Dig Dis Sci (2009) 54:212–217 DOI 10.1007/s10620-008-0360-5

REVIEW

CT Colonography Can Be an Adjunct to Optical Colonoscopy in CRC Screening Vivek V. Gumaste

Received: 10 January 2008 / Accepted: 3 June 2008 / Published online: 10 July 2008 Ó Springer Science+Business Media, LLC 2008

Abstract CT colonography or virtual colonoscopy is a fairly new modality that has the potential to play a significant role in screening for colon cancer. CT colonography is an attractive option for two specific reasons. First, it is non-invasive and, second, it obviates the need for sedation. It thus overcomes the two major drawbacks of optical colonoscopy. CT colonography cannot be a stand-alone technique for colorectal cancer screening because, unlike conventional colonoscopy, it does not possess a therapeutic option or a definite diagnostic capability. However, CT colonography can be a cost-effective complement to traditional colonoscopy if it is reasonably priced and if appropriate cut-off levels ([6 mm polyp) are used to increase its sensitivity. Keywords CRC screening
CT colonography
Virtual colonoscopy

Introduction Colon cancer is the second leading cause of cancer-related deaths in the United States accounting for approximately 55,000 mortalities in 2006 [1]. Over 100,000 new cases of colon cancer are projected to occur every year [1]. Most

colorectal cancers arise from pre-cancerous adenomatous polyps that take about 5–10 years to become malignant. Provided these polyps are detected and removed in a timely fashion, colon cancer can be prevented, thereby defining a definite role for screening in the management of colon cancer. According to current recommendations, all men and women (without any predisposing factors) over the age of 50 years are eligible candidates for colorectal cancer (CRC) screening [2]. This amounts to approximately 60 million people in the United States as per last census and constitutes a sizable number. Currently, there are several proposed methods for colon cancer screening, for example fecal occult blood testing, flexible sigmoidoscopy, total colonoscopy, barium enema, and virtual colonoscopy. Of these colonoscopy is regarded as the gold standard. CT colonography (CTC), the most recent of these modalities, seems an attractive option for two specific reasons. First, it is non-invasive and, second, it obviates the need for sedation. It thus overcomes the two major drawbacks of optical colonoscopy.

Techniques, Protocol, and Interpretation V. V. Gumaste Department of Medicine, Mount Sinai Services at Elmhurst, Elmhurst General Hospital, Elmhurst, NY, USA V. V. Gumaste Mount Sinai School of Medicine, City University of New York, Manhattan, NY, USA V. V. Gumaste (&) Chief Division of Gastroenterology, Mount Sinai Services at Elmhurst, 79-01 Broadway, New York, NY 11373, USA e-mail: [email protected]

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In this novel technology, data from computed tomography are used to generate two-dimensional and three-dimensional displays of the colon [3–11], which enables more detailed evaluation (Fig. 1). Two types of CT equipment (single detector and multidetector) have been utilized for this purpose. The MDCT (multi-detector) scanner has the advantage of faster imaging and better spatial resolution in comparison with a single detector CT. Faster imaging is less uncomfortable (for the

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fixed pathology, for example polyps [15]. Scanning in both positions also opens up obscured areas of the colon leading to improved per-patient and per-polyp sensitivity [18]. Anti-spasmodics The use of antispasmodics, for example glucagon and hyoscine butyl bromide, is controversial. Antispasmodics may reduce discomfort and enhance colonic distension. Objective data from studies has produced mixed results [19, 20]. The ACR practice guidelines suggest that glucagon may be used to counter spasm or allay patient discomfort [15]. Fig. 1 Colon polyp as seen on CTC and conventional colonoscopy (images courtesy of Perry Pickhardt, MD)

