J Clin Pathol 1985;38:1119-1126

Defining duodenitis: quantitative histological study ofmucosal responses and their correlationsD JENKINS, A GOODALL, FR GILLET, BB SCOTT

From the Departments ofMedicine and Pathology, Lincoln County Hospital, Lincoln, and the OperationalResearch Unit, Trent Regional Health Authority, Sheffield

SUMMARY Biopsies from 56 patients with endoscopically normal duodenal bulbs, duodenitis, orduodenal ulceration were studied for counts of plasma cells, polymorphs, and eosinophils andextent of gastric metaplasia, villous atrophy, and mucosal oedema. A correlation matrix showedthat the counts of different types of plasma cells were closely correlated with each other and thatthere was also a close correlation between the presence of intraepithelial polymorphs, villousatrophy, and gastric metaplasia.

Cluster and discriminant analysis indicated that the histological changes could be grouped bytheir statistical association into three simple categories: normal, which includes many casesincorrectly labelled in some classification systems as mild or chronic duodenitis; histologicallydefined mild duodenitis, characterisedcby an appreciable plasma cell response and oedema usu-ally with intraepithelial polymorph infiltration and gastric metaplasia; and severe duodenitis, withan appreciable polymorph response and villous atrophy but decreased plasma cells. Decreasedplasma cells may be an important indication of peptic ulceration.

Various attempts have been made to classify andgrade duodenitis either subjectively or by descrip-tive histology.' -4 The subjective classification wassupported by some quantitative data in one study.2Increasing evidence shows that there are- problemswith both the validity and the repeatability of thistype of histological classification.5 Mathematicalmethods of classification based on the statisticalassociations between quantitative and qualitativefeatures do not depend on prior assumptions aboutnormal or abnormal groups and provide a valid wayof classifying histological changes. These methodshave received only limited use in medical sciencebecause of the difficulty of applying them to subjec-tive data and criteria.6 The availability of semi-automatic image analysis facilitates the collection ofnumerical and histological data that are more suitedto statistical study. Cluster analysis permits thegrouping of biopsies on the basis of statistical associ-ations between chosen features such as cell countsand morphometric measurements. It also permitsstatistical definition of the normal range by observa-tion of the clustering of borderline cases withinobviously normal or abnormal groups. Discriminantanalysis allows the investigator to determine which

Accepted for publication 3 June 1985

features are most important in ascribing cases to theselected groups.We have shown previously that IgA plasma cell

counts are significantly increased in duodenitis ofWhitehead grades 1 and 2 but that all plasma cellcounts are decreased in grade 3,7 although it isknown that total cellularity of the lamina propriaincreases with grade.2 We therefore analysed statis-tically the interrelationship between the variouspopulations of inflammatory cells and morphometricmeasurements of mucosal volume, villous atrophy,and gastric metaplasia in a large number ofduodenal bulb biopsies from controls and frompatients with either non-specific duodenitis orduodenitis associated with ulcers by computing acorrelation matrix and performing cluster anddiscriminant analysis. The correlation matrix canthrow light on the integration of pathological pro-cesses in duodenitis, and the cluster and discrimin-ant analyses can provide the basis for a histologicalclassification of duodenitis; these analyses arepotentially suitable for a more widespread applica-tion to biopsy pathology.

Patients and methods

Fifty six patients undergoing routine upper gastroin-1119

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testinal endoscopy, mainly for the investigation ofabdominal pain, were studied. The duodenal bulbappeared to be normal in 25 patients (mean age 46).Fourteen had an ulcer in the bulb (mean age 69).Seventeen were thought to have duodenitis (meanage 62), with erythema alone in eight and erosionsin nine. In six patients more than one biopsy wasused, giving a total of 63 biopsies (26 from normalbulbs, 17 from ulcerated bulbs, and 20 from bulbswith duodenitis).

BIOPSYEndoscopy was performed with an Olympus GIF-Tendoscope in most cases and an Olympus GIF-Qendoscope in the remaining cases. Biopsies weretaken from the duodenal bulb with either FB-13Kor FB-24K forceps. The biopsies, removed from theforeceps by shaking in Ringer's solution, wereoriented on plastic mesh and fixed in formalin aspreviously described.8 Only biopsies that were welloriented and of adequate size were used.

