The role of high-resolution endoscopy and narrow-band imaging in the evaluation of upper GI...

ORIGINAL ARTICLE: Clinical Endoscopy

The role of high-resolution endoscopy and narrow-band imaging in theevaluation of upper GI neoplasia in familial adenomatous polyposis

Maria Lopez-Ceron, MD,1,2 Frank J. C. van den Broek, MD, PhD,1 Elisabeth M. Mathus-Vliegen, MD, PhD,1

Karam S. Boparai, MD, PhD,1 Susanne van Eeden, MD, PhD,3 Paul Fockens, MD, PhD,1

Evelien Dekker, MD, PhD1

Amsterdam, The Netherlands

Background: The Spigelman classification stratifies cancer risk in familial adenomatous polyposis (FAP) patientswith duodenal adenomatosis. High-resolution endoscopy (HRE) and narrow-band imaging (NBI) may identifylesions at high risk.

Objective: To compare HRE and NBI for the detection of duodenal and gastric polyps and to characterizeduodenal adenomas harboring advanced histology with HRE and NBI.

Design: Prospective, nonrandomized, comparative study. Retrospective image evaluation study.

Setting: Tertiary-care center.

Patients: Thirty-seven FAP patients undergoing surveillance upper endoscopies.

Intervention: HRE endoscopy was followed by NBI. The number of gastric polyps and Spigelman staging werecompared. Duodenal polyp images were systematically reviewed in a learning and validation phase.

Main Outcome Measurements: Number of gastric and duodenal polyps detected by HRE and NBI andprevalence of specific endoscopic features in duodenal adenomas with advanced histology.

Results: NBI did not identify additional gastric polyps but detected more duodenal adenomas in 16 examina-tions, resulting in upgrades of the Spigelman stage in 2 cases (4.4%). Pictures of 168 duodenal adenomas (44%advanced histology) were assessed. In the learning phase, 3 endoscopic features were associated with advancedhistology: white color, enlarged villi, and size �1 cm. Only size �1 cm was confirmed in the validation phase(odds ratio 3.0; 95% confidence interval, 1.2-7.4).

Limitations: Nonrandomized study, scant number of high-grade dysplasia adenomas.

Conclusion: Inspection with NBI did not lead to a clinically relevant upgrade in the Spigelman classification anddid not improve the detection of gastric polyps in comparison with HRE. The only endoscopic feature thatpredicted advanced histology of a duodenal adenoma was size �1 cm. (Gastrointest Endosc 2013;77:542-50.)

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Familial adenomatous polyposis (FAP) is an inheritedautosomal dominant condition caused by a germinal mu-tation in the adenomatous polyposis coli gene in whichmore than 100 adenomas are found in the colorectum.

Abbreviations: FAP, familial adenomatous polyposis; HRE, high-resolution endoscopy; NBI, narrow-band imaging.

DISCLOSURE: E. Dekker and P. Fockens received research support andequipment on loan from Olympus, Japan. No other financial relation-ships relevant to this publication were disclosed.

Copyright © 2013 by the American Society for Gastrointestinal Endoscopy0016-5107/$36.00http://dx.doi.org/10.1016/j.gie.2012.11.033

Received September 19, 2012. Accepted November 21, 2012. D

542 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 4 : 2013

urthermore, patients with FAP harbor multiple adenomashroughout the upper GI tract, especially in the duode-um.1 Because preventive colectomy is performed rou-inely in patients with FAP, survival of these patients has

urrent affiliations: Department of Gastroenterology and Hepatology, Ac-demic Medical Centre, Amsterdam, The Netherlands (1), Department ofastroenterology and Hepatology, Hospital Clinic, Barcelona, Spain (2),epartment of Pathology, Academic Medical Centre, Amsterdam, Theetherlands (3).

eprint requests: Evelien Dekker, MD, PhD, Department of Gastroenterologynd Hepatology, Academic Medical Centre, Meibergdreef, 9 1105 AZ, Am-terdam, The Netherlands.

f you would like to chat with an author of this article, you may contact Dr
ekker at [email protected].
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mailto:[email protected]

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Lopez-Ceron et al High-resolution endoscopy and NBI in familial adenomatous polyposis

improved. However, upper GI malignancies and desmoiddisease are now the leading causes of death in thesepatients.2 Duodenal adenomatosis is a frequent finding inFAP patients, its prevalence varying from 65% to 92%,depending on the age of patients.3-6 The lifetime cumula-ive risk for developing duodenal cancer in these patientsas been estimated at 4% to 10%.7,8

