Margriet C. de Haan

Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: a randomised controlled trial

BACKGROUND Screening for colorectal cancer is widely recommended, but the preferred strategy remains unidentified. We aimed to compare participation and diagnostic yield between screening with colonoscopy and with non-cathartic CT colonography. METHODS Members of the general population, aged 50-75 years, and living in the regions of Amsterdam or Rotterdam, identified via the registries of the regional municipal administration, were randomly allocated (2:1) to be invited for primary screening for colorectal cancer by colonoscopy or by CT colonography. Randomisation was done per household with a minimisation algorithm based on age, sex, and socioeconomic status. Invitations were sent between June 8, 2009, and Aug 16, 2010. Participants assigned to CT colonography who were found to have one or more large lesions (≥10 mm) were offered colonoscopy; those with 6-9 mm lesions were offered surveillance CT colonography. The primary outcome was the participation rate, defined as number of invitees undergoing the examination relative to the total number of invitees. Diagnostic yield was calculated as number of participants with advanced neoplasia relative to the total number of invitees. Invitees and screening centre employees were not masked to allocation. This trial is registered in the Dutch trial register, number NTR1829. FINDINGS 1276 (22%) of 5924 colonoscopy invitees participated, compared with 982 (34%) of 2920 CT colonography invitees (relative risk [RR] 1·56, 95% CI 1·46-1·68; p<0·0001). Of the participants in the colonoscopy group, 111 (9%) had advanced neoplasia of whom seven (<1%) had a carcinoma. Of CT colonography participants, 84 (9%) were offered colonoscopy, of whom 60 (6%) had advanced neoplasia of whom five (<1%) had a carcinoma; 82 (8%) were offered surveillance. The diagnostic yield for all advanced neoplasia was 8·7 per 100 participants for colonoscopy versus 6·1 per 100 for CT colonography (RR 1·46, 95% CI 1·06-2·03; p=0·02) and 1·9 per 100 invitees for colonoscopy and 2·1 per 100 invitees for CT colonography (RR 0·91, 0·66-2·03; p=0·56). The diagnostic yield for advanced neoplasia of 10 mm or more was 1·5 per 100 invitees for colonoscopy and 2·0 per 100 invitees for CT colonography, respectively (RR 0·74, 95% CI 0·53-1·03; p=0·07). Serious adverse events related to the screening procedure were post-polypectomy bleedings: two in the colonoscopy group and three in the CT colonography group. INTERPRETATION Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography. The diagnostic yield for advanced neoplasia per 100 invitees was similar for both strategies, indicating that both techniques can be used for population-based screening for colorectal cancer. Other factors such as cost-effectiveness and perceived burden should be taken into account when deciding which technique is preferable. FUNDING Netherlands Organisation for Health Research and Development, Centre for Translational Molecular Medicine, and the Nuts Ohra Foundation.

Overinterpretation and Misreporting of Diagnostic Accuracy Studies: Evidence of “Spin”

PURPOSE To estimate the frequency of distorted presentation and overinterpretation of results in diagnostic accuracy studies. MATERIALS AND METHODS MEDLINE was searched for diagnostic accuracy studies published between January and June 2010 in journals with an impact factor of 4 or higher. Articles included were primary studies of the accuracy of one or more tests in which the results were compared with a clinical reference standard. Two authors scored each article independently by using a pretested data-extraction form to identify actual overinterpretation and practices that facilitate overinterpretation, such as incomplete reporting of study methods or the use of inappropriate methods (potential overinterpretation). The frequency of overinterpretation was estimated in all studies and in a subgroup of imaging studies. RESULTS Of the 126 articles, 39 (31%; 95% confidence interval [CI]: 23, 39) contained a form of actual overinterpretation, including 29 (23%; 95% CI: 16, 30) with an overly optimistic abstract, 10 (8%; 96% CI: 3%, 13%) with a discrepancy between the study aim and conclusion, and eight with conclusions based on selected subgroups. In our analysis of potential overinterpretation, authors of 89% (95% CI: 83%, 94%) of the studies did not include a sample size calculation, 88% (95% CI: 82%, 94%) did not state a test hypothesis, and 57% (95% CI: 48%, 66%) did not report CIs of accuracy measurements. In 43% (95% CI: 34%, 52%) of studies, authors were unclear about the intended role of the test, and in 3% (95% CI: 0%, 6%) they used inappropriate statistical tests. A subgroup analysis of imaging studies showed 16 (30%; 95% CI: 17%, 43%) and 53 (100%; 95% CI: 92%, 100%) contained forms of actual and potential overinterpretation, respectively. CONCLUSION Overinterpretation and misreporting of results in diagnostic accuracy studies is frequent in journals with high impact factors. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120527/-/DC1.

