classical barrett esophagus contrasted with barrett-type epithelium at normal-appearing...

Classical Barrett Esophagus Contrasted with Barrett-Type Epithelium atNormal-Appearing Esophagogastric Junction

Comparison of Demographic, Endoscopic, and Histologic Features

M. Voutilainen, M. Fa rkkila , J.-P. Mecklin, M. Juhola, P. Sipponen & The Central FinlandEndoscopy Study Group*Depts. of Medicine, Surgery, and Pathology, Jyva¨skyla Central Hospital, Jyva¨skyla; Dept. ofGastroenterology, Helsinki University Hospital, Helsinki; and Dept. of Pathology, Jorvi Hospital,Espoo; Finland

Voutilainen M, Farkkila M, Mecklin J-P, Juhola M, Sipponen P, The Central Finland Endoscopy StudyGroup. Classical Barrett esophagus contrasted with Barrett-type epithelium at normal-appearingesophagogastric junction. Comparison of demographic, endoscopic, and histologic features. Scand JGastroenterol 2000;35:2–9.

Background: Incomplete intestinal metaplasia or specialized columnar epithelium (SCE) is the histologichallmark of Barrett esophagus (BE), but it may also occur at a normal-appearing gastroesophageal junctionwithout BE. We studied whether differences occur between BE patients and those with SCE at thesquamocolumnar junction but without BE (abbreviated JSCE), in terms of endoscopic and histologic signsof gastroesophageal reflux disease (GERD) andHelicobacter pylorigastritis.Methods: A total of 1059consecutive patients referred for endoscopy in one hospital district in Finland were enrolled in the study.Biopsy specimens (at least two from each site) were obtained from the gastric antrum and the corpus of thestomach and from the esophagogastric junction and distal esophagus.Results:Classical BE was detectedin 25 (2%) and JSCE in 99 (9%) patients. Dysplasia in the metaplastic mucosa was observed in six BEpatients but in none of the JSCE patients (P< 0.001). In multivariate analysis the independent risk factorsfor BE were endoscopic erosive esophagitis (odds ratio (OR), 6.08; 95% confidence interval (CI), 2.50–14.82), male sex (OR, 3.02; 95% CI, 1.20–7.65), and age (OR, 1.02 per year; 95% CI, 1.00–1.06). Theindependent risk factors for JSCE were endoscopic erosive esophagitis (OR, 1.88; 95% CI, 1.08–3.29) andage (OR, 1.03; 95% CI, 1.02–1.05) but notH. pylori infection (OR, 1.57; 95% CI, 0.83–2.97) or chronicgastritis (OR, 0.88; 95% CI, 0.44–1.75). In univariate analysis, however, JSCE was associated with antral-predominant atrophic gastritis (77%H. pylori-positive). Unlike in JSCE patients, male sex stronglypredominated among BE patients (P = 0.01). The mean ages of BE and JSCE patients did not differ.Conclusions:Both BE and JSCE without BE increase in prevalence with age, and both associate withendoscopic erosive esophagitis but not withH. pylori gastritis. However, because of the marked sexdisparity, JSCE cannot be a direct precursor of BE, and some factors other than GERD alone also play arole in the pathogenesis of BE. Compared with BE, dysplasia is a rare finding in JSCE, and endoscopicsurveillance with biopsy specimens from JSCE patients without dysplasia is not recommended.

Key words: Barrett esophagus; gastroesophageal reflux disease;Helicobacter pylori; specializedcolumnar epithelium

Markku Voutilainen, M.D., Jyva¨skylaCentral Hospital, Dept. of Medicine, FIN-40620 Jyva¨skyla, Finland(fax: �358 17-3645062)

The prevalences and incidences of gastroesophagealreflux disease (GERD) and esophageal and cardiaadenocarcinomas are on the increase (1–5). Barrett

esophagus is a consequence of GERD and may progress toadenocarcinoma through progressive worsening of dysplasiain the transformed mucosa (6–8). In addition to a parallelincrease in prevalence, esophageal and cardia adenocarcino-

mas show similar demographic and clinical features: they aremale-predominant diseases (2, 3, 9) that often associate withBarrett-type intestinal metaplasia in the underlying mucosa(10–13). The clinical behavior of esophageal and cardiaadenocarcinomas is also quite similar (9).

