The effect of fundoplication on proliferative and anti-apoptotic activity of esophageal mucosa in gastroesophageal reflux disease: 4-year follow-up study

Abstract

The capacity of fundoplication to prevent esophageal adenocarcinoma is controversial. Development of cancer is associated with proliferation and anti-apoptosis, for which little data exist as to their response to fundoplication. Therefore, we wanted to clarify the effect of fundoplication on the magnitude of Ki-67 and B-cell lymphoma 2 (Bcl-2) during 48 months of follow up. Ki-67 and Bcl-2 were assessed quantitatively from biopsies of the esophagogastric junction (EGJ) and from the distal and proximal esophagus of 20 patients with gastroesophageal reflux disease (GERD) treated by fundoplication. An upper gastrointestinal endoscopy was performed preoperatively and postoperatively at 6 months for 20 patients and 48 months for 16 patients, respectively. Ki-67 and Bcl-2 were compared to those of 7 controls. Compared to the preoperative level, Ki-67 was elevated in the distal (P = 0.012) and proximal (P = 0.007) esophagus at 48 months. Compared to control values, Ki-67 was lower at 6 months in the EGJ (P = 0.037) and the proximal esophagus (P = 0.003) and higher at 48 months in the distal esophagus (P = 0.002). Compared to control values, Bcl-2 was lower at 6 months in the EGJ (P = 0.038). Correlations between Ki-67 and Bcl-2 were positive in the EGJ (P > 0.001) and in the distal (P = 0.001) and proximal esophagus (P = 0.013). Proliferative activity after fundoplication increased during long-term follow up in the distal esophagus despite a normal fundic wrap and objective healing of GERD.