STAINING TECHNIQUEThe fixed specimens were embedded into paraplast.Tissue sections were cut at 2 ,um thickness perpen-dicular to the luminal surface, mounted on glassslides, and dried overnight at 37°C. For most countssections were stained with haematoxylin and eosin.For plasma cell counts sections were stained for IgA,IgM, IgE, and IgG by the peroxidase-antiperoxidaseimmunoperoxidase technique9 after initial trypsin-isation'° and counterstained with Harris's hae-matoxylin. The primary antiserum was titrated foreach case as described previously.7 To measure theextent of gastric metaplasia sections were stained bythe periodic acid Schiff reaction after diastase diges-tion.

MEASUREMENTSMeasurements and cell counts on the stained sec-tions were carried out using a MOPPET image ana-lyser. An image of the stained sections was pro-jected at standard magnification on to the digitisingtablet by a Leitz Neopromar projection microscope.The MOP stylus was fitted with a ballpoint pen toprovide a permanent record of the field examined.Four contiguous non-overlapping fields wereexamined on each section. A field was defined as thearea between the mucosal surface and muscularismucosae bounded by two lines perpendicular to themuscularis mucosae. The following five measure-ments were made on each field: mucosal length, thelength of the muscularis mucosae; area of laminapropria; length of villous epithelium; length of cryptepithelium; and length of epithelium occupied bygastric metaplasia. A micrometer slide was used to

Jenkins, Goodall, Gillet, Scottconvert area and length measurements on the pro-jected image into absolute measurements. The fol-lowing cell counts were made: polymorphs in cryptepithelium, villous epithelium, and lamina propria;eosinophils in the lamina propria; and IgA, IgM,IgE,and IgG plasma cells in the lamina propria. Allmeasurements, counts, and processing were per-formed blind on randomised specimens to minimiseexperimental and observer bias. As an index of vill-ous atrophy the ratio of total length of surfaceepithelium to length of muscularis mucosae was cal-culated. As an index of mucosal oedema the ratio ofarea of the lamina propria to length of muscularismucosae was calculated. With these ratios the indexof villous atrophy was independent of the index ofmucosal oedema. Each biopsy was graded accordingto the Whitehead classification2: grade 0 was nor-mal; grade 1 showed increased lamina propria cellu-larity but normal general morphology of surfaceepithelium; grade 2 showed an abnormality of thesurface epithelium; and grade 3 showed erosions ofthe surface epithelium.

STATISTICAL METHODSAll analyses were performed on an ICL 2960 com-puter. PACKAGEX (Government Statistical Ser-vice Computing Liaison Unit, 1981) was used tocalculate a correlation matrix for the measurements,and cell counts were taken. Significant levels of cor-relations between the variables were identified by atwo tailed t test.

Cluster analysis enabled the biopsies to be dividedinto groups on the basis of recorded similarities inthe measurements and cell counts. The analysis wasperformed by the computer package PMMD (MBYoungman, School of Education, University of Not-tingham, version 5:1976). The package uses therelocation method of clustering, and the error sumof squares was selected as the measure of similarity.A discriminant analysis package provided by

PMMD was used to investigate the differences be-tween the clusters. The method estimates multivari-ate functions that maximise the differences betweengroups. The percentage of correct classifications bythe discriminant functions was evaluated using thedistance formula of relocation analysis, individualsbeing assigned to the cluster for which the distancevalue was the smallest.

Results

Fig. 1 shows the correlation matrix. There werestrong correlations between the counts of all the dif-ferent plasma cell types (p < 0.0005). Mucosaloedema correlated strongly with the counts ofpolymorphs and IgG plasma cells in the lamina

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Defining duodenitis: quantitative histological study of muscosal responses and their correlations

Counts of polymorphs Villous atrophy mGestricin crypt epithelium index metaplasia

Fig. 1 Correlation matrix showing statistical correlationsbetween: counts ofplasma ceUls producing IgA, 1gM, IgG,and IgE; counts ofpolymorphs and eosinophils in thelamina propria per mm ofunderlying muscularis mucosae;counts ofintraepithelial polymorphs in villous and cryptepithelium and extent ofgastric metaplasia per mm ofepithelium, together with indices of villous atrophy andmucosal volume (oedema index). Thick line: p < 0O0005;thin line: p < 0-001; pecked line: p < 0 01.

propria (p < 0.0005), but lapolymorphs were not directly correplasma cell counts. Polymorphs in crepithelium correlated strongly (p <each other and with gastric metaepithelial polymorphs and villouscorrelated with each other atsignificance.There was a highly significant but

correlation (p < 0-001) betweenplasma cells and polymorph colepithelium, but this seemed to be the

14-

12

v 10-

40,V 8 -

06-0Z 4

2-

0

0

0

0

0

.

