REVIEW
Surveillance in Barrett’s Esophagus: A Failed PremiseJohn M. Inadomi

GI Health Outcomes, Policy and Economics (HOPE) Research Program, University of California;
Clinical Gastroenterology, San Francisco General Hospital, CA, USA(Received for publication on April 24, 2008)(Revised for publication on June 18 2008)(Accepted for publication on July 17, 2008)

Abstract
Background : It is recommended that patients in whom Barrett’s esophagus is diagnosed undergo surveillance endoscopy. However, multiple issues regarding the efficacy and feasibilityof surveillance remain.
Methods : Quantitative techniques were used to examine surveillance in patients with Barrett’s esophagus. A retrospective case-control study was performed to determine whether
surveillance endoscopy prolonged survival in a cohort of U.S. veterans diagnosed withesophageal adenocarcinoma. Cost-effectiveness analysis was employed to compare competing strategies of management for patients with Barrett’s esophagus to determine whether
surveillance strategies using alternative biomarkers could out-perform dysplasia based surveillance, and whether new techniques for eradicating Barrett’s metaplasia would constitute cost-effective strategies.
Results : Surveillance did not improve long-term survival among veterans diagnosed withesophageal adenocarcinoma. Lead-time bias has confounded previous reports claiming theefficacy of endoscopic surveillance. Cost-effectiveness analysis revealed that while screening 50-year old Caucasian males with heartburn may be cost-effective, surveillance even at
5 year intervals among patients with Barrett’s esophagus without dysplasia exceeded thethreshold of cost-effective care. If a biomarker were developed whose sensitivity and specificity to predict cancer development exceeded 80%, this could represent a more viable strategy than dysplasia-based surveillance and overcome the inherent inter- and intra-observer
variations in dysplasia diagnosis that currently limit the effectiveness of surveillance programs. Finally, techniques that reduce cancer incidence such as endoscopic mucosal resection or ablation will likely be more cost-effective than current surveillance strategies that
rely on early detection of cancer.
Conclusions : Current recommendations for the management of patients with Barrett’s
esophagus are flawed. Future guidelines should include alternative markers of cancer risk
and focus on strategies that reduce cancer incidence instead of cancer detection. (Keio J Med
58 (1) : 12－18, March 2009)

Keywords: Barrett’s esophagus, surveillance, screening, esophageal adenocarcinoma
Background

American College of Gastroenterology guidelines is thepresence of endoscopically identifiable columnar appearing mucosa within the tubular esophagus in which histological examination reveals the presence of intestinal
metaplasia.1 While it has become routine practice toBarrett’s esophagus is the accepted precursor responsible for the majority if not all cases of esophageal adenocarcinoma. The definition of Barrett’s esophagus per the

Presented at the 1541st meeting of the Keio Medical Society in Tokyo, November 14, 2007
Reprint request to: John M. Inadomi, M.D., Professor of Medicine, Dean M. Craig Endowed Chair in Gastrointestinal Medicine, Director, GI Health Outcomes, Policy and Economics (HOPE) Research Program, University of California, San Francisco, Chief, Clinical Gastroenterology, San Francisco General
Hospital, 1001 Potrero Avenue, San Francisco, CA 94110, Tel: +1-415-206-4749, Email: jinadomi@medsfgh.ucsf.edu
12Keio J Med 2009; 58 (1):12－18

