Oesophagealhistology in reflux oesophagitis · gastro-oesophageal reflux.9-" Few studies have assessed the practical value of these histological criteria in the routine assessment

J Clin Pathol 1985;38:1265-1272

Oesophageal histology in reflux oesophagitisBJ COLLINS, H ELLIOTT,* JM SLOAN,* RJ McFARLAND,t AHG LOVE

From the Department ofMedicine, The Queen's University ofBelfast, *The Royal Victoria Hospital, Belfast,and tThe Ulster Hospital, Belfast, Northern Ireland

SUMMARY Multiple specimens taken at oesophageal suction biopsy were obtained from 56patients, of whom 44 had symptoms of gastro-oesophageal reflux and 24 had endoscopic evi-dence of erosive oesophagitis. Biopsies were examined independently by two histopathologistsfor the following criteria for reflux: epithelial hyperplasia, vascular dilatation and congestion,neutrophil infiltration, and eosinophil infiltration. The incidence of these criteria in patients withand without endoscopic evidence of oesophagitis or symptoms of reflux was investigated. It wasconcluded that vascular dilatation and epithelial hyperplasia, defined as basal zone thickness> 15% and papillary elongation >66%, can be detected most reliably, but their diagnosticaccuracy is limited unless multiple biopsies are examined.

Accurate assessment of excessive gastro-oesophageal reflux has proved difficult as symptomsof reflux may be absent or atypical and the endo-scopic appearance of the oesophageal mucosa maybe normal.' 3 Recent reports have focused on thediagnostic value of prolonged monitoring ofoesophageal pH, but this technique is technicallydifficult and time consuming.45 An alternativeapproach has been to examine oesophageal mucosalbiopsies for histological markers of abnormal reflux.

Different histological criteria have been proposedas indicators of abnormal reflux, and these includeneutrophil6 and eosinophil infiltration, vasculardilatation,8 and epithelial hyperplasia.9-" Graspbiopsies taken during endoscopy are often crushedand tangential, so that histological assessment isdifficult. The use of a Quinton suction or hydraulictube biopsy instrument, however, has been recom-mended to obtain well orientated tissue,'2 and thistechnique was used to establish the criteria ofepithelial hyperplasia for diagnosing abnormalgastro-oesophageal reflux.9-"Few studies have assessed the practical value of

these histological criteria in the routine assessmentof patients with suspected reflux oesophagitis. Wetherefore documented the incidence of the differentcriteria in oesophageal suction biopsies frompatients with reflux symptoms. Furthermore, toassess the reproducibility of a histological diagnosiswe examined the agreement in diagnosis betweentwo histopathologists when each was asked to assess

Accepted for publication 1 July 1985

the oesophageal biopsies independently and withoutclinical information.

Material and methods

Fifty six patients including 23 men (age range 18-75years) were studied. Forty four presented withheartburn associated with regurgitation or dys-phagia, or both, as their major complaints. Symp-toms were graded according to the criteria ofDemeester et a14 before endoscopic examination orhistological assessment was performed. The highestobtainable score was 9, representing a patient withheartburn that interfered with daily activities,episodes of pulmonary aspiration secondary to re-gurgitation, and dysphagia requiring admission tohospital for relief of meat impaction (Table 1).Patients were included in the study if they had asymptom score of 3 or more and at least two symp-toms of reflux.The remaining 12 patients presented with epigas-

tric or midabdominal pain and denied any symptomsof reflux. None had any endoscopic abnormality ofthe oesophagus or any gastroduodenal abnormalityother than mild gastritis. A record of cigarette andalcohol consumption was obtained from all patients.A routine endoscopy was carried out on all

patients using an Olympus GIF-D3 or GIF-Q endo-scope. The distance between the oesophagogastricjunction and the incisor teeth was carefully noted.When the endoscope was removed a Quinton suc-tion biopsy instrument with a capsule containingfour biopsy ports was inserted into the oesophagus.

