Primary Motility  Disorders of the  Esophagus
 The Esophageal
 Mucosa
 The
 Esophagogastric  Junction
 Barrett's
 Esophagus

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OESO©2015
 
Volume: Barrett's Esophagus
Chapter: Screening and surveillance
 

What is the cost-effectiveness of long-term surveillance of Barrett's patients after antireflux surgery?

S.R. DeMeester (Los Angeles)

Rationale for surveillance endoscopy

In contrast to screening endoscopy, surveillance endoscopy is done in patients known to have Barrett's to follow-up their Barrett's. The rationale for endoscopic surveillance in patients with Barrett's is twofold: to detect progression of disease toward cancer, and to allow early intervention while cure is still likely. Inherent in this rationale is the necessity that the surveillance will be frequent enough that rarely, if ever, does the disease progress beyond an early, curable stage during the surveillance interval, and that once disease progression is detected an intervention is performed. Continued surveillance despite disease progression may help clarify the natural history of the disease, but does little to benefit the patient. Controversy exists, however, about the point at which there has been sufficient progression to warrant intervention, and what intervention should be done.

Provenzale et al. used a Markov model of decision analysis to demonstrate that aggressive endoscopic surveillance combined with esophagectomy for high-grade dysplasia (HGD) would markedly reduce the incidence of cancer in patients with Barrett's esophagus, and increase both overall and quality-adjusted life expectancy [1]. The predictions of the model have now been verified in several clinical series where patients with adenocarcinoma detected within a surveillance program were found to have earlier stage tumors and a significantly improved long-term survival following esophagectomy compared to patients who presented de novo with symptoms [2, 3]. However, the most important factor in determining both the impact and the cost-effectiveness of a surveillance program for Barrett's is the risk of adenocarcinoma in an individual patient with Barrett's esophagus. This number has been difficult to pin down, but most believe it to be in the range of 0.5-1% per year. A recent meta-analysis placed the risk at 0.5% per year, but this meta-analysis included groups of patients being followed after antireflux surgery, a procedure that increasingly is being shown to decrease the incidence of cancer in Barrett's patients [4, 5]. Consequently, inclusion of these postfundoplication patients in the metaanalysis likely falsely lowered the rate from what should be expected in a group of untreated or perhaps medically treated patients with Barrett's.

Cost of surveillance for Barrett's

The cost effectiveness of surveillance endoscopy for Barrett's has recently been compared to mammography for the detection of breast cancer (Table I) [6]. The cost per cancer detected and the cost per patient cured was similar, but the cost per life-year saved was dramatically lower for surveillance endoscopy in Barrett's patients than mammography in women. This likely is because outside of a surveillance program esophageal cancer often presents in an advanced stage, and the clinical course is rapidly fatal. In contrast, the lag time between mammography and palpable detection of breast cancer is shorter, and the clinical course with breast cancer is often quite protracted.

Table I. Comparison of the cost of surveillance mammography for breast cancer to the cost of surveillance endoscopy for patients with Barrett's esophagus (data from [6]).

Provenzale et al. recently reanalyzed the utility of screening in Barrett's patients again using the Markov model they had previously described [7]. They confirmed that surveillance for Barrett's had an incremental cost-utility ratio that compared favorably with other common medical practices such as mammography for breast cancer. In their analysis the two critical parameters for decisions about surveillance were the incidence of cancer and the quality of life after esophagectomy. They found that if the incidence of cancer is 1% then surveillance every 2 years provides the greatest gain in quality-adjusted life expectancy. However, the model also pointed out that the benefits of surveillance are lost if there is a high operative mortality and poor quality of life associated with esophagectomy. Consequently, it is imperative that patients with HGD and early esophageal adenocarcinoma found in Barrett's surveillance programs be treated at centers experienced with esophageal surgery in order to realize the benefits of surveillance. One last consideration is that this analysis did not take into consideration new techniques such as photodynamic therapy and endoscopic mucosal resection that may be useful for treating some patients with HGD or early malignancy. It is likely that these procedures will also impact the overall assessment of cost effectiveness for surveillance in patients with Barrett's esophagus, and new analyses should be done taking these options into consideration as more long-term efficacy data becomes available.

