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CT-colonography in population-based colorectal cancer screening

de Haan, M.C.

Link to publication

Citation for published version (APA):de Haan, M. C. (2012). CT-colonography in population-based colorectal cancer screening.

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2Chapter

Diagnosti c value ofCT-colonography as

compared to colonoscopy in an asymptomati c screening populati on: a meta-analysis

Margriet C. de Haan Rogier E. van Gelder

Anno Graser Shandra Bipat

Jaap Stoker

European Radiology 2011;21:1747-1763

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Abstract

ObjectivesPrevious meta-analyses on CT-colonography included both average and high risk individuals, which may overestimate the diagnostic value in screening. A meta-analysis was performed to obtain the value of CT-colonography for screening.

Materials and methods A search was performed using PubMed, Embase and Cochrane. Article selection and critical appraisal was done by two reviewers. Inclusion criteria: prospective, randomised trials or cohort studies comparing CT-colonography with colonoscopy (≥50 participants), ≥95% average risk participants ≥50 years. Study characteristics and 2×2 contingency tables were recorded. Sensitivity and specificity estimates were calculated per patient and per polyp (≥6 mm, ≥10 mm), using univariate and bivariate analyses.

Results Five of 1,021 studies identified were included, including 4,086 participants (<1% high risk). I2-values showed substantial heterogeneity, especially for 6–9 mm polyps and adenomas: 68.1% vs. 78.6% (sensitivity per patient). Estimated sensitivities for patients with polyps or adenomas ≥6 mm were 75.9% and 82.9%, corresponding specificities 94.6% and 91.4%. Estimated sensitivities for patients with polyps or adenomas ≥10 mm were 83.3% and 87.9%, corresponding specificities 98.7% and 97.6%. Estimated sensitivities per polyp for advanced adenomas ≥6 mm and ≥10 mm were 83.9% and 83.8%.

Conclusion Compared to colonoscopy, CT-colonography has a high sensitivity for adenomas ≥10 mm. For (advanced) adenomas ≥6 mm sensitivity is somewhat lower.

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| Accuracy of CTC in screening: meta-analysis

IntroductionComputed tomography (CT)-colonography has been studied for screening for (precursors of) colorectal cancer (CRC) and the Multisociety Task Force on Colorectal Cancer has indicated CT-colonography as an acceptable technique for CRC screening1,2. However, recently the National Institute of Health has published a statement regarding CRC screening concluding that there is still lack of information regarding the use of CT-colonography as screening technique in an average risk population3. Also other guidelines state that there is insufficient evidence yet4,5.

Several meta-analyses have been published on the diagnostic value of CT-colonography including both average risk and high risk individuals, but no meta-analysis has been published including average risk individuals only6-10. Individuals are considered to be at average risk if they have no symptoms, no personal history of CRC, adenomatous polyps or inflammatory bowel disease and no family history of advanced neoplasia11. By including studies containing high risk populations, the diagnostic value of CT-colonography in an average risk population might be overestimated. It is known that the estimated diagnostic value of a technique depends on factors such as disease prevalence and spectrum.

Therefore, the aim of this meta-analysis was to estimate the diagnostic value of CT-colonography to detect (advanced) adenomas and CRC in an average risk population aged 50 to 75 years.

Materials and methods

Literature searchArticles were obtained from the electronic databases PubMed, Embase and Cochrane, without restrictions with respect to the publication date and language. Lists of synonyms for CT-colonography were produced (Figure 1) and combined using the Boolean operator “OR”. The same was done for colonoscopy. Both search results were combined, using the Boolean operator “AND”. By reading title and abstract of all retrieved articles, two observers identified possible relevant papers, based on the inclusion and exclusion criteria described below. The remaining articles were retrieved as full-text articles and independently checked by two reviewers. Disagreement regarding inclusion was resolved by consensus. Reference lists of the final selection of articles were checked manually to identify other relevant papers. If additional information of an article considered for inclusion was needed

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due to incomplete data or description of the methods, the corresponding authors were contacted.

Inclusion and exclusion criteriaInclusion criteria were prospective, randomised trials or cohort studies, in humans ≥50 years, in which at least 50 predominantly asymptomatic average risk subjects (≥95%) underwent CT-colonography and completed colonoscopy for verification within 3 months. In addition, eligible studies needed to report the detection of colorectal polyps (adenomatous and non-adenomatous), advanced neoplasia and CRC and should include true positive (TP), false positive (FP), true negative (TN) and false negative (FN) values. Studies that included predominantly high risk subjects (symptomatic, history of hereditary CRC, personal history of polyps, CRC or IBD) were excluded, as well as studies that performed CT-colonography as a consequence of incomplete colonoscopy or studies that only performed colonoscopy after positive findings on CT-colonography.

Quality assessmentSystematic assessment of quality and documentation of relevant data of the selected articles was performed independently by two reviewers, using a standardized form. To grade the study quality, the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used with special focus on the characteristics of the included study population, index test and reference test12. We assessed whether the inclusion and exclusion criteria were described clearly and would result in a representative screening cohort. In addition, the presence of a disease progression bias and a verification bias was determined: did all participants receive their reference test within 3 months? Furthermore, we assessed whether the index test did not form part of the reference standard, whether all subjects received the same reference test, if the test results of both test were interpreted without knowledge of the other test results and whether withdrawals or uninterpretable test results were reported. Results are presented in Appendix 1.

StudypopulationThe following patient characteristics were documented: number of asymptomatic and symptomatic subjects, sex ratio, mean or median age with age range and CT-colonography indication.

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Imaging featuresThe following characteristics were documented regarding the imaging features of CT-colonography: bowel preparation, dietary restrictions, tagging and bowel distension, use of spasmolytical drugs and type of CT-system and CT-parameters, the positioning of the patient and the use of intravenous contrast medium during CT-colonography. For colonoscopy, the type of bowel preparation and dietary restrictions were documented.

ImaginganddiagnosticcriteriaThe following characteristics were documented regarding image analysis of both CT-colonography and colonoscopy: number of diagnostic examinations, number and experience of CT-colonography readers and endoscopists, reading strategy on CT-colonography, use of segmental unblinding or second look colonoscopy, determination of size on CT-colonography and during colonoscopy and histopathological confirmation.

DataextractionFor the analysis per patient, 2×2 contingency tables were constructed to be able to calculate the sensitivity and specificity values for the following type of lesions: all polyps, adenomatous polyps, advanced adenomas (defined as an adenoma with >25% villous features, size ≥10 mm and/or high-grade dysplasia)13, advanced neoplasia and CRC. For each type of lesion, except for CRC, data were collected using the following thresholds: 6–9 mm, ≥6 mm and ≥10 mm, based on the associated potential CRC risk14-16.

For the analysis per polyp, we extracted TP and FN findings to calculate the sensitivity of all polyps, (advanced) adenomas and advanced neoplasia for the same thresholds.

