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Diffusion weighted imaging (DWI) and intravoxel incoherent motion (IVIM) have been explored to assess liver tumors and diffused liver diseases. IVIM reflects the microscopic translational motions that occur in voxels in magnetic resonance (MR) DWI. In biologic tissues, molecular diffusion of water and microcirculation of blood in the capillary network can be assessed using IVIM DWI. The most commonly applied model to describe the DWI signal is a bi-exponential model, with a slow compartment of diffusion linked to pure molecular diffusion (represented by the coefficient D slow ), and a fast compartment of diffusion, related to microperfusion (represented by the coefficient D fast ). However, high variance in D fast estimates has been consistently shown in literature for liver IVIM, restricting its application in clinical practice. This variation could be explained by the presence of another very fast compartment of diffusion in the liver. Therefore, a tri-exponential model would be more suitable to describe the DWI signal. This article reviews the published evidence of the existence of this additional very fast diffusion compartment and discusses the performance and limitations of the tri-exponential model for liver IVIM in current clinical settings.

Objectives: To determine whether bi- or tri-exponential models, and full or segmented fittings, better fit the intravoxel incoherent motion (IVIM) imaging signal of healthy livers., Methods: Diffusion-weighted images were acquired with a 3 T scanner using a respiratory-triggered echo-planar sequence and 16 b-values (0-800 s/mm 2 ). Eighteen healthy volunteers had their livers scanned twice in the same session, and then once in another session. Liver parenchyma region-of-interest-based measurements were processed with bi-exponential and tri-exponential models, with both full fitting and segmented fitting (threshold b-value = 200 s/mm 2 )., Results: With the signal of all scans averaged, bi-exponential model full fitting showed D slow  = 1.14 × 10 -3  mm 2 /s, D fast  = 193.6 × 10 -3  mm 2 /s, and perfusion fraction (PF) = 16.9%, and segmented fitting showed D slow  = 0.98 × 10 -3  mm 2 /s, D fast  = 42.2 × 10 -3  mm 2 /s, and PF = 23.3%. IVIM parameters derived from the tri-exponential model were similar for full fitting and segmented fitting, with slow (D' slow  = 0.98 × 10 -3  mm 2 /s; F' slow  = 76.4 or 76.6%), fast (D' fast  = 15.1 or 15.4 × 10 -3  mm 2 /s; F' fast  = 11.8 or 11.7%) and very fast (D' Vfast  = 445.0 or 448.8 × 10 -3  mm 2 /s; F' Vfast  = 11.8 or 11.7%) diffusion compartments. The tri-exponential model provided an overall better fit than the bi-exponential model. For the bi-exponential model, full fitting provided a better fit at very low and low b-values compared with segmented fitting, with the latter tending to underestimate D fast ; however, the segmented method demonstrated lower error in signal prediction for high b-values. Compared with full fitting, tri-exponential segmented fitting offered better scan-rescan reproducibility., Conclusion: For healthy liver, tri-exponential modeling is preferred to bi-exponential modeling. For the bi-exponential model, segmented fitting underestimates D fast , but offers a more accurate estimation of D slow ., (© 2019 John Wiley & Sons, Ltd.)

Background: Iodinated and gadolinium-based contrast media (ICM; GBCM) induce immediate hypersensitivity (IH) reactions. Differentiating allergic from non-allergic IH is crucial; allergy contraindicates the culprit agent for life. We studied frequency of allergic IH among ICM or GBCM reactors., Methods: Patients were recruited in 31 hospitals between 2005 and 2009. Clinical symptoms, plasma histamine and tryptase concentrations and skin tests were recorded. Allergic IH was diagnosed by intradermal tests (IDT) with the culprit CM diluted 1:10, "potentially allergic" IH by positive IDT with pure CM, and non-allergic IH by negative IDT., Findings: Among 245 skin-tested patients (ICM = 209; GBCM = 36), allergic IH to ICM was identified in 41 (19.6%) and to GBCM in 10 (27.8%). Skin cross-reactivity was observed in 11 patients with ICM (26.8%) and 5 with GBCM (50%). Allergy frequency increased with clinical severity and histamine and tryptase concentrations (p < 0.0001). Cardiovascular signs were strongly associated with allergy. Non-allergic IH was observed in 152 patients (62%) (ICM:134; GBCM:18). Severity grade was lower (p < 0.0001) and reaction delay longer (11.6 vs 5.6 min; p < 0.001). Potentially allergic IH was diagnosed in 42 patients (17.1%) (ICM:34; GBCM:8). The delay, severity grade, and mediator release were intermediate between the two other groups., Interpretation: Allergic IH accounted for < 10% of cutaneous reactions, and > 50% of life-threatening ones. GBCM and ICM triggered comparable IH reactions in frequency and severity. Cross-reactivity was frequent, especially for GBCM. We propose considering skin testing with pure contrast agent, as it is more sensitive than the usual 1:10 dilution criteria.

