Adverse events, short- and long-term outcomes of extra corporeal liver therapy in the intensive care unit: 16 years experience with MARS® in a single center.

BACKGROUND: Molecular Adsorbent Recirculating System (MARS®) is a non-biological artificial liver device. The benefit risk ratio between uncertain clinical effects and potential adverse events remains difficult to assess. We sought to describe adverse events related to MARS® therapy as well as biological and clinical effects. METHODS: All intensive care unit (ICU) admissions to whom MARS® therapy was prescribed from March 2005 to August 2021 were consecutively and prospectively included. The main endpoint was the incidence of adverse events related to MARS® therapy. Secondary endpoints were the biological and clinical effects of MARS® therapy. RESULTS: We reported 180 admissions treated with MARS® therapy. Among the 180 admissions, 56 (31.1%) were for acute-on-chronic liver failure, 32 (17.8%) for acute liver failure, 28 (15.5%) for post-surgery liver failure, 52 (28.9%) for pruritus and 12 (6.7%) for drug intoxication. At least one adverse event occurred in 95 (52.8%) admissions. Thrombocytopenia was the most frequent adverse event which was recorded in 55 admissions (30.6%). Overall, platelets count was 131 (± 95) × 109/L before and 106 (± 72) × 109/L after MARS® therapy (p < .001). After MARS® therapy, total bilirubin was significantly decreased in all groups (p < 0.05). Hepatic encephalopathy significantly improved in both the acute-on-chronic and in the acute liver failure group (p = 0.01). In the pruritus group, pruritus intensity score was significantly decreased after MARS® therapy (p < 0.01). CONCLUSION: In this large cohort of patients treated with MARS® therapy we report frequent adverse events. Thrombocytopenia was the most frequent adverse event. In all applications significant clinical and biological improvements were shown with MARS® therapy.

Agreement Between 2-Dimensional Shear Wave and Transient Elastography Values for Diagnosis of Advanced Chronic Liver Disease.

BACKGROUND & AIMS: Inter-platform variation in liver stiffness evaluation (LSE) could hinder dissemination and clinical implementation of new ultrasound methods. We aimed to determine whether measurements of liver stiffness by bi-dimensional shear wave elastography (2D-SWE) with a Supersonic Imagine apparatus are comparable to those made by vibration-controlled transient elastography (VCTE). METHODS: We collected data from 1219 consecutive patients with chronic liver disease who underwent LSE by VCTE and 2D-SWE (performed by blinded operators), on the same day, at a single center in France from September 2011 through June 2019. We assessed the ability of liver stiffness value distributions and 2D-SWE performances to identify patients with compensated advanced chronic liver disease (cACLD) according to the Baveno VI criteria, based on VCTE cut-off values. RESULTS: VCTE and 2D-SWE values correlated (Pearson's correlation coefficient, 0.882; P < .0001; Lin concordance coefficient, 0.846; P < .0001). The median stiffness values were 6.7 kPa with VCTE (interquartile range, 4.8-11.6 kPa) and 7.1 kPa with 2D-SWE (interquartile range, 5.4-11.1 kPa) (P = .736). 2D-SWE values were slightly higher in the low percentiles and lower in the high percentiles; the best match with VCTE values were at approximately 7-9 kPa. The area under the curve of 2D-SWE for identifying of VCTE values below 10 was 0.964 (95% CI, 0.952-0.976) and for VCTE values above 15 kPa was 0.976 (95% CI, 0.963-0.988), with Youden index-associated cut-off values of 9.5 and 13kPa and best accuracy cut-off values of 10 kPa and 14 kPa, respectively. A 2D-SWE cut-off value of 10 kPa detected VCTE values below 10k Pa with 92% sensitivity, 87% specificity, and 91% accuracy. CONCLUSIONS: Measurement of liver stiffness by VCTE or 2D-SWE produces comparable results. 2D-SWE accurately identifies patients with cACLD according to the Baveno VI criteria based on VCTE cut-off values. A 10 kPa 2D-SWE cut-off value can be used to rule out cACLD.

Study protocol of the HYPER-LIV01 trial: a multicenter phase II, prospective and randomized study comparing simultaneous portal and hepatic vein embolization to portal vein embolization for hypertrophy of the future liver remnant before major hepatectomy for colo-rectal liver metastases.