If needed, a request for additional data was send to the corresponding author. If possible, the following matching algorithm was used: the lesion should be at least <50% margin of error in size and should be found in the same or adjacent segment.

StatisticalanalysisHeterogeneity of sensitivity or specificity was assessed using I2-statistics17. If I2-values were >25%, we considered these data significantly heterogeneous, and random-effects analyses were performed. In case ofI2-values <25%, fixed-effects approaches were used. For the per patient analyses, we used bivariate models18 to obtain summary estimates of

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sensitivity and specificity with 95% confidence intervals. For the per polyp analyses, we used univariate models to obtain summary estimates of sensitivity with 95% confidence intervals. All analyses were performed using SAS software (SAS 9.2 procNlmixed, SAS Institute, Cary, NC, USA). Publication bias was examined by constructing funnel plots.

Perpatient The x-axis consisted of the natural logarithm of the diagnostic odds ratio (= (TP X TN) / (FN X FP)). On the y-axis, we plotted the number of patients.

Per lesion The x-axis consisted of the sensitivity, and on the y-axis we plotted the number of patients.Egger’s regression tests were used to examine the asymmetry of the funnel plots. A significant regression coefficient (p value<0.05) indicates an association between sample size and the diagnostic values.

ResultsThe initial search yielded 1,841 articles (Figure 1). By excluding doubles, 1,021 articles remained. After screening on title and abstract, 1,008 articles were excluded. The most frequent reasons for exclusion were study design, study population (i.e. high risk) or non-related to CT-colonography or screening for polyps and CRC (i.e. IBD, MR-colonography). After assessment of 13 full text publications, seven articles were excluded, because they included only (n=2)19,20 or predominantly (n=4) high risk participants (16.7%, 37.0%, 76.6% and 80.4%, respectively)21-24 or because colonoscopy was only offered to a small selection of the participants (n=1)25. Finally, six articles were included in this systematic review describing the results found in five prospective cohort studies26-31. Screening of title and abstract of references and related articles did not result in additional relevant articles.

PatientcharacteristicsPatient characteristics are outlined in Table 1. We included five studies with in total 4,086 patients (54% male). Four studies26-28,30,31 did have a study population of over 200 average risk subjects; the largest population comprised 2,249 average risk subjects27. The smallest study had a population of 68 participants at average risk 29. All studies provided a clear description of patient characteristics and the inclusion and exclusion criteria. Three studies included high risk subjects: 2.6%30,31, 5.2%28 and 11.3%27, respectively. The

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corresponding authors of these papers were contacted to obtain data concerning average risk patients only. This succeeded in two out of three studies, resulting in a total of four datasets containing data of average risk subjects only26-29 and one study including 2.6% high risk participants30,31. Resulting in a total of 4,086 participants, of which 37 were at high risk (0.9%). The mean age varied between 55 and 60.5 years, the minimal age was 50 in four studies26-29.

Figure 1: Flowchart of search strategy, search date: 21st of July, 2010

1

Figure 1: Flowchart of search strategy, search date: 21st of July, 2010

PubMed 920 results

Embase 881 results

Cochrane 40 results

Pubmed, Embase, Cochrane 1841 results in total

1828 studies excluded 820 duplicate studies

1008 did not match inclusion/exclusion criteria (based on screening title and abstract, by 2 independent readers)

13 full text articles Scored for validity and relevance by 2 independent readers

7 articles excluded - predominantly high risk participants (n=5)

- reference test was performed, only if index test was positive (n=2)

6 articles (describing 5 different studies) eligible for review

Produce list of synonyms

(Colonography (includes: CT colonography, CT colonography screening, virtual colonography) OR colography OR CTC OR computerized tomographic colonoscopy OR virtual colonoscopy OR virtual endoscopy OR ct colonoscopy OR ct pneumocolon)

AND (Colonoscopy (includes: optical colonoscopy) OR coloscopy OR OC)

Date of search: July 21, 2010

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Tabl

e 1

Patie

nt c

hara

cter

istics

incl

uded

stud

ies

Auth

orM

ultic

entr

e or

sin

gle

cent

re tr

ial

(n) a

nd d

esig

n

Incl

usio

n cr

iteria

Excl

usio

n cr

iteria

Num

ber o

f sub

ject

s,

incl

uded

in a

naly

sisM

:FAg

e (m

ean,

m

edia

n,

rang

e)

Gras

er 2

009

[26]

Sing

le,

pros

pecti

ve≥5

0 ye

ar

asym

ptom

atica

prio

r OC

prev

ious

5 y

ears

;po

sitive

fam

ily h

istor

y fo

r CRC

or h

ered

itary

CRC

sy

ndro

mes

;hi

stor

y of

IBD;

body

wei

ght >

150

kg;

seve

re c

ardi

ovas

cula

r or p

ulm

onar

y di

seas

e

311

parti

cipa

nts

4 ex

clud

ed: 2

no

colo

nosc

opy

and

2 in

com

plet

e co

lono

scop

yIn

clud

ed in

ana

lysis

307

171:

140

60.5

59.7

50-8

1

John

son

2008

[2

7]M

ulti

(n=1

5),

pros

pecti

ve≥5

0 ye

aras

ympt

omati

cbpr

ior O

C pr

evio

us 5

yea

rs;

positi

ve fa

mily

hist

ory

for C

RC o

r fam

ilial

pol

ypos

is sy

ndro

me;

pers

onal

hist

ory

of IB

D, p

olyp

s and

/or C

RC;

positi

ve F

OBT

;se

rious

med

ical

con

ditio

n th

at in

crea

ses c

ompl

icati

on ri

sk

colo

nosc

opy

2,24

91,

088:

1,16

158

.057

.050

-86

Kim

200

8 [2

8]Si

ngle

, pr

ospe

ctive

≥50

year

asym

ptom

aticc

prio

r OC

prev

ious

5 y

ears

;po

sitive

fam

ily h

istor

y fo

r CRC

or h

ered

itary

CRC

synd

rom

es

(FAP

or H

NPC

C);

hist

ory

of IB

D, a

deno

mat

ous p

olyp

s, b

owel

obs

truc

tion,

isc

hem

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oliti

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olor

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gery

;po

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FO

BT p

revi

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mon

ths;

med

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con

ditio

n th

at p

recl

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the

use

of b

owel

pr

epar

ation

or c

olon

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229

159:

7058

.1n.

a50

-76

Mac

ari

2004

[2

9]Si

ngle

, pr

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ctive

≥50

year

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(not

spec

ified

)

prio

r sig

moi

dosc

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DBCE

exa

min

ation

or c

olon

osco

py;

positi

ve fa

mily

hist

ory

for C

RC,

hist

ory

of p

olyp

s;po

sitive

FO

BT;

