Theoretical Analysis

The management of Barrett's esophagus remains a controversial area. Most patients will die from Barrett's rather than from an esophageal adenocarcinoma. However, in a patient with Barrett's esophagus, it is now possible to remove abnormal areas and resurface the entire lower esophagus using a variety of endoscopic techniques. The question remains, who should be treated? Many studies have looked at treating metaplasic Barrett's, which can be easily ablated. Currently, ablation is not widely used nor recommended for patients with metaplasia only. Most usually, treatment is restricted to patients who are detected to have high-grade dysplasia, at risk of malignant degeneration, or patients with an early Barrett's adenocarcinoma. Other strategies are being explored for the large numbers of patients with Barrett's metaplasia. Treatment of dysplasia demands an "obsession with regression" whereas "prevention of progression" is the correct approach for metaplasia. Most patients in this latter group can have excellent symptom control on PPI therapy. It is highly appropriate that this is being formally addressed, at the epicenter of the epidemic, by Cancer Research U.K. and National Cancer Research Network in the United Kingdom. They are supporting a large randomized trial on chemoprevention using aspirin and esomeprazole—Aspirin and Esomeprazole Chemoprevention Trial (AspECT). The trial has commenced, and, due to its size, will inform many of our future management strategies (71).

It is appropriate, while awaiting long-term data, to conduct a "Gedanken" thought experiment. The purpose is to estimate the effect of endoscopic eradication of high-grade dysplasia xtrapolating from current data. This would involve detection and destruction of dysplasia followed by continued surveillance.

FIGURE 6 A "theoretical experiment" detection, destruction of dysplasia. The continuous lines indicate the incidence of high-grade dysplasia, esophageal adenocarcinoma, and the mortality from esophageal adenocarcinoma. The circles (blue and crimson) represent the data available from 1998, when trials of ablation started, and indicate that high-grade dysplasia could be eradicated and thus the incidence, and the mortality and incidence of esophageal adenocarcinoma considerably reduced. Abbreviations: HGD, high-grade dysplasia; PDT, photodynamic therapy.

FIGURE 6 A "theoretical experiment" detection, destruction of dysplasia. The continuous lines indicate the incidence of high-grade dysplasia, esophageal adenocarcinoma, and the mortality from esophageal adenocarcinoma. The circles (blue and crimson) represent the data available from 1998, when trials of ablation started, and indicate that high-grade dysplasia could be eradicated and thus the incidence, and the mortality and incidence of esophageal adenocarcinoma considerably reduced. Abbreviations: HGD, high-grade dysplasia; PDT, photodynamic therapy.

The assumptions are:

1. Patients progression to adenocarcinoma is through detected Barrett's esophagus and highgrade dysplasia (72).

2. The incidence of esophageal cancer continues to rise, and the mortality continues to parallel the incidence.

3. Figure 6 presents the theoretical analysis and suggests that the mortality and possibly the incidence of esophageal adenocarcinoma could be considerably reduced.

This minimally invasive solution to the eradication of high-grade dysplasia in Barrett's esophagus has been subject to a detailed cost-effective analysis (73). It was compared with (i) no preventive strategy, (ii) elective surgical esophagectomy, (iii) endoscopic ablation, and (iv) surveillance endoscopy. The strategy of endoscopic ablation provided the longest quality-adjusted life expectancy. Endoscopic surveillance was cheaper but associated with shorter survival, and the authors conclude that optimal utilization of healthcare resources was achieved by endo-scopic ablation (73).

Effect of Surgery on the Natural History of Barrett's Esophagus

The place of surgery in controlling the natural history of Barrett's esophagus relates to three areas. These are the symptoms, the benign and malignant complications. The majority of patients with Barrett's remain symptomatic for life with partial relief by taking acid suppression medication.

Effect on Surgery on the Natural History of Symptoms

The rationale for antireflux surgery in the management of patients with Barrett's esophagus comes from the understanding that the degree of reflux in these patients is at the severe end of the reflux spectrum (74). This has been best documented by pH and bile reflux monitoring (75). The degree of exposure of the esophagus to acid in the average patient with Barrett's is more than twice that of patients with esophagitis and an even greater difference to those without tissue injury. It is clear to see why acid suppression with PPIs is less effective in this group, compared to refluxers with less tissue injury and it creates a group of patients for whom there is more to gain by stopping the reflux completely with a surgical procedure. Even when symptoms are controlled with PPIs, there is still a pathological exposure of the esophagus to acid and to bile in patients with Barrett's esophagus (76).

There is some debate in the literature about the effectiveness of antireflux surgery in patients with Barrett's esophagus. Most surgical authors believe that there is no significant difference in the effectiveness of the common operation (Nissen fundoplication) for patients with Barrett's esophagus compared to patients without Barrett's. As surgeons, the authors do recognize that the patients with Barrett's esophagus have more edema in the wall of the esophagus, and more peri-esophagitis with adhesions, making the dissection slightly more demanding. Despite this it is our experience and that of others (77) that the technical achievement of a completed fundoplication is still straightforward in patients with Barrett's esophagus. In the laparoscopic approach to antireflux surgery, there is no difference in rates of conversion to open surgery among patients with or without Barrett's. The subsequent disruption of the repair or recurrence of reflux is said by some authors to be a bigger problem in patients with Barrett's esophagus than those without Barrett's (78,79). The literature overall favors the view that patients after antireflux surgery with Barrett's may do marginally worse than those without. Recurrent symptoms occur in 25% of Barrett's patients (range 45-155) compared to 10% (5-15%) in those without Barrett's. There is a wide range of opinion on this: Parrilla et al. (80) state that there is no difference between those refluxers with or without Barrett's metaplasia in terms of symptomatic and 24-hour pHmetry follow-up (8% failure with Barrett's vs. 10% without Barrett's). Others have documented anatomical disruption of the wrap, to be twice as common in Barrett's (12%) compared to those with uncomplicated gastroesophageal reflux disease (5%) (79).

Effect of Surgery on the Natural History of Benign Complications

The literature on the effect of antireflux surgery on complications in Barrett's esophagus is limited to peptic stricture. The other complications of bleeding and perforation are too rare for any useful cohort studies or prospective trials. Table 1 describes three studies which have looked at nonrandomized (81,82) and randomized (83) cohorts of patients with Barrett's esophagus who were treated by either continuation of acid suppression or by antireflux surgery. In the nonrandomized studies, it is important to look at the case selection. In both, the indication for surgery included a requirement for symptoms to persist despite acid suppression medication. Thus, the patient group who were offered surgery were initially those patients who were worse than those left on medical therapy. After successful antireflux surgery, patients in both groups were asymptomatic initially, and in each study, follow-up over three to five years showed a significant recurrence of symptoms of reflux and in symptomatic peptic stricture. The literature shows a clear benefit in both symptomatic outcome and prevention of stricture after antireflux surgery for patients with Barrett's esophagus (evidence level 1b and 2b, recommendation Grade B).

Effect of Surgery on the Natural History of Malignant Degeneration

From the standpoint of tumor biology, it has been believed for some time that patients with reflux injury in their esophageal epithelium are at an increased risk of developing adenocarcinoma through the metaplastic process of Barrett's esophagus. A logical hypothesis is that if the reflux

TABLE 1 Comparison of Medical Vs. Surgical Treatment of Reflux Disease and Barrett's Esophagus

Author

Number in study

Length F'up yrs

Recurrent stricture

Symptoms reflux

Med rx

Surg rx

Med rx

Surg rx

McEntee 1991

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