Incidental lesions found on CT colonography: their nature and frequency

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1 The British Journal of Radiology, 78 (2005), DOI: /bjr/ E 2005 The British Institute of Radiology Incidental lesions found on CT colonography: their nature and frequency 1 T XIONG, MCh, 1 M RICHARDSON, BSc (Hons), AMINA, 1 R WOODROFFE, MSc, 2 S HALLIGAN, MD, FRCOG, FRCR, 3 D MORTON and 1 R J LILFORD, PhD, FRCOG, FRCP 1 Department of Public Health and Epidemiology, Public Health Building, The University of Birmingham, Edgbaston, Birmingham B15 2TT, 2 Department of Intestinal Imaging, St. Mark s Hospital, Watford Road, Northwick Park, London HA1 3UJ and 3 Department of Surgery, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK Abstract. CT colonography has been used to detect colonic polyps and cancers, but its effect in practice will also be influenced by the frequency with which extracolonic lesions of various types are detected. We performed a systematic review of the types of incidental lesions found on CT colonography. This is necessary to model the benefits and harms of detecting extracolonic lesions. Primary clinical studies of extracolonic findings on CT colonography were identified from electronic databases, scanning reference lists and hand searches of relevant journals and conference proceedings. A data collection proforma was used to collect information on extracolonic findings. 17 discreet studies were identified, involving 3488 patients. In total 40% of patients were recorded to have abnormalities and many had more than one abnormality. Nearly 14% of patients had further investigations and 0.8% were given immediate treatment. Extracolonic cancers were detected in 2.7% (0.9% had N0M0 cancers) and 0.9% had an aortic aneurysm. The number of extracolonic findings was high in all studies. While only a small population were judged important, the prevalence of serious lesions outside the colon was nevertheless higher than in many other screening programs. Introduction CT colonography uses a combination of helical CT scanning and complex image rendering to image the large bowel and is able to produce images that simulate those seen on conventional video-endoscopy; hence the alternative term virtual colonoscopy [1, 2]. The sensitivity and specificity of this new health technology for neoplasia (i.e. cancers and polyps) is likely to be superior to the established imaging test, barium enema, and similar to video colonoscopy [2]. The results of studies, which have measured the accuracy of colonography by conducting both this test and colonoscopy sequentially on the same patients, have been reviewed elsewhere [1]. One of the intriguing features of colonography, however, is its ability to detect extracolonic lesions sometimes referred to as incidental findings, because the whole abdomen, pelvis and lower lung fields are imaged, as opposed to just the colorectum. These incidental findings have been classified according to their importance: i.e. highly important, possibly important and unimportant. An holistic assessment of the benefits and drawbacks of colonography as compared with other diagnostic and screening methods, must include an assessment of the benefits and harms which result from the detection of these lesions. In some cases, lives may be saved by detecting disease at a stage when it is still curable. In others, unnecessary procedures may be performed, with resultant complications, anxiety and use of resources. Received 21 April 2004 and accepted 19 August This study was sponsored by the Health Technology Assessment Programme of the Department of Health in England. The views are those of the authors. A rational assessment of the balance sheet, contingent on finding these incidental lesions, must begin with careful enumeration of the frequency and nature of such lesions. We therefore performed a systematic review of studies of incidental lesions found in the course of colonography carried out for the purposes of screening or diagnosis. Methods Identification of studies We included primary clinical studies of extracolonic and incidental findings on CT colonography. According to the guidance from the NHS Centre for Reviews and Dissemination [3], we identified studies by searching electronic databases, scanning reference list of papers and consulting experts in the specialty. No date or language limits were placed on the searches. We also hand searched selected journals. We found no