patient is holding his/her breath during the procedure) and produces fewer respiratory artifacts [12]. Additionally a MDCT makes for better 3D reconstructions [13]. Practice guidelines from the American College of Radiology (ACR) recommend the use of a multidetector CT with a slice collimation of 3 mm or less and reconstruction intervals of 1.5 mm or less. Thinner slices decrease the false positive rate [14]. Preparation A clean well prepared and adequately distended colon is a prerequisite for a high quality CTC examination. Patients need to undergo a 24-h colonic preparation similar to that required for colonoscopy and direct contrast barium enema (DCBE). This usually involves adherence to a clear liquid diet for 24 h and the ingestion of a laxative the day before. Residual liquid interferes with the diagnostic imaging of CTC [15]. Poly(ethylene glycol) (a favorite with endoscopists) results in relatively larger amounts of residual fluid and is less suitable for this procedure [16]. Cathartics, for example sodium phosphate and magnesium citrate, produce a ‘‘dry prep’’ with little fluid left behind and are the preferred agents. Adequate colonic distension is essential for thorough visualization of all areas of the colon. While most centers use room air for distension, carbon dioxide is used in some institutions. Carbon dioxide, unlike the nitrogen in room air, is readily absorbed through the colonic wall and excreted through the lungs resulting in diminished post procedural discomfort. In one study involving CTC, carbon dioxide resulted in less patient discomfort and improved colonic distension compared with room air [17]. Position CT scanning is performed in both supine and prone positions. Supine and prone images help distinguish mobile stool from

Tagging Despite vigorous preparation, retained stool can still pose a problem in accurate interpretation. Efforts continue to tag fecal material in an attempt to distinguish fecal material from polyps. Tagging techniques involve the use of barium and/or iodine solution along with meals. Although initial results have proved to be promising [3, 21], tagging is still considered experimental and is not included in the American College of Radiology practice guidelines. If refined significantly, fecal tagging can usher in an era of prepless CTC. Toxicity Exposure to ionizing radiation during CTC has been an area of concern and would assume increased importance were CTC to be used as a mass-screening tool. Macari et al. have indicated that by proper technique the combined effective radiation dose for CTC can be as low as 5 mSv (milli Sieverts) for men and 7.8 mSv for women, which is similar to the radiation exposure encountered during a double-contrast barium enema [22]. Lifetime risk of cancer at such levels of exposure is about 0.14% for a 50 year-old and about half that for a 70-year-old. With optimization of CTC protocols, this danger can be minimized further [23]. Time The actual procedure takes about 15 min. Interpretation Image processing and interpretation are done using specialized software. The software extracts the images from the air-filled colon and removes the impression of the opacified residual fluid. In addition, the system creates a centerline through which the colonic lumen can be navigated. A trained radiologist takes about 20 min to evaluate the final images.

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Complications Although initially acclaimed as a risk-free procedure, increased usage has revealed that perforations can occur with CTC. Sosna et al. [28] were the first to highlight this complication, noting nine perforations in 24,365 examinations (0.04%). Another survey documented 13 perforations (four asymptomatic) among 17,067 procedures, a rate of 0.08% [29]. Cardiovascular Complications Fig. 2 Colon cancer as depicted in 2D and 3D views reproduced with permission from: http://www.med.nyu.edu/virtualcolonoscopy/ (images courtesy of Michael Macari, MD)

Cardiovascular complications are less likely with CTC in comparison with traditional colonoscopy [30].

2D versus 3D

Contraindications

Sensitivity and specificity for detecting polyps at the 5 and 10 mm threshold did not change with either 2D or 3D (‘‘fly-through’) technique [24]. A primary 2D review is adequate in most cases for interpretation. Both views tend to be complementary and must be available for accurate interpretation regardless of whether one uses 2D or 3D as the primary modality (Fig. 2).

CTC should not be performed immediately after colonoscopic polypectomy or if a large biopsy has been taken during the procedure. Air insufflation in this setting is more likely to produce a perforation. Also CTC should not be done in cases where tissue sampling is warranted, for example in IBD surveillance.

Computer-Aided Detection

Efficacy

Computer aided detection systems use software to highlight possible polyps for further evaluation by radiologists [13]. A recent study [25] indicated that computer-aided detection significantly improves per-polyp detection for less experienced readers.