6868

men

55 n.a

50-6

7

Pick

hard

t 20

03 [3

0,31

]M

ulti

(n=4

), pr

ospe

ctive

50-7

9 ye

aras

ympt

omati

cd

aver

age

risk

40-7

9 ye

aras

ympt

omati

cd

positi

ve fa

mily

hi

stor

y of

CRC

prio

r OC

prev

ious

10

year

s or p

rior b

ariu

m e

nem

a pr

evio

us

5 ye

ars;

positi

ve fa

mily

hist

ory

for h

ered

itary

CRC

synd

rom

es (F

AP

or H

NPC

C);

hist

ory

of IB

D, a

deno

mat

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olyp

s or C

RC;

positi

ve g

uaia

c-ba

sed

stoo

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t pre

viou

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onth

s;m

edic

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ondi

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that

pre

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phos

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epar

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;pr

egna

ncy

1,25

3 pa

rtici

pant

s20

exc

lude

d: 6

in

adeq

uate

pre

para

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8

inco

mpl

ete

colo

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6 in

com

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C In

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: 1,

233

(3%

hig

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k)

728:

505

57.8

56 40-7

9

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a asymptomatic = free of symptoms of colonic diseases such as melena, haematochezia, diarrhoea, relevant changes in stool frequency or abdominal painb asymptomatic = no melena, anemia or hematochezia more than ones last 6 months, no lower abdominal painc asymptomatic = no significant GI signs or melena, hematochezia, iron-deficiency anemia, weight loss or abdominal pain within 6 months before studyd asymptomatic = no iron deficiency anemia last 6 months, no melena or hematochezia last 12 months, no unintentional weight loss >10 lb (4.5kg) last 12 months

BowelpreparationandCT-colonographyprocedureBowel preparation and CT-colonography procedure are outlined in Appendix 2.

Three studies used an extensive bowel preparation predominantly based on 4 litres polyethylene glycol26-28 combined with a clear liquid diet26, a low-residue diet28 or dietary restrictions depending on the institutional standard of the clinical centres where the examinations were done27. The remaining two studies both used a more limited preparation based on sodium phosphate29-31. One study combined this with a clear liquid diet30,31, the dietary restrictions of the other study were not specified29.

Three studies used oral tagging26,27,30,31, one study did use intravenous contrast medium28. Of one study it was not specified whether the participants received tagging29. Bowel preparation was the same for colonoscopy, as both colonoscopy and CT-colonography were performed on the same day in all studies.

Bowel distension methods varied between the studies. Two studies used (primarily) automated CO2 insufflation, combined with butyl scopolamine bromide (Buscopan, Boehringer, Ingelheim, Germany)26 or glucagon hydrochloride (GlucaGen, Novo Nordisk A’S, Bagsvaerd, Denmark) as spasmolytical drug27. Three studies used manual room air28-31. In one study no spasmolytical drug was administered28, it was not specified whether spasmolytical drugs were used in the remaining two studies29-31. Two studies used at least 4 slice CT equipment29-31, two studies used at least 16 slice CT27,28 and one study used 64 slice CT26.

StudycharacteristicsStudy characteristics are outlined in Appendix 3. All participants received CT-colonography and colonoscopy on the same day. Different reference standards were used. One study used the colonoscopy results without knowledge of the CT-colonography findings29, two studies used the colonoscopy result after segmental unblinding as reference26,30,31, one study used colonoscopy (followed by a second look colonoscopy if lesions ≥10 mm reported on CT-colonography were missed on the initial colonoscopy) combined with

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histopathology as reference27 and another study used the histopathology results of the polyps that were removed during colonoscopy after segmental unblinding28. It is unclear whether there were any withdrawals in the selected studies. Uninterpretable results of CT-colonography or colonoscopy (outlined in Table 1) were reported and excluded from the analyses in two studies26,30,31.

Image analysisThe characteristics of the readers and the reading strategy are outlined in Appendix 3. The minimal experience of the CT-colonography readers was specified in four out of five studies, and varied between 25 and 100 examinations26-28,30,31. In one study the only reader had 5 years of reading experience29. Two studies used 2D read as primary reading strategy28,29, two studies used 3D read26,30,31 and one study used both reading strategies at random27. None of the included studies specified whether CAD was used. The experience of the endoscopists and use of different scopes of the included studies was not specified in most studies27,29-31. One study had been done by gastroenterologists with a minimum experience of 1,000 colonoscopies26, while the gastroenterologists in another study had a prior experience of 3,000 colonoscopies28.

Size measurement of the polyp was done by the use of an open biopsy forceps26,28,29, by a calibrated linear Probe30,31 or determined by the pathologist27. In all studies histopathology confirmation was available.

DataextractionFour studies used a matching algorithm almost the same as the one described in the methods26,28-31. These studies considered a CT-colonography finding to correspond with a colonoscopy lesion, if it was found in the same or adjacent segment. In addition it should be at least within 50% margin of error in size28, in the same or adjacent size category26,30,31 or should have a size difference of less than 4 mm29 to be considered as a true positive. The fifth study27 used a different matching algorithm: one or more lesions should be in the same size category, irrespective of location. Of this study new data were requested and received, using the matching algorithm as specified in the methods section.

Per patient data for each of the different size categories regarding all polyps and adenomas respectively, could be obtained in three respectively four of the five studies (Table 2). Per polyp data for each of the different size categories regarding all polyps could be obtained in all studies while per

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polyp data for adenomas could be obtained in four studies and per polyp data of advanced adenomas and CRC in three of the five studies (Table 3).

Corresponding I2-values for heterogeneity are reported in Tables 2 and 3. The results of individual studies are shown in forest plots (Figures 2 and 3).

Table 2 Results regarding all polyps, (advanced) adenomatous polyps, colorectal cancer, advanced neoplasia: per patient

All polyps (n=2,853)

6-9 mm ≥6 mm ≥10 mm

TP FP FN TN TP FP FN TN TP FP FN TN

Graser [26] N = 307 25 6 4 272 50 10 6 241 25 4 2 276

Johnson [27] N = 2,249 78 58 51 2,062 156 75 70 1,948 78 17 19 2,135

Kim [28] N = 229 23 14 15 177 36 20 17 156 13 6 2 208

Macari [29] N = 68 n.a. n.a. n.a. n.a. n.a. n.a. n.a. n.a. 3 1 0 64

Estimated sensitivityI2 heterogeneitya

Estimated specificityI2 heterogeneitya

68.1 (52.9-80.2)68.2% (29.2-85.7)

96.5 (93.9-98.0)83.7% (61.7-93.1)

75.9 (62.3-85.8)77.0% (46.0-90.2)

94.6 (90.4-97.0)90.4% (78.5-95.7)

83.3 (76.8-89.0)0.0% (0.0-82.0)

98.7 (97.6-99.3)60.1% (15.2-81.2)

Adenomatous polyps (n=4,018)

