B. Dustin Pooler

Opportunistic Screening for Osteoporosis Using Abdominal Computed Tomography Scans Obtained for Other Indications

BACKGROUND Osteoporosis is a prevalent but underdiagnosed condition. OBJECTIVE To evaluate computed tomography (CT)-derived bone mineral density (BMD) assessment compared with dual-energy x-ray absorptiometry (DXA) measures for identifying osteoporosis by using CT scans performed for other clinical indications. DESIGN Cross-sectional study. SETTING Single academic health center. PATIENTS 1867 adults undergoing CT and DXA (n = 2067 pairs) within a 6-month period over 10 years. MEASUREMENTS CT-attenuation values (in Hounsfield units [HU]) of trabecular bone between the T12 and L5 vertebral levels, with an emphasis on L1 measures (study test); DXA BMD measures (reference standard). Sagittal CT images assessed for moderate-to-severe vertebral fractures. RESULTS CT-attenuation values were significantly lower at all vertebral levels for patients with DXA-defined osteoporosis (P < 0.001). An L1 CT-attenuation threshold of 160 HU or less was 90% sensitive and a threshold of 110 HU was more than 90% specific for distinguishing osteoporosis from osteopenia and normal BMD. Positive predictive values for osteoporosis were 68% or greater at L1 CT-attenuation thresholds less than 100 HU; negative predictive values were 99% at thresholds greater than 200 HU. Among 119 patients with at least 1 moderate-to-severe vertebral fracture, 62 (52.1%) had nonosteoporotic T-scores (DXA false-negative results), and most (97%) had L1 or mean T12 to L5 vertebral attenuation of 145 HU or less. Similar performance was seen at all vertebral levels. Intravenous contrast did not affect CT performance. LIMITATION The potential benefits and costs of using the various CT-attenuation thresholds identified were not formally assessed. CONCLUSION Abdominal CT images obtained for other reasons that include the lumbar spine can be used to identify patients with osteoporosis or normal BMD without additional radiation exposure or cost. PRIMARY FUNDING SOURCE National Institutes of Health.

Simultaneous screening for osteoporosis at CT colonography: bone mineral density assessment using MDCT attenuation techniques compared with the DXA reference standard.

The purpose of this study was to evaluate the utility of lumbar spine attenuation measurement for bone mineral density (BMD) assessment at screening computed tomographic colonography (CTC) using central dual‐energy X‐ray absorptiometry (DXA) as the reference standard. Two‐hundred and fifty‐two adults (240 women and 12 men; mean age 58.9 years) underwent CTC screening and central DXA BMD measurement within 2 months (mean interval 25.0 days). The lowest DXA T‐score between the spine and hip served as the reference standard, with low BMD defined per World Health Organization as osteoporosis (DXA T‐score ≤ −2.5) or osteopenia (DXA T‐score between −1.0 and −2.4). Both phantomless quantitative computed tomography (QCT) and simple nonangled region‐of‐interest (ROI) multi‐detector CT (MDCT) attenuation measurements were applied to the T12–L5 levels. The ability to predict osteoporosis and low BMD (osteoporosis or osteopenia) by DXA was assessed. A BMD cut‐off of 90 mg/mL at phantomless QCT yielded 100% sensitivity for osteoporosis (29 of 29) and a specificity of 63.8% (143 of 224); 87.2% (96 of 110) below this threshold had low BMD and 49.6% (69 of 139) above this threshold had normal BMD at DXA. At L1, a trabecular ROI attenuation cut‐off of 160 HU was 100% sensitive for osteoporosis (29 of 29), with a specificity of 46.4% (104 of 224); 83.9% (125 of 149) below this threshold had low BMD and 57.5% (59/103) above had normal BMD at DXA. ROI performance was similar at all individual T12–L5 levels. At ROC analysis, AUC for osteoporosis was 0.888 for phantomless QCT [95% confidence interval (CI) 0.780–0.946] and ranged from 0.825 to 0.853 using trabecular ROIs at single lumbar levels (0.864; 95% CI 0.752–0.930 at multivariate analysis). Supine‐prone reproducibility was better with the simple ROI method compared with QCT. It is concluded that both phantomless QCT and simple ROI attenuation measurements of the lumbar spine are effective for BMD screening at CTC with high sensitivity for osteoporosis, as defined by the DXA T‐score.

