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Screening for esophageal adenocarcinoma
Screening for Esophageal Adenocarcinoma: An Evidence-Based Approach Lauren B. Gerson, MD, George Triadafilopoulos, MD Adenocarcinoma of the esophagus and the gastroesophageal junction is the twentieth most common malignancy in the United States. In developed countries, the incidence of esophageal adenocarcinoma is increasing 5% to 10% per year. Despite the use of endoscopy for earlier detection, mortality from esophageal adenocarcinoma has not declined. Using an evidence-based approach, we review screening methods for esophageal adenocarcinoma, including the use of a symptom questionnaire, identification of patients with a family history of Barrett’s esophagus, peroral or transnasal endoscopy, barium swallow, fecal occult blood testing, and brush and bal-
loon cytology. Screening has not been shown to reduce rate of progression of Barrett’s esophagus to esophageal cancer. Many treatment options for dysplastic Barrett’s esophagus or early carcinoma appear effective, but long-term follow-up data are not available. There is currently insufficient evidence supporting population-based screening for Barrett’s esophagus. Several risk factors, including severe reflux symptoms, male sex, and obesity, may identify patients with gastroesophageal reflux disease who are at the greatest risk of the development of cancer. Am J Med. 2002;113:499 –505. ©2002 by Excerpta Medica, Inc.
A
MATERIAL AND METHODS
denocarcinoma of the esophagus and the gastroesophageal junction is the twentieth most common malignancy in the United States (1), responsible for approximately 6000 deaths per year. It is more prevalent in men than women (7:1) and usually presents between the ages of 60 and 70 years (2). Its incidence has increased recently in developed countries (3–5). These increases, particularly in white men, have been approximately 5% to 10% per year, a faster pace than virtually any other cancer (6). Despite an increased public awareness of the disease and the use of endoscopy for its earlier detection, mortality from esophageal cancer has not declined (7–10). Surgery remains the main therapy, but early diagnosis may allow complete tumor resection and improve the chance for cure (11). Barrett’s esophagus, a metaplastic condition resulting from chronic gastroesophageal reflux, is the primary risk factor for esophageal cancer. Other risk factors are male sex, Caucasian race, obesity, and chronic symptoms of gastroesophageal reflux disease (12–14). Most patients with esophageal adenocarcinoma have never been screened for Barrett’s esophagus (5,15).
We performed a systematic review of the literature published in English from 1996 to January 2002, using MEDLINE to obtain references for each screening method discussed. We included the search terms Barrett’s esophagus and esophageal adenocarcinoma. Abstracts corresponding to potentially relevant titles were reviewed, and articles were retrieved for data collection. We used an evidence-based approach to the literature, using a standard scoring system (16). Evidence was placed in one of five categories. All references were examined independently by the two authors who assigned a categorical rating to each statement if an evidence-based approach was appropriate. If there was a difference of opinion, a consensus was obtained. Evidence labeled as category A refers to evidence from randomized clinical trials. Category B refers to evidence from cohort or casecontrol studies. Category C is evidence from case reports or flawed clinical trials. Evidence from category D is limited to the clinical experience of the authors. Evidence labeled as category E refers to insufficient evidence to form an opinion.
Why Screen?
From the Department of Gastroenterology and Hepatology (LBG), Stanford University School of Medicine, Stanford, California and VA Palo Alto Health Care System (GT), Palo Alto, California. Dr. Gerson is supported by a Glaxo-Wellcome Institute for Digestive Health (GIDH) Healthcare Advancement Award. Requests for reprints should be addressed to Lauren B. Gerson, MD, MSc, Division of Gastroenterology and Hepatology, A149, Stanford University, Stanford, California 94305-5202, or lgerson@leland. stanford.edu. Manuscript submitted October 2, 2001, and accepted in revised form May 7, 2002. ©2002 by Excerpta Medica, Inc. All rights reserved.
Most adenocarcinomas of the esophagus and the gastroesophageal junction result from malignant (dysplastic) change in Barrett’s esophagus (Evidence-B) (17–19). Thus, efforts in screening have focused on the detection of Barrett’s esophagus, which is typically present for several years before cancer develops, often without causing symptoms (Evidence-B) (20,21). Evidence from casecontrol studies suggests that patients with Barrett’s esophagus who undergo regular endoscopic surveillance present with tumors that are smaller, lower grade, and earlier stage compared with those of patients who present with symptoms referable to the malignancy, such as dys0002-9343/02/$–see front matter 499 PII S0002-9343(02)01234-2
Screening for Esophageal Carcinoma/Gerson et al
Table. Summary of Available Screening Tests for Esophageal Adenocarcinoma Screening Test
Type of Study
Questionnaire Peroral endoscopy Barium swallow Fecal occult blood Brush cytology Balloon cytology
Case-control Prospective Case series Case-control Cohort study Cohort study
Family history
Case-control
Range of Sensitivity (%)
Estimated Cost ($)
Reference(s)
60–70 90–100 NA 20 89 80 (high-grade) 25 (low-grade) NA
$0 ⫹⫹ ⫹ ⫹ ⫹⫹ ⫹
14,27–32 33–36,53,54 37,38 39–41 42–46 47
$0
48–52
⫹ ⫽ $50 to $500; ⫹⫹ ⫽ ⬎$500 to 1500; NA ⫽ not available.
phagia (Evidence-B) (21,22). In general, 75% of patients enrolled in a Barrett’s surveillance program will present with resectable tumors compared with 25% of patients who have not received prior surveillance (Evidence-B) (10,23,24). The 5-year survival of patients undergoing surveillance approaches 60%, compared with less than 20% in patients without previously identified Barrett’s esophagus (Evidence-B) (25,26). Only 5% of patients undergoing resection have a prior diagnosis of Barrett’s esophagus, suggesting that most patients at risk of the disease have not undergone screening (Evidence-B) (15).