other systematic reviews focusing on extracolonic lesions (see Appendix 1 for full search strategies). One reviewer (TX) examined titles, abstracts and keywords of citations, as given on electronic databases, and selected those which mentioned the concept of extracolonic lesions. Where possible the full text of all of potentially relevant citations was then obtained. All retrieved references were exported to Reference Manager v 10.0 (Thompson ResearchSoft, Thompson Corp., Berkley, CA). Data extraction and synthesis One reviewer (TX) decided whether studies met the inclusion criteria and this was checked by a second reviewer (MR). Using a standardized, piloted, data collection proforma, these 22 The British Journal of Radiology, January 2005

2 Incidental lesions found on CTC: their nature and frequency two reviewers independently extracted data from papers on extracolonic findings from CT colonography. We first collected methodological information: i.e. whether or not the population was clearly described; whether the author stated that consecutive cases were studied; whether the data collection was prospective or retrospective; and whether the investigations were carried out for diagnostic or screening purposes (Table 1). This process was carried out independently by two investigators (TX and MR) and any differences resolved in a three way meeting (TX, MR and RL). We then extracted the substantive data from each study. We recorded the total number of incidental lesions and the total number of patients who had an abnormality (since patients could have more than one lesion). The number of lesions classified as important by the author was noted. However, different authors had different thresholds for their classification and they tended to classify important in terms of the need for a clinical response (i.e. before further investigations had been carried out), rather than whether detection was likely to have been beneficial in retrospect (i.e. in the light of knowledge gleaned from further investigations). We therefore also recorded the incidence of two specific types of lesion where early detection may be life-saving: early (N0M0) cancer and abdominal aortic aneurysm. We also noted the number of further investigations performed and the number of patients who required immediate treatment. Lastly, we recorded the number of incidental lesions found in long-term follow-up, which had not been detected at the original colonography. We assembled data in three separate tables. First, data from full papers published in peer-reviewed articles dealing with patients given a bowel preparation were included in Table 2 (series 1). We assembled data collected from conference proceedings in Table 3 (series 2), on the grounds that these are generally less comprehensive and had been subject to less stringent quality control than the full articles. In some papers, although the focus was on primary CT diagnosis of colorectal cancers, full bowel preparation was not used since the population investigated was the frail elderly, in whom CT was being requested as an alternative to either barium enema (which has a high technical failure rate in this group) [16, 17] or video colonoscopy (which suffers from an increased rate of adverse events in this group) [6, 16, 17]. This might be expected to decrease sensitivity for colonic neoplasia. However, the incidence of extracolonic findings, might be expected to be increased in this group since they are older and clinical presentation is frequently non-specific. We therefore assembled data from these papers in Table 4 (series 3). Results 17 studies were identified from the above searches [4 20], including 13 full papers and four conference proceedings, of which only the abstracts were available. We then scrutinized the reference lists of relevant papers and detected one further reference [21]. However, the latter was also a conference proceeding, which was unobtainable through the library. We describe the features of the 18 studies on which reports could be retrieved in Table 1. Only six of the reports clearly stated that consecutive cases were studied. 