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Lymph node metastases in cancer: a new way to look at things.

We studied patients with Barrett esophagus who had undergone a fundoplication at least 5 years before and found that there was significantly more deoxyribonucleic acid (DNA) methylation in columnar tissue from patients with an abnormal 24-hour pH study (a result of a failed fundoplication) than in those with a normal pH study (an intact fundoplication). We did not have preoperative DNA methylation profiles for our fundoplication patients, and so for part of our analysis, we measured DNA methylation in columnar tissue from a separate cohort of patients with Barrett esophagus who had not had an operation. We found that tissue from patients with a failed fundoplication had comparable levels of DNA methylation to that from unoperated patients. From these results, we concluded that reflux was associated with DNA methylation and further that abnormal reflux was associated with increased methylation. We would have preferred to have esophageal tissues from our surgical patients before their operation so that we could compare the DNA methylation levels before and after the operation in the same patient. Such tissues were not available. It would not be practical to establish groups, which were comparable in every parameter that can be measured to characterize reflux. We dichotomized our patients into 2 broad groups, normal or abnormal reflux, and showed that only normal levels of reflux were associated with low levels of DNA methylation. No patient had detectable dysplasia before operation. To the best of our knowledge, we were the first to objectively measure reflux in fundoplication patients this length of time after surgery and so be able to compare regression between patients with proven normal reflux (intact fundoplication) and patients with abnormal reflux (failed fundoplication). No underlying intestinal metaplasia was seen in any biopsies of squamous epithelium. While a number of factors may influence regression of Barrett esophagus, our point is that if reflux is controlled to normal levels then regression may be seen.