Which Screening Test Should Be Performed for Population Screening? For a screening test to be applicable to large populations, it needs to be inexpensive, reliable, and acceptable. Many different screening tests for detecting esophageal cancer have been used; their costs and sensitivities are shown in the Table. Questionnaire. The simplest and least expensive screening test for esophageal adenocarcinoma is a questionnaire about symptoms, but this may be reliable only when the tumor is relatively advanced. Recent work has focused on questionnaires that assess the severity of heartburn symptoms. A large case-control study in Sweden that included 189 patients with esophageal adenocarcinoma and 820 controls demonstrated that the severity and duration of gastroesophageal reflux symptoms were associated with an increased risk of cancer (Evidence-B) (14). Patients with daily long-standing heartburn and regurgitation had an odds ratio ⬎ 40 for the developent of cancer. Obesity was also a significant risk factor, with an odds ratio of 16 for obese patients (body mass index ⬎ 30 kg/m2) compared with normal-weight patients (Evidence B) (27). When long-standing reflux and obesity were considered together, the odds ratio approached 180. Other potential risk factors for esophageal adenocarcinoma, such as vegetable and fruit consumption (28) and tobacco and alcohol use (29), were not identified as important (EvidenceB). However, heartburn symptoms were only present in 60% of the patients with cancer, implying that many pa500
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tients who develop esophageal adenocarcinoma do not have previous reflux symptoms. We administered a symptom questionnaire to 517 patients with gastroesophageal reflux disease (99 with Barrett’s esophagus) to identify which patients with chronic reflux symptoms should be screened for Barrett’s esophagus (Appendix) (30). Male sex, higher scores on questions about symptoms of heartburn, painful swallowing (odynophagia), and nocturnal symptoms increased the likelihood of Barrett’s esophagus, whereas higher scores for dysphagia, pain relief with food, belching, or nausea decreased the likelihood. We created a prediction model for Barrett’s esophagus that incorporated patient age, sex, and ethnicity, and the scores from the symptom questions. The model-based probability for Barrett’s esophagus approached 70% for patients with the highest scores, and was 1.4% for patients with the lowest scores (Evidence-B). Other case-control studies have found an association between frequent gastroesophageal reflux symptoms and Barrett’s esophagus [Evidence-B] (31,32). These studies also did not find an association between tobacco or alcohol consumption and Barrett’s esophagus. Endoscopy. Flexible upper endoscopy should detect all esophageal cancers, since the whole surface of the esophagus and the gastroesophageal junction can be visualized. While most endoscopy is performed under conscious intravenous sedation in the United States, transnasal endoscopy has been introduced, particularly for population screening. Transnasal endoscopy offers several advantages: it can be performed in the office without sedation, thus avoiding the small risk of complications (⬍1%) associated with intravenous sedation; it requires less time to perform; and it appears to be equally tolerable for patients without missing important pathology (Evidence-A) (33–35). In a population screening program, willingness to undergo the screening test is crucial. When we offered endoscopic screening for Barrett’s esophagus to 727 asymptomatic patients who were scheduled for sigmoidoscopy for colorectal cancer screening, approximately 50% of
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those invited agreed to participate (Evidence-B) (36). We found a 25% prevalence of Barrett’s esophagus in our sample, which was composed primarily of male veterans. These patients are now being surveyed for the development of esophageal adenocarcinoma; it is not known whether screening of asymptomatic adults affects mortality from esophageal adenocarcinoma. Barium swallow. Barium swallow, like endoscopy, examines the lumen of the esophagus and stomach. Although it is less costly and has a lower complication rate than does endoscopy, it has a poor sensitivity for detecting Barrett’s esophagus or early adenocarcinoma. Small studies (⬍30 patients) of patients with Barrett’s esophagus have concluded that there are no radiological findings specific for Barrett’s esophagus (Evidence-B) (37,38). Common radiological features in patients with Barrett’s esophagus, such as thickened and irregular mucosal folds, hiatal hernia, esophageal stricture, esophageal ulcer, distal esophageal widening, granular or reticular mucosal pattern, and intramural pseudodiverticula, are also seen in patients with reflux esophagitis. Furthermore, barium swallow does not allow histologic assessment for intestinal metaplasia or dysplasia. Therefore, barium swallow is not an acceptable method for screening and surveillance of Barrett’s esophagus. Fecal occult blood tests. Fecal occult blood testing is performed to enhance detection of colorectal neoplasia. Performance of upper endoscopy has been suggested in patients with fecal occult blood and a normal colonoscopy, even if the patient denies upper gastrointestinal symptoms. In one study, an upper gastrointestinal source of occult bleeding was identified in 13% (n ⫽ 67) of 498 asymptomatic patients with positive fecal occult blood tests and normal colonoscopy who underwent subsequent upper endoscopy (Evidence-B) (39). Forty patients had peptic ulcer disease, 1 had esophageal carcinoma, and 6 had Barrett’s esophagus. A smaller study of 70 patients with normal colonoscopy and positive fecal occult blood testing found that 19 (27%) had important findings on upper endoscopy, including 2 with Barrett’s esophagus (40). To determine the sensitivity and specificity of fecal occult blood testing for the detection of esophageal cancer, a retrospective study examined the accuracy of occult blood testing in 124 patients with upper digestive tract diseases, including 10 with esophageal cancer (41). Two of the 10 patients with esophageal cancer had a positive test (sensitivity, 20%) (Evidence-B). Although the number of patients with cancer was small, the evidence suggests that fecal occult blood testing is an insensitive means of screening for esophageal adenocarcinoma. Brush cytology. Esophageal brushings are reasonably sensitive for detecting metaplasia, but less sensitive than
histologic assessment. For example, a prospective study comparing the two methods found that 17 (81%) of 21 patients with Barrett’s metaplasia demonstrated histologically had columnar cells with the characteristic villin staining pattern seen with cytology, whereas all normal squamous cells, blood cells, and gastric columnar cells did not have villin expression (Evidence-B) (42). The value of brush cytology for the detection of dysplasia has also been studied. In a prospective assessment using brush cytology compared with standard surveillance biopsy in 162 patients (87 with esophageal or gastroesophageal junction adenocarcinoma, 65 with nondysplastic, and 10 with dysplastic Barrett’s esophagus), 82 (89%) of 92 patients with carcinoma or high-grade dysplasia had true-positive malignant cytology (43). Seven (11%) of 65 patients with nondysplastic but inflamed Barrett’s esophagus had false-positive malignant cytology (sensitivity, 89%). However, surgical treatment decisions should not be made on the basis of cytology alone, since the results can be misleading in the presence of severe inflammation. Similar studies have also concluded that the addition of brush cytology to histology appears to increase the cost of the evaluation without augmenting the diagnostic yield (Evidence-B) (44 – 46). Balloon cytology. Blind nonendoscopically-directed balloon cytological sampling has been suggested as a less costly alternative to endoscopic biopsy for surveillance. In a study comparing balloon cytology with subsequent brush cytology and biopsy in 63 patients, adequate columnar epithelium was obtained in 52 (83%) of the patients with balloon cytology and 59 (97%) of 61 with brush cytology (47). Balloon cytology obtained abnormal cells in 6 of 8 patients with adenocarcinoma, both patients with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia. The sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% (8/10), but only 25% (2/8) for low-grade dysplasia. Compared with balloon cytology, brush cytology was abnormal in all 11 patients with high-grade dysplasia or carcinoma (sensitivity, 100%), but only 2 of 9 patients with low-grade dysplasia (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells (specificity, 95%) compared with none of the patients by balloon cytology. Therefore, based on limited data, neither technique is sensitive for the detection of low-grade dysplasia (Evidence-B). Family history. A familial association of Barrett’s esophagus and gastroesophageal reflux has been described in several case series (Evidence-C) (48 –50). To investigate this relation further, a case-control study was performed at the Mayo Clinic (51). Reflux symptoms were significantly more prevalent among parents and siblings of patients with adenocarcinoma (43% [20/46] vs. 23% [11/48], P ⫽ 0.03) and patients with Barrett’s esophagus (46% [33/71] vs. 27% [22/81], P ⫽ 0.01), compared with
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controls. No significant difference was found for the reflux esophagitis group. A case-control study of 418 subjects in the United Kingdom found that reflux symptoms were more likely in relatives of patients with gastroesophageal reflux disease or Barrett’s esophagus than in relatives of nondyspeptic controls (Evidence-B) (52). These studies support a genetic predisposition towards Barrett’s esophagus (Evidence-B). The effects of screening relatives of patients with Barrett’s esophagus or esophageal carcinoma on mortality from this disease are not known.