Background & Aims: Idarubicin shows high cytotoxicity against hepatocellular carcinoma (HCC) cells, a high hepatic extraction ratio, and high lipophilicity leading to stable emulsions with lipiodol. A dose-escalation phase I trial of idarubicin&#95;lipiodol (without embolisation) was conducted in patients with cirrhotic HCC to estimate the maximum-tolerated dose (MTD) and to assess the safety, efficacy, and pharmacokinetics of the drug, and the health-related quality of life achieved by patients., Methods: Patients underwent two sessions of treatment with a transarterial idarubicin&#95;lipiodol emulsion without embolisation. The idarubicin dose was escalated according to a modified continuous reassessment method. The MTD was defined as the dose closest to that causing dose-limiting toxicity (DLT) in 20% of patients., Results: A group of 15 patients were enrolled, including one patient at 10 mg, four patients at 15 mg, seven patients at 20 mg, and three patients at 25 mg. Only two patients experienced DLT: oedematous ascitic decompensation and abdominal pain at 20 and 25 mg, respectively. The calculated MTD of idarubicin was 20 mg. The most frequent grade ≥3 adverse events were biological. One month after the second session, the objective response rate was 29% (complete response, 0%; partial response, 29%) based on modified Response Evaluation Criteria In Solid Tumours. The median time to progression was 5.4 months [95% confidence limit (CI) 3.0-14.6 months] and median overall survival was 20.6 months (95% CI 5.7-28.7 months). Pharmacokinetic analysis of idarubicin showed that the mean C max of idarubicin after intra-arterial injection of the idarubicin-lipiodol emulsion is approximately half the C max after intravenous administration. Health-related quality of life results confirmed the good safety results associated with use of the drug., Conclusions: The MTD of idarubicin was 20 mg after two chemolipiodolisation sessions. Encouraging safety results, and patient responses and survival were observed. A phase II trial has been scheduled., Lay Summary: There is a need for transarterial regimens that improve the responses and survival of patients with unresectable HCC. In this phase I trial, we showed that two sessions of treatment with a transarterial idarubicin&#95;lipiodol emulsion without embolisation was well tolerated and gave promising efficacy in terms of tumour control and patient survival., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Radiofrequency ablation is the recommended treatment for patients with hepatocellular carcinoma who have lesions smaller than 3 cm and are therefore not candidates for surgery. Microwave ablation is a more recent technique with certain theoretical advantages that have not yet been confirmed clinically. We aimed to compare the efficacy of both techniques in the treatment of hepatocellular carcinoma lesions of 4 cm or smaller., Methods: We did a randomised controlled, single-blinded phase 2 trial at four tertiary university centres in France and Switzerland. Patients with chronic liver disease and hepatocellular carcinoma with up to three lesions of 4 cm or smaller who were not eligible for surgery were randomised to receive microwave ablation (experimental group) or radiofrequency ablation (control group). Randomisation was centralised and done by use of a fixed block method (block size 4). Patients were randomly assigned by a co-investigator by use of the sealed opaque envelope method and were masked to the treatment; physicians were not masked to treatment, since the devices used were different. The primary outcome was the proportion of lesions with local tumour progression at 2 years of follow-up. Local tumour progression was defined as the appearance of a new nodule with features typical of hepatocellular carcinoma in the edge of the ablation zone. All analyses were done in the per-protocol population. The study is completed, but patients will continue to be followed up for 5 years. This study is registered with ClinicalTrials.gov, number NCT02859753., Findings: Between Nov 15, 2011, and Feb 27, 2015, 152 patients were randomly assigned: 76 patients to receive microwave ablation and 76 patients to receive radiofrequency ablation. For the per-protocol analysis, five patients were excluded from the microwave ablation group as were three patients from the radiofrequency ablation group. Median follow-up was 26 months (IQR 18-29) in the microwave ablation group and 25 months (18-34) in the radiofrequency ablation group. At 2 years, six (6%) of 98 lesions had local tumour progression in the microwave ablation group as did 12 (12%) of 104 in the radiofrequency ablation group (risk ratio 1·62, 95% CI 0·66-3·94; p=0·27). Complications were infrequent, with only two grade 4 complications (two events of arterial bleeding requiring embolisation, both in the microwave ablation group) and three grade 3 complications (pneumothorax; lesion of the umbilical vein; and intrahepatic segmental necrosis, all in the radiofrequency ablation group). No treatment-related deaths were reported., Interpretation: Although we did not find that microwave ablation was more effective than radiofrequency ablation for treatment of hepatocellular carcinoma lesions of 4 cm or smaller, our results show that the proportion of lesions with local tumour progression at 2 years of follow-up was low with both tested percutaneous methods., Funding: Microsulis (AngioDynamics)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome, and type 2 diabetes. NAFLD is also seen in patients with endocrinopathies. However, the relationship between endocrine diseases and the development of NAFLD is not well known. In this study, we set out to determine whether liver fat content (LFC) was associated with IGF1 levels in people with pituitary diseases (PD). Eighty-nine patients with pituitary diseases and 74 healthy controls were included in this study. LFC was measured using MRI. Hepatic steatosis was defined as LFC>5.5%. Patients with PD were older, and had a higher BMI than healthy controls. LFC was significantly higher in people with PD than in controls (6.5% vs. 3.2%; p<0.001). LFC was negatively associated with the IGF1 level. The prevalence of steatosis was higher in PD patients than in controls (36.3% vs. 14.8%; p=0.002). In multivariate analysis, which included patients and controls, the predictive variables for steatosis were age, BMI and IGF1 levels, whereas the presence of pituitary diseases and gender were not associated with steatosis. Our data showed that LFC was strongly associated with IGF1 levels. These results suggest that steatosis associated with PD is probably a consequence of a low IGF1 level in these patients., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: To assess the association between final polytetrafluoroethylene (PTFE)-covered stent transjugular intrahepatic portosystemic shunt (TIPS) angiographic parameters and free shunt revision survey., Methods: Series of two comparison groups were generated with persistence of varices or not, the 25 th , 50 th , and 75 th percentile as cutoff for each angle and a 15-mm distance as cutoff for distance D. Kaplan Meier free shunt revision curves were then created and compared with Log Rank test., Results: Mean follow-up was 455 days. Thirteen (19.4%) patients had shunt revision. Significant free shunt revision survey difference was found between post-procedural angiographic persistent varices group and the group without varices (P=0.0001). Shunt revision rate at 3, 12 and 24 months was respectively 13%, 29%, and 39% in the group with varices versus 0%, 2.7% and 2.7% in the group without. No difference was found between groups for angles A, B, C and distance D., Conclusions: Persistence of gastric or esophageal varices on final trans-TIPS angiography increases TIPS revision rate after PTFE-covered stent shunt creation whereas geometric parameters have no influence., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Liver MRI is recommended as the preoperative imaging strategy in liver metastatic colorectal cancers., Objective: The aim of the study was to assess for the first time the use of liver MRI in a French population-based cancer registry., Patients and Methods: All liver-only metastatic colorectal cancers resected for their primary tumour diagnosed between 2009 and 2013 were included. Nonconditional logistic regression was used to search for associations between the MRI order and the characteristics of patients and tumours., Results: The primary tumour and liver metastases were resected for cure in 30% (69/233) of cases, and in 72% of these liver MRI was performed before resection of the liver metastases. Preoperative MRI ordering was not significantly higher in patients younger than 70 years when compared with that in older patients. Among patients who did not undergo resection of their liver metastasis, 22% had undergone a liver MRI. After adjustment for comorbidities, the probability of having undergone an MRI was higher for patients managed in the university hospital (P=0.004) and lower in those managed in nonuniversity hospitals (P=0.002) compared with the mean of odds for all facilities. Patients more than or equal to 70 years were 2.4 times less likely than younger patients to undergo an MRI (P=0.043)., Conclusion: Liver MRI was underused in patients with colorectal liver-only synchronous metastasis undergoing curative resection for metastases and in elderly patients.

Aim: To prospectively evaluate the performance of Doppler-ultrasonography (US) for the detection of transjugular intrahepatic portosystemic shunt (TIPS) dysfunction within a multicenter cohort of cirrhotic patients., Methods: This study was conducted in 10 french teaching hospitals. After TIPS insertion, angiography and liver Doppler-US were carried out every six months to detect dysfunction (defined by a portosystemic gradient ≥ 12 mmHg and/or a stent stenosis ≥ 50%). The association between ultrasonographic signs and dysfunction was studied by logistic random-effects models, and the diagnostic performance of each Doppler criterion was estimated by the bootstrap method. This study was approved by the ethics committee of Tours., Results: Two hundred and eighteen pairs of examinations performed on 87 cirrhotic patients were analyzed. Variables significantly associated with dysfunction were: The speed of flow in the portal vein ( P = 0.008), the reversal of flow in the right ( P = 0.038) and left ( P = 0.049) portal branch, the loss of modulation of portal flow by the right atrium ( P = 0.0005), ascites ( P = 0.001) and the overall impression of the operator ( P = 0.0001). The diagnostic performances of these variables were low; sensitivity was < 58% and negative predictive value was < 73%. Therefore, dysfunction cannot be ruled out from Doppler-US., Conclusion: The performance of Doppler-US for the detection of TIPS dysfunction is poor compared to angiography. New tools are needed to improve diagnosis of TIPS dysfunction., Competing Interests: Conflict-of-interest statement: The authors of this manuscript having no conflicts of interest to disclose.