6-9 mm ≥6 mm ≥10 mm

TP FP FN TN TP FP FN TN TP FP FN TN

Graser [26] N = 307 19 12 2 274 42 18 4 243 23 6 2 276

Johnson [27] N = 2,249 62 61 30 2,096 137 78 45 1,989 75 17 15 2,142

Kim [28] N = 229 22 6 11 190 31 18 12 168 9 12 1 207

Pickhardt [30,31] N = 1,233 104 170 16 943 149 217 19 848 45 47 3 1,138


Estimated specificityI2 heterogeneitya

78.6 (66.1-87.3)79.4% (54.2-90.8)

95.0 (89.7-97.6)98.1% (96.9-98.8)

82.9 (73.6-89.4)80.2% (56.0-91.1)

91.4 (84.1-95.5)98.4% (97.6-99.0)

87.9 (82.1-92.0)14.6% (0.0-87.0)

97.6 (95.0-98.9)92.5% (85.3-96.2)

Advanced adenomas ≥6 mm, advanced neoplasia ≥6 mm and CRC (n=2,785)

Advanced adenomas ≥6 mmc

Colorectal cancerc Advanced neoplasia ≥6 mmc

Sensitivity sensitivity sensitivity

Graser [26] N = 307 92.6% 100% 92.9%

Johnson [27] N = 2,249 83.3% 100% 84.0%

Kim [28] N = 229 87.5%b 100% 88.2%b

a If I2-values of sensitivity and/or specificity were larger than 25%, data were considered as significantly heterogeneous b No lesions <6mm foundc Not possible to calculate estimated sensitivity and specificity due to small numbers, data regarding TP, FP, FN and TN values not available

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DataanalysisperpatientAll polyps Estimated sensitivities for polyps ≥6 mm and ≥10 mm (regardless of histology) were 75.9% (95%CI 62.3–85.8) and 83.3% (95%CI 76.8–89.0), while corresponding specificities were 94.6% (95%CI 90.4–97.0) and 98.7% (95%CI 97.6–99.3).Adenomas Estimated sensitivities for adenomas ≥6 mm and ≥10 mm were 82.9% (95%CI 73.6–89.4) and 87.9% (95%CI 82.1–92.0), while corresponding specificities were 91.4% (95%CI 84.1–95.5) and 97.6% (95%CI 95.0–98.9). Estimated sensitivities of all polyps and adenomatous polyps of 6–9 mm are available in Table 2.Advanced adenomas, CRC and advanced neoplasia Estimated results for the detection of advanced adenomas, advanced neoplasia and CRC were not calculated, as a consequence of the small number of participants with these findings (Table 2).

Data analysis per polypAll polyps Estimated sensitivities for polyps ≥6 mm and ≥10 mm (regardless of histology), were 74.3% (95%CI 61.6–83.3) and 83.7% (95%CI 76.6–89.0). Adenomas Estimated sensitivities for adenomas ≥6 mm and ≥10 mm were 80.0% (95%CI 66.9–88.7) and 85.9% (95%CI 80.4–90.0).Advanced adenomas Estimated sensitivities for advanced adenomas ≥6 mm and ≥10 mm were 83.9% (95%CI 77.6–88.7) and 83.3% (95%CI 77.1–88.8). Estimated sensitivities for polyps and (advanced) adenomas of 6–9 mm, are presented in Table 3.Advanced neoplasia and CRC Estimated sensitivities for advanced neoplasia and CRC by CT-colonography were not calculated, as a consequence of the small number of CRCs (n=6) that were detected in the included studies. In all studies, no CRCs were missed (Table 3).

PublicationbiasThe data points in the funnel plots are symmetrically distributed in a funnel shape suggesting the absence of publication bias (Appendix 4a–5b). In addition, the Egger’s regression tests showed no associations between sample size and diagnostic values (data not shown).

Table 3 Results regarding all polyps, (advanced) adenomatous polyps, colorectal cancer and advanced neoplasia: per polyp

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All polyps (n=4,086 participants) 6-9 mm ≥6 mm ≥10 mm

TP FN TP FN TP FN

Graser [26] N = 307 49 7 84 9 35 2

Johnson [27] N = 2,249 113 74 203 97 90 23

Kim [28] N = 229 44 34 60 40 16 6

Macari [29] N = 68 9 8 12 8 3 0

Pickhardt [30,31] N = 1,233 209 54 278 66 69 12


69.7 (56.2-80.6)88.6% (77.8-94.2)

74.3 (61.6-83.8)89.3% (79.3-94.4)

83.7 (76.6-89.0)33.3% (0.0-56.9)

Adenomatous polyps (n=4,018 participants)6-9 mm ≥6 mm ≥10 mm

TP FN TP FN TP FN

Graser [26] N = 307 37 4 67 6 30 2

Johnson [27] N = 2,249 81 49 167 68 86 19

Kim [28] N = 229 31 21 44 25 13 4

Pickhardt [30,31] N = 1,233 133 26 180 30 47 4


75.7 (60.3-86.5)88.5% (75.9-94.5)

80.0 (66.9-88.7)89.2% (77.7-94.8)

85.9 (80.4-90.0)44.9% (2.8-68.8)

Advanced adenomas (n=2,785 participants)6-9 mm ≥6 mm ≥10 mm

TP FN TP FN TP FN

Graser [26] N = 307 6 0 36 2 30 2

Johnson [27] N = 2,249 0 0 86 19 86 19

Kim [28] N = 229 6 2 19 6 13 4


n.a.n.a.

83.9 (77.6-88.7)51.8% (16.2-72.3)

83.8 (77.1-88.8)32.3% (0.0-93.0)

Colorectal cancer (n=2,785 participants)6-9 mm ≥6 mm ≥10 mm

TP FN TP FN TP FN

Graser [26] N = 307 0 0 1 0 1 0

Johnson [27] N = 2,249 0 0 4 0 4 0

Kim [28] N = 229 0 0 1 0 1 0

Not possible to calculate estimated sensitivity due to small numbers

Advanced neoplasia (n=2,785 participants)6-9 mm ≥6 mm ≥10 mm

TP FN TP FN TP FN

Graser [26] N = 307 6 0 37 2 31 2

Johnson [27] N = 2,249 0 0 90 19 90 19

Kim [28] N = 229 6 2 20 6 14 4

Not possible to calculate estimated sensitivity due to small numbers

a If I2-values of sensitivity and/or specificity were larger than 25%, data were considered as significantly heterogeneous

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Figure 2 Forest plot of per patient sensitivity and specificity, including sensitivity and specificity estimates, for all polyps. Summary statistics: estimated sensitivities for polyps ≥6 mm and ≥10 mm were 75.9% (95% CI 62.3–85.8) and 83.3% (95% CI 76.8–89.0), corresponding estimated specificities 94.6% (90.4–97.0) and 98.7% (97.6–99.3)