Incomplete intestinal metaplasia, or so-called specializedcolumnar epithelium, is the histologic hallmark of Barrettesophagus (8), but metaplasia of this type may also occur atnormal-looking squamocolumnar junction without Barrett*The members of The Study Group are listed in the Appendix.

ORIGINAL ARTICLE

Scandinavian University Press 2000

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esophagus(14–17). The significance of the specializedcolumnarepitheliumat thesquamocolumnarjunctionwithoutBarrettesophagusremainscontroversial:it is consideredto belinked to GERD (18–20) or to be secondaryto multifocalatrophicHelicobacterpylori gastritis(21,22).

The aim of the present study was to compare thedemographic,endoscopic,andhistologicfeaturesof patientswith classicalBarrett esophaguswith thoseof patientswithspecializedcolumnar epithelium at the normal-appearingsquamocolumnarjunction (junctional specializedcolumnarepithelium (JSCE)) but without Barrett esophagus.Ourhypothesiswas that, like classicalBarrett esophagus,JSCEwithout Barrettesophagusalsoassociateswith GERD.

Patients and Methods

PatientsA total of 1562 consecutive patients sent to upper

gastrointestinalendoscopyover a 4-month period wereenrolled in the presentstudy at Jyvaskyla CentralHospitaland its municipal district. The hospitaldistrict is a referralareaof approximately242,000inhabitants.Indicationsfor the

endoscopywere identified by questionnairescompletedforeachpatientby their generalpractitioners.The main indica-tions for uppergastrointestinalendoscopywereclassifiedasfollows: 1) dyspepticsymptom(s),2) ulcer-type epigastricpain, 3) heartburnand/or regurgitation, 4) dysphagia,5)weight loss, 6) vomiting, 7) non-cardiacchest pain, 8)anemia, 9) acute gastrointestinalbleeding, 10) duodenalbiopsyspecimenfor suspectedor known celiacdisease,11)surveillancefor Barrettesophagus,and12) unspecified.

Ulcer-type abdominal pain was defined as burning orgnawing pain located in the epigastrium.Heartburn wasdefinedasthe presenceof substernalburningsensation,and(acid) regurgitationas the upward flow of bitter- or sour-tastingfluid into the throator mouth.Dysphagiawasdefinedas difficulty on swallowing solid and/or liquid foods.Dyspepsiawasdefinedasotherchronic/recurrentsymptomscenteredin theupperabdomen:discomfortor painnot typicalof ulcer-typepain, bloating or distention,belching,or earlysatiety. Non-cardiac chest pain was defined as recurrentretrosternalpainwithoutcardiacabnormalityafterreasonableevaluation (clinical examination, electrocardiogram,andtreadmill exercise).Includedin the ‘unspecified’groupwere

Fig. 1. The gastroesophagealjunction (EGJ)is at the level of the proximal endof the gastricfolds. Thesquamocolumnarjunction(SCJ)is formedby thepalesquamousesophagealepitheliumandredcolumnarmucosa.ThenormalSCJis coincidentwith theEGJ(A, C). Columnar-lined(CLE) esophagusis definedascircumferentialor finger-like extensionof SCJorally from the EGJ(B, D). By definition, incompleteintestinalmetaplasia(specializedcolumnarepithelium)detectedin biopsyspecimensobtainedfrom CLEis thediagnosticcriterion for Barrettesophagus.In this presentation,Barrett-typeepitheliumdetectedinbiopsy specimensfrom acrossor immediately distal to normal-appearingSCJ (A) was classifiedasjunctional specializedcolumnarepithelium.

ScandJ Gastroenterol2000(1)

Barrett EsophagusversusJunctionalEpithelium 3

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patientswho could not be classifiedin any of the abovecategories.The clinical datawerecollectedvia a structurednon-validatedquestionnairecompletedby thegeneralpracti-tionerswho sentthepatientsto endoscopy.

