Outcome Of Antireflux Surgery In Patients With Barrett’s Esophagus
Few studies have focused on the alleviation of symptoms after anti¬reflux surgery in patients with Barrett’s esophagus (BE). Those that are avail¬able document excellent to good results in 72 to 95% of patients at 5 years following surgery.
Several studies have compared medical and surgical therapy. Attwood and associates, in a prospective but nonrandomized study, reported on 45 patients undergoing either medical (26) or surgi¬cal (19) treatment of BE. The groups were similar in age, length of Barrett’s segment, and the percentage of time during which pH was less than 4, and length of follow-up. Improvement of symptoms was dramatic after antireflux surgery. Symptoms of heartburn or dysphagia recurred in 88% of patients treated with medical therapy alone, and 21% after antireflux surgery. Complications, most com¬monly the development of an esophageal stricture, occurred in 38% of medically treated patients and 16 percent of surgically treated patients (p < 0.05) over the 3-year follow-up period. One patient in each group developed esophageal adenocarcinoma. It was con¬cluded that antireflux surgery was superior to acid suppression for both the control of symptoms and the prevention of complications in patients with BE. Other nonrandomized comparisons of medical and surgical therapy have reported similar results.
Parrilla and colleagues recently reported an update of a study originally published in the British Journal of Surgery in 1996. One hundred one patients were enrolled over 18 years (1982 to 2000). Median follow-up was 6 years. Medical therapy consisted of 20 mg of omeprazole (PPI) twice daily since 1992 in all medically treated patients. Surgical therapy consisted of an open 1.5 to 3.0 cm Nissen, over a 48 to 50F bougie, with division of the short gastric arteries in 39% of patients, and crural closure in all. Symptomatic outcome in the two groups was nearly identical, although esophagitis and/or Stricture persisted in 20% of the medically treated patients, com¬pared to only 3 to 7% of patients following antireflux surgery. Fifteen percent of patients had abnormal acid exposure after surgery. Al¬though pH data were not routinely collected in patients on PPI ther¬apy, in the subgroup of 12 patients that did have 24-hour monitoring on treatment, three of 12 (25%) had persistently high esophageal acid exposure, and most (75%) had persistently high bilirubin exposure.
The outcome of laparoscopic Nissen fundoplication in patients with BE has been assessed at 1 to 3 years after surgery Hofstetter and colleagues reported the experience at the University of Southern California (USC) with 85 patients with BE at a median of 5 years after surgery. Fifty-nine patients had long and 26 had-short segment Barrett’s; 50 had a laparoscopic approach. Reflux symptoms were absent in 67 of 85 patients (79%). Eighteen (20%) devel¬oped recurrent symptoms, while four patients were back on daily acid-suppressive medication. Seven patients underwent a secondary repair and were asymptomatic, raising the eventual successful outcome to 87%. Postoperative 24-hour pH was normal in 17 of 21 patents (81%). Ninety-nine percent of the patients considered themselves cured (77%) or improved (22%), and 97% were satis¬fied with the surgery. Farrell and associates also reported symptomatic outcome of laparoscopic Nissen fundoplication in 50 patients with both long ¬and short-segment BE. Mean scores for heartburn, regurgitation, and dysphagia all improved dramatically post-Nissen. Importantly, there was no significant decrement in symptom scores when 1-year results were compared to those at 2 to 5 years postoperatively. They did find a higher prevalence of “anatomic” failures requiring re-operation in patients with BE when compared to non-Barren’s patients with GERD. Others have reported similar results. Taken together these studies document the ability of antireflux surgery to provide long¬ term symptomatic relief in patients with BE.
Long-Term Results
Three relevant questions arise concerning the fate, over time, of the metaplastic tissue found in Barren’s esophagus: (1) Does anti¬reflux surgery cause regression of Barrett’s epithelium? (2) Does it prevent progression? and (3) Can the development of Barren’s metaplasia be prevented by early antireflux surgery in patients with reflux disease’?