A comprehensive literature review was performed on liver intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) technique and its applications. Heterogeneous data have been reported. IVIM parameters are magnetic field strength dependent to a mild extent. A lower Dslow (D) value at 3 T than at 1.5 T and higher perfusion fraction (PF) value at 3 T than at 1.5 T were noted. An increased number of b values are associated with increased IVIM parameter measurement accuracy. With the current status of art, IVIM technique is not yet capable of detecting early stage liver fibrosis and diagnosing liver fibrosis grades, nor can it differentiate liver tumors. Though IVIM parameters show promise for tumor treatment monitoring, till now how PF and Dfast (D*) add diagnostic value to Dslow or apparent diffusion coefficient (ADC) remains unclear. This paper shows the state-of-art IVIM MR technique is still not able to offer reliable measurement for liver. More works on the measurement robustness are warranted as they are essential to justify follow-up clinical studies on patients., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Nonalcoholic fatty liver disease is very frequent in type 2 diabetes, with increased risk of further development of liver fibrosis. Animal studies have shown that GLP-1 receptor agonists may reduce liver lipogenesis. However, data in humans are scarce., Objective: To study the effect of liraglutide 1.2 mg/d on liver fat content (LFC) in patients with uncontrolled type 2 diabetes and to evaluate the factors potentially associated with liraglutide-induced modification of LFC., Design, Setting, Participants: LFC was measured by proton magnetic resonance spectroscopy before and after 6 months of liraglutide treatment in 68 patients with uncontrolled type 2 diabetes mellitus., Intervention: Liraglutide 1.2 mg/d., Outcome Measure: Change in LFC., Results: Treatment with liraglutide was associated with a significant decrease in body weight, HbA1C, and a marked relative reduction in LFC of 31% (P < 0.0001). No significant modification of LFC was observed in a parallel group of patients 6 months after intensification of the antidiabetic treatment with insulin. The reduction in LFC and body weight were highly correlated (r = 0.490; P < 0.0001). In multivariate analysis, the reduction in LFC was independently associated with baseline LFC (P < 0.0001), age (P = 0.010), and reduction in body weight (P < 0.0001), triglycerides (P = 0.019), and HbA1c (P = 0.034). In the patients who had no significant decrease in body weight, no significant reduction in LFC was observed., Conclusions: Six months of treatment with liraglutide 1.2 mg/d significantly reduced LFC in patients with inadequately controlled type 2 diabetes and this effect was mainly driven by body weight reduction. Further studies are needed to confirm that this reduction in LFC may significantly reduce fibrosis progression., (Copyright © 2017 by the Endocrine Society)

Objectives: The objective of this study was to explore the association between health-related quality of life (HRQoL) and the recommended phase 2 dose in a phase I clinical trial according to the Time to HRQoL deterioration approach (TTD)., Setting: This is a phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads performed in cirrhotic patients with hepatocellular carcinoma. Patients had to complete the EORTC QLQ-C30 HRQoL questionnaire at baseline and at days 15, 30 and 60 after TACE., Participants: Patients aged ≥18 years with HCC unsuitable for curative treatments were evaluated for the study (N=21)., Primary and Secondary Outcome Measurements: The primary objective was to determine the maximum tolerated dose (MTD) of idarubicin loaded after a single TACE session. MTD was defined as the dose level closest to that causing dose-limiting toxicity in 20% of patients. HRQoL was the secondary end point., Results: Between March 2010 and March 2011, 9, 6 and 6 patients were included at idarubicin dose levels of 5, 10 and 15 mg, respectively. Calculated MTD of idarubicin was 10 mg. At the 10 mg idarubicin dose, patients presented a longer TTD than at 5 mg, for global health status (HR=0.91 (95% CI 0.18 to 4.72)), physical functioning (HR=0.38 (0.04 to 3.22)), fatigue (HR=0.67 (0.18 to 2.56)) and pain (HR=0.47 (0.05 to 4.24))., Conclusions: These HRQoL results were consistent with the estimated MTD, with a median TTD for global health status of 41 days (21 to NA) at 5 mg, 23 days (20 to NA) at 10 mg and 25 days (17 to NA) at 15 mg. These results show the importance of studying HRQoL in phase I trials., Trial Registration Number: NCT01040559; Post-results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: It has recently been shown that an allele in the glucokinase regulatory protein (GCKR) gene was associated with increased liver fat content in obese children. In this study, we set out to determine whether GCKR rs1260326 polymorphism was associated with liver fat content in patients with type 2 diabetes., Methods: Three hundred and eight patients with type 2 diabetes were included in this study. Liver fat content was evaluated using 1H-MR spectroscopy., Results: In our population, carriers of the rs1260326 minor T allele had a higher liver fat content than did carriers of the C allele homozygote (12.4 ± 9.6 vs. 10.3 ± 9.1 %, p = 0.03). The number of patients with steatosis was significantly higher in minor T allele carriers than in C allele homozygote carriers (70.7 vs. 55.4 %; p = 0.008). In multivariate analysis, the predictive variables for steatosis were BMI [odds ratio (OR) 1.08; 95 % confidence interval (CI) 1.03-1.13; p = 0.002], statin therapy (yes) [OR 0.54; 95 % CI 0.31-0.94; p = 0.03], metformin therapy (yes) [OR 2.67; 95 % CI 1.50-4.75; p < 0.001], and rs1260326 GCKR polymorphism (TT+CT) [OR 1.99; 95 % CI 1.14-3.47; p = 0.01]., Conclusions: This study shows that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fat content was related to GCKR rs1260326 polymorphism independent of BMI, triglyceride levels, and age.

Von Meyenburg complexes, or biliary hamartomas, are frequently incidentally detected. They are usually easy to characterize with magnetic resonance imaging. However, in some occasions they are difficult to differentiate from other liver lesions, in particular from small liver metastases. Von Meyenburg complexes are developmental malformations of the ductal plate. They can be found in association with Caroli disease and Caroli syndrome. Like other ductal plate malformations, Von Meyenburg complexes associated with cholangiocarcinoma have been described and their relationship has been established. This review provides an update on the etiopathogenesis of Von Meyenburg complexes, illustrates the imaging features on ultrasound, CT and MRI of this condition and discusses the most common diagnostic pitfalls. The relationships between Von Meyenburg complexes and the various ductal plate malformations and the most recent literature data regarding the relationships between Von Meyenburg complexes and cholangiocarcinoma are presented., (Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To investigate the relationship between the improved stability of an anticancer drug-lipiodol emulsion and pharmacokinetic (PK) profile for transarterial chemoembolisation (TACE) of hepatocellular carcinoma (HCC)., Methods: The stability of four doxorubicin- or idarubicin-lipiodol emulsions was evaluated over 7 days. PK and clinical data were recorded after TACE with the most stable emulsion in eight unresectable HCC patients, after institutional review board approval., Results: The most stable emulsion was the one that combined idarubicin and lipiodol (1:2 v:v). At 7 days, the percentages of aqueous, persisting emulsion and oily phases were 50-0-50, 33-0-67, 31-39-30, and 10-90-0 for the doxorubicin-lipiodol (1:1 v:v), doxorubicin-lipiodol (1:2 v:v), idarubicin-lipiodol (1:1 v:v), and the idarubicin-lipiodol (1:2 v:v) emulsion, respectively. After TACE, mean idarubicin Cmax and AUC0-24h were 12.5 ± 9.4 ng/mL and 52 ± 16 ng/mL*h. Within 24 h after injection, 40% of the idarubicin was in the liver, either in vessels, tumours, or hepatocytes. During the 2 months after TACE, no clinical grade >3 adverse events occurred. One complete response, five partial responses, one stabilisation, and one progression were observed at 2 months., Conclusion: This study showed a promising and favourable PK and safety profile for the idarubicin-lipiodol (1:2 v:v) emulsion for TACE., Key Points: • Transarterial chemoembolisation (TACE) regimens that improve survival in hepatocellular carcinoma are needed. • Improved emulsion stability for TACE resulted in a favourable pharmacokinetic profile. • Preliminary safety and efficacy data for the idarubicin-lipiodol emulsion for TACE were encouraging.

