Colorectal Cancer: Performance and Evaluation for CT Colonography Screening- A Multicenter Cluster-randomized Controlled Trial.

Background Most radiologists reporting CT colonography (CTC) do not undergo compulsory performance accreditation, potentially lowering diagnostic sensitivity. Purpose To determine whether 1-day individualized training in CTC reporting improves diagnostic sensitivity of experienced radiologists for 6-mm or larger lesions, the durability of any improvement, and any associated factors. Materials and Methods This prospective, multicenter cluster-randomized controlled trial was performed in National Health Service hospitals in England and Wales between April 2017 and January 2020. CTC services were cluster randomized into intervention (1-day training plus feedback) or control (no training or feedback) arms. Radiologists in the intervention arm attended a 1-day workshop focusing on CTC reporting pitfalls with individualized feedback. Radiologists in the control group received no training. Sensitivity for 6-mm or larger lesions was tested at baseline and 1, 6, and 12 months thereafter via interpretation of 10 CTC scans at each time point. The primary outcome was the mean difference in per-lesion sensitivity between arms at 1 month, analyzed using multilevel regression after adjustment for baseline sensitivity. Secondary outcomes included per-lesion sensitivity at 6- and 12-month follow-up, sensitivity for flat neoplasia, and effect of prior CTC experience. Results A total of 69 hospitals were randomly assigned to the intervention (31 clusters, 80 radiologists) or control (38 clusters, 59 radiologists) arm. Radiologists were experienced (median, 500-999 CTC scans interpreted) and reported CTC scans routinely (median, 151-200 scans per year). One-month sensitivity improved after intervention (66.4% [659 of 992]) compared with sensitivity in the control group (42.4% [278 of 655]; difference = 20.8%; 95% CI: 14.6, 27.0; P < .001). Improvements were maintained at 6 (66.4% [572 of 861] vs 50.5% [283 of 560]; difference = 13.0%; 95% CI: 7.4, 18.5; P < .001) and 12 (63.7% [310 of 487] vs 44.4% [187 of 421]; difference = 16.7%; 95% CI: 10.3, 23.1; P < .001) months. This beneficial effect applied to flat lesions (difference = 22.7%; 95% CI: 15.5, 29.9; P < .001) and was independent of career experience (≥1500 CTC scans: odds ratio = 1.09; 95% CI: 0.88, 1.36; P = .22). Conclusion For radiologists evaluating CT colonography studies, a 1-day training intervention yielded sustained improvement in detection of clinically relevant colorectal neoplasia, independent of previous career experience. Clinical trial registration no. NCT02892721 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Pickhardt in this issue. An earlier incorrect version appeared online and in print. This article was corrected on February 28, 2022.

Influence of diffusion weighted imaging and contrast enhanced T1 sequences on the diagnostic accuracy of magnetic resonance enterography for Crohn's disease.

OBJECTIVES: To evaluate the additional diagnostic benefit of diffusion weighted imaging (DWI) and contrast enhanced (CE) images during MR enterography (MRE) of Crohn's disease. METHODS: Datasets from 73 patients (mean age 32; 40 male) (28 new-diagnosis, 45 relapsed) were read independently by two radiologists selected from a pool of 13. Radiologists interpreted datasets using three sequential sequence blocks: (1) T2 weighted and steady state free precession gradient echo (SSFP) images alone (T2^); (2) T2 weighted and SSFP images with DWI (T2 + DWI^) and; (3) T2 weighted images, SSFP, DWI and post-contrast enhanced (CE) T1 images (T2 + DWI + CE^), documenting presence, location, and activity of small bowel disease. For each sequence block, sensitivity and specificity (readers combined) was calculated against an outcome-based construct reference standard. RESULTS: 59/73 patients had small bowel disease. Per-patient sensitivity for disease detection was essentially identical (80 % [95 % CI 72, 86], 81 % [73,87], and 79 % [71,86] for T2^, T2 + DWI^and T2 + DWI + CE^respectively). Specificity was identical (82 % [64 to 92]). Per patient sensitivity for disease extent was 56 % (47,65), 56 % (47,65) and 52 % (43 to 61) respectively, and specificity was 82 % (64 to 92) for all blocks. Sensitivity for active disease was 97 % (90,99), 97 % (90,99) and 98 % (92,99), and specificity was also comparable between all sequence combination reads. Results were consistent across segments and newly diagnosed/relapse patients. CONCLUSION: There is no additional diagnostic benefit of adding either DWI or CE to T2 FSE and SSFP sequences for evaluating small bowel Crohn's disease, suggesting MRE protocols can be simplified safely.