14 were clearly prospective studies. Three of the studies dealt with colonography as a screening test, while 14 studied diagnostic colonographies. It was not possible to be clear on this issue in the remaining paper. Most of the studies were rather small: only three included more than 200 patients and one included as few as 37 patients. We discerned that two full papers [5, 11] emanated from the same centre the Mayo clinic. The most recent paper [5] did not make it clear whether or not the two series overlapped. We therefore contacted two of the authors, who confirmed that the first paper did indeed contaminate the second (we would like to thank Amy Hara and Joel Fletcher from the Mayo for their help in elucidating this issue). We excluded the earlier paper and did not include it in Table 2. Findings from full papers, excluding papers dealing specifically with the frail elderly, are given in Table 2. The mean age of patients included was the mid 60s in five studies, with slightly older and younger patients in the remaining studies. As expected, the mean age in papers Table 1. Description of papers Author Do they describe population clearly? Do they state consecutive cases? Was it prospective or retrospective study? Hellstrom M, et al, 2004 [20] Yes No Prospective Diagnostic Pickhardt PJ, et al, 2003 [13] Yes Yes Prospective Screening Ginnerup PB, et al, 2003 [12] Yes Yes Prospective Diagnostic Gluecker TM, et al, 2003 [5] Yes Yes Prospective Screening Munikrishnan V, et al, 2003 [4] Yes No Prospective Diagnostic Pineau BC, et al, 2003 [17] No No Prospective Diagnostic Robinson P, et al, 2002 [6] Yes Yes Retrospective Diagnostic Rajapaksa R, et al, 2002 [7] No No Prospective Diagnostic Hopper KD, et al, 2001 [21] No No?? Edwards JT, et al, 2001 [8] Yes No Retrospective Diagnostic Miao YM, et al, 2000 [14] Yes Yes Prospective Diagnostic Hara A, et al, 2003 [18] No No Prospective Diagnostic Hara AK, et al, 2002 [19] No No Prospective Diagnostic Hara AK, et al, 2000 [10] Yes Yes Retrospective Screening Dachman AH, et al, 1998 [9] No No Prospective Diagnostic Morrin MM, et al, 1999 [11] No No Prospective Diagnostic Domjan J, et al, 1998 [15] Yes No Prospective Diagnostic Day JJ, et al, 1993 [16] Yes No Prospective Diagnostic Were the cases screening or diagnostic tests? The British Journal of Radiology, January

3 24 The British Journal of Radiology, January 2005 Table 2. Extracolonic findings on CT colonography from primary papers (excluding diagnosis in the frail elderly) Author Full Number Age range text of patients (median) Contrast Abnormalities present Patients Total Important present a Confirmed cancers N0M0 b All the Aortic Further Immediate Important cancers b aneurysm b investigations treatment incidental lesions found in follow-up Author s Additional estimate of comments additional cost c Hellstrom M, et al, 2004 [20] Yes (66) No ? ?? Pickhardt PJ, et al, 2003 [13] Yes (57.8) No ? 2?? Ginnerup PB, et al, 2003 [12] Yes (61) No 49 68? ?? Nine patients needed further investigation but one refused Gluecker TM, et al, 2003 [5] Yes (64) No $ Average added costs per CT colonography Munikrishnan V, et al [4] Edwards JT, et al, 2001 [8] Miao YM, et al, 2000 [14] Morrin MM, et al, 1999 [11] Dachman AH, et al, 1998 [9] examination $34.33 Yes (68) Yes 25 25? 3 8 2??? $180 The estimated cost of a multislice CT colonography study was $180 Yes (65) No 15 15?? ?? The single cancer was an unconfirmed hypernephroma Yes (71) No 24 25? ???? Yes (62)? ???? Yes (58) Yes ?? 1? Two data points (the number of patients with an abnormality and the number of important abnormalities) were not included in the paper but were ascertained from another paper by the principal author (reference) in which the index paper was quoted a Important as defined by author. In many cases the diagnosis of important was prospective (i.e. potentially important, e.g. large ovary cyst), rather than retrospective (i.e. turned out to be important, e.g. ovarian carcinoma). These are total lesions found. b Total lesions include any that may have been detected previously by other means. The cancers include 12 liver metastases. c Total cost contingent on discovery of an incidental lesion. T Xiong, M Richardson, R Woodroffe et al