Diagnostic Performance of Multidetector Computed Tomography for Suspected Acute Appendicitis

BACKGROUND Use of preoperative computed tomography for suspected acute appendicitis has dramatically increased since the introduction of multidetector CT (MDCT) scanners. OBJECTIVE To evaluate the diagnostic performance of MDCT for suspected acute appendicitis in adults. DESIGN Analysis of MDCT findings and clinical outcomes of consecutive adults referred for MDCT for suspected appendicitis from January 2000 to December 2009. SETTING Single academic medical center in the United States. PATIENTS 2871 adults. MEASUREMENTS Interpretation of nonfocused abdominopelvic MDCT scans by radiologists who were aware of the study indication. Posttest assessment of diagnostic performance of MDCT for acute appendicitis, according to the reference standard of final combined clinical, surgical, and pathology findings. RESULTS 675 of 2871 patients (23.5%) had confirmed acute appendicitis. The sensitivity, specificity, and negative and positive predictive values of MDCT were 98.5% (95% CI, 97.3% to 99.2%) (665 of 675 patients), 98.0% (CI, 97.4% to 98.6%) (2153 of 2196 patients), 99.5% (CI, 99.2% to 99.8%) (2153 of 2163 patients), and 93.9% (CI, 91.9% to 95.5%) (665 of 708 patients), respectively. Positive and negative likelihood ratios were 51.3 (CI, 38.1 to 69.0) and 0.015 (CI, 0.008 to 0.028), respectively. The overall rate of negative findings at appendectomy was 7.5% (CI, 5.8% to 9.7%) (54 of 716 patients), but would have decreased to 4.1% (28 of 690 patients) had surgery been avoided in 26 cases with true-negative findings on MDCT. The overall perforation rate was 17.8% (120 of 675 patients) but progressively decreased from 28.9% in 2000 to 11.5% in 2009. Multidetector computed tomography provided or suggested an alternative diagnosis in 893 of 2122 patients (42.1%) without appendicitis or appendectomy. LIMITATION Possible referral bias, because some patients whose appendicitis was difficult to diagnose on clinical grounds may not have been referred for MDCT for evaluation of suspected appendicitis. CONCLUSION Multidetector computed tomography is a useful test for routine evaluation of suspected appendicitis in adults. PRIMARY FUNDING SOURCE None.

Assessment of volumetric growth rates of small colorectal polyps with CT colonography: a longitudinal study of natural history

BACKGROUND The clinical relevance and in-vivo growth rates of small (6-9 mm) colorectal polyps are not well established. We aimed to assess the behaviour of such polyps with CT colonography assessments. METHODS In this longitudinal study, we enrolled asymptomatic adults undergoing routine colorectal cancer screening with CT colonography at two medical centres in the USA. Experienced investigators (PJP, DHK, JLH) measured volumes and maximum linear sizes of polyps in vivo with CT colonography scans at baseline and surveillance follow-up. We defined progression, stability, and regression on the basis of a 20% volumetric change per year from baseline (20% or more growth classed as progression, 20% growth to -20% reduction classed as stable, and -20% or more reduction classed as regression). We compared findings with histological subgroups confirmed after colonoscopy when indicated. This study is registered with ClinicalTrials.gov, number NCT00204867. FINDINGS Between April, 2004, and June, 2012, we screened 22,006 asymptomatic adults and included 243 adults (mean age 57·4 years [SD 7·1] and median age 56 years [IQR 52-61]; 106 [37%] women), with 306 small colorectal polyps. The mean surveillance interval was 2·3 years (SD 1·4; range 1-7 years; median 2·0 years [IQR 1·1-2·3]). 68 (22%) of 306 polyps progressed, 153 (50%) were stable, and 85 (28%) regressed, including an apparent resolution in 32 (10%) polyps. We established immediate histology in 131 lesions on colonoscopy after final CT colonography. 21 (91%) of 23 proven advanced adenomas progressed, compared with 31 (37%) of 84 proven non-advanced adenomas, and 15 (8%) of 198 other lesions (p<0·0001). The odds ratio for a growing polyp at CT colonography surveillance to become an advanced adenoma was 15·6 (95% CI 7·6-31·7) compared with 6-9 mm polyps detected and removed at initial CT colonography screening (without surveillance). Mean polyp volume change was a 77% increase per year for 23 proven advanced adenomas and a 16% increase per year for 84 proven non-advanced adenomas, but a 13% decrease per year for all proven non-neoplastic or unresected polyps (p<0·0001). An absolute polyp volume of more than 180 mm(3) at surveillance CT colonography identified proven advanced neoplasia (including one delayed cancer) with a sensitivity of 92% (22 of 24 polyps), specificity of 94% (266 of 282 polyps), positive-predictive value of 58% (22 of 38 polyps), and negative-predictive value of 99% (266 of 268 polyps). Only 16 (6%) of the 6-9 mm polyps exceeded 10 mm at follow-up. INTERPRETATION Volumetric growth assessment of small colorectal polyps could be a useful biomarker for determination of clinical importance. Advanced adenomas show more rapid growth than non-advanced adenomas, whereas most other small polyps remain stable or regress. Our findings might allow for less invasive surveillance strategies, reserving polypectomy for lesions that show substantial growth. Further research is needed to provide more information regarding the ultimate fate of unresected small polyps without significant growth. FUNDING US National Institutes of Health, National Cancer Institute.