What Is the Risk of Cancer in Patients with Barrett’s Esophagus? Although approximately 10% to 14% of patients with gastroesophageal reflux disease will develop Barrett’s esophagus, only 0.4% per year will develop esophageal adenocarcinoma (Evidence-B) (55). This equates to a 15% to 20% lifetime risk of cancer. A prospective study of 1099 patients with Barrett’s esophagus from the Hines Veterans Affairs Hospital demonstrated that 12 (16%) of the 75 patients with high-grade dysplasia developed adenocarcinoma during a mean (⫾ SD) surveillance period of 7.3 ⫾ 4.4 years, whereas 22 (2%) of 1057 patients with Barrett’s esophagus developed cancer during this period (rate of 0.3% per year) (Evidence-B) (56). This study and others have also demonstrated that overall survival is not changed in patients with Barrett’s esophagus compared with the general population (Evidence-B) (57).
What Treatments Are Available to Reduce the Risk of Cancer in Barrett’s Esophagus? Currently, there is no evidence that screening reduces the rate of progression of Barrett’s esophagus to esophageal adenocarcinoma. However, there are many treatments for dysplastic Barrett’s esophagus and early adenocarcinoma. Traditionally, esophagectomy is offered to patients with high-grade dysplasia because esophageal carcinoma is detected in up to 30% of resected specimens (Evidence-B) (58 – 60). However, because many patients with Barrett’s esophagus are not surgical candidates, nonsurgical treatment options have been developed. For example, endoscopic mucosal resection has been proposed as treatment for superficial neoplastic lesions that can be recognized endoscopically. In a prospective study of 92 patients (including 6 with high-grade dysplasia in Barrett’s esophagus, 6 with esophageal adenocarcinoma, and 7 with uncertain pathology), complete endoscopic resection was achieved in 90 patients (89%), which included 16 (84%) of the patients with esophageal pathology. No recurrences were documented during at least a 2-year follow-up (Evidence-B) (61). However, in another study of 64 patients (61 with early esophageal cancer) undergoing endoscopic mucosal resection, recurrent or metachronous cancers were detected in 9 patients (14%), 502
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with a mean follow-up of 12 ⫾ 8 months (Evidence-B) (62). Another treatment option, photodynamic therapy, has been used in patients with high-grade dysplasia or early carcinoma to eliminate dysplasia. In a series of 100 patients, including 73 with high-grade dysplasia and 13 with adenocarcinoma, complete elimination of dysplasia occurred in 88 (88%) of the patients with high-grade dysplasia and 10 (77%) of the patients with cancer (Evidence-B) (63). However, dysplasia developed in 11 patients 4 months to 3 years after initial therapy and persisted in 16 patients after treatment. In addition, 34 patients developed esophageal strictures that required dilation. Endoscopic laser therapy has also been used in patients with high-grade dysplasia and early adenocarcinoma in combination with proton pump inhibitor therapy (64,65). However, residual intestinal metaplasia has been detected in many of these patients during follow-up endoscopy (Evidence-B). Recently, argon plasma coagulation was used in 10 patients with high-grade dysplasia or early cancer, 8 of whom had no cancer recurrence after a mean follow-up of 24 months (Evidence-B) (66). Treatments for nondysplastic Barrett’s esophagus also include electrocoagulation and argon plasma coagulation. Three trials of electrocoagulation in combination with acid suppression have had promising results. In one series of 14 patients with Barrett’s esophagus undergoing Nissen fundoplication who were treated with electrocoagulation, no patients had recurrent intestinal metaplasia after a mean of 22 months of follow-up (Evidence-B) (67). Two other series demonstrated residual intestinal metaplasia in 18% to 27% of patients after electrocoagulation (Evidence-B) (68,69). Similar results have been demonstrated using argon plasma coagulation in combination with acid suppression, with residual intestinal metaplasia seen in 1% to 47% of patients at follow-up endoscopy (Evidence-B) (70 –72). When argon treatment followed Nissen fundoplication in 30 patients with Barrett’s esophagus, recurrence of short segments of intestinal metaplasia was detected only in the 2 patients with recurrent acid reflux (Evidence-B) (73). Although long-term follow-up of these treatments is not available, these studies suggest that early identification of dysplasia and cancer in Barrett’s esophagus can provide the opportunity for endoscopic treatment to prevent the development of invasive neoplastic disease (Evidence-B).
Should There Be Population Screening for Barrett’s Esophagus? Although evidence from questionnaire studies suggests that patients with severe symptoms of gastroesophageal reflux disease should be screened for Barrett’s esophagus, large series have also demonstrated that the majority of patients with Barrett’s esophagus who develop malignancy never report symptoms before presentation with
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cancer. Therefore, if all potential cases of Barrett’s esophagus are to be identified, there should be consideration for population screening to include patients without frequent reflux symptoms. The question of endoscopic screening for Barrett’s esophagus in asymptomatic adults at age 50 years was investigated in a prospective study of 110 adults undergoing sigmoidoscopy for routine colorectal cancer screening (Evidence-B) (36). Exclusion criteria included symptoms of gastroesophageal reflux disease occurring more than once a month, use of medications for heartburn, or previous endoscopy. The mean age of the participants was 61 ⫾ 9 years (range, 50 – 80 years), and most subjects were male (92% [n ⫽ 101]), white (73% [n ⫽ 80]), and veterans (94% [n ⫽ 104]). Intestinal metaplasia extending above the gastroesophageal junction was detected in 28 subjects (25%); 8 (7%) who had long (ⱖ3 cm) segments of Barrett’s esophagus, and 19 (17%) who had short segments (⬍3 cm). When interviewed carefully about the frequency of prior heartburn symptoms, 51% (n ⫽ 56) of the participants never had heartburn in the past, 28% (n ⫽ 31) had heartburn after meals occurring one to two times per year, and all of the remaining patients had heartburn after meals occurring no more than once a month. Patients with Barrett’s esophagus were no more likely to be obese, to be consumers of tobacco or alcohol, to report a family history of heartburn, or to use antacids more than once a month, than were those without Barrett’s esophagus. The results from this preliminary study suggest that the prevalence of Barrett’s esophagus in asymptomatic elderly male veterans is at least equal to that in patients with pathologic gastroesophageal reflux disease (Evidence-B). However, evidence that population screening will reduce mortality from esophageal cancer is required before screening can be recommended.