perform screening to detect Barrett’s esophagus in populations believed to be at high risk for the development ofesophageal adenocarcinoma, namely people with symptoms consistent with gastroesophageal reflux, little evidence supports this practice.1 Moreover, one is facedwith the dilemma of how best to conduct surveillance after screening has diagnosed Barrett’s esophagus. Problems with the grading of dysplasia, the major factor bywhich management is stratified for purposes of surveillance or intervention, inter- and intra-observer variability, sampling error and unclear natural history compoundthe complexity of issues surrounding optimal care of patients with Barrett’s esophagus.
The purpose of this review is to critically examine the
key areas that impact the effectiveness of screening andsurveillance for Barrett’s esophagus. The main points tobe covered include determination of the efficacy of
screening to reduce mortality from esophageal adenocarcinoma, identification of the economic impact of screening and surveillance, and exploration into whether better
alternatives to surveillance exist and should be pursued.
The Risk of Cancer
The risk of cancer among patients with Barrett’s
esophagus, while not precisely documented, is lower
than initially reported. Early studies quoted a cancer incidence as high as 2% annual risk.2 More recent data
downgrade the risk to 0.5% annual risk of cancer,3 withpublication bias likely explaining the discrepancy between the new and old estimates. Dysplasia has beenused as the means to stratify patients’ risk of cancer, withthe risk being lowest in those without dysplasia andhighest in those with high grade dysplasia.2, 4-6 However, a concerning proportion of patients who eventuallydevelop cancer do not have dysplasia on their initial biopsies.7
The association between H. pylori and esophageal adenocarcinoma is complex. The distinction between adenocarcinoma of the distal esophagus and adenocarcinomaof the cardia is difficult if not impossible to make basedon histology or pathology codes. Therefore H. pylori associated gastric cardia adenocarcinoma cannot be separate from Barrett’s esophagus associated distal esophageal adenocarcinoma when analyzing information fromadministrative databases. Screening for either disease involves upper gastrointestinal endoscopy where detectionof early stage cancer can be achieved. A more complex
association may be present from an epidemiological perspective. The time trends in the United States for peptic
ulcer disease, and by inference H. pylori infection, is inversely associated with the time trend for Barrett’s
esophagus and esophageal adenocarcinoma.8 For thisreason there is speculation that the rise in gastroesophageal reflux disease, Barrett’s esophagus and associated13

esophageal adenocarcinoma is due to the population decline in H. pylori infection. While unproven, it has beensuggested that chronic gastric inflammation from H. pylori infection decreases acid secretion thereby providing
protection against acid-associated esophageal injury. Environmental conditions that have reduced H. pylori infection in the U.S. may then allow unopposed acid secretion to persist through adulthood resulting in the increased prevalence of gastroesophageal reflux disease
and associated complications including esophageal adenocarcinoma.8
Current Guidelines for Screening and Surveillance
The American College of Gastroenterology recently
updated its guidelines for screening and surveillance in
Barrett’s esophagus.1 Recall that screening is defined as
testing an average-risk population for the presence ofdisease while surveillance involves repeated testing in acohort previously identified at high risk for disease progression. The yield from screening would be highest
among Caucasian men age 50 years and older withsymptoms of gastroesophageal reflux disease since although the risk of esophageal adenocarcinoma is risingin all races and genders, the greatest increase has been
observed in this cohort. It should be noted that environmental factors play in important role in cancer development and race and/or gender may be a surrogate for thesefactors; therefore it is premature to eliminate non-Whites
or women from consideration of screening. Recommendations from the American Gastroenterological Association and the American College of Gastroenterology support surveillance among persons diagnosed with Barrett’s
esophagus.1, 9, 1 0 The interval between surveillance endoscopies depends on the presence and severity of dysplasia: no dysplasia on 2 exams allows for a 3-5 year interval, low-grade dysplasia prompts 1 year intervals
while high-grade dysplasia can be managed by surveillance every 3 months. Alternatively, high-grade dysplasia can be treated by endoscopic ablation (photodynamic
therapy, radiofrequency ablation) or mucosal resection.
Although some centers still perform esophagectomy fora diagnosis of high-grade dysplasia this is no longer routinely advocated by the guidelines. Esophagectomy isrecommended for cancer, although newer reports indicate that lesions confirmed by endoscopic ultrasound(EUS) to be confined to the mucosa can be successfully
treated endoscopically.11, 12
Evidence Supporting Surveillance among Patientswith Barrett’s Esophagus
Although evidence proving the efficacy of screening todetect Barrett’s esophagus is lacking, several retrospective studies illustrate a mortality benefit from surveil-

