title: Antireflux surgery and esophageal mucosal DNA damage.
abstract: Gastroesophageal reflux disease (GERD) is characterized by reflux of gastroduodenal contents, esophagitis and oxidative tissue damage in the distal esophagus. It may ultimately lead to the development of a pre-malignant Barrett's esophagus and subsequently to carcinoma. Antireflux surgery is an effective therapeutic tool to relieve GERD symptoms and to normalize the reflux to the distal esophagus. However, antireflux surgery may be insufficient to restore oxidative insult, which can promote DNA adduct formation and subsequent initiation of carcinogenesis. Controversy exists whether antireflux surgery can reverse the development of carcinoma in the mucosa. We aimed to test the effect of antireflux surgery on DNA adduct formation in the esophagus. Patients (n = 19) with objectively confirmed GERD underwent antireflux surgery and were followed up for 6 months after which a symptom evaluation, control endoscopy, biopsy and pH-measurements were performed. The amounts of DNA adducts in the proximal and distal mucosa of the esophagus were measured using the 32-P-postlabelling method. After the surgery, esophageal acid exposure was normalized in all the patients and symptoms were relieved in all but one patient. Endoscopic examinations showed that erosive esophagitis had healed in all the cases 6 months after the surgery. Barrett's esophagus was found in six cases in preoperative biopsies. The amount of DNA adducts in the distal esophagus was higher than in the proximal esophagus both pre- and postoperatively. Antireflux surgery did not change this pattern and was thus not capable of reducing DNA adduct formation. The level of DNA damage was similar in the patients having Barrett's esophagus compared to the rest of the patients. Antireflux surgery is insufficient to normalize DNA damage due to GERD. Our observations suggest that antireflux surgery is perhaps not effective in the prevention of carcinogenesis because of the persisting DNA damage.
authors.affiliation: Department of Surgery, Tampere University Hospital, Tampere, Finland. niku.oksala@pshp.fi
authors.forename: Niku K J
authors.initials: NK
authors.lastname: Oksala
authors.forename: Mustafa
authors.initials: M
authors.lastname: Atalay
authors.forename: Tuomo K
authors.initials: TK
authors.lastname: Rantanen