J. Richard Choi

Location of Adenomas Missed by Optical Colonoscopy

Context How often does colonoscopy miss adenomas? Contribution During a multicenter screening trial, experienced colonoscopists performed same-day optical (OC) and virtual colonoscopy (VC) on 1233 asymptomatic adults. Optical colonoscopy performed without knowledge of the VC findings missed 55 of 511 polyps; 21 of these polyps were adenomas measuring 6 mm or greater. Adenomas missed by OC were usually on the proximal side of a fold or near the anal verge. Virtual colonoscopy missed 14% of the adenomas that measured 6 mm or greater that were de-tected by OC. Implications Neither OC nor VC is a perfect test: Each misses 10% to 14% of adenomas that measure 6 mm or greater. The Editors Optical colonoscopy (OC) is widely accepted as the gold standard for detecting colorectal neoplasia (1, 2). However, even in the most experienced hands, this skilled examination is understandably not infallible. Retrospective analysis has suggested that the OC miss rate for adenomas 10 mm or greater is approximately 10% (3). More recently, prospective back-to-back or tandem colonoscopy studies have reported miss rates for 10-mm adenomas ranging from 0% to 6% (4, 5). However, in addition to evaluating relatively small populations of patients with a high prevalence of polyps, a notable weakness common to these studies was that they used OC as its own reference standard. In a large, prospective, multicenter trial that was primarily intended to evaluate the performance of virtual colonoscopy (VC) in asymptomatic adults (6), we also had a unique opportunity to evaluate the adenoma miss rate on OC by segmentally unblinding the results from same-day VC. By using a reference standard other than OC itself for comparison, we could uncover lesions that may be systematically missed on repeated colonoscopies. These data not only provide novel insight into OC miss rates but also indicate the relative blind spots where more attention could be focused. Methods Study Design The institutional review boards at all 3 participating medical centers approved the study protocol for same-day VC and OC, and all patients provided written informed consent. We recruited asymptomatic adults who were referred for colorectal cancer screening. Exclusion criteria were a positive stool guiaic test result or iron deficiency anemia within the past 6 months; rectal bleeding, hematochezia, or unintentional weight loss of more than 10 pounds within the past 12 months; OC within the past 10 years or barium enema within the past 5 years; personal history of adenomatous polyps, colorectal cancer, or inflammatory bowel disease; and family history of familial adenomatous polyposis or nonpolyposis cancer syndromes. Between May 2002 and June 2003, 1253 asymptomatic adults enrolled in the study. Eight patients were excluded because of failure to reach the cecum at OC, 6 patients were excluded because of inadequate colonic preparation, and another 6 patients were excluded because of computed tomography (CT) system failure. The final study group comprised 1233 asymptomatic adults (728 men and 505 women; mean age, 57.8 years) who successfully completed same-day VC and OC. Study participants underwent colonic preparation with oral intake of 90 mL of phospho-soda and 10 mg of bisacodyl. To opacify residual colonic fluid and stool for VC examination, patients also consumed dilute oral contrast as previously described (7). Our CT protocol and VC technique have also been detailed previously (6). To briefly summarize, we obtained supine and prone CT acquisitions on multidetector scanners after patient-controlled rectal insufflation of room air. One of 6 trained radiologists interpreted VC studies by using a commercially available CT colonography system (Viatronix V3D-Colon, version 1.2, Viatronix, Inc., Stony Brook, New York). We used the 3-dimensional endoluminal fly-through view primarily for detecting polyps and 2-dimensional images for confirmation and problem solving. We measured polyps on the 3-dimensional view and recorded them by segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, or rectum). We defined the proximal colon as including the cecum to the splenic flexure. We prospectively rated diagnostic confidence for each detected lesion on a 3-point scale (most certain, intermediate, and least certain). One of 17 experienced colonoscopists performed OC immediately after VC interpretation by using standard commercial video colonoscopes (Olympus, Inc., Melville, New York). The colonoscope was advanced to the cecum and then sequentially withdrawn into more distal segments for polyp detection. The colonoscopist measured polyps by using a calibrated linear probe, which is more accurate than either visual or biopsy forceps estimation (8). Our polyp-matching algorithm requires VC and OC agreement according to size (within a 50% margin of error) and location (within the same or adjacent