0

0 5 10 15Coefficient of error

Fig. 2 Graph oferror associated with sucfusions. Greatest increase occurs when numreduced from three to two.

imina propria

10 20 30Coefficient of error

Fig. 3 Dendrogram showing procedure for analysis.Largest errors associated with fusion occur between threeand two cluster level.

lated with any ween the plasma cell response and acute inflammat-typt and villous ory cells in the epithelium and variables of epithelial0.0005) with abnormality, relating what are otherwise two sepa-

plasia. Villous rate patterns of response.atrophy also Using cluster analysis a graph of the error (Fig. 2)

this level of associated with successive cluster fusions showedthat the greatest increase in error occurred when the

lower level of number of clusters was reduced from three to two.aounts of IgG Little extra error was introduced by reducing fromonts in crypt five to three clusters, but some increase was evidentonly link bet- in the transition from six clusters to five. Hence the

three and six cluster solutions seemed to be of inter-est. On examination the six cluster solution con-sisted of two large groups and four very small ones(two of these contained only one case). The threecluster solution comprised two large clusters and asmaller one of five cases and offered a less frag-mented classification. Fig. 3 gives a more detailedpicture of the analysis structure, showing that thelargest errors associated with fusion occurred be-tween the three and two cluster levels. The threecluster solution, therefore, seemed to provide a val-uable division. Fig. 4 shows the profile chart and

2( 25 Table 1 the values of the measurements for the threecluster solution. Table 2 shows the relation between

cessive cluster the clusters and the Whitehead grades.zber ofclusters is Cluster 1 may be taken as showing the normal

range defined statistically by cluster analysis. It

I I I

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Jenkins, Goodall, Gillet, Scott

Fig. 4 Profiles ofthree clusters expressedas standard deviation ofeach measurementfrom mean.

included all but one biopsy defined as normal on theWhitehead scale and some additional cases. IgAplasma cells predominated, but there were alsosome IgM, IgG, and IgE plasma cells. Eosinophilswere sometimes present in the lamina propria, andsome gastric metaplasia, occasionally quite exten-sive, could be seen in the surface epithelium, alongwith occasional polymorphs mostly confined to thevillous compartment of the surface epithelium.

Cluster 2 showed increased plasma cell counts andincreased mucosal volume compared with cluster 1(p < 0.001). Intraepithelial polymorphs were alsoincreased. The increase was most significant in thecrypt epithelium (p < 0.001). Intraepithelialpolymorphs in the villous epithelium, lamina pro-pria, polymorphs and eosinophil counts, and the

Table 2 Numbers ofbiopsies in each category

Cluster Whitehead grade

0 1 2 3

1 22 18 3 02 1 6 8 03 0 1 1 3

extent of gastric metaplasia were all increased, butthere was a wide overlap with cluster 1 and theincreases were significant only at the p < 0 005level. There was no significant villous atrophy asmeasured by our index. Cluster 2 mostly comprisedcases classified as grade 1 or 2 with the Whiteheadclassification.

Table 1 Values ofmeasurements in each cluster

Variable Cluster 1 (n = 43) Cluster 2 (n = 15) Cluster 3 (n = 5)Range Mean (SD) Range Mean (SD) Range Mean (SD)