The duration of the main symptom was classified asfollows: 1) lessthan1 week,2) from 1 week to lessthan1month,3) from 1 monthto lessthan6 months,and4) morethan 6 months.Theuse of antacids,histamine-2-receptorblocking agents(H2RAs), proton pump inhibitors (PPIs),misoprostol, and prokinetic agents (cisapride) during themonthprecedingendoscopywasrecorded.To detectthetrueprevalenceof endoscopicerosive esophagitis,the patientsusingmedicationfor uppergastrointestinalsymptomsbeforeendoscopywereexcludedfrom furtheranalysis.PatientswithpreviousH. pylori eradicationor gastric surgerywere alsoeliminated.

EndoscopyIn uppergastrointestinalendoscopy(nopremedicationwas

givenbeforeendoscopy)the junctionbetweentheesophagusand the stomachwas identified at the level of the proximalgastricfolds (23,24). The normalsquamocolumnarmucosaljunction (SCJ),or Z-line, is locatedat essentiallythe samelevel as the esophagogastricjunction (EGJ) (25) and iswithout any irregularity or finger-like upward projections(26). In patientswith hiatalherniaanSCJlocatedup to 2 cmorally from the EGJ was considerednormal (24). With thepatient in the left lateral position, the measurementsweredone with an endoscopeusing the incisor teeth as thereferencepoint. Thebiopsyspecimensobtainedimmediatelydistal to the SCJ were called junctional or cardia biopsyspecimens.If any abnormal lining, one or many mucosaltongues,or an upward shift of the SCJ was observedonendoscopy,biopsy specimenswere obtained from these

lesionsto verify Barrett esophagus(definedas the presenceof esophagealincompleteintestinalmetaplasiaof any length(27)). The appearancesof normal and columnar-linedesophagusarepresentedin Fig. 1.

The presenceof one or more non-confluentor confluenterosionswas classified as endoscopicerosive esophagitis(28). Patientswith erosive esophagitiswere classified ashavingendoscopy-positiveGERD.Gastricor duodenalulcerwas defined as a lesion at least 0.5cm in diameter withunequivocaldepth, locatedin the gastric or duodenalbulbmucosa.

Biopsyspecimenswereobtainedfrom the following sites:gastric antrum 2 cm or more from the pylorus, greatercurvatureof the gastricbody, esophagus2–3cm abovetheZ-line, andimmediatelydistal to normal-appearingSCJ(twospecimensfrom eachsite). If circumferentialor tongue-likeupwardextensionof the SCJfrom the EGJwasdetectedonendoscopy,biopsyspecimenswereobtainedseparatelyfromthis columnar-appearingmucosain thedistalesophagus.Theendoscopicdatawererecordedon a structuredquestionnaireby the physicians(n = 23) performing the procedures.Thestudy protocol (documentationof endoscopicfindings andbiopsysamplingtechnique)wasagreedon beforethestudy.

HistologyThebiopsyspecimenswereexaminedby five pathologists

at the Dept. of Pathologyat Jyvaskyla CentralHospital.Allweretrainedto recognizethegastritis-relatedandesophagitis-related variablesand cardia intestinal metaplasiasubtypesbefore the study. The histologic data were recordedon astructuredquestionnaire.Formalin-fixed biopsy specimenswere embeddedin paraffin and tissuesectionsstainedwithhematoxylinand eosin,alcian blue (pH 2.5)–periodicacid-Schiff, andmodifiedGiemsa.

Table I. The prevalences(numberand percentage)of variousclinical characteristicsand indicationsfor endoscopyin the patientseries(n = 1562).Thefinal studypopulation(n = 1059)wasselectedfrom thegrouppresentedin this tableby excludingthosewith previousgastricsurgery,Helicobacterpylori eradicationtherapy,or useof medicationfor uppergastrointestinalsymptoms

nSymptoms> 6 months Medication* BE JSCE

Dyspepticsymptoms 400 238(60%) 139 3 25Ulcer-typepain 161 63 (39%) 39 1 11Refluxsymptoms 219 139(63%) 65 4 15Dysphagia 38 12 (32%) 6 0 3Weight loss 52 19 (37%) 11 1 2Vomiting 108 39 (36%) 22 0 7Non-cardiacchestpain 72 37 (51%) 12 1 4Anaemia 138 61 (44%) 11 1 8Acute GI bleeding 33 4 0 6Duodenalbiopsy 54 3 0 1Barrettsurveillance† 26 6 14 10Unspecified 261 3 25Total 1562 28 117Includedin presentstudy 1059 25 99

* Histamine-2-receptorblocking agents,protonpumpinhibitors,sucralfate,antacids,prokinetics.† In this studyesophagealspecializedcolumnarepitheliumwasdetectedin only 14 of the26 patientswith previouslydiagnosedBarrett

esophagus.


