, according to a Nordic retrospective study.
Risk of EAC was higher among patients who underwent surgery, and risk appeared to increase over time, suggesting that postoperative patients should continue to participate in surveillance programs, reported lead author Jesper Lagergren, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues.
“Antireflux surgery with fundoplication increases the ability of the gastroesophageal anatomic and physiological barrier to prevent reflux, and can thus prevent any carcinogenic gastric content from reaching the esophagus, including both acid and bile,” the investigators wrote in Gastroenterology, noting that surgery reduces esophageal acid exposure to a greater degree than medication. “Antireflux surgery may thus prevent esophageal adenocarcinoma better than antireflux medication.”
Three meta-analyses to date, however, have failed to provide consistent support for this hypothesis.
“Most of the studies included in these meta-analyses came from single centers, were of small sample size, examined only one treatment arm, and had a short or incomplete follow-up, and ... were hampered by heterogeneity among the included studies,” they noted.
For the present study, Dr. Lagergren and colleagues analyzed national registry data from 33,939 patients with Barrett’s esophagus in Denmark, Finland, Norway, and Sweden. Out of this group, 542 patients (1.6%) had undergone antireflux surgery, while the remainder were managed with antireflux medication.
In both groups, approximately two-thirds of the patients were men. The median age at enrollment was about a decade higher in the medication group (66 vs. 54 years), and this group also tended to have more comorbidities.
After a follow-up period as long as 32 years, the absolute rates of EAC were 1.3% and 2.6% in the medication and surgery groups, respectively. Multivariate analysis, with adjustments for sex, age, year, comorbidities, and age, revealed that postsurgical patients had a 90% increased risk of EAC (hazard ratio [HR], 1.9; 95% CI, 1.1-3.5), versus patients treated with antireflux medication alone.
The relatively higher risk of EAC appeared to increase over time, based on a nonsignificant hazard ratio of 1.8 during the 1- to 4-year follow-up period (HR, 1.8; 95% CI, 0.6-5.0), versus a significant, fourfold risk elevation during the 10- to 32-year follow-up period (HR, 4.4; 95% CI, 1.4-13.5).
“In this cohort of patients with Barrett’s esophagus, the risk of esophageal adenocarcinoma did not decrease after antireflux surgery compared with antireflux medication,” the investigators wrote. “Instead, the risk was increased throughout the follow-up among patients having undergone antireflux surgery.”
Dr. Lagergren and colleagues suggested that the reason for relatively higher cancer risk in the group that underwent surgery likely stems from early and prolonged acid exposure.
“[P]erforming antireflux surgery after years of GERD may be too late to enable a cancer-preventative effect, and most of the patients first diagnosed with Barrett’s esophagus reported a history of many years of GERD symptoms,” they wrote, suggesting that carcinogenic processes had already been set in motion by the time surgery was performed.
“[P]atients with Barrett’s esophagus who undergo antireflux surgery remain at an increased risk of esophageal adenocarcinoma and should continue taking part in surveillance programs,” the investigators concluded.
The study was funded by the Swedish Cancer Society, Swedish Research Council, and Stockholm County Council. The investigators disclosed no conflicts of interest.