IgM 32-301 117(62-7) 94-920 281 (201)** 14-64 44-6 (22-1)IgG 11-236 55-8 (45-4) 30-657 178 (165)** 10-84 35-2 (28-7)IgA (cells/mm muscularis

mucosae) 97-557 307 (122) 377-1070 626 (194)** 33-187 120 (62-0)**IgE 24-227 124 (51-7) 127-426 225 (85.4)** 14-61 32-0 (19-3)*Eosinophils 0-70 23-4 (16-6) 5-104 45*5 (30.7)* 23-108 55-2 (32-7)Polymorphs 1-139 14-9 (22.8) 7-271 51.6 (66&5)* 43-1010 286 (408)*VE polymophs/mm VE 0-5 1-29 (1-01) 0-6 2-80 (2-13 * 6-16 9 40 (4.67)**CE polymorphs/mm CE 0-2 0-325 (0-552) 0-5 1-40 (1-452** 0-4 1-80 (1.482**Gastric metaplasia (%) 0-89-5 10-5 (19-8) 0-77 34-4 (28.3) 0-97-7 57-3 (36.3)Oedema index 0-090-0-223 0-164 (0O33)- -- 165-388-- 2701(0.065)** 0-124-0-340 0-209 (0-096)VA index 1-75-6-86 3-50(1-06) 2-63-3-95 3-15(0-545) 1-17-1-94 1-63 (0320)**

**p < 0-001 v cluster 1.p < 0-005 v cluster 1.VE = Villous epithelium. CE = Crypt epithelium. VA = Villous atrophy.

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Defining duodenitis: quantitative histological study ofmuscosal responses and their correlations

Cluster 3 showed appreciable villous atrophycompared with both cluster 1 and cluster 2 (p <0.001), a highly significant (p < 0-001) reduction inIgA and IgE plasma cells, and reduced IgG and IgMplasma cells. There were also very significantincreases in polymorphs in the villous and cryptepithelium, the lamina propria, and the gastricmetaplasia compared with cluster 1 (p < 0-001).The increase in villous epithelial polymorph countswas also highly significant compared with cluster 2(p < 0.001). Cluster 3 included all Whitehead grade3 biopsies but also other cases.Using discriminant analysis, the discrimination

between clusters was highly significant with a valueof Wilk's lambda of 0-03 (p < 0X0001) and two dis-criminant functions, explaining 100% of the overallvariance. Function 1 was chiefly associated withpolymorph counts in the villous epithelium andlamina propria and with the villous atrophy index.This permitted a clear separation of cluster 3 fromclusters 1 and 2. Function 2 was characterised by theplasma cell counts and the oedema index and per-mitted separation of clusters 1 and 2.The discriminant function correctly classified 87%

of the cases studied, although the result was biasedbecause the cases classified were those used in esti-mation of the functions.

Discussion

The finding of inflammatory changes in the mucosaof the duodenal bulb in patients with pepticduodenal ulceration and the presence of similarchanges in both dyspeptic and asymptomaticpatients without evidence of gross peptic ulcerationhas stimulated considerable effort to identify theimportance of these changes in relation to the clini-cal course of peptic ulcer disease.3'4 7 11-13 The aim ofsuch effort is to decide which changes are of value indeveloping a reproducible histological classificationfor use in the diagnosis of dyspeptic symptoms, inthe study of the clinical course of dyspepsia,doudenitis, and peptic ulcer disease, and as a guideto treatment. Definition of duodenitis has, however,proved to be extremely difficult. The underlyingcause remains elusive, although increased secretionof gastric acid may have a role, so a satisfactoryaetiological definition is not possible.

Endoscopic changes have shown only a varyingcorrelation with histological changes,'3 further com-plicating definition of the abnormal state, and his-tological abnormalities have often been reported tooccur in asymptomatic subjects studied as controls.3This has led to a questioning of the importance ofinflammatory changes in the duodenal mucosa, par-ticularly a slight or moderate increase in lympho-

cytes, plasma cells, and other so called chronicinflammatory cells.4

Several quantitative histological studies ofduodenitis have been performed. A decrease in theratio of surface to volume and an increase in totalcell density in the lamina propria have been shown.2Hasan etal, using microdissection, confirmed theoccurrence of villous atrophy and crypt hyperplasiain visually inflamed areas of both ulcerative andsevere non-specific duodenitis.'4 We have shownthat both villous atrophy, as measured by the ratioof mucosal epithelial length to length of muscularismucosae, and increased mucosal volume are fea-tures of duodenitis. Only one previous mor-phometric study examined in detail the counts ofdifferent types of inflammatory cells in the laminapropria and epithelium.'5 This showed that in areasof endoscopic severe duodenitis plasma cells, lym-phocytes, and polymorphs in the lamina propriawere increased and that in the epithelium there werepolymorphs and increased numbers of lymphocytes.Our results agree with these findings. Computationof the correlation matrix showed statistical correla-tions between cell populations and measurements ofvillous atrophy, oedema, and extent of gastric meta-plasia. This "inflammatory matrix" shows the com-plex interrelations of the mucosal response to injuryseen in both ulcerative and non-specific duodenitis.It suggests, overall, a dual pattern of response-thatis, an immune response reflected in changes inplasma cell population and an acute inflammatoryresponse closely related to the indicators of epithel-ial damage, gastric metaplasia and villous atrophy.

