Evidence of Benefit
Squamous Cell Cancer
Squamous cell carcinoma of the esophagus does not have a highly prevalent predisposing condition, although the incidence increases in persons who have had long-standing exposure to tobacco and alcohol, achalasia, head and neck squamous cell cancer attributable most likely to long-standing alcohol and/or tobacco exposure, tylosis,[4,5] history of lye ingestion, celiac sprue, and, in South America and China, hot liquid ingestion. The etiological role of human papillomavirus infection in squamous cell cancer is under study.[9,10]
Efforts at early detection of squamous cell cancer of the esophagus have concentrated on cytological or endoscopic screening of populations in countries where there is a high incidence. While these programs have demonstrated that it is possible to detect squamous cell cancers in an early asymptomatic stage, a study from China assessed one-time endoscopic screening on the outcome of patients with esophageal cancer. In this study, communities were chosen nonrandomly in Cixian County, Hibei Province; 14 villages in the north were intervention communities and ten villages in the south were control communities. The intervention was one-time endoscopy, completed by experts, using Lugol's iodine staining to identify dysplasia or occult cancer. After biopsy was obtained and read, dysplasia and occult cancers were treated by endoscopic mucosal resection or argon plasma coagulation. Among the 6,827 participants aged 40 to 69 years in the intervention group, 3,319 volunteers were screened. Among the 6,200 participants aged 40 to 69 years in the control group, 797 individuals were interviewed. Outcome in each group was monitored to assess incidence and mortality of esophageal squamous cancer. In a 10-year follow-up, there were 542 cases of fatal esophageal squamous cell carcinoma (ESCC), a reduction in cumulative mortality from 5.05% in the control group to 3.35% in the intervention group (P < .001), and lower incidence of ESCC in the intervention group (5.92% vs. 4.17%, P < .001). Potential weaknesses of the study include the following:
- Participants were not randomly assigned but rather came from different villages, in which underlying rates may have differed geographically (northern vs. southern villages), and it was not clear what the baseline cancer rates were.
- It was not clear whether cause of death (e.g., ESCC) or cancer incidence was assessed in a blinded manner, which might have been important for assignment of what is a subjective assessment.
Esophageal cytological screening studies have been reported from China,[12,13] Iran, South Africa,[15,16] Italy, and Japan. In the United States, such efforts have been focused on individuals perceived to be at higher risk.[19,20] Studies of primary endoscopic screening have been reported from France  and Japan.
Comparisons of both Chinese and U.S. cytological diagnoses with concurrent histological findings showed low (14% to 36%) sensitivities for the cytological detection of biopsy-proven cancers. Specificity ranged from 90% to 99% with a positive predictive value of 23% to 94%. The development of uniform and accurate cytological criteria will require formal cytological-histological correlation studies of esophageal lesions. Such studies should become more feasible with the increasing availability of endoscopy in high-risk populations.
The efficacy of surveillance cytology or endoscopy for high-risk patients with tylosis or long-standing achalasia is not known.
Adenocarcinoma of the Esophagus
Considerable debate has ensued concerning the risk of cancer in patients with Barrett esophagus. Prospective studies have reported annual esophageal cancer incidence rates ranging from 0.2% to 1.9%. Concern over publication bias has led some authors to suggest that the risk may be lower than the literature suggests. A risk of 0.5% per year for development of adenocarcinoma is now thought to be a reasonable estimate for Barrett esophagus.
Barrett esophagus is strongly associated with gastroesophageal reflux disease (GERD), and the changes of Barrett esophagus can be found in approximately 10% of patients who have GERD. However, GERD is very common; surveys have found that approximately 20% of adult Americans experience symptoms of GERD, such as heartburn, at least once each week. The likelihood of finding Barrett esophagus on endoscopy is related to the duration of symptoms of gastroesophageal reflux. In a series of 701 individuals, 4% of those with symptoms for less than 1 year had Barrett esophagus on endoscopy, whereas Barrett esophagus was found in 21% of those with more than 10 years of symptoms of GERD. It has been estimated that physicians identify only approximately 5% of the population who have Barrett esophagus. There is insufficient evidence that population screening for Barrett esophagus reduces cancer mortality.[29,30]
Surveillance of Barrett esophagus involves the use of tests to identify preneoplastic changes or curable neoplasms in patients who are known to have Barrett esophagus. Certain factors are essential in the implementation of an effective surveillance protocol, including low risk of the surveillance method, correct histological diagnosis of dysplasia, proof that surgical resection for high-grade dysplasia will decrease the risk of cancer, and successful resection of cancer. The interval between endoscopic evaluations is typically determined by histologic findings, in accordance with published guidelines by gastroenterological committees. GERD should be treated prior to surveillance endoscopy to minimize confusion caused by inflammation in the interpretation of biopsy specimens. The technique of random, four-quadrant biopsies taken every 2 cm in the columnar-lined esophagus for standard histological evaluation has been recommended by some clinicians. For patients with no dysplasia, surveillance endoscopy at an interval of every 2 to 3 years has been recommended. For patients with low-grade dysplasia, surveillance every 6 months for the first year has been recommended, followed by annual endoscopy if the dysplasia has not progressed in severity. For patients with high-grade dysplasia, two options have been recommended: surgical resection or repeated endoscopic evaluation until the diagnosis of intramucosal carcinoma is made. Although widely adopted in clinical practice, these practices are based on uncontrolled series and the opinion of expert gastrointestinal endoscopists and pathologists.
Other techniques to potentially identify dysplastic epithelium that could then be sampled extensively include chromoendoscopy  and laser-induced fluorescence spectroscopy.[30,33]
Evidence of Harm
Screening for esophageal cancer by the use of blind nonendoscopically directed balloon cytological sampling for squamous cell carcinoma is minimally inconvenient and uncomfortable. Endoscopic screening for esophageal adenocarcinoma is expensive, inconvenient, and usually requires sedation.
Complications such as perforation and bleeding can occur. The incidence of complications including perforation, respiratory arrest, and myocardial infarction, has been estimated to be 0 to 13 per 10,000 procedures with an associated mortality of 0 to 0.8 per 10,000 procedures.[34,35]
Individuals who are informed they have Barrett esophagus may consider themselves to be ill even though their risk of developing cancer is very low.
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- Wei WQ, Chen ZF, He YT, et al.: Long-Term Follow-Up of a Community Assignment, One-Time Endoscopic Screening Study of Esophageal Cancer in China. J Clin Oncol 33 (17): 1951-7, 2015.
- Shen O, Liu SF, Dawsey SM, et al.: Cytologic screening for esophageal cancer: results from 12,877 subjects from a high-risk population in China. Int J Cancer 54 (2): 185-8, 1993.
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- Yokoyama A, Ohmori T, Makuuchi H, et al.: Successful screening for early esophageal cancer in alcoholics using endoscopy and mucosa iodine staining. Cancer 76 (6): 928-34, 1995.
- Dawsey SM, Shen Q, Nieberg RK, et al.: Studies of esophageal balloon cytology in Linxian, China. Cancer Epidemiol Biomarkers Prev 6 (2): 121-30, 1997.
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