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Table 1 Symptoms ofgastro-oesophageal reflux

Severity ofsymptoms Grade Degree of incapacity

Heartburn: flow ofgastric contents into oesophagusNone 0 No heartburnMinimal 1 Occasional episodesModerate 2 Reason for medical visitSevere 3 Interference with daily activitiesRegurgitation: flow ofgastric contents into mouthNone 0 No regurgitationMinimal 1 Occasional episodesModerate 2 Predictable on position or strainingSevere 3 Episodes of pulmonary aspirationDysphagiaNone 0 No dysphagiaMinimal 1 Occasional episodesModerate 2 Requires liquids to clearSevere 3 Episodes of meat impaction requiring medical treatment

Value for heartburn plus regurgitation plus dysphagia = total symptomatic score.

This was positioned to obtain the biopsies about 5cm above the oesophagogastric junction. Suctionwas applied with a 20 ml syringe and the biopsyknife fired manually. If only one or no biopsy wasobtained the instrument was introduced a secondtime. Informed written consent was obtained fromeach patient before endoscopy, and all biopsies weretaken in the routine assessment of oesophageal dis-ease.

Biopsies were orientated carefully on gauze, fixedin 10% buffered formalin solution, sectioned at 5,.m, and stained with haematoxylin and eosin. If sec-tions were poorly orientated additional levels wereexamined. When all sections had been collected theywere submitted in a randomised fashion and withoutendoscopic or clinical information for histologicalassessment, carried out independently by two his-topathologists, to assess interobserver variation indiagnosis. Intraobserver variation was assessed bycoding the biopsies and resubmitting them to theconsultant pathologist.

HISTOLOGICAL ASSESSMENTThe following variables were assessed in each sec-tion:1 Basal zone height, expressed as percentage of

epithelial thickness.2 Papillary length, expressed as percentage of

epithelial thickness.3 Dilatation of intraepithelial blood vessels.4 Congestion of intraepithelial blood vessels.5 The presence of neutrophils.6 The presence of eosinophils.7 The presence of lymphocyte aggregates.The thickness of the basal cell zone was estimated

using an eyepiece graticule in areas of the biopsythat showed perpendicular orientation of at leasttwo consecutive papillae to the mucosal surface. Ifthe basal zone thickness varied in any section the

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Fig. 1 Oesophageal suction biopsy from asymptomaticsubject, showing thin basal zone layer and papillae less than50% ofepithelial thickness. Haematoxylin and eosin. x 100(original magnification).

maximum value was recorded. Papillary length wasalso estimated in areas that showed perpendicularorientation of papiliae to the mucosal surface, andmaximum values were recorded (Figs. 1-3).Ismail-Beigi' s criteria for epithelial hyperplasia weremet if one or more biopsies showed a basal zoneheight , 15% and in the same region of the biopsy apapillary length >66%. Behar and Sheahandescribed epithelial hyperplasia as the occurrence ofbasal zone height >'15% and papillary length >'50%in at least two biopsies. In several patients, however,

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1267Oesophageal histology in reflux oesophagitis

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Fig. 2 Oesophageal suction biopsy from patient witherosive oesophagitis, showing considerable papillaryelongation, mild basal zone hyperplasia, and dilated bloodvessel. Haematoxylin and eosin. x 80 (originalmagnification).

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Fig. 3 Oesophageal suction biopsy from patient witherosive oesophagitis, showing mild papillary elongation andmoderate basal zone hyperplasia. Haematoxylin and eosin.x 200 (original magnification).

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Control 1 2L Groups -'Fig. 4 Basal zone thickness (%o) reported by consultanthistopathologist in control subjects, in patients with refluxsymptoms and normal endoscopic appearance (group 1),and in patients with refilux symptoms and erosiveoesophagitis (group 2).

only one biopsy was adequately orientated forassessment, and we accepted this criterion if it wasfound in one or more biopsies.