Burden of colonoscopy compared to non-cathartic CT-colonography in a colorectal cancer screening programme: randomised controlled trial

Objective CT-colonography has been suggested to be less burdensome for primary colorectal cancer (CRC) screening than colonoscopy. To compare the expected and perceived burden of both in a randomised trial. Design 8844 Dutch citizens aged 50–74 years were randomly invited for CRC screening with colonoscopy (n=5924) or CT-colonography (n=2920). Colonoscopy was performed after full colon lavage, or CT-colonography after limited bowel preparation (non-cathartic). All invitees were asked to complete the expected burden questionnaire before the procedure. All participants were invited to complete the perceived burden questionnaire 14 days later. Mean scores were calculated on 5-point scales. Results Expected burden: 2111 (36%) colonoscopy and 1199 (41%) CT-colonography invitees completed the expected burden questionnaire. Colonoscopy invitees expected the bowel preparation and screening procedure to be more burdensome than CT-colonography invitees: mean scores 3.0±1.1 vs 2.3±0.9 (p<0.001) and 3.1±1.1 vs 2.2±0.9 (p<0.001). Perceived burden: 1009/1276 (79%) colonoscopy and 801/982 (82%) CT-colonography participants completed the perceived burden questionnaire. The full screening procedure was reported as more burdensome in CT-colonography than in colonoscopy: 1.8±0.9 vs 2.0±0.9 (p<0.001). Drinking the bowel preparation resulted in a higher burden score in colonoscopy (3.0±1.3 vs 1.7±1.0, p<0.001) while related bowel movements were scored more burdensome in CT-colonography (2.0±1.0 vs 2.2±1.1, p<0.001). Most participants would probably or definitely take part in a next screening round: 96% for colonoscopy and 93% for CT-colonography (p=0.99). Conclusion In a CRC screening programme, colonoscopy invitees expected the screening procedure and bowel preparation to be more burdensome than CT-colonography invitees. In participants, CT-colonography was scored as more burdensome than colonoscopy. Intended participation in a next screening round was comparable.

Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial.

BackgroundColorectal cancer (CRC) is the second most prevalent type of cancer in Europe. Early detection and removal of CRC or its precursor lesions by population screening can reduce mortality. Colonoscopy and computed tomography colonography (CT colonography) are highly accurate exams and screening options that examine the entire colon. The success of screening depends on the participation rate. We designed a randomized trial to compare the uptake, yield and costs of direct colonoscopy population screening, using either a telephone consultation or a consultation at the outpatient clinic, versus CT colonography first, with colonoscopy in CT colonography positives.Methods and design7,500 persons between 50 and 75 years will be randomly selected from the electronic database of the municipal administration registration and will receive an invitation to participate in either CT colonography (2,500 persons) or colonoscopy (5,000 persons) screening. Those invited for colonoscopy screening will be randomized to a prior consultation either by telephone or a visit at the outpatient clinic. All CT colonography invitees will have a prior consultation by telephone. Invitees are instructed to consult their general practitioner and not to participate in screening if they have symptoms suggestive for CRC. After providing informed consent, participants will be scheduled for the screening procedure. The primary outcome measure of this study is the participation rate. Secondary outcomes are the diagnostic yield, the expected and perceived burden of the screening test, level of informed choice and cost-effectiveness of both screening methods.DiscussionThis study will provide further evidence to enable decision making in population screening for colorectal cancer.Trial registrationDutch trial register: NTR1829

Evaluation of a standardized CT colonography training program for novice readers.