0.4 0.5 0.6 0.7 0.8 0.9 1

Sensitivity of CT-colonography for the detection of polyps, per patient (including 95% CI)

All polyps ≥10 mm

Johnson [27]

Pooled (I2 = 77.0%)

Johnson [27]

Graser [26]

Kim [28]

Pooled (I2 = 0.0%)

Macari [29]

Graser [26]

Kim [28]

All polyps ≥6 mm

0.7 0.75 0.8 0.85 0.9 0.95 1

Specificity of CT-colonography for the detection of polyps, per patient (including 95% CI)

Johnson [27]

Graser [26]

Kim [28]

Pooled (I2 = 90.4%)

Johnson [27]

Graser [26]

Kim [28]

Pooled (I2 = 60.1%)

Macari [29]

All polyps ≥10 mm

All polyps ≥6 mm

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Figure 3 Forest plot of per patient sensitivity and specificity, including sensitivity and specificity estimates, for adenomas. Summary statistics: estimated sensitivities for adenomas ≥6 mm and ≥10 mm were 82.9 (73.6–89.4) and 87.9 (82.1– 92.0), corresponding estimated specificities 91.4 (84.1–95.5) and 97.6 (95.0–98.9)

0.4 0.5 0.6 0.7 0.8 0.9 1

Sensitivity of CT-colonography for the detection of adenomas, per patient (including 95% CI)

Johnson [27]

Pickhardt [30,31]

Graser [26]

Pooled (I2 = 80.2%)

Kim [28]

Adenomas ≥6 mm

Adenomas ≥10 mm

Johnson [27]

Pickhardt [30,31]

Graser [26]

Pooled (I2 = 14.6%)

Kim [28]

0.7 0.75 0.8 0.85 0.9 0.95 1

Specificity of CT-colonography for the detection of adenomas, per patient (including 95% CI)

Johnson [27]

Pickhardt [30,31]

Graser [26]

Pooled (I2 = 98.4%)

Kim [28]

Adenomas ≥6 mm

Adenomas ≥10 mm

Johnson [27]

Pickhardt [30,31]

Graser [26]

Pooled (I2 = 92.5%)

Kim [28]

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DiscussionThis systematic review demonstrates an estimated per patient sensitivity and specificity of CT-colonography for the detection of adenomas ≥6 mm of 82.9% (95%CI 74–89%) and 91.4% (95%CI 84–96%) in asymptomatic screening participants. The estimated per patient sensitivity and specificity for adenomas ≥10 mm, were 87.9% (95%CI 82–92%) and 97.6% (95%CI 95–99%). The estimated per patient sensitivities for all colorectal polyps were slightly lower. All six CRCs were detected by CT-colonography.

As we obtained additional data of the studies in which high risk participants were excluded27,28, the study results might not be identical to previously published data. In addition, the results of Johnson et al27 are different then published before, as we used a different matching algorithm then the one that was used in their study, resulting in lower sensitivities and higher specificities.

There are a few explanations available for the substantial variability between studies in sensitivity and specificity. The largest study27 (n=2,249 participants), did not report lesions <5 mm found on CT-colonography (while a colonoscopy lesion of 6 mm could match a CT-colonography lesion of 3 mm) and performed no second look colonoscopy for colonoscopy negative CT-colonography lesions <10 mm . Obviously, both factors will probably result in a lower sensitivity for medium sized adenomas and a less prominent difference in the detection of adenomas ≥10 mm compared to the studies of Graser26 and Pickhardt30,31. The second explanation could be the use of primary 2D or primary 3D read: those studies with the highest sensitivities for the detection of adenomas used primary 3D read26,30,31; the other studies used primary 2D read28,29 or both methods randomly27. However, there is conflicting evidence regarding the possible difference of sensitivity when using primary 2D or 3D read32,33.

To our knowledge this is the first meta-analysis in which the diagnostic value of CT-colonography is compared to colonoscopy for the detection of (adenomatous) polyps and CRC in an average risk population. Previously, at least five systematic reviews6-10 were published describing the diagnostic value of CT-colonography in general (not specified for (advanced) adenomas), including both average risk and high risk populations. By comparing our results to the estimated sensitivities per patient for polyps 6–9 mm and ≥10 mm published previously, we found lower sensitivities, especially when looking at polyps of 6–9 mm. Estimated sensitivities per patient for polyps 6–9 mm published before

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were 59%, 70%, 84% and 86%, respectively6-8,10, while we calculated an estimated sensitivity of 68.1%. Estimated sensitivities per patient for polyps ≥10 mm were 76%, 85%, 88% and 93%, respectively6-8,10, while we calculated an estimated sensitivity of 83.3%. The fifth meta-analysis reported results using different thresholds9.

Our study has several strengths. We aimed to use data on average risk participants only and collected data regarding all polyps, (advanced) adenomas and CRC. This provided the possibility to estimate the diagnostic value of CT-colonography for adenomas and CRC in a screening setting. In order to perform an unbiased study selection, two reviewers independently selected possible relevant articles.

Our study also has several limitations. Although we tried to include only individuals at average risk, we could not obtain these data from one study30,31. Therefore, 37 individuals (0.9%) at high risk were included. However, it is assumable that this will be daily practice in screening and it is unlikely that this small number will have a substantial impact on the results. Secondly, participants of two studies comprised the majority of included participants, which might give the impression that this meta-analysis is actually a two study meta-analysis. However, the results of the two largest studies were heterogeneous and, moreover, were not at one end of the spectrum of the sensitivity or specificity range. Therefore it is unlikely that the larger studies skewed the results in one direction (of higher or lower values). Furthermore, sensitivity and specificity estimates were calculated using statistical analyses in which the individual studies are weighted by number of included participants18. Thirdly, we did not calculate the negative predictive value (NPV) because the prior probability of a negative outcome was high34. Fourthly, it is known that colonoscopy is not 100% sensitive for colorectal lesions and therefore no perfect reference standard35. Using the colonoscopy results after segmental unblinding and compared with histology, would be the best reference standard. Fifthly, because of limited data we were not able to calculate estimated sensitivities per patient for the detection of advanced adenomas, advanced neoplasia and CRC.

In summary, this meta-analysis of prospective studies studying the diagnostic value of CT-colonography compared to colonoscopy in an average risk population, shows that CT-colonography has a good sensitivity for (advanced) adenomas ≥10 mm. For (advanced) adenomas ≥6 mm sensitivity is somewhat lower.

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Acknowledgment The authors acknowledge the authors of the included studies26,28-31 and the American College of Radiology Imaging Network27 for providing us with additional data.

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16. Lieberman D, Moravec M, Holub J, Michaels L, Eisen G. Polyp size and advanced histology in patients undergoing colonoscopy screening: implications for CT colonography. Gastroenterology 2008; 135: 1100–1105.

17. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.