segment). After the colonoscopist evaluated a given segment, a study nurse unblinded the VC results for the previous segment. For any suspected polyp seen on VC that measured 5 mm or greater but was not seen on the initial blinded OC, the colonoscopist closely reexamined that segment and could review the VC images for guidance. We sent all retrieved polyps for histologic examination. For all cases in which a colorectal neoplasm measuring 6 mm or greater was found on second-look OC, we retrospectively reviewed both the VC and OC images. We recorded polyp characteristics, such as size, morphologic characteristic (sessile, pedunculated, or flat), and location on VC. If the polyp was situated on a colonic fold on VC, we further subcategorized it as being located on the back (proximal) side, front (distal) side, or edge of the fold. We analyzed both supine and prone VC sets for all cases. The primary reason that diminutive polyps measuring 5 mm at VC were included for potential unblinding at OC was that, given the relative error in polyp measurement, such polyps found on second-look OC might, in fact, measure 6 mm or greater. This allows for more accurate assessment of the OC miss rate at the 6-mm threshold. We did not include unblinded polyps that measured 5 mm or less on both VC and OC examinations in the final analysis. All study participants completed a detailed questionnaire on their personal and family medical history. For the purposes of this study, particular attention was given to the question about previous abdominal or pelvic surgery, since adhesions could conceivably result in a more difficult colonoscopic examination. Statistical Analysis Prospective OC performance was compared against the enhanced reference standard of second-look OC after segmental unblinding of VC results. We estimated exact binomial 95% CIs for OC miss rates. We used the chi-square test to compare the frequency of previous abdominal surgery among patients with and without polyps missed at OC and also to compare the OC miss rates among the 3 medical centers. We calculated the 95% CIs by using Stata software, version 7.0 for Windows (Stata Corp., College Station, Texas), and performed the chi-square tests by using SAS software, version 8.0 for Windows (SAS Institute, Inc., Cary, North Carolina). Role of the Funding Source The funding source had no role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results The performance characteristics of VC from this prospective, multicenter screening trial, using OC as the reference standard, have been previously reported (6). Our technique of segmental unblinding also allows for a separate assessment of OC by using the blinded VC results for comparison, which is the focus of this study. We identified 1310 polyps at OC in the 1233 asymptomatic adults; 511 (39.0%) of these polyps measured 5 mm or greater (Figure 1).Of these 511 polyps, 55 (10.8%) were found only on second-look OC after segmental unblinding of VC results. Twenty-four (43.6%) of the 55 unblinded lesions were nonadenomatous, including 16 hyperplastic polyps. Of the 31 missed neoplasms, 10 adenomas that measured only 5 mm were excluded from further analysis because of their diminutive size (9). Including unblinded lesions, 554 adenomas were detected on OC in this screening sample; 210 of these measured 6 mm or greater and 51 measured 10 mm or greater. Figure 1. Polyp flowchart. In 20 patients (17 men and 3 women; mean age, 58.2 years), 21 adenomas measuring 6 mm or greater (range, 6 mm to 17 mm; mean, 8.1 mm) were found on OC only after the VC results were unblinded, which represent the lesions of primary interest for this study (Table). The corresponding adenoma miss rate on prospective OC examination was 10.0% (95% CI, 6.3% to 14.9%) (21 of 210 adenomas) at a 6-mm cutoff. The 20 patients with missed adenomas that measured 6 mm or greater represented only 1.6% of the study sample (20 of 1233 patients) but 11.9% of patients with adenomas 6 mm or greater (20 of 168 patients). At 8-mm and 10-mm thresholds, the OC adenoma miss rates by polyp were 10.5% (CI, 5.2% to 18.5%) (10 of 95 adenomas) and 11.8% (CI, 4.4% to 23.9%) (6 of 51 adenomas), respectively. The 10 patients with missed adenomas 8 mm or greater represented 12.2% (10 of 82 patients) of all patients with neoplasms of this size or greater; the 6 patients with missed adenomas 8 mm or greater represented 12.5% of all patients with neoplasms 10 mm or greater. Table. Characteristics of Neoplasms Missed at Prospective Colonoscopic Evaluation Seventeen (81.0%) of the 21 unblinded neoplasms 6 mm or greater were tubular adenomas, 3 (14.3%) were tubulovillous adenomas, and 1 (4.8%) was an adenocarcinoma. Seven (33.3%) of the 21 unblinded polyps were classified as advanced lesions (that is, size 10 mm or high-grade dysplasia, prominent villous component, or focus of malignancy). There were 15 sessile lesions, 4 pedunculated lesions, and 2 flat les