In the first arm of response all the various types ofplasma cells are closely correlated with each other.We showed previously7 that IgA plasma cellsincrease significantly with severity of duodenitis,provided the overlying epithelium is not eroded, andthat this may represent an important basicimmunological response to any mucosal injury; butthe present study also shows important correlationsbetween IgG plasma cells, as well as IgA plasmacells, and mucosal oedema and between IgG plasmacells and the presence of crypt intraepithelialpolymorphs. There may be an important role forIgG in mediating the migration of polymorphs andthe development of mucosal oedema, and, interest-ingly, staining of the epithelium for IgG is increasedin duodenitis (unpublished observations).The second arm of response is related to this

immune response through the IgG plasma cellcounts and relates intraepithelial polymorphs toepithelial and villous abnormalities measured byboth the extent of gastric metaplasia and the ratio ofsurface length to mucosal length. This second armdraws attention to the importance of polymorphs in

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duodenitis and their possible role in causing or

responding to epithelial damage. Polymorphs are

normally only a minor constituent of the duodenalbulb lamina propria or epithelium; mucosalpolymorphs have been proposed as a reliablemarker for important duodenitis.'4 12 15 Shoushaetal, in a non-quantitative study, suggested thatthere was a relation between polymorphs and gastricmetaplasia.'6 Other studies reported that gastricmetaplasia may occur during the healing of ulcersproduced experimentally in animals'" and may beassociated with hyperchlorhydria in animals.'8 Inman, however, Patrick et al found that although gas-

tric metaplasia was more common in higher acidstates, it was not more extensive.'9A study of random biopsies showed an association

of villous atrophy with frank duodenal ulcerationand that it was much less conspicuous in non-

ulcerative dyspepsia;20 studies of ulcers induced withcysteamine in animals have shown that the flatteningof villi occurs as an early stage in the development ofduodenal ulceration.2' The association that we

found between villous atrophy and intraepithelialpolymorphs is consistent with progressive loss ofsurface area associated with active inflammationresulting in ulceration. The patterns of response may

reflect the limited repertoire of response of theduodenal mucosa to injury as much as the initiatingpathological cause.

Previous attempts to classify duodenitis and todetermine the normal range have depended on sub-jective examination and arbitrary definition ofcategories. Whitehead recognised three grades ofduodenitis with progressive villous atrophy, increas-ing cell density in the lamina propria, and changes inthe surface epithelium (intraepithelial polymorphsand gastric metaplasia).2 His is a complicatedclassification using major defining criteria and alsominor "related" features. A correlation between theWhitehead grade and the ratio of epithelial length toarea and the lamina propria cell density has beenshown.2 This, in itself, is not sufficient to validate theclassification, and doubt has been cast on the impor-tance of the mild grade of duodenitis characterisedby an increase in "chronic inflammatory cells." Analternative approach has been to classify the changesinto acute and chronic on the basis of the presenceof polymorph infiltration.4 This takes account of theimportance of polymorphs in the inflammatory pro-cess in duodenitis and has been claimed to correlatewith symptoms, but the importance of the "chronic'group who do not show any polymorph componentremains unclear.The application of cluster analysis to quantitative

morphometric data facilitates the statistical deter-mination of groups of similar features. This provides