Interobserver variation in the interpretation of magnetic resonance enterography in Crohn's disease.

OBJECTIVES: To evaluate interobserver variability for diagnosis of disease presence and extent of small bowel and colonic Crohn's disease using MR enterography (MRE). METHODS: Data from the first 73 consecutive patients (mean age 32, 33F, 28 new diagnosis, 45 suspected relapse) recruited to a multicentre, prospective diagnostic accuracy trial evaluating MRE for small bowel Crohn's disease were each read independently by three (from a pool of 20) radiologists. Radiologists documented presence and segmental location of small bowel Crohn's disease and recorded morphological mural/extramural parameters for involved segments. Per patient percentage agreement for disease presence and extent were calculated against an outcome-based construct reference standard (averaged between pairs of readers). Prevalence-adjusted bias-adjusted κ (PABAK) was calculated. RESULTS: Agreement for small bowel disease presence for new diagnosis/relapsed patients was 68%(κ = 0.36)/ 78% (κ = 0.56) and 43%(κ = 0.14)/ 53% for disease extent (κ = 0.07), respectively. For disease presence, all three radiologists agreed correctly with the reference standard in 41/59 (69%) of patients with small bowel involvement, and in 8/14 (57%) cases of without small bowel disease. Agreement was highest for multisegment disease, greater than 5 cm in length, with mural thickness>6 mm, and increased mural T2 signal. Agreement for colonic disease presence was 61% (κ = 0.21 fair agreement) for new diagnosis/ 60% (κ = 0.20, slight agreement) for relapsed patients. CONCLUSION: There is a reasonable agreement between radiologists for small bowel disease presence using MRE for newly diagnosed Crohn's disease, and patients with suspected relapse, respectively. Agreement is lower for disease extent. ADVANCES IN KNOWLEDGE: There is reasonable agreement between radiologists for small bowel disease presence using MRE for newly diagnosed (68%) Crohn's disease, and patients with suspected relapse (78%). Agreement is lower for disease extent (43% new diagnosis and 53% suspected relapse).

MR enterographic manifestations of small bowel Crohn disease.

Magnetic resonance (MR) enterography is a clinically useful technique for the evaluation of both intraluminal and extraluminal small bowel disease, particularly in younger patients with Crohn disease. MR enterography offers the advantages of multiplanar capability and lack of ionizing radiation. It allows evaluation of bowel wall contrast enhancement, wall thickening, and edema, findings useful for the assessment of Crohn disease activity. MR enterography can also depict other pathologic findings such as lymphadenopathy, fistula and sinus formation, abscesses, and abnormal fold patterns. Even subtle disease manifestations may be detected when adequate distention of the small bowel is achieved, although endoscopic and double-contrast barium small bowel techniques remain superior in the depiction of changes in early Crohn disease (eg, aphthoid ulceration). Further research will be needed to determine whether MR imaging enhancement patterns may reliably help discriminate between active and inactive disease.

Compulsive hoarding: an interpretative phenomenological analysis.

BACKGROUND: This project aimed to explore the experiences of people who compulsively hoard and how they make sense of their own hoarding behaviours. METHOD: A total of 11 compulsive hoarders were recruited and interviewed using a simple semi-structured interview format, designed for the purposes of the study. The resulting transcribed interviews were analyzed using interpretive-phenomenological analysis. RESULTS: Four super-ordinate discrete, but interacting, themes were found: (1) childhood factors; (2) the participants' relationship to their hoarded items; (3) cognitive and behavioural avoidance of discard; and (4) the impact of hoarding on self, others and the home environment. The themes as a whole described people entrapped in massively cluttered physical environments of their own making. Efforts at discard appeared consistently sabotaged by cognitive/behavioural avoidance, thereby creating maintaining factors of associated personal distress and environmental decline. CONCLUSIONS: The results are discussed in the context of the extant evidence concerning hoarding, the distinct contribution made by the current results and the identified methodological shortcomings of the research approach.

