Meta-research: How many diagnostic or prognostic models published in radiological journals are evaluated externally?

OBJECTIVES: Prognostic and diagnostic models must work in their intended clinical setting, proven via "external evaluation", preferably by authors uninvolved with model development. By systematic review, we determined the proportion of models published in high-impact radiological journals that are evaluated subsequently. METHODS: We hand-searched three radiological journals for multivariable diagnostic/prognostic models 2013-2015 inclusive, developed using regression. We assessed completeness of data presentation to allow subsequent external evaluation. We then searched literature to August 2022 to identify external evaluations of these index models. RESULTS: We identified 98 index studies (73 prognostic; 25 diagnostic) describing 145 models. Only 15 (15%) index studies presented an evaluation (two external). No model was updated. Only 20 (20%) studies presented a model equation. Just 7 (15%) studies developing Cox models presented a risk table, and just 4 (9%) presented the baseline hazard. Two (4%) studies developing non-Cox models presented the intercept. Just 20 (20%) articles presented a Kaplan-Meier curve of the final model. The 98 index studies attracted 4224 citations (including 559 self-citations), median 28 per study. We identified just six (6%) subsequent external evaluations of an index model, five of which were external evaluations by researchers uninvolved with model development, and from a different institution. CONCLUSIONS: Very few prognostic or diagnostic models published in radiological literature are evaluated externally, suggesting wasted research effort and resources. Authors' published models should present data sufficient to allow external evaluation by others. To achieve clinical utility, researchers should concentrate on model evaluation and updating rather than continual redevelopment. CLINICAL RELEVANCE STATEMENT: The large majority of prognostic and diagnostic models published in high-impact radiological journals are never evaluated. It would be more efficient for researchers to evaluate existing models rather than practice continual redevelopment. KEY POINTS: • Systematic review of highly cited radiological literature identified few diagnostic or prognostic models that were evaluated subsequently by researchers uninvolved with the original model. • Published radiological models frequently omit important information necessary for others to perform an external evaluation: Only 20% of studies presented a model equation or nomogram. • A large proportion of research citing published models focuses on redevelopment and ignores evaluation and updating, which would be a more efficient use of research resources.

Prognostic factors to identify resolution of small bowel obstruction without need for operative management: systematic review.

OBJECTIVES: To identify imaging, clinical, and laboratory variables potentially prognostic for surgical management of small bowel obstruction. METHODS: Two researchers systematically reviewed indexed literature 2001-2021 inclusive for imaging, clinical, and laboratory variables potentially predictive of surgical management of small bowl obstruction and/or ischaemia at surgery, where performed. Risk of bias was assessed. Contingency tables for variables reported in at least 5 studies were extracted and meta-analysed to identify strong evidence of association with clinical outcomes, across studies. RESULTS: Thirty-one studies were ultimately included, reporting 4638 patients (44 to 313 per study). 11 (35%) studies raised no risk of bias concerns. CT was the modality reported most (29 studies, 94%). Meta-analysis of 21 predictors identified 5 strongly associated with surgical intervention, 3 derived from CT (peritoneal free fluid, odds ratio [OR] 3.24, 95%CI 2.45 to 4.29; high grade obstruction, OR 3.58, 95%CI 2.46 to 5.20; mesenteric inflammation, OR 2.61, 95%CI 1.94 to 3.50; abdominal distension, OR 2.43, 95%CI 1.34 to 4.42; peritonism, OR 3.97, 95%CI 2.67 to 5.90) and one with conservative management (previous abdominopelvic surgery, OR 0.58, 95%CI 0.40 to 0.85). Meta-analysis of 10 predictors identified 3 strongly associated with ischaemia at surgery, 2 derived from CT (peritoneal free fluid, OR 3.49, 95%CI 2.28 to 5.35; bowel thickening, OR 3.26 95%CI 1.91 to 5.55; white cell count, OR 4.76, 95%CI 2.71 to 8.36). CONCLUSIONS: Systematic review of patients with small bowel obstruction identified four imaging, three clinical, and one laboratory predictors associated strongly with surgical intervention and/or ischaemia at surgery. CLINICAL RELEVANCE STATEMENT: Via systematic review and meta-analysis, we identified imaging, clinical, and laboratory predictors strongly associated with surgical management of small bowel obstruction and/or ischaemia. Multivariable model development to guide management should incorporate these since they display strong evidence of potential utility. KEY POINTS: • While multivariable models incorporating clinical, laboratory, and imaging factors could predict surgical management of small bowel obstruction, none are used widely. • Via systematic review and meta-analysis we identified imaging, clinical, and laboratory variables strongly associated with surgical management and/or ischaemia at surgery. • Development of multivariable models to guide management should incorporate these predictors, notably CT scanning, since they display strong evidence of potential utility.