Feasibility of simultaneous computed tomographic colonography and fully automated bone mineral densitometry in a single examination.

Purpose: To show the feasibility of calculating the bone mineral density (BMD) from computed tomographic colonography (CTC) scans using fully automated software. Materials and Methods: Automated BMD measurement software was developed that measures the BMD of the first and second lumbar vertebrae on computed tomography and calculates the mean of the 2 values to provide a per patient BMD estimate. The software was validated in a reference population of 17 consecutive women who underwent quantitative computed tomography and in a population of 475 women from a consecutive series of asymptomatic patients enrolled in a CTC screening trial conducted at 3 medical centers. Results: The mean (SD) BMD was 133.6 (34.6) mg/mL (95% confidence interval, 130.5-136.7; n = 475). In women aged 42 to 60 years (n = 316) and 61 to 79 years (n = 159), the mean (SD) BMDs were 143.1 (33.5) and 114.7 (28.3) mg/mL, respectively (P < 0.0001). Fully automated BMD measurements were reproducible for a given patient with 95% limits of agreement of −9.79 to 8.46 mg/mL for the mean difference between paired assessments on supine and prone CTC. Conclusions: Osteoporosis screening can be performed simultaneously with screening for colorectal polyps.

Normalized Distance Along the Colon Centerline: A Method for Correlating Polyp Location on CT Colonography and Optical Colonoscopy

OBJECTIVE The ability to accurately locate a polyp found on CT colonography (CTC) at subsequent optical colonoscopy (OC) is an important part of the successful implementation of CTC for colorectal cancer screening. The purpose of this study was to determine whether a polyps normalized distance along the colon centerline derived from CTC data can accurately predict its location on OC. MATERIALS AND METHODS The polyp population consisted of 152 polyps in 121 patients. CTC polyp findings were verified by same-day segmentally-unblinded OC. Each polyps normalized distance along the colon centerline was computed by dividing its distance from the anorectal junction measured along the colon centerline by the length of the colon at CTC. The predicted polyp location at OC was computed by multiplying the normalized distance along the colon centerline by the colon length at OC (i.e., the distance to the cecum as determined at full colonoscope insertion). The differences between the true and predicted polyp locations at OC were compared using paired Students t tests, linear regression, prediction interval assessment, and Bland-Altman analyses. RESULTS The differences between the true and predicted polyp locations at OC using the supine and prone CTC-normalized distances along the colon centerline were 2.2 +/- 10.5 cm (mean +/- SD; n = 136) and 1.5 +/- 10.5 cm (n = 135), respectively. The predicted location was within 10 cm of its true location for 71.3% (97/136) to 74.8% (101/135) of polyps and within 20 cm of its true location for 93.3% (126/135) to 93.4% (127/136) of polyps. CONCLUSION By computing the normalized distance along the colon centerline of a polyp found at CTC, the location of a polyp at OC can be predicted to within 10 cm (i.e., 1 colonoscope mark) for the majority of polyps.