Background: Nonalcoholic fatty liver disease (NAFLD) is independently associated with atherosclerosis in nondiabetic individuals. In type 2 diabetic patients, the link between fatty liver and atherosclerosis is less clear. Here, we assessed whether liver fat content evaluated using (1)H-magnetic resonance spectroscopy ((1)H-MRS) was independently associated with prevalent carotid plaque as a marker of atherosclerosis in type 2 diabetic patients., Methods: One hundred and forty-four prospectively enrolled patients with type 2 diabetes underwent liver fat content measurement using (1)H-MRS and carotid plaque assessment using ultrasound. Multiple logistic regressions were used to identify factors associated with carotid plaque., Results: Mean ± SD liver fat content was 9.86±8.12%. Carotid plaque prevalence was 52.1% (75/144). Patients without plaque were younger (P=0.006) and had a smaller visceral fat area (P=0.015), lower reported prevalence of previous cardiovascular events or current statin therapy (P=0.002), and higher liver fat content than those with plaque (P=0.009). By multivariable logistic regression, increased liver fat content independently predicted the absence of carotid plaque [odds ratios (ORs), 0.94; 95% confidence intervals (CIs), 0.89-0.99; P=0.017]., Conclusions: Liver fat content measured by (1)H-MRS is higher in type 2 diabetic patients without carotid plaque compared to those with plaque. This study suggests that increased liver fat content could be associated with a relative protection against carotid atherosclerosis in patients with type 2 diabetes mellitus.

Aim: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with Type 2 diabetes. Recently, it has been suggested that NAFLD is also frequently associated with Type 1 diabetes and diabetic complications. In this study, we set out to determine whether Type 1 diabetes was associated with liver fat content measured using magnetic resonance imaging., Methods: One hundred and twenty-eight patients with Type 1 diabetes, 264 patients with Type 2 diabetes and 67 participants without diabetes were included in this study. Hepatic steatosis was defined as a liver fat content > 5.5%., Results: People with Type 1 diabetes and controls were similar for age and BMI. Liver fat content was significantly higher in patients with Type 2 diabetes than in patients with Type 1 diabetes and controls. In the control group, nine people (13.4%) had steatosis compared with six (4.7%) patients with Type 1 diabetes (P = 0.04). Among patients with Type 2 diabetes group, 166 (62.8%) had steatosis. In multivariate analysis that included patients with Type 1 diabetes and participants without diabetes, steatosis was associated only with BMI, whereas age, sex, statin therapy and Type 1 diabetes were not. In patients with Type 1 diabetes, there was no correlation between liver fat content and estimated glomerular filtration rate or carotid intima media thickness., Conclusions: Our data showed that Type 1 diabetes was not associated with an increased prevalence of steatosis. Moreover, our study provided no specific arguments concerning a link between liver fat content and diabetic complications in patients with Type 1 diabetes., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Background: The purpose is to assess the short- and mid-term outcomes of microwave ablation (MWA) of small renal tumours in selected patients., Methods: From August 2012 to February 2015, 29 renal tumours in 23 patients (17 male, 6 female, mean age 75 years) were treated by percutaneous MWA under imaging guidance. The tumours were 1-4.7 cm in diameter (mean size, 2.7 cm). Therapeutic effects were assessed at follow-up with magnetic resonance imaging (MRI). All patients were followed up for 2-25 months (mean, 12.2 months) to observe the therapeutic effects and complications. Changes in renal function at day 1 after treatment were statistically analyzed using the Student paired t-test or the paired Wilcoxon test., Results: Technical success was achieved in all cases. One severe bleeding complication post-procedure occurred leading to death. No other unexpected side effects were observed after the MWA procedures. Clinical effectiveness was 100%. None of the patients showed recurrence on MRI imaging follow-up. No significant changes in renal function were noted after treatment (P=0.57)., Conclusions: Our preliminary study demonstrates that the use of MWA for the treatment of small renal tumours can be applied as safely and efficiently as other ablative techniques in selected patients not eligible for surgery.

Postoperative liver failure is a severe complication of major hepatectomies, in particular in patients with a chronic underlying liver disease. Portal vein embolization (PVE) is an approach that is gaining increasing acceptance in the preoperative treatment of selected patients prior to major hepatic resection. Induction of selective hypertrophy of the non-diseased portion of the liver with PVE in patients with either primary or secondary hepatobiliary, malignancy with small estimated future liver remnants (FLR) may result in fewer complications and shorter hospital stays following resection. Additionally, PVE performed in patients initially considered unsuitable for resection due to lack of sufficient remaining normal parenchyma may add to the pool of candidates for surgical treatment. A thorough knowledge of hepatic segmentation and portal venous anatomy is essential before performing PVE. In addition, the indications and contraindications for PVE, the methods for assessing hepatic lobar hypertrophy, the means of determining optimal timing of resection, and the possible complications of PVE need to be fully understood before undertaking the procedure. Technique may vary among operators, but cyanoacrylate glue seems to be the best embolic agent with the highest expected rate of liver regeneration for PVE. The procedure is usually indicated when the remnant liver accounts for less than 25-40% of the total liver volume. Compensatory hypertrophy of the non-embolized segments is maximal during the first 2 weeks and persists, although to a lesser extent during approximately 6 weeks. Liver resection is performed 2 to 6 weeks after embolization. The goal of this article is to discuss the rationale, indications, techniques and outcomes of PVE before major hepatectomy.

Visceral artery aneurysms (VAA) include splanchnic and renal artery aneurysms. They represent a rare clinical entity, although their detection is rising due to an increased use of cross-sectional imaging. Rupture is the most devastating complication, and is associated with a high morbidity and mortality. In addition, increased percutaneous endovascular interventions have raised the incidence of iatrogenic visceral artery pseudoaneurysms (VAPAs). For this reason, elective repair is preferable in the appropriately chosen patient. Controversy still exists regarding their treatment. Over the past decade, there has been steady increase in the utilization of minimally invasive, non-operative interventions, for vascular aneurysmal disease. All VAAs and VAPAs can technically be fixed by endovascular techniques but that does not mean they should. These catheter-based techniques constitute an excellent approach in the elective setting. However, in the emergent setting it may carry a higher morbidity and mortality. The decision for intervention has to take into account the size and the natural history of the lesion, the risk of rupture, which is high during pregnancy, and the relative risk of surgical or radiological intervention. For splanchnic artery aneurysms, we should recognize that we are not, in reality, well informed about their natural history. For most asymptomatic aneurysms, expectant treatment is acceptable. For large, symptomatic or aneurysms with a high risk of rupture, endovascular treatment has become the first-line therapy. Treatment of VAPAs is always mandatory because of the high risk of rupture. We present our point of view on interventional radiology in the splanchnic arteries, focusing on what has been achieved and the remaining challenges.

Over the past three decades, transcatheter arterial embolization has become the first-line therapy for the management of acute nonvariceal upper gastrointestinal bleeding that is refractory to endoscopic hemostasis. Advances in catheter-based techniques and newer embolic agents, as well as recognition of the effectiveness of minimally invasive treatment options, have expanded the role of interventional radiology in the treatment of bleeding for a variety of indications. Transcatheter arterial embolization is a fast, safe, and effective minimally invasive alternative to surgery, when endoscopic treatment fails to control acute bleeding from the upper gastrointestinal tract. This article describes the role of arterial embolization in the management of acute nonvariceal upper gastrointestinal bleeding and summarizes the literature evidence on the outcomes of endovascular therapy in such a setting., (Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Acute variceal bleeding is a life-threatening condition that requires a multidisciplinary approach for effective therapy. The transjugular intrahepatic portosystemic shunt (TIPS) procedure is a minimally invasive image-guided intervention used for secondary prevention of bleeding and as salvage therapy in acute bleeding. Emergency TIPS should be considered early in patients with refractory variceal bleeding once medical treatment and endoscopic sclerotherapy fail, before the clinical condition worsens. Furthermore, admission to specialized centers is mandatory in such a setting and regional protocols are essential to be organized effectively. This procedure involves establishment of a direct pathway between the hepatic veins and the portal veins to decompress the portal venous hypertension that is the source of the patient's bleeding. The procedure is technically challenging, especially in critically ill patients, and has a mortality of 30%-50% in the emergency setting, but has an effectiveness greater than 90% in controlling bleeding from gastro-esophageal varices. This review focuses on the role of TIPS in the setting of variceal bleeding, with emphasis on current indications and techniques for TIPS creation, TIPS clinical outcomes, and the role of adjuvant embolization of varices., (Copyright © 2015 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Transarterial chemoembolization (TACE) is the recommended treatment for patients suffering from intermediate, B stage, hepatocellular carcinoma. Despite an undisputed pharmacokinetic advantage, TACE with microspheres has not been shown to be superior in terms of survival compared to conventional TACE using Lipiodol(®). The best guarantee to reduce toxicity and maximize the efficacy of TACE is to strictly observe the contraindications for the procedure (Child-Pugh>B8, reduced portal flow, very large tumor, any technical contraindication and renal impairment), and rigorous application of the administration requirements for the Lipiodol(®) emulsion or loaded microspheres (assessment of hepatic vascularization investigating for accessory vascularization, injection methods). Tumor response should be assessed after four weeks by CT or MRI using the modified RECIST criteria., (Copyright © 2015. Published by Elsevier Masson SAS.)

