Some patients who have been diagnosed with Barrett's esophagus will develop dysplasia and, in some cases, esophageal carcinoma (strength of recommendation [SOR]: A, based on consistent cohort studies). Endoscopic surveillance is recommended for all patients with Barrett's esophagus as it is superior to other methods for detecting esophageal cancer (SOR: B, based on systematic review)

Grover, Michael

Kesler, Ellen

Strickland, Carmen

University of Missouri: MOspace

VOL 55, NO 3 / MARCH 2006 243w w w. j f p o n l i n e . c o mCLINICAL INQUIRIESE V I D E N C E - B A S E D A N S W E RC L I N I C A L C O M M E N T A R YHow should patients with Barrett’s esophagus be monitored?Reduced monitoring for most patients with Barrett’s esophagus appears safeFamily physicians have long been at the mercy ofexpert opinion when considering how to monitorpatients with Barrett’s esophagus. This review ofthe evidence clearly shows that the days of yearlyEGD for all Barrett’s esophagus patients are over. Unlike other conditions—such as cervical dysplasia, where monitoring and therapies toremove dysplasia are proven to save lives—Barrett’s esophagus progresses slowly and unpredictably. Thus, until technological advancesallow identification of higher risk Barrett’s esophagus patients, an EGD every 3 years forthose without dysplasia seems to be a reasonablemonitoring interval. Perhaps most importantly,family physicians can reassure Barrett’s esophagus patients in the community that they are likely to live a normal lifespan and die of something other than esophageal cancer.Paul Crawford, MDUSAF–Eglin Family Practice Residency, Eglin Air Force Base, FlaSome patients who have been diagnosed withBarrett’s esophagus will develop dysplasia and, in some cases, esophageal carcinoma (strength of recommendation [SOR]: A, based on consistentcohort studies). Endoscopic surveillance is recommended for all patients with Barrett’s esophagus as it is superior to other methods fordetecting esophageal cancer (SOR: B, based onsystematic review). The degree of dysplasia notedon biopsy specimens correlates with the risk ofesophageal carcinoma development and shouldguide the frequency of subsequent evaluations(SOR: B, based on consistent cohort studies). The optimal frequency of endoscopy has yet to bedetermined in any randomized trial. Recommendations from the 2002 AmericanCollege of Gastroenterology (ACG) PracticeGuideline provide guidance as to the frequency of endoscopy surveillance but were not based on an explicit systematic review of the literature(SOR: C, based on expert opinion; see TABLE 1).Michael Grover, DO, Carmen Strickland, MDDepartment of Family Medicine, Mayo Clinic, Scottsdale, ArizEllen Kesler, MLSNorthwest AHEC, Rowan Regional Medical Center, Salisbury, NC■ Evidence summaryBarrett’s esophagus has been defined as “achange in the esophageal epithelium of anylength that can be recognized at endoscopyand is confirmed to have intestinal metaplasia by biopsy of the tubular esoph-agus.”1 Intestinal metaplasia is a pre-malignant lesion for adenocarcinoma ofthe esophagus. Surveillance by serialendoscopy with biopsy has been recom-mended in an effort to find high-grade dysplasia or carcinoma in an early, asymp-tomatic, and potentially curable stage.1–4Approximately 75% of patients involvedin a Barrett’s esophagus surveillance pro-gram will present with resectable tumors,compared with only 25% of those notreceiving surveillance.4A recent systematic review assessingscreening tools for esophageal carcinomafound standard endoscopy to be superior(90%–100% sensitivity) to other less Endoscopic surveillance for esophageal cancer is recommended for all patientswith Barrett’sesophagus246 VOL 55, NO 3 / MARCH 2006  THE JOURNAL OF FAMILY PRACTICECLINICAL INQUIRIESFAST TRACKinvasive methods such as questionnaire(60%–70%), and fecal occult blood testing(20%).4 Additional endoscopy tools suchas brush and balloon cytology increasedthe cost of surveillance without anyimprovement in diagnostic