Association Between Visceral Adiposity and Colorectal Polyps on CT Colonography

OBJECTIVE The purpose of this article is to determine whether there is an association between visceral adiposity measured on CT colonography (CTC) and colorectal polyps. MATERIALS AND METHODS Patients who underwent CTC and same-day optical colonoscopy (n = 1186) were analyzed. Visceral adipose tissue volumes and volume percentages relative to total internal body volume were measured on slices in the L2-L3 regions on supine CTC scans with validated fully automated software. Student t test, odds ratio, logistic regression, and receiver operating characteristic analyses were performed. RESULTS For subjects with (n = 345) and without (n = 841) adenomatous polyps, the mean (± SD) volume percentages were 31.2% ± 10.8% and 28.2% ± 11.3%, respectively (p < 0.0001). For subjects with (n = 244) and without (n = 942) hyperplastic polyps, the volume percentages were 31.8% ± 10.7% and 28.3% ± 11.2%, respectively (p < 0.0001). Comparing the lowest and highest quintiles of volume percentage, the odds ratios for having at least one adenomatous polyp or hyperplastic polyp versus no polyp were 2.06 (95% CI, 1.36-3.13) and 1.71 (95% CI, 1.08-2.71), and the prevalence of having adenomatous polyps or hyperplastic polyps increased by 14% and 8%, respectively. CONCLUSION Subjects with higher visceral adiposity measurements on CTC have a greater risk for the presence of colonic polyps.

CT Colonography Computer-Aided Polyp Detection: Effect on Radiologist Observers of Polyp Identification by CAD on Both the Supine and Prone Scans

RATIONALE AND OBJECTIVES To determine whether the display of computer-aided detection (CAD) marks on individual polyps on both the supine and prone scans leads to improved polyp detection by radiologists compared to the display of CAD marks on individual polyps on either the supine or the prone scan, but not both. MATERIALS AND METHODS The acquisition of patient data for this study was approved by the Institutional Review Board and was Health Insurance Portability and Accountability Act-compliant. Subsequently, the use of the data was declared exempt from further institutional review board review. Four radiologists interpreted 33 computed tomography colonography cases, 21 of which had one adenoma 6-9 mm in size, with the assistance of a CAD system in the first reader mode (ie, the radiologists reviewed only the CAD marks). The radiologists were shown each case twice, with different sets of CAD marks for each of the two readings. In one reading, a true-positive CAD mark for the same polyp was displayed on both the supine and prone scans (a double-mark reading). In the other reading, a true-positive CAD mark was displayed either on the supine or prone scan, but not both (a single-mark reading). True-positive marks were randomized between readings and there was at least a 1-month delay between readings to minimize recall bias. Sensitivity and specificity were determined and receiver operating characteristic (ROC) and multiple-reader multiple-case analyses were performed. RESULTS The average per polyp sensitivities were 60% (38%-81%) versus 71% (52%-91%) (P = .03) for single-mark and double-mark readings, respectively. The areas (95% confidence intervals) under the ROC curves were 0.76 (0.62-0.88) and 0.79 (0.58-0.96), respectively (P = NS). Specificities were similar for the single-mark compared with the double-mark readings. CONCLUSION The display of CAD marks on a polyp on both the supine and prone scans led to more frequent detection of polyps by radiologists without adversely affecting specificity for detecting 6-9 mm adenomas.

Automated measurement of colorectal polyp height at CT colonography: hyperplastic polyps are flatter than adenomatous polyps.