Jenkins, Goodall, Gillet, Scotta basis for the purely morphological classificationwhich is not dependent on arbitrary subjectivejudgments about the nature or cause of the proces-ses under investigation. Such a classification doesnot entail assumptions about aetiology orpathogenesis; it is not necessarily of biologicalimportance but can be evaluated further to deter-mine its value in diagnosis and treatment. The dis-criminant analysis permits the statistical investiga-tion of the significance of each measurement bydetermining the differences between the clusters.From the study of the available morphometric

data a pattern of three clusters emerged. Cluster 1includes all cases that are classified as normal onsubjective classification and many cases classified asmild duodenitis (Whitehead grade 1). The failure ofquantitative methods to separate this category sug-gests that "mild duodenitis" represents only theextremes of the normal range, at least as far aschanges in mucosal architecture, gastric metaplasia,eosinophils, plasma cells, and polymorphs are con-cerned. This is consistent with previous studies thathave suggested that both mild endoscopic and" chronic" histological doudenitis are of doubtfulclinical importance. Some gastric metaplasia and afew intraepithelial polymorphs, mostly in the villousepithelium, are consistent with the normal state. It isnot surprising that some evidence of inflammationand repair, as well as immunological response, is anormal feature of a mucosa that is constantlyexposed to gastric acid and ingested irritants even inthe normal state.

Cluster 2 is also a large cluster and includes mostcases of histological duodenitis of moderate degree(Whitehead grade 2) and some classified as mild(Whitehead grade 1). The most prominent featuresof this group are increased numbers of plasma cellsand the presence of oedema, but the profile showsthat as well as these there is usually, but not always,some polymorph response and increased gastricmetaplasia, although a decrease in epithelial surfaceis not a feature. Generally, these features and bothimmune and acute inflammatory arms of responseare present. There would appear to be nojustification for a further separation of acute andchronic types as distinct diagnostic entities withinthis category. There is, however, a third, small butdistinctive cluster of cases with a large number ofboth intraepithelial and lamina propria polymorphsbut decreased plasma cells. These changes areaccompanied by severe villous atrophy. This clusterincludes not only all cases of microscopic ulceration(erosions) and. therefore of grade 3 in the White-head classification but also some cases without frankmicroscopic ulceration. All except one patient hadeither an ulcer or severe erosions at endoscopy, sug-

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Defining duodenitis: quantitative histological study of muscosal responses and their correlations