4 M. Voutilainenet al.

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Gastritis and H. pylori infection were classified aspreviously described (29). The presenceof incompleteintestinalmetaplasia(specializedcolumnarepithelium)wasexamined in the biopsy specimensobtained immediatelydistal to normal-appearingSCJandshowinghistologicsignsof mucosa of the cardia type (30). Complete intestinalmetaplasia(type-I intestinalmetaplasia)is characterizedbythepresenceof gobletcellswith noacidicmucinsin adjacentcolumnar-appearingcells.Incompleteintestinalmetaplasiaorspecializedcolumnarepithelium(types-II and -III intestinalmetaplasia)is characterizedby acidic mucinsin both gobletcells andcolumnar-appearingcells (31,32). The presenceofincomplete intestinal metaplasiawas consideredthe diag-nostic criterion for Barrett-type epithelium. Examples ofnormal gastric cardia mucosa,chronic inflammationat thegastric cardia (‘carditis’), and complete and incompleteintestinalmetaplasiaarepresentedin Fig. 2.

Histologic esophagitiswas diagnosedon the basisof themodifiedcriteriaof Ismail-Beigiet al. (33,34): elongationof

papillaeinto theupperone-thirdof thesquamousepitheliumwith or without the infiltration of inflammatorycells. Thedetectionof incompleteintestinalmetaplasiain theesophagusregardlessof the endoscopiclength of the change wasconsidered diagnostic for Barrett esophagus.Dysplasia,when present,was classifiedby two pathologistsindepen-dently. Low- and high-gradedysplasiawere classified inaccordancewith Haggitt (8).

StatisticsThe chi-squareand the Fischerexact testswere usedto

comparenon-continuousvariables,andtheMann–WhitneyUtestthecontinuousvariables.P values<0.05wereconsideredsignificant.Multiple logistic regressionanalysiswasappliedto detectindependentrisk factorsfor Barrettesophagusandspecializedcolumnar epithelium at the normal-appearingSCJ.Oddsratios (OR) with 95% confidenceintervals(95%CI) were calculatedfor the risk factors.Statisticalanalysesweredonewith SPSS8.0 for Windowssoftware.

TableII. Demographic,endoscopic,andhistologicfindingsin patientswith Barrettesophagus(BE) or with incompleteintestinalmetaplasia(specializedcolumnarepithelium(JSCE))at normal-lookinggastroesophagealjunction,or without BE or JSCE.The BE andJSCEgroupswerecomparedwith thenon-BE,non-JSCEgroup

BE,n = 25

JSCE,n = 99

Non-BE,non-JSCE,n = 935

Meanage† 63 (58–69)* 64 (62–67)*** 56 (55–57)Male to femaleratio 2.4 : 1*** 1 : 1.3 1 : 1.6Chronicreflux symptoms 4% 7% 6%Histologic esophagitis 50%** 22% 26%Endoscopicesophagitis 52%*** 22%** 12%Helicobacterpylori-positive 37% 51%‡ 40%Chronicgastritis 55% 65%# 56%Duodenalulcer 4% 1% 3%Gastriculcer 4% 6% 4%

* P< 0.05;** P� 0.01;*** P� 0.001,‡ P = 0.05,# P = 0.10.† Years(95%confidenceinterval).

Table III. Numbersandprevalences(in parentheses)of Barrett esophagus(BE) andjunctionalspecializedcolumnarepithelium(JSCE)indifferent typesof gastritis†.Theseare the prevalencesof patientswith BE, JSCE,or non-BE,non-JSCEamongthosewith the specifichistologictypeandtopographyof gastritis.TheBE andJSCEgroupswerecomparedwith thenon-BEnon-JSCEgroup

Histologic typeandtopographyof gastritis

Non-BE,non-JSCE(referencegroup),

n = 896JSCE,n = 92

BE,n = 16

Normalgastrichistology(n = 446) 407 (45%) 33 (36%)‡ 6 (37%)Antral-predominantnonatrophicgastritis

