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 .

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.

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.

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).

Retinol-binding protein 4 is an independent factor associated with triglycerides and a determinant of very low-density lipoprotein-apolipoprotein B100 catabolism in type 2 diabetes mellitus.

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 (ß=0.273, P<0.0001), apolipoprotein (apo) B (ß=0.258, P<0.0001), and liver fat (ß=0.191, P=0.002) and negatively with high-density lipoprotein cholesterol (ß=-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.

Intravoxel incoherent motion diffusion-weighted imaging in nonalcoholic fatty liver disease: a 3.0-T MR study.

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.

Macroscopic heterogeneity of liver fat: an MR-based study in type-2 diabetic patients.

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.

Prediction for steatosis in type-2 diabetes: clinico-biological markers versus 1H-MR spectroscopy.

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.

Liver methylene fraction by dual- and triple-echo gradient-echo imaging at 3.0T: Correlation with proton MR spectroscopy and estimation of robustness after SPIO administration.

PURPOSE: To assess the systematic errors in liver methylene fraction (LMF) resulting from fat-fat interference effects with dual- and triple-echo gradient-recalled-echo Dual/Triple GRE) sequences and to test the robustness of these sequences after iron overloading. MATERIALS AND METHODS: Forty type-2 diabetic patients underwent LMF measurement by 3.0T ¹H magnetic resonance spectroscopy (corrected for T1 and T2 decays) as the reference standard and liver fat fraction (%Fat) measurement by four Dual/Triple GRE sequences with 20° and 60° flip angle (α), corrected for T1 recovery. The same four sequences were repeated in eight patients after ferumoxide injection. Corrections for systematic errors were determined from the linear regressions (spectroscopy LMF values over Dual/Triple GRE %Fat values). Robustness was tested using Wilcoxon's signed-rank test. RESULTS: Fat-fat interference effects produced a ∼10% relative systematic error and T2* decay produced a 1.9%-4.2% absolute systematic error in LMF. When comparing before and after ferumoxide, dual-echo imaging with α = 20° and α = 60°, even when corrected, showed absolute differences of 7.23% [2.81%-10.25%] (P = 0.0117) and 5.65% [1.89%-8.216.8%] (P = 0.0117), respectively; compared to only 1.17% [0.08%-2.83%] (P = 0.0251) and 1.15% [0.37%-2.73%] (P = 0.2626) with triple-echo imaging and α = 20° and α = 60°, respectively. CONCLUSION: Triple-echo imaging with α = 60° corrected for both T1 recovery and fat-fat interference effects is robust after superparamagnetic iron oxide (SPIO) administration and can reliably quantify LMF.

PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes.

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.

Screening of anticancer drugs for chemoembolization of hepatocellular carcinoma.

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.

Liver diffusion-weighted MR imaging: the tower of Babel?

There is a growing amount of literature regarding diffusion-weighted imaging (DWI) of the liver. The apparent diffusion coefficient (ADC) was introduced in 1986 and is used extensively in studies. However, methods for calculating ADC vary considerably and the value of the ADC strongly depends on the b values chosen for its calculation. Indeed, the ADC incorporates the effects of both diffusion and perfusion, which can vary independently. Since signal attenuation as a function of b follows a bi-exponential pattern, other diffusion/perfusion coefficients can be calculated using DWI, and these may provide more meaningful measurements than the ADC. The absence of standardization for both the terminology and the methodology in DWI of the liver makes it difficult for readers to understand the technique used and strongly limits comparisons between studies. Here, we review the main principles of DWI of the liver, the limits of the ADC, and the exciting capabilities of multi-parametric DWI. We also insisted on the need for a common language for DWI of the liver.

MRI diagnosis and follow-up of hepatic infarction in a patient with antiphospholipid syndrome in early pregnancy.

Hepatic infarction is rare in hemolysis, elevated liver enzymes, and low platelets syndrome. We described a case of a 24-year-old woman who was admitted at week 17 of pregnancy with an antiphospholipid syndrome. Magnetic resonance imaging was the imaging modality of choice for diagnosing hepatic infarction, guiding treatment, ensuring the early detection of bleeding, and monitoring liver recovery.

Visceral fat area is an independent predictive biomarker of outcome after first-line bevacizumab-based treatment in metastatic colorectal cancer.

BACKGROUND: Adipose tissue releases angiogenic factors that may promote tumour growth. OBJECTIVE: To determine whether body mass index (BMI), subcutaneous fat area (SFA) and visceral fat area (VFA) are associated with outcomes in patients given first-line bevacizumab-based treatment for metastatic colorectal cancer (MCC). Patients CT was used to measure SFA and VFA in 120 patients with MCC who received bevacizumab-based treatment (bevacizumab group, n=80) or chemotherapy alone (chemotherapy group, n=40) as first-line treatment. Associations linking BMI, SFA and VFA to tumour response, time-to-progression (TTP) and overall survival (OS) were evaluated. RESULTS: In the bevacizumab group, median follow-up lasted for 24 months (3-70). BMI, SFA and VFA values above the median (ie, high BMI, high VFA and high SFA) were significantly associated with absence of a response. TTP was shorter in patients with high BMI (9 vs 12 months; p=0.01) or high VFA (9 vs 14 months; p=0.0008). High VFA was associated with shorter OS (p=0.0493). By multivariate analysis, high VFA was independently associated with response, TTP and OS (HR=7.18, p=0.008, HR=5.79, p=0.005 and HR=2.88, p=0.027, respectively). In the chemotherapy group, median follow-up lasted for 30 months (4-84). BMI, SFA and VFA were not associated with response, TTP or OS. In the whole population, interaction between VFA and bevacizumab administration was significant for response (OR=3.31, p=0.005) and TTP (HR=1.64, p=0.022), thereby confirming the results. CONCLUSION: This study provides the first evidence that high VFA independently predicts a poorer outcome in patients given first-line bevacizumab-based treatment for MCC. However, this predictive biomarker needs to be validated in a different dataset.

