colorectal cancer ( crc ) is the second cause of cancer - related death   and generally results from the transformation of clinically silent adenomas   that are sought by screening tests . persistence or sudden occurrence of various abdominal symptoms is often considered an indication to search or rule out colonic abnormalities , including crc or precancerous polyps . literature suggests that the use of optical colonoscopy ( oc ) is warranted only for subjects with rectal bleeding and unexplained weight loss , whereas the other symptoms specificity remain questionable , , . meanwhile , the current diagnosis guidelines for individuals with average - risk for crc only apply if there is no gastrointestinal symptom or complain , raising potentially important concerns . indeed , as long as all symptoms are considered equivalent in terms of diagnostic yield , individuals with nonspecific gastrointestinal symptoms are evaluated , when needed , by oc , causing potential congestion of the facilities by low resection - rate procedures , , . second , patient compliance to current crc screening guidelines is low . almost 50% of asymptomatic subjects 50 years of age and older escape screening programs over a period of 10 years , while subjects with nonspecific gastrointestinal symptoms agree to undergo colonic explorations , for reassurance in a greater percentage . computed tomography ( ct ) colonography ( ctc ) has emerged over the past decade as an accurate and less invasive alternative to oc in series of symptomatic patients , . similarly good results were obtained in series of asymptomatic subjects . to our knowledge , there are little data evaluating the test - positive rate according to gastrointestinal symptoms at ctc in the literature . we therefore evaluate in this study , the distribution of clinically significant colonic findings and extra - colonic at ctc , according to symptoms and age through a review of a 7-year experience in a single non - academic center . our institutional review board approved the study and authorized this retrospective patient data analysis without further consent . we searched our hospital records for all subjects who completed a ctc procedure between june 2003 and august 2010 . this search yielded 9122 subjects ( 3822 males , 5300 females , average age : 60.11    13.75 years , range : 1896 years ) . indications for ctc included screening and direct referral ( n  =  8573 ) , secondary referral after incomplete oc ( n  =  285 ) , and double contrast barium enema ( dcbe ) referral change ( n  =  264 ) . this referral change was justified by the non - superiority of dcbe over ctc for colonic lesions in several studies , . written informed consent was given by all subjects prior to procedures . 1761 subjects with a familial or personal history of polyps or colorectal cancer , genetic conditions , inflammatory bowel disease , who were at increased- or high - risk for colorectal cancer   were excluded . the remaining 7361 subjects , with average - risk   for crc ( general population ) ( 3073 males , 4288 females , average age : 60.3    13.9 years , range 1896 years ) were evaluated . their clinical status with regard to the presence of the following gastrointestinal symptoms , prior to ctc was retrieved from the referral forms and/or gathered by patient 's anamnesis and all other available patient data , including : ( i ) abdominal pain , ( ii ) constipation , ( iii ) diarrhea , ( iv ) irregular bowel movement , ( v ) bloating , ( vi ) melena , ( vii ) rectal bleeding , and ( viii ) unexplained weight loss . we retrospectively assigned the subjects to three main groups , according to the purported clinical importance of these symptoms regarding the level of specificity for crc : group a included the asymptomatic subjects ; group b , the patients with one or more nonspecific symptom(s ) ( i  vii ) in the absence of an established  alarm  symptom ( vii and viii ) , who were assigned to group c. all patients underwent the same standardized procedure that consisted into three steps including patient preparation , scanning and data interpretation . the preparation involved two steps including cathartic colonic cleansing and residual fluid tagging . for patients in good general condition , colonic cleansing was achieved by a one - day clear liquid diet , one bottle of sodium phosphate preparation ( fleet - phospho - soda , wolfs , zwijndrecht , belgium ) and 4 tablets of bisacodyl ( dulcolax , boehringer ingelheim , ingelheim , germany ) . for frail patients , cleansing consisted into 2 days of low - residue diet combined to 8  g of magnesium sulphate on the examination day 's morning , in addition to 2 tablets