Magnetic Resonance Enterography and Histology in Patients With Fibrostenotic Crohn's Disease: A Multicenter Study

INTRODUCTION Magnetic resonance enterography (MRE) is useful for detecting bowel strictures, whereas a number of imaging biomarkers may reflect severity of fibrosis burden in Crohn's disease (CD). This study aimed to verify the association of MRE metrics with histologic fibrosis independent of inflammation. METHODS This prospective European multicenter study performed MRE imaging on 60 patients with CD with bowel strictures before surgical resection. Locations of 61 histological samples were annotated on MRE examinations, followed by central readings using the Chiorean score and measurement of delayed gain of enhancement (DGE), magnetization transfer ratio, T2-weighted MRI sequences (T2R), apparent diffusion coefficient (ADC), and the magnetic resonance index of activity (MaRIA). Correlations of histology and MRE metrics were assessed. Least Absolute Shrinkage and Selection Operator and receiver operator characteristic (ROC) curve analyses were used to select composite MRE scores predictive of histology and to estimate their predictive value. RESULTS ADC and MaRIA correlated with fibrosis (R = -0.71, P < 0.0001, and 0.59, P < 0.001) and more moderately with inflammation (R = -0.35, P < 0.01, and R = 0.53, P < 0.001). Lower or no correlations of fibrosis or inflammation were found with DGE, magnetization transfer ratio, or T2R. Least Absolute Shrinkage and Selection Operator and ROC identified a composite score of MaRIA, ADC, and DGE as a very good predictor of histologic fibrosis (ROC area under the curve = 0.910). MaRIA alone was the best predictor of histologic inflammation with excellent performance in identifying active histologic inflammation (ROC area under the curve = 0.966). DISCUSSION MRE-based scores for histologic fibrosis and inflammation may assist in the characterization of CD stenosis and enable development of fibrosis-targeted therapies and clinical treatment of stenotic patients

Does MR imaging help to evaluate intestinal fibrosis ? : Results with a murine model of radio-induced colitis

L’apparition de fibrose pariétale dans la maladie de Crohn est responsable de sténoses et fistules, principales indications chirurgicales. Le but de notre travail était d’évaluer différentes séquences IRM pour différencier l’inflammation de la fibrose à partir d’un modèle original de colite radio-induite. Nous avons inclus un groupe « contrôle » de 10 rats, un groupe « inflammation » avec inflammation et fibrose sous-muqueuse de 24 rats et un groupe « mixte » avec inflammation et fibrose transmurale de 39 rats. Nous avons montré que ce modèle était reproductible et mis au point sur une IRM petit animal 7 T des séquences dont les résultats étaient homogènes, montrant la qualité à la fois des séquences et du modèle. Les signes IRM ont été comparés à l’analyse histologique des pièces (inflammation et fibrose). Les séquences utilisées (pondération T2 et T1, diffusion, transfert d’aimantation et perfusion sans injection) montraient des différences significatives entre les rats des groupes inflammation et mixte. Les séquences ayant la meilleure performance diagnostique pour différencier les deux groupes étaient l’intensité en pondération T2, la diffusion et le transfert d’aimantation. Les combinaisons de signes IRM ayant les meilleures AUC étaient celles comprenant la perfusion, à 0.95 pour la meilleure. Une analyse multivariée de la corrélation entre les signes IRM et les scores histologiques d’inflammation et de fibrose a montré de plus que la perfusion était le seul paramètre lié à la fibrose. Les perspectives sont maintenant de tester ces séquences pour évaluer des traitements anti-fibrosants en cours de développement et de les transposer à des patients pour mieux adapter la prise en charge thérapeutique.Crohn's disease transmural bowel wall inflammation can lead to fibrosis causing luminal narrowing and stricture formation which are the main indications to surgery. The aim of our study was to evaluates MR sequences to distinguish inflammation from fibrosis using an original model of radiation-induced colitis. We included a “control” group of 10 rats, an “inflammation” group of 24 rats with inflammation and submucosal fibrosis and a “mixed” group of 39 rats with inflammation and transmural fibrosis. We showed that this model was very reproducible and developed sequences on a 7 T MR which results were homogeneous, showing both the quality of the sequences and of the model. MR data were compared with the histological analysis (inflammation and fibrosis) of the resection pieces. MR sequences (T2 and T1 weighted, diffusion weighted, magnetization transfer and FAIR perfusion) showed significant differences between irradiated and control rats and between inflammation and mixed groups. Sequences with the best AUC to differentiate the two groups were T2-weighted intensity, diffusion and magnetization transfer. The combinations of MR signs with the best AUC were those including perfusion, at 0.95 for the best. A multivariate analysis of the correlations between MR imaging and pathologic inflammation and fibrosis scores showed that perfusion was the only parameter related to fibrosis. Prospects are now to test these sequences to evaluate antifibrotic treatments currently under development and to transpose these sequences to patients to evaluate intestinal fibrosis and improve patients’ management

Sequential Arterial and Portal Vein Embolization in Patients with Cirrhosis and Hepatocellular Carcinoma: The Hospital Beaujon Experience

When feasible, hepatic resection is the treatment of choice for large hepatocellular carcinoma (HCC). Because HCC is often developed on chronic liver disease, which is known to have limited regeneration capacity, major hepatic resections are often contraindicated. Portal vein embolization (PVE) has been introduced to extend the indications for major hepatic resection and to increase the safety of the surgical procedure. However, hypertrophy after PVE is often less than in normal liver. It has been suggested that preoperative sequential arterial embolization and PVE have a strong anticancer effect and could increase the rate of hypertrophy more than PVE alone. In our experience, sequential arterial embolization and PVE effectively increase the future liver remnant and induce a high rate of complete tumor necrosis. This combined procedure should broaden the indication for major resection in chronic liver disease

Is visual radiological evaluation of liver tumour burden in patients with neuroendocrine tumours reproducible?