In 1989, Spigelman et al1 published a study in whichduodenal adenomatosis in FAP patients was divided into 5stages considering number, size, and polyp histology. Thisgrouping allowed an estimation of the risk of developingduodenal carcinoma, which was confirmed in subsequentstudies.9,10 The Spigelman classification has been adopted

orldwide as the method of staging duodenal adenoma-osis in patients with FAP. Regrettably, this staging systemas never been validated, and in prospective studies itsredictive value was not as good as desired.3,7,9 The de-

velopment of duodenal cancer in patients with initial lowSpigelman stages has been described as well as changes tomore favorable stages in subsequent endoscopies in pa-tients with initial Spigelman stage IV.9

In the last decade, multiple novel endoscopic techniquessuch as high-resolution endoscopy (HRE) and narrow-bandimaging (NBI) have been introduced, allowing more accu-rate detection and characterization of GI lesions.11 A recentretrospective analysis demonstrated that the introduction ofHRE technology in the endoscopy unit, together with ageing,was the most important reason for higher Spigelman stagesover the years.12 The introduction of new technologies inFAP surveillance may lead to the detection of more duodenallesions, which could result in higher Spigelman staging butmight not necessarily relate to an increased cancer risk. Ad-vanced imaging techniques also could play a role in thecharacterization of polyps at risk for malignant degeneration,allowing more targeted biopsies, a more representativeSpigelman stage, and/or a better prediction of the risk ofdeveloping duodenal cancer.

The aim of this prospective study was to identify endo-scopic features of duodenal adenomas with advanced his-tology in FAP patients with HRE and NBI. Secondarily, weaimed to compare HRE and NBI for the assessment of theSpigelman classification of duodenal adenomatosis and tocompare the accuracy of both techniques in the detectionof gastric polyps.

PATIENTS AND METHODS

Patient identification and invitationConsecutive FAP patients scheduled for duodenal sur-

veillance endoscopy were identified at the outpatientclinic of the Academic Medical Centre in Amsterdam. Eli-gibility for this study consisted of a proven diagnosis offamilial adenomatous polyposis, either by having an APCor MutYH gene mutation on genetic testing or by thepresence of more than 100 adenomatous colorectal polyps
on colonoscopy. Exclusion criteria were (1) noncorrect- w
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ble coagulopathy, (2) age �18 years, and (3) inability toive informed consent. Suitable patients received an invi-ation and informed consent form. This study was ap-roved by the medical ethical committee of the Academicedical Centre in Amsterdam.

ndoscopic equipmentFor duodenal surveillance in FAP patients, two endos-

opies were performed as recommended in current guide-ines: a forward-viewing gastroduodenoscopy to inspecthe stomach and duodenum and a side-viewing duode-oscopy to inspect the papilla of Vater and periampullaryegion.13 An HRE system equipped with NBI and opticalagnification (GIF-Q240Z; Olympus, Tokyo, Japan) wassed for forward-viewing examinations. A standard duo-enoscope (TJF-160R, Olympus, Hamburg, Germany) wassed for side-viewing examinations. Because HRE andBI were not available in this model, ampullary and peri-mpullary lesions were not included in the analysis.

ndoscopy protocolAfter written informed consent, patients were sched-

led for duodenal surveillance endoscopy. Conscious se-ation was given with midazolam (2.5-10 mg intrave-ously) supplemented with fentanyl (50-100 �g) whenecessary. Antispasmodic medication was given at theiscretion of the endoscopist. A research assistant wasresent during all endoscopies to register the findings in aase record form.

First, a forward-viewing endoscopy was performed,tarting in the HRE mode. The examined area was dividednto 3 segments: second and third part of the duodenum,uodenal bulb, and stomach. After completion of inspec-ion with HRE in one segment, the endoscopist switchedhe imaging mode to NBI for a second inspection. Thisrocess was repeated for each segment of the duodenumnd the stomach. Information in both HRE and NBI modesas registered separately in each segment. The total num-er and size of the detected polyps with both HRE and NBIas assessed. Size was estimated by using an open biopsy

orceps (8 mm). If the polyps were too numerous to beounted, the number was estimated, and the largest size

Take-home Message

● Inspection with narrow-band imaging did not lead to aclinically relevant upgrade in the Spigelmanclassifications and did not improve the detection ofgastric polyps in comparison with high-resolutionendoscopy.