14

lance to detect and treat early cancer. These studies compared mortality from esophageal adenocarcinoma among
patients who had previously undergone endoscopy withthose who did not receive endoscopy and showed thatmortality was significantly reduced among those who
had previous endoscopy.1 3-1 6 However, the retrospective nature of these studies could not exclude bias due tolead or length time effects, nor could the studies exclude
confounding by indication, ascertainment bias or otherfactors. In fact, it is likely that a part if not all of the effect of surveillance endoscopy on mortality is based onlead time bias. Lead-time bias occurs when a screening
and surveillance program appears to prolong survival,
but in reality only the duration with which the diagnosis
is known is prolonged and the actual lifetime is not increased. For example let us assume that twin brothers
develop cancer at the same time and die five years later.
One of the brothers undergoes a screening test prior tothe onset of symptoms and is diagnosed at an earlier,pre-symptomatic stage, while the other brother does notundergo screening and is diagnosed only after symptoms
develop. The brother in whom screening was performed
will have an apparent survival with cancer that is longer
than the brother who did not undergo screening. Screening, however, did not prolong the lifespan of that brother;rather, screening merely allowed a diagnosis to be obtained at an earlier time and the duration with which thepatient survives with cancer appears to be longer. Thus,
lead-time bias is present when a patient undergoing
screening and surveillance appears to have longer life
when in actuality this gain is merely due to the added
time between early diagnosis achieved through surveillance and the point at which symptoms would haveprompted diagnosis had screening and surveillance notbeen conducted. We conducted a study in which the durability of the mortality benefit was examined and foundthat although 5-year survival appeared lengthened bysurveillance this benefit disappeared with longer followup, indicating the presence of lead-time bias.17 Thus themortality benefit from surveillance endoscopy has notbeen confirmed and remains to be proven through prospective clinical trials.
Another problem with our current management of Barrett’s esophagus is that the incidence of cancer diagnosed
through surveillance is lower than the prevalence of cancer found at screening. Screening will discover prevalentcancers while surveillance will identify incident cancers.
A cohort of patients with Barrett’s esophagus followed
for a mean of 7.3 years reported that the prevalence ofcancer diagnosed within the 1st year of the identificationof Barrett’s esophagus was 4.2% in contrast to the incidence of cancer, which was 2.1%.4 In essence, the people who are destined to develop esophageal adenocarcinoma already have it by the time we diagnose Barrett’s
esophagus. The only way a surveillance strategy will be

Inadomi JM: Surveillance in Barrett’s Esophagus

useful is if we alter our method of screening to detect
Barrett’s earlier than is currently practiced, prior to thedevelopment of cancer.
The Cost-effectiveness of Screening and
Surveillance to Decrease Mortality from
Esophageal Adenocarcinoma
Prior discussion notwithstanding, even if one assumes
that surveillance decreases mortality by detecting cancer
at a treatable stage there are economic barriers to implementation of surveillance. Using estimates from published retrospective studies, we compared screening withvarious strategies of surveillance to no screening or surveillance among patients at elevated risk of cancer, specifically White men over the age of 50 years with symptoms of gastroesophageal reflux disease. Through mathematical modeling using computer simulation we estimated that screening may be cost-effective compared to
no screening in this population through the identificationof patients with prevalent cancer as well as patients with
dysplasia associated Barrett’s esophagus that indicates ahigher risk of cancer development.18 However, we also
showed that continued surveillance among patients withBarrett’s esophagus in the absence of dysplasia was unlikely to be feasible at costs considered reasonable bysociety. Figure 1 illustrates the various costs and benefits associated with no screening or surveillance compared to screening with surveillance limited to patientswith dysplasia and Barrett’s esophagus, versus surveillance for patients without dysplasia at intervals of 2-5
years. The relatively modest incremental cost-effectiveness ratio (ICER) depicted by the slope of the line connecting the no screening or surveillance strategy with thescreening with surveillance for dysplasia strategy indicate a cost-effectiveness less than $50,000 per qualityadjusted life-year gained, which is the threshold U.S. society is willing to pay. In contrast, however, the steepline connecting the strategies in which surveillance isperformed for patients without dysplasia indicate that
this practice is extremely expensive with costs over
$380,000 per quality-adjusted life-year gained. An extensive sensitivity analysis was conducted and despite
variation of input parameters within the entire range reported in the published literature, screening with surveillance limited to patients with Barrett’s esophagus anddysplasia remained cost-effective in 99% of simulations.
Conversely, continued surveillance for patient with Barrett’s esophagus in the absence of dysplasia was nevercost-effective at a threshold of $50,000 per life year
saved and only feasible at a threshold of $100,000 in 7%of simulations. These results indicate that the conclusions of the analyses are robust and unlikely to change
significantly unless new data significantly contradictcurrent literature regarding the natural history of Barrett’Keio J Med 2009; 58 (1):12－18