4 The British Journal of Radiology, January 2005 Table 3. Extracolonic findings on CT colonography from conference proceedings Author Pineau BC, et al, 2003 [17] Hara A, et al, 2003 d [18] Hara AK, et al, 2002 d [19] Rajapaksa R, et al, 2002 [7] Hopper KD, et al, 2001 [21] Full Number of Age range Contrast Abnormalities text patients (median) present Patients Total Important present a Confirmed cancers N0M0 b All the Aortic Further Immediate Important cancers b aneurysm b investigations treatment incidental lesions found in follow-up Author s Additional comments estimate of additional cost c No (60) No 162? 39??????? All patients had at least one extracolonic finding No 40? Yes? 65?? 6 3???? Prone images without IV contrast and supine images with IV contrast No 50? Yes? 16?? 2 1???? Prone images without IV contrast and supine images with IV contrast No 200?? ?? 0 5??? Two patients with liver lesions suspicious for metastases No 100?? 90? 10?? 1???? The data shown here were quoted from a reference to a conference proceeding a Important as defined by author. In many cases the diagnosis of important was prospective (i.e. potentially important, e.g. large ovary cyst), rather than retrospective (i.e. turned out to be important, e.g. ovarian carcinoma). These are total lesions found. b Total lesions include any that may have been detected previously by other means. c Total cost contingent on discovery of an incidental lesion. d We have sought clarification from the author about any possible contamination between these series, but have received no reply to date. IV, intravenous. Incidental lesions found on CTC: their nature and frequency 25

5 T Xiong, M Richardson, R Woodroffe et al dealing with the frail elderly (Table 4) was considerably higher. Contrast was used in five of all studies. The number of abnormalities was high in all three series. In total 40% (1314/3280) of patients were recorded to have abnormalities. The percentage of people with an abnormality was 36% (930/2565), 65% (316/483) and 29% (68/232) in the three series, respectively. The total number of abnormalities was even greater, since many patients had more than one abnormality. The total number of abnormalities as a proportion of people screened was 58% (1483/2565), 66% (190/290) and 26% (90/350), respectively, in the three series. These calculations are based on those authors who provided both the relevant numerator and denominator information (some studies did not record the total number of abnormalities only the number of patients with at least one abnormality). In addition some other papers did not give the number of patients with a diagnosis only the total number of incidental lesions found (see Tables 2 4). To sum up, extracolonic abnormalities are common, even when the frail elderly are excluded. Indeed, in six of the studies the total number of abnormalities found was greater than the number of patients entered. In a number of studies, authors graded the lesions according to their importance. The total number of important findings among 2787 patients was 292 (10.5%). As previously stated, they use different criteria to classify lesions as important and in all cases importance was based on clinical relevance in terms of the need for further investigations. For this reason, we also separately abstracted cases with relatively common serious diseases cancers and abdominal aortic aneurysms. When we did this, the proportion of lesions of confirmed importance was much smaller; a total of 2.7% (81/3005) had cancers and 0.9% (30/ 3305) had aortic aneurysms. Six studies recorded the size of aortic aneurysms. 16 aneurysms were detected in these studies; 3 (19%) were over 5.5 cm in size and the remainder were between 3 cm and 5.5 cm. A total of 0.9% (24/2549) patients had N0M0 cancers. Again, these calculations are based on those authors who provided both the relevant numerator and denominator information (see Tables 2 4). The number of further investigations carried out was also quite large in some case it even exceeded the number of lesions regarded as important by the author. A total of 13.8% (188/1362) of patients had further investigation. The incidence of immediate treatment was only given in six studies and averaged 0.8% (17/2237). Two studies gave the incidence of lesions found during long-term follow-up. Among these two studies the probability of finding yet a further lesion on long-term follow-up was 2.7% (3/110). Eight studies explicitly record the nature of early stage (N0M0) primary extracolonic cancers; Table 5 lists these cancers by their primary organ. Among a total of 2549 patients, 6 kidney cancers (0.24%), 5 ovarian cancers (0.20%), 5 lung cancers (0.20%), 4 pancreatic cancers (0.16%) and 1 liver cancer (0.04%) were found. These prevalence figures are all higher than the 25-year incidence figures recorded, for example, in the Surveillance, Epidemiology and End Results (SEER) database [25]. Discussion A number of points stand out clearly from this dataset. First, the total incidence of incidental lesions is high; at Table 4. Extracolonic findings on CT colonography in frail and elderly patients Additional comments Author s estimate of additional cost c Important incidental lesions found in follow-up Immediate treatment All the Aortic Further cancers b aneurysm b investigations Important Confirmed present a cancers N0M0 b Abnormalities present Intravenous contrast Age range (median) Number of patients Author Full text Patients Total Yes (76) No ??? Oral contrast was given Robinson P, et al, 2002 [6] Yes (84) No? 22?? 