Unreported Vertebral Body Compression Fractures at Abdominal Multidetector CT

PURPOSE To retrospectively assess the prevalence and clinical outcomes of unreported vertebral compression fractures at abdominal computed tomography (CT). MATERIALS AND METHODS This HIPAA-compliant study had institutional review board approval; the need for informed consent was waived for this retrospective analysis. A total of 2041 consecutive adult patients (1640 women, 401 men; age range, 19-94 years) underwent both abdominal multidetector CT and dual-energy x-ray absorptiometry (DXA) within 6 months of each other between 2000 and 2007, before sagittal CT reconstructions were obtained routinely. Transverse (axial) and retrospective sagittal multidetector CT reconstructions were reviewed for the presence of moderate or severe vertebral body compression fractures of the lower thoracic and lumbar spine by using the Genant visual semiquantitative method. Twenty-six patients were excluded for evidence of pathologic fracture or for technical factors limiting compression fracture detection. Electronic medical records were reviewed for patients with moderate or severe compression fractures to determine whether the fracture was reported at prospective CT interpretation, was known previously, or was diagnosed subsequently. Correlation was made with central DXA T scores. Statistical analysis was performed with the Student t test and Fisher exact test. RESULTS At least one moderate or severe vertebral body compression fracture was identified retrospectively at CT in 97 patients (mean age, 70.8 years). Fractures involved one level in 67 and multiple levels in 30 patients, for a total of 141 fractures. In 81 (84%) patients, prospective CT diagnosis was not made. Patients in whom fractures were reported prospectively were significantly older and were more likely to have a severe compression fracture (P < .05). In 52 (64%) patients with an unreported fracture, the vertebral compression fracture was not known clinically. In 18 patients, subsequent diagnosis of a compression fracture was determined by means of another imaging study (median interval, 7 months). At DXA, 39 (48%) of 81 patients with unreported vertebral body compression fractures had a nonosteoporotic T score (greater than -2.5). CONCLUSION Most clinically important vertebral body compression fractures in nontrauma patients at risk for low bone mineral density may go unreported at abdominal multidetector CT if sagittal reconstructions are not routinely evaluated.