15

Fig. 1 Cost Effectiveness Analysis. The x-axis depicts benefit measured in units of quality adjusted life years (QALYs). The y-axis
denotes the costs (U.S.$) associated with various strategies including no screening or surveillance, screening with surveillance limited
to patients with Barrett’s esophagus and dysplasia, screening with surveillance for patients with Barrett’s and no dysplasia at 5-, 4-, 3-,
or 2-year intervals. The lines depict the incremental cost-effectiveness ratio (ICER) between non-dominated strategies. (Reproduced
from “Screening and Surveillance for Barrett Esophagus in High-Risk Groups: A Cost-Utility Analysis.” Inadomi, et al., Annals ofInternal Medicine, Feb 2003; 138 Fig. 2)

s esophagus or heighten the efficacy of surveillance toreduce mortality. Thus current guidelines recommend a
strategy that is apparently beyond the budget that societal standards have established.
Biomarkers in Barrett’s Esophagus
Implicit in the recommendation to screen patients withsymptoms of gastroesophageal reflux disease is the useof heartburn as a biomarker to identify those with Barrett’s esophagus. While heartburn is indeed a strong risk
factor for the development of esophageal adenocarcinoma,19 the absence of heartburn does not necessarily exclude Barrett’s. Fully 40% of patients diagnosed withesophageal adenocarcinoma do not report significant
heartburn symptoms five years or more prior to the diagnosis of cancer.1 9 Indeed, while the prevalence of Barrett’s esophagus among patients with heartburn is approximately 10%2 0, 2 1 other studies have revealed theprevalence of Barrett’s among patients without heartburn
to be as high as 25%.2 2, 2 3 It is clear that any strategy
that relies upon the presence of heartburn to prompt
screening will fail to identify a significant proportion of
the patients with Barrett’s esophagus.
The risk of cancer among patients with Barrett’s

esophagus is lower than initially reported and despite theincrease in cancer incidence, insufficient to allow any intervention including surveillance to achieve the thresholdnecessary to be economically feasible. Further risk stratification is attempted through the use of dysplasia as themarker to identify patients with Barrett’s esophagus at
highest risk for cancer development and utilize the gradeof dysplasia to dictate the interval between surveillanceendoscopies and to possible indicate when interventions
such as ablation therapy or endoscopic mucosal resection
are indicated. The fallacies of this recommendation are
the well-recognized deficiencies of dysplasia with regards to inter- and intra-observer variation, sampling error and the potentially evanescent nature of dysplasia.
Studies have indicated that the correlation for the diagnosis of dysplasia between even expert pathologists isonly fair.24, 25 This problem is compounded when taken
to the level of the community pathologist and only partially rectified by the recommendation to have all diagnoses of dysplasia reviewed by a second expert pathologist. The diagnosis of dysplasia cannot be considered astable, linear process. Data from longitudinal studies illustrate that low-grade dysplasia can be seen at sometime during follow-up in approximately two-thirds of patients with Barrett’s esophagus;4, 7 however, most pa-