The effect of computer-aided detection markers on visual search and reader performance during concurrent reading of CT colonography.

OBJECTIVE: We aimed to identify the effect of computer-aided detection (CAD) on visual search and performance in CT Colonography (CTC) of inexperienced and experienced readers. METHODS: Fifteen endoluminal CTC examinations were recorded, each with one polyp, and two videos were generated, one with and one without a CAD mark. Forty-two readers (17 experienced, 25 inexperienced) interpreted the videos during infrared visual search recording. CAD markers and polyps were treated as regions of interest in data processing. This multi-reader, multi-case study was analysed using multilevel modelling. RESULTS: CAD drew readers' attention to polyps faster, accelerating identification times: median 'time to first pursuit' was 0.48 s (IQR 0.27 to 0.87 s) with CAD, versus 0.58 s (IQR 0.35 to 1.06 s) without. For inexperienced readers, CAD also held visual attention for longer. All visual search metrics used to assess visual gaze behaviour demonstrated statistically significant differences when "with" and "without" CAD were compared. A significant increase in the number of correct polyp identifications across all readers was seen with CAD (74 % without CAD, 87 % with CAD; p < 0.001). CONCLUSIONS: CAD significantly alters visual search and polyp identification in readers viewing three-dimensional endoluminal CTC. For polyp and CAD marker pursuit times, CAD generally exerted a larger effect on inexperienced readers. KEY POINTS: • Visual gaze is attracted by computer-assisted detection (CAD) marks on polyps • Inexperienced readers' gaze is affected more by CAD than experienced readers. • CAD marks could mean that the unannotated endoluminal surface is relatively neglected. • Correct polyp identification is increased significantly by CAD.

Small Polyps at Endoluminal CT Colonography Are Often Seen But Ignored by Radiologists.

OBJECTIVE: The objective of our study was to describe the characteristics of polyps viewed but then dismissed incorrectly by radiologists at endoluminal CT colonography (CTC), eye movements during these errors, and features provoking false-positive diagnoses. MATERIALS AND METHODS: Forty-two radiologists viewed 30 endoluminal CTC videos, each depicting a polyp, while their eye movements were tracked. Half of the videos had computer-assisted detection (CAD), and half did not. Classification errors were defined when proven polyps were seen but dismissed. Eye movements during these errors and during correct polyp identifications were compared with multilevel modeling. Polyps were divided subsequently into "difficult to classify" and "easy to classify" using a classification error threshold of more than 15%. Polyp diameter, height, and subjective conspicuity and the proportion of time viewed were compared between groups. RESULTS: Eye tracking revealed that 97% of false-negative polyp diagnoses were nonetheless preceded by the reader observing the polyp. The difficult polyps were significantly smaller than the easy polyps (mean diameter, 5.4 vs 8.2 mm, respectively p = 0.014) and were subjectively less conspicuous (median score, 4 vs 2; p = 0.0032). Readers spent proportionally less time viewing difficult polyps than viewing easy polyps (29.0% of the time they were on-screen vs 42.6%, respectively; p = 0.01) regardless of the presence of CAD. CONCLUSION: Even small and subjectively inconspicuous polyps attract reader gaze, but they are nonetheless ignored. These errors are made rapidly even with CAD. Efforts to improve reader performance at CTC should focus on decision making rather than detection alone.

Tracking eye gaze during interpretation of endoluminal three-dimensional CT colonography: visual perception of experienced and inexperienced readers.

PURPOSE: To identify and compare key stages of the visual process in experienced and inexperienced readers and to examine how these processes are used to search a moving three-dimensional ( 3D three-dimensional ) image and their relationship to false-negative errors. MATERIALS AND METHODS: Institutional review board research ethics approval was granted to use anonymized computed tomographic (CT) colonographic data from previous studies and to obtain eye-tracking data from volunteers. Sixty-five radiologists (27 experienced, 38 inexperienced) interpreted 23 endoluminal 3D three-dimensional CT colonographic videos. Eye movements were recorded by using eye tracking with a desk-mounted tracker. Readers indicated when they saw a polyp by clicking a computer mouse. Polyp location and boundary on each video frame were quantified and gaze data were related to the polyp boundary for each individual reader and case. Predefined metrics were quantified and used to describe and compare visual search patterns between experienced and inexperienced readers by using multilevel modeling. RESULTS: Time to first pursuit was significantly shorter in experienced readers (hazard ratio, 1.22 [95% confidence interval: 1.04, 1.44]; P = .017) but other metrics were not significantly different. Regardless of expertise, metrics such as assessment, identification period, and pursuit times were extended in videos where polyps were visible on screen for longer periods of time. In 97% (760 of 787) of observations, readers correctly pursued polyps. CONCLUSION: Experienced readers had shorter time to first eye pursuit, but many other characteristics of eye tracking were similar between experienced and inexperienced readers. Readers pursued polyps in 97% of observations, which indicated that errors during interpretation of 3D three-dimensional CT colonography in this study occurred in either the discovery or the recognition phase, but rarely in the scanning phase of radiologic image inspection.