18. Reitsma JB, Glas AS, Rutjes AW, Scholten RJ, Bossuyt PM, Zwinderman AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol 2005; 58: 982–990.

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20. Fidler JL, Johnson CD, MacCarty RL, Welch TJ, Hara AK, Harmsen WS. Detection of flat lesions in the colon with CT colonography. Abdom Imaging 2002; 27: 292–300.

21. Wessling J, Domagk D, Lugering N, et al. Virtual colonography: identification and differentiation of colorectal lesions using multi-detector computed tomography. Scand J Gastroenterol 2005; 40: 468–476.

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23. Pineau BC, Paskett E, Chen GJ, et al. Virtual colonoscopy using oral contrast compared with colonoscopy for the detection of patients with colorectal polyps. Gastroenterology 2003; 125: 304–310.

24. Iannaccone R, Laghi A, Catalano C, et al. Detection of colorectal lesions: lower-dose multi-detector row helical CT colonography compared with conventional colonoscopy. Radiology 2003; 229: 775–781.

25. An S, Lee KH, Kim YK, et al. Screening CT colonography in an asymptomatic averagerisk Asian population: a 2-year experience in a single institution. Am J Roentgenol 2008; 191: W100–W106

26. Graser A, Stieber P, Nagel D, et al. Comparison of CT colonography, colonoscopy, sigmoidoscopy and faecal occult blood tests for the detection of advanced adenoma in an average risk population. Gut 2009; 58: 241–248.

27. Johnson CD, Chen MH, Toledano AY, et al. Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med 2008; 359: 1207–1217.

28. Kim YS, Kim N, Kim SH, et al. The efficacy of intravenous contrast-enhanced 16-raw multidetector CT colonography for detecting patients with colorectal polyps in an asymptomatic population in Korea. J Clin Gastroenterol 2008; 42: 791–798.

29. Macari M, Bini EJ, Jacobs SL, et al. Colorectal polyps and cancers in asymptomatic average-risk patients: evaluation with CT colonography. Radiology 2004; 230:629–636.

30. Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003; 349: 2191–2200.

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31. Pickhardt PJ, Choi JR, Hwang I, Schindler WR. Nonadenomatous polyps at CT colonography: prevalence, size distribution, and detection rates. Radiology 2004; 232: 784–790.

32. Pickhardt PJ, Lee AD, Taylor AJ, et al. Primary 2D versus primary 3D polyp detection at screening CT colonography. AJR Am J Roentgenol 2007; 189: 1451–1456.

33. De Vries AH, Liedenbaum MH, Bipat S, et al. Primary uncleansed 2D versus primary electronically cleansed 3D in limited bowel preparation CT-colonography. Is there a difference for novices and experienced readers? Eur Radiol 2009; 19: 1939–1950.

34. Howson, Colin, Peter Urbach. Scientific reasoning: The Bayesian approach. Open Court 1993.

35. Van Rijn JC, Reitsma JB, Stoker J, Bossuyt PM, van Deventer SJ, Dekker E. Polyp miss rate determined by tandem colonoscopy: a systematic review. Am J Gastroenterol 2006; 101: 343–350.

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Appendix 1 Ta

ble

4 Q

ualit

y as

sess

men

t of a

ll in

clud

ed st

udie

s usin

g th

e Q

UADA

S-to

ol

Gra

ser,

2009

[26]

John

son,

200

8 [2

7]Ki

m,

2008

[28]

Mac

ari,

2004

[2

9]Pi

ckha

rdt,

2003

[30,

31]

Spec

trum

of p

atien

ts re

pres

enta

tive

of th

e pa

tient

s who

will

rece

ive

the

test

in

pra

ctice

?Ye

sYe

sYe

sYe

sYe

s

Wer

e se

lecti

on c

riter

ia c

lear

ly d

escr

ibed

?Ye

sYe

sYe

sYe

sYe

s

Is th

e re

fere

nce

stan

dard

like

ly to

cor

rect

ly c

lass

ify th

e ta

rget

con

ditio

n?Ye

sYe

sYe

sYe

sYe

s

Is th

e tim

e pe

riod

betw

een

refe

renc

e st

anda

rd a

nd in

dex

test

shor

t eno

ugh

to p

reve

nt c

hang

e of

the

targ

et c

ondi

tion

betw

een

the

two

test

s?a

Yes,

sam

e da

yYe

s, sa

me

day

Yes,

sam

e da

yYe

s, sa

me

day

Yes,

sam

e da

y

Did

all s

ubje

cts r

ecei

ve v

erifi

catio

n us

ing

a re

fere

nce

stan

dard

of d

iagn

osis

?Ye

sYe

sYe

sYe

sYe

s

Did

all s

ubje

cts r

ecei

ve th

e sa

me

refe

renc

e st

anda

rd re

gard

less

of t

he in

dex

test

resu

lt?Ye

sYe

sYe

sYe

sYe

s

Was

the

refe

renc

e st

anda

rd in

depe

nden

t of t

he in

dex

test

?N

obN

o, p

artly

cN

obYe

sN

ob

Exec

ution

of t

he in

dex

test

des

crib

ed in

suffi

cien

t det

ail t

o pe

rmit

repl

ica-

tion?

Yes

Yes

Yes

Yes

Yes

Exec

ution

of t

he re

fere

nce

stan

dard

des

crib

ed in

suffi

cien

t det

ail t

o pe

rmit

repl

icati

on?

Yes

Yes

Yes

Yes

Yes

Wer

e th

e in

dex

test

resu

lts in

terp

rete

d w

ithou

t kno

wle

dge

of th

e re

sults

of

the

refe

renc

e st

anda

rd?

Yes

Yes

Yes

Yes

Yes

Wer

e th

e re

fere

nce

stan

dard

resu

lts in

terp

rete

d w

ithou

t kno

wle

dge

of th

e re

sults

of t

he in

dex

test

?Ye

sYe

sYe

sYe

sYe

s

Wer

e th

e sa

me

clin

ical

dat

a av

aila

ble

whe

n te

st re

sults

wer

e in

terp

rete

d as

w

ould

be

avai

labl

e w

hen

the

test

is u

sed

in p

racti

ce?