16

Inadomi JM: Surveillance in Barrett’s Esophagus

tients do not progress to high-grade dysplasia or cancer
and many regress to non-dysplastic metaplasia on subsequent surveillance examinations. While this may indicate
sampling error since dysplasia may be focal and difficult
to locate during endoscopy, an equally plausible explanation that has not been refuted is that dysplasia can regress as well as progress over time. Dysplasia may be
the best biomarker currently available to predict likelihood of progression to cancer but it is seriously flawed
and surveillance strategies that rely upon dysplasia to
dictate clinical management will never be optimal.25
One of the functions of decision analysis is to identify
factors most likely to influence study conclusions.26, 27 In
the case of published studies of surveillance in Barrett’s
esophagus the method of detection of patients at highrisk of cancer development was a significant factor andif methods were developed that improved beyond the capability of dysplasia the impact of surveillance could
significantly improve. For the purposes of surveillance itwould be important for a biomarker to not merely identify patients in whom cancer was already present but also
accurately determine which patients were most likely todevelop cancer.28 We have examined this aspect of diagnosis in more detailed decision analysis using alternative
methods of risk stratification, specifically asking whether
flow cytometry could be a viable option for determining
which patient with Barrett’s esophagus should under surveillance. In a decision analysis study we compared traditional surveillance stratification by dysplasia withstratification by flow cytometry where only patients inwhom abnormal flow is present would undergo surveillance endoscopy.2 9 The results of this analysis indicatethat using current estimates for the ability of flow cytometry to predict development of cancer, this technique toidentify patients with Barrett’s esophagus in whom toperform surveillance is inferior to the use of dysplasia as
the biomarker. Improvements in the ability of flow cytometry or another biomarker to predict cancer development could potentially surpass dysplasia-mediated surveillance if the sensitivity and specificity exceeded
80-90% in the accuracy of predicting cancer development. Costs of the biomarker would also be importantsince if the test approached $1000 the accuracy would
need to substantially improve beyond 90% accuracy.
This study demonstrated that while current technology isinsufficient for alternative biomarkers to surpass dysplasia as the preferred method of stratification, the thresholdfor biomarker development has been set and will likely
be attainable in the future.
Therapy for Barrett’s Esophagus
Beyond diagnosis and stratification, the most pressing
issue with regards to Barrett’s management involves successful eradication of Barrett’s metaplasia and dysplasia.

We and others have examined photodynamic therapy(PDT) for high-grade dysplasia associated with Barrett’s
esophagus.3 0-3 3 These analyses uniformly support theuse of ablation as opposed to immediate esophagectomy
or enhanced surveillance in this patient population. Despite the high cost and relatively high rate of complications (stricture and perforation) PDT performs favorablycompared to alternatives, mainly due to its ability to potentially avert esophagectomy, which is associated with adecrement in quality of life. In fact, these analyses indicate that immediate esophagectomy for high-grade dysplasia is not only more expensive than surveillance but
also expected to yield fewer quality adjusted life-years
due to the negative impact on quality of life. The longterm effectiveness of PDT should be identified prior towidescale adoption of this strategy; additionally, complications such as strictures, perforations and the relatively
high rate of recurrent intestinal metaplasia in the treatedsegment, especially recurrence beneath normal squamous epithelium, termed subsquamous intestinal metaplasia (SSIM), constitute significant barriers to this therapy. Based on the negative aspects of PDT it is not recommended for patients with low-grade or no dysplasia.
Radiofrequency ablation (RFA) holds the potential for
ablation of metaplasia and dysplasia with reduced risksof complications seen with PDT. While data are hampered by short-term reporting, promise exists for thisform of therapy for not only patients with dysplasia but
also perhaps patients without dysplasia. Data with followup ranging from 12-14 months indicate that 80-90% of
HGD or LGD may be ablated, while complete eradication of intestinal metaplasia may occur in 50-97% withfollow-up out to 30 months.34-38 Data from these trials
also indicate a rate of stricture formation or perforation
far below that associated with PDT; moreover, post-therapy SSIM appears to be extremely rare, which also is anadvantage for RFA. Formal economic analysis comparing RFA to PDT or surveillance strategies are forthcoming; however, it is likely that RFA will be a cost-effective
alternative for patients with Barrett’s esophagus andhigh-grade dysplasia since the costs and complication
rate are lower than PDT and efficacy appears to be similar. Prior to adoption of RFA, however, long-term resultsmust be obtained, specifically concerning the durabilityof ablation, whether cancer risk is truly reduced andwhether surveillance may be discontinued after ablationis complete.
Endoscopic mucosal resection (EMR) also holds promise as an intervention that may reduce cancer incidence.
Specialized techniques and tools have been developed tofacilitate EMR, increasing the prevalence of this technique throughout the endoscopic community. At present
EMR is best used to remove visible lesions including
raised, ulcerated or depressed lesions. In this capacityand either alone or in conjunction with other ablativeKeio J Med 2009; 58 (1):12－18