The availability of intra-arterial hepatic therapies (radio and/or chemo-embolisation, intra-arterial hepatic chemotherapy) has convinced radiologists to perfect their knowledge of the anatomy of the liver arteries. These sometimes, complex procedures most often require selective arterial catheterization. Knowledge of the different arteries in the liver and the peripheral organs is therefore essential to optimize the procedure and avoid eventual complications. This paper aims to describe the anatomy of the liver arteries and the variants, applying it to angiography images, and to understand the implications of such variations in interventional radiological procedures., (Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Purpose: To determine whether a mono-, bi- or tri-exponential model best fits the intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) signal of normal livers., Materials and Methods: The pilot and validation studies were conducted in 38 and 36 patients with normal livers, respectively. The DWI sequence was performed using single-shot echoplanar imaging with 11 (pilot study) and 16 (validation study) b values. In each study, data from all patients were used to model the IVIM signal of normal liver. Diffusion coefficients (Di ± standard deviations) and their fractions (fi ± standard deviations) were determined from each model. The models were compared using the extra sum-of-squares test and information criteria., Results: The tri-exponential model provided a better fit than both the bi- and mono-exponential models. The tri-exponential IVIM model determined three diffusion compartments: a slow (D1 = 1.35 ± 0.03 × 10(-3) mm(2)/s; f1 = 72.7 ± 0.9 %), a fast (D2 = 26.50 ± 2.49 × 10(-3) mm(2)/s; f2 = 13.7 ± 0.6 %) and a very fast (D3 = 404.00 ± 43.7 × 10(-3) mm(2)/s; f3 = 13.5 ± 0.8 %) diffusion compartment [results from the validation study]. The very fast compartment contributed to the IVIM signal only for b values ≤15 s/mm(2) CONCLUSION: The tri-exponential model provided the best fit for IVIM signal decay in the liver over the 0-800 s/mm(2) range. In IVIM analysis of normal liver, a third very fast (pseudo)diffusion component might be relevant., Key Points: • For normal liver, tri-exponential IVIM model might be superior to bi-exponential • A very fast compartment (D = 404.00 ± 43.7 × 10 (-3) mm (2) /s; f = 13.5 ± 0.8 %) is determined from the tri-exponential model • The compartment contributes to the IVIM signal only for b ≤ 15 s/mm(2).

The liver segmentation system, described by Couinaud, is based on the identification of the three hepatic veins and the plane passing by the portal vein bifurcation. Nowadays, Couinaud's description is the most widely used classification since it is better suited for surgery and more accurate for the localisation and monitoring of intra-parenchymal lesions. Knowledge of the anatomy of the portal and venous system is therefore essential, as is knowledge of the variants resulting from changes occurring during the embryological development of the vitelline and umbilical veins. In this paper, the authors propose a straightforward systematisation of the liver in six steps using several additional anatomical points of reference. These points of reference are simple and quickly identifiable in any radiological examination with section imaging, in order to avoid any mistakes in daily practice. In fact, accurate description impacts on many diagnostic and therapeutic applications in interventional radiology and surgery. This description will allow better preparation for biopsy, portal vein embolisation, transjugular intrahepatic portosystemic shunt, tumour resection or partial hepatectomy for transplantation. Such advance planning will reduce intra- and postoperative difficulties and complications., (Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Intractable hematuria from the bladder or the prostate can be life-threatening and its management remains a difficult clinical problem. Severe bleeding can arise as a result of radiation cystitis, bladder carcinoma, cyclophosphamide-induced cystitis, severe infection, transurethral resection of the prostate and prostate cancer. When irrigation of the bladder through a three-way catheter and fulguration of the bleeding lesions fail to stop the hematuria, a life-threatening situation can develop, when blood transfusion fails to keep pace with the rate of blood loss. Patients with massive uncontrollable hematuria are often elderly and unfit for cystectomy as a treatment. Many urologists have had to manage this difficult problem, and several different treatments have been attempted and described, with varying degrees of success. Transcatheter arterial embolization of the vesical or prostatic arteries is occasionally indicated in these patients when all other measures have failed. There is limited published experience with this procedure, but success in 90% of patients is reported when the vesical or prostatic arteries can be identified. The aim of this review is to describe the current place of transcatheter arterial embolization in the management of severe bladder or prostate bleeding after failed conservative therapy, and to review its efficacy and morbidity., (Copyright © 2014 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: A phase I dose-escalation trial of transarterial chemoembolisation (TACE) with idarubicin-loaded beads was performed in cirrhotic patients with hepatocellular carcinoma (HCC)., Aim: To estimate the maximum-tolerated dose (MTD) and to assess safety, efficacy, pharmacokinetics and quality of life., Methods: Patients received a single TACE session with injection of 2 mL drug-eluting beads (DEBs; DC Bead 300-500 μm) loaded with idarubicin. The idarubicin dose was escalated according to a modified continuous reassessment method. MTD was defined as the dose level closest to that causing dose-limiting toxicity (DLT) in 20% of patients., Results: Twenty-one patients were enrolled, including nine patients at 5 mg, six patients at 10 mg, and six patients at 15 mg. One patient at each dose level experienced DLT (acute myocardial infarction, hyperbilirubinaemia and elevated aspartate aminotransferase (AST) at 5-, 10- and 15-mg, respectively). The calculated MTD of idarubicin was 10 mg. The most frequent grade ≥3 adverse events were pain, elevated AST, elevated γ-glutamyltranspeptidase and thrombocytopenia. At 2 months, the objective response rate was 52% (complete response, 28%, and partial response, 24%) by modified Response Evaluation Criteria in Solid Tumours. The median time to progression was 12.1 months (95% CI 7.4 months--not reached); the median overall survival was 24.5 months (95% CI 14.7 months--not reached). Pharmacokinetic analysis demonstrated the ability of DEBs to release idarubicin slowly., Conclusions: Using drug-eluting beads, the maximum-tolerated dose of idarubicin was 10 mg per TACE session. Encouraging responses and median time to progression were observed. Further clinical investigations are warranted (NCT01040559)., (© 2014 John Wiley & Sons Ltd.)