Mural Crohn disease: correlation of dynamic contrast-enhanced MR imaging findings with angiogenesis and inflammation at histologic examination--pilot study.

PURPOSE: To determine mural perfusion dynamics in Crohn disease by using dynamic contrast material-enhanced magnetic resonance (MR) imaging and to correlate these with histopathologic markers of inflammation and angiogenesis. MATERIALS AND METHODS: Ethical permission was given by the University College London Hospital ethics committee, and informed consent was obtained from all participants. Eleven consecutive patients with Crohn disease (eight female patients, three men; mean age, 39.5 years; range, 16.4-66.6 years) undergoing elective small-bowel resection were recruited between July 2006 and December 2007. Harvey-Bradshaw index, C-reactive protein (CRP) level, and disease chronicity were recorded. Preoperatively, dynamic contrast-enhanced MR imaging was performed through the section of bowel destined for resection, and slope of enhancement, time to maximum enhancement, enhancement ratio, the volume transfer coefficient K(trans), and the extracellular volume fraction v(e) were calculated for the affected segment. Ex vivo surgical specimens were imaged to facilitate imaging-pathologic correlation. Histopathologic sampling of the specimen was performed through the imaged tissue, and microvascular density (MVD) was determined, together with acute and chronic inflammation scores. Correlations between clinical, MR imaging, and histopathologic data were made by using the Kendall rank correlation and linear regression. RESULTS: Disease chronicity was positively correlated with enhancement ratio (correlation coefficient, 0.82; P = .002). Slope of enhancement demonstrated a significant negative correlation with MVD (correlation coefficient, -0.86; P < .001). There was a negative correlation between CRP level and slope of enhancement (correlation coefficient, -0.77; P = .006). Neither acute nor chronic inflammation score correlated with any other parameter. CONCLUSION: Certain MR imaging-derived mural hemodynamic parameters correlate with disease chronicity and angiogenesis in Crohn disease, but not with histologic and clinical markers of inflammation. Data support the working hypothesis that microvessel permeability increases with disease chronicity and that tissue MVD is actually inversely related to mural blood flow.

Mural inflammation in Crohn disease: location-matched histologic validation of MR imaging features.

PURPOSE: To validate proposed magnetic resonance (MR) imaging features of Crohn disease activity against a histopathologic reference. MATERIALS AND METHODS: Ethical permission was given by the University College London hospital ethics committee, and informed written consent was obtained from all participants. Preoperative MR imaging was performed in 18 consecutive patients with Crohn disease undergoing elective small-bowel resection. The Harvey-Bradshaw index, the C-reactive protein level, and disease chronicity were recorded. The resected bowel was retrospectively identified at preoperative MR imaging, and wall thickness, mural and lymph node/cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated images, gadolinium-based contrast material uptake, enhancement pattern, and mesenteric signal intensity on T2-weighted fat-saturated images were recorded. Precise histologic matching was achieved by imaging the ex vivo surgical specimens. Histopathologic grading of acute inflammation with the acute inflammatory score (AIS) (on the basis of mucosal ulceration, edema, and quantity and depth of neutrophilic infiltration) and the degree of fibrostenosis was performed at each site, and results were compared with MR imaging features. Data were analyzed by using linear regression with robust standard errors of the estimate. RESULTS: AIS was positively correlated with mural thickness and mural/CSF signal intensity ratio on T2-weighted fat-saturated images (P < .001 and P = .003, respectively) but not with mural enhancement at 30 and 70 seconds (P = .50 and P = .73, respectively). AIS was higher with layered mural enhancement (P < .001), a pattern also commonly associated with coexisting fibrostenosis (75%). Mural/CSF signal intensity ratio on T2-weighted fat-saturated images was higher in histologically edematous bowel than in nonedematous bowel (P = .04). There was no correlation between any lymph node characteristic and AIS. CONCLUSION: Increasing mural thickness, high mural signal intensity on T2-weighted fat-saturated images, and a layered pattern of enhancement reflect histologic features of acute small-bowel inflammation in Crohn disease.