Four large studies [3, 4, 10, 31] and several smaller ones have attempted to evaluate the sensitivity and specificity of CTC in detecting polyps. The results of these studies have been aggregated in four meta-analysis reports [24, 32–34]. Sensitivity

Inter-observer Variability Studies have reported low inter-observer variability with kappa values as low as 0.56. These results could be due to software imperfections and learning curve effects [11]. Patient Discomfort and Acceptance Patients have reported more pain and discomfort during CTC than during conventional colonoscopy. In one study [3] 54% recalled greater discomfort with CTC compared to 38% with conventional colonoscopy. Van Gelder [26] assessed patient acceptability immediately after each of the procedures and five weeks later. Initially, 71% favored CTC; but this figure dropped to 61%, five weeks later when patients took into account the results of both tests and subsequent management decisions. Taylor et al. [27] similarly found increased preference for CTC in the immediate post-procedure period but overall patient satisfaction was in favor of colonoscopy.

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The sensitivity of CTC seems to be directly related to the size of the polyp. For polyps[10 mm in size the sensitivity in meta-analysis reports ranged from 77% to 88%. With polyps 6–9 mm in size the sensitivity was between 62% and 70%. The sensitivity was poorest for polyps \5 mm, ranging from 43% to 56%. The sensitivity however was heterogeneous with wide confidence intervals (Table 1). With a polyp size greater than 10 mm there was less heterogeneity. However in three of the four larger studies the sensitivity even for polyps [10 mm was 55, 59, and 63%. Specificity Specificity for polyps [10 mm ranged from 95% to 97%. When the threshold was decreased to include smaller sized polyps the specificity decreased slightly to 85%. Overall the results for specificity were more homogenous than sensitivity values (see Table 2).

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Table 1 Sensitivity \6 mm

[9 mm

Group

Studies

Patients

6-9 mm

Rossman and Korsten [24]

30

NSa

56% (CI 42–70)

63% (CI 52–75)

82% (CI76–88)

Mulhall BP et al. [32]

33

6,393

48% (CI 25–70)

70% (CI 55–84)

85% (CI 79–91)

Sosna et al. [34]

14

1,324

43% (CI 39–47)

62% (CI 58–67)

88% (CI 84–93)

b

Category 3 Halligan et al. [33]

24

4181

c

NC

70% (CI 63-76)

a

Not stated

b

Category 1: polyps [ 10 mm; Category 2: polyps [ 5 mm; Category 3: all polyps Not calculated, because of extreme heterogeneity

c

Table 2 Specificity Size (mm)

Specificity

[10

97% (CI 95–99)

[6

86% (CI 76–93)

Sosna et al. [34]

[10

95% (CI 94–97)

Mulhall et al. [32]

[10

97% (CI 97–96)

Halligan et al. [33]

6–9

93% (CI 91–95)

\6

92% (CI 89–96)

Colon Cancer Screening CTC cannot be a stand-alone technique for colorectal cancer screening because, unlike conventional colonoscopy (the gold standard), it does not have: 1 2

a therapeutic option; or definite diagnostic capability (Table 3).

Polyps detected by CTC will have to be removed using conventional colonoscopy for CRC screening to be effective. In addition, indeterminate lesions will also warrant further evaluation by optical colonoscopy and biopsy.

Table 3 CTC versus conventional colonoscopy CTC

Conventional

Invasive

No

Yes

Preparation required

Yes

Yes

Sedation

No

Yes

Time

15 min

30–40 min

Interpretation

20 min

Simultaneous

Recovery

No

Yes

Therapeutic potential

No

Yes

Radiation exposure

Yes

No

Perforation

Yes

Yes

Category 1b 77% (CI 70-83)

Severe capacity issues currently hamper conventional colonoscopy as a screening test. Paucity of gastroenterologists and lack of space and equipment have all resulted in long waiting periods. While CTC cannot assume center stage independently, because of its inherent drawbacks, it can play a useful role as an adjunct if this modality can be refined to accurately identify: 1 2

Indications

Category 2

b

those patients who will not require further testing with optical colonoscopy; and those patients who will require subsequent colonoscopy.

