this regard.

Methods: The study group consisted of 45 patients: 20 under medical treatment with 40 mg/day of proton pump inhibitors (PPIs) and 25 after Nissen fundoplication (NFP). After a median follow-up of 8 years (range, 5–10 years), the values of Ki-67, p53, and apoptosis were analyzed in all patients before treatment (n = 45) and then 1 year (n = 45), 3 years (n = 45), 5 years (n = 45), and 10 years (n = 25) afterwards in both groups of treatment. These values were also analyzed in 2 subgroups of patients with successful medical and surgical treatment.

Results: Both Ki-67 and p53 remained stable after NFP, whereas they increased progressively in patients under PPIs with statistically significant differences between the 2 groups. Conversely, the apoptotic index increased progressively after NFP and decreased in the patients under PPIs with significant differences at 3, 5, and 10 years of follow-up. On comparing the subgroups of successful treatment the same differences were found.

Conclusions: Barrett's epithelium remains more stable after a long-term follow-up in patients with BE treated surgically than in those under PPIs even in the absence of abnormal rates of acid reflux.

Some validated biomarkers of malignancy (Ki-67, p53, and apoptosis) were compared between 2 groups of patients with Barrett's esophagus undergoing medical or surgical treatment. The results showed that Barrett's epithelium tends to remain more stable after a long-term follow-up in patients following antireflux surgery than in patients under medical therapy.

*Department of Surgery

Research Unit of Experimental Surgery

Department of Pathology

§Department of Immunology, Cancer Research Program, IMIM-Hospital del Mar, CIBERehd, Barcelona, Spain

Endoscopy Unit University Hospital V Arrixaca, CIBERehd, Murcia, Spain.

Reprints: Pascual Parrilla, MD, PhD, Department of Surgery, University Hospital V, Arrixaca, El Palmar. 30120-Murcia, Spain. E-mail:

Disclosure: This work has been supported by grants from the FIS (Fondo de Investigaciones Sanitarias) (PI09/1808), Fundación Mutua Madrileña and Fundación Séneca (08823/PI/08).

© 2012 Lippincott Williams & Wilkins, Inc.