(n = 390,79%Hp)352 (39%) 30 (33%) 8 (50%)

Antral-predominantatrophicgastritis(n = 91, 77%Hp)

68 (7%) 22 (24%)*** 1 (6%)

Corpus-predominantatrophicgastritis(n = 51, 37%Hp)

46 (5%) 5 (5%) 0

Mutifocal atrophicgastritis(n = 29, 63%Hp)

26 (3%) 2 (2%) 1 (6%)

Chronicgastritis,any type(n = 558,70%Hp)

489 (55%) 59 (64%)‡ 10 (63%)

*** P< 0.001;‡ P = 0.08;Hp = Helicobacterpylori detectedhistologically.† Thedataon thehistologicandtopographictypeof gastritiscouldbereliably determinedin 16 BE, 92 JSCE,and896non-BEnon-JSCE

patients(n = 1004).



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EthicsThis study was approved by the ethics committee of

JyvaskylaCentralHospital.Thepatientsgavetheir informedconsentbeforethestudy.

Results

The original study populationof 1562 patientsincluded28with Barrett esophagus(BE) and 117 with incompleteintestinal metaplasia at normal-looking SCJ (junctionalspecializedcolumnar epithelium (JSCE)). Of the 28 BEpatients 14 (50%) had been referred to endoscopyforsurveillance.The indicationsfor gastroscopyare shown inTableI. Threegastriccancersandoneesophagealadenocar-cinoma(the latter in a patientwith BE) wereobservedin thestudypopulation.Thefinal studypopulationwasdrawnfromthe cohort shown in Table I by excluding patients withpreviousH. pylori eradicationtherapyor gastricsurgeryandthoseusingmedicationfor uppergastrointestinalsymptomsbefore the endoscopy.Thus the final study populationconsistedof 1059patients.

Themeanageof thefinal studypopulation(n = 1059)was57 years(95% CI, 56–58)andconsistedof 429 men (40%)and637women(60%),with a maleto femaleratio of 1:1.5.BE wasdetectedin 25 (2%) andJSCEin 99 (9%) patients.The meanlength of Barrett epitheliumwas 6 cm (95% CI,4–8).Thirteenof the 25 (52%) BE patients were in thesurveillanceprogram.Dysplasiain the metaplasicmucosawas observedin six BE patientsbut in none of the JSCEpatients(P< 0.001).All of thesix BE patientswith dysplasiain the metaplasticmucosawere men (P = 0.08). One BEpatient but none of the JSCE patients had esophagealadenocarcinoma.

Both BE and JSCE were associatedwith endoscopicerosiveesophagitisand increasingage,but only BE was a

male-predominantlesion(TableII). Thesexratiosof theBEand JSCE patients differed significantly (P = 0.01). Thepresenceof chronic heartburnand/or regurgitation(longerthan6 months)andpepticulcer diseaseshowedno associa-tions with either BE or JSCE.The prevalencesof H. pyloriinfectionandchronicgastritiswerehigherin theJSCEgroupthan in the non-BE non-JSCEgroup, but not statisticallysignificantlyso (TableII).

In the non-BE non-JSCEgroup 197 patients(21%) usednon-steroidalanti-inflammatorydrugs(NSAIDs), comparedwith 4 BE patients(16%,P = 0.5)and26JSCEpatients(26%,P = 0.2). In univariate analysisthe presenceof JSCEwasstronglyassociatedwith antral-predominantatrophicgastritis(TableIII). JSCEwasdetectedin 33%of theBE patientsandin 10%of thenon-BEgroup(P = 0.02).

Variables with a P value �0.10 in univariate analysis(Tables II and III) were included in multivariate analysis.Logistic regressionanalysisshowedthat malesex,age,andendoscopicerosiveesophagitiswereindependentrisk factorsfor BE. Endoscopy-positiveGERDandagewererisk factorsfor JSCE(TableIV). AlthoughH. pylori infectionandchronicantral-predominantatrophic gastritis showedsignificant ornear-significantassociationswith JSCEin univariateanalysis,they were not independentrisk factors for JSCE in themultivariateanalysis(TablesII, III, andIV).