techniques results appear quite favorable.11, 12, 39-42 Reports of extended resection of flat mucosa have been
published; however, it is likely that such extensive therapy will require considerable expertise and not be routinely available in clinical practice.
Summary
Barrett’s esophagus is the accepted precursor of esophageal adenocarcinoma. Despite the ability of Barrett’s
esophagus to be identified by endoscopy with biopsy it
is unclear that screening for its presence and surveillance
to detect cancer among patients diagnosed with this lesion is effective or economically feasible. Barriers to thisstrategy include the poor sensitivity of heartburn to identify all Barrett’s patients, poor specificity of Barrett’s topredict progression to cancer, and poor discrimination ofdysplasia to further identify a sub-group of patients inwhom the risk of cancer is sufficiently high to warrant
intervention. Furthermore, the necessity of esophagectomy to treat cancer diminishes the health impact of surveillance based on the decrement in quality of life associated with surgery.
From perspectives of both efficacy and cost-effectiveness it is imperative that screening and surveillance strategies be built around interventions that decrease the riskof cancer as opposed to merely treating cancer at a stage
that is hopefully curable. In short, it is always better toprevent than to treat cancer. Specifically, ablation of Barrett’s esophagus among patients who have been identified to be at imminent risk of cancer would be an ideal
goal. Risk stratification beyond the simple diagnosis ofintestinal metaplasia is necessary to improve targeting ofinterventions that will incur morbidity, mortality andcost. Certainly histological assessment of dysplasia will
be insufficient. Better biomarkers are needed, which will
require improved understanding of the mechanism of theinciting events, proliferation and progression of intestinal metaplasia to dysplasia and cancer. Whether emerging techniques such as PDT, RFA or EMR will fulfill thetherapeutic void remain to be seen and we will await results of long-term trials of these modalities. In the meantime it is difficult to support screening of patients with
reflux symptoms to identify Barrett’s esophagus. Moreover, our current recommendations to perform endoscopy with biopsy at surveillance intervals based on thepresence of dysplasia are at most minimally effective
and at least misleading in terms of the actual benefit accrued. Finally, surveillance in itself cannot improve survival without leading to interventions that alter the natural history of Barrett’s esophagus and at present our interventions have little evidence to support their implementation.

17

References
1. Wang KK, Sampliner RE: Updated Guidelines 2008 for the Diagnosis, Surveillance and Therapy of Barrett’s Esophagus. Am J
Gastroenterol 2008; 103: 788－797
2. Hameeteman W, Tytgat GN, Houthoff HJ, van den Tweel JG: Barrett’s esophagus: development of dysplasia and adenocarcinoma.
Gastroenterology 1989; 96: 1249－1256
3. Shaheen NJ, Crosby MA, Bozymski EM, Sandler RS: Is there
publication bias in the reporting of cancer risk in Barrett’s esophagus? Gastroenterology 2000; 119: 333－338
4. Schnell TG, Sontag SJ, Chejfec G, Aranha G, Metz A, O’Connell
S, Seidel UJ, Sonnenberg A: Long-term nonsurgical managementof Barrett’s esophagus with high-grade dysplasia. Gastroenterology 2001; 120: 1607－1619
5. Robertson CS, Mayberry JF, Nicholson DA, James PD, Atkinson
M: Value of endoscopic surveillance in the detection of neoplasticchange in Barrett’s oesophagus. Br J Surg 1988; 75: 760－763
6. Reid BJ, Blount PL, Rubin CE, Levine DS, Haggitt RC, Rabinovitch PS: Flow-cytometric and histological progression to malignancy in Barrett’s esophagus: prospective endoscopic surveillanceof a cohort. Gastroenterology 1992; 102: 1212－1219
7. Sharma P, Falk GW, Weston AP, Reker D, Johnston M, Sampliner
RE: Dysplasia and cancer in a large multicenter cohort of patientswith Barrett’s esophagus. Clin Gastroenterol Hepatol 2006; 4: 566－572
8. el-Serag HB, Sonnenberg A: Opposing time trends of peptic ulcer
and reflux disease. Gut 1998; 43: 327－333
9. Wang KK, Wongkeesong M, Buttar NS: American Gastroenterological Association technical review on the role of the gastroenterologist in the management of esophageal carcinoma. Gastroenterology 2005; 128: 1471－1505
10. Wang KK, Wongkeesong M, Buttar NS: American Gastroenterological Association medical position statement: Role of the gastroenterologist in the management of esophageal carcinoma. Gastroenterology 2005; 128: 1468－1470
11. Buttar NS, Wang KK, Lutzke LS, Krishnadath KK, Anderson
MA: Combined endoscopic mucosal resection and photodynamic
therapy for esophageal neoplasia within Barrett’s esophagus. Gastrointest Endosc 2001; 54: 682－688
12. Pacifico RJ, Wang KK, Wongkeesong LM, Buttar NS, Lutzke LS:
Combined endoscopic mucosal resection and photodynamic therapy versus esophagectomy for management of early adenocarcinoma in Barrett’s esophagus. Clin Gastroenterol Hepatol 2003; 1:
252－257
13. Streitz JM Jr, Andrews CW Jr, Ellis FH Jr.: Endoscopic surveillance of Barrett’s esophagus. Does it help? J Thorac Cardiovasc
Surg 1993; 105: 383－387
14. Peters JH, Clark GW, Ireland AP, Chandrasoma P, Smyrk TC, DeMeester TR: Outcome of adenocarcinoma arising in Barrett’s
esophagus in endoscopically surveyed and nonsurveyed patients. J
Thorac Cardiovasc Surg 1994; 108: 813－821
15. van Sandick JW, van Lanschot JJ, Kuiken BW, Tytgat GN, Offerhaus GJ, Obertop H: Impact of endoscopic biopsy surveillance ofBarrett’s oesophagus on pathological stage and clinical outcomeof Barrett’s carcinoma. Gut 1998; 43: 216－222
16. Corley DA, Levin TR, Habel LA, Weiss NS, Buffler PA: Surveillance and survival in Barrett’s adenocarcinomas: a populationbased study. Gastroenterology 2002; 122: 633－640
17. Rubenstein JH, Sonnenberg A, Davis J, McMahon L, Inadomi
JM: Effect of a prior endoscopy on outcomes of esophageal adenocarcinoma among United States veterans. Gastrointestinal Endoscopy 2008; 65: 849－855
18. Inadomi JM, Sampliner R, Lagergren J, Lieberman D, Fendrick
AM, Vakil N: Screening and surveillance for Barrett esophagus in
high-risk groups: a cost-utility analysis. Ann Intern Med 2003;