2 3???? Oral contrast was given Domjan J, et al, 1998 [15] Yes (80) Yes 14 14?? 4 0? 1?? Administrations of intravenous contrast were at the discretion of the radiologist, and the incidence of use is not given Day JJ, et al, 1993 [16] a Important as defined by author. In many cases the diagnosis of important was prospective (i.e. potentially important, e.g. large ovary cyst), rather than retrospective (i.e. turned out to be important, e.g. ovarian carcinoma). These are total lesions found. b Total lesions include any that may have been detected previously by other means. The cancers include four liver metastases. c Total cost contingent on discovery of an incidental lesion. 26 The British Journal of Radiology, January 2005

6 Incidental lesions found on CTC: their nature and frequency Table 5. Extracolonic early stage cancers found on CT colonography by organ of primary Pickhardt PJ, et al, 2003 [13] Gluecker TM, et al, 2003 [5] Munikrishnan V, et al, 2003 [4] Miao YM, et al, 2000 [14] Robinson P, et al, 2002 [6] Ginnerup PB, et al, 2003 [12] Morrin MM, et al, 1999 [11] Dachman AH, et al, 1998 [9] Number of patients Ovary Lymphoma 1 1 Lung Kidney Liver 1 1 Pancreas Choloangiocarcinoma 1 1 Bladder 1 1 All N0M0 cancers Total least 2015 incidental lesions were found in a total of 3488 patients (58%). Second, the number of lesions requiring further investigation was also rather high; 13.8% among the six studies where this information was given. Moving on to consider serious lesions, we confine our attention in the first instance to Table 2. The incidence of serious diseases was low, relative to the total number of lesions found; 0.8% of all patients needed immediate treatment and 3.7% had either cancer or an aortic aneurysm. Thus, although many lesions are deemed important, in terms of the need for investigation, the actual incidence of serious diseases detected by this diagnostic method is considerably lower. For example, the large study by Gluecker [5], including 681 consecutive cases, found 8 aneurysms and 4 cancers; an incidence of just under 2% for either type of lesion. Late cancers have a high mortality, but 0.4% of patients in Gluecker s series had a N0M0 cancer in this study. Across all studies where these data are recorded, 0.9% of patients had N0M0 cancers. This includes Table 4 elderly and frail patients and if these are excluded the percentage of these early lesions was 0.6% (15/2354). However, a detection rate for early cancer of about 6 per 1000 is significant in both clinical and epidemiological terms. For example, the prevalence of breast cancer in breast screening programmes is similar (range from 5.6 to 8.5 per 1000 women) [22], and the prevalence of ovarian cancer in ovarian cancer screening programmes is very much lower (about 1 per 2000 women) [23]. Indeed, the prevalence of early colorectal cancer detected by this modality in screening studies is of similar magnitude (0.7% had N0M0 bowel cancer) [24]. It therefore transpires that colonography may be an important method for the detection of early cancers other than colon cancers, although we recognize that this modality also detects colonic lesions in their premalignant phase (i.e. colonic adenomas). Nearly half (42%) of cancers detected were of an early stage N0M0. Detection of lesions at this stage is, of course, most likely to result in health gains. From these data we therefore tentatively suggest that CT colonography, even without the use of contrast, may be an important potential modality, net of its effect on detecting colonic lesions. That said, it is important not to extrapolate the potential benefits of detecting early lesions uncritically from the prognoses of such lesions detected in normal clinical practice. This is because the prognoses of lesions detected in early stage may differ systematically according to method of detection. A crucial concept that relates to the effects of detecting early lesions is sojourn time. The fact that the