Surveillance frequency and risk factors for Barrett's progression

The recommended frequency for endoscopic surveillance in Barrett's patients is based upon available data about the likelihood of progression to cancer, and the risks associated with the surveillance procedure. Currently the most important identifiable risk factor for progression to cancer is the presence of dysplasia within the Barrett's mucosa. Patients with low-grade dysplasia (LGD) are one step closer to cancer, and LGD can rapidly progress to HGD and cancer in some patients. Consequently, it is recommended that patients with LGD undergo more frequent surveillance, generally every 6 months, for at least the first year [8].

An important area of investigation is focused on identifying particular risk factors for progression in patients with Barrett's to better define the population that would benefit most from surveillance endoscopy. Reid et al. have used flow cytometry to augment histology and further stratify the risk of progression to cancer in patients with Barrett's with and without dysplasia [9]. They found that both aneuploidy and increased 4N fractions were associated with an increased incidence of esophageal adenocarcinoma in those patients with histology showing negative, indefinite, or LGD. However, in patients with HGD the incidence of cancer was so high that flow cytometry did not further stratify patients in regards to risk of cancer. Based on their findings they suggested that in those patients without HGD and with no aneuploidy or increased 4N on flow cytometry, surveillance endoscopy intervals could be lengthened to as much as 5 years apart. Conversely, patients with flow cytometry abnormalities or HGD are at significant risk for esophageal adenocarcinoma and should be watched closely.

Recent papers by Weston et al. have explored the factors associated with persistence of intestinal metaplasia (IM) and a poor outcome with medical therapy for Barrett's [10, 11]. They defined a poor outcome as progression to HGD or cancer. The three factors significantly associated with progression on medical therapy were: dysplasia at diagnosis or during follow-up (p < 0.03), a hiatal hernia = 3cm in size (p < 0.02), and an increasing length of Barrett's > 2 cm (p = 0.009). They noted that proton pump inhibitor (PPI) use was not associated with a risk for poor outcome; however, they divided patients taking PPIs into 3 groups depending on whether they took a PPI qd, bid, or with cisapride. Had they compared any use of a PPI to only H2-blocker use they would have noted that 0/38 patients on H2-blockers had a poor outcome compared to 10/70 using a PPI (p = 0.036 by chi-square). The obvious conclusion is that those patients on PPIs have worse disease and thus a greater risk for a poor outcome on medical therapy, and that is exactly the point. These Barrett's patients, like those with dysplasia, large hernias, and long-segments of IM, should be treated with antireflux surgery rather than acid-suppression.

Previously it was also felt that the length of IM represented a risk factor for the likelihood of progression to cancer. Intuitively it makes sense that since longer segments of IM have more mucosa at risk for progression, the incidence of cancer should be higher in these patients than it is in those with short segment Barrett's. However, a recent manuscript by Rudolph et al. found that there was no significant difference in the risk of developing cancer for long versus short segments of Barrett's [12]. Consequently, we advise our patients with any length of IM within the esophagus to undergo surveillance endoscopy, and do not alter the surveillance interval based on the length of Barrett's.

A final issue in regard to surveillance endoscopy is the safety of the procedure. Recently Levine et al. reviewed the University of Washington experience after 1,458 endoscopies with a total of 50,833 biopsies in 705 patients with Barrett's over a 15-year period [13]. There were no deaths, and although the overall complication rate was 1.6%, most were minor and self-limited.

Current practice in regards to surveillance for Barrett's

A recent survey of practice patterns for Barrett's surveillance among gastroenterologists in the US by Falk et al. found that while the concept of surveillance was widely embraced, there was considerable variation in techniques and intervals for the surveillance [14]. They reported that 98% of community physicians and 89% of academic physicians practiced surveillance for their patients with Barrett's. One concern, though, is that the response rate for the survey was only 45%. Consequently the results may have been skewed in that clinicians with an interest in Barrett's were more likely to complete the survey, and were also more likely to recommend surveillance. Evidence for this possibility comes from Patti et al. They questioned patients with Barrett's who were being evaluated for antireflux surgery and found that only 62% had undergone surveillance endoscopy after their diagnosis of Barrett's [15]. Gross et al. also reported a survey of practice patterns for Barrett's surveillance in the United States [16]. They found that most gastroenterologists (66%) agreed that surveillance was an effective way of detecting adenocarcinoma at an early, curable stage. However, they found that physicians who were reimbursed mainly on a fee-for-service basis were 2.5 times more likely to recommend aggressive surveillance than were physicians reimbursed through other mechanisms. This finding held true despite adjusting for the age of the physicians, patient volume, and perceived risk of cancer. They concluded that there could be strong non-clinical factors that influence physician management of patients with Barrett's.