Yes

Yes

Yes

Yes

Yes

Wer

e un

inte

rpre

tabl

e/ in

term

edia

te te

st re

sults

repo

rted

?Ye

sYe

s, p

artly

dU

ncle

arU

ncle

arYe

s

Wer

e w

ithdr

awal

s fro

m th

e st

udy

expl

aine

d?U

ncle

are

Unc

lear

eU

ncle

are

Unc

lear

eU

ncle

are

VALI

DYe

sYe

sYe

sYe

sYe

s

RELE

VAN

TYe

sYe

sYe

sYe

sYe

s

21646 BW deHaan F.indd 46 22-03-12 22:55

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47


a De

fined

as <

3 m

onth

s.

b Re

fere

nce

stan

dard

= c

olon

osco

py a

fter s

egm

enta

l unb

lindi

ng o

r sec

ond

look

col

onos

copy

.c Re

fere

nce

stan

dard

= c

olon

osco

py fo

llow

ed b

y a

seco

nd lo

ok c

olon

osco

py if

ther

e w

as n

o m

atch

for p

olyp

s >9

mm

on

CT-c

olon

ogra

phy.

d O

f the

2,6

00 su

bjec

ts re

crui

ted,

69

subj

ects

wer

e ex

clud

ed in

the

anal

ysis

as a

con

sequ

ence

of i

ncom

plet

e co

lono

scop

y an

d/or

CT-

colo

nogr

aphy

resu

lts, n

ot fu

rthe

r spe

cifie

d.e In

non

e of

the

stud

ies w

as e

xpla

ined

whe

ther

ther

e w

ere

any

with

draw

als f

rom

the

stud

y.

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Appendix 2Ta

ble

5 CT

-col

ongr

aphy

imag

ing

char

acte

ristic

s

Auth

orPr

epar

ation

, inc

ludi

ng

diet

ary

rest

rictio

ns*

Tagg

ing*

Bran

ch n

ame

and

type

of s

cann

erBo

wel

dis

tens

ion,

m

anua

l or a

utom

atic

Spas

mol

ytica

l dr

ugs

Tech

nica

l asp

ect

Gra

ser,

2009

[26]

Exte

nsiv

e:

4L P

EG

4x5

mg

bisa

cody

l 30

ml s

odiu

mph

osph

ate

Clea

r liq

uid

diet

50 m

l iop

amid

ol

Siem

ens S

omat

on

Sens

ation

, m

ultis

lice:

64

Both

:74

% a

utom

ated

CO

2 in

suffl

ation

26%

man

ual r

oom

ai

r ins

ufflati

on

buty

lscop

ola-

min

20

mg/

ml i

.v.

Supi

ne a

nd p

rone

;Co

llim

ation

0.6

mm

;Sl

ice

thic

knes

s 0.7

5 m

m;

Reco

nstr

uctio

n in

terv

al

0.5

mm

;Tu

be v

olta

ge 1

20 k

Vp;

Ref 7

0mAs

supi

ne (3

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mSv

) and

30m

As p

rone

(1

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Sv)

John

son,

200

8 [2

7]Ex

tens

ive:

10

mg

bisa

cody

l (or

cur

-re

nt in

stitu

tiona

l sta

ndar

d)

com

bine

d w

ith

- PEG

in 4

2%

- sod

ium

phos

phat

e in

54%

- mag

nesiu

m c

itrat

e in

4%

O

R ot

her s

ubst

ance

s in

<1%

Diet

dep

ende

d on

dai

ly

prac

tice

in e

ach

parti

cipa

t-in

g ce

ntre

bariu

m su

lfate

in

4%

OR

iodi

nate

d co

ntra

st in

1%

OR

both

in 9

4%

OR

neith

er in

dica

ted

in 1

%

Siem

ens (

58%

), GE

(3

4%),

Phili

ps (4

%),

Tosh

iba

(4%

)

Mul

tislic

e:

16 sl

ice

in 4

7%40

slic

e in

4%

64 sl

ice

in 5

0%

Both

:au

tom

ated

CO

2 in

suffl

ation

was

use

d pr

imar

ily, i

f col

onic

in

suffl

ation

was

in-

adeq

uate

, man

ual

insu

fflati

on o

f roo

m

air w

as u

sed

92%

glu

cago

n 1

mg

s.c.

7-

15 m

inut

es

befo

re e

xam

i-na

tion

Supi

ne a

nd p

rone

;Co

llim

ation

0.5

-1.0

mm

;Sl

ice

thic

knes

s 1.0

-1.2

5 m

m;

Reco

nstr

uctio

n in

terv

al

0.8m

m;

Peak

vol

tage

120

kV;

50 e

ffecti

ve m

As

Kim

, 20

08 [2

8]Ex

tens

ive,

bas

ed o

n pa

rtici

-pa

nt’s

pref

eren

ce:

- 4L

PEG

in 7

1%

- 90m

l so

dium

phos

phat

e 29

%Al

l sub

ject

s rec

eive

d 10

mg

bisa

cody

l the

day

bef

ore

the

proc

edur

e an

d 20

mg

bisa

cody

l 1h

befo

re C

TC

Low

-res

idue

die

t

No,

i.v.

150

ml i

opro

-m

ide

Siem

ens S

omat

on

Sens

ation

, mul

-tis

lice:

16

Man

ual r

oom

air

insu

fflati

on

No

Supi

ne a

nd p

rone

;Co

llim

ation

2.0

mm

; Sl

ice

thic

knes

s 2.0

mm

;Re

cons

truc

tion

inte

rval

1.

0mm

;Tu

be v

olta

ge 1

20 k

Vp;

50 e

ffecti

ve m

As p

rone

, 12

0 eff

ectiv

e m

As su

pine

21646 BW deHaan F.indd 48 22-03-12 22:55

Chapter 2 |

49


Mac

ari,

2004

[2

9]Li

mite

d:2

x 45

ml p

hosp

hoso

da o

n th

e da

y pr

ior t

o th

e st

udy

Diet

not

spec

ified

Not

spec

ified

Siem

ens P

lus 4

Vo

lum

e Zo

om,

Mul

tislic

e: 4

Man

ual r

oom

air

insu

fflati

on(m

inim

um o

f 40

puffs

)

Not

spec

ified

Supi

ne a

nd p

rone

;Co

llim

ation

4x1

mm

;Sl

ice

thic

knes

s 1.2

5 m

m;

Reco

nstr

uctio

n in

terv

al

1 m

m;

Tube

vol

tage

120

kVp

;50

effe

ctive

mAs

Pick

hard

t, 20

03

[30,

31]

Lim

ited:

90m

l sod

ium

pho

spha

te10

mg

bisa

cody

l

Clea

r liq

uid

diet

500

ml o

f bar

ium

(2.1

%

) 12

0 m

l dia

trizo

ate

meg

lum

ine

and

diat

ri-zo

ate

sodi

um

GE L

ight

spee

d or

Li

ghtS

peed

Ultr

a,

Mul

tislic

e: 4

or 8

Man

ual r

oom

air

insu

fflati

onN

ot sp

ecifi

edSu

pine

and

pro

ne;

Colli

mati

on 1

.25-

2.5

mm

;Sl

ice

thic

knes

s unc

lear

;Re

cons

truc

tion

inte

rval

of

1mm

;Tu

be v

olta

ge 1

20kV

p;10

0 m

As

21646 BW deHaan F.indd 49 22-03-12 22:55

50

| co

lore

ctal

can

cer s

cree

ning

CT-c

olon

ogra

phy

in p

opul

ation

-bas

ed |

Appendix 3Ta

ble

6 Ch

arac

teris

tics o

f rea

ders

and

refe

renc

e st

anda

rd

Auth

orCT

C re

ader

s,

expe

rienc

eCT

C re

adin

g st

rate

gyCT

C re

port

Endo

scop

ists

Mea

sure

men

t of

pol

yp (O

C)Se

gmen

tal

unbl

indi

ng (S

U)

or se

cond

look

co

lono

scop

y (S

LC)