Detection of extracolonic pathologic findings with CT colonography: a discrete choice experiment of perceived benefits versus harms.

PURPOSE: To determine the maximum rate of false-positive diagnoses that patients and health care professionals were willing to accept in exchange for detection of extracolonic malignancy by using computed tomographic (CT) colonography for colorectal cancer screening. MATERIALS AND METHODS: After obtaining ethical approval and informed consent, 52 patients and 50 health care professionals undertook two discrete choice experiments where they chose between unrestricted CT colonography that examined intra- and extracolonic organs or CT colonography restricted to the colon, across different scenarios. The first experiment detected one extracolonic malignancy per 600 cases with a false-positive rate varying across scenarios from 0% to 99.8%. One experiment examined radiologic follow-up generated by false-positive diagnoses while the other examined invasive follow-up. Intracolonic performance was identical for both tests. The median tipping point (maximum acceptable false-positive rate for extracolonic findings) was calculated overall and for both groups by bootstrap analysis. RESULTS: The median tipping point for radiologic follow-up occurred at a false-positive rate greater than 99.8% (interquartile ratio [IQR], 10 to >99.8%). Participants would tolerate at least a 99.8% rate of unnecessary radiologic tests to detect an additional extracolonic malignancy. The median tipping-point for invasive follow-up occurred at a false-positive rate of 10% (IQR, 2 to >99.8%). Tipping points were significantly higher for patients than for health care professionals for both experiments (>99.8 vs 40% for radiologic follow-up and >99.8 vs 5% for invasive follow-up, both P < .001). CONCLUSION: Patients and health care professionals are willing to tolerate high rates of false-positive diagnoses with CT colonography in exchange for diagnosis of extracolonic malignancy. The actual specificity of screening CT colonography for extracolonic findings in clinical practice is likely to be highly acceptable to both patients and health care professionals. Online supplemental material is available for this article.

Non- or full-laxative CT colonography vs. endoscopic tests for colorectal cancer screening: a randomised survey comparing public perceptions and intentions to undergo testing.

OBJECTIVES: Compare public perceptions and intentions to undergo colorectal cancer screening tests following detailed information regarding CT colonography (CTC; after non-laxative preparation or full-laxative preparation), optical colonoscopy (OC) or flexible sigmoidoscopy (FS). METHODS: A total of 3,100 invitees approaching screening age (45-54 years) were randomly allocated to receive detailed information on a single test and asked to return a questionnaire. Outcomes included perceptions of preparation and test tolerability, health benefits, sensitivity and specificity, and intention to undergo the test. RESULTS: Six hundred three invitees responded with valid questionnaire data. Non-laxative preparation was rated more positively than enema or full-laxative preparations [effect size (r) = 0.13 to 0.54; p < 0.0005 to 0.036]; both forms of CTC and FS were rated more positively than OC in terms of test experience (r = 0.26 to 0.28; all p-values < 0.0005). Perceptions of health benefits, sensitivity and specificity (p = 0.250 to 0.901), and intention to undergo the test (p = 0.213) did not differ between tests (n = 144-155 for each test). CONCLUSIONS: Despite non-laxative CTC being rated more favourably, this study did not find evidence that offering it would lead to substantially higher uptake than full-laxative CTC or other methods. However, this study was limited by a lower than anticipated response rate. KEY POINTS: • Improving uptake of colorectal cancer screening tests could improve health benefits • Potential invitees rate CTC and flexible sigmoidoscopy more positively than colonoscopy • Non-laxative bowel preparation is rated better than enema or full-laxative preparations • These positive perceptions alone may not be sufficient to improve uptake • Health benefits and accuracy are rated similarly for preventative screening tests.

Method for tracking eye gaze during interpretation of endoluminal 3D CT colonography: technical description and proposed metrics for analysis.