Background: Transarterial chemoembolisation (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity., Aim: To identify predictive factors of severe TACE-related toxicity in patients with unresectable HCC., Methods: All HCC patients who underwent TACE at the Dijon University Hospital between 2008 and 2011 were included in this retrospective study. Severe TACE-related toxicity was defined as the occurrence of any adverse event grade ≥ 4, or any adverse event that caused a prolongation of hospitalisation of >8 days, or any additional hospitalisation within 1 month after TACE. Factors predicting toxicity were identified using a logistic regression model. The robustness of the final model was confirmed using bootstrapping (500 replications)., Results: 124 patients were included, median age was 67 years and 90% were male; 22 patients (18%) experienced severe TACE-related toxicity. Factors that independently predicted severe TACE-related toxicity in multivariate analysis were total tumour size (OR, 1.15 cm(-1); 95%CI, 1.04-1.26; p=0.01), and high serum AST levels (OR, 1.10 per 10 IU/l; 95%CI, 1.01-1.21; p=0.04). The results were confirmed by bootstrapping., Conclusions: Total tumour size and high serum AST levels were predictive factors of severe TACE-related toxicity in this hospital-based series of patients with unresectable HCC., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Aims: The link between diabetic retinopathy (DR) and adipokines is controversial. Some studies suggest that visceral fat and adipokines could be additional risk factors for DR. The aim of this study was to determine the relationship between abdominal fat or adipokine secretion and DR in patients with type 2 diabetes mellitus (DM)., Methods: A total of 179 patients with type 2 DM were included. Each patient underwent measurement of plasma adiponectin and leptin and an evaluation of body fat distribution (visceral and subcutaneous) with MRI. The severity of DR was evaluated according to the classification of the American Academy of Ophthalmology. Patients were classified in 3 groups: absence of DR, mild and moderate DR, and advanced DR (severe, proliferative and laser-treated DR)., Results: There were no significant differences between the 3 groups for adiponectin, leptin and visceral or subcutaneous fat accumulation. Patients with DR had a mean duration of diabetes, serum creatinine concentration and percentage of macroalbuminuria significantly higher than patients without DR (p < 0.001, p = 0.003 and p < 0.001, respectively). Serum adiponectin increased with the diabetic nephropathy stage (p = 0.007)., Conclusions: Our study suggests that body fat distribution and adipokine secretion are not associated with DR in patients with type 2 DM., (© 2013 S. Karger AG, Basel.)

Acute variceal hemorrhage, a life-threatening condition that requires a multidisciplinary approach for effective therapy, is defined as visible bleeding from an esophageal or gastric varix at the time of endoscopy, the presence of large esophageal varices with recent stigmata of bleeding, or fresh blood visible in the stomach with no other source of bleeding identified. Transfusion of blood products, pharmacological treatments and early endoscopic therapy are often effective; however, if primary hemostasis cannot be obtained or if uncontrollable early rebleeding occurs, transjugular intrahepatic portosystemic shunt (TIPS) is recommended as rescue treatment. The TIPS represents a major advance in the treatment of complications of portal hypertension. Acute variceal hemorrhage that is poorly controlled with endoscopic therapy is generally well controlled with TIPS, which has a 90% to 100% success rate. However, TIPS is associated with a mortality of 30% to 50% in such a setting. Emergency TIPS should be considered early in patients with refractory variceal bleeding once medical treatment and endoscopic sclerotherapy failure, before the clinical condition worsens. Furthermore, admission to specialized centers is mandatory in such a setting and regional protocols are essential to be organized effectively. This review article discusses initial management and then focuses on the specific role of TIPS as a primary therapy to control acute variceal hemorrhage, particularly as a rescue therapy following failure of endoscopic approaches.

Purpose: To assess the interobserver reproducibility of the quantification of the visceral and subcutaneous fat by computed tomography from an umbilical slice and study the effect of the level of the slice (slice going through the navel versus a slice going through disc L3-L4)., Materials and Methods: Forty-four breast cancer patients who had a CT-scan were included in this study. This is a double blind (junior versus senior) retrospective study to determine the interobserver reproducibility. A junior observer studied the variation between two levels of slice by selecting an image going through L3-L4 and the navel., Results: The measurement of the fat obtained from an umbilical slice seemed to be well correlated and consistent with that obtained from a slice with a disc reference (L3-L4). The interobserver reproducibility is good for the quantification of the umbilical fat (Spearman and Lin at 0.9921 and 0.985 [P<0.001] for the visceral fat)., Conclusion: The interobserver reproducibility of the single slice CT-scan measurement going through the navel (easily detected) is excellent and may therefore be used in oncology as a predictive tool to measure a characteristic of the host and not the tumor., (Copyright © 2013 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.)

Background: There is still no consensus about the best chemotherapeutic agent for transarterial chemoembolization (TACE). A recent in vitro study demonstrated that idarubicin, an anthracycline, was by far the most cytotoxic drug on human hepatocellular carcinoma (HCC) cell lines. Idarubicin is much more lipophilic than doxorubicin, leading to higher cell penetration through lipidic membranes and greater accumulation of the drug in the lipiodol. Furthermore, idarubicin has the ability to overcome multidrug resistance. Therefore, we designed this pilot human study to evaluate the safety and efficacy of lipiodol TACE using idarubicin., Methods: In 21 consecutive patients treated by lipiodol TACE with idarubicin (10 mg) for HCC, safety data, tumor response (Response Evaluation Criteria in Solid Tumors, mRECIST), time to treatment failure (TTTF), and overall survival were evaluated., Results: Postembolization syndrome was observed after 30.9% (17 of 55) of sessions. No patient died from a TACE-related complication. No hematological grade 3-5 adverse event was observed. At least one grade 3 or higher adverse event occurred in 19% (4 of 21) of patients. On imaging, no progression was encountered; four patients (24%) exhibited stable disease, 12 (57%) exhibited a partial response, and five (19%) exhibited a complete response. Median TTTF was 16.7 months (Kaplan-Meier analysis). At 6 months, 94.7% (95% confidence interval [CI] 68.1-99.2) of patients did not reach treatment failure, whereas treatment failure was not reached in 50.6% (95% CI 21.6-73.9) of patients at 1 year. Overall survival was 83.5% (95% CI 57-94.4) at 1 year., Conclusion: Idarubicin seems safe and effective in lipiodol TACE of HCC. This warrants further study to determine the potential of this drug to replace doxorubicin for TACE.

Objective: Retinol-binding protein 4 (rbp4) is an adipokine secreted by adipocytes and liver, whose levels are elevated in type 2 diabetes mellitus (T2DM). Plasma levels of rbp4 and triglycerides are strongly correlated in T2DM. However, we do not know whether this association is direct or indirect via liver fat content, and the link between rbp4 and triglyceride metabolism remains unknown., Methods and Results: Liver fat measurement by proton spectroscopy was performed in 221 patients with T2DM, and an in vivo kinetic study with stable isotopes was carried out in 14 patients with T2DM. In multivariate analysis, triglycerides were associated positively with rbp4 (β=0.273, P<0.0001), apolipoprotein (apo) B (β=0.258, P<0.0001), and liver fat (β=0.191, P=0.002) and negatively with high-density lipoprotein cholesterol (β=-0.442, P<0.0001). rbp4 was correlated positively with apoB100 very-low-density lipoprotein (VLDL) pool (r=0.62, P=0.017) and negatively with VLDL-apoB100 total fractional catabolic rate (r=-0.66, P=0.001). In multivariate analysis, rbp4 (P=0.015), plasma triglycerides (P=0.024), and sex (P=0.026) were independently associated with VLDL-apoB100 total fractional catabolic rate., Conclusions: In T2DM, plasma rbp4 level is associated with plasma triglycerides, independently of liver fat content. There is a strong independent negative correlation between plasma rbp4 and VLDL-apoB100 total fractional catabolic rate. These data suggest that rbp4 may be involved in the pathophysiology of hypertriglyceridemia in T2DM by reducing VLDL catabolism.