CT colonography and computer-aided detection: effect of false-positive results on reader specificity and reading efficiency in a low-prevalence screening population.

PURPOSE: To retrospectively evaluate the effect of increasing numbers of computer-aided detection (CAD)-generated false-positive (FP) marks on reader specificity and reporting times by using computed tomographic (CT) colonography in a low-prevalence screening population. MATERIALS AND METHODS: Ethics committee approval and informed consent were obtained for this HIPAA-compliant study. Four readers each read 48 data sets (26 men, 22 women; mean age, 57 years) from a screening population (three containing polyps) without CAD application, followed by review of the CAD output and recorded findings and diagnostic confidence. The 45 data sets that were designated as normal were chosen such that 22 generated 15 or fewer FP CAD marks and 23 generated more than 15 FP CAD marks. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated with and without CAD. The relationships between the number of CAD FP marks and reader confidence, reporting times, and correct data set classification were analyzed by using linear and logistic regression. RESULTS: Across all readers, CAD resulted in four additional FP detections. Overall reader sensitivity and specificity (6-mm polyp threshold) before and after CAD application were 0.75 (95% confidence interval [CI]: 0.43, 0.95) versus 0.83 (95% CI: 0.52, 0.98) and 0.96 (95% CI: 0.91, 0.98) versus 0.93 (95% CI: 0.88, 0.96), respectively. The area under the ROC curve increased from 0.57 (95% CI: 0.34, 0.80) to 0.61 (95% CI: 0.42, 0.80). There was no correlation between an increasing number of CAD FP marks and reader confidence (P = .71) or correct study classification (P = .23), but there was a positive correlation with CAD-assisted reading times (0.06 [95% CI: 0.02, 0.10], P = .002). CONCLUSION: Increasing numbers of CAD FP marks did not adversely influence correct reader study classification or diagnostic confidence, although reporting times did increase.

Immunotherapy of murine prostate cancer using whole tumor cells killed ex vivo by herpes simplex viral thymidine kinase/ganciclovir suicide gene therapy.

Whole cell cancer vaccines are currently under clinical evaluation. Their immunogenicity may depend on the mode of death of the vaccine cells prior to uptake by professional antigen-presenting cells and crosspriming of T cells. Destruction of tumor in vivo by genetic prodrug activation therapy leads to a marked local and systemic immune response, local T-cell infiltration and the establishment of T-cell memory. We postulated that this immunostimulation may be due to induction of danger signals and the inherent immunogenicity of products of HSVtk/ganciclovir kill. Using established models of murine prostate cancer, we have evaluated the efficacy of anti-tumor vaccines comprising irradiated allogeneic or autologous whole cells expressing HSVtK, which are first killed in vitro by prodrug activation using ganciclovir. HSVtk/ganciclovir-induced cell kill was through the induction of apoptosis. The vaccine was found to be effective in both models and superior to traditional irradiated whole tumor cells even after single doses. Protection against tumor challenge was associated with marked proliferative and Th1 cytokine responses. This approach would be applicable clinically in terms of ease of vaccine production, safety, storage and avoidance of potential toxicities of in vivo gene transfer.

Nonlaxative PET/CT colonography: feasibility, acceptability, and pilot performance in patients at higher risk of colonic neoplasia.