Is There Potential Harm from Endoscopic Screening? Endoscopic screening for esophageal adenocarcinoma can be inconvenient, unpleasant, and expensive for patients. In addition, the findings from the screening endoscopic examination can lead to possible psychological distress. Patients labeled as having Barrett’s esophagus might consider themselves to be ill even though their risk of developing cancer is very low. For example, productive steelworkers who were found to be hypertensive subsequently suffered from increased absenteeism, lost income, and adoption of a sick role that was independent of treatment (Evidence-B) (74,75). In another study, women labeled with gestational diabetes were more likely to report deterioration of their health and their infants’ health up to 5 years after their diagnosis (Evidence-B) (76). To date, no studies have been published regarding
potential adverse effects from the diagnosis and subsequence surveillance of Barrett’s esophagus. In addition to the potential psychological harm associated with screening, complications from upper endoscopy (perforation and bleeding) can occur. The incidence of complications, including perforation, respiratory arrest, and myocardial infarction, has been estimated to be 0 –13 per 10,000 procedures (77– 80), with an associated mortality of 0 – 0.8 per 10,000 procedures (Evidence-B). These complications are expected to be lower with unsedated, transnasal endoscopy (54).
CONCLUSION Risk factors identified by questionnaire, primarily longstanding frequent gastroesophageal reflux symptoms, male sex, and obesity, may identify patients with gastroesophageal reflux disease who potentially should undergo screening for Barrett’s esophagus to prevent the development of esophageal carcinoma. More data are required before population screening for Barrett’s esophagus can be recommended. Evidence from cohort studies suggests that patients in a Barrett’s surveillance program will present with cancers at an earlier stage and may have improved survival rates.
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esophageal adenocarcinoma. Gastroenterology. 1997;113:1449 – 1456. Trudgill NJ, Kapur KC, Riley SA. Familial clustering of reflux symptoms. Am J Gastroenterol. 1999;94:1172–1178. Zaman A, Hapke R, Sahagun G, Katon RM. Unsedated peroral endoscopy with a video ultrathin endoscope: patient acceptance, tolerance, and diagnostic accuracy. Am J Gastroenterol. 1998;93: 1260 –1263. Padda S, Ramirez F. Accuracy in the diagnosis of short-segment Barrett’s esophagus: the role of endoscopic experience. Gastrointest Endosc. 2001;54:605–608. Drewitz DJ, Sampliner RE, Grewal HS. The incidence of adenocarcinoma in Barrett’s esophagus: a prospective study of 170 patients followed 4.8 years. Am J Gastroenterol. 1997;92:212–215. Schnell TG, Sontag SJ, Chejfec G, et al. Long-term nonsurgical management of Barrett’s esophagus with high-grade dysplasia. Gastroenterology. 2001;120:1607–1619. Eckardt VF, Kanzler G, Bernhard G. Life expectancy and cancer risk in patients with Barrett’s esophagus: a prospective controlled investigation. Am J Med. 2001;111:33–37. Zaninotto G, Parenti AR, Ruol A, et al. Oesophageal resection for high-grade dysplasia in Barrett’s oesophagus. Br J Surg. 2000;87: 1102–1105. Saubier EC, Gouillat C, Samaniego C, et al. Adenocarcinoma in columnar-lined Barrett’s esophagus. Analysis of 13 esophagectomies. Am J Surg. 1985;150:365–369. Edwards MJ, Gable DR, Lentsch AB, Richardson JD. The rationale for esophagectomy as the optimal therapy for Barrett’s esophagus with high-grade dysplasia. Ann Surg. 1996;223:585–589. Ahmad NA, Kockman ML, Long WB, et al. Efficacy, safety, and clinical outcomes of endoscopic mucosal resection: a study of 101 cases. Gastrointest Endosc. 2002;55:390 –396. Ell C, May A, Gossner L, et al. Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett’s esophagus. Gastroenterology. 2000;118:670 –677. Overholt BF, Panjehpour M, Haydek JM. Photodynamic therapy for Barrett’s esophagus: follow-up in 100 patients. Gastrointest Endosc. 1999;49:1–7. Gossner L, May A, Stolte M, et al. KTP laser destruction of dysplasia and early cancer in columnar-lined Barrett’s esophagus. Gastrointest Endosc. 1999;49:8 –12. Sharma P, Jaffe PE, Bhattacharyya A, Sampliner RE. Laser and multipolar electrocoagulation ablation of early Barrett’s adenocarcinoma: long-term follow-up. Gastrointest Endosc. 1999; 49:442–446. Van Laethem JL, Jagodzinski R, Peny MO, et al. Argon plasma coagulation in the treatment of Barrett’s high-grade dysplasia and in situ adenocarcinoma. Endoscopy. 2001;33:257–261. Montes CG, Brandalise NA, Deliza R, et al. Antireflux surgery followed by bipolar electrocoagulation in the treatment of Barrett’s esophagus. Gastrointest Endosc. 1999;50:173–177. Sharma P, Bhattacharyya A, Garewal HS, Sampliner RE. Durability of a new squamous epithyelium after endoscopic reversal of Barrett’s esophagus. Gastrointest Endosc. 1999;50:159 –164. Kovacs BJ, Chen YK, Lewis TD, et al. Successful reversal of Barrett’s esophagus with multipolar electrocoagulation despite inadequate acid suppression. Gastrointest Endosc. 1999;49:547–553. Van Laethem JL, Cremer M, Peny MO, et al. Eradication of Barrett’s mucosa with argon plasma coagulation and acid suppression: immediate and mid term results. Gut. 1998;43:747–751. Pereira-Lima JC, Busnello JV, Saul C, et al. High power setting argon plasma coagulation for the eradication of Barrett’s esophagus. Am J Gastroenterol. 2000;95:1661–1668.