Intraepithelial vessels of >50 ,um diameter werearbitrarily classified as dilated (Fig. 2). The diameterof the largest vessel was recorded for each section.Measurements were made only on vessels seen inthe well orientated sections of the biopsy and whenthey appeared to be in transverse section. Conges-tion of the vessels was diagnosed if large numbers ofred cells were seen in the vessel lumen. This was asubjective assessment by each histopathologist. Acareful search for intraepithelial and subepithelialneutrophils, eosinophils, and aggregates of lympho-cytes was made on each section.

STATISTICAL ANALYSISA comparison of maximum basal zone height andpapillary length between patients with and withoutreflux symptoms was made using the Mann-WhitneyU test from data provided by the consultant his-topathologist. The incidence of the different his-tological criteria for diagnosing reflux oesophagitiswas compared between groups by using the x2 test.

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ResultU

Patients were divided into three groups on the basisof their symptoms and endoscopic examination, andthe histological findings in each group were com-

pared. The 12 patients with no symptoms of refluxand a normal endoscopic appearance were assignedto the control group. Of the 44 patients with symp-

toms of reflux, 20 had no endoscopic abnormality ofthe oesophageal mucosa. These were designatedgroup 1. The remaining 24 patients with symptomsof reflux had erosions and friability of theoesophageal mucosa and were considered to havedefinite reflux oesophagitis. They were designatedgroup 2.One specimen only was obtained from eight of the

56 patients biopsied. Although two or more biopsieswere obtained from the remaining 48 patients, onlyone biopsy was adequately orientated for fullassessment in 14 patients (five from group 1, sixfrom group 2, and three from the control group). Allthe biopsies were poorly orientated in four patients,so that full histological assessment was impossible,and these were excluded from further analysis. Thusone or more biopsies were assessed from 52patients, of whom 12 were control patients, 19 fromgroup 1, and 21 from group 2. Two or more biopsieswere assessed from 30 patients, of whom seven werecontrol patients, 12 from group 1, and 11 fromgroup 2.A wide range of basal zone heights and papillary

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Fig. 5 Papillary length (%lo) reported by consultanthistopathologist in control subjects, in patients with refluxsymptoms and normal endoscopic appearance (group 1),and in patients with refilix symptoms and erosiveoesophagitis (group 2).

Table 2 Histological findings in patients for whom one or more biopsies was examined

Diagnostic criteria No. (%o) ofpatients

Controls (n - 12) Group I (n - 19) Group 2 (n = 21)

Basal zone height > 15% 4 (33) 8 (42) 14 (67)Papillary length 2 50% 7 (58) 16 84) 20 95)Papillary length > 66% 3 (25) 8 42) 14 67)Behar and Sheahan criteria 3 (25) 7 37) 14 67)Ismail-Beigi criteria 2 1) 6 32) 11 52)Eosinophils 3 25) 5 29 11 52Neutrophils 1 (8) 4 21 8 38Lymphocyte aggregates 11 (92) 14 74) 16 76)Dilated vascular channels 4 (33) 9 47) 15 (71)Congested vascular channels 5 (42) 11 58) 16 (76)

Table 3 Histological findings in patents for whom two or more biopsies were examined

Diagnostic criteria No (%) ofpatentsControls (n = 7) Group I (n = 12) Group 2 (n = 11)

Behar and Sheahan criteria 1 (14) 3 (25) 9 (82)Ismail Beigi criteria 0 2 (17) 7 (64)Eosinophils 2 (29) 2 (17) 7 (64Neutrophils 0 3 (25) 5 (45)Lymphocyte aggregates 6 (86) 10 (83 9 82)Dilated vascular channels 2 (29) 9 (75) 9 (82)

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1269Oesophageal histology in reflux oesophagitis

Table 4 Influence ofcigarettes and alcohol on incidence ofhyperplastic epithelial changes in oesophageal biopsies (figuresare numbers (%o) ofpatients)

Reflix criteria Cigarette conswnption Alcohol consumption

Smokers (n = 9) Non-smokers (n = 31) Drinkers (n = 16) Non-drinkers (n = 24)