Acute nonvariceal upper gastrointestinal bleeding (UGIB) is a major medical emergency problem associated with significant morbidity and mortality. Endoscopy is considered the first method of choice to detect and treat UGIB. Endoscopic therapy usually achieves primary hemostasis, but 10%-30% of these patients have repeat bleeding. In patients in whom hemostasis is not achieved with endoscopic techniques, treatment with transcatheter angiographic embolization (TAE) or surgery is needed. Surgical intervention is usually an expeditious and gratifying endeavor, but it can be associated with high operative mortality rates. A large number of studies support the use of TAE as salvage therapy as an alternative to surgery. However, few studies have compared the results of TAE with that of emergency surgery in terms of efficiency, the frequency of repeat bleeding, and complications. Recently, Ang et al retrospectively compared the outcome of TAE and surgery as salvage therapy of UGIB after failed endoscopic treatment. There were no significant differences in 30 d mortality, complication rates and length of stay although higher rebleeding rates were observed after TAE compared with surgery. In this commentary, we discuss the advantages and drawbacks of these two therapeutic strategies for UGIB. We also attempt to define the exact role of TAE for acute nonvariceal UGIB.

Objective: To assess the heterogeneity of liver fat deposition with MR of the liver in type-2 diabetic (T2D) patients., Methods: We enrolled 121 consecutive T2D patients. The reference standard was 3.0-T (1)H-MR spectroscopy. Hepatic steatosis was defined as liver fat content (LFC) ≥5.56 %. A triple-echo gradient-echo sequence corrected for T1 recovery and T2* decay was used to calculate LFC in left and right livers and hepatic segments. Analyses were performed using a linear mixed model., Results: Fifty-nine (48.8 %) patients had liver steatosis, whereas 62 (51.2 %) did not. Steatosis was greater in the right than in the left liver (P < 0.0001) [mean difference: 1.32 % (range: 0.01-8.75 %)]. In seven patients (5.8 %), LFC was <5.56 % in one side of the liver, whereas it was ≥5.56 % in the other. Steatosis of the left and right liver was heterogeneous at the segmental level in both non-steatotic (P < 0.001 and P < 0.0001 respectively) and steatotic (P < 0.0001 and P = 0.0002 respectively) patients [mean maximum difference: 3.98 % (range: 0.74-19.32 %)]. In 23 patients (19 %), LFC was <5.56 % in one segment, whereas it was ≥5.56 % in at least one other., Conclusion: Overall, the mean segmental/lobar variability of steatosis is low. However, segmental variability can sometimes lead to a misdiagnosis., Key Points: There is a need for methods quantifying steatosis over a large region. Steatosis is usually greater in the right than left lobe of the liver. Steatosis within both left and right hepatic lobes is segmentally heterogeneous. Segmental variability of steatosis can result in misdiagnosis.

Unlabelled: We investigated how liver fat content (LFC) influences cholesterol metabolism by quantifying liver fat using proton magnetic resonance spectroscopy and by measuring the serum concentrations of lathosterol, a marker of cholesterol synthesis, and sitosterol and campesterol, two markers of cholesterol absorption. We also evaluated whether this relationship could be modified by statin therapy. The study was conducted in 263 patients with type 2 diabetes, 137 of whom (52.0%) received statin therapy., Results: One hundred and sixty-five patients (62.7%) had steatosis (LFC>5.5%). We performed specific analyses in patients without statin therapy and in patients treated with statin therapy. In both groups, the lathosterol to cholesterol ratio correlated positively with LFC, and in multivariate analysis, the lathosterol to cholesterol ratio was associated with LFC independently of age, gender and BMI. Sitosterol and campesterol concentrations were not associated with LFC., Conclusions: Our study suggests that in patients with type 2 diabetes, LFC is associated with an increase in cholesterol synthesis that is independent of obesity or diabetes mellitus. Statin therapy does not modify this relationship., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To compare pure molecular diffusion, D, perfusion-related diffusion, D*, and perfusion fraction, f, determined from diffusion-weighted (DW) magnetic resonance (MR) imaging on the basis of the intravoxel incoherent motion (IVIM) theory in patients with type 2 diabetes with and without liver steatosis., Materials and Methods: This prospective study was approved by the appropriate ethics committee, and written informed consent was obtained from all patients. Between December 2009 and September 2011, 108 patients with type 2 diabetes (51 men, 57 women; mean age, 50 years) underwent 3.0-T single-voxel point-resolved proton MR spectroscopy of the liver (segment VII) to calculate the liver fat fraction from water (4.76 ppm) and methylene (1.33 ppm) peaks, corrected for T1 and T2 decay. Steatosis was defined as a liver fat fraction of at least 5.56%. DW imaging was performed by using a single-shot echo-planar sequence with 11 b values (0, 5, 15, 25, 35, 50, 100, 200, 400, 600, 800 sec/mm2). Liver D, D*, and f were measured and compared in patients with and patients without steatosis (Mann-Whitney test)., Results: The mean liver fat fraction was 7.8% (standard deviation, 9%; range, 0.99%-45%). Forty patients had liver steatosis. D was significantly lower in steatotic compared with nonsteatotic livers (mean, 1.03×10(-3) mm2/sec±0.23 [standard deviation] vs 1.24×10(-3) mm2/sec±0.15, respectively; P<.0001), as was D* (mean, 72.2×10(-3) mm2/sec±61.4 vs 110.6×10(-3) mm2/sec±79; P=.0025). However, f was significantly higher in steatotic compared with nonsteatotic livers (mean, 33.8%±9.4 vs 26.9%±8.8; P=.0003)., Conclusion: D is significantly decreased in steatosis. The reduction in D* reflects decreased liver parenchymal perfusion in steatosis. Therefore, steatosis can affect diffusion parameters obtained with IVIM., (© RSNA, 2012.)

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome and type 2 diabetes. Although dietary fat contributes substantially to the accumulation of liver fat, the role of individual fatty acids in this accumulation is unclear., Objective: In this study, we set out to determine whether liver fat content (LFC), was associated with red blood cell fatty acid (RBC-FA) composition in people with type 2 diabetes., Design, Settings, and Participants: One hundred and sixty-two type 2 diabetic patients were included in this study. LFC was measured using (1)H-MR Spectroscopy. RBC-FA composition was measured by gas chromatography., Results: One hundred and nine (67.2%) patients had steatosis. Patients with steatosis had a higher BMI (p = 0.0005), and higher plasma triglyceride levels (p = 0.009) than did patients without steatosis. We report a significant association between palmitic acid (16:0), palmitoleic acid (16:1n-7) concentrations and ratio of monounsaturated to saturated fatty acid (palmitoleic acid to palmitic acid) and higher liver fat content. Total polyunsaturated fatty acid (PUFA), homo-gamma-linolenic acid (20:3n-6), docosahexaenoic acid (22:6n-3), and arachidonic acid (20:4 n-6) were associated with lower LFC., Conclusions: Our data showed that an increased erythrocytes long-chain n-3 and n-6 fatty acids was associated with a lower prevalence of steatosis in patients with type 2 diabetes. These results suggest that n-3 and n-6 fatty acids supplementation could be a promising treatment for NAFLD in patients with type 2 diabetes., (Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: The SteatoTest, fatty liver index (FLI) and hepatic steatosis index (HSI) are clinico-biological scores of steatosis validated in general or selected populations. Serum adiponectin (s-adiponectin) and retinol binding protein 4 (s-RBP4) are adipokines that could predict liver steatosis. We investigated whether the Steatotest, FLI, HSI, s-adiponectin and s-RBP4 could be valid predictors of liver steatosis in type-2 diabetic (T2D) patients., Methods: We enrolled 220 consecutive T2D patients. Reference standard was 3.0 T (1)H-MR spectroscopy (corrected for T1 and T2 decays). Intraclass correlation coefficients (ICCs), Kappa statistic measures of agreement, receiver operating characteristic (ROC) curves were assessed., Results: Median liver fat content was 91 mg triglyceride/g liver tissue (range: 0-392). ICCs among the Steatotest, FLI, HSI, s-adiponectin, s-RBP4 and spectroscopy were low: 0.384, 0.281, 0.087, -0.297 and 0.048. Agreement between scores and spectroscopy was poor (Kappa range: 0.042-0.281). The areas under the ROC curves were low: 0.674, 0.647, 0.637, 0.616 and 0.540. S-adiponectin and s-RBP4 levels were strongly related to the presence of diabetic nephropathy (P = 0.0037 and P = 0.004; Mann-Whitney)., Conclusion: The SteatoTest, FLI, HSI, s-adiponectin, s-RBP4 are not valid predictors of steatosis in T2D patients. Clino-biological markers cannot replace (1)H-MR spectroscopy for the assessment of liver fat in this population., Key Points: (1) H-MR spectrosopy can reliably estimate the weight fraction of liver steatosis. Type-2 diabetes provides an interesting model for assessing liver steatosis. Clinico-biological markers seem to be invalid predictors for steatosis in type-2 diabetes.