PURPOSE To determine how many computed tomographic (CT) colonography training studies have to be evaluated by novice readers to obtain an adequate level of competence in polyp detection. MATERIALS AND METHODS The study was approved by the Institutional Review Board. Informed consent was obtained from all participants. Six physicians (one radiologist, three radiology residents, two researchers) and three technicians completed a CT colonography training program. Two hundred CT colonographic examinations with colonoscopic verification were selected from a research database, with 100 CT colonographic examinations with at least one polyp 6 mm or larger. After a lecture session and short individual hands-on training, CT colonography training was done individually with immediate feedback of colonoscopy outcome. Per-polyp sensitivity was calculated for four sets of 50 CT colonographic examinations for lesions 6 mm or larger. By using logistic regression analyses, the number of CT colonographic examinations to reach 90% sensitivity for lesions 6 mm or larger was estimated. Reading times were registered. RESULTS The average per-polyp sensitivity for lesions 6 mm or larger was 76% (207 of 270) in the first set of 50 CT colonographic examinations, 77% (262 of 342) in the second (P = .96 vs first set), 80% (310 of 387) in the third (P = .67 vs first set), and 91% (261 of 288) in the fourth (P = .018). The estimated number of CT colonographic examinations for a sufficient sensitivity was 164. Six of nine readers reached this level of competence within 175 CT colonographic examinations. Reading times decreased significantly from the first to the second set of 50 CT colonographic examinations for six readers. CONCLUSION Novice CT colonography readers obtained sensitivity equal to that of experienced readers after practicing on average 164 CT colonographic studies.

Reasons for participation and nonparticipation in colorectal cancer screening: a randomized trial of colonoscopy and CT colonography.

Objectives:We compared reported reasons for participation and nonparticipation in colorectal cancer (CRC) screening between colonoscopy and computed tomographic (CT) colonography in a randomized controlled trial.Methods:We randomly invited 8,844 people for screening by colonoscopy or CT colonography. On a questionnaire, invitees indicated reasons for participation or nonparticipation and indicated the most decisive reason.Results:The most frequently cited reasons to accept screening were early detection of precursor lesions and CRC, and contribution to science. The most frequently cited reasons to decline were the unpleasantness of the examination, the inconvenience of the preparation, a lack of symptoms, and “no time/too much effort.” Among colonoscopy nonparticipants, elderly invitees cited inconvenience less often, and absence of symptoms more often, than did the group overall. The reason reported most frequently as the most decisive reason not to participate was the unpleasantness of the examination among colonoscopy nonparticipants, and “no time/too much effort” and lack of symptoms among CT colonography nonparticipants.Conclusions:In light of these results, future screening programs could tailor the information provided to invitees.

Clinical indications for computed tomographic colonography: European Society of Gastrointestinal Endoscopy (ESGE) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) Guideline

This is an official guideline of the European Society of Gastrointestinal Endoscopy (ESGE) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR). It addresses the clinical indications for the use of computed tomographic colonography (CTC). A targeted literature search was performed to evaluate the evidence supporting the use of CTC. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations 1 ESGE/ESGAR recommend computed tomographic colonography (CTC) as the radiological examination of choice for the diagnosis of colorectal neoplasia. ESGE/ESGAR do not recommend barium enema in this setting (strong recommendation, high quality evidence). 2 ESGE/ESGAR recommend CTC, preferably the same or next day, if colonoscopy is incomplete. Delay of CTC should be considered following endoscopic resection. In the case of obstructing colorectal cancer, preoperative contrast-enhanced CTC may also allow location or staging of malignant lesions (strong recommendation, moderate quality evidence). 3 When endoscopy is contraindicated or not possible, ESGE/ESGAR recommend CTC as an acceptable and equally sensitive alternative for patients with symptoms suggestive of colorectal cancer (strong recommendation, high quality evidence). 4 ESGE/ESGAR recommend referral for endoscopic polypectomy in patients with at least one polyp  ≥  6  mm in diameter detected at CTC. CTC surveillance may be clinically considered if patients do not undergo polypectomy (strong recommendation, moderate quality evidence). 5 ESGE/ESGAR do not recommend CTC as a primary test for population screening or in individuals with a positive first-degree family history of colorectal cancer (CRC). However, it may be proposed as a CRC screening test on an individual basis providing the screenee is adequately informed about test characteristics, benefits, and risks (weak recommendation, moderate quality evidence).