72. Schulz H, Miehlke S, Antos D, et al. Ablation of Barrett’s epithelium by endoscopic argon plasma coagulation in combination with high-dose omeprazole. Gastrointest Endosc. 2000;51:659 –663. 73. Tigges H, Fuchs KH, Maroske J, et al. Combination of endoscopic argon plasma coagulation and antireflux surgery for treatment of Barrett’s esophagus. J Gastrointest Surg. 2001;5:251–259. 74. Haynes RB, Sackett DL, Taylor DW, et al. Increased absenteeism from work after detection and labeling of hypertensive patients. N Engl J Med. 1978;299:741–744. 75. Johnston ME, Gibson ES, Terry CW, et al. Effects of labelling on income, work and social function among hypertensive employees. J Chronic Dis. 1984;37:417–423. 76. Feig DS, Chen E, Naylor CD. Self-perceived health status of women three to five years after the diagnosis of gestational diabetes: a survey of cases and matched controls. Am J Obstet Gynecol. 1998;178:386 – 393. 77. Silvis SE, Nebel O, Rogers G, et al. Endoscopic complications. Results of the 1974 American Society for Gastrointestinal Endoscopy Survey. JAMA. 1976;235:928 –930. 78. Clarke GA, Jacobson BC, Hammett RJ, Carr-Locke DL. The indications, utilization and safety of gastrointestinal endoscopy in an extremely elderly patient cohort. Endoscopy. 2001;33:580 –584. 79. Sieg A, Hachmoeller-Eisenbach U, Eisenbach T. Prospective evaluation of complications in outpatient GI endoscopy: a survey among German gastroenterologists. Gastrointest Endosc. 2001;53:620 –627. 80. Schauer PR, Schwesinger WH, Page CP, et al. Complications of surgical endoscopy. A decade of experience from a surgical residency training program. Surg Endosc. 1997;11:8 –11.
APPENDIX Questionnaire for Barrett’s Esophagus Prediction Model (30) Please circle your response to the questions below. When we ask about your symptoms, please use the following scale: 0 ⫽ no problem 1 ⫽ mild problem (can be ignored if you do not think about it) 2 ⫽ moderate problem (cannot be ignored, but does not affect your daily activities) 3 ⫽ severe problem (affects your daily activities) Please answer the following questions about your heartburn symptoms as if you were not taking any prescription medications: Symptom
Score
1. Do you have heartburn (burning in the chest or throat)? 2. Do you have difficulty swallowing food or liquids? 3. Does it hurt when you swallow? 4. Do you feel sick to your stomach after a meal? 5. Do you belch? 6. Does the pain in your belly wake you up at night? 7. Is the pain in your belly relieved by eating?
0 1 2 3
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0 0 0 0 0 0
1 1 1 1 1 1
2 2 2 2 2 2
3 3 3 3 3 3
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loon cytology. Screening has not been shown to reduce rate of progression of Barrett’s esophagus to esophageal cancer. Many treatment options for dysplastic Barrett’s esophagus or early carcinoma appear effective, but long-term follow-up data are not available. There is currently insufficient evidence supporting population-based screening for Barrett’s esophagus. Several risk factors, including severe reflux symptoms, male sex, and obesity, may identify patients with gastroesophageal reflux disease who are at the greatest risk of the development of cancer. Am J Med. 2002;113:499 –505. ©2002 by Excerpta Medica, Inc.
A
MATERIAL AND METHODS
denocarcinoma of the esophagus and the gastroesophageal junction is the twentieth most common malignancy in the United States (1), responsible for approximately 6000 deaths per year. It is more prevalent in men than women (7:1) and usually presents between the ages of 60 and 70 years (2). Its incidence has increased recently in developed countries (3–5). These increases, particularly in white men, have been approximately 5% to 10% per year, a faster pace than virtually any other cancer (6). Despite an increased public awareness of the disease and the use of endoscopy for its earlier detection, mortality from esophageal cancer has not declined (7–10). Surgery remains the main therapy, but early diagnosis may allow complete tumor resection and improve the chance for cure (11). Barrett’s esophagus, a metaplastic condition resulting from chronic gastroesophageal reflux, is the primary risk factor for esophageal cancer. Other risk factors are male sex, Caucasian race, obesity, and chronic symptoms of gastroesophageal reflux disease (12–14). Most patients with esophageal adenocarcinoma have never been screened for Barrett’s esophagus (5,15).
We performed a systematic review of the literature published in English from 1996 to January 2002, using MEDLINE to obtain references for each screening method discussed. We included the search terms Barrett’s esophagus and esophageal adenocarcinoma. Abstracts corresponding to potentially relevant titles were reviewed, and articles were retrieved for data collection. We used an evidence-based approach to the literature, using a standard scoring system (16). Evidence was placed in one of five categories. All references were examined independently by the two authors who assigned a categorical rating to each statement if an evidence-based approach was appropriate. If there was a difference of opinion, a consensus was obtained. Evidence labeled as category A refers to evidence from randomized clinical trials. Category B refers to evidence from cohort or casecontrol studies. Category C is evidence from case reports or flawed clinical trials. Evidence from category D is limited to the clinical experience of the authors. Evidence labeled as category E refers to insufficient evidence to form an opinion.
Why Screen?
From the Department of Gastroenterology and Hepatology (LBG), Stanford University School of Medicine, Stanford, California and VA Palo Alto Health Care System (GT), Palo Alto, California. Dr. Gerson is supported by a Glaxo-Wellcome Institute for Digestive Health (GIDH) Healthcare Advancement Award. Requests for reprints should be addressed to Lauren B. Gerson, MD, MSc, Division of Gastroenterology and Hepatology, A149, Stanford University, Stanford, California 94305-5202, or lgerson@leland. stanford.edu. Manuscript submitted October 2, 2001, and accepted in revised form May 7, 2002. ©2002 by Excerpta Medica, Inc. All rights reserved.
Most adenocarcinomas of the esophagus and the gastroesophageal junction result from malignant (dysplastic) change in Barrett’s esophagus (Evidence-B) (17–19). Thus, efforts in screening have focused on the detection of Barrett’s esophagus, which is typically present for several years before cancer develops, often without causing symptoms (Evidence-B) (20,21). Evidence from casecontrol studies suggests that patients with Barrett’s esophagus who undergo regular endoscopic surveillance present with tumors that are smaller, lower grade, and earlier stage compared with those of patients who present with symptoms referable to the malignancy, such as dys0002-9343/02/$–see front matter 499 PII S0002-9343(02)01234-2
Screening for Esophageal Carcinoma/Gerson et al
Table. Summary of Available Screening Tests for Esophageal Adenocarcinoma Screening Test
Type of Study
Questionnaire Peroral endoscopy Barium swallow Fecal occult blood Brush cytology Balloon cytology
Case-control Prospective Case series Case-control Cohort study Cohort study
Family history
Case-control
Range of Sensitivity (%)
Estimated Cost ($)
Reference(s)
60–70 90–100 NA 20 89 80 (high-grade) 25 (low-grade) NA
$0 ⫹⫹ ⫹ ⫹ ⫹⫹ ⫹
14,27–32 33–36,53,54 37,38 39–41 42–46 47
$0
48–52
⫹ ⫽ $50 to $500; ⫹⫹ ⫽ ⬎$500 to 1500; NA ⫽ not available.
phagia (Evidence-B) (21,22). In general, 75% of patients enrolled in a Barrett’s surveillance program will present with resectable tumors compared with 25% of patients who have not received prior surveillance (Evidence-B) (10,23,24). The 5-year survival of patients undergoing surveillance approaches 60%, compared with less than 20% in patients without previously identified Barrett’s esophagus (Evidence-B) (25,26). Only 5% of patients undergoing resection have a prior diagnosis of Barrett’s esophagus, suggesting that most patients at risk of the disease have not undergone screening (Evidence-B) (15).