BACKGROUND: In patients undergoing major liver resection, portal vein embolization (PVE) has been widely used to induce hypertrophy of the non-embolized liver in order to prevent post-hepatectomy liver failure. PVE is a safe and effective procedure, but does not always lead to sufficient hypertrophy of the future liver remnant (FLR). Hepatic vein(s) embolization has been proposed to improve FLR regeneration when insufficient after PVE. The sequential right hepatic vein embolization (HVE) after right PVE demonstrated an incremental effect on the FLR but it implies two different procedures with no time gain as compared to PVE alone. We have developed the so-called liver venous deprivation (LVD), a combination of PVE and HVE during the same intervention, to optimize the phase of liver preparation before surgery. The main objective of this randomized phase II trial is to compare the percentage of change in FLR volume at 3 weeks after LVD or PVE. METHODS: Patients eligible to this multicenter prospective randomized phase II study are subjects aged from 18 years old suffering from colo-rectal liver metastases considered as resectable and with non-cirrhotic liver parenchyma. The primary objective is the percentage of change in FLR volume at 3 weeks after LVD or PVE using MRI or CT-Scan. Secondary objectives are assessment of tolerance, post-operative morbidity and mortality, post-hepatectomy liver failure, rate of non-respectability due to insufficient FLR or tumor progression, per-operative difficulties, blood loss, R0 resection rate, post-operative liver volume and overall survival. Objectives of translational research studies are evaluation of pre- and post-operative liver function and determination of biomarkers predictive of liver hypertrophy. Sixty-four patients will be included (randomization ratio 1:1) to detect a difference of 12% at 21 days in FLR volumes between PVE and LVD. DISCUSSION: Adding HVE to PVE during the same procedure is an innovative and promising approach that may lead to a rapid and major increase in volume and function of the FLR, thereby increasing the rate of resectable patients and limiting the risk of patient's drop-out. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov on 15th February 2019 (NCT03841305).

Quantification of liver fat content in liver and primary liver lesions using triple-echo-gradient-echo MRI.

OBJECTIVES: To quantify and compare the fat fraction of background liver and primary liver lesions using a triple-echo-gradient-echo sequence. M&M: This IRB-approved study included 128 consecutive patients who underwent a liver MRI for lesion characterization. Fat fraction from the whole lesion volume and the normal liver parenchyma were computed from triple-echo (consecutive in-phase, opposed-phase, in-phase echo times) sequence. RESULTS: Forty-seven hepatocellular carcinoma (HCCs), 25 hepatocellular adenomas (HCAs), and 56 focal nodular hyperplasia (FNH) were included. The mean intralesional fat fraction for various lesions was 7.1% (range, 0.5-23.6; SD, 5.6) for HCAs, 5.7% (range, 0.8-14; SD, 2.9) for HCCs, and 2.3% (range, 0.8-10.3; SD, 1.9) for FNHs (p = 0.6 for HCCs vs HCA, p < 0.001 for FNH vs HCCs or HCA). A fat fraction threshold of 2.7% enabled distinction between HCA and FNH with a sensitivity of 80% and a specificity of 77%. The mean normal liver parenchyma fat fraction was lower than the intralesional fat fraction in the HCC group (p = 0.04) and higher in the FNH group (p = 0.001), but not significantly different in the HCA group (p = 0.51). CONCLUSION: Triple-echo-gradient-echo is a feasible technique to quantify fat fraction of background liver and primary liver lesions. Intralesional fat fraction obtained from lesion whole volume is greater for HCCs and HCA compared to FNH. When trying to distinguish FNH and HCA, an intralesional fat fraction < 2.7% may orient toward the diagnosis of FNH. KEY POINTS: • Triple-echo technique is feasible to quantify intralesional fat fraction of primary liver lesions. • Whole volume intralesional fat fraction is greater for HCCs and HCA compared to FNH. • An intralesional fat fraction < 2.7% may orient toward the diagnosis of FNH.

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 chemoembolization of hepatocellular carcinoma using TANDEM® microspheres.

Transarterial chemoembolization (TACE) combines intra-arterial delivery of a chemotherapeutic agent with selective embolization to obtain a synergistic effect. TACE is recognized as the standard treatment of hepatocellular carcinoma patients at an intermediate stage. If conventional TACE, defined as the injection of an emulsion of a drug with ethiodized oil, still has a role to play, the development of drug-eluting beads has allowed many improvements and optimization of the technique. TANDEM® microspheres are second-generation drug-loadable microspheres. This device raised a special interest due to its tightly calibrated