A large number of patients undergoing screening colonoscopy have normal or negative studies with regard to adenomas or cancers. In a recent study 3,056 of 3,163 patients (96.6%) undergoing screening colonoscopy had negative results [35]. CTC, by its high specificity (86– 97%), has shown that it can accurately identify this subset preventing further testing by optical colonoscopy leading to a decreased load on gastroenterologists. In a Markov model, primary CTC screening with subsequent optical colonoscopy as required resulted in a 77.6% reduction in the number of optical colonoscopies [36]. The size of a polyp is directly related to its clinical significance. One study identified advanced pathology in 1.9% of 1–5 mm polyps, 7.5% in 6–9 mm polyps, and 39.7% in polyps [10 mm [37]. The ACG guidelines recommend colonoscopy and polypectomy for patients with intermediate sized polyps; that is 6 mm and larger [38]. While CTC has a good sensitivity (77–88%) in detecting polyps [10 mm, it is less accurate in detecting polyps 6– 9 mm in size (sensitivity (62–70%); that means approximately one-third of patients with significant sized polyps will be ‘‘missed’’. If CTC can be further improved (by standardizing the equipment, refining software, and reducing inter-observer variability) to attain sensitivity levels in the vicinity of 80–90% for intermediate sized polyps, it can play a more useful role in screening for colon cancer. Its exact place in CRC screening is still being debated. Studies so far have not indicated that CTC as an initial test

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will increase adherence rates [39]. Increased compliance will result in increased polypectomies and a significant decrease in colorectal cancer incidence. However if CTC is merely going to displace candidates from undergoing colonoscopy, it may result in an opposite outcome [40]. Some reports [40] have hinted at a dual approach: CTC as a first choice for patients with low polyp prevalence (women [50 but \60) and optical colonoscopy with clearing polypectomy for healthy patients greater than 60 years of age who are more likely to have polyps. A reasonable option is to allow the patient to make an informed decision about which would be his/her first choice with the full knowledge that an abnormal CTC would eventually need subsequent colonoscopy. Vijan et al. [41] used a Markov model to assess the costeffectiveness of CTC in screening for colorectal neoplasia starting at age 50 and up to 80 years. CTC done every ten years reduced the cancer risk to 2.3% at a cost of $8,150 per life year saved. When the frequency of CTC was reduced to five years the effectiveness improved with a cancer risk of 1.3% but the cost went up to $13,460. Optical colonoscopy in this report reduced the cancer risk to 1.2% at a cost of $8,090. In this study the cost of colonoscopy was $653, compared with $559 for CTC. Another study [36], which evaluated the cost-effectiveness of CTC using a similar Markov model, produced slightly different results. In this report the authors modified the criteria by using a cut-off level of [6 mm for sensitivity; the costs used for calculation were higher for colonoscopy ($696) and lower for CTC ($478). The overall cost per life-year saved relative to no screening was $4,361 for CTC with a 6 mm threshold compared with $9,180 for optical colonoscopy. The incremental cost went up astronomically by $118,440 when polyps under 6 mm were included but produced minimal benefit in colorectal cancer risk, which decreased marginally from 37.8% to 36.5%. CTC can be a cost-effective complement to traditional colonoscopy in CRC screening if it is reasonably priced and if appropriate cut-off levels ([6 mm polyp) are used to increase its sensitivity. Other Indications CTC has proved to be a useful modality in the following conditions: 1 2 3 4

failed colonoscopy; evaluation of the colon proximal to an obstructing lesion; CRC screening in patients with contraindications to colonoscopy or who refuse optical colonoscopy; and patients with coagulaopathy, intolerance to sedation, and who refuse other screening options.

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