PURPOSE: To develop an eye-tracking method applicable to three-dimensional (3D) images, where the abnormality is both moving and changing in size. MATERIALS AND METHODS: Research ethics committee approval was granted to record eye-tracking data from six inexperienced readers who inspected eight short (<30 seconds) endoluminal fly-through videos extracted from computed tomographic (CT) colonography examinations. Cases included true-positive and false-positive polyp detections from a previous study (polyp diameters, 5-25 mm). Eye tracking was performed with a desk-mounted tracker, and readers indicated when they saw a polyp with a mouse click. The polyp location on each video frame was quantified subsequently by using a circular mask. Gaze data related to each video frame were calculated relative to the visible polyp boundary and used to identify eye movements that pursue a polyp target as it changes size and position during fly-through. Gaze data were then related to positive polyp detections by readers. RESULTS: Tracking eye gaze on moving 3D images was technically feasible. Gaze was successfully classified by using pursuit analysis, and pursuit-based gaze metrics were able to help discriminate different reader search behaviors and methods of allocating visual attention during polyp identification. Of a total of 16 perceptual errors, 15 were recognition errors. There was only one visual search error. The largest polyp (25 mm) was seen but not recognized by five of six readers. CONCLUSION: Tracking a reader's gaze during endoluminal interpretation of 3D data sets is technically feasible and can be described with pursuit-based metrics. Perceptual errors can be classified into visual search errors and recognition errors. Recognition errors are more frequent in inexperienced readers.

CT colonography: external clinical validation of an algorithm for computer-assisted prone and supine registration.

PURPOSE: To perform external validation of a computer-assisted registration algorithm for prone and supine computed tomographic (CT) colonography and to compare the results with those of an existing centerline method. MATERIALS AND METHODS: All contributing centers had institutional review board approval; participants provided informed consent. A validation sample of CT colonographic examinations of 51 patients with 68 polyps (6-55 mm) was selected from a publicly available, HIPAA compliant, anonymized archive. No patients were excluded because of poor preparation or inadequate distension. Corresponding prone and supine polyp coordinates were recorded, and endoluminal surfaces were registered automatically by using a computer algorithm. Two observers independently scored three-dimensional endoluminal polyp registration success. Results were compared with those obtained by using the normalized distance along the colonic centerline (NDACC) method. Pairwise Wilcoxon signed rank tests were used to compare gross registration error and McNemar tests were used to compare polyp conspicuity. RESULTS: Registration was possible in all 51 patients, and 136 paired polyp coordinates were generated (68 polyps) to test the algorithm. Overall mean three-dimensional polyp registration error (mean ± standard deviation, 19.9 mm ± 20.4) was significantly less than that for the NDACC method (mean, 27.4 mm ± 15.1; P = .001). Accuracy was unaffected by colonic segment (P = .76) or luminal collapse (P = .066). During endoluminal review by two observers (272 matching tasks, 68 polyps, prone to supine and supine to prone coordinates), 223 (82%) polyp matches were visible (120° field of view) compared with just 129 (47%) when the NDACC method was used (P < .001). By using multiplanar visualization, 48 (70%) polyps were visible after scrolling ± 15 mm in any multiplanar axis compared with 16 (24%) for NDACC (P < .001). CONCLUSION: Computer-assisted registration is more accurate than the NDACC method for mapping the endoluminal surface and matching the location of polyps in corresponding prone and supine CT colonographic acquisitions.

Systematic review: bias in imaging studies - the effect of manipulating clinical context, recall bias and reporting intensity.

OBJECTIVES: To perform a systematic review of diagnostic test accuracy studies which manipulate or investigate the context of interpretation. In particular, those which modify or conceal sample characteristics (e.g. disease prevalence or reporting intensity) or research setting ("laboratory" versus "field"). We also investigated recall bias. METHODS: We searched the biomedical literature to March 2010 using 3 complementary strategies. Inclusion criteria were: imaging studies quantifying the effect on diagnosis of modifying the context of observers' interpretations, varying disease prevalence, concealing sample characteristics, reporting intensity and recall bias. RESULTS: 11247 abstracts were reviewed, 201 full texts examined and 12 ultimately included. There were 5 to 9520 patients and 2 to 129 observers per study. Nine studies investigated clinical review bias of sample level information. Only 3 studies investigated prevalence, 2 of which investigated maximum enrichment well below the levels often used by researchers. We identified no research specifically directed at concealing disease prevalence. Available research found no evidence of recall bias or "washout" on study results. CONCLUSIONS: Several sources of bias central to the design of diagnostic test accuracy studies are poorly researched; the implications for evidence-based-practice remain uncertain. Research is suggested to guide methodological design, particularly in the context of screening. KEY POINTS: Imaging research studies often ignore the possible effect of disease prevalence It is unclear how the expectation of disease influences radiological interpretation The potential effect of observer recall bias is poorly researched Such factors might introduce bias into radiological research methodology This systematic review attempts to illustrate these points.