Ismail-Beigi 4 (44) 13 (42) 9 (56) 8 (33)Behar and Sheahan 5 (56) 16 (52) 11 (69) 10 (42)

Table 5 Percentage agreement in diagnosis between pathologists for each histological criterion

Diagnositc criteria Controls Group 1 Group 2 Total

Ismail-Beigi criteria 75 71 84 77Behar and Sheahan criteria 58 53 84 67Dilated vessels 83 71 90 81Neutrophils 92 85 67 79Eosinophils 83 75 57 70

Table 6 Mean percentage values for basal zone height and papillary length recorded by each pathologist

Basal zone height Papillary length

Pathologist 1 Pathologist 2 Pathologist 1 Pathologist 2

Controls 12-3 22-5 50-8 62-4Group 1 14-7 26-3 59-1 64-5Group 2 17-3 29-4 66-8 72-5

lengths were recorded for each group (Figs. 4 and5). No significant difference was detected for basalzone height between patients in the control group

and those in groups 1 or 2. Patients in group 2,however, had longer papillae than either those ingroup 1 (p < 0.05) or those in the control group (p< 0.01).

Table 2 details the incidence of the criteria ofepithelial hyperplasia described by Ismail-Beigi andby Behar and Sheahan and the other criteria ofexcessive reflux detected by the consultant his-topathologist. A higher diagnostic sensitivity was

noted for most of the criteria when only data frompatients who had multiple biopsies suitable forassessment were analysed (Table 3).Of the patients with two or more biopsies avail-

able for histological assessment (Table 3), thosewith erosive oesophagitis had a higher incidence ofthe criteria of epithelial hyperplasia described byBehar and Sheahan (p < 0-05) and by Ismail-Beigi(p < 0.05) than the control group (X2 test). Dilatedintraepithelial blood vessels were found more com-

monly in the patients with erosive oesophagitis thanin the control group, but this difference did notreach significance (0.05 < p < 0.10); x2 test. Nosignificant differences were detected for the othercriteria. When patients in whom only one biopsy wasavailable for histological assessment were includedin the analysis differences between patients witherosive oesophagitis and control patients were less

pronounced (Table 2). Only the criteria of Beharand Sheahan showed a significantly higher incidencein the group with erosive oesophagitis than in thecontrol group (p < 0 05; X2 test).

Patients in groups 1 and 2 were combined to per-mit an assessment of the influence of smoking andalcohol on hyperplastic epithelial changes in sus-pected or definite reflux oesophagitis. No significantdifference in the detection of these changes betweensmokers and non-smokers, or between drinkers andnon-drinkers, was observed (X2 test). Epithelialhyperplasia was more common in patients whodrank alcohol, but this did not reach significance (X2test) (Table 4).

Table 5 details the agreement between the twohistopathologists on the detection of histologicalcriteria. The main area of disagreement was in thereporting of basal zone height: higher values wereconsistently recorded by one observer (Table 6).

Reassessment of coded biopsies from 43 patientsaccording to the criteria of Ismail-Beigi by one ofthe pathologists, who did not know the results of hisprevious diagnosis, showed that the same diagnosiswas made in 39 cases, representing an agreement of91%.DiscussionThis study examined the value of the Quinton suc-tion biopsy instrument in obtaining adequateoesophageal mucosal biopsies. At least one biopsy

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was well orientated in 52 out of 56 patients, so thatthe criteria for epithelial hyperplasia could be evalu-ated. Difficulty was experienced in obtaining biop-sies from some patients with erosive oesophagitis,and reinsertion of the instrument was required.Mucus and blood, or air rising from the stomach,were probably factors that interfered with the biopsytechnique. Histological assessment is not, however,essential to establish a diagnosis in such patients,and grasp biopsies under direct vision may be moreappropriate to assess complicating lesions such asdysplasia and Barretfts metaplasia.