Alternative Diagnoses to Suspected Appendicitis at CT

PURPOSE To assess alternative diagnoses in adults undergoing computed tomography (CT) for suspected acute appendicitis in routine clinical practice. MATERIALS AND METHODS This retrospective study was HIPAA compliant and institutional review board approved; informed consent was waived. A total of 1571 consecutive adults were referred from emergency department or urgent care settings for evaluation of suspected acute appendicitis at a single academic medical center from January 2006 to December 2009. Diagnoses given by board-certified radiologists at nonfocused abdominopelvic CT and ultimate clinical diagnoses by a combination of clinical, surgical, pathologic, and other radiologic findings were analyzed. Comparisons were made by using the Fisher exact test and Mann-Whitney test, where appropriate, with a two-tailed P value of less than .05 used as the criterion for statistical significance. RESULTS A specific diagnosis at CT examination was made in 867 of 1571 (55.2%) patients. Acute appendicitis was favored in 371 of 1571 (23.6%) patients. An alternative diagnosis other than appendicitis was suggested in 496 of 1571 (31.6%) patients. Among patients with an alternative CT diagnosis, 204 of 496 (41.1%) were hospitalized and 109 of 496 (22.0%) underwent surgical or image-guided intervention for diagnoses other than appendicitis, compared with rates of 14.1% and 4.4%, respectively, among patients in whom a specific diagnosis was not made at CT (P < .0001). The most common broad categories of disease included nonappendiceal gastrointestinal conditions (46.0%), gynecologic conditions (21.6%), genitourinary conditions (16.9%), and hepatopancreaticobiliary conditions (7.7%). CONCLUSION In adult patients clinically suspected of having acute appendicitis, abdominopelvic CT frequently identifies an alternative cause for symptoms, which often requires hospitalization and surgery for treatment.

Serrated Polyps at CT Colonography: Prevalence and Characteristics of the Serrated Polyp Spectrum

Purpose To report the prevalence and characteristics of serrated polyps identified in a large, average-risk population undergoing screening computed tomographic (CT) colonography. Materials and Methods This HIPAA-compliant retrospective study was approved by the institutional review board of the University of Wisconsin School of Medicine and Public Health. The need for informed consent was waived. Nine thousand six hundred examinations from 8289 patients were enrolled in a single-institution CT colonography-based screening program (from 2004 to 2011) and were evaluated for the presence of nondiminutive serrated lesions and advanced adenomas. The prevalence and characteristics of these lesions were tabulated. Generalized estimating equation regressions of polyp characteristics that may contribute to visualization of serrated lesions were investigated, including polyp size, location, and morphologic appearance; histologic findings; and presence or absence of contrast material tagging. Results Nondiminutive serrated lesions (≥6 mm) were seen at CT colonography-based screening with a prevalence of 3.1% (254 of 8289 patients). Sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs) constituted 36.8% (137 of 372) and 4.3% (16 of 372) of serrated lesions, respectively; hyperplastic polyps (HPs) accounted for 58.9% (219 of 372 lesions). SSA and TSA tended to be large (mean size, 10.6 mm and 14.1 mm, respectively), with size categories and polyp subgroups significantly associated (P < .0001). SSA tended to be proximal in location (91.2%, 125 of 137 lesions) and flat in morphologic appearance (39.4%, 54 of 137 lesions) compared with TSA and HP. The presence of high-grade dysplasia in serrated lesions was uncommon when compared with advanced adenomas (one of 372 lesions vs 22 of 395 lesions, respectively; P < .0001). Multivariate analysis showed that contrast material tagging markedly improved serrated polyp detection with an odds ratio of 40.4 (95% confidence interval: 10.1, 161.4). Conclusion Serrated lesions are seen at CT colonography-based screening with a nondiminutive prevalence of 3.1%. These lesions tend to be large, flat, and proximal in location. Adherent contrast material coating on these polyps aids in their detection, despite an often flat morphologic appearance. (©) RSNA, 2016 Online supplemental material is available for this article.

Variation in Diagnostic Performance among Radiologists at Screening CT Colonography

PURPOSE To assess the variation in diagnostic performance among radiologists at screening computed tomographic (CT) colonography. MATERIALS AND METHODS In this HIPAA-compliant, institutional review board-approved study, 6866 asymptomatic adults underwent first-time CT colonographic screening at a single center between January 2005 and November 2011. Results of examinations were interpreted by one of eight board-certified abdominal radiologists (mean number of CT colonographic studies per reader, 858; range, 131-2202). Findings at CT colonography and subsequent colonoscopy were recorded, and key measures of diagnostic performance, including adenoma and advanced neoplasia detection rate, were compared among the radiologists. RESULTS The overall prevalence of histopathologically confirmed advanced neoplasia was 3.6% and did not differ significantly among radiologists (range, 2.4%-4.4%; P = .067; P = .395 when one outlier was excluded). Overall, 19.5% of polyps detected at CT colonography proved to be advanced neoplasia and did not differ significantly among radiologists (range, 14.4%-23.2%; P = .223). The overall per-polyp endoscopic confirmation rate was 93.5%, ranging from 80.0% to 97.6% among radiologists (P = .585). The overall percentage of nondiagnostic CT colonographic examinations was 0.7% and was consistent among radiologists (range, 0.3%-1.1%; P = .509). CONCLUSION Consistent performance for adenoma and advanced neoplasia detection, as well as other clinically relevant end points, were observed among radiologists at CT colonographic screening.