● In this study, a duodenal adenoma larger than 1 cm had a3-fold increased risk of harboring advanced histology.This trait is easily and homogeneously estimated duringendoscopy, as shown by the good interrater agreement.

as recorded. Biopsy specimens were systematically

olume 77, No. 4 : 2013 GASTROINTESTINAL ENDOSCOPY 543

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High-resolution endoscopy and NBI in familial adenomatous polyposis Lopez-Ceron et al

taken as explained below. Lesions that were not initiallydetected by HRE but were detected by NBI at the secondinspection were pictured and biopsied separately.

Histologic samples were processed by using standardprocedures and evaluated by a staff pathologist special-ized in gastroenterology. Biopsies were classified at his-tology according to the type of epithelium (inflammatoryor hyperplastic polyp, tubular, tubulovillous, or villousadenoma) and degree of dysplasia (none, low grade, highgrade, or cancer) according to the updated Vienna criteriafor the diagnosis of GI neoplasia, omitting the categorymoderate dysplasia.14 A modified Spigelman classification

as applied in agreement with this, as previously de-cribed (Table 1).15,16 Advanced histology was defined as

the presence of either high-grade dysplasia and/or tubu-lovillous or villous morphology.

Duodenum. Pictures and biopsy specimens weretaken from all polyps �10 mm, all suspicious polyps(defined by the presence of a central depression, irregularsurface, or irregular vascular pattern), and a random sam-ple of polyps between 1 and 9 mm, up to a total maximumnumber of 10 polyps biopsied per patient. Two images ofeach lesion were taken with HRE and NBI: an overviewimage and a zoomed detailed image. All biopsy specimenswere linked to the corresponding pictures, which weresubsequently selected for the standardized image evalua-tion section of this study if they met the following criteria:a minimum of one zoomed and one overview picture perlesion, at least one of them with HRE and the other withNBI, and of sufficient quality (Fig. 1).

Stomach. Overview pictures were taken from fundicgland polyps and any other gastric polyps before theywere biopsied. Fundic gland polyps were not biopsiedunless they looked irregular or remarkable. Antral lesionswere always biopsied.

Image evaluation protocol for duodenalpolyps

Selected HRE and NBI images of duodenal polyps wereassigned to one of the phases for image evaluation: ex-

TABLE 1. Modified Spigelman classification.1,15,16,*

Criteria 1 point

Polyp no. 1-4

Polyp size 1-4 mm

Histology Tubularadenoma

Dysplasia Low grade

*Stage 0, 0 points; stage I, 1-4 points; stage II, 5-6 points; stage III, 7-8 points; s

ploratory phase, learning phase, and validation phase, l


ccording to a methodology described by Kara et al.17

mage selection was made by one expert in endoscopicmaging (F.v.d.B.) in the exploratory and learning phasesnd by another expert (M.L.C.) in the validation phase.mages were selected according to the criteria describedarlier. Each polyp was evaluated under HRE and NBIith and without zoom, so the final score was made on allf the images available for the polyp. In each phase, themages were evaluated on a computer screen (HP CompaqA2205wg 22-inch Widescreen LCD Monitor (Hewlett-ackard, California, USA)).

Exploratory phase. Polyp images from the first 16atients and the corresponding histology were reviewedy a specialized GI pathologist (S.v.E.) and two experts inndoscopic imaging (E.M.V., E.D.) in an unblinded man-er. Images were selected by another expert (F.v.d.B.).fter a thorough review of the HRE and NBI images, a listf specific endoscopic characteristics of duodenal polypsas drawn up to develop a standardized form that wassed for image evaluation in the following phases. Themages of patients used in this phase were excluded fromurther data analysis. All subsequent images and the ac-ompanying histology were divided into a learning set andvalidation set in a ratio of 1:2, respectively.Learning phase. Images were evaluated by two experts

n endoscopic imaging (E.D. and F.v.d.B.), blinded for clin-cal and histologic data. F.v.d.B. was in charge of both imageelection and image evaluation. To avoid bias, he had accesso patient data only after the image evaluation took place.he pictures were assessed for each feature on the standard-

zed form. The score was the result of the assessment of theeatures with both techniques (HRE and NBI). They were firstvaluated by each expert individually, and in case of dis-greement, a consensus was reached afterward by discus-ion. The association between each endoscopic feature andhe presence of advanced histology in every lesion wasnvestigated.