It has been our practice to recommend yearly surveillance endoscopy and biopsy to all patients with Barrett's, regardless of length. We increase the frequency to every 6 months for patients with LGD, and generally recommend esophagectomy for patients with HGD. Sampliner and the Practice Parameters Committee of the American College of Gastroenterology have recently suggested that surveillance may be extended to every 23 years in Barrett's patients without dysplasia on biopsies from two annual endoscopies [8]. For patients with LGD they recommend that surveillance endoscopy be performed at 6monthly intervals for the first year, and subsequently done yearly if there has been no change.

While there is increasing evidence that an antireflux operation alters the natural history of Barrett's, there is insufficient evidence to identify a point at which surveillance endoscopy no longer is necessary. Available data would certainly suggest that surveillance should be done routinely for the first 5 years, as it seems that this is the real risk period for patients with a functioning fundoplication. Additionally, the presence of recurrent symptoms or documented failure of the fundoplication would mandate continued surveillance endoscopy. Hopefully as more data become available about the risk of progression after antireflux surgery a point will be determined at which surveillance is no longer necessary in patients with a functioning fundoplication.

References

1. Provenzale D, Kemp JA, Arora S, Wong JB. A guide for surveillance of patients with Barrett's esophagus. Am J Gastroenterol 1994;89:670-680.

2. 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;108:813-822.

3. van Sandick JW, van Lanschot JJB, Kuiken BW, Tytgat GNJ, Offerhaus GJA, Obertop H. Impact of endoscopic biopsy surveillance of Barrett's oesophagus on pathological stage and clinical outcome of Barrett's carcinoma. Gut 1998;43:216-222.

4. 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(2):333-338. Comment in Gastroenterology 2000;119(2):587-589.

5. DeMeester SR, DeMeester TR. Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy. Ann Surg 2000;231:303-321.

6. Streitz JM Jr, Ellis FH Jr, Tilden RL, Erickson RV. Endoscopic surveillance of Barrett's esophagus: a cost-effectiveness comparison with mammographic surveillance for breast cancer. Am J Gastroenterol 1998;93:911-915.

7. Provenzale D, Schmitt C, Wong JB. Barrett's esophagus: a new look at surveillance based on emerging estimates of cancer risk. Am J Gastroenterol 1999;94(8):2043-2053.

8. Sampliner RE. Practice guidelines on the diagnosis, surveillance, and therapy of Barrett's esophagus. The Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol 1998;93:1028-1032.

9. 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(7):16691676.

10. Weston AP, Badr AS, Hassanein RS. Prospective multivariate analysis of factors predictive of complete regression of Barrett's esophagus. Am J Gastroenterol 1999;94:3420-3426. Comment in Am J Gastroenterol 1999;94(12):3395-3396.

11. Weston AP, Badr AS, Hassanein RS. Prospective multivariate analysis of clinical, endoscopic, and histological factors predictive of the development of Barrett's multifocal high-grade dysplasia or adenocarcinoma. Am J Gastroenterol 1999;94:3413-3419. Comment in Am J Gastroenterol 1999;94(12):3395-3396.

12. Rudolph RE, Vaughan TL, Storer BE, Haggitt RC, Rabinovitch PS, Levine DS, Reid BJ. Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus. Ann Intern Med 2000;132(8):612-620.

13. Levine DS, Blount PL, Rudolph RE, Reid BJ. Safety of a systematic endoscopic biopsy protocol in patients with Barrett's esophagus. Am J Gastroenterol 2000;95(5),:1152-1157.

14. Falk GW, Ours TM, Richter JE. Practice patterns for surveillance of Barrett's esophagus in the united states. Gastrointest Endosc 2000;52(2):197-203.

15. Patti MG, Arcerito M, Feo CV, Worth S, De Pinto M, Gibbs VC, Gantert W, Tyrrell D, Ferrell LF, Way LW. Barrett's esophagus: a surgical disease. J Gastrointest Surg 1999;3(4):397-404.

16. Gross CP, Canto MI, Hixson J, Powe NR. Management of Barrett's esophagus: a national study of practice patterns and their cost implications.Am J Gastroenterol 1999;94(12):3440-3447.


Publication date: August 2003 OESO©2015