**4. Other uses of CTC**

In a subsequent study of 2,531 asymptomatic patients, radiologists trained in CTC reported the accuracy of finding histologically confirmed adenomas [37]. The sensitivity for large ad‐ enomas [10 mm or larger) and medium-sized adenomas (6 – 9 mm) was 90% and 78% re‐ spectively [37]. CTC failed to detect a lesion measuring 10 mm or more in diameter in 10% of patients [37]. Pickhart et al. found that the positive predictive values (PPV) for polyps with threshold sizes 6 mm, 8 mm, and 10 mm are: 92.3%, 93.0%, and 93.1% respectively [38]. Others have also found that for significant adenomas, the PPV of CTC is high and ranges

Meta-analysis is a tool that attempts to summarize varying results across multiple studies. Meta-analysis of data suggests CTC has excellent per-patient average sensitivity and aver‐ age specificity for detection of adenomatous polyps and cancer [40]. In one meta-analysis, 2,610 patients were included for study [41]. Large polyps (10 mm or greater) had a per-pa‐ tient average sensitivity of 93% (95% CI,73% - 98%) and specificity of 97% 9(95% CI, 95% - 99%) [41]. The sensitivity and specificity decreased to 86% (95% CI: 75% - 93%) and 86% (95% CI, 76% - 93%), respectively, when the threshold was lowered to include medium sized polyps (6 mm to 9 mm). These findings are similar to another more recent meta-analysis us‐ ing average risk patients that found a sensitivity of 87% and specificity of 97.6% for polyps

One of the problems of evaluating the test performance of CTC is the use of OC as the gold standard because OC has a miss-rate for polyps and cancer as well. In one study, Pickhardt et al. compared 1,233 asymptomatic adults who underwent same-day CTC and blinded seg‐ mental OC [43]. Polyps that were detected by CTC but initially missed by OC were consid‐ ered missed polyps for OC. It was found that OC had a miss rate of 12% for adenomas 10 mm or greater. Of the missed polyps on OC, 14/15 (93.3%) non-rectal neoplasms were locat‐ ed on a fold. Five of 6 (83.3%) missed rectal lesions were located within 10 cm of the anal

Another study analyzed 286 tandem colonoscopies [44]. The OC miss rates for adenomas 5 mm and larger and advanced adenomas (≥ 10 mm or high grade dysplasia) were: 11% and 9% respectively [44]. Therefore, OC does have a significant miss rate for adenomas 5 mm and larger and/or advanced adenomas. In fact, the OC miss-rate is similar to the CTC missrate for polyps 6-9 mm in size [27]. It should also be pointed out that in screening studies, CTC and OC have similar detection rates for advanced neoplastic polyps and cancer, 3.2% vs. 3.4% respectively [45]. OC detects significantly more adenomas less than 5 mm of size although the benefit of this remains to be seen [46]. In summary, CTC appears to have simi‐ lar sensitivity to OC in detecting polyps 5 mm or greater when performed by readers with

The detection of flat adenomas are a major concern for colo-rectal cancer screening since these polyps are at a higher risk of harboring advanced pathology and are more difficult to detect by CTC as well as OC [48, 49]. In the general population, there is wide variation in the reported incidence of flat lesions, which may in part be due to the lack of a uniform defini‐ tion of flat polyps. Various definitions of flat polyps have been used in CTC studies. For ex‐

from 96 – 99% [37, 39].

256 Colonoscopy and Colorectal Cancer Screening - Future Directions

at least 10 mm in size [42].

verge [43].

high experience [47].

#### **4.1. After incomplete colonoscopy**

Sometimes OC can not be completed to the cecum due to technical factors such as prior ab‐ dominal surgery, colon length and number of flexures [61]. An important use of CTC is ex‐ amination of the colon after incomplete OC [62]. In a retrospective study, 88/546 patients had lesions 6 mm or greater on CTC after incomplete OC. OC was repeated if findings on CTC were significant. The PPV of CTC for masses, large polyps, and medium polyps were 90.9% and 91.7%, and 64.7% respectively [63].

It may be valuable to perform a low-dose diagnostic CT before rectal tube insertion in pa‐ tients referred for incomplete colonoscopy. In one study of 262 patients referred for incom‐ plete OC, colon perforation was found on the low-dose CT scans of two of the 262 patients (0.8%; 95% CI, 0.1-2.7%) [64]. One of these patients had no symptoms; the other had mild abdominal discomfort at the time of CTC. Therefore, the rate of occult colonic perforation after incomplete colonoscopy may warrant a spot CT prior to full examination.

sigmoid resection in patients with ovarian cancer in one study were: 100%, 64.7%, 72.7% and

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http://dx.doi.org/10.5772/52544