Validation phase. In this stage, the experts (E.D. and.v.d.B.) scored the images separately. Only the featureshat remained associated with advanced histology in the

Score

2 points 3 points

5-20 �20

5-10 mm �10 mm

Tubulovillousadenoma

Villous adenoma

— High grade

, 9-12 points.

earning phase were assessed in the validation phase.

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They were blinded for histology, for clinical data, and fromeach other’s opinions.

Statistical analysisDescriptive statistics were used to characterize the

study population. Because continuous variables in thisstudy had a skewed distribution, they were summarizedby median and range. The relationship between endo-scopic features and histopathologic outcome was investi-gated with univariate and multivariate logistic regressionanalysis. The association of advanced histology with eachendoscopic feature was analyzed several times, groupingtheir categories in different ways to conform binary vari-ables. The most discriminative P value was used to choosethe definitive binary variable. A P value of .1 was used asthe cut-off point for defining an “association” in the learn-ing set, but in the validation set it was lowered to .05. Theassociation was first tested with a univariate analysis. Fac-tors that were found to be significantly associated withadvanced histology were again evaluated with multivari-ate analysis. To test the reproducibility of these findings,interrater agreement was calculated with kappa analysis. A

Figure 1. Overview and zoomed endoscopic pictures with high-resolutitubular adenoma with low-grade dysplasia in the second duodenal portiowith NBI. C, Zoomed endoscopic picture with HRE. D, Zoomed endosigh-resolution endoscopy; NBI, narrow-band imaging.

score of �0.20 was considered poor, 0.21 to 0.40 fair, 0.41 t


o 0.60 moderate, 0.61 to 0.80 good, and 0.81 to 1.00 veryood. All statistical analyses were performed by using atatistical software package (Statistical Package for theocial Sciences 12.0.1; SPSS Inc, Chicago, Ill).

alculation of sample sizeBecause NBI has never been used for characterization

f duodenal polyps, we could not assess the diagnosticield of NBI for these means. However, a calculation cane made in terms of detection. In a recent study withigh-resolution chromoendoscopy, 66% of patients had apigelman stage III or IV.18 With HRE alone, we assumedstage III or IV in 45% of our patients. We hypothesized

n increase of 21% in adenoma detection with NBI, with aower of 90% (� error 0.1) and a significance level of 5%� error 0.05). A within-subjects design for 1-sided mea-urement resulted in a sample size of 46 procedures.

ESULTS

atientsFrom June 8, 2006 to September 9, 2008, 39 FAP pa-

doscopy and narrow-band imaging as well as a histologic section of aOverview endoscopic picture with HRE. B, Overview endoscopic picture

picture with NBI. E, Histologic section (H&E, orig. mag. �20). HRE,

on enn. A,copic

ients underwent one or more endoscopies for screening


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or surveillance of duodenal adenomatosis. Two caseswere excluded for the analysis because of lack of infor-mation about NBI (n � 1) and because of biopsy damage(n � 1). Thirty-seven patients (45 procedures) were in-luded (22 female, median age 49 years, range 28-78ears). All of them except one had undergone colectomy,ither total (n � 29) or subtotal (n � 7) and receivedegular duodenal surveillance according to the Spigelmantage. Twelve patients had an ampullary lesion, 8 haderiampullary lesions, and 4 presented both ampullarynd periampullary lesions. There were no screening ex-minations in these cohorts. Because some patients un-erwent surveillance upper endoscopies more than onceuring the study period, 45 consecutive procedures wereerformed in total by two endoscopists (E.D. and E.M.V.).he endoscopists had access to clinical data and previousxaminations of the patients as well as histopathologyesults, if applicable.

Detection of duodenal and gastric polypsDetection of duodenal polyps. The second look with

NBI detected additional polyps in 16 procedures (35.6%),leading to an upgrade in the Spigelman score for 5 of them(11.1%). In 4, the score changed from the second group(5-20 polyps) to the third group (�20); and in one casefrom the first group (�5) to the second (5-20). In twoexaminations (4.4%), the largest polyp detected with NBIwas larger than the largest polyp detected with HRE, butthis resulted in a upgrade in the Spigelman score for sizein only one procedure (2.2%). None of the polyps di-agnosed by NBI had a worse histology or degree ofdysplasia.

