Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI

© 2016 St. Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI 0.985-0.994) respectively. Small biases (=3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using Hepa-Fat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF

Fat deposition decreases diffusion parameters at MRI: a study in phantoms and patients with liver steatosis

Assess the effect of fat deposition on the MRI diffusion coefficients in lipid emulsion-based phantoms and patients with proven isolated liver steatosis

Strong time dependence of the 76-gene prognostic signature for node-negative breast cancer patients in the TRANSBIG multicenter independent validation series.

PURPOSE: Recently, a 76-gene prognostic signature able to predict distant metastases in lymph node-negative (N(-)) breast cancer patients was reported. The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment. EXPERIMENTAL DESIGN: Gene expression profiling of frozen samples from 198 N(-) systemically untreated patients was done at the Bordet Institute, blinded to clinical data and independent of Veridex. Genomic risk was defined by Veridex, blinded to clinical data. Survival analyses, done by an independent statistician, were done with the genomic risk and adjusted for the clinical risk, defined by Adjuvant! Online. RESULTS: The actual 5- and 10-year time to distant metastasis were 98% (88-100%) and 94% (83-98%), respectively, for the good profile group and 76% (68-82%) and 73% (65-79%), respectively, for the poor profile group. The actual 5- and 10-year overall survival were 98% (88-100%) and 87% (73-94%), respectively, for the good profile group and 84% (77-89%) and 72% (63-78%), respectively, for the poor profile group. We observed a strong time dependence of this signature, leading to an adjusted hazard ratio of 13.58 (1.85-99.63) and 8.20 (1.10-60.90) at 5 years and 5.11 (1.57-16.67) and 2.55 (1.07-6.10) at 10 years for time to distant metastasis and overall survival, respectively. CONCLUSION: This independent validation confirmed the performance of the 76-gene signature and adds to the growing evidence that gene expression signatures are of clinical relevance, especially for identifying patients at high risk of early distant metastases.Journal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Validation and clinical utility of a 70-gene prognostic signature for women with node-negative breast cancer.

BACKGROUND: A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients. METHODS: Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from five European centers were divided into high- and low-risk groups based on the gene signature classification and on clinical risk classifications. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis-free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]-positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups. RESULTS: The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low- and high-clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively. CONCLUSIONS: The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.Journal ArticleMulticenter StudyResearch Support, Non-U.S. Gov'tValidation Studiesinfo:eu-repo/semantics/publishe

Non-hyperfunctioning neuroendocrine tumours of the pancreas: MR imaging appearance and correlation with their biological behaviour

OBJECTIVE: To describe MR imaging features of non-hyperfunctioning neuroendocrine pancreatic tumours by comparing them to histopathology and to determine the accuracy of MR imaging in predicting biological behaviour. MATERIALS AND METHODS: After institutional review board approval, we retrospectively reviewed 45 patients with pathologically proven NF-NET of the pancreas and 651 preoperative MR/MRCP examinations. Of the NF-NETS, 29/45 (64.4 %) were G1 and 16/45 (35.5 %) were G2. Image analysis included the lesion maximum diameter, vascular encasement, extrapancreatic spread, signal intensity on T1- and T2-weighted, contrast enhancement features, and presence of metastases. Tumour vessel density was calculated on the histological specimen using a grid. RESULTS: The median maximum diameter of NF-NETs was 20 mm (range 5-200 mm). Eighty per cent of the NF-NETs were hypointense on T1-weighted images, 82.2 % were hyperintense on T2-weighted images, and 75.6 % were hypervascular. Overall MRI accuracy showed a mean AUC of 0.86 compared to pathology. Lesions with a maximum diameter of 30 mm irregular margins, absence of a cleavage plane with the main pancreatic duct, vascular encasement, extrapancreatic spread and abdominal metastases were significantly associated with malignant NF-NETs. No correlation was found between the tumour vessel density and contrast-enhanced MR imaging pattern. CONCLUSIONS: Hyperintensity on T2-weighted images and iso-/hypervascularity occurred in 27/45 (60.0 %) of NF-NETs. MRI identifies malignant NF-NETs with a sensitivity of 93.3 % and a specificity of 76.9 % (AUC\u2009=\u20090.85). KEY POINTS: \u2022 Non-hyperfunctioning neuroendocrine pancreatic tumours (NF-NET) pose a difficult diagnostic challenge. \u2022 On T2-weighted MRI, 82.2 % of neuroendocrine tumours appeared hyperintense. \u2022 MR imaging showed 0.94 sensitivity and 0.77 specificity in predicting biological behaviour. \u2022 The hyper-/isointensity during dynamic MRI did not correlate with vessel density at pathology

Predicting response to neoadjuvant chemotherapy in primary breast cancer using volumetric helical perfusion computed tomography: a preliminary study

To investigate whether CT-derived vascular parameters in primary breast cancer predict complete pathological response (pCR) to neoadjuvant chemotherapy (NAC).Twenty prospective patients with primary breast cancer due for NAC underwent volumetric helical perfusion CT to derive whole tumour regional blood flow (BF), blood volume (BV) and flow extraction product (FE) by deconvolution analysis. A pCR was achieved if no residual invasive cancer was detectable on pathological examination. Relationships between baseline BF, BV, FE, tumour size and volume, and pCR were examined using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was performed to assess the parameter best able to predict response. Intra- and inter-observer variability was assessed using Bland-Altman statistics.Seventeen out of 20 patients completed NAC with four achieving a pCR. Baseline BF and FE were higher in patients who achieved a pCR compared with those who did not (P = 0.032); tumour size and volume were not significantly different (P &gt; 0.05). ROC analysis revealed that BF and FE were able to identify responders effectively (AUC = 0.87; P = 0.03). There was good intra- and inter-observer agreement.Primary breast cancers which exhibited higher levels of perfusion before treatment were more likely to achieve a pCR to NAC.aEuro cent CT-derived vascular parameters may be useful in breast cancer treatment.aEuro cent Perfusion CT can help predict response to neoadjuvant chemotherapy in breast cancer.aEuro cent Baseline blood flow and flow extraction product are higher in complete pathological responders.</p