yield.The degree of dysplasia on esophagealbiopsy in Barrett’s esophagus patients iscurrently the best indicator of risk of pro-gression to esophageal carcinoma. Thedata reviewed by the ACG for the practiceguideline was drawn from several prospec-tive studies and one available registry. In sum, a total of 783 Barrett’s esophaguspatients were followed for a mean of 2.9 to7.3 years. Esophageal carcinoma developedin 2% of patients with no dysplasia, 7% ofpatients with low-grade dysplasia (LGD)and 22% of patients with high-grade dys-plasia (HGD).1 The ACG recommenda-tions regarding frequency of esophagogas-troduodenoscopy (EGD) were not basedon an explicit critical appraisal of the liter-ature. Recent cohort studies are consistentwith recommendations for graded surveil-lance frequency. A randomized clinical trialto determine optimal endoscopic frequencyand benefit has not been reported.Several concerns have been raisedregarding the utility of degree of dysplasiain determining optimal frequency of endo-scopic surveillance. First, the progression ofesophageal lesions over time is unpre-dictable. Skacel et al5 reported a series of 34patients with LGD at initial pathologicexamination. On subsequent surveillanceendoscopy with repeat biopsy, 73% nolonger demonstrated dysplasia. Suchpatients can be allowed to return to havingsurveillance every 3 years. In addition to the non-linear progres-sion of dysplasia, inter-rater reliability of theinterpretation of pathology specimens variessubstantially. Adequate reliability has beendemonstrated among pathologists assigningresults to 2 categories (either no dysplasiaand LGD or HGD and carcinoma) (κ=0.7).Assignment to four distinct pathologicgrades, however, was not reliable (κ=0.46,where 1.0 is complete agreement).1 In orderto make a diagnosis of HGD or carcinoma,interpretation must be independently con-firmed by 2 expert pathologists.1–3Recommendations for frequent endo-scopic surveillance are also weakened by theoverall low rate of mortality fromesophageal carcinoma noted in Barrett’sesophagus patients. A recent populationbased study demonstrated that there was nodifference in overall mortality in those witha Barrett’s esophagus diagnosis comparedwith the general population.6 An increasedrisk of death from esophageal carcinomawas seen in patients with Barrett’s esopha-gus (4.7% seen in Barrett’s esophaguspatients compared with 0.8% predicted inthe general population; P<.05). The overallincreased effect on mortality, however, wasT A B L EDYSPLASIA DOCUMENTATION FOLLOW-UP ENDOSCOPYNone Two EGDs with biopsy 3 yearsLow-grade Highest grade on repeat 1 year until no dysplasiaHigh-grade Repeat EGD with biopsy to Focal: every 3 monthsrule out cancer/document Multifocal: interventionhigh-grade dysplasia; expert Mucosal irregularity: EMRpathologist confirmationACG, American College of Gastroenterology; EGD, esophagogastroduodenoscopy; EMR, endoscopic mucosal resection. Intervention: ie, esophagectomy. Ablative therapies only in the setting of a clinical trial or for those unable to tolerate surgery. Grade of dysplasia and recommendations for Barrett’s esophagus surveillance as proposed by the ACGHow should patients with Barrett’s esophagus be monitored? ▲VOL 55, NO 3 / MARCH 2006 247w w w. j f p o n l i n e . c o mThe degree of dysplasia onesophageal biopsyis the best indicator of risk of progression to esophageal carcinomaFAST TRACKrelatively small. Esophageal carcinomaaccounted for less then 5% of deaths inBarrett’s esophagus patients reported dur-ing the study’s 6-year follow-up period. Data from prospective studies pub-lished after 2002 may better predict prognosis for Barrett’s esophaguspatients.6–9 Even lower rates of progressionto esophageal carcinoma (<0.5% a year or<1/220 patient-years) have been reportedin these studies drawing from the generalpopulation rather than referred patients,likely stemming from differences in gendermix, patient age, and risk factors.In addition to grade of dysplasia, thelength of the