18
138: 176－186
19. Lagergren J, Bergstrom R, Lindgren A, Nyren O: Symptomatic
gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999; 340: 825－831
20. Spechler SJ, Goyal RK: Barrett’s esophagus. N Engl J Med 1986;
315: 362－371
21. Cameron AJ: Epidemiologic studies and the development of Barrett’s esophagus. Endoscopy 1993; 25: 635－636
22. Weston AP, Krmpotich P, Makdisi WF, Cherian R, Dixon A, McGregor DH, Banerjee SK: Short segment Barrett’s esophagus:
clinical and histological features, associated endoscopic findings,
and association with gastric intestinal metaplasia. Am J Gastroenterol 1996; 91: 981－986
23. Gerson LB, Shetler K, Triadafilopoulos G: Prevalence of Barrett’s
esophagus in asymptomatic individuals. Gastroenterology 2002;
123: 461－467
24. Reid BJ, Haggitt RC, Rubin CE, Roth G, Surawicz CM, Van Belle
G, Lewin K, Weinstein WM, Antonioli DA, Goldman H, et al.:Observer variation in the diagnosis of dysplasia in Barrett’s
esophagus. Hum Pathol 1988; 19: 166－178
25. Reid BJ, Blount PL, Rabinovitch PS: Biomarkers in Barrett’s
esophagus. Gastrointest Endosc Clin N Am 2003; 13: 369－397
26. Weinstein MC, Siegel JE, Gold MR, Kamlet MS, Russell LB:
Recommendations of the Panel on Cost-effectiveness in Healthand Medicine. JAMA 1996; 276: 1253－1258
27. Gold MR, Siegel JE, Russell LB, Weinstein MC: Cost-effectiveness in health and medicine. ed. New York: Oxford University
Press, 1996
28. Reid BJ, Levine DS, Longton G, Blount PL, Rabinovitch PS: Predictors of progression to cancer in Barrett’s esophagus: baseline
histology and flow cytometry identify low- and high-risk patient
subsets. Am J Gastroenterol 2000; 95: 1669－1676
29. Rubenstein JH, Vakil N, Inadomi JM: The cost-effectiveness ofbiomarkers for predicting the development of oesophageal adenocarcinoma. Aliment Pharmacol Ther 2005; 22: 135－146
30. Vij R, Triadafilopoulos G, Owens DK, Kunz P, Sanders GD: Costeffectiveness of photodynamic therapy for high-grade dysplasia in
Barrett’s esophagus. Gastrointestinal Endoscopy 2004; 60: 739－
756
31. Shaheen NJ, Inadomi JM, Overholt BF, Sharma P: What is thebest management strategy for high grade dysplasia in Barrett’s oesophagus? A cost effectiveness analysis. Gut 2004; 53: 1736－
1744
32. Hur C, Nishioka NS, Gazelle GS: Cost-effectiveness of photodynamic therapy for treatment of Barrett’s esophagus with highgrade dysplasia. Digestive Diseases & Sciences 2003; 48: 1273－
1283