of bisacodyl and 100  ml of contrast agent ( gastrografin , schering ag , berlin , germany ) twice a day . in patients with renal insufficiency , cardiac failure or severe hypertension , preparation consisted in 3 days of low - residue diet with 2l of moviprep ( norgine , heverlee , belgium ) ( propylene - glycol  +  ascorbic acid ) and 4 tablets of bisacodyl the day before the study . residual fluid tagging was obtained by ingestion of 100  ml gastrografin the evening before the procedure and total colonic residual fluid volume was reduced by using a suppository of bisacodyl approximately 2  h before examination , except for patients who underwent ctc after incomplete oc . these patients drank 100  ml of gastrografin and inserted a suppository of bisacodyl 1  h before the procedure . before data acquisition , an iv injection of 20  mg/1  ml of buscopan ( butylhyoscinbromid  boehringer ingelheim , bruxelles , belgium ) was performed and a rectal cannula was inserted for colonic distension with an automatic carbon dioxide insufflator vmx-1010a ( vimap technologies , girona , spain ) . a 32-row ( ge lightspeed vct , ge healthcare , milwaukee , wi ) until 09/2010 , then a 64-row ( ge discovery ct750 hd , ge healthcare , milwaukee , wi ) multislice scanners were used for image acquisitions . parameters consisted into 1.2  mm - thick slices with a 0.625  mm reconstruction interval , using a 50  ma  s low - dose protocols with variable kv , adjusted to body - density for dose reduction , supplemented since 2010 by an adaptive statistical iterative reconstruction algorithm ( asir ) ( ge healthcare , milwaukee , wi ) . two acquisitions were performed : the first in supine position and the second , either in prone position , or right decubitus for unfit and obese patients . immediate review of the images was performed by a radiologist in all cases . in 897 patients ( 10% ) , a third acquisition was ordered because of a segmental collapse preventing confident analysis . reading was performed offline on a workstation ( advantage windows , ge healthcare , milwaukee , wi ) with a software ( colon vcar ) allowing filet - view , supplemented by  computer aided diagnosis reconstruction algorithms , image display preferences and reading principles used for interpretation are described elsewhere . each finding was assigned to both a colonic segment and a distance to the anal margin . clinically significant colonic findings were defined as either 6  mm polyps , masses or others requiring work - up or treatment . clinical files , and reports were searched for repeat ctc , oc and surgical procedures after the initial ctc , when applicable . a reviewer was requested to match ctc and the reference standard findings , using available location by segment , and/or distance from the anal margin . we did not attempt to match using the size criteria because of known size discrepancies between oc and ctc polyp measurement . using an  intention to treat algorithm , per - patient ctc diagnostic values for the diagnosis of clinically significant colonic findings were calculated . patients with at least one matched finding were considered true - positive while patients with ctc findings unmatching the reference standard were considered as false - positive . those with no finding at ctc and at least one positive finding on the reference standards were considered false - negative . for patients with several colonic findings , two clinicians having access to all available data were requested to determine in consensus , the most significant with regard to crc . for example , an individual with both a > 6  mm colonic polyp and a non - neoplastic colonic mass accounted , for only the first . in addition , they were requested to establish a potential correspondence between the clinical symptoms and ctc colonic and significant extra - colonic findings ( i.e. : e4 grade of the ctc reporting and data system , unrelated to a colonic disease ) . continuous variables are compared using analysis of variance , and two - tailed t - tests are used for direct comparison between two groups . we used a regression analysis to evaluate the impact of the group of symptoms , age and gender on the test - positive rate . our institutional review board approved the study and authorized this retrospective patient data analysis without further consent . we searched our hospital records for all subjects who completed a ctc procedure between june 2003 and august 2010 . this search yielded 9122 subjects ( 3822 males , 5300 females , average age : 60.11    13.75 years , range : 1896 years ) . indications for ctc included screening and direct referral ( n  =  8573 ) , secondary referral after incomplete oc ( n  =  285 ) , and double contrast barium enema ( dcbe ) referral change ( n  =  264 ) . this referral change was justified by the non - superiority of dcbe over ctc for colonic lesions in several studies , . written informed consent was given by all subjects prior to procedures . 