Evidence of Tri-Exponential Decay for Liver Intravoxel Incoherent Motion MRI: A Review of Published Results and Limitations.

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 Dslow), and a fast compartment of diffusion, related to microperfusion (represented by the coefficient Dfast). However, high variance in Dfast 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.

Comparison of tri-exponential decay versus bi-exponential decay and full fitting versus segmented fitting for modeling liver intravoxel incoherent motion diffusion MRI.

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/mm2 ). 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/mm2 ). RESULTS: With the signal of all scans averaged, bi-exponential model full fitting showed Dslow  = 1.14 × 10-3  mm2 /s, Dfast  = 193.6 × 10-3  mm2 /s, and perfusion fraction (PF) = 16.9%, and segmented fitting showed Dslow  = 0.98 × 10-3  mm2 /s, Dfast  = 42.2 × 10-3  mm2 /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  mm2 /s; F'slow  = 76.4 or 76.6%), fast (D'fast  = 15.1 or 15.4 × 10-3  mm2 /s; F'fast  = 11.8 or 11.7%) and very fast (D'Vfast  = 445.0 or 448.8 × 10-3  mm2 /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 Dfast ; 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 Dfast , but offers a more accurate estimation of Dslow .

Persistence of gastric or esophageal varices on final angiography increases transjugular intrahepatic portosystemic shunt revision rate after polytetrafluoroethylene-covered stent shunt creation.

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 25th, 50th, and 75th 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.

Efficacy of microwave ablation versus radiofrequency ablation for the treatment of hepatocellular carcinoma in patients with chronic liver disease: a randomised controlled phase 2 trial.

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).

Intra-arterial idarubicin_lipiodol without embolisation in hepatocellular carcinoma: The LIDA-B phase I trial.

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_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_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 Cmax of idarubicin after intra-arterial injection of the idarubicin-lipiodol emulsion is approximately half the Cmax 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_lipiodol emulsion without embolisation was well tolerated and gave promising efficacy in terms of tumour control and patient survival.

Liver Fat Content in People with Pituitary Diseases: Influence of Serum IGF1 Levels.

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.

Immediate Hypersensitivity to Contrast Agents: The French 5-year CIRTACI Study.

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.

Evaluation of Doppler-ultrasonography in the diagnosis of transjugular intrahepatic portosystemic shunt dysfunction: A prospective study.

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.

Current use of MRI in patients with liver metastatic colorectal cancer: a population-based study.

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.

Liver intravoxel incoherent motion (IVIM) magnetic resonance imaging: a comprehensive review of published data on normal values and applications for fibrosis and tumor evaluation.

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.

Effect of Liraglutide Therapy on Liver Fat Content in Patients With Inadequately Controlled Type 2 Diabetes: The Lira-NAFLD Study.

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.

An explorative study to assess the association between health-related quality of life and the recommended phase II dose in a phase I trial: idarubicin-loaded beads for chemoembolisation of hepatocellular carcinoma.

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.

Improved stability of lipiodol-drug emulsion for transarterial chemoembolisation of hepatocellular carcinoma results in improved pharmacokinetic profile: Proof of concept using idarubicin.

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.

GCKR polymorphism influences liver fat content in patients with type 2 diabetes.

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.

Image-guided percutaneous microwave ablation of small renal tumours: short- and mid-term outcomes.

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.

Preoperative portal vein embolization in liver cancer: indications, techniques and outcomes.

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.

Endovascular management of visceral artery aneurysms: When to watch, when to intervene?

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.

Liver fat content is negatively associated with atherosclerotic carotid plaque in type 2 diabetic patients.

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.

Intravoxel incoherent motion diffusion-weighted imaging in the liver: comparison of mono-, bi- and tri-exponential modelling at 3.0-T.

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).