Background: Visual semi-quantitative assessment of liver tumour burden for neuroendocrine tumour liver metastases is often used in patient management and outcome. However, published data on the reproducibility of these evaluations are lacking. Objective: The aim of this study was to evaluate the interobserver and intraobserver agreement of a visual semi-quantitative assessment of liver tumour burden using CT scan. Methods: Fifty consecutive patients (24 men and 26 women, mean aged 54 years) were retrospectively reviewed by four readers (two senior radiologists, one junior radiologist and one gastroenterologist) who assessed the liver tumour burden based on a visual semi-quantitative method with four classes (0–10, 11–25, 26–50 and ≥50%). Interobserver and intraobserver agreement were assessed by weighted kappa coefficient and percentage of agreement. The intraclass correlation was calculated. Results: Agreement among the four observers for the evaluation of liver tumour burden was substantial, ranging from 0.62 to 0.73 (P < 0.0001). The intraclass coefficient was 0.977 (P < 0.0001). Intraobserver agreement was 0.78 and ICC was 0.97. Conclusion: Reproducibility of the visual semi-quantitative evaluation of liver tumour burden is good and is independent of the level of experience of the readers. We therefore suggest that clinical studies in patients with neuroendocrine liver metastases use this method to categorise liver tumour burden

Hepatic veins as a site of clot formation following liver resection

Pulmonary embolism occurs more frequently after hepatectomy than previously thought but is infrequently associated with peripheral deep vein thrombosis. In this paper, we report 2 cases of postoperative hepatic vein thrombosis after liver resection. Both patients had undergone major hepatectomy of a non-cirrhotic liver largely exposing the middle hepatic vein. Clots were incidentally found in the middle hepatic vein 4 and 17 d after surgery despite routine systemic thrombo-prophylaxis with low molecular weight heparin. Coagulation of the transition plan in a context of mutation of the prothrombin gene and inflammation induced biloma were the likely predisposing conditions. Clots disappeared following curative anticoagulation. We conclude that thrombosis of hepatic veins may occur after liver resection and is a potential source of pulmonary embolism

Detection of liver micrometastases from colorectal origin by perfusion CT in a rat model

BACKGROUND: Some patients with colorectal carcinoma have liver metastases (LMs) which cannot be detected by conventional imaging. This study aimed to assess whether hepatic perfusion changes induced by micrometastases can be detected by perfusion computed tomography (CT). METHODS: LMs were produced in rats by injecting carcinoma cells into the portal vein. Perfusion CT was performed at microscopic (day 10), interval (day 17), and macroscopic stage (day 34). Perfusion parameters were computed using a dual-input one-compartmental model. RESULTS: Micro and macro LMs presented a mean diameter of 0.5 and 2.6 mm, respectively. Compared to controls, LMs at interval (1.1 mm) and macroscopic stage induced significant perfusion changes: a decrease of 42% (P=0.004) and 41% (P=0.029) in hepatic transit time and an increase of 292% (P=0.073) and 240% (P=0.001) in portal delay, respectively. CONCLUSIONS: LMs with a mean diameter between 1.1 and 2.6 mm induced significant hepatic perfusion changes, detected by CT. Such detection may help to select patients and propose chemotherapy at the time of primary tumor resection

Epithelial-to-mesenchymal transition and acquired resistance to sunitinib in a patient with hepatocellular carcinoma

Background & AimsBased on the success of sorafenib, several anti-angiogenic therapies are currently evaluated in advanced hepatocellular carcinomas. Few biological data are currently available from patients that may help understanding mechanisms of acquired resistance to these drugs. Herein, we report translational data from a post-treatment surgical specimen in a patient who experienced acquired resistance to sunitinib.MethodsClinical, radiological, and pathological data were collected before treatment, under treatment, and at the time of tumor progression. In addition, a biomolecular analysis was performed at the time of progression.ResultsIn this patient with non-alcoholic steatohepatitis, initial response to sunitinib was followed by tumor progression within 6months of treatment, requesting salvage surgical resection. Surprisingly, pathological examination on post-treatment specimens revealed the presence of two juxtaposed tissue components containing either sarcomatoid-like mesenchymal cells or well- to moderately-differentiated hepatocellular carcinoma cells. Cancer cells retain a high α-fetoprotein expression in both components. However, while cells from carcinoma expressed E-cadherin but no vimentin, cancer cells from the mesenchymal component highly expressed vimentin and lost E-cadherin protein expression as measured by immunostaining. HMGA2 and Ki67 mRNA were also expressed at higher levels in mesenchymal than in carcinoma cells.ConclusionThis case report suggests the occurrence of an epithelial-to-mesenchymal transition in discrete areas of hepatocellular carcinomas developing resistance to sunitinib