Discussion

Thepresentobservationssuggestthat,aswith BE, junctionalspecializedcolumnar epithelium is associatedwith endos-copy-positiveGERDandmaythereforebeconsidereda localmucosal injury resulting from gastroesophagealreflux. H.pylori was not significantly associatedwith JSCE or BE.However, the infection was assayedonly by means ofhistology,which mayhaveunderestimatedits truefrequencyrateamongthe presentpatients(35). On the otherhand,notevenantral-predominantatrophicgastritiswith highH. pyloriprevalenceshoweda significant associationwith JSCE inmultivariateanalysis,suggestingthatJSCEor BE canhardlybe explainedas a direct result of H. pylori gastritis. Thesignificant associationbetweenantral-predominantatrophicgastritisandJSCEin univariateanalysis,however,suggeststhatH. pylori maybeindirectly involved in thepathogenesisof JSCE.The link could be the high acid output that is aspecialfeatureof subjectswith antral-predominantgastritis(36).GERDpatientsreportedlyhavehigherpeakacidoutputthannon-GERDpatients(37).

A strongassociationbetweencardiaintestinalmetaplasiaand H. pylori infection has been reportedpreviously (21,22,38), but thesestudieshave not differentiatedbetweencompleteandincompletetypesof intestinalmetaplasia,whichmay severelybias results.In our earlier investigationsweobservedthat the complete type of intestinal metaplasiaassociateswith H. pylori infection but not with endoscopicerosive esophagitis,as is the case for JSCE (39). Thus,

TableIV. Resultsof multivariateanalysisof potentialpathogeneticandassociatedfactorsfor Barrett esophagusand junctional specia-lized columnarepithelium.Factorsincludedwerefoundto associateat P level 0.10or lessin theunivariateanalyses

OR (95%CI)*

BarrettesophagusAge 1.03(1.00– 1.06)‡Male sex 3.20(1.27– 8.12)Endoscopicesophagitis 6.57(2.69– 16.06)Microscopicesophagitis 1.84(0.75– 4.5)

JunctionalspecializedcolumnarepitheliumEndoscopicesophagitis 1.76(1.01– 3.09)Age 1.03(1.01– 1.05)‡H. pylori 1.02(0.62– 1.70)Antral-predominantatrophicgastritis 1.48(0.40– 5.59)H. pylori andantral-predominantatrophic

gastritis†2.13(0.49– 9.25)

* Oddsratio with 95%confidenceinterval.† = InteractionbetweenHelicobacterpylori and antral-predomi-

nantatrophicgastritis.‡ Peryear.



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completeand incompletetypesof metaplasiaat the gastro-esophagealjunction showsignificantdifferenceswith regardto their associationwith GERDandH. pylori gastritis,anditis thereforeessentialto differentiatebetweenthesemetaplasiasubtypes.

One-third of the JSCE patients showed histologicallynormal stomachs.This further supportsthe hypothesisthatspecialized columnar epithelium at the esophagogastricjunction is not the result of multifocal atrophic gastritisbut a local lesion occurring independentlyof H. pyloriinfection or gastritis. Oberg et al. (19) have reportedthatcardiaSCEassociateswith diminishedpressureof the lower

esophagealsphincter,with increasedacid exposureof theesophagealmucosa,and with esophagitis.The exposureofgastric cardia mucosato bile acids and lysolecithin mayalso play a role in the developmentof intestinalmetaplasia(40,41).

Whether JSCE could progress through dysplasia intoadenocarcinoma,and whether junctional SCE progressesinto BE, remain importantbut unansweredquestions.Longand short segmentsof intestinal metaplasiain the loweroesophagushave been shown to occur in patients withesophagealand cardia adenocarcinomas(11,13). Thesecancersshowsimilar clinical (9) andepidemiologicfeatures

Fig. 2. The normal gastric cardia mucosacontainsloosely packedmucus-secretingcells resemblinggastric antral mucosa(A, hematoxylin and eosin stain). Chronic inflammation at the gastric cardia(‘carditis’) is characterizedby theinfiltration of laminapropriaby lymphocytesandplasmacells(B). Thepresenceof goblet cells is the diagnostic hallmark for intestinal metaplasiaat the gastric cardia.Incomplete intestinal metaplasia(D) is characterizedby acidic mucins in goblet cells and adjacentcolumnar-appearingcellsstainedwith varioustonesof redandblue(alcianblue(pH 2.5)–periodicacid-Schiff stain),whereasthe complete-typeintestinalmetaplasiais devoidof thesemucins(C).