Routine processing of suction biopsies resulted inmore inadequately orientated specimens than wehad expected. We recommend, therefore, that pref-erably four or five suction biopsies should be takenfrom each patient to ensure that two or more speci-mens will be adequately orientated for histologicalassessment. We would probably have shown a grea-ter sensitivity of criteria of histological reflux if wehad obtained more samples from each patient. Ourresults, however, serve to illustrate the likely diag-nostic yield that would result if the current recom-mendation of at least two biopsies from each patientwas followed in routine clinical practice.New criteria for the diagnosis of reflux

oesophagitis cannot be derived from the data in thisinvestigation as the presence or absence of abnormalgastro-oesophageal reflux was not formally tested.Possibly, a few of our control patients were" refluxers," presenting with atypical abdominalsymptoms. The definition of a perfect control sub-ject remains difficult, however, even when pro-longed monitoring of oesophageal pH is used, asmost asymptomatic volunteers show occasionalepisodes of gastro-oesophageal reflux.'3 None theless, further assessment of the specificity ofhistological criteria for reflux will require studies ofasymptomatic subjects who have been shown tohave normal reflux patterns during pH monitoring.

Demeester et al carried out prolonged pHmonitoring in over 100 patients with symptoms ofreflux and erosive oesophagitis and found abnormalgastro-oesophageal reflux in 90%.14 Thus it is worthassessing the sensitivity of different histologicalcriteria in the diagnosis of reflux oesophagitis frombiopsy findings in patients of group 2. Patients withsymptoms of reflux but a normal endoscopicappearance are more difficult to categorise, asDemeester et al found abnormal reflux in only 55%of similar patients.'4

Before 1970 the histological diagnosis ofoesophagitis rested on the presence of lymphocytesand neutrophils.6 In this study subepithelial accumu-lation of lymphocytes was observed in most biopsyspecimens, including those from all but one of the


control patients. This finding supports the view ofother investigators that these cells do not signaloesophageal inflammation.9 Subepithelial neu-trophils were detected in one control patient and ineight patients with erosive oesophagitis (38%). Thisobservation is in keeping with the consensus thatneutrophil infiltration in blind oesophageal biopsiesis a specific but relatively insensitive marker foroesophagitis.'5 A much higher yield would probablybe obtained in endoscopic biopsies taken underdirect vision from the margin of oesophageal ero-sions.Winter et al recently recommended that

intraepithelial eosinophils should be a specific diag-nostic criterion for reflux oesophagitis.7 Most oftheir patients were aged under 5 years, and onlythree asymptomatic control subjects were biopsied.Eosinophils were detected in only 52% of ourpatients with erosive oesophagitis, and this low sen-sitivity limits the diagnostic value. As these cellswere also found in three of 12 control biopsiesfurther evaluation of the specificity of this criterionis required.

Hyperplastic epithelial changes have been mostwidely accepted as histological criteria for the diag-nosis of excessive reflux. Formal evaluation of thesecriteria, however, has been undertaken in only a fewcentres, and one major report failed to confirm theirdiagnostic value.'5 Different methods of assessingbasal zone height and papillary length were used indifferent studies, and some investigators applieddetailed but time consuming morphometric meas-urements.'5 In our study considerable variation inbasal zone height and papillary length was fre-quently observed in the same biopsy specimen. Asmacroscopic oesophageal mucosal damage is oftenfocal in its distribution we considered it appropriateto report basal zone and papillary dimensions in themost abnormal region of each biopsy. Thisapproach, which was also used by Ismail-Beigi andcolleagues,9 permitted a rapid assessment of eachspecimen.Our finding of increased papillary length in

patients with erosive oesophagitis agrees with otherreports. Considerable overlap with normal values,however, was observed, and the diagnostic value ofthis feature alone was limited. Only 52% of patientswith erosive oesophagitis satisfied the criteria ofIsmail-Beigi, 67% fulfilling the less rigorous fea-tures described by Behar and Sheahan. The rela-tively low sensitivity of these criteria in this study isdisappointing, especially considering that only themost abnormal appearances were reported for eachbiopsy. Some improvement in the sensitivity of thesecriteria of reflux was noted when we examined onlydata from patients in whom at least two well orien-