OBJECTIVE Hyperplastic polyps are more difficult to detect than adenomatous polyps at CT colonography (CTC), and it has been theorized that this difference in detectability is because hyperplastic polyps are flatter. Using automated software that computes polyp height, we determined whether hyperplastic colonic polyps on CTC are indeed flatter than adenomatous polyps of comparable width. MATERIALS AND METHODS At three medical centers, 1,186 patients underwent oral contrast-enhanced CTC and same-day optical colonoscopy (OC) with segment unblinding for colorectal cancer screening. One hundred eighty-five of the patients had at least one hyperplastic or adenomatous polyp 6-10 mm visible at both OC and CTC, where size was determined by a calibrated guidewire at OC. To assess flatness, the heights of the polyps at CTC were measured using a validated automated software program. The heights and height-to-width ratios of the hyperplastic polyps were compared with those of the adenomatous polyps using a Students t test (two-tailed, unpaired, unequal variance). RESULTS There were 176 adenomatous and 83 hyperplastic polyps visible at segment-unblinded OC. The fraction of these polyps that were measurable at CTC using the automated software was not significantly different for adenomatous versus hyperplastic polyps (158/176 [89.8%] vs 73/87 [83.9%], respectively; p = 0.2). The average height-to-width ratios using automated width measurements were 15% less for hyperplastic polyps: 0.39 +/- 0.20 (n = 158) and 0.33 +/- 0.19 (n = 73) for adenomatous and hyperplastic polyps, respectively (p = 0.03). When polyps of comparable OC size or CTC width were considered, the heights of hyperplastic polyps were up to 27% less than those of adenomatous polyps. CONCLUSION For 6-10 mm polyps of a given size as determined by OC or a given width at CTC, hyperplastic polyps tend to be flatter (i.e., have lower height) compared with adenomatous polyps.

Temporal and Multiinstitutional Quality Assessment of CT Colonography

OBJECTIVE The purpose of this study was to investigate the variability of CT colonography (CTC) scan quality obtained within and between institutions by using previously validated automated quality assessment (QA) software that assesses colonic distention and surface area obscured by residual fluid. MATERIALS AND METHODS The CTC scans of 120 patients were retrospectively selected, 30 from each of four institutions. The bowel preparation included oral contrast material for fecal and fluid tagging. Patients at one institution (institution 4) drank half the amount of oral contrast material compared with the patients at the other three institutions. Fifteen of the CTC scans were from the beginning of the protocol studied at each institution and 15 scans were from the same protocol acquired approximately 1 year later in the study. We used previously validated QA software to automatically measure the mean distention and residual fluid of each of five colonic segments (ascending, transverse, descending, sigmoid, and rectum). Adequate distention was defined as a colonic diameter of at least 2 cm. Residual fluid was determined by the percentage of colonic surface area covered by fluid. We compared how the quality varied across multiple institutions and over time within the same institution. RESULTS No significant difference in the amount of colonic distention among the four institutions was found (p = 0.19). However, the distention in the prone position was significantly greater than the distention in the supine position (p < 0.001). Patients at institution 4 had about half the amount of residual colonic fluid compared with patients at the other three institutions (p < 0.01). The sigmoid and descending colons were the least distended segments, and the transverse and descending colons contained the most fluid on the prone and supine scans, respectively. More recently acquired studies had greater distention and less residual fluid, but the differences were not statistically significant (p = 0.30 and p = 0.96, respectively). CONCLUSION Across institutions, a significant difference can exist in bowel preparation quality for CTC. This study reaffirms the need for standardized bowel preparation and quality monitoring of CTC examinations to reduce poor CTC performance.

Associations among pericolonic fat, visceral fat, and colorectal polyps on CT colonography.

To determine the association between pericolonic fat and colorectal polyps using CT colonography (CTC).

Automatic procedure to distinguish colonic polyps located on fold vs. not on fold

Performance of Computed Tomographic Colonography (CTC) Computer Aided Detection (CTC CAD) depends sensitively on a set of features chosen to characterize a polyp candidate. Most of the features are derived from some shape related characteristics which are calculated at the points located within the boundaries of a polyp candidate. This approach ignores information from the part of the colonic wall stretching beyond the limits of a polyp candidate. We found that almost 90% of small and medium size polyps missed by our CAD program were located on haustral folds. This suggests that two different classifiers (for detections on a fold and not on a fold) could be used which are better tuned to the local characteristics. Therefore, we developed an automated method to verify independently if a given polyp candidate is located on a fold. This is done by checking the intensity profile along normals originating from the points on the colonic wall which are close to but outside of a patch marking a polyp candidate.