Registration of the endoluminal surfaces of the colon derived from prone and supine CT colonography.

PURPOSE: Computed tomographic (CT) colonography is a relatively new technique for detecting bowel cancer or potentially precancerous polyps. CT scanning is combined with three-dimensional (3D) image reconstruction to produce a virtual endoluminal representation similar to optical colonoscopy. Because retained fluid and stool can mimic pathology, CT data are acquired with the bowel cleansed and insufflated with gas and patient in both prone and supine positions. Radiologists then match visually endoluminal locations between the two acquisitions in order to determine whether apparent pathology is real or not. This process is hindered by the fact that the colon, essentially a long tube, can undergo considerable deformation between acquisitions. The authors present a novel approach to automatically establish spatial correspondence between prone and supine endoluminal colonic surfaces after surface parameterization, even in the case of local colon collapse. METHODS: The complexity of the registration task was reduced from a 3D to a 2D problem by mapping the surfaces extracted from prone and supine CT colonography onto a cylindrical parameterization. A nonrigid cylindrical registration was then performed to align the full colonic surfaces. The curvature information from the original 3D surfaces was used to determine correspondence. The method can also be applied to cases with regions of local colonic collapse by ignoring the collapsed regions during the registration. RESULTS: Using a development set, suitable parameters were found to constrain the cylindrical registration method. Then, the same registration parameters were applied to a different set of 13 validation cases, consisting of 8 fully distended cases and 5 cases exhibiting multiple colonic collapses. All polyps present were well aligned, with a mean (+/- std. dev.) registration error of 5.7 (+/- 3.4) mm. An additional set of 1175 reference points on haustral folds spread over the full endoluminal colon surfaces resulted in an error of 7.7 (+/- 7.4) mm. Here, 82% of folds were aligned correctly after registration with a further 15% misregistered by just onefold. CONCLUSIONS: The proposed method reduces the 3D registration task to a cylindrical registration representing the endoluminal surface of the colon. Our algorithm uses surface curvature information as a similarity measure to drive registration to compensate for the large colorectal deformations that occur between prone and supine data acquisitions. The method has the potential to both enhance polyp detection and decrease the radiologist's interpretation time.

Evidence review and status update on computed tomography colonography.

Computed tomographic (CT) colonography is being implemented increasingly in the USA and Europe, and in many centers it has become the radiological technique of choice for imaging the whole colorectum. Although high diagnostic accuracy has been demonstrated in both screening and symptomatic populations, controversy persists regarding implementation, who should interpret the examination, and its cost effectiveness, particularly in the context of primary colorectal cancer screening. Published research in recent years has demonstrated efficacy in a wide range of patient groups, striking technical improvements, and high levels of patient acceptability. New developments continue in the fields of computer aided detection, digital cleansing, and integration into positron emission tomography. The purpose of this review is to bring the reader up-to-date with the latest developments in CT colonography, in particular, those of the last year.

Prognostic biomarkers to identify patients likely to develop severe Crohn's disease: a systematic review.

BACKGROUND: Identification of biomarkers that predict severe Crohn's disease is an urgent unmet research need, but existing research is piecemeal and haphazard. OBJECTIVE: To identify biomarkers that are potentially able to predict the development of subsequent severe Crohn's disease. DESIGN: This was a prognostic systematic review with meta-analysis reserved for those potential predictors with sufficient existing research (defined as five or more primary studies). DATA SOURCES: PubMed and EMBASE searched from inception to 1 January 2016, updated to 1 January 2018. REVIEW METHODS: Eligible studies were studies that compared biomarkers in patients who did or did not subsequently develop severe Crohn's disease. We excluded biomarkers that had insufficient research evidence. A clinician and two statisticians independently extracted data relating to predictors, severe disease definitions, event numbers and outcomes, including odds/hazard ratios. We assessed risk of bias. We searched for associations with subsequent severe disease rather than precise estimates of strength. A random-effects meta-analysis was performed separately for odds ratios. RESULTS: In total, 29,950 abstracts yielded just 71 individual studies, reporting 56 non-overlapping cohorts. Five clinical biomarkers (Montreal behaviour, age, disease duration, disease location and smoking), two serological biomarkers (anti-Saccharomyces cerevisiae antibodies and anti-flagellin antibodies) and one genetic biomarker (nucleotide-binding oligomerisation domain-containing protein 2) displayed statistically significant prognostic potential. Overall, the strongest association with subsequent severe disease was identified for Montreal B2 and B3 categories (odds ratio 4.09 and 6.25, respectively). LIMITATIONS: Definitions of severe disease varied widely, and some studies confounded diagnosis and prognosis. Risk of bias was rated as 'high' in 92% of studies overall. Some biomarkers that are used regularly in daily practice, for example C-reactive protein, were studied too infrequently for meta-analysis. CONCLUSIONS: Research for individual biomarkers to predict severe Crohn's disease is scant, heterogeneous and at a high risk of bias. Despite a large amount of potential research, we encountered relatively few biomarkers with data sufficient for meta-analysis, identifying only eight biomarkers with potential predictive capability. FUTURE WORK: We will use existing data sets to develop and then validate a predictive model based on the potential predictors identified by this systematic review. Contingent on the outcome of that research, a prospective external validation may prove clinically desirable. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016029363. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 45. See the NIHR Journals Library website for further project information.