Evolution of Screen-Detected Small (6-9 mm) Polyps After a 3-Year Surveillance Interval: Assessment of Growth With CT Colonography Compared With Histopathology

Objectives:Volumetric growth assessment has been proposed for predicting advanced histology at surveillance computed tomography (CT) colonography (CTC). We examined whether is it possible to predict which small (6–9 mm) polyps are likely to become advanced adenomas at surveillance by assessing volumetric growth.Methods:In an invitational population-based CTC screening trial, 93 participants were diagnosed with one or two 6–9 mm polyps as the largest lesion(s). They were offered a 3-year surveillance CTC. Participants in whom surveillance CTC showed lesion(s) of ≥6 mm were offered colonoscopy. Volumetric measurements were performed on index and surveillance CTC, and polyps were classified into growth categories according to ±30% volumetric change (>30% growth as progression, 30% growth to 30% decrease as stable, and >30% decrease as regression). Polyp growth was related to histopathology.Results:Between July 2012 and May 2014, 70 patients underwent surveillance CTC after a mean surveillance interval of 3.3 years (s.d. 0.3; range 3.0–4.6 years). In all, 33 (35%) of 95 polyps progressed, 36 (38%) remained stable, and 26 (27%) regressed, including an apparent resolution in 13 (14%) polyps. In 68 (83%) of the 82 polyps at surveillance, histopathology was obtained; 15 (47%) of 32 progressing polyps were advanced adenomas, 6 (21%) of 28 stable polyps, and none of the regressing polyps.Conclusions:The majority of 6–9 mm polyps will not progress to advanced neoplasia within 3 years. Those that do progress to advanced status can in particular be found among the lesions that increased in size on surveillance CTC.

Colon distension and scan protocol for CT-colonography: An overview

This article reviews two important aspects of CT-colonography, namely colonic distension and scan parameters. Adequate distension should be obtained to visualize the complete colonic lumen and optimal scan parameters should be used to prevent unnecessary radiation burden. For optimal distension, automatic carbon dioxide insufflation should be performed, preferably via a thin, flexible catheter. Hyoscine butylbromide is - when available - the preferred spasmolytic agent because of the positive effect on insufflation and pain/burden and its low costs. Scans in two positions are required for adequate distension and high polyp sensitivity and decubitus position may be used as an alternative for patients unable to lie in prone position. The great intrinsic contrast between air or tagging and polyps allows the use of low radiation dose. Low-dose protocol without intravenous contrast should be used when extracolonic findings are deemed unimportant. In patients suspected for colorectal cancer, normal abdominal CT scan protocols and intravenous contrast should be used in supine position for the evaluation of extracolonic findings. Dose reduction can be obtained by lowering the tube current and/or voltage. Tube current modulation reduces the radiation dose (except in obese patients), and should be used when available. Iterative reconstructions is a promising dose reducing tool and dual-energy CT is currently evaluated for its applications in CT-colonography. This review also provides our institutions insufflation procedure and scan parameters.

Comparing the Diagnostic Yields of Technologists and Radiologists in an Invitational Colorectal Cancer Screening Program Performed with CT Colonography

PURPOSE To compare the diagnostic yields of a radiologist and trained technologists in the detection of advanced neoplasia within a population-based computed tomographic (CT) colonography screening program. MATERIALS AND METHODS Ethical approval was obtained from the Dutch Health Council, and written informed consent was obtained from all participants. Nine hundred eighty-two participants (507 men, 475 women) underwent low-dose CT colonography after noncathartic bowel preparation (iodine tagging) between July 13, 2009, and January 21, 2011. Each scan was evaluated by one of three experienced radiologists (≥800 examinations) by using primary two-dimensional (2D) reading followed by secondary computer-aided detection (CAD) and by two of four trained technologists (≥200 examinations, with colonoscopic verification) by using primary 2D reading followed by three-dimensional analysis and CAD. Immediate colonoscopy was recommended for participants with lesions measuring at least 10 mm, and surveillance was recommended for participants with lesions measuring 6-9 mm. Consensus between technologists was achieved in case of discordant recommendations. Detection of advanced neoplasia (classified by a pathologist) was defined as a true-positive (TP) finding. Relative TP and false-positive (FP) fractions were calculated along with 95% confidence intervals (CIs). RESULTS Overall, 96 of the 982 participants were referred for colonoscopy and 104 were scheduled for surveillance. Sixty of 84 participants (71%) referred for colonoscopy by the radiologist had advanced neoplasia, compared with 55 of 64 participants (86%) referred by two technologists. Both the radiologist and technologists detected all colorectal cancers (n = 5). The relative TP fraction (for technologists vs radiologist) for advanced neoplasia was 0.92 (95% CI: 0.78, 1.07), and the relative FP fraction was 0.38 (95% CI: 0.21, 0.67). CONCLUSION Two technologists serving as a primary reader of CT colonographic images can achieve a comparable sensitivity to that of a radiologist for the detection of advanced neoplasia, with far fewer FP referrals for colonoscopy.