Hist

opa-

thol

ogy

CTC

lesi

on tP

co

mpa

red

to

colo

nosc

opy

Refe

renc

est

anda

rd

Gra

ser,

2009

[26]

3 ab

dom

inal

radi

-ol

ogist

, >30

0 CT

C ex

amin

ation

s

prim

ary

3D

(2D

prob

lem

so

lvin

g)

Loca

tion

Size

2D

6 ga

stro

ente

r-ol

ogist

s >1,

000

colo

nosc

opie

s

open

bio

psy

forc

eps

SU, d

irect

ly S

LCYe

ssa

me/

adja

cent

se

gmen

t and

siz

e ca

tego

ry

colo

nos-

copy

re-

sults

afte

r se

gmen

tal

unbl

indi

ng

John

son,

20

08 [2

7]15

radi

olog

ists,

>5

00 C

TC e

xam

i-na

tions

or 1

.5 d

ay

trai

ning

sess

ion,

w

ith d

etec

tion

rate

≥90

% fo

r po

lyps

≥10

mm

(q

ualif

ying

exa

mi-

natio

n)

at ra

ndom

: 50

% p

rimar

y 2D

(3D

prob

-le

m so

lvin

g)

50%

prim

ary

3D (2

D pr

ob-

lem

solv

ing)

Loca

tion

Size

2D

Onl

y le

sions

≥5

mm

repo

rted

Degr

ee o

f di

agno

stic

confi

denc

e

perf

orm

ed o

r di

rect

ly su

per-

vise

d by

an

expe

rienc

ed

gast

roen

tero

lo-

gist

(inf

orm

a-tio

n re

gard

ing

expe

rienc

e no

t co

llect

ed)

dete

rmin

ed

from

pat

holo

gy

repo

rt u

nles

s no

t com

plet

ely

rese

cted

, the

n co

lono

scop

y-de

rived

esti

-m

ates

wer

e us

ed

SLC

<90

days

if

lesio

ns >

9 m

m

wer

e de

tect

ed

on C

TC

Yes

one

or m

ore

lesio

ns m

et

the

crite

ria fo

r siz

e (6

-9 m

m

or >

9 m

m)

iden

tified

colo

nosc

o-py

+/-

SLC

+

hist

opa-

thol

ogy

Kim

, 20

08 [2

8]2

abdo

min

al ra

di-

olog

ist, >

100

CTC

exam

inati

ons

prim

ary

2D

(3D

prob

lem

so

lvin

g)

Loca

tion

Size

2D

Mor

phol

ogy

5 ga

stro

ente

r-ol

ogist

s>3

,000

colo

nos-

copi

es

open

bio

psy

forc

eps

SU, d

irect

ly S

LCYe

ssa

me/

adja

cent

se

gmen

t, siz

e of

lesio

ns

shou

ld b

e at

le

ast <

50%

m

argi

n of

er

ror,

sim

ilar

mor

phol

ogy

Perp

atien

t: hi

stop

a-th

olog

y

(all

poly

ps

resu

lting

O

C +

SU)

Per p

olyp

:co

lono

s-co

py a

fter

segm

enta

l un

blin

ding

21646 BW deHaan F.indd 50 22-03-12 22:55

Chapter 2 |

51


Mac

ari,

2004

[29]

1 ra

diol

ogist

, 5

year

s CTC

read

ing

expe

rienc

e

prim

ary

2D

(3D

prob

lem

so

lvin

g)

Loca

tion

Size

(not

spec

i-fie

d)M

orph

olog

y

1 ga

stro

ente

r-ol

ogist

with

5

year

s exp

eri-

ence

and

1 G

E fe

llow

with

di

rect

supe

rvi-

sion

open

bio

psy

forc

eps

Non

eYe

ssa

me/

adja

cent

se

gmen

t, siz

e di

ffere

nce

≤3

mm

, sim

ilar

mor

phol

ogy

colo

nosc

o-py

with

out

know

ledg

e of

CTC

find

-in

gs

Pick

hard

t, 20

03

[30,

31]

6 ra

diol

ogist

s, ≥

25

CTC

exam

inati

ons

prim

ary

3D

(2D

prob

lem

so

lvin

g)

Loca

tion

Size

3D

Mor

phol

ogy

Degr

ee o

f di

agno

stic

confi

denc

e

14 g

astr

oent

er-

olog

ists

3 co

lore

ctal

su

rgeo

nsSe

vera

l yea

rs

expe

rienc

e

calib

rate

d lin

ear p

robe

SU, d

irect

ly S

LC

if fin

ding

on

CTC

≥5 m

m

Yes

sam

e/ad

jace

nt

segm

ent,

size

of le

sions

sh

ould

be

at

leas

t <50

%

mar

gin

of

erro

r

colo

nos-

copy

re-

sults

afte

r se

gmen

tal

unbl

indi

ng

21646 BW deHaan F.indd 51 22-03-12 22:55

52

| co

lore

ctal

can

cer s

cree

ning

CT-c

olon

ogra

phy

in p

opul

ation

-bas

ed |

Appendix 4Figure 4 a Funnel plot per patient, all polyps, b Funnel plot per patient, adenomas

2500,00 6-9 mm>=6 mm>=10 mm

2000,00

1500,00

1000,00

500,00

0,00

2,00 3,00 4,00 5,00 6,00 7,00Natural logarithm of the diagnostic odds ratio

Num

ber o

f pati

ents

2500,00 6-9 mm>=6 mm>=10 mm

2000,00

1500,00

1000,00

500,00

0,00

2,00 3,00 4,00 5,00 6,00 7,00

Num

ber o

f pati

ents

Natural logarithm of the diagnostic odds ratio

21646 BW deHaan F.indd 52 22-03-12 22:55

Chapter 2 |

53


Appendix 5Figure 5 a Funnel plot per polyp, all polyps, b Funnel plot per polyp, adenomas

2500,00 6-9 mm>=6 mm>=10 mm

2000,00

1500,00

1000,00

500,00

0,00

0,50 0,60 0,70 0,80 0,90 1,00

Num

ber o

f pati

ents

2500,00 6-9 mm>=6 mm>=10 mm

2000,00

1500,00

1000,00

500,00

0,00

0,50 0,60 0,70 0,80 0,90 1,00

Num

ber o

f pati

ents

Sensitivity per lesion

Sensitivity per lesion

21646 BW deHaan F.indd 53 22-03-12 23:20

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