UNLABELLED: CT colonography without bowel preparation is a safer and better-tolerated alternative to full laxation protocols, but comparative sensitivity and specificity are potentially reduced. Uptake of (18)F-FDG by colonic neoplasia is well described, and combining PET with nonlaxative CT colonography could improve accuracy. The purpose was to prospectively test the technical feasibility and acceptability of combined nonlaxative PET/CT colonography in patients at higher risk of colorectal neoplasia and to provide pilot data on diagnostic performance. METHODS: Fifty-six patients (median age, 64 y; 30 women) at high risk of colonic neoplasia underwent nonlaxative PET/CT colonography with barium fecal tagging within 2 wk of scheduled colonoscopy. Colonic segmental distension was graded 1 (poor) to 3 (good). A radiologist, experienced in CT colonography, and nuclear medicine physician in consensus analyzed the datasets. The diagnostic performance for standalone CT colonography and combined PET/CT colonography was compared with the reference colonoscopy. Patient experience for 25 items (each scored from 1 to 7) pertaining to satisfaction, worry, and physical discomfort was canvassed after both PET/CT colonography and colonoscopy. RESULTS: Distension was good in 298 of 334 segments (89%; 95% confidence interval [CI], 85%-92%). Patients experienced more physical discomfort during colonoscopy (median, 4; interquartile range [IQR], 2-7) than during PET/CT colonography (median, 5; IQR, 3-7; P = 0.03) and were more willing to undergo PET/CT colonography again (36/43 [84%; 95% CI, 73%-95%] vs. 31/43 [72%; 95% CI, 59%-86%]; P = 0.001). Twenty-one patients had 54 polyps according to colonoscopy (10 with at least 1 polyp >or=6 mm and 8 with at least 1 polyp >or=10 mm). Of 14 polyps 6 mm or greater, 12 (86%; 95% CI, 67%-100%) were (18)F-FDG-avid, including all those 10 mm or greater (mean standardized uptake value, 10.1). CT colonography sensitivity for polyps 6 mm or larger was 92.9% (95% CI, 79.4%-100%) and was not improved by the addition of PET. However, combined PET/CT colonography review improved per-patient positive predictive value for a polyp 10 mm or greater from 73% (95% CI, 39-92) to 100% (95% CI, 60-100). CONCLUSION: In this feasibility study, simultaneous PET acquisition during nonlaxative CT colonography is technically feasible, is well tolerated, and potentially improves specificity.

Paediatric CT: the effects of increasing image noise on pulmonary nodule detection.

BACKGROUND: A radiation dose of any magnitude can produce a detrimental effect manifesting as an increased risk of cancer. Cancer development may be delayed for many years following radiation exposure. Minimizing radiation dose in children is particularly important. However, reducing the dose can reduce image quality and may, therefore, hinder lesion detection. OBJECTIVE: We investigated the effects of reducing the image signal-to-noise ratio (SNR) on CT lung nodule detection for a range of nodule sizes. MATERIALS AND METHODS: A simulated nodule was placed at the periphery of the lung on an axial CT slice using image editing software. Multiple copies of the manipulated image were saved with various levels of superimposed noise. The image creation process was repeated for a range of nodule sizes. For a given nodule size, output images were read independently by four Fellows of The Royal College of Radiologists. RESULTS: The overall sensitivities in detecting nodules for the SNR ranges 0.8-0.99, 1-1.49, and 1.5-2.35 were 40.5%, 77.3% and 90.3%, respectively, and the specificities were 47.9%, 73.3% and 75%, respectively. The sensitivity for detecting lung nodules increased with nodule size and increasing SNR. There was 100% sensitivity for the detection of nodules of 4-10 mm in diameter at SNRs greater than 1.5. CONCLUSION: Reducing medical radiation doses in children is of paramount importance. For chest CT examinations this may be counterbalanced by reduced sensitivity and specificity combined with an increased uncertainty of pulmonary nodule detection. This study demonstrates that pulmonary nodules of 4 mm and greater in diameter can be detected with 100% sensitivity provided that the perceived image SNR is greater than 1.5.

CT colonography: optimisation, diagnostic performance and patient acceptability of reduced-laxative regimens using barium-based faecal tagging.