When total Spigelman scores were compared, the in-spection with NBI led to an upstage in two patients (4.4%)(Table 2). In one, the Spigelman stage increased from II toIII because of a higher score for polyp number and size. Inthe other, a rise in the score for polyp number resulted in

TABLE 2. No. of patients staged according toSpigelman classification with HRE and NBI.*

Narrow-band imaging

0 I II III IV

HRE

0 4 0 0 0 0

I 0 3 0 0 0

II 0 0 3 1 0

III 0 0 0 16 1

IV 0 0 0 0 17

HRE, High-resolution endoscopy; NBI, narrow-band imaging.*Coincident cases are highlighted in bold, and discordant ones arehighlighted in italics.

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Detection of gastric polyps. The presence of fundicland and antral polyps (Fig. 2) was noted in 30 (81.1%)nd 11 (29.7%) patients, respectively. Eight antral polypsere tubular adenomas with low-grade dysplasia, 3 were

nflammatory polyps, and in one pathology did not showbnormalities. All antral polyps but one were detectedith HRE and then confirmed with NBI. One lesion wasetected only with NBI, but histology revealed a healingrosion.

tandardized image evaluation protocolIn all procedures, pictures of 270 lesions were gathered

n total. Of these, 168 fulfilled the criteria for eligibility anduality and were grouped into 3 sets. The content of thehases of the protocol is outlined in Figure 3, and aummary of the findings is shown in Table 3.

Exploratory phase. The pictures from the first 16

igure 2. Tubular adenomas with low-grade dysplasia in the antrum. A,oomed picture with high-resolution endoscopy. B, Zoomed pictureith narrow-band imaging.

atients included 24 adenomas (of which 3 showed high-

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grade dysplasia and 13 villous morphology) and 6 imagesof normal-appearing mucosa. The list of endoscopic fea-tures developed in consensus after reviewing the images isdepicted in Table 4. This form was used for image assess-

ent in the following phase of the study.Learning phase. Pictures of 48 duodenal lesions (12

atients) were assessed in this phase. Eight lesions werexcluded because of lack of histologic diagnosis (3 le-

Figure 3. Flow chart describing the content and findings in each phanarrow-band imaging; OR, odds ratio.

TABLE 3. Summary of the findings in each phase of the image e

Exploratory phase

No. of patients 16

No. of endoscopic examinations 16

No. of adenomas assessed 24

No. of adenomas with advancedhistology (TV/V/HGD)

16 (13/0/3)

No. of adenocarcinomas 0

TV, Tubulovillous; V, villous; HGD, high-grade dysplasia.*Some patients were included in more than one phase as they could have diff

ions) and a diagnosis different from duodenal adenoma m


4 normal mucosa, 1 duodenitis). Forty adenomas werenally included. A univariate and multivariate analysis waserformed to evaluate a possible relationship betweenndoscopic features and advanced histology (Table 5). Inhis set of images, no adenomas with high-grade dysplasiaor pure villous morphology were found. Therefore, theroup of adenomas with advanced histology was made upf 17 adenomas with tubulovillous morphology only. After

the image evaluation protocol. HRE, high-resolution endoscopy; NBI,

tion protocol for duodenal polyps.*

earning phase Validation phase Total

12 19 35

14 22 52

40 98 162

17 (17/0/0) 43 (37/1/7) 76 (67/1/10)

0 0 0

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associated with advanced histology: white color of all villi(P � .013), enlarged villi (regular and irregular) (P � .045),and an estimated lesion size �1 cm (P � .074).