Crohn's disease causes inflammation of the intestines. Traditional treatment uses drugs, such as steroids, at a gradually increasing dose as symptoms worsen. Newer 'biological' drugs may stop disease, but are not used as an early treatment because they are expensive and have serious side effects. Using biologicals early means knowing which patients will develop severe disease in the future. A 'prognostic biomarker' is a measurement made on a patient that predicts a future outcome. A lot of research has attempted to identify biomarkers that predict severe Crohn's disease, but research is haphazard and of variable quality. We therefore carried out a 'systematic review', which identifies research in a comprehensive and unbiased fashion. We found nearly 30,000 research papers, 71 of which were acceptable quality and described 56 groups of Crohn's disease patients. We then used a statistical method called 'meta-analysis' to combine results from multiple studies. This allowed us to identify the most promising biomarkers to predict future severe disease. We found five clinical biomarkers (e.g. age and smoking), two blood biomarkers and one genetic biomarker that seemed reasonably able to predict future severe Crohn's disease. However, we also found that most research was poorly performed and frequently confused diagnosis (current disease) with prognosis (future disease). Some commonly used biomarkers were not sufficiently investigated. We were surprised to identify so few prognostic biomarkers in the face of a seemingly vast amount of research. Future research should be better conducted and not confuse diagnosis with prognosis. We will use statistical methods to combine the promising biomarkers that we identified into a 'prognostic model', which is a mathematical formula that provides the likelihood of developing severe disease in the future. We will then test how well this works by using patient data from existing Crohn's disease databases.

Magnetic Resonance of the Small Bowel: How to Do It.

Small bowel magnetic resonance (MR) imaging has been clinically implemented for many years, albeit with variation in study technique. Considerable research has been performed during this time regarding optimum patient preparation, choice of enteric contrast medium, and MR imaging sequence protocol but findings have not been universally implemented. However, evidence-based consensus statements have recently been published from the United States and Europe. This article summarizes key findings from this guidance and presents practice examples from the authors' own institution.

Polyp characteristics correctly annotated by computer-aided detection software but ignored by reporting radiologists during CT colonography.

PURPOSE: To retrospectively describe the characteristics of polyps incorrectly dismissed by radiologists despite appropriate computer-aided detection (CAD) prompting during computed tomographic (CT) colonography. MATERIALS AND METHODS: Ethics committee approval and patient informed consent were obtained from institutions that provided the data sets used in this HIPAA-compliant study. A total of 111 polyps that had a diameter of at least 6 mm and were detected with CAD were collated from three previous studies in which researchers investigated radiologist performance with and without CAD (total, 25 readers). Two new observers graded each polyp with predefined criteria, including polyp size, morphology, and location; data set quality; ease of visualization; tagging use and polyp coating; colonic curvature; CAD mark obscuration; and number of false-positive findings. The 86 polyps that were missed before CAD (those that were unreported by one or more original readers) were divided into those that remained unreported after CAD (no CAD gain, n = 36) and those that were reported correctly by at least one additional reader (CAD gain, n = 50). Logistic-regression analysis and the Fisher exact and Mann-Whitney tests were used to compare the results of both groups with each other and with a control group of 25 polyps, all of which were detected by readers without CAD. RESULTS: Before CAD, polyps 10 mm in diameter or larger, those that were rated easy to visualize, and those that were uncoated by tagged fluid were less likely to be missed (72%, 76%, and 80% of control polyps vs 43%, 43%, and 59% of missed polyps, respectively; P < .001, P < .01, and P < .03, respectively). After CAD, the odds of CAD gain decreased with increasing polyp size (odds ratio, 0.92; 95% confidence interval: 0.85, 1.00; P = .04) and irregular morphology (odds ratio, 0.28; 95% confidence interval: 0.08, 0.92; P = .04). CONCLUSION: Larger irregular polyps are a common source of incorrect radiologist dismissal, despite correct CAD prompting.