Individual accuracy of reading polyps with CTC is highly variable among radiologists and depends largely on training and experience [86-88]. There is a significant learning curve in‐ volved in the interpretation of CTC studies, with performance improving with operator ex‐ perience [89, 90]. Radiologists working in nonacademic centers may have less accurate results than would be expected from published data originating from experienced academic centers [91]. The steep learning curve involved with reading CTC has led some thought leaders to advise against widespread colorectal cancer screening programs with CTC out‐

False negatives are a major concern, i.e. missing significant lesions. It appears that many false negatives are due to observer error and not due to the technical capabilities of CTC. For instance in one study, 53% of missed polyps (60 of 114) were attributed to observer-related errors, and 26% were attributed to errors classified as technical [92]. This implies that with improvements in reader skill the sensitivity of finding significant lesions would be accepta‐ ble and comparable to OC [90]. Technical factors that appear to be associated with higher accuracy include meticulous bowel preparation and inflation, multidetector CT, combined

Radiation exposure at the time of CTC screening leads to a slight but increased risk of devel‐ oping cancer at a future time [94]. Therefore, reducing radiation exposure is a major chal‐ lenge for CTC screening.Currently, CTC scanning delivers a significant amount of X-ray radiation exposure to the patient [95]. In 2004, a survey of 28 institutions revealed the me‐ dian effective dose of radiation was 5.1 mSv (range 1.2 mSv - 11.7 mSv) per position and the

Given current CT technology, a simple and effective strategy to reduce radiation would be to lower the mAs level (i.e. deliver less X-ray photons to the body) during the data acquisi‐ tion. This strategy would however, lead to a higher noise signal in the acquired data. Recent efforts on modeling a solution to avoid this noise artifact are aimed at minimizing the noise prior or during image reconstruction. Despite the great effort on this solution in the past

A feasibility study examined low radiation doses from 10mAs to 40 mAs using adaptive statistical iterative reconstruction (ASIR) models [98]. Eighteen patients were scanned with a standard 50 mAs CTC dose in the supine position and a reduced dose of 25 mAs with 40%

decade, CTC still faces challenges at a mAs level lower than 50 [97].

100%, respectively [85].

side of academic centers [29].

**6. Radiation exposure**

median mAs value was 67 mAs[96].

**5. Reader experience and accuracy**

two and three-dimensional visualization [28, 93].

#### **4.2. For symptoms**

CTC is being increasingly used for the radiological evaluation of colorectal symptoms. In symptomatic patients, CTC is equivalent to OC for diagnosing colon cancer and clinically significant polyps [65]. In a retrospective study of 1,177 older symptomatic patients, 59 inva‐ sive CRC were detected [66]. Three small colorectal cancers were missed by CTC. CTC has a high sensitivity (95%) and negative predictive value (99.7%) in excluding a CRC in patients with colorectal symptoms [66].

#### **4.3. Inflammatory bowel disease and diverticulitis**

CTC may be useful for diagnosing and managing patients with inflammatory bowel disease (IBD) [67]. CTC correctly identified acute and chronic IBD in 63.6%, and 100% of cases, re‐ spectively [68]. CTC was also helpful in assessing post-op strictures in Crohn's disease pa‐ tients [69]. Perianastomotic narrowing or stenosis was detected by CTC in 11 of 15 patients. The sensitivity and specificity for perianastomatic narrowing were 73% and 100% respec‐ tively [69]. The risk of perforation, especially in patients with severe active colitis is a poten‐ tial worry. Currently there is not enough data to measure the true risk in patients with severe active disease [70].

Examination of the colon is usually necessary after an adequate rest period for evaluation of patients with diverticulitis. CTC appears comparable to OC in the evaluation of these pa‐ tients and is a reasonable alternative in follow-up of patients with symptomatic diverticular disease [71]. Diverticulosis may however, increase the chance of having a false positive test for polyps on CTC due to the appearance of inverted diverticula and fecoliths[72]. On the other hand, CTC may be helpful in diagnosing complications of diverticular disease and in‐ flammatory bowel disease, such as colo-vesicular fistulae [73].

#### **4.4. Detection of tumor for surgery**

CTC is very useful in detecting colon cancer after incomplete colonoscopy and also for eval‐ uating potential metastases [74-76]. CTC can help localize polyps or cancer prior to laparo‐ scopic surgery and detect synchronous lesions beyond the reach of OC due to obstructing lesions [77, 78]. In fact, CTC is superior to OC in the localization of colonic tumors prior to surgery [79]. CTC is also a safe and useful method for preoperative examination of the prox‐ imal colon after metallic stent placement in patients with acute colon obstruction caused by cancer [80].

CTC is useful in surveillance after surgery for colo-rectal cancer, detecting local recurrence and metastasis [81-84]. In patients with ovarian cancer CTC may be helpful in detecting rec‐ tosigmoid wall involvement wall and predict the need for rectosigmoid resection [85]. The sensitivity, specificity, PPV and negative predictive value of CTC for the prediction of recto‐ sigmoid resection in patients with ovarian cancer in one study were: 100%, 64.7%, 72.7% and 100%, respectively [85].