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Oesophageal histology in refiux oesophagitistated biopsies were obtained. This observation againhighlights the importance of taking sufficient biop-sies so that multiple specimens are available for his-tological assessment.As Ismail-Beigi and Behar and Sheahan derived

their criteria from studies of predominantly malepatients in Veterans Administration hospitals9"excessive cigarette or alcohol consumption mightpossibly have influenced the histological appear-ances. Our finding of more abnormal biopsies inpatients who drank alcohol is interesting, especiallyas no patient was a heavy drinker (>60 g alcohol/day), and further assessment of this relation isrequired.The site of biopsy may also be important. Our

biopsies were taken 5 cm proximal to theoesophagogastric junction, and although Ismail-Beigi and Pope reported random distribution of"reflux" lesions over the distal 8 cm of theoesophagus,'0 possibly biopsies taken closer to thisjunction would show more histological abnormalityin patients with reflux. Weinstein reported epithelialhyperplasia in biopsies from asymptomatic subjectstaken within 2 cm of the oesophagogastric junc-tion.'6 Thus the specificity of these criteria may beimpaired if more distal biopsies are taken.

Dilated and congested vessels have beendescribed in oesophageal biopsies from patients withreflux oesophagitis and those with oesophageal var-ices.8 '" A trend towards vessel dilatation being morecommon in patients with erosive oesophagitis wasobserved in this study, but four of 12 controlpatients had similar abnormalities. Possibly, slightdilatation of intraepithelial vessels occurs whenblood is squeezed into the oesophageal epitheliumduring the biopsy procedure, or as a reaction to thepreceding endoscopic examination. It would beinteresting to evaluate further this criterion in biop-sies from control subjects.

If any histological criterion is to find wide accep-tance for routinely diagnosing excessive reflux it isimportant for it to be recognised accurately by thehistopathologist. Our observations of the indepen-dent reporting of the same biopsies by two pathol-ogists showed fairly good agreement in the interpre-tation of biopsies. Vascular dilatation was an easilyrecognised phenomenon, and over 80% of biopsieswere classified in the same way by the two pathol-ogists.The principal area of disagreement was the meas-

urement of basal zone height, and, as a result, Beharand Sheahan's criteria of epithelial hyperplasia pro-vided the most difficulty, with only 67% of patientsbeing classified in the same way. As papillary length>50% was observed in most patients, irrespective ofsymptoms, measurements of basal zone height were

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the deciding factor for this histological marker.Periodic acid Schiff staining has been used to aiddefinition of the basal zone layer in oesophagealbiopsies,'8 but in some preliminary studies we foundno advantage with this stain, and other investigatorshave been similarly disappointed.'9Agreement between the pathologists using the

criteria of Ismail-Beigi was better: 77% of patientswere classified in the same way. Here, the moreobjectively defined measurements of papillarylength were the major determinant of the presenceor absence of this histological marker. Furthermore,when one pathologist re-examined biopsies from 43of these patients he made the same diagnosis, usingIsmail-Beigi's criteria, in 90% of them.We conclude that the suction biopsy instrument

provides satisfactory well orientated tissue samplesfor histological assessment, although in somepatients it is difficult to obtain multiple biopsies. Theaccuracy of histological diagnosis of refluxoesophagitis seems to be limited unless multiplebiopsies are examined. No totally reliable diagnosticcriteria have emerged, and the established criteriaare not detected in all patients with oesophagitis,even when multiple biopsies are examined. Vasculardilatation and the criteria of Ismail-Beigi can berecognised fairly easily in biopsy specimens, butfurther assessment of the relevance of vascular dila-tation is required. As Ismail-Beigi's criteria aremore easily detected by different pathologists thanthose of Behar and Sheahan we suggest that they aremost suitable for the routine diagnostic assessmentof oesophageal biopsies by a general histopathol-ogist.