Validation phase. Images of 102 lesions (19 patients)were evaluated in this section. Four lesions were excludedbecause of a normal histologic diagnosis in 3 and because ofbiopsy damage in 1. Ninety-eight adenomas were finallyanalyzed (7 with high-grade dysplasia, 37 with tubulovillous,and 1 with villous histology). Experts scored the picturesindividually for white villi and enlarged villi and estimatedlesion size �1 cm. Both univariate and multivariate analyses

ith pooled data from both experts showed that the only

TABLE 4. Standardized evaluation form developed in consensu

Endosco

Image overall quality Poor Moderate

Mucosal pattern Normal villi Round/oval

Overall color Darker than normal Equal as normal

Vascular pattern No vessels Normal regular ves

Surface Smooth Bumpy

Shape (ParisClassification)

0-Is (sessile) 0-IIa (flat-elevated

Villi No Normal

Edge Sharp/cleardemarcation

Gradual/uncleardemarcation

Estimated size No lesion �5 mm

TABLE 5. Learning phase. Evaluation of the association of endo

Endoscopic features

Univar

OR

Villous mucosal pattern 5.727

White color of all villi 3.733

Irregular surface 4.222

Large villi (regular and irregular) 5.194

No or thin regular vessels 4.375

Estimated size >1 cm 3.590

Flat-elevated morphology (0-IIa,Paris classification)

1.528

Gradual demarcation 1.462

OR, Odds ratio.*(P, �.1).†Predictive features of advanced histology in this phase are highlighted in boin the univariate analysis were included in the multivariate analysis.

ndoscopic feature that independently predicted advanced a


istology in a duodenal adenoma was an estimated size �1m, with an odds ratio (OR) of 3.0 (95% confidence intervalCI], 1.2-7.4; P � .016) (Table 6).

Interrater agreement was measured. For lesions �1 cm,good degree of concordance (kappa value 0.651) was

ound, and for the rest of the features a moderate concor-ance was encountered: white villi (kappa 0.459) andnlarged villi (kappa 0.428).

ISCUSSION

The aim of this study was to evaluate the use of HRE

the assessment of duodenal lesions.

atures

Good Excellent

Tubular/long Branched Irregular Villous

Some white villi All white villi

Thick/irregular vessels

One or moredepressions

Heavily irregular

0-IIb (flat) 0-IIc (depressed)

Regular large Irregular large

5-10 mm 1-2 cm �2 cm

ic features of duodenal adenomas with advanced histology.†

nalysis Multivariate analysis

P value OR P value

*.052 0.913 .946

*.054 20.655 *.013

*.050 0.426 .592

*.018 25.610 *.045

.201 — —

*.094 6.725 *.074

.523 — —

.554 — —

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gastric polyps in FAP patients. The use of NBI for detectionof duodenal adenomas resulted in an upgrade in totalSpigelman score in only 2 cases (4.4%), and NBI did notdetect any additional gastric adenoma. Furthermore, weaimed to detect endoscopic features of duodenal ade-nomas that would predict advanced histology (eithertubulovillous or villous components and/or high-gradedysplasia). After analyzing 8 different traits by both HREand NBI, the only one that was significantly associatedwith advanced histology was an estimated polyp size�1 cm, with a 3-fold increased risk (OR 3, 95% CI,1.2-7.4). This characteristic was appreciated with a goodinterrater agreement.

With respect to detection of duodenal polyps, this is thefirst study in which NBI is evaluated. Some studies haveinvestigated the role of new technologies such as high-resolution imaging and chromoendoscopy in FAP patients,specifically addressing the increased adenoma detectionrates.16,18,19 A recent publication by our group showedn increase in high Spigelman stages over a medianollow-up of 19.5 years. This phenomenon was explainedy both ageing and technical improvements, the changerom low-resolution to high-resolution being the mostelevant factor.12

The use of chromoendoscopy in the assessment ofduodenal adenomatosis in FAP has been specifically eval-uated in two studies. The first showed a significant in-crease in number and size of duodenal polyps detectedwith chromoendoscopy.19 However, these results wereot confirmed by a second study.18 This difference inndings might be explained by the use of conventionalesolution imaging in the first study as opposed to HRE inhe second. This suggests that chromoendoscopy might beore helpful in detecting polyps during conventional res-lution endoscopy than in HRE because HRE actuallymproves the detection by itself. Reasoning in the sameine, this could be the explanation for the lack of a relevantffect of NBI over HRE in duodenal adenomatosis stagingn our study.