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(2–4). In contrastto the resultsof Morales et al. (42), thepresentstudyshowedthat the prevalenceof junctionalSCEwas higher in BE than in non-BE patients,supportingthehypothesisthat JSCEis relatedto BE.

The male to femaleratio wasmuchhigher in BE than inJSCEpatients,and dysplasticlesionsoccurredonly in themale BE patients.Esophagealand cardia carcinomasarestrongly male-predominantdiseasesin Finland (43). Thismale predominancesupportsthe hypothesisthat junctionalandesophagealadenocarcinomasmay developdirectly fromBarrett epithelium. However, this cannot be the case forJSCE,in which maleandfemalecasesoccurequallyoften.IfJSCE predisposesto cardia carcinomas,some additionalfactorsthat areboundto malesexmustplay a role. Oneofthese factors might be smoking habit, which reportedlyincreasesthe risk of esophagealandcardiaadenocarcinomas(44,45).

ThepresentstudyshowedthatJSCEdid not associatewithreflux symptoms;most casesof JSCE were observedinpatients referred for endoscopyfor indications other thansymptomssuggestiveof GERD. Becausemost GERD anddyspepticpatientsaretreatedby generalpractitionerswithoutendoscopy(46), mostcasesof JSCEremainundiagnosedinroutine clinical practice.A high prevalenceof JSCEin thepresentendoscopyseriesmeansthatJSCEis a very commonlesion.Therefore,screeningprogramsto detectJSCEcasesarehardlyindicatedbecausethecancerrisk obviouslyis onlyslightly increased.Unlike BE, theprevalenceof dysplasiainjunctional SCE seemsto be low, and endoscopicbiopsysurveillanceof patientswith JSCEbut without dysplasiamaynot be cost-effective.The clinical significanceof a JSCEdiagnosismay be that it objectively identifiespatientswhohaveor areat risk of havingGERD.Weonly usedendoscopicerosive esophagitisas the diagnosticcriterion for GERD,however,which underestimatesthe true incidenceof GERD,becauseendoscopicerosive esophagitisreportedly has apositivepredictivevalueof only 75%for GERDdeterminedby 24-hpH monitoring(47).

In conclusion,the presentstudy showedthat, like BE,incompleteintestinal metaplasiaimmediatelydistal to nor-mal-appearingSCJ(JSCE)associateswith endoscopicero-siveesophagitisbutnotwith H. pylori gastritis.Differencesindemographicssuggest,however,thatJSCEandBE arein factseparateclinical entitiesandthatadditionalfactorsplayarolein the possible progressionof JSCE to BE. The risk ofdetectingjunctionalintestinalmetaplasiawith dysplasiais solow in patientswith typical reflux symptomsthat this riskshouldnot be the determinantof whetherpatientis referredfor endoscopy.Further, endoscopicsurveillanceof JSCEpatientswithout dysplasiato preventjunctional adenocarci-nomasis not recommended.

Acknowledgement

Preliminaryresultsof this study were presentedat the 11th

World Congressesof Gastroenterologyin Vienna,Austria,in1998.

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AppendixIn addition to the authors,the following investigatorsaremembersof The Central Finland EndoscopyStudy Group:Liisa Ahlskog-Muraja, Teuvo Antikainen, Sirpa Antila,Jorma Anttinen, Matti Hallikas, Kari-Pekka Hamalainen,Heikki Janhunen,Matti Kairaluoma, Kerkko Karjalainen,PekkaKauranen,Matti Kolu, Heikki Korhonen,Jari Korho-nen, Ritva Koskela, Raimo Krees, Ilkka Kunnamo, VesaKarja, Paivi Laaksonen,Matti Laukkanen,ReinoLiisanantti,Marja Lohman, Kari Mauranen,Timo Mantynen, KyostiNuorva,SeppoNyyssonen,AnteroPalmu,Ulla Palmu,MattiPellinen,PerttiSarkka, Harri Selanne,TuulaTervo,MarianneUdd, andJukkaViinikka.

Received24 June1999Accepted30 August1999



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classical barrett esophagus contrasted with barrett-type epithelium at normal-appearing...

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