Which Screening Test Should Be Performed for Population Screening? For a screening test to be applicable to large populations, it needs to be inexpensive, reliable, and acceptable. Many different screening tests for detecting esophageal cancer have been used; their costs and sensitivities are shown in the Table. Questionnaire. The simplest and least expensive screening test for esophageal adenocarcinoma is a questionnaire about symptoms, but this may be reliable only when the tumor is relatively advanced. Recent work has focused on questionnaires that assess the severity of heartburn symptoms. A large case-control study in Sweden that included 189 patients with esophageal adenocarcinoma and 820 controls demonstrated that the severity and duration of gastroesophageal reflux symptoms were associated with an increased risk of cancer (Evidence-B) (14). Patients with daily long-standing heartburn and regurgitation had an odds ratio ⬎ 40 for the developent of cancer. Obesity was also a significant risk factor, with an odds ratio of 16 for obese patients (body mass index ⬎ 30 kg/m2) compared with normal-weight patients (Evidence B) (27). When long-standing reflux and obesity were considered together, the odds ratio approached 180. Other potential risk factors for esophageal adenocarcinoma, such as vegetable and fruit consumption (28) and tobacco and alcohol use (29), were not identified as important (EvidenceB). However, heartburn symptoms were only present in 60% of the patients with cancer, implying that many pa500
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tients who develop esophageal adenocarcinoma do not have previous reflux symptoms. We administered a symptom questionnaire to 517 patients with gastroesophageal reflux disease (99 with Barrett’s esophagus) to identify which patients with chronic reflux symptoms should be screened for Barrett’s esophagus (Appendix) (30). Male sex, higher scores on questions about symptoms of heartburn, painful swallowing (odynophagia), and nocturnal symptoms increased the likelihood of Barrett’s esophagus, whereas higher scores for dysphagia, pain relief with food, belching, or nausea decreased the likelihood. We created a prediction model for Barrett’s esophagus that incorporated patient age, sex, and ethnicity, and the scores from the symptom questions. The model-based probability for Barrett’s esophagus approached 70% for patients with the highest scores, and was 1.4% for patients with the lowest scores (Evidence-B). Other case-control studies have found an association between frequent gastroesophageal reflux symptoms and Barrett’s esophagus [Evidence-B] (31,32). These studies also did not find an association between tobacco or alcohol consumption and Barrett’s esophagus. Endoscopy. Flexible upper endoscopy should detect all esophageal cancers, since the whole surface of the esophagus and the gastroesophageal junction can be visualized. While most endoscopy is performed under conscious intravenous sedation in the United States, transnasal endoscopy has been introduced, particularly for population screening. Transnasal endoscopy offers several advantages: it can be performed in the office without sedation, thus avoiding the small risk of complications (⬍1%) associated with intravenous sedation; it requires less time to perform; and it appears to be equally tolerable for patients without missing important pathology (Evidence-A) (33–35). In a population screening program, willingness to undergo the screening test is crucial. When we offered endoscopic screening for Barrett’s esophagus to 727 asymptomatic patients who were scheduled for sigmoidoscopy for colorectal cancer screening, approximately 50% of
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those invited agreed to participate (Evidence-B) (36). We found a 25% prevalence of Barrett’s esophagus in our sample, which was composed primarily of male veterans. These patients are now being surveyed for the development of esophageal adenocarcinoma; it is not known whether screening of asymptomatic adults affects mortality from esophageal adenocarcinoma. Barium swallow. Barium swallow, like endoscopy, examines the lumen of the esophagus and stomach. Although it is less costly and has a lower complication rate than does endoscopy, it has a poor sensitivity for detecting Barrett’s esophagus or early adenocarcinoma. Small studies (⬍30 patients) of patients with Barrett’s esophagus have concluded that there are no radiological findings specific for Barrett’s esophagus (Evidence-B) (37,38). Common radiological features in patients with Barrett’s esophagus, such as thickened and irregular mucosal folds, hiatal hernia, esophageal stricture, esophageal ulcer, distal esophageal widening, granular or reticular mucosal pattern, and intramural pseudodiverticula, are also seen in patients with reflux esophagitis. Furthermore, barium swallow does not allow histologic assessment for intestinal metaplasia or dysplasia. Therefore, barium swallow is not an acceptable method for screening and surveillance of Barrett’s esophagus. Fecal occult blood tests. Fecal occult blood testing is performed to enhance detection of colorectal neoplasia. Performance of upper endoscopy has been suggested in patients with fecal occult blood and a normal colonoscopy, even if the patient denies upper gastrointestinal symptoms. In one study, an upper gastrointestinal source of occult bleeding was identified in 13% (n ⫽ 67) of 498 asymptomatic patients with positive fecal occult blood tests and normal colonoscopy who underwent subsequent upper endoscopy (Evidence-B) (39). Forty patients had peptic ulcer disease, 1 had esophageal carcinoma, and 6 had Barrett’s esophagus. A smaller study of 70 patients with normal colonoscopy and positive fecal occult blood testing found that 19 (27%) had important findings on upper endoscopy, including 2 with Barrett’s esophagus (40). To determine the sensitivity and specificity of fecal occult blood testing for the detection of esophageal cancer, a retrospective study examined the accuracy of occult blood testing in 124 patients with upper digestive tract diseases, including 10 with esophageal cancer (41). Two of the 10 patients with esophageal cancer had a positive test (sensitivity, 20%) (Evidence-B). Although the number of patients with cancer was small, the evidence suggests that fecal occult blood testing is an insensitive means of screening for esophageal adenocarcinoma. Brush cytology. Esophageal brushings are reasonably sensitive for detecting metaplasia, but less sensitive than
