Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.
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ABSTRACT: The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists.This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participants had CTC and colonoscopy on the same day. CTC images were interpreted independently by trained gastroenterologists and radiologists. The main outcome was the accuracy of CTC in the detection of neoplasms ?6?mm in diameter, with colonoscopy results as the reference standard. Detection sensitivities of polypoid vs. nonpolypoid lesions were also evaluated.Of the 1,257 participants, 1,177 were included in the final analysis: 42 (3.6%) were at average risk of colorectal cancer, 456 (38.7%) were at elevated risk, and 679 (57.7%) had recent positive immunochemical fecal occult blood tests. The overall per-participant sensitivity, specificity, and positive and negative predictive values for neoplasms ?6?mm in diameter were 0.90, 0.93, 0.83, and 0.96, respectively, among gastroenterologists and 0.86, 0.90, 0.76, and 0.95 among radiologists (P<0.05 for gastroenterologists vs. radiologists). The sensitivity and specificity for neoplasms ?10?mm in diameter were 0.93 and 0.99 among gastroenterologists and 0.91 and 0.98 among radiologists (not significant for gastroenterologists vs. radiologists). The CTC interpretation time by radiologists was shorter than that by gastroenterologists (9.97 vs. 15.8?min, P<0.05). Sensitivities for pedunculated and sessile lesions exceeded those for flat elevated lesions ?10?mm in diameter in both groups (gastroenterologists 0.95, 0.92, and 0.68; radiologists: 0.94, 0.87, and 0.61; P<0.05 for polypoid vs. nonpolypoid), although not significant (P>0.05) for gastroenterologists vs. radiologists.CTC interpretation by gastroenterologists and radiologists was accurate for detection of polypoid neoplasms, but less so for nonpolypoid neoplasms. Gastroenterologists had a higher accuracy in the detection of neoplasms ?6?mm than did radiologists, although their interpretation time was longer than that of radiologists.
Accuracy of CT Colonography for Detection of Polypoid and Nonpolypoid Neoplasia by Gastroenterologists and Radiologists: A Nationwide Multicenter Study in Japan.
The American journal of gastroenterology 20161025 1
<h4>Objectives</h4>The objective of this study was to assess prospectively the diagnostic accuracy of computer-assisted computed tomographic colonography (CTC) in the detection of polypoid (pedunculated or sessile) and nonpolypoid neoplasms and compare the accuracy between gastroenterologists and radiologists.<h4>Methods</h4>This nationwide multicenter prospective controlled trial recruited 1,257 participants with average or high risk of colorectal cancer at 14 Japanese institutions. Participant ...[more]
Project description:Little is known about the immunoediting process in precancerous lesions. We explored this aspect of benign colorectal adenomas with a descriptive analysis of the immune pathways and immune cells whose regulation is linked to the morphology and size of these lesions. Two series of polypoid and nonpolypoid colorectal adenomas were used in this study: 1) 84 samples (42 lesions, each with matched samples of normal mucosa) whose gene expression data were used to quantify the tumor morphology- and size-related dysregulation of immune pathways collected in the Molecular Signature Database, using Gene Set Enrichment Analysis; 2) 40 other lesions examined with immunohistochemistry to quantify the presence of immune cells in the stromal compartment. In the analysis of transcriptomic data, 429 immune pathways displayed significant differential regulation in neoplasms of different morphology and size. Most pathways were significantly upregulated or downregulated in polypoid lesions versus nonpolypoid lesions (regardless of size). Differential pathway regulation associated with lesion size was observed only in polypoid neoplasms. These findings were mirrored by tissue immunostaining with CD4, CD8, FOXP3, MHC-I, CD68, and CD163 antibodies: stromal immune cell counts (mainly T lymphocytes and macrophages) were significantly higher in polypoid lesions. Certain markers displayed significant size-related differences regardless of lesion morphology. Multivariate analysis of variance showed that the marker panel clearly discriminated between precancerous lesions of different morphologies and sizes. Statistical analysis of immunostained cell counts fully support the results of the transcriptomic data analysis: the density of infiltration of most immune cells in the stroma of polypoid precancerous lesions was significantly higher than that observed in nonpolypoid lesions. Large neoplasms also have more immune cells in their stroma than small lesions. Immunoediting in precancerous colorectal tumors may vary with lesion morphology and stage of development, and this variability could influence a given lesion's trajectory to cancer.
Project description:To assess the variation in diagnostic performance among radiologists at screening computed tomographic (CT) colonography.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.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).Consistent performance for adenoma and advanced neoplasia detection, as well as other clinically relevant end points, were observed among radiologists at CT colonographic screening.