Inadomi JM: Surveillance in Barrett’s Esophagus
33. Comay D, Blackhouse G, Goeree R, Armstrong D, Marshall JK:
Photodynamic therapy for Barrett’s esophagus with high-grade
dysplasia: a cost-effectiveness analysis. Can J Gastroenterol 2007;
21: 217－222
34. Sharma VK, Wang KK, Overholt BF, Lightdale CJ, Fennerty MB,
Dean PJ, Pleskow DK, Chuttani R, Reymunde A, Santiago N,
Chang KJ, Kimmey MB, Fleischer DE: Balloon-based, circumferential, endoscopic radiofrequency ablation of Barrett’s esophagus:
1-year follow-up of 100 patients. Gastrointest Endosc 2007; 65:
185－195
35. Roorda AK, Marcus SN, Triadafilopoulos G: Early experience
with radiofrequency energy ablation therapy for Barrett’s esophagus with and without dysplasia. Dis Esophagus 2007; 20: 516－
522
36. Gondrie JJ, Pouw RE, Sondermeijer CMT, Peters FP, Curvers
WL, Rosmolen WD, Ten Kate F, Fockens P, Bergman JJ. Effective treatment of early Barrett’s neoplasia with stepwise circumferential and focal ablation using the HALO system. Endoscopy
2008; 40: 370－379
37. Gondrie JJ, Pouw RE, Sondermeijer CMT, Peters FP, Curvers
WL, Rosmolen WD, Ten Kate F, Fockens P, Bergman JJ: Stepwise
circumferential and focal ablation of Barrett’s esophagus withhigh-grade dysplasia: results of the first prospective series of 11
patients. Endoscopy 2008; 40: 359－369
38. Fleischer DE , Overholt BF, Sharma VK, Reymunde A, Kimmey
MB, Chuttani R, Chang KC, Lightdale CJ, Santiago N, Pleskow
DK, Dean PJ, Wang KK: Endoscopic ablation of Barrett’s esophagus: A multi-center study with 2.5-year follow-up. Gastrointestinal Endoscopy 2008; 68: 867-876
39. Ell C, May A, Gossner L, Pech O, Gunter E, Mayer G, Henrich R,
Vieth M, Muller H, Seitz G, Stolte M: Endoscopic mucosal resection of early cancer and high-grade dysplasia in Barrett’s esophagus. Gastroenterology 2000; 118: 670－677
40. Ell C, May A, Pech O, Gossner L, Guenter E, Behrens A, Nachbar
L, Huijsmans J, Vieth M, Stolte M: Curative endoscopic resectionof early esophageal adenocarcinomas (Barrett’s cancer). Gastrointest Endosc 2007; 65: 3－10
41. Lopes CV, Hela M, Pesenti C, Bories E, Caillol F, Monges G,
Giovannini M: Circumferential endoscopic resection of Barrett’s
esophagus with high-grade dysplasia or early adenocarcinoma.
Surg Endosc 2007; 21: 820－824
42. May A, Gossner L, Pech O, Muller H, Vieth M, Stolte M, Ell C:
Intraepithelial high-grade neoplasia and early adenocarcinoma inshort-segment Barrett’s esophagus (SSBE): curative treatment using local endoscopic treatment techniques. Endoscopy 2002; 34:
604－610