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.

Outcome of transcatheter arterial embolization for bladder and prostate hemorrhage.

PURPOSE: We evaluated the efficacy and outcomes of transcatheter arterial embolization for intractable bladder or prostate bleeding after failed conservative treatment. MATERIALS AND METHODS: We retrospectively studied the records of 2 women and 18 men with a mean +/- SD age of 73 +/- 17.2 years referred between 1999 and 2008 for selective pelvic angiography after failed conventional therapy. Embolization was feasible in 18 patients, including bilateral and unilateral embolization in 13 and 5, respectively. It consisted of superselective distal particulate or glue embolization of the vesical or prostatic arteries in 11 patients, selective proximal coil or gelatin sponge particle occlusion of the anterior division of the internal iliac artery in 2, the 2 techniques in 3 and coil blockade in 2. Clinical bleeding control and post-embolization angiography findings were used to assess outcomes. RESULTS: The technical success rate was 90% (18 of 20 cases). Bleeding was controlled after the first procedure in 15 of 18 patients (83.3%) and after a repeat procedure in the remaining 3. The periprocedural mortality rate was 20% (4 of 20 patients) and all deaths were related to underlying conditions. No major complications related to catheterization occurred. Late bleeding recurrence was reported in 4 of the 14 survivors (28.6%). Mean post-embolization followup was 16 months (range 15 days to 56 months). During followup 6 more patients died, including 2 of repeat bleeding. CONCLUSIONS: Selective angiographic embolization is safe and effective to control refractory, life threatening bladder or prostate bleeding. This procedure should be considered the treatment of choice since it usually obviates the need for emergency surgery in these severely ill patients.

Raltitrexed and oxaliplatin hepatic arterial infusion for advanced colorectal cancer: a retrospective study.

The aim of this study was to evaluate the efficacy and safety of combined hepatic arterial infusion (HAI), which is a combination of raltitrexed and oxaliplatin, in refractory colorectal carcinoma with only liver metastases. Seventeen consecutive patients with unresectable metastatic colorectal cancer, after the failure of two lines of systemic chemotherapy, were treated with HAI raltitrexed (3 mg/m over 1 h) followed by oxaliplatin (130 mg/m over 2 h) every 3 weeks between January 2006 and January 2009. All patients presented with the metastatic disease limited to the liver and had failed at least two lines of chemotherapy, which contained oxaliplatin, irinotecan and a fluoropyrimidine. The median number of cycles was six (range 1-15). We observed three complete responses and eight partial responses among assessable patients (overall response rate in intention to treat, 65%; 95% confidence interval, 44.3-87.7%). The median time to progression was 10.5 months and the median survival time was 27.5 months. Toxicity included grade 3-4 neutropenia (in 17%), grade 3-4 thrombopenia (in 17%), and grade 2 abdominal pain (in 47%). In conclusion, the combination regimen of HAI raltitrexed and oxaliplatin is feasible and promising in patients who presented isolated hepatic metastases of colorectal cancer after failure of irinotecan and oxaliplatin treatment. Further evaluation of this combination is required.

Preoperative embolization or ligature of the uterine arteries in preparation for conservative uterine fibroma surgery.

OBJECTIVE: To compare the efficacy, feasibility and morbidity of two preparation techniques for conservative uterine myoma surgery: temporary embolization and temporary surgical ligature of the uterine arteries. DESIGN: Retrospective study. SETTING: Gynecological Surgery and Interventional Radiology departments, Centre Hospitalier Universitaire of Dijon, France. POPULATION: A total of 100 women undergoing myomectomy between 2000 and 2008. METHODS: Three groups were constituted: (1) no preparation (43 patients), (2) uterine artery embolization (UAE) (30 patients) and (3) temporary surgical ligature of the uterine arteries (SLUA) (27 patients). The choice of technique depended on the number, size and topography of the fibromas. MAIN OUTCOMES MEASURES: Quantification of peroperative blood loss, delta hemoglobin, complications, subsequent fertility. RESULTS: Blood loss and delta hemoglobin were both lower in group 2 (p = 0.026 and p = 0.0002) and in group 3 (p = 0.048 and p = 0.001), respectively, than in group 1. The two preparation techniques were efficient. SLUA increased the duration of the operation (p < 0.0001). Hospitalization was longer following UAE (p = 0.0001). The rate of complications was 16.3, 23.3 and 3.7%, and of synechiae 9.3, 13.3 and 0% for groups 1, 2 and 3, respectively. The number of pregnancies was 8, 5 and 6 after a mean postoperative period of 5.6, 4.3 and 3.9 years, respectively. CONCLUSION: Both UAE and SLUA for myomectomy are feasible, reproducible and effective techniques for reducing peroperative blood loss. Use of these techniques must be generalized in patients with a high risk of hemorrhage, but may be compatible with subsequent fertility.

Chronic mesenteric ischemia: efficacy and outcome of endovascular therapy.

Chronic mesenteric ischemia is a rare condition caused by occlusive disease of the mesenteric vessels and manifested most commonly as abdominal pain. While the traditional therapy in symptomatic patients has been surgery, recent improvements in interventional devices and refinement in techniques have increased the popularity of endovascular treatment. The high procedural success and the low complication rate make the catheter-based approach an interesting alternative to surgery. Percutaneous angioplasty and stenting is now recognized as a minimally invasive means of obtaining good long-term results and is consequently suggested for the primary treatment of chronic mesenteric ischemia. This article presents a review of the literature on indications and technical aspects of endovascular treatment, with emphasis on short- and long-term outcomes.