How should patients with Barrett's esophagus be monitored?

Barrett's esophagus has been defined as "a change in the esophageal epithelium of any length that can be recognized at endoscopy and is confirmed to have intestinal metaplasia by biopsy of the tubular esophagus. Intestinal metaplasia is a pre-malignant lesion for adenocarcinoma of the esophagus. Surveillance by serial endoscopy with biopsy has been recommended in an effort to find high-grade dysplasia or carcinoma in an early, asymptomatic, and potentially curable stage. Approximately 75% of patients involved in a Barrett's esophagus surveillance program will present with resectable tumors, compared with only 25% of those not receiving surveillance. A recent systematic review assessing screening tools for esophageal carcinoma found standard endoscopy to be superior (90%-100% sensitivity) to other less invasive methods such as questionnaire (60%-70%), and fecal occult blood testing (20%). Additional endoscopy tools such as brush and balloon cytology increased the cost of surveillance without any improvement in diagnostic yield. The degree of dysplasia on esophageal biopsy in Barrett's esophagus patients is currently the best indicator of risk of progression to esophageal carcinoma. The data reviewed by the ACG for the practice guideline was drawn from several prospective studies and one available registry. In sum, a total of 783 Barrett's esophagus patients were followed for a mean of 2.9 to 7.3 years. Esophageal carcinoma developed in 2% of patients with no dysplasia, 7% of patients with low-grade dysplasia (LGD) and 22% of patients with high-grade dysplasia (HGD). The ACG recommendations regarding frequency of esophagogastroduodenoscopy (EGD) were not based on an explicit critical appraisal of the literature. Recent cohort studies are consistent with recommendations for graded surveillance frequency. A randomized clinical trial to determine optimal endoscopic frequency and benefit has not been reported. Several concerns have been raised regarding the utility of degree of dysplasia in determining optimal frequency of endoscopic surveillance. First, the progression of esophageal lesions over time is unpredictable. Skacel et al reported a series of 34 patients with LGD at initial pathologic examination. On subsequent surveillance endoscopy with repeat biopsy, 73% no longer demonstrated dysplasia. Such patients can be allowed to return to having surveillance every 3 years. In addition to the non-linear progression of dysplasia, inter-rater reliability of the interpretation of pathology specimens varies substantially. Adequate reliability has been demonstrated among pathologists assigning results to 2 categories (either no dysplasia and LGD or HGD and carcinoma) (κ=0.7). Assignment to four distinct pathologic grades, however, was not reliable (κ=0.46, where 1.0 is complete agreement). In order to make a diagnosis of HGD or carcinoma, interpretation must be independently confirmed by 2 expert pathologists. Recommendations for frequent endoscopic surveillance are also weakened by the overall low rate of mortality from esophageal carcinoma noted in Barrett's esophagus patients. A recent population based study demonstrated that there was no difference in overall mortality in those with a Barrett's esophagus diagnosis compared with the general population. An increased risk of death from esophageal carcinoma was seen in patients with Barrett's esophagus (4.7% seen in Barrett's esophagus patients compared with 0.8% predicted in the general population; P<.05). The overall increased effect on mortality, however, was relatively small. Esophageal carcinoma accounted for less then 5% of deaths in Barrett's esophagus patients reported during the study's 6-year follow-up period. Data from prospective studies published after 2002 may better predict prognosis for Barrett's esophagus patients. Even lower rates of progression to esophageal carcinoma (<0.5% a year or <1/220 patient-years) have been reported in these studies drawing from the general population rather than referred patients, likely stemming from differences in gender mix, patient age, and risk factors. In addition to grade of dysplasia, the length of the dysplastic Barrett's esophagus segment is emerging as a potentially predictive risk factor. While the ACG cautions that esophageal cancer has been reported in patients with so-called "short segment" Barrett's esophagus (SSBE) (≤3 cm), recent prospective studies have shown an increased risk of carcinoma development with long segment Barrett's esophagus (LSBE). Weston et al reported a 2.4% progression rate to HGD or esophageal carcinoma with SSBE and no dysplasia compared with 6.8% with LSBE (P=.002). If patients had LGD, the rate of progression to esophageal carcinoma with SSBE was 5.3% and jumped to 35% in patients with LSBE (P<.001). Conio et al reported that 4 of 5 cases of esophageal carcinoma noted through surveillance had LSBE. Hage et al reported a significantly increased risk of progression to HGD or esophageal carcinoma with long segment disease (P<.02). While currently still considered investigational, DNA content flow cytometry may be a future tool used in risk stratification. Reid et al report a 5-year cumulative risk of esophageal carcinoma of 1.7% in Barrett's esophagus patients with negative, low-grade or indefinite grades of dysplasia. Subsequent application of flow cytometry allowed for further stratification of these low-risk patients. Those with neither aneuploidy nor an increased 4N had a 5-year cumulative risk of cancer of 0% while the risk for those with abnormalities on cytometry increased to 28% (relative risk=19; P<.001).