BJ Collins was in receipt of a Royal Victoria Hospi-tal research fellowship throughout this study.

References

'Wranne B, Areskog M, Tibbling L. The acid perfusion test as adifferential diagnostic aid in patients with chest pain. Acta MedScand 1981;644 (suppl):59-61.

2 Johnson LF, Demeester TR, Hagitt RC. Endoscopic signs forgastroesophageal reflux objectively evaluated. GastrointestEndosc 1976;22: 151-5.

3Breen KJ, Whelan G. The diagnosis of reflux oesophagitis: anevaluation of five investigative procedures. Aust NZ J Surg1978;48: 156-61.

4Demeester TR, Johnson LF. The evaluation of objective meas-urements of gastroesophageal reflux and their contribution topatient management. Surg Clin North Am 1976;56:39-53.

5 Branicki FJ, Evans DF, Ogilvie AL, Atkinson M, Hardcastle JD.Ambulatory monitoring of oesophageal pH in refluxoesophagitis using a portable radiotelemetry system. Gut1982;23:992-8.

6Ballem CM, Fletcher HW, McKenna RD. The diagnosis ofoesophagitis. Am J Dig Dis 1960; 5:88-93.

7Winter HS, Madara JL, Stafford RJ, Grand RI, Quinlan J,Goldman H. Intra-epithelial eosinophils: a new diagnostic

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1272criterion for reflux oesophagitis. Gastroenterology 1982;83:818-23.

8 Geboes K, Desmet V, Vantrappen G, Mebis J. Vascular changesin the esophageal mucosa. An early histological sign ofesophagitis. Gastrointest Endosc 1980; 26:29-32.

Ismail-Beigi F, Horton PF, Pope II CE. Histological conse-quences of gastroesophageal reflux in man. Gastroenterology1970;S8: 163-74.

'° Ismail-Beigi F, Pope II CE. Distribution of the histologicalchanges of gastroesophageal reflux in the distal esophagus ofman. Gastroenterology 1974;66: 1109-13.

Behar J, Sheahan DC. Histological abnormalities in refluxesophagitis. Archives of Pathology 1975; 99:387-91.

Komorowski RA, Leinicke JA. Comparison of fiberoptic endo-scope and Quinton tube esophageal biopsies in esophagitis.Gastrointest Endosc 1978;24: 154-5.

13 Spence RAJ, Collins BJ, Parks TG, Love AHG. Does ageinfluence normal gastro-oesophageal reflux? Gut (in press).

4 Demeester TR, Wang CI, Wernly JA, et al. Technique, indica-tions and clinical use of 24 hour esophageal pH monitoring. JThorac Cardiovasc Surg 1980;79:656-70.


5Seefield U, Krejs GJ, Siebermann RE, Blum AL. Esophagealhistology in gastroesophageal reflux. Morphometric findings insuction biopsies. Dig Dis 1977; 22:956-64.

16 Weinstein WM, Bogoch ER, Bowes KL. The normal humanesophageal mucosa: a histological reappraisal. Gastroenterol-ogy 1975;68:40-4.

7 Spence RAJ, Sloan JM, Johnston GW, Greenfield A.Oesophageal mucosal changes in patients with varices. Gut1983;24: 1024-9.

18 Sladen GE, Riddell RH, Willoughby JMT. Oesophagoscopy,biopsy and acid perfusion test in diagnosis of 'refluxoesophagitis." Br Med J 1975;i: 71-6.

9 Jarvis LR, Dent J, Whitehead R. Morphometric assessment ofreflux oesophagitis in fibreoptic biopsy specimens. J ClinPathol 1985;38:44-8.

Requests for reprints to: Dr BJ Collins, Department ofMedicine, The Queen's University of Belfast, Institute ofClinical Science, Grosvenor Road, Belfast BT12 6BJ,Northern Ireland.

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Oesophagealhistology in reflux oesophagitis · gastro-oesophageal reflux.9-" Few studies have assessed the practical value of these histological criteria in the routine assessment