SummaryBackgroundMagnetic resonance enterography (MRE) and ultrasound are used to image Crohn's disease, but their comparative accuracy for assessing disease extent and activity is not known with certainty. Therefore, we did a multicentre trial to address this issue.MethodsWe recruited patients from eight UK hospitals. Eligible patients were 16 years or older, with newly diagnosed Crohn's disease or with established disease and suspected relapse. Consecutive patients had MRE and ultrasound in addition to standard investigations. Discrepancy between MRE and ultrasound for the presence of small bowel disease triggered an additional investigation, if not already available. The primary outcome was difference in per-patient sensitivity for small bowel disease extent (correct identification and segmental localisation) against a construct reference standard (panel diagnosis). This trial is registered with the International Standard Randomised Controlled Trial, number ISRCTN03982913, and has been completed.Findings284 patients completed the trial (133 in the newly diagnosed group, 151 in the relapse group). Based on the reference standard, 233 (82%) patients had small bowel Crohn's disease. The sensitivity of MRE for small bowel disease extent (80% [95% CI 72–86]) and presence (97% [91–99]) were significantly greater than that of ultrasound (70% [62–78] for disease extent, 92% [84–96] for disease presence); a 10% (95% CI 1–18; p=0·027) difference for extent, and 5% (1–9; p=0·025) difference for presence. The specificity of MRE for small bowel disease extent (95% [85–98]) was significantly greater than that of ultrasound (81% [64–91]); a difference of 14% (1–27; p=0·039). The specificity for small bowel disease presence was 96% (95% CI 86–99) with MRE and 84% (65–94) with ultrasound (difference 12% [0–25]; p=0·054). There were no serious adverse events.InterpretationBoth MRE and ultrasound have high sensitivity for detecting small bowel disease presence and both are valid first-line investigations, and viable alternatives to ileocolonoscopy. However, in a national health service setting, MRE is generally the preferred radiological investigation when available because its sensitivity and specificity exceed ultrasound significantly.FundingNational Institute of Health and Research Health Technology Assessment.
BRCA1 is a tumour suppresser gene frequently mutated in familial breast cancer and thought to influence the progression of sporadic breast cancer. Decreased BRCA1 mRNA and protein expression has been identified in breast cancer cell lines and sporadic breast tumours. Here the prognostic significance of reduced BRCA1 protein expression is investigated in primary operable breast cancer. Immunohistochemical analysis was used to determine the level of BRCA1 protein expression in 100 breast cancers. BRCA1 expression was compared with known prognostic factors and survival to investigate its prognostic significance. BRCA1 nuclear expression was reduced by varying amounts in breast carcinomas. A progressive loss of BRCA1 expression correlated well with higher histological grade (p = 0.002) and an excess of medullary/atypical medullary/grade 3 ductal carcinomas (p = 0.0001). When adjusted for grade, patients with loss of BRCA1 expression had a significantly longer disease-free survival time. Loss of BRCA1 expression associated with high-grade breast tumours suggests that BRCA1 may play an important role in the pathogenesis of sporadic breast cancer.
Background: The growth pattern of colorectal cancer is seldom investigated. This cohort study aimed to explore tumour growth rate in colorectal cancers managed non-surgically or deemed not resectable, and to determine its implication for prognosis. Methods: Consecutive patients with colonic or rectal adenocarcinoma were identified through the colorectal multidisciplinary team database at Leeds Teaching Hospitals NHS Trust over a 2-year interval. Patients who received no treatment (surgery, stenting, colonic defunctioning procedures, chemotherapy, radiotherapy) and who underwent CT twice more than 5 weeks apart were included. Multidetector CT/three-dimensional image analysis was performed independently by three experienced radiologists. Results: Of 804 patients reviewed, 43 colorectal cancers were included in the final analysis. Median age at first CT was 80 (73-85) years and the median interval between scans was 150 (i.q.r. 72-471) days. An increase in T category was demonstrated in 31 of 43 tumours, with a median doubling time of 211 (112-404) days. The median percentage increase in tumour volume was 34⋅1 (13⋅3-53⋅9) per cent per 62 days. The all-cause 3-year mortality rate was 81 per cent (35 of 43) with a median survival time of 1⋅1 (0⋅4-2⋅2) years after the initial diagnostic scan. In those obstructed, the relative risk of death from subsequent perforation was 1⋅26 (95 per cent c.i. 1⋅07 to 1⋅49; P = 0⋅005). Conclusion: This study documented a median doubling time of 211 days, with a concerning suggestion of tumour progression, which has implications for the current management standard.
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