1761 subjects with a familial or personal history of polyps or colorectal cancer , genetic conditions , inflammatory bowel disease , who were at increased- or high - risk for colorectal cancer   were excluded . the remaining 7361 subjects , with average - risk   for crc ( general population ) ( 3073 males , 4288 females , average age : 60.3    13.9 years , range 1896 years ) were evaluated . their clinical status with regard to the presence of the following gastrointestinal symptoms , prior to ctc was retrieved from the referral forms and/or gathered by patient 's anamnesis and all other available patient data , including : ( i ) abdominal pain , ( ii ) constipation , ( iii ) diarrhea , ( iv ) irregular bowel movement , ( v ) bloating , ( vi ) melena , ( vii ) rectal bleeding , and ( viii ) unexplained weight loss . we retrospectively assigned the subjects to three main groups , according to the purported clinical importance of these symptoms regarding the level of specificity for crc : group a included the asymptomatic subjects ; group b , the patients with one or more nonspecific symptom(s ) ( i  vii ) in the absence of an established  alarm  symptom ( vii and viii ) , who were assigned to group c. all patients underwent the same standardized procedure that consisted into three steps including patient preparation , scanning and data interpretation . the preparation involved two steps including cathartic colonic cleansing and residual fluid tagging . for patients in good general condition , colonic cleansing was achieved by a one - day clear liquid diet , one bottle of sodium phosphate preparation ( fleet - phospho - soda , wolfs , zwijndrecht , belgium ) and 4 tablets of bisacodyl ( dulcolax , boehringer ingelheim , ingelheim , germany ) . for frail patients , cleansing consisted into 2 days of low - residue diet combined to 8  g of magnesium sulphate on the examination day 's morning , in addition to 2 tablets of bisacodyl and 100  ml of contrast agent ( gastrografin , schering ag , berlin , germany ) twice a day . in patients with renal insufficiency , cardiac failure or severe hypertension , preparation consisted in 3 days of low - residue diet with 2l of moviprep ( norgine , heverlee , belgium ) ( propylene - glycol  +  ascorbic acid ) and 4 tablets of bisacodyl the day before the study . residual fluid tagging was obtained by ingestion of 100  ml gastrografin the evening before the procedure and total colonic residual fluid volume was reduced by using a suppository of bisacodyl approximately 2  h before examination , except for patients who underwent ctc after incomplete oc . these patients drank 100  ml of gastrografin and inserted a suppository of bisacodyl 1  h before the procedure . before data acquisition , an iv injection of 20  mg/1  ml of buscopan ( butylhyoscinbromid  boehringer ingelheim , bruxelles , belgium ) was performed and a rectal cannula was inserted for colonic distension with an automatic carbon dioxide insufflator vmx-1010a ( vimap technologies , girona , spain ) . a 32-row ( ge lightspeed vct , ge healthcare , milwaukee , wi ) until 09/2010 , then a 64-row ( ge discovery ct750 hd , ge healthcare , milwaukee , wi ) multislice scanners were used for image acquisitions . parameters consisted into 1.2  mm - thick slices with a 0.625  mm reconstruction interval , using a 50  ma  s low - dose protocols with variable kv , adjusted to body - density for dose reduction , supplemented since 2010 by an adaptive statistical iterative reconstruction algorithm ( asir ) ( ge healthcare , milwaukee , wi ) . two acquisitions were performed : the first in supine position and the second , either in prone position , or right decubitus for unfit and obese patients . immediate review of the images was performed by a radiologist in all cases . in 897 patients ( 10% ) , a third acquisition was ordered because of a segmental collapse preventing confident analysis . reading was performed offline on a workstation ( advantage windows , ge healthcare , milwaukee , wi ) with a software ( colon vcar ) allowing filet - view , supplemented by  computer aided diagnosis  ( cad ) assistance from january 2009 , and electronic cleansing from june 2010 . reconstruction algorithms , image display preferences and reading principles used for interpretation are described elsewhere . each finding was assigned to both a colonic segment and a distance