prevalence was higher than the 25-year incidence implies quite long sojourn times and suggests that only once or infrequent screening may be effective in reducing eventual mortality. However, very long sojourn times suggest that the number of years of life gained might be quite modest and some lesions may never progress; at the limit, this must be the case where prevalence exceeds lifetime incidence. Future modelling will have to make assumptions about these variables and incorporate further information that will eventually be obtained, for example from the US Prostate, Lung, Colorectal and Ovarian (PLCO) screening study [26]. We also observe that this is early days for this form of diagnosis or screening. The publications which we cite are often based on incomplete data sets. For example, in many cases they do not clearly indicate that consecutive cases were studied. Nevertheless, some of the papers (such as that of Gluecker and colleagues) are of high quality [5]. The data from Gluecker study are very much in line with those from the other studies in Table 2. However, we will be the first to argue that bigger and more comprehensive datasets are required. Lastly, practically all of the studies used symptomatic patients rather than those with a population risk for colorectal cancer. It is therefore possible that the condition that prompted the investigation, was extracolonic (especially in the frail elderly group). If so, the common finding of such lesions would add further weight to arguments for the use of this method for diagnosis, but it would also suggest that lower utility would result from detection of extracolonic lesions in a screening program. However, we think that the incidental lesions revealed by this modality would generally have been silent, i.e. they are truly incidental, except for the frail elderly and we analysed this group separately for this reason. If we are right, the possibility of finding serious lesions outside the colon should be added to the colon related benefits of this screening modality, although the model would need to include the costs of investigations and interventions prompted by the method. These costs would have to be broadly defined to include the anxiety and other morbidity associated with investigation of incidental lesions. References 1. Dachman AH. Diagnostic performance of virtual colonoscopy. Abdom Imaging 2002;27: Fenlon HM, Nunes DP, Schroy PC 3rd, Barish MA, Clarke PD, Ferrucci JT. A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps. N Engl J Med 1999;341: The British Journal of Radiology, January

7 T Xiong, M Richardson, R Woodroffe et al 3. NHS CRD. Undertaking systematic reviews of research on effectiveness: CRD s guidance for those carrying out or commissioning reviews. CRD report number 4 (2nd edn). NHS Centre for Reviews and Dissemination, University of York, Munikrishnan V, Gillams AR, Lees WR, Vaizey CJ, Boulos PB. Prospective study comparing multislice CT colonography with colonoscopy in the detection of colorectal cancer and polyps. Dis Colon Rectum 2003;46: Gluecker TM, Johnson CD, Wilson LA, Maccarty RL, Welch TJ, Vanness DJ, et al. Extracolonic findings at CT colonography: evaluation of prevalence and cost in a screening population. Gastroenterology 2003;124: Robinson P, Burnett H, Nicholson DA. The use of minimal preparation computed tomography for the primary investigation of colon cancer in frail or elderly patients. Clin Radiol 2002;57: Rajapaksa R, Macari M, Bini EJ. Prevalence and impact of extracolonic findings in patients undergoing CT colonography. Am J Gastroenterol 2002;97(Suppl. 1):S Edwards JT, Wood CJ, Mendelson RM, Forbes GM. Extracolonic findings at virtual colonoscopy: implications for screening programs. Am J Gastroenterol 2001;96: Dachman AH, Kuniyoshi JK, Boyle CM, Samara Y, Hoffmann KR, Rubin DT, et al. CT colonography with three-dimensional problem solving for detection of colonic polyps. AJR Am J Roentgenol 1998;171: Hara AK, Johnson CD, Maccarty RL, Welch TJ. Incidental extracolonic findings at CT colonography. Radiology 2000;215: Morrin MM, Kruskal JB, Farrell RJ, Goldberg SN, McGee JB, Raptopoulos V. Endoluminal CT colonography after an incomplete endoscopic colonoscopy. AJR Am J Roentgenol 1999;172: Ginnerup PB, Rosenkilde M, Christiansen TE, Laurberg S. Extracolonic findings at computed tomography colonography are a challenge. Gut 2003;52: Pickhardt PJ, Choi JR, Hwang I, Butler JA, Puckett ML, Hildebrandt