Fig. 5 Photomicrograph ofrepresentative example of Fig. 6 Photomicrograph ofbiopsy of Cluster 2.Cluster 1. Normal defined statistically includes a range of Histologically defined mild duodenitis is characterised byvillous morphology andplasma cell counts, butpolymorphs increase in mucosal volume andplasma cell counts. Usually,are sparse. Original magnification x 125. there is also definite intraepithelial polymorph infitration.

~~~~~~~~~~~~Pr,.vpnrp nfnnIvmnmhv in rrvnt onitholiuim is a uswfillgesting that this pattern of mucosal reaction mayrepresent a stage before ulceration.

Quantitative histological and immunocytochemi-cal evaluation is too cumbersome a technique to beapplied routinely to the diagnosis of duodenal biop-sies, but a simple classification of histologicalappearances based on this study is possible on aroutine basis without detailed measurement. Thenormal biopsy has a range of appearances, includinga moderate number of plasma cells, some gastricmetaplasia, and occasional intraepithelial poly-morphs (Fig. 5).

Histologically defined duodenitis of mild grade(Fig. 6) is characterised not only by increasedplasma cells but also by definite mucosal oedemaand may be accompanied by increased numbers ofpolymorphs in the villous, and particularly the crypt,epithelium and lamina propria and increased gastricmetaplasia. Polymorphs and gastric metaplasia maynot be present in every case that shows definiteabnormality, but there is no statistical justificationfor separating biopsies with "acute" and "chronic"changes.Severe duodenitis (Fig. 7) is characterised by vill-

ous atrophy, heavy polymorph infiltration of villousand crypt epithelium and lamina propria, anddecreased plasma cells, although total cellularitymay be increased.

Severe duodenitis seems to be of clinical impor-

feature. Original magnification x 125.

Fig. 7 Photomicrograph ofsevere duodenitis (Cluster 3)showing marked villous atrophy. Plasma cells are decreasedbut total cellularity is high as polymorphs are present inlarge numbers. Original magnification x 125.

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tance in relation to peptic ulceration. The establish-ment of simple definitions for normality, histologi-cally defined mild duodenitis, and severe duodenitisby the application of statistical methods to quantita-tive histological data will facilitate further study ofthe clinical importance of duodenitis and its relationto the clinical course of peptic ulcer disease. Thesuccess of this study suggests that the methodsdescribed here could be applied to determine theimportance of a "chronic inflammatory" infiltrate inother histopathological material and to classify pat-terns of inflammatory response when an aetiologicalclassification is impossible.

We thank Mr PM Stephenson for technical help andMrs F Obee for secretarial help. We thank the TrentRegional Health Authority research committee forgenerous financial support.

References

'Cotton PB, Price AB, Tighe JR, Beale JSM. Preliminary evalua-tion of "duodenitis" by endoscopy and biopsy. Br Med J1973;iii:430-3.

2 Whitehead R, Roca M, Meikle DD, Skinner J, Truelove SC. Thehistological classification of duodenitis in fibreoptic biopsyspecimens. Digestion 1975;13:129-36.

3Kreuning J, Bosman FT, Kuiper G, Wal AM, Lindeman J. Gas-tric and duodenal mucosa in " healthy individuals. J Clin Pathol1978;31:69-77.

4Greenlaw R, Sheahan DG, de Luca V, Miller D, Myerson D,Myerson P. Gastroduodenitis-a broader concept of pepticulcer disease. Dig Dis Sci 1980;25:660-72.

Silcocks PBS. Measuring repeatability and validity of histologicaldiagnosis-a brief review with some practical examples. J ClinPathol 1983;36: 1269-75.

6Jones JH, Lennard-Jones JE, Morson BC, et al. Numerical tax-onomy and discriminant analysis applied to non-specific colitis.Q J Med 1973;42:715-32.

Jenkins, Goodall, Gillet, Scott'Scott BB, Goodali A, Stephenson P, Jenkins D. Duodenal bulb

plasma cells in duodenitis and duodenal ulceration. Gut (inpress).

Scott BB, Losowsky MS. Peroral small-intestinal biopsy: experi-ence with the hydraulic multiple biopsy instrument in routineclinical practice. Gut 1976; 17:740-3.

9Taylor CR. Immunoperoxidase techniques. Arch Pathol LabMed 1978; 102:113-21.

'Curran RC, Gregory J. The unmasking of antigens in paraffinsections by trypsin. Experimentia (Basle) 1977;33:1400-1.

"Thomson WO, Joffe SN, Robertson AG, Lee FD, Imrie CW,Blumgart LH. Is duodenitis a dyspeptic myth? Lancet1977;i: 1197-8.

2 Joffe SN, Lee FD, Blumgart LM. Duodenitis. Clin Gastroenterol1978;7:635-50.

3 Shousha S, Spiller RC, Parkins RA. The endoscopically abnor-mal duodenum in patients with dyspepsia: biopsy findings in60 cases. Histopathology 1983;7:23-34.

4 Hasan M, Sircus W, Ferguson A. Duodenal mucosal architecturein non-specific and ulcer-associated duodenitis. Gut1981;22:637-41.

"Hasan M, Hay F, Sircus W, Ferguson A. Nature of theinflammatory cell infiltrate in duodenitis. J Clin Pathol1983;36:280-8.

16 Shousha S, Parkins RA, Bull TB. Chronic duodenitis with gastricmetaplasia: electron microscopic study including comparisonwith normal. Histopathology 1983;7:873-85.

'' Florey HW, Harding HE. A humoral control of the secretion ofBrunner's glands. Proc R Soc Lond Biol 1935;117:68-77.

8 Rhodes J. Experimental production of gastric epithelium in theduodenum. Gut 1964;5:454-8.

9 Patrick WJA, Denham D, Forrest APM. Mucous change in thehuman duodenum: a light and electron microscopic study andcorrelation with disease and gastric acid secretion. Gut1974; 15: 767-76.

20 Gear EV, Dobbins WO. The histological spectrum of proximalduodenal biopsy in adult males. Am J Med Sci 1969;257:90-9.

21 Kirkegaard P, Olsen PS, Poulsen SS, Nexu E. Epidermal growthfactor inhibits cysteamine-induced duodenal ulcers. Gastroen-terology 1983;85: 1277-83.

Requests for reprints to: Dr D Jenkins, Department ofHistopathology, Whittington Hospital, Highgate Hill,London N19 5NF, England.

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responses and their correlations.histological study of mucosal Defining duodenitis: quantitative

D Jenkins, A Goodall, F R Gillet and B B Scott

doi: 10.1136/jcp.38.10.11191985 38: 1119-1126 J Clin Pathol 

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