to the anal margin . clinically significant colonic findings were defined as either 6  mm polyps , masses or others requiring work - up or treatment . clinical files , and reports were searched for repeat ctc , oc and surgical procedures after the initial ctc , when applicable . a reviewer was requested to match ctc and the reference standard findings , using available location by segment , and/or distance from the anal margin . we did not attempt to match using the size criteria because of known size discrepancies between oc and ctc polyp measurement . using an  intention to treat algorithm , per - patient ctc diagnostic values for the diagnosis of clinically significant colonic findings were calculated . patients with at least one matched finding were considered true - positive while patients with ctc findings unmatching the reference standard were considered as false - positive . those with no finding at ctc and at least one positive finding on the reference standards were considered false - negative . for patients with several colonic findings , two clinicians having access to all available data were requested to determine in consensus , the most significant with regard to crc . for example , an individual with both a > 6  mm colonic polyp and a non - neoplastic colonic mass accounted , for only the first . in addition , they were requested to establish a potential correspondence between the clinical symptoms and ctc colonic and significant extra - colonic findings ( i.e. : e4 grade of the ctc reporting and data system , unrelated to a colonic disease ) . continuous variables are compared using analysis of variance , and two - tailed t - tests are used for direct comparison between two groups . we used a regression analysis to evaluate the impact of the group of symptoms , age and gender on the test - positive rate . 903 out of the 7361 ( 12% , 95%ci 1113% ) subjects had at least one clinically significant colonic finding at ctc . histopathological diagnoses and/or etiology for the confirmed findings are given in table 1 , showing that the abnormalities were most commonly of mucosal origin . comparison of ctc to oc and/or surgery was possible for 692/903 ( 77% ; 95%ci 0.0740.79 ) of these subjects . in addition , repeat ctc , oc and/or surgery was performed within a range of 660 months in 1198 subjects with negative ctc findings for the following reasons : 656 patients underwent oc including programmed screening tests in 168 , exacerbation of a non - alarm  gastrointestinal symptom or occurrence of a new symptom in 443 , and occurrence of an  alarm  symptom in 48 . 527 patients underwent a second ctc including programmed screening tests in 287 , new or exacerbated  non alarm symptoms in 216 and  alarm symptoms  in 24 . five patients were false - negative ( 2 with > 6  mm polyps and 3 with cancers ) . all controlled cases , yield a 637/642 ( 99.2% , 95%ci 0.980.99 ) true - positive fraction and a 55/692 ( 7.95% , 95%ci 0.050.09 ) false - positive fraction . the average number of symptoms per patient was 1.54    0.35 ( 3800 , 1524 , 662 , 29 and 3 patients had respectively 1 , 2 , 3 , 4 and 5 symptoms ) . abdominal pain and constipation were the most frequent , while unexplained weight loss was the least frequent symptom . groups a , b and c included respectively 1343 , 5329 and 689 patients ; their demographic characteristics are given in table 2 . the average age in group c ( 64.37    14.61 years ) was significantly higher than in both groups a ( 60.96    11.22 years ) and b ( 59.43    14.31 years ) ( p  <  0.001 ) . the male / female ratio was lower in group b ( 0.63 ) versus group a ( 1.03 ) ( p  <  0.001 ) . the rate of e4 findings in the c - rad reporting system was significantly higher in group c ( 44/689 , 6.4% , 95%ci 0.040.08 ) versus groups a ( 26/1343 , 1.9% , 95%ci 0.010.03 ) and b ( 64/5329 , 1.2% , 95%ci 0.010.02 ) ( p  <  0.001 ) . the regression analysis showed that the group of symptom ( b  <  c ) , gender ( f  <  m ) and age all significantly impacted the test - positive rate at ctc . when pooling patients by age groups ( table 3 ) , the test - positive rate in group c ( 138/689 , 20.0% , 95%ci 0.170.23 ) was significantly higher than in groups a ( 79/1343 , 5.8% , 95%ci 0.040.07 ) and b ( 420/5329 , 7.8% , 95%ci 0.070.08 ) ( p  <  0.001 ) , then , across all ages , except for patients younger than 50 years of age whose test - positive rate in groups c , a and b were respectively ( 6/96 , 6.25% , 95%ci 0.010.11 ) , ( 5/173 , 2.9% , 95%ci 0.000.05 ) and ( 47/1241 , 3.8% , 95%ci 0.020.04 ) ( p  =  0.412 ) . both the true - positive fraction that was consistently above 97% in all groups ( p  =  0.991 ) and