To establish the optimum barium-based reduced-laxative tagging regimen prior to CT colonography (CTC). Ninety-five subjects underwent reduced-laxative (13 g senna/18 g magnesium citrate) CTC prior to same-day colonoscopy and were randomised to one of four tagging regimens using 20 ml 40%w/v barium sulphate: regimen A: four doses, B: three doses, C: three doses plus 220 ml 2.1% barium sulphate, or D: three doses plus 15 ml diatriazoate megluamine. Patient experience was assessed immediately after CTC and 1 week later. Two radiologists graded residual stool (1: none/scattered to 4: >50% circumference) and tagging efficacy for stool (1: untagged to 5: 100% tagged) and fluid (1: untagged, 2: layered, 3: tagged), noting the HU of tagged fluid. Preparation was good (76-94% segments graded 1), although best for regimen D (P = 0.02). Across all regimens, stool tagging quality was high (mean 3.7-4.5) and not significantly different among regimens. The HU of layered tagged fluid was higher for regimens C/D than A/B (P = 0.002). Detection of cancer (n = 2), polyps > or =6 mm (n = 21), and < or =5 mm (n = 72) was 100, 81 and 32% respectively, with only four false positives > or =6 mm. Reduced preparation was tolerated better than full endoscopic preparation by 61%. Reduced-laxative CTC with three doses of 20 ml 40% barium sulphate is as effective as more complex regimens, retaining adequate diagnostic accuracy.

Immunotherapy of murine prostate cancer using whole tumour cells killed ex vivo by cytosine deaminase/5-fluorocytosine suicide-gene therapy.

OBJECTIVE: To evaluate the efficacy of antitumour vaccines comprising irradiated allogeneic or autologous whole cells expressing cytosine deaminase (CD) which are first killed ex vivo by prodrug activation using 5-fluorocytosine (5-FC), as the immunogenicity of tumour cells used as irradiated vaccines depends both on antigen expression and on the mode of their death. MATERIALS AND METHODS: The PA3 rat prostate cell line and MATLyLu, an androgen-insensitive subline, were grown and transfected with CD (designated PCD and MCD). In vitro drug-sensitivity was assessed in the cell lines using a viability assay, and the mode of cell death quantified by assessing apoptosis. Bax and bcl-2 expression were assessed by Western blot analysis. For in vivo experiments, male 8-10-week-old Lobund-Wistar rats were vaccinated (using vehicle in control groups) with 5 x 10(6) cells, all cells being irradiated before injection, to give groups with PA3, PCD, PCD killed with 5-FC, MatLyLu, MCD, and MCD killed with 5-FC. After 7 days all animals were given a subcutaneous tumour challenge of PA3 cells, and tumour volume measured subsequently. Immune responses were assessed in splenocytes. RESULTS: The efficiency of cell kill varied between the cell lines assessed, but cell death was by induced apoptosis. Single doses of vaccine were most effective in the allogeneic setting, causing significantly slower growth of syngeneic tumour challenge (P < 0.01), and 25% better survival at 50 days (P < 0.02) than irradiated untransfected cells. This was consistent with the greater proliferative response after allogeneic than autologous vaccination. CONCLUSION: The immunogenicity of irradiated tumour cells is enhanced when they are killed ex-vivo using suicide-gene therapy. This approach would be clinically applicable in terms of ease of vaccine production, safety, storage and avoidance of potential toxicities of in vivo gene transfer.

Heated tumour cells of autologous and allogeneic origin elicit anti-tumour immunity.

Vaccination with established tumour cell lines may circumvent the problem of obtaining autologous tumour cells from patients, but may also need immunological adjuvants. Up-regulation of heat shock proteins within tumour cell vaccines has resulted in increased immunogenicity in some models, but this has yet to be demonstrated for allogeneic (MHC-disparate) cell vaccines. This was investigated here using a rat model for prostate tumour cell vaccination. Heating of tumour cells (42 degrees C, 1 h) elicited significant increases in HSP70 expression. Vaccination with heated autologous PAIII cells elicited protection against PAIII challenge in 60% of rats >50 days compared to 0% with unheated vaccine and was associated with an increased Th1 (IFNgamma) immune response. Heated allogeneic MLL cells elicited significant protection against PAIII challenge, in contrast to unheated cells. The principle was confirmed in two mouse models, although the allogeneic melanoma vaccine K1735 elicited the best protection when heated and administered mixed with autologous dendritic cells. Thus, while heating of vaccine cells in some models is highly beneficial, and is a means of enhancing immunogenicity without genetic modification or inclusion of potentially toxic adjuvants, additional immune enhancement may be required.