Diagnostic accuracy of MRI in assessing tumor regression and identifying complete response in patients with locally advanced rectal cancer after neoadjuvant treatment.

BACKGROUND: The diagnostic accuracy of Magnetic Resonance Imaging (MRI) in restaging locally advanced rectal cancers (LARC) after neoadjuvant chemo-radio therapy (NCRT) has been under recent scrutiny. There is limited data on the accuracy of MRI and its timing in assessing tumor regression grade (TRG) and in identifying patients with complete response (CR). NCRT seems to cause tissue inflammation and oedema which renders reading the scans difficult for radiologist. AIM: This study aims to assess the accuracy of MRI at different time intervals after NCRT in staging TRG and in identifying CR. Inter-observer agreement between 2 blinded radiologists will also be assessed. METHOD: In this retrospective analysis, all patients diagnosed with LARC between January 2003 and 2014, who underwent long-course NCRT, who had at least one post-treatment MRI scan, and who underwent surgery with available pathology results are included. Histopathology staging is considered the reference standard. Accuracy of MRI in T staging and in TRG staging is assessed using weighted kappa. Accuracy, sensitivity, and specificity in identifying CR are calculated from a 2 × 2 contingency table. Inter-observer agreement between two-staging blinded radiologists is calculated using weighted kappa. These are calculated at 2 different time intervals after completion of NCRT. RESULTS: 114 patients were identified who had a first post-treatment MRI scan at an average of 6.2 weeks after completion of NCRT. A subgroup of 68 patients had a second post-treatment MRI at an average of 10.4 weeks. Pathology results were available for 103 patients. By the second post-treatment scan, an additional 25% of patients experienced downstaging; accuracy in T staging increased from 43% to 57.4%; accuracy in TRG staging rose from 28.2% to 38.1%; accuracy in identifying CR rose from 83.4% to 84.1%. Inter-observer agreement in T staging rose from 0.1 for first post-treatment MRI to 0.206 for second post-treatment MRI. CONCLUSION: This study advocates that restaging should occur at 10 weeks rather than the standard 6 weeks. This results in higher complete response rates and higher concordance with pathological specimens. Our results also showed that it is easier for radiologists to stage the MRI scans, resulting in higher inter-rater agreements.

Prognostic biomarkers to identify patients destined to develop severe Crohn's disease who may benefit from early biological therapy: protocol for a systematic review, meta-analysis and external validation.

BACKGROUND: It is believed increasingly that patients with severe Crohn's disease are best treated early with biological therapy, which may ameliorate subsequent disease course and diminish long-term complications. However, we cannot predict currently which new presentations of Crohn's disease are destined to develop severe disease so treatment cannot be targeted to the most appropriate patients. Accordingly, via systematic review and meta-analysis we aim to identify if biomarkers of disease activity are able to predict development of severe disease. METHODS/DESIGN: We will search the primary literature and conference proceedings for studies of biomarkers of all types including clinical, endoscopic, radiological, faecal, urinary, serological, genetic, and histological. Precise definition of "severe" disease is elusive so we will include sensitivity analysis to account for different definitions. We will use the CHARMS checklist to frame our question and to extract data. We will extract the study design, setting, participant characteristics, biomarker(s) investigated, and study outcomes. Bias will be assessed via the PROBAST tool. We will present the results using narrative and graphical methods. We will present the summary by meta-analysis where there are sufficient studies with reasonable homogeneity, using methods appropriate to the type of data extracted. Heterogeneity will be presented via Forest and ROC plots. DISCUSSION: If this systematic review and meta-analysis identifies biomarkers that appear sufficiently predictive for subsequent severe disease course, we aim to combine them in a predictive model, followed by external validation using individual patient data. A predictive model able to identify new presentations of Crohn's disease destined to develop severe disease subsequently would have considerable clinical utility for patient management. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016029363 .

Assessment of the Incremental Benefit of Computer-Aided Detection (CAD) for Interpretation of CT Colonography by Experienced and Inexperienced Readers.