the false - positive fraction did no differ among all groups ( p  =  0.240 ) . in a recent meta - analysis evaluating the value of various symptoms for crc in primary care , jellema et al . found large heterogeneities in the sensitivity and specificity of most symptoms . rectal bleeding and unexplained weight loss have consistently higher specificity than the others , according to another recent meta - analysis . similarly to studies using oc , the test - positive rate at ctc in our study was higher in patients with these  alarm  symptoms than in asymptomatic subjects and those with minor gastrointestinal symptoms ( p  <  0.05 ) . although the average age was also significantly higher in the  alarm  symptoms group ( p  <  0.05 ) , age was not a key determinant , since similar differences were observed in all age groups above 50 years . in terms of crc diagnostic recommendations , a test - positive rate around 20% makes oc the procedure of choice in patients with  alarm an exception to this rule , though requiring stronger evidence , may be patients aged less than 50 years . their findings prevalence was 6/96 ( 6.25% ; 95%ci 0.010.11 ) , i.e. : higher than in age - matched patients , but comparable to the overall prevalence in the other groups . due to the low specificity of the remaining gastrointestinal symptoms ( alone or in combination ) , diagnostic recommendations currently fails to avoid oc facilities congestion by procedures yielding low rates of resection , , , , . exception made of melena and hemorrhoids , the  non - alarm  symptoms evaluated in this study are commonly described in patients with irritable bowel syndrome ( ibs ) which is a functional bowel disorder affecting 715% of the general population in the usa , women being twice more often afflicted than men , . its diagnosis nicely illustrates the dichotomy between the daily management of gastrointestinal symptoms and evidence - based diagnostic recommendations . indeed , the diagnosis of ibs is based exclusively on clinical criteria , but , up to 75% of clinicians believe that it should be ascertained by exclusion of organic disease . for this purpose , approximately half of the patients with known or suspected ibs have undergone at least one diagnostic oc procedure . lastly , it has been estimated that 25% of the oc procedures performed in the usa are for patients with  non - alarm  gastrointestinal symptoms , although the actual risk of crc in these patients is not higher than in asymptomatic individuals in several studies reporting very close ranges of test - positive rate at oc among ibs ( range 1.99.3% ) and asymptomatic individuals ( range 4.512.1% ) , . several reasons could be advocated for this dichotomy , including physicians and patient 's anxiety , symptoms severity and the lack of evidence that other diagnostic procedures may be as accurate or cost - effective than oc . to our knowledge , our study is the first evaluating colonic findings according to gastrointestinal symptoms using ctc . this was possible as , since 2002 , ctc has progressively become a routine procedure in our institution , acknowledged both by our gastroenterologists , general practitioners and patients . non - alarm  symptoms were low and comparable to those reported using oc . in both groups , the test - positive rate increased roughly linearly with aging ( p  <  0.05 ) . non - alarm  symptoms may indeed benefit from accurate noninvasive diagnostic procedures . in our series of 5329 patients with non - alarm  symptoms , 4088 were older than 50 years of age : it may thus be emphasized that these symptoms were an incentive to comply with screening guidelines and should therefore be carefully sought . although patients under 50 years of age and suspected of ibs should not undergo any colonic exploration , many of them unfortunately do in most institutions , including ours . in our series , this malpractice applies to 1241 patients ( 23% referred by gastroenterologists ) for whom ctc has a low test - positive rate in good correlation with other series , but represent the most comprehensive and the less harmful option as compared to oc , the standard of reference . in this setting , our study confirmed that ctc has a high true - positive fraction and a low false - positive fraction for polyps and crc in all groups ,   clearly advocating for its recommendation in patients with , the main disadvantage of ctc , namely the inability to perform polypectomy , may raise cost - effectiveness issues . in our study , at least 420 additional oc were performed in the group of patients with non - alarm  symptoms , while approximately 5000 potential diagnostic oc procedures were replaced by less