histologic assessment. For example, a prospective study comparing the two methods found that 17 (81%) of 21 patients with Barrett’s metaplasia demonstrated histologically had columnar cells with the characteristic villin staining pattern seen with cytology, whereas all normal squamous cells, blood cells, and gastric columnar cells did not have villin expression (Evidence-B) (42). The value of brush cytology for the detection of dysplasia has also been studied. In a prospective assessment using brush cytology compared with standard surveillance biopsy in 162 patients (87 with esophageal or gastroesophageal junction adenocarcinoma, 65 with nondysplastic, and 10 with dysplastic Barrett’s esophagus), 82 (89%) of 92 patients with carcinoma or high-grade dysplasia had true-positive malignant cytology (43). Seven (11%) of 65 patients with nondysplastic but inflamed Barrett’s esophagus had false-positive malignant cytology (sensitivity, 89%). However, surgical treatment decisions should not be made on the basis of cytology alone, since the results can be misleading in the presence of severe inflammation. Similar studies have also concluded that the addition of brush cytology to histology appears to increase the cost of the evaluation without augmenting the diagnostic yield (Evidence-B) (44 – 46). Balloon cytology. Blind nonendoscopically-directed balloon cytological sampling has been suggested as a less costly alternative to endoscopic biopsy for surveillance. In a study comparing balloon cytology with subsequent brush cytology and biopsy in 63 patients, adequate columnar epithelium was obtained in 52 (83%) of the patients with balloon cytology and 59 (97%) of 61 with brush cytology (47). Balloon cytology obtained abnormal cells in 6 of 8 patients with adenocarcinoma, both patients with high-grade dysplasia, and 2 of 8 patients with low-grade dysplasia. The sensitivity of balloon cytology for high-grade dysplasia or carcinoma was 80% (8/10), but only 25% (2/8) for low-grade dysplasia. Compared with balloon cytology, brush cytology was abnormal in all 11 patients with high-grade dysplasia or carcinoma (sensitivity, 100%), but only 2 of 9 patients with low-grade dysplasia (sensitivity, 22%). Two of 39 patients without dysplasia had abnormal cells (specificity, 95%) compared with none of the patients by balloon cytology. Therefore, based on limited data, neither technique is sensitive for the detection of low-grade dysplasia (Evidence-B). Family history. A familial association of Barrett’s esophagus and gastroesophageal reflux has been described in several case series (Evidence-C) (48 –50). To investigate this relation further, a case-control study was performed at the Mayo Clinic (51). Reflux symptoms were significantly more prevalent among parents and siblings of patients with adenocarcinoma (43% [20/46] vs. 23% [11/48], P ⫽ 0.03) and patients with Barrett’s esophagus (46% [33/71] vs. 27% [22/81], P ⫽ 0.01), compared with
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controls. No significant difference was found for the reflux esophagitis group. A case-control study of 418 subjects in the United Kingdom found that reflux symptoms were more likely in relatives of patients with gastroesophageal reflux disease or Barrett’s esophagus than in relatives of nondyspeptic controls (Evidence-B) (52). These studies support a genetic predisposition towards Barrett’s esophagus (Evidence-B). The effects of screening relatives of patients with Barrett’s esophagus or esophageal carcinoma on mortality from this disease are not known.
What Is the Risk of Cancer in Patients with Barrett’s Esophagus? Although approximately 10% to 14% of patients with gastroesophageal reflux disease will develop Barrett’s esophagus, only 0.4% per year will develop esophageal adenocarcinoma (Evidence-B) (55). This equates to a 15% to 20% lifetime risk of cancer. A prospective study of 1099 patients with Barrett’s esophagus from the Hines Veterans Affairs Hospital demonstrated that 12 (16%) of the 75 patients with high-grade dysplasia developed adenocarcinoma during a mean (⫾ SD) surveillance period of 7.3 ⫾ 4.4 years, whereas 22 (2%) of 1057 patients with Barrett’s esophagus developed cancer during this period (rate of 0.3% per year) (Evidence-B) (56). This study and others have also demonstrated that overall survival is not changed in patients with Barrett’s esophagus compared with the general population (Evidence-B) (57).
What Treatments Are Available to Reduce the Risk of Cancer in Barrett’s Esophagus? Currently, there is no evidence that screening reduces the rate of progression of Barrett’s esophagus to esophageal adenocarcinoma. However, there are many treatments for dysplastic Barrett’s esophagus and early adenocarcinoma. Traditionally, esophagectomy is offered to patients with high-grade dysplasia because esophageal carcinoma is detected in up to 30% of resected specimens (Evidence-B) (58 – 60). However, because many patients with Barrett’s esophagus are not surgical candidates, nonsurgical treatment options have been developed. For example, endoscopic mucosal resection has been proposed as treatment for superficial neoplastic lesions that can be recognized endoscopically. In a prospective study of 92 patients (including 6 with high-grade dysplasia in Barrett’s esophagus, 6 with esophageal adenocarcinoma, and 7 with uncertain pathology), complete endoscopic resection was achieved in 90 patients (89%), which included 16 (84%) of the patients with esophageal pathology. No recurrences were documented during at least a 2-year follow-up (Evidence-B) (61). However, in another study of 64 patients (61 with early esophageal cancer) undergoing endoscopic mucosal resection, recurrent or metachronous cancers were detected in 9 patients (14%), 502
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with a mean follow-up of 12 ⫾ 8 months (Evidence-B) (62). Another treatment option, photodynamic therapy, has been used in patients with high-grade dysplasia or early carcinoma to eliminate dysplasia. In a series of 100 patients, including 73 with high-grade dysplasia and 13 with adenocarcinoma, complete elimination of dysplasia occurred in 88 (88%) of the patients with high-grade dysplasia and 10 (77%) of the patients with cancer (Evidence-B) (63). However, dysplasia developed in 11 patients 4 months to 3 years after initial therapy and persisted in 16 patients after treatment. In addition, 34 patients developed esophageal strictures that required dilation. Endoscopic laser therapy has also been used in patients with high-grade dysplasia and early adenocarcinoma in combination with proton pump inhibitor therapy (64,65). However, residual intestinal metaplasia has been detected in many of these patients during follow-up endoscopy (Evidence-B). Recently, argon plasma coagulation was used in 10 patients with high-grade dysplasia or early cancer, 8 of whom had no cancer recurrence after a mean follow-up of 24 months (Evidence-B) (66). Treatments for nondysplastic Barrett’s esophagus also include electrocoagulation and argon plasma coagulation. Three trials of electrocoagulation in combination with acid suppression have had promising results. In one series of 14 patients with Barrett’s esophagus undergoing Nissen fundoplication who were treated with electrocoagulation, no patients had recurrent intestinal metaplasia after a mean of 22 months of follow-up (Evidence-B) (67). Two other series demonstrated residual intestinal metaplasia in 18% to 27% of patients after electrocoagulation (Evidence-B) (68,69). Similar results have been demonstrated using argon plasma coagulation in combination with acid suppression, with residual intestinal metaplasia seen in 1% to 47% of patients at follow-up endoscopy (Evidence-B) (70 –72). When argon treatment followed Nissen fundoplication in 30 patients with Barrett’s esophagus, recurrence of short segments of intestinal metaplasia was detected only in the 2 patients with recurrent acid reflux (Evidence-B) (73). Although long-term follow-up of these treatments is not available, these studies suggest that early identification of dysplasia and cancer in Barrett’s esophagus can provide the opportunity for endoscopic treatment to prevent the development of invasive neoplastic disease (Evidence-B).