The common belief that Barrett’s epithelium cannot be reversed a likely false. DeMeester and associates reported that after antireflux surgery, loss of intestinal metaplasia (IM) in patients with visible BE was rare, but occurred in 73% of patients with inapparent IM of the cardia. This suggests that the metaplastic process may indeed be reversible if reflux is eliminated early in its process, that cardiac mucosa is dynamic, and that as opposed to IM extending several cen¬timeters into the esophagus, IM of the cardia is more likely to regress following antireflux surgery. Gurski and colleagues recently re¬viewed pre- and post treatment endoscopic biopsies from 77 Barrett’s patients treated surgically and 14 treated with PPIs. Post treatment histology was classified as having regressed if two consecutive biopsies taken more than 6 months apart, plus all subsequent biopsies, showed loss of IM or loss of dysplasia. Histopathologic regres¬sion occurred in 28 of 77 patients (36.4%) following antireflux surgery, and in one of 14 (7.1%) patients treated with PPIs alone (p < 0.03). After surgery, regression from low-grade dysplastic to nondysplastic BE occurred in 17 of 25 (68%) patients and from L\l to no IM in 11 of 52 (21.2%) patients. Both types of regres¬sion were significantly more common in short- (<3 cm) com¬pared to long-segment (>3 cm) Barren’s esophagus. Eight patients progressed; five from IM alone to low-grade dysplasia, and three from low- to high-grade dysplasia. All those who progressed had long-segment BE. On multivariate analysis, the presence of short¬ segment Barren’s, and the type of treatment, were significantly as¬sociated with regression; age, sex, surgical procedure, and preop¬erative LES and pH characteristics were not. The median time of biopsy-proven regression was 18.5 months after surgery, with 95% occurring within 5 years. Although these studies do not conclusively prove the ability of anti-reflux surgery to reverse the changes of early BE they do provide encouragement that given early changes, the process may indeed be reversible.
Recent evidence suggests that the development of BE may even be preventable. Although a very difficult hypothesis to study, Oberg Ana coworkers followed a cohort of 69 patients with short-segment, nonintestinalized, columnar-lined esophagus (CLE) over a median of 5 years of surveillance endoscopy. Forty-nine of the patients were maintained on PPI therapy and 20 had antireflux surgery. Patients with antireflux surgery were 10 times less likely to develop IM in these CLE segments over a follow-up span of nearly 15 years than those on medical therapy. This rather remarkable observation supports the two-step hypothesis of the development of BE (cardiac metaplasia followed by intestinal metaplasia), and suggests that the second step can be prevented if reflux disease is recognized and treated early and aggressively.
Current data indicate that patients with BE should remain in an endoscopic surveillance program following antireflux surgery. A pathologist should review biopsy specimens with exper¬tise in the field using compound light microscopes. If low-grade dysplasia is confirmed, biopsies should be repeated after 12 weeks of high-dose acid suppression therapy using compound light microscopes. If high-grade dysplasia is evident on more than one biopsy spec¬imen when viewed under a microscope, esophageal resection is advisable because of the more than 50% probability that an invasive cancer is already present. Early detection and resection have been shown to decrease the mortality rate from esophageal cancer in these patients.
Since BE results from chronic uncontrolled gastroesophageal reflux, and esophageal adenocarcinoma is virtually always associ¬ated with intestinal metaplasia, there are strong theoretical grounds for halting the progression toward malignancy by permanently and effectively stopping reflux of gastric contents. Thus prevention of progression, not regression, becomes the central issue. Although some cancers have developed after antireflux surgery, the absence of pre-existent dysplasia prior to surgery or the efficacy of the op¬erative procedure in reducing 24-hour esophageal acid exposure to normal has not been documented. If the dysplasia is reported as lower grade or indeterminant, then inflammatory change often confused with dysplasia should be suppressed by a course of acid suppression therapy in high doses for 2 to 3 weeks, followed by rebiopsy of the Barrett’s segment.
There is a growing body of evidence to attest to the ability of fundoplication to protect against dysplasia and invasive malignancy (diagnosed with the use of compound light microscopes). Three studies suggest that an effective antireflux procedure can im¬pact the natural history of BE in this regard. Two prospective ran¬domized studies found less adenocarcinoma in the surgically treated groups when studied under compound light microscopes. Parrilla and associates reported that although the develop¬ment of dysplasia and adenocarcinoma was no different overall, the subgroup of surgical patients with normal postoperative pH studies developed significantly less dysplasia and had no adenocarcinoma. Spechler identified one adenocarcinoma 11 to 13 years after antire¬flux surgery, compared to four following medical treatment. Most of these authors concluded that there is a critical need for future trials exploring the role of antireflux surgery in protecting against the development of dysplasia in patients with BE.
Data from the Mayo Clinic strongly suggest that antireflux surgery impacts the development of adenocarcinoma in patients with BE. The authors reviewed the outcome of 118 patients with BE undergoing antireflux surgery between 1960 and 1990. Three cancers occurred over an 18.5-year follow-up period, all within the first 3 years after surgery. The fact that the development of adeno¬carcinoma, diagnosed with the use of compound light microscopes, was clustered in the early years after antireflux surgery, and not randomly dispersed throughout the follow-up period, sug¬gests that antireflux surgery altered the natural history of the disease. Hammeetman has shown that once dysplasia has developed, carci¬noma ensues in an average of 3 years. The occurrence of all observed cancers in the first few years suggests that the point of no return in the dysplasia-cancer sequence had already occurred prior to the time of antireflux surgery.