expensive ctc procedures , putting obviously the cost - effectiveness balance in favor of a primary diagnostic procedure by ctc in our institution . in addition , offering a same - day oc after positive ctc scenario currently prevent the need for a second bowel preparation in most institutions including ours . the ability to detect clinically significant extra - colonic abnormalities ( e4 ) may also impact ctc cost - effectiveness . a total number of 134 individuals had e4 findings , which represent an asset for ctc . interestingly , the rate of e4 findings distribution per group was quite similar to the test - positive rate distribution , prevailing thus in older patients . lastly , the concern of exposure to ionizing radiation during ctc , has dropped significantly with the latest generation of scanners . in our institution , the combined dose for supine and prone acquisitions of an average - sized subject is approximately 3  msv ( i.e. : levels comparable to the annual environmental scatter doses ) . some limitations may be applied to this study and its conclusions , the first of which is its retrospective nature that resulted into several patients lost to follow - up and clinical data missing . histopathological data were also missing in several patient from mis - retrieved polypectomies that are , however , not uncommon . the same design forced us to pool symptoms in two groups , resulting into potential masking of the effect of one or several underrepresented individual symptom(s ) on the ctc test - positive rate . moreover , age of symptoms onset , their intensity and duration lacked , preventing a better detailed relationship between symptoms and test - positive rate . reported diagnostic values of ctc , though comparable with previously reported studies , are subject to verification bias , since oc was mostly performed when ctc was positive . in addition , most of the unverified ctc positive cases were small polyps , which probably decreased artificially the false - positive rate . lastly , patients with at least one gastrointestinal symptom largely outnumbered asymptomatic subjects in our study , with 6929 out of the 7361 average - risk subjects for crc having at least one symptom . this selection bias was caused by a progressive referral replacement of dcbe by ctc during the study period . non - alarm  gastrointestinal symptoms and even young patients with  alarm  symptoms for crc have nearly similarly low test - positive rates at ctc . overall , the rate of colonic and extra - colonic findings increased with age , male gender and the presence of  alarm  symptoms for crc . the high diagnostic value of ctc in all patient groups makes it the examination of choice in low - yield patients ; who include asymptomatic subjects and those with
purposewe evaluated the rate of significant colonic and extra - colonic abnormalities at computed tomography colonography ( ctc ) , according to symptoms and age.materials and methodswe retrospectively evaluated 7361 consecutive average - risk subjects ( 3073 males , average age : 60.3    13.9 ; range 1896 years ) for colorectal cancer ( crc ) who underwent ctc . 
 they were divided into three groups according to clinical symptoms : 1343 asymptomatic individuals ( group a ) , 899 patients with at least one  alarm  symptom for crc , including rectal bleeding and unexplained weight loss ( group c ) , and 5119 subjects with other gastrointestinal symptoms ( group b ) . 
 diagnostic and test - positive rates of ctc were established using optical colonoscopy ( oc ) and/or surgery as reference standard . 
 in addition , clinically significant extra - colonic findings were noted.results903 out of 7361 ( 12% , 95% confidence interval ( ci ) 0.110.13 ) subjects had at least one clinically significant colonic finding at ctc . 
 ctc true positive fraction and false positive fraction were respectively 637/642 ( 99.2% , 95%ci 0.980.99 ) and 55/692 ( 7.95% , 95%ci 0.050.09 ) . 
 the pooled test - positive rate in group c ( 138/689 , 20.0% , 95%ci 0.170.23 ) was significantly higher than in both groups a ( 79/1343 , 5.9% , 95%ci 0.040.07 ) and b ( 420/5329 , 7.5% , 95%ci 0.070.08 ) ( p  <  0.001 ) . 
 aging and male gender were associated to a higher test positive rate . the rate of clinically significant extra - colonic findings was significantly higher in group c ( 44/689 , 6.4% , 95%ci 0.040.08 ) versus groups a ( 26/1343 , 1.9% , 95%ci 0.010.02 ) and b ( 64/5329 , 1.2% , 95%ci 0.010.02 ) ( p  <  0.001).conclusionboth test - positive and significant extra - colonic finding rates at ctc are significantly increased in the presence of  alarm  gastrointestinal symptoms especially in older patients .