Because HRE and NBI both provide highly detaileducosal images, they could potentially provide informa-

TABLE 6. Validation phase. Evaluation of the association of endPooled analysis of data from both experts.†

Endoscopic features

Univariate analysi

OR P value

White villi 1.440 .374

Large villi 1.862 .132

Estimated size >1 cm 3.304 *.007

OR, Odds ratio; CI, confidence interval.*(P, �.1).†The only predictive feature of advanced histology in this phase is highlighted

ion on the histology of a lesion. Endoscopes with HRE s


nd NBI are widely available, and their use for character-zation of lesions throughout the GI tract has been exten-ively studied. Barrett’s esophagus is the only condition forhich NBI could differentiate high-grade dysplasia andarly cancer from low-grade dysplasia and nonneoplasticissue with a high sensitivity (71%-100%) but variable spec-ficity (33%-99%).20 To our knowledge, this is the firsttudy in which both HRE and NBI are evaluated for char-cterization of duodenal adenomas in FAP patients. Re-arding characterization of neoplasia in the duodenum, insmall study in 14 non-FAP patients, pinecone/leaf-

haped and irregular villi as seen with NBI showed 100%ccuracy for the identification of ampullary neoplasia (ad-noma and adenocarcinoma) versus nonneoplastic le-ions.21 No data on advanced histology were assessed.

Unfortunately, our study did not lead to the identifica-ion of endoscopic features that predicted advanced his-ology in a duodenal adenoma other than its large size,hich defines the lesion as advanced22 and can be easilyssessed by HRE (or even low-resolution endoscopy)lone. We have investigated whether the deletion of theharacteristic “size,” which was so dominantly present,rom the multivariate analysis would change the associa-ion of the other characteristics with advanced histology,ut we could not find any relevant feature (results nothown). The increase in size of the polyps has beenreviously described as one of the factors that causes anncrease in the Spigelman stage,3 but a higher Spigelmantage does not necessarily imply advanced histology le-ions. Because large lesions will contain high-grade dys-lasia or villous changes more often,15 it could be arguedhat endoscopic polypectomy for all polyps �1 cm shoulde performed. If this strategy indeed prevents major duo-enal surgery and/or duodenal cancer, it should be theubject of a large, prospective trial.

A major limitation of this study is the sequential use ofRE followed by NBI in the detection of polyps, whichould have resulted in a biased advantage for NBI. Despitehis, NBI did not increase the detection of duodenal andastric polyps. Hence, we can infer that the role of NBI inhis situation is limited. Another drawback was the ab-

pic features of duodenal adenomas with advanced histology.

Multivariate analysis

5% CI OR P value 95% CI

5-3.219 1.149 .752 0.485-2.720

9-4.183 1.294 .571 0.531-3.150

2-7.840 3.003 *.017 1.218-7.406

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2


ogy in the learning phase of the image evaluation part ofthe study. However, in the validation phase, enough le-sions of every type were present. This represents a limi-tation because the endoscopic features in the learningphase were assessed only with respect to tubular versustubulovillous morphology, and a significant associationwith high-grade dysplasia may have been missed. More-over, the overall prevalence of high-grade dysplasia andvillous morphology in our group of patients is so low(11/76 � 14.5%) that it is difficult to draw a conclusion.

On the other hand, it could be argued that one of thexperts (E.D.) fulfilling the image evaluation protocol alsoerformed some of the endoscopies and this could repre-ent a bias because she was not blinded for clinical andistopathologic data during the endoscopy. However, themage evaluation took place months or years after thendoscopies were done (depending on the phase), witho access to clinical or histologic data. Also, the names ofhe patients were deleted from the images, thus eliminat-ng the risk of bias.

In summary, NBI did not improve the detection ofuodenal and gastric polyps, and HRE and NBI have aimited role in the characterization of duodenal adenomasith advanced histology in FAP. Our results indicate that auodenal adenoma �1 cm has a 3-fold increased risk of

harboring advanced histology. This trait is easily and ho-mogeneously estimated during endoscopy, as shown bythe good interrater agreement. Our findings may supportthe resection of adenomas �1 cm in order to delay majorsurgery. However, endoscopic removal of duodenal le-sions is also associated with major complications23 andherefore should be performed only in patients who willenefit from it.

We believe that the Spigelman classification should beeevaluated and might be simplified by putting more em-hasis on size, extension, location (papillary or extra-apillary), villous and tubulovillous architecture, andigh-grade dysplasia. This would offer endoscopists a bet-er risk-stratification of these patients and timely endo-copic therapy in an effort to prevent major duodenalurgery and development of duodenal cancer.

CKNOWLEDGMENT

We thank Christine Cohen for logistic and researchupport and Hans Reitsma for statistical support.

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