dysplastic Barrett’s esopha-gus segment is emerging as a potentiallypredictive risk factor. While the ACG cau-tions that esophageal cancer has beenreported in patients with so-called “shortsegment” Barrett’s esophagus (SSBE) (≤3 cm),1 recent prospective studies haveshown an increased risk of carcinomadevelopment with long segment Barrett’sesophagus (LSBE).7–9 Weston et al7 report-ed a 2.4% progression rate to HGD oresophageal carcinoma with SSBE and nodysplasia compared with 6.8% with LSBE(P=.002). If patients had LGD, the rate ofprogression to esophageal carcinoma withSSBE was 5.3% and jumped to 35% inpatients with LSBE (P<.001). Conio et al8reported that 4 of 5 cases of esophagealcarcinoma noted through surveillance hadLSBE. Hage et al9 reported a significantlyincreased risk of progression to HGD oresophageal carcinoma with long segmentdisease (P<.02).While currently still considered investi-gational, DNA content flow cytometrymay be a future tool used in risk stratifica-tion. Reid et al10 report a 5-year cumulativerisk of esophageal carcinoma of 1.7% inBarrett’s esophagus patients with negative,low-grade or indefinite grades of dysplasia.Subsequent application of flow cytometryallowed for further stratification of theselow-risk patients. Those with neither aneu-ploidy nor an increased 4N had a 5-yearcumulative risk of cancer of 0% while therisk for those with abnormalities oncytometry increased to 28% (relativerisk=19; P<.001).Recommendations from OthersThe French Society of Digestive Endoscopyhas published guidelines on monitoringBarrett’s esophagus.3 Their recommenda-tions differ only slightly from the ACG inadvocating a slightly increased frequency of EGD surveillance based on degree of dysplasia, and utilizing the length of the dys-plastic segment in decision-making. Neitherthe American Academy of FamilyPhysicians nor the US Preventive ServicesTask Force make any specific recommenda-tions about Barrett’s esophagus surveillance. R E F E R E N C E S1. Sampliner RE. Updated guidelines for the diagnosis,surveillance, and therapy of Barrett’s esophagus. Am JGastroenterol 2002; 97:1888–1895.2. Management of Barrett’s esophagus. The Society forSurgery of the Alimentary Tract (SSAT), AmericanGastroenterological Association (AGA), AmericanSociety for Gastrointestinal Endoscopy (ASGE)Consensus Panel. J Gastrointest Surg 2000; 4:115–116. 3. Boyer J, Robaszkiewicz M. Guidelines of the FrenchSociety of Digestive Endoscopy: Monitoring ofBarrett’s esophagus. The Council of the French Societyof Digestive Endoscopy. Endoscopy 2000; 32:498–499. 4. Gerson LB, Triadafilopoulos G. Screening foresophageal adenocarcinoma: an evidence-basedapproach. Am J Med 2002; 113:499–505.5. Skacel M, Petras RE, Gramlich TL, et al. The diagnosisof low grade dysplasia in Barrett’s esophagus and itsimplications for disease progression. Am JGastroenterol 2000; 95:3383–3387.6. Anderson LA, Murray LJ, Murphy SJ, et al. Mortality inBarrett’s oesophagus: results from a population basedstudy. Gut 2003; 52:1081–1084. 7. Weston, AP, Sharma P, Mathur S, et al. Risk stratifica-tion of barrett’s esophagus: updated prospective mul-tivariate analysis. Am J Gastroenterol 2004;99:1657–1666. 8. Conio M, Blanchi S, Laertosa G, et al. Long-term endo-scopic surveillance of patients with Barrett’s esopha-gus. Incidence of dysplasia and adenocarcinoma: aprospective study. Am J Gastroenterol 2003;98:1931–1939. 9. Hage M, Siersema PD, van Dekken H, Steyerber EW,Dees J, Kuipers EJ. Oesophageal cancer incidence andmortality in patients with long-segment Barrett’soesophagus after a mean follow-up of 12.7 years.Scand J Gastroenterol 2004; 39:1175–1179. 10. Reid, BJ, Levine, DS, Longton, G, Blount P, RabinovitchPS. Predictors of progression to cancer in Barrett’sesophagus: baseline histology and flow cytometryidentify low- and high-risk patient subsets. Am JGastroenterol 2000; 95:1669–1676.

How should patients with Barrett's esophagus be monitored?

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