Should There Be Population Screening for Barrett’s Esophagus? Although evidence from questionnaire studies suggests that patients with severe symptoms of gastroesophageal reflux disease should be screened for Barrett’s esophagus, large series have also demonstrated that the majority of patients with Barrett’s esophagus who develop malignancy never report symptoms before presentation with
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cancer. Therefore, if all potential cases of Barrett’s esophagus are to be identified, there should be consideration for population screening to include patients without frequent reflux symptoms. The question of endoscopic screening for Barrett’s esophagus in asymptomatic adults at age 50 years was investigated in a prospective study of 110 adults undergoing sigmoidoscopy for routine colorectal cancer screening (Evidence-B) (36). Exclusion criteria included symptoms of gastroesophageal reflux disease occurring more than once a month, use of medications for heartburn, or previous endoscopy. The mean age of the participants was 61 ⫾ 9 years (range, 50 – 80 years), and most subjects were male (92% [n ⫽ 101]), white (73% [n ⫽ 80]), and veterans (94% [n ⫽ 104]). Intestinal metaplasia extending above the gastroesophageal junction was detected in 28 subjects (25%); 8 (7%) who had long (ⱖ3 cm) segments of Barrett’s esophagus, and 19 (17%) who had short segments (⬍3 cm). When interviewed carefully about the frequency of prior heartburn symptoms, 51% (n ⫽ 56) of the participants never had heartburn in the past, 28% (n ⫽ 31) had heartburn after meals occurring one to two times per year, and all of the remaining patients had heartburn after meals occurring no more than once a month. Patients with Barrett’s esophagus were no more likely to be obese, to be consumers of tobacco or alcohol, to report a family history of heartburn, or to use antacids more than once a month, than were those without Barrett’s esophagus. The results from this preliminary study suggest that the prevalence of Barrett’s esophagus in asymptomatic elderly male veterans is at least equal to that in patients with pathologic gastroesophageal reflux disease (Evidence-B). However, evidence that population screening will reduce mortality from esophageal cancer is required before screening can be recommended.
Is There Potential Harm from Endoscopic Screening? Endoscopic screening for esophageal adenocarcinoma can be inconvenient, unpleasant, and expensive for patients. In addition, the findings from the screening endoscopic examination can lead to possible psychological distress. Patients labeled as having Barrett’s esophagus might consider themselves to be ill even though their risk of developing cancer is very low. For example, productive steelworkers who were found to be hypertensive subsequently suffered from increased absenteeism, lost income, and adoption of a sick role that was independent of treatment (Evidence-B) (74,75). In another study, women labeled with gestational diabetes were more likely to report deterioration of their health and their infants’ health up to 5 years after their diagnosis (Evidence-B) (76). To date, no studies have been published regarding
potential adverse effects from the diagnosis and subsequence surveillance of Barrett’s esophagus. In addition to the potential psychological harm associated with screening, complications from upper endoscopy (perforation and bleeding) can occur. The incidence of complications, including perforation, respiratory arrest, and myocardial infarction, has been estimated to be 0 –13 per 10,000 procedures (77– 80), with an associated mortality of 0 – 0.8 per 10,000 procedures (Evidence-B). These complications are expected to be lower with unsedated, transnasal endoscopy (54).
CONCLUSION Risk factors identified by questionnaire, primarily longstanding frequent gastroesophageal reflux symptoms, male sex, and obesity, may identify patients with gastroesophageal reflux disease who potentially should undergo screening for Barrett’s esophagus to prevent the development of esophageal carcinoma. More data are required before population screening for Barrett’s esophagus can be recommended. Evidence from cohort studies suggests that patients in a Barrett’s surveillance program will present with cancers at an earlier stage and may have improved survival rates.
REFERENCES 1. Ries LAG, Eisner MP, Kosary CL, et al., eds. SEER Cancer Statistics Review, 1973–1978. Bethesda, Maryland: National Cancer Institute; 2001. 2. Rogers EL, Goldkind SF, Iseri OA, et al. Adenocarcinoma of the lower esophagus. A disease primarily of white men with Barrett’s esophagus. J Clin Gastroenterol. 1996;8:613–618. 3. Heitmiller RF, Sharma RR. Comparison of prevalence and resection rates in patients with esophageal squamous cell carcinoma and adenocarcinoma. J Thorac Cardiovasc Surg. 1996;112:130 –136. 4. Botterweck AA, Schouten LJ, Volovics A, et al. Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten European countries. Int J Epidemiol. 2000;29:645–654. 5. Bytzer P, Christensen PB, Damkier P, et al. Adenocarcinoma of the esophagus and Barrett’s esophagus: a population-based study. Am J Gastroenterol. 1999;94:86 –91. 6. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA. 1991; 265:1287–1289. 7. Braghetto I, Csendes A, Cornejo A, et al. Survival of patients with esophageal cancer subjected to total thoracic esophagectomy. Rev Med Chil. 2000;128:64 –74. 8. Karl RC, Schreiber R, Boulware D, et al. Factors affecting morbidity, mortality, and survival in patients undergoing Ivor Lewis esophagogastrectomy. Ann Surg. 2000;231:635–643. 9. Kelsen DP, Ginsberg R, Pajak TF, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998;339:1979 –1984. 10. Salazar JD, Doty JR, Lin JW, et al. Does cell type influence postesophagectomy survival in patients with esophageal cancer? Dis Esophagus. 1998;11:168 –171.
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APPENDIX Questionnaire for Barrett’s Esophagus Prediction Model (30) Please circle your response to the questions below. When we ask about your symptoms, please use the following scale: 0 ⫽ no problem 1 ⫽ mild problem (can be ignored if you do not think about it) 2 ⫽ moderate problem (cannot be ignored, but does not affect your daily activities) 3 ⫽ severe problem (affects your daily activities) Please answer the following questions about your heartburn symptoms as if you were not taking any prescription medications: Symptom
Score
1. Do you have heartburn (burning in the chest or throat)? 2. Do you have difficulty swallowing food or liquids? 3. Does it hurt when you swallow? 4. Do you feel sick to your stomach after a meal? 5. Do you belch? 6. Does the pain in your belly wake you up at night? 7. Is the pain in your belly relieved by eating?
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0 0 0 0 0 0
1 1 1 1 1 1
2 2 2 2 2 2
3 3 3 3 3 3
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