Project description:Improved colonoscopy is revealing precancerous lesions that were frequently missed in the past, and ?30% of those detected today have nonpolypoid morphologies ranging from slightly raised to depressed. To characterize these lesions molecularly, we assessed transcription of 23,768 genes in 42 precancerous lesions (25 slightly elevated nonpolypoid and 17 pedunculated polypoid), each with corresponding samples of normal mucosa. Nonpolypoid versus polypoid morphology explained most gene expression variance among samples; histology, size, and degree of dysplasia were also linked to specific patterns. Expression changes in polypoid lesions frequently affected cell-cycling pathways, whereas cell-survival dysregulation predominated in nonpolypoid lesions. The latter also displayed fewer and less dramatic expression changes than polypoid lesions. Paradigmatic of this trend was progressive loss through the normal > nonpolypoid > polypoid > cancer sequence of TMIGD1 mRNA and protein. This finding, along with TMIGD1 protein expression patterns in tissues and cell lines, suggests that TMIGD1 might be associated with intestinal-cell differentiation. We conclude that molecular dysregulation in slightly elevated, nonpolypoid, precancerous colorectal lesions may be somewhat less severe than that observed in classic adenomatous polyps.
Project description:BackgroundNonpolypoid adenomas are a subgroup of colorectal adenomas that have been associated with a more aggressive clinical behaviour compared to their polypoid counterparts. A substantial proportion of nonpolypoid and polypoid adenomas lack APC mutations, APC methylation or chromosomal loss of the APC locus on chromosome 5q, suggesting the involvement of other Wnt-pathway genes. The present study investigated promoter methylation of several Wnt-pathway antagonists in both nonpolypoid and polypoid adenomas.MethodsQuantitative methylation-specific PCR (qMSP) was used to evaluate methylation of four Wnt-antagonists, SFRP2, WIF-1, DKK3 and SOX17 in 18 normal colorectal mucosa samples, 9 colorectal cancer cell lines, 18 carcinomas, 44 nonpolypoid and 44 polypoid adenomas. Results were integrated with previously obtained data on APC mutation, methylation and chromosome 5q status from the same samples.ResultsIncreased methylation of all genes was found in the majority of cell lines, adenomas and carcinomas compared to normal controls. WIF-1 and DKK3 showed a significantly lower level of methylation in nonpolypoid compared to polypoid adenomas (p?<?0.01). Combining both adenoma types, a positive trend between APC mutation and both WIF-1 and DKK3 methylation was observed (p?<?0.05).ConclusionsMethylation of Wnt-pathway antagonists represents an additional mechanism of constitutive Wnt-pathway activation in colorectal adenomas. Current results further substantiate the existence of partially alternative Wnt-pathway disruption mechanisms in nonpolypoid compared to polypoid adenomas, in line with previous observations.
Project description:ObjectivesConventional colonoscopy with white light illumination detects colonic adenomas based on structural changes alone and is limited by a high miss rate. We aim to demonstrate an integrated imaging strategy that combines wide-field endoscopy and confocal endomicroscopy in real time to visualize molecular expression patterns in vivo to detect premalignant colonic mucosa.MethodsA peptide specific for claudin-1 is labeled with Cy5.5 and administrated intravenously in genetically engineered mice that develop adenomas spontaneously in the distal colon. Wide-field endoscopy is used to identify the presence of nonpolypoid and polypoid adenomas. Anatomic landmarks are used to guide placement of a confocal endomicroscope with side-view optics to visualize claudin-1 expression patterns with subcellular resolution.ResultsWide-field fluorescence images show peak uptake in colon adenoma at ?1 hour after systemic peptide administration, and lesion margins are clearly defined. Further examination of the lesion using a confocal endomicroscope shows dysplastic crypts with large size, elongated shape, distorted architecture, and variable dimension compared with normal. The mean fluorescence intensity is significantly higher for dysplasia than normal. Increased claudin-1 expression in dysplasia vs normal is confirmed ex vivo, and the binding pattern is consistent with the in vivo imaging results.DiscussionWide-field endoscopy can visualize molecular expression of claudin-1 in vivo to localize premalignant colonic mucosa, and confocal endomicroscopy can identify subcellular feature to distinguish dysplasia from normal.
Project description:The aim was to analyze the transcriptome of different types of preneoplastic colorectal lesions in comparison with that of the corresponding normal mucosa.
Project description:The aim was to analyze the transcriptome of different types of preneoplastic colorectal lesions in comparison with that of the corresponding normal mucosa. Eighty samples were analyzed: 40 precancerous colorectal lesions and the corresponding normal mucosa from the same colonic segment where the lesion was taken. 24/40 lesions were nonpolypoid, 16/42 lesions were polypoid.
Project description:To conduct post-hoc analysis of National CT Colonography Trial data and compare the sensitivity and specificity of computed tomographic (CT) colonography in participants younger than 65 years with those in participants aged 65 years and older.Of 2600 asymptomatic participants recruited at 15 centers for the trial, 497 were 65 years of age or older. Approval of this HIPAA-compliant study was obtained from the institutional review board of each site, and informed consent was obtained from each subject. Radiologists certified in CT colonography reported lesions 5 mm in diameter or larger. Screening detection of large (≥10-mm) histologically confirmed colorectal neoplasia was the primary end point; screening detection of smaller (6-9-mm) colorectal neoplasia was a secondary end point. The differences in sensitivity and specificity of CT colonography in the two age cohorts (age < 65 years and age ≥ 65 years) were estimated with bootstrap confidence intervals (CIs).Complete data were available for 477 participants 65 years of age or older (among 2531 evaluable participants). Prevalence of adenomas 1 cm or larger for the older participants versus the younger participants was 6.9% (33 of 477) versus 3.7% (76 of 2054) (P < .004). For large neoplasms, mean estimates for CT colonography sensitivity and specificity among the older cohort were 0.82 (95% CI: 0.644, 0.944) and 0.83 (95% CI: 0.779, 0.883), respectively. For large neoplasms in the younger group, CT colonography sensitivity and specificity were 0.92 (95% CI: 0.837, 0.967) and 0.86 (95% CI: 0.816, 0.899), respectively. Per-polyp sensitivity for large neoplasms for the older and younger populations was 0.75 (95% CI: 0.578, 0.869) and 0.84 (95% CI: 0.717, 0.924), respectively. For the older and younger groups, per-participant sensitivity was 0.72 (95% CI: 0.565, 0.854) and 0.81 (95% CI: 0.745, 0.882) for detecting adenomas 6 mm in diameter or larger.For most measures of diagnostic performance and in most subsets, the difference between senior-aged participants and those younger than 65 years was not statistically significant.
Project description:Cervical cancer remains among the most common cancers in women worldwide and can be prevented by vaccination. The Ministry of Health, Labour and Welfare of Japan suspended active recommendation of regular human papillomavirus (HPV) vaccines in 2013 because of various symptoms including chronic pain and motor impairment. This nationwide case-control study from April 2013 to March 2017 targeted women aged 20-24 years old at cervical screening. We compared HPV vaccination exposure between those with abnormal and normal cytology. Abnormal cytology was classified based on the results of histological test and we calculated the odds ratio (OR) and 95% confidence interval (CI) of the above endpoints and vaccination exposure using the conditional logistic regression model and estimated vaccine effectiveness using the formula (1 - OR) × 100. A total of 2483 cases and 12 296 controls (one-to-five matching) were eligible in 31 municipalities in Japan. The distribution of histological abnormalities among cases was 797 CIN1 (including dysplasia) (32.1%), 165 CIN2 (6.7%), 44 CIN3 (1.8%), and eight squamous cell carcinoma (SCC) (0.3%). The OR of HPV vaccination compared with no vaccination for abnormal cytology, CIN1+, CIN2+, and CIN3+ versus controls was 0.42 (95% CI, 0.34-0.50), 0.42 (95% CI, 0.31-0.58), 0.25 (95% CI, 0.12-0.54), and 0.19 (95% CI, 0.03-1.15), respectively, equating to a vaccine effectiveness of 58.5%, 57.9%, 74.8%, and 80.9%, respectively. Eight patients had SCC, none was vaccinated. This nationwide case-control study in Japan demonstrated a substantial risk reduction in abnormal cytology and CIN among women who did versus those who did not receive HPV vaccination.
Project description:PurposeTo evaluate the ability of additional analysis of computed tomographic (CT) colonography images to provide a comprehensive osteoporosis assessment.Materials and methodsThis Health Insurance Portability and Accountability Act-compliant study was approved by our institutional review board with a waiver of informed consent. Diagnosis of osteoporosis and assessment of fracture risk were compared between biomechanical CT analysis and dual-energy x-ray absorptiometry (DXA) in 136 women (age range, 43-92 years), each of whom underwent CT colonography and DXA within a 6-month period (between January 2008 and April 2010). Blinded to the DXA data, biomechanical CT analysis was retrospectively applied to CT images by using phantomless calibration and finite element analysis to measure bone mineral density and bone strength at the hip and spine. Regression, Bland-Altman, and reclassification analyses and paired t tests were used to compare results.ResultsFor bone mineral density T scores at the femoral neck, biomechanical CT analysis was highly correlated (R(2) = 0.84) with DXA, did not differ from DXA (P = .15, paired t test), and was able to identify osteoporosis (as defined by DXA), with 100% sensitivity in eight of eight patients (95% confidence interval [CI]: 67.6%, 100%) and 98.4% specificity in 126 of 128 patients (95% CI: 94.5%, 99.6%). Considering both the hip and spine, the classification of patients at high risk for fracture by biomechanical CT analysis--those with osteoporosis or "fragile bone strength"--agreed well against classifications for clinical osteoporosis by DXA (T score ?-2.5 at the hip or spine), with 82.8% sensitivity in 24 of 29 patients (95% CI: 65.4%, 92.4%) and 85.7% specificity in 66 of 77 patients (95% CI: 76.2%, 91.8%).ConclusionRetrospective biomechanical CT analysis of CT colonography for colorectal cancer screening provides a comprehensive osteoporosis assessment without requiring changes in imaging protocols.