HA, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003;349: Miao YM, Amin Z, Healy J, Burn P, Murugan N, Westaby D, et al. A prospective single centre study comparing computed tomography pneumocolon against colonoscopy in the detection of colorectal neoplasms. Gut 2000;47: Domjan J, Blaquiere R, Odurny A. Is minimal preparation computed tomography comparable with barium enema in elderly patients with colonic symptoms? Clin Radiol 1998;53: Day JJ, Freeman AH, Coni NK, Dixon AK. Barium enema or computed tomography for the frail elderly patient? Clin Radiol 1993;48: Pineau BC, Manus S, Phillips K, Chen GJ, Mikulaninec C, Han P, et al. Prevalence of extracolonic findings at virtual colonoscopy. Am J Gastroenterol 2003;98(Suppl. 1):S Hara A, Leighton JA, Sharma V, Heigh RI. CT colonography with IV contrast: colon polyp enhancement and improved evaluation of extracolonic findings. 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Appendix 1: Search strategy for electronic databases and hand search run in March 2004 Pubmed N Text terms used and the corresponding number of papers retrieved: Search Terms Result #1 Colonography 350 #2 Virtual colonoscopy 322 #3 Colography 19 #4 CT colonoscopy 723 #5 Virtual endoscopy 713 #6 CT pneumocolon 10 #7 CT OR computed tomography OR computerized tomography #8 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 #9 Extracolonic findings 288 #10 #8 AND #9 35 #11 Extracolonic lesions 82 #12 #8 AND #11 14 #13 Incidental findings 824 #14 Colon OR colonic OR colorectal #15 #8 AND #13 AND #14 6 #16 Incidental lesions 926 #17 #8 AND #14 AND #16 9 N We obtained in total 64 papers from searches in Pubmed. We then removed the duplicate titles from each search, which resulted in the retrieval of 43 different papers. Other electronic databases searched N We also repeated the searches in the following databases: Databases ISI Web of Knowledge 23 EMBASE 9 OVID 10 ScienceDirect 9 Cochrane database 0 Result 28 The British Journal of Radiology, January 2005

8 Incidental lesions found on CTC: their nature and frequency N Six papers overlapped across the four databases, providing a yield of 36 papers from these searches. Hand searched following relevant journals Gastroenterology. Diseases of the Colon and Rectum. The American Journal of Gastroenterology. Radiology. British Journal of Radiology. European Journal of Radiology. European Radiology. (from January 2003 to February 2004). Conference proceedings handsearched N Boston Medical Center. Proceedings of the Fourth International Symposium of Virtual Colonoscopy, Boston, USA October N American College of Gastroenterology. Proceedings of the 68th Annual Scientific Meeting of the American College of Gastroenterology, Baltimore, USA October N American College of Gastroenterology. Proceedings of the 67th Annual Scientific Meeting of the American College of Gastroenterology, Washington, USA October N ASCRS. Proceedings of the meeting of the American- Society-of-Colon-and-Rectal-Surgeons, New Orleans, LO, USA June N ASCRS. Proceedings of the meeting of the American- Society-of-Colon-and-Rectal-Surgeons, Chicago, IL, USA June N AGA. Digestive Disease Week 2003 Meeting. Proceedings of the 104th Annual Meeting of the American-Gastroenterological-Association. Orlando, FL, USA May N AGA. Proceedings of the Annual Meeting of the American-Gastroenterological-Association. San Francisco, CA, USA May N AGA. Digestive Disease Week 2001 Meeting. Proceedings of the 102nd Annual Meeting of the American-Gastroenterological-Association. Atlanta, GA, USA May N RSNA. Proceedings of the 89th Scientific Assembly and Annual Meeting of the Radiological-Society-of- North-America. Chicago, IL, USA. 30 November 05 December N RSNA. Proceedings of the 88th Scientific Assembly and Annual Meeting of the Radiological-Society-of- North-America. Chicago, IL, USA December N RSNA. Proceedings of the 87th Scientific Assembly and Annual Meeting of the Radiological-Society-of- North-America. Chicago, IL, USA November N RSNA. Proceedings of the 86th Scientific Assembly and Annual Meeting of the Radiological-Society-of- North-America. Chicago, IL, USA. 26 November 01 December N European Congress of Radiology. ECR 2003 Conference, Vienna, Austria, Mar N ECR. Proceedings of the 14th Annual Meeting of the European Congress of Radiology. Vienna, Austria March N ECR. Proceedings of the 13th Annual Meeting of the European Congress of Radiology. Vienna, Austria March The British Journal of Radiology, January