Colorectal Polyps Missed with Optical Colonoscopy Despite Previous Detection and Localization with CT Colonography

PURPOSE To retrospectively evaluate and characterize nondiminutive colorectal polyps prospectively detected by using computed tomographic (CT) colonography but not confirmed with subsequent nonblinded optical colonoscopy (OC). MATERIALS AND METHODS This study was institutional review board approved; the need for signed informed consent was waived. Over 113 months, 9336 adults (mean age, 57.1 years) underwent CT colonography, which yielded 2606 nondiminutive (≥6 mm) polyps. Of 1731 polyps that underwent subsequent nonblinded OC (ie, endoscopists provided advanced knowledge of specific polyp size, location, and morphologic appearance at CT colonography), 181 (10%) were not confirmed with initial endoscopy (ie, discordant), of which 37 were excluded (awaiting or lost to follow-up). After discordant polyp review, 66 of the 144 lesions were categorized as likely CT colonography false-positive findings (no further action) and 78 were categorized as potential OC false-negative (FN) findings. RESULTS Thirty-one of 144 (21.5%) of all discordant lesions were confirmed as FN findings at OC, including 40% (31 of 78) of those with OC and/or CT colonography follow-up. OC FN lesions were an average of 8.5 mm ± 3.3 in diameter and were identified with higher confidence at prospective CT colonography (on a 3-point confidence scale: mean, 2.8 vs 2.3; P = .001). OC FN findings were more likely than concordant polyps to be located in the right colon (respectively, 71% [22 of 31] vs 47% [723 of 1535]; P = .010). Most (81% [21 of 26]) OC FN lesions that were ultimately resected were neoplastic (adenomas or serrated lesions), of which 43% (nine of 21) were characterized as advanced lesions, and 89% (eight of nine) of advanced lesions occurred in the right colon. CONCLUSION In clinical practice, polyps prospectively identified with CT colonography but not confirmed with subsequent nonblinded (ie, despite a priori knowledge of the CT colonography findings) OC require additional review because a substantial proportion may be FN findings. Most FN findings found with OC demonstrated clinically significant histopathologic results, and a majority of advanced lesions occurred in the right colon.

Subclonal diversity arises early even in small colorectal tumours and contributes to differential growth fates

Objective and design The goal of the study was to determine whether the mutational profile of early colorectal polyps correlated with growth behaviour. The growth of small polyps (6–9 mm) that were first identified during routine screening of patients was monitored over time by interval imaging with CT colonography. Mutations in these lesions with known growth rates were identified by targeted next-generation sequencing. The timing of mutational events was estimated using computer modelling and statistical inference considering several parameters including allele frequency and fitness. Results The mutational landscape of small polyps is varied both within individual polyps and among the group as a whole but no single alteration was correlated with growth behaviour. Polyps carried 0–3 pathogenic mutations with the most frequent being in APC, KRAS/NRAS, BRAF, FBXW7 and TP53. In polyps with two or more pathogenic mutations, allele frequencies were often variable, indicating the presence of multiple populations within a single tumour. Based on computer modelling, detectable mutations occurred at a mean polyp size of 30±35 crypts, well before the tumour is of a clinically detectable size. Conclusions These data indicate that small colon polyps can have multiple pathogenic mutations in crucial driver genes that arise early in the existence of a tumour. Understanding the molecular pathway of tumourigenesis and clonal evolution in polyps that are at risk for progressing to invasive cancers will allow us to begin to better predict which polyps are more likely to progress into adenocarcinomas and which patients are at greater risk of developing advanced disease.