Background: There is no consensus about the most effective method for transarterial chemoembolisation of hepatocellular carcinoma., Aim: The aim of this phase II trial was to compare the efficacy and toxicity of lipiodol transarterial chemoembolisation with amiodarone in association with pirarubicin or doxorubicin versus lipiodol transarterial chemoembolisation with anthracycline alone in a control group., Methods: Patients with unresectable hepatocellular carcinoma and Child-Pugh A/B7 were considered eligible for the trial. transarterial chemoembolisation was repeated every 6 weeks for a maximum of 4 sessions., Results: Thirteen patients were randomised in the amiodarone group, and 14 were randomised in the control group. The two groups were comparable with respect to their baseline characteristics. The objective response rate according to the EASL criteria was 62% (95% CI 35-88) in the amiodarone group and 50% (95% CI 24-76) in the control group. At 1 and 2 years, survival rates were 77% (95% CI 44-92) and 52% (95% CI 22-75) in the amiodarone group, and 57% (95% CI 28-78) and 40% (95% CI 15-65) in the control group, respectively. There was no difference between the two groups in terms of toxicity., Conclusions: The results of this study suggest that lipiodol transarterial chemoembolisation with anthracycline and amiodarone was safe but did not increase survival compared with lipiodol transarterial chemoembolisation with anthracycline alone in patients with hepatocellular carcinoma., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Context: Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance., Objective: In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in unselected patients with type 2 diabetes., Design, Setting and Participants: Two hundred and thirty-four patients with type 2 diabetes were included in this study., Main Outcome Measures: LFC was evaluated using (1) H-MR spectroscopy; fibrosis was measured using the non-invasive FibroTest(®)., Results: Advanced liver fibrosis (stage F2 or above) was observed in 10.2% of the patients while 149 (63.6%) patients had steatosis. The prevalence of steatosis and fibrosis was higher in minor G allele carriers than that in C allele homozygote carriers (70.3 vs 57.1%; P=0.04 and 14.7 vs 7.5%; P=0.07 respectively). In multivariate analysis, the predictive variables for advanced liver fibrosis were age (≥60) (P=0.005), sex (female) (P=0.004) and rs 738409 PNPLA3 polymorphism (P=0.01); body mass index (BMI) and LFC were not associated with liver fibrosis., Conclusions: This study confirms that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fibrosis was related to the rs738409 polymorphism independent of BMI or LFC., (© 2011 John Wiley & Sons A/S.)

The aim of this study was to select the best candidate drug for transarterial chemoembolization by in-vitro cytotoxic evaluations of 11 anticancer drugs on three human hepatocellular carcinoma (HCC) cell lines. The SNU-398, HepG2, and SNU-449 human HCC cell lines were exposed for 30 min to 11 concentrations of doxorubicin, epirubicin, idarubicin, mitoxantrone, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, gemcitabine, mitomycin C, or paclitaxel. Cytotoxicity was measured using a quantitative colorimetric assay. For each drug and cell line, we calculated the drug concentration that caused 90% cell death (IC90). To enable comparisons of drugs with different concentration ranges, we computed the cytotoxic index (CyI) as the ratio of maximal drug concentration of more than IC90. Parameters were estimated using nonlinear regression models. Idarubicin was the most active drug on all three cell lines. With SNU-398 cells, the idarubicin CyI was 2.4-fold, 2.5-fold, 57-fold, 148-fold, and more than 58 748-fold higher than the CyIs of mitoxantrone, epirubicin, doxorubicin, gemcitabine, and other drugs, respectively. With HepG2 cells, the idarubicin CyI was 27-fold, 28-fold, 51-fold, and more than 1343-fold higher than the CyIs of doxorubicin, epirubicin, mitoxantrone, and other drugs, respectively. On the resistant SNU-449 cell line, the idarubicin CyI was 2.9-fold and 14-fold higher than the CyIs of paclitaxel and gemcitabine, respectively, the only other drugs effective on this cell line. Among 11 chemotherapeutic agents including doxorubicin, cisplatin, and epirubicin, the most effective on three HCC cell lines was idarubicin. Further clinical investigations are needed to evaluate the safety and efficacy of idarubicin for transarterial chemoembolization in HCC.

Purpose: To evaluate the efficacy of pre-myomectomy uterine artery embolization with gelatin sponge particles to reduce operative blood loss and facilitate removal of fibroids., Materials and Methods: This retrospective study included 33 women (mean age, 36 years; range, 24-45 years), of whom at least 18 wished to preserve fertility. They presented with at least one large myoma (mean diameter, 90 mm; range, 50-150 mm) and had undergone preoperative uterine artery embolization with resorbable gelatin sponge by unilateral femoral approach between December 2001 and November 2008. Clinical, radiological and surgical data were available for all patients. Mean haemoglobin levels before and after surgery were compared with Student's t-test., Results: No complication or technical failure of embolization occurred. The myomectomies were performed during laparotomy (25 cases) or laparoscopy (8 cases). Dissection of fibroids was easier (mean, 3 per patient; range, 1-11), with a mean operating time of 108±50 min (range, 30-260 min). Bloodless surgery was the rule with a mean estimated peroperative blood loss of 147±249 mL (range, 0-800 mL). Mean pre-(12.9±1.3g/dL) and post-therapeutic (11.4±1.2g/dL) haemoglobin levels were not statistically different (p>0.05). There was no need for blood transfusion. None of the patients required hysterectomy. The mean duration of hospital stay was 7.5±1.3 days (range, 3-12 days)., Conclusion: Preoperative uterine artery embolization is effective in reducing intraoperative blood loss and improves the chances of performing conservative surgery. It should be considered a useful adjunct to myomectomy in women at high hemorrhagic risk or who refuse blood transfusion., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Transarterial chemoembolization (TACE) is the standard treatment in patients with unresectable non-metastatic hepatocellular carcinoma (HCC). New drug eluting beads aim at improving efficacy of TACE in retaining as long as possible the anticancer drug within the tumor. Our monocentric study compares direct hospital medical costs, according to two different methods, for a first course of conventional TACE and for a first course of TACE using drug eluting beads in 30 patients with HCC. The average cost of a first course of conventional TACE valued by the analytic accounting system is 4 332 € versus 3 577 € for a first course of TACE using drug eluting beads. The average cost of a first course of conventional TACE valued by the official tariffs from the new French Diagnosis Related Group prospective payment system is 4 507 € (+175 €) versus 2 852 € (-725 €) for a first course of TACE using drug eluting beads. Our study shows that a first TACE using drug eluting beads, valued by the official tariffs from the new French Diagnosis Related Group prospective payment system, is significantly (p  =  0.006) less expensive than a first conventional TACE.