OBJECTIVES: To quantify the incremental benefit of computer-assisted-detection (CAD) for polyps, for inexperienced readers versus experienced readers of CT colonography. METHODS: 10 inexperienced and 16 experienced radiologists interpreted 102 colonography studies unassisted and with CAD utilised in a concurrent paradigm. They indicated any polyps detected on a study sheet. Readers' interpretations were compared against a ground-truth reference standard: 46 studies were normal and 56 had at least one polyp (132 polyps in total). The primary study outcome was the difference in CAD net benefit (a combination of change in sensitivity and change in specificity with CAD, weighted towards sensitivity) for detection of patients with polyps. RESULTS: Inexperienced readers' per-patient sensitivity rose from 39.1% to 53.2% with CAD and specificity fell from 94.1% to 88.0%, both statistically significant. Experienced readers' sensitivity rose from 57.5% to 62.1% and specificity fell from 91.0% to 88.3%, both non-significant. Net benefit with CAD assistance was significant for inexperienced readers but not for experienced readers: 11.2% (95%CI 3.1% to 18.9%) versus 3.2% (95%CI -1.9% to 8.3%) respectively. CONCLUSIONS: Concurrent CAD resulted in a significant net benefit when used by inexperienced readers to identify patients with polyps by CT colonography. The net benefit was nearly four times the magnitude of that observed for experienced readers. Experienced readers did not benefit significantly from concurrent CAD.

Mechanisms of hyoscine butylbromide to improve adenoma detection: A case-control study of surface visualization at simulated colonoscope withdrawal.

BACKGROUND AND STUDY AIMS: Antispasmodics may improve mucosal visualization during colonoscope withdrawal, potentially improving polyp and adenoma detection. Meta-analysis and case-control studies suggest a 9 % to 13 % relative increase in adenoma and polyp detection. We aimed to assess the impact of hyoscine butylbromide on the expected visualization during colonoscope withdrawal using a CT colonography (CTC) simulation. PATIENTS AND METHODS: Datasets from a previous CTC study examining the effect of antispasmodic were re-analyzed with customised CTC software, adjusted to simulate a standard colonoscopic view. Eighty-six patients received intravenous (IV) hyoscine butylbromide 20 mg, 40 mg or no antispasmodic. Main outcome measurements at unidirectional flythrough, simulating colonoscope withdrawal, were percentage colonic surface visualization, numbers and sizes of unseen areas, and colonic length. RESULTS: Use of antispasmodic was associated with a significant relative increase in percentage surface visualization of 2.6 % to 3.9 %, compared with no antispasmodic, P < 0.006. Total numbers of missed areas and intermediate sized (300 - 1000 mm(2)) missed areas were significantly decreased, by approximately 20 %. There were no differences between the 20-mg and 40-mg doses. Mean colonic length (161 - 169 cm) was unchanged by antispasmodic. CONCLUSIONS: IV hyoscine butylbromide at simulated colonoscope withdrawal was associated with significant increases in surface visualization, which might explain up to half the improvement in adenoma detection seen in clinical studies.

Quantifying public preferences for different bowel preparation options prior to screening CT colonography: a discrete choice experiment.

OBJECTIVES: CT colonography (CTC) may be an acceptable test for colorectal cancer screening but bowel preparation can be a barrier to uptake. This study tested the hypothesis that prospective screening invitees would prefer full-laxative preparation with higher sensitivity and specificity for polyps, despite greater burden, over less burdensome reduced-laxative or non-laxative alternatives with lower sensitivity and specificity. DESIGN: Discrete choice experiment. SETTING: Online, web-based survey. PARTICIPANTS: 2819 adults (45-54 years) from the UK responded to an online invitation to take part in a cancer screening study. Quota sampling ensured that the sample reflected key demographics of the target population and had no relevant bowel disease or medical qualifications. The analysis comprised 607 participants. INTERVENTIONS: After receiving information about screening and CTC, participants completed 3-4 choice scenarios. Scenarios showed two hypothetical forms of CTC with different permutations of three attributes: preparation, sensitivity and specificity for polyps. PRIMARY OUTCOME MEASURES: Participants considered the trade-offs in each scenario and stated their preferred test (or chose neither). RESULTS: Preparation and sensitivity for polyps were both significant predictors of preferences (coefficients: -3.834 to -6.346 for preparation, 0.207-0.257 for sensitivity; p<0.0005). These attributes predicted preferences to a similar extent. Realistic specificity values were non-significant (-0.002 to 0.025; p=0.953). Contrary to our hypothesis, probabilities of selecting tests were similar for realistic forms of full-laxative, reduced-laxative and non-laxative preparations (0.362-0.421). However, they were substantially higher for hypothetical improved forms of reduced-laxative or non-laxative preparations with better sensitivity for polyps (0.584-0.837). CONCLUSIONS: Uptake of CTC following non-laxative or reduced-laxative preparations is unlikely to be greater than following full-laxative preparation as perceived gains from reduced burden may be diminished by reduced sensitivity. However, both attributes are important so a more sensitive form of reduced-laxative or non-laxative preparation might improve uptake substantially.