Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions.

BACKGROUND: Helicobacter pylori (H. pylori) infection has been associated with a long-term risk of precancerous gastric conditions (PGC) even after H. pylori eradication. AIM: To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC, before/after H. pylori eradication. METHODS: We studied 85 consecutive patients with H. pylori-related gastritis with/without PGC before and 6 mo after proven H. pylori eradication. Kimura-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications, were applied to assess the endoscopic extension of atrophy and intestinal metaplasia. The histological result was considered to be the gold standard. The Sydney System, the Operative-Link on Gastritis-Assessment, and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis, atrophy and intestinal metaplasia, whereas dysplasia was graded according to World Health Organization classification. Serum anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was suspected. RESULTS: After H. pylori eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia, disappeared or decreased in 100% and 96.5% of patients respectively, whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not change. Low-Grade Dysplasia prevalence was similar on random biopsies before and after H. pylori eradication (17.6% vs 10.6%, P = 0.19), but increased in patients with visible lesions (0% vs 22.4%, P < 0.0001). At a multivariate analysis, the probability for detecting dysplasia after resolution of H. pylori-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia, greater alcohol consumption, and anti-parietal cell antibody and/or anti-intrinsic factor positivity [odds ratio (OR) = 3.88, 95% confidence interval (CI): 1.31-11.49, P = 0.01; OR = 3.10, 95%CI: 1.05-9.12, P = 0.04 and OR = 5.47, 95%CI: 1.33-22.39, P < 0.04, respectively]. CONCLUSION: High-Resolution White-Light Endoscopy with Narrow-Band Imaging allows an accurate diagnosis of Low-Grade Dysplasia on visible lesions after regression of H. pylori-induced chronic gastritis. Patients with an overlap between autoimmune/H. pylori-induced gastritis may require more extensive gastric mapping.

Comparing CT colonography and flexible sigmoidoscopy: a randomised trial within a population-based screening programme.

IMPORTANCE AND AIMS: The role of CT colonography (CTC) as a colorectal cancer (CRC) screening test is uncertain. The aim of our trial was to compare participation and detection rate (DR) with sigmoidoscopy (flexible sigmoidoscopy (FS)) and CTC in a screening setting. DESIGN SETTING AND PARTICIPANTS: We conducted two randomised clinical trials (RCTs). (1) Participation RCT: individuals, aged 58 years, living in Turin (Italy), were randomly assigned to be invited to FS or CTC screening; (2) detection RCT: residents in northern Italy, aged 58-60, giving their consent to recruitment, were randomly allocated to CTC or FS. Polyps ≥6 mm at CTC, or 'high-risk' distal lesions at FS, were referred for colonoscopy (TC). MAIN OUTCOME MEASURES: Participation rate (proportion of invitees examined); DR of advanced adenomas or CRC (advanced neoplasia (AN)). RESULTS: Participation was 30.4% (298/980) for CTC and 27.4% (267/976) for FS (relative risk (RR) 1.1; 95% CI 0.98 to 1.29). Among men, participation was higher with CTC than with FS (34.1% vs 26.5%, p=0.011). In the detection RCT, 2673 subjects had FS and 2595 had CTC: the AN DR was 4.8% (127/2673, including 9 CRCs) with FS and 5.1% (133/2595, including 10 CRCs) with CTC (RR 1.08; 95% CI 0.85 to 1.37). Distal AN DR was 3.9% (109/2673) with FS and 2.9% (76/2595) with CTC (RR 0.72; 95% CI 0.54 to 0.96); proximal AN DR was 1.2% (34/2595) for FS vs 2.7% (69/2595) for CTC (RR 2.06; 95% CI 1.37 to 3.10). CONCLUSIONS AND RELEVANCE: Participation and DR for FS and CTC were comparable. AN DR was twice as high in the proximal colon and lower in the distal colon with CTC than with FS. Men were more likely to participate in CTC screening. TRIAL REGISTRATION NUMBER: NCT01739608; Pre-results.

Stromal contribution to the colorectal cancer transcriptome.

Recent studies identified a poor-prognosis stem/serrated/mesenchymal (SSM) transcriptional subtype of colorectal cancer (CRC). We noted that genes upregulated in this subtype are also prominently expressed by stromal cells, suggesting that SSM transcripts could derive from stromal rather than epithelial cancer cells. To test this hypothesis, we analyzed CRC expression data from patient-derived xenografts, where mouse stroma supports human cancer cells. Species-specific expression analysis showed that the mRNA levels of SSM genes were mostly due to stromal expression. Transcriptional signatures built to specifically report the abundance of cancer-associated fibroblasts (CAFs), leukocytes or endothelial cells all had significantly higher expression in human CRC samples of the SSM subtype. High expression of the CAF signature was associated with poor prognosis in untreated CRC, and joint high expression of the stromal signatures predicted resistance to radiotherapy in rectal cancer. These data show that the distinctive transcriptional and clinical features of the SSM subtype can be ascribed to its particularly abundant stromal component.

Computer-aided detection for computed tomographic colonography screening: a prospective comparison of a double-reading paradigm with first-reader computer-aided detection against second-reader computer-aided detection.

OBJECTIVES: The objective of this study was to prospectively compare diagnostic performance and time efficiency of a double-reading paradigm in which a first-reader computer-aided detection (CAD) is followed by a fast 2-dimensional review (DR FR-CAD) with those of a double reading with second-reader CAD (SR CAD). MATERIALS AND METHODS: The local ethical committee approved this study. Consecutive immunological patients who have positive results for fecal immunological test who were scheduled for colonoscopy were enrolled for a 10-month period. Computed tomographic colonography studies were read with CAD (CAD COLON-1.20; im3D, Turin, Italy) by using both SR CAD (applied after unassisted interpretation primary 2-dimensional) and DR FR-CAD (CAD-prompts evaluation followed by a fast 2-dimensional review) in randomized order with the radiologist for each reading paradigm masked to the other reader's results.Per-patient sensitivity and specificity of unassisted and CAD-assisted readings for detecting 6-mm adenomas or larger were calculated by using unblinding colonoscopy as reference standard. Reporting times were also calculated. Pairwise comparisons were performed. RESULTS: A total of 182 participants (median age, 65 years; range, 58-76) were included in the final analysis. Of these, 93 (51%) had at least 1 cancer or a 6-mm adenoma or larger. At the 6-mm threshold, sensitivity of unassisted reading (79.6%; 95% confidence interval [CI], 69.9-87.2) increased significantly with the use of both SR CAD (86.0%; 95% CI, 77.3%-92.3%) and DR FR-CAD (89.2%; 95% CI, 81.1%-94.7%), without differences between CAD readings (P = 0.500). No significant differences in specificity among the 3 paradigms were observed. Double reading with first-reader CAD required less reading time than that for SR CAD (378 vs 496; Δ118 seconds; P < 0.001) and was 59 seconds longer than the unassisted reading (P = 0.058). CONCLUSIONS: When compared with unassisted reading, a double-reading paradigm in which first-reader CAD is followed by a fast 2-dimensional review improves the adenoma detection rate to the same level achieved by a second-reader CAD while decreasing reporting times.

Efficacy of computer-aided detection as a second reader for 6-9-mm lesions at CT colonography: multicenter prospective trial.

PURPOSE: To assess the effect of computer-aided detection (CAD) as a second reader on the sensitivity and specificity of computed tomographic (CT) colonography in detecting 6-9-mm colorectal cancer (CRC) lesions. MATERIALS AND METHODS: Individuals with clinical indications for colonoscopy--either for symptoms or as part of participating in a surveillance program or CRC screening--were prospectively enrolled at one of 10 academic centers between July 2007 and May 2009. Institutional review board approval was obtained at each clinical site, and all participants provided written informed consent. All participants underwent CT colonography and colonoscopy on the same day. Experienced readers interpreted the CT colonography images unassisted and then reviewed all colorectal lesion-like structures pinpointed by the CAD algorithm. Segmental unblinding of CT colonoscopy findings at colonoscopy was utilized. The sensitivity and specificity of unassisted and CAD-assisted reading in identifying individuals with 6-9-mm lesions were calculated and compared by means of pairwise analysis. RESULTS: A total of 618 participants (mean age, 57.9 years; 54.5% male) were included in the final analysis. Of these participants, 464 (75.1%) had no lesions 6 mm or larger, and 52 (8.4%) had 6-9-mm lesions. The sensitivity of CT colonography with unassisted reading and that with CAD-assisted reading in identifying individuals with 6-9-mm lesions was 65.4% (95% confidence interval [CI]: 50.9%, 78.0%) and 76.9% (95% CI: 63.2%, 87.5%; P = .016), respectively. No significant change in specificity was observed: The specificity of CT colonography with unassisted and that with CAD-assisted reading was 91.8% (95% CI: 88.9%, 94.1%) and 90.9% (95% CI: 88.0%, 93.4%; P = .063), respectively. Evaluation of CAD candidates required an additional 1.6 minutes (25th-75th percentile: 1.0 minute to 3.4 minutes). CONCLUSION: The addition of CAD to reading performed by experienced readers resulted in a significant benefit in the detection of 6-9-mm polyps at CT colonography in this cohort. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120376/-/DC1.

Diagnostic accuracy of computed tomographic colonography for the detection of advanced neoplasia in individuals at increased risk of colorectal cancer.

CONTEXT: Computed tomographic (CT) colonography has been recognized as an alternative for colorectal cancer (CRC) screening in average-risk individuals, but less information is available on its performance in individuals at increased risk of CRC. OBJECTIVE: To assess the accuracy of CT colonography in detecting advanced colorectal neoplasia in asymptomatic individuals at increased risk of CRC using unblinded colonoscopy as the reference standard. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, cross-sectional study. Individuals at increased risk of CRC due to either family history of advanced neoplasia in first-degree relatives, personal history of colorectal adenomas, or positive results from fecal occult blood tests (FOBTs) were recruited in 11 Italian centers and 1 Belgian center between December 2004 and May 2007. Each participant underwent CT colonography followed by colonoscopy on the same day. MAIN OUTCOME MEASURES: Sensitivity and specificity of CT colonography in detecting individuals with advanced neoplasia (ie, advanced adenoma or CRC) 6 mm or larger. RESULTS: Of 1103 participants, 937 were included in the final analysis: 373 cases in the family-history group, 343 in the group with personal history of adenomas, and 221 in the FOBT-positive group. Overall, CT colonography identified 151 of 177 participants with advanced neoplasia 6 mm or larger (sensitivity, 85.3%; 95% confidence interval [CI], 79.0%-90.0%) and correctly classified results as negative for 667 of 760 participants without such lesions (specificity, 87.8%; 95% CI, 85.2%-90.0%). The positive and negative predictive values were 61.9% (95% CI, 55.4%-68.0%) and 96.3% (95% CI, 94.6%-97.5%), respectively; after group stratification, a significantly lower negative predictive value was found for the FOBT-positive group (84.9%; 95% CI, 76.2%-91.3%; P < .001). CONCLUSIONS: In a group of persons at increased risk for CRC, CT colonography compared with colonoscopy resulted in a negative predictive value of 96.3% overall. When limited to FOBT-positive persons, the negative predictive value was 84.9%.

Computed tomography colonography in routine clinical practice.

OBJECTIVE: To describe the experience of a radiology unit in using open access computed tomography (CT) colonography instead of double-contrast barium enema in patients who refused or had an incomplete first-attempt colonoscopy. METHODS: All consecutive patients who underwent CT colonography from December 1998 to August 2001 were recalled and evaluated. Patients in whom CT colonography showed intraluminal growths were sent for colonoscopy, performed using deep sedation if the first attempt failed. RESULTS: A total of 463 consecutive CT colonography examinations were performed: 304 patients were re-traceable and were evaluated. In 85 cases CT colonography reported the presence of intraluminal growth. Colonoscopy confirmed the presence of 74 of the 94 polyps, and of 43 of the 48 cancers found at CT colonography. Colonoscopy also diagnosed an additional two cancers in two patients with CT colonography findings of inflammatory changes, and an additional 26 polyps in 16 patients. On a per-lesion basis, the positive predictive value of CT colonography was 73%, 80% and 87% for polyps /= 10 mm, respectively, and was 90% for cancer. On a per-patient basis, the positive predictive value was 60%, 72% and 89% for lesions /= 10 mm, respectively, and was 93% for cancer. CONCLUSION: CT colonography on an open access basis can be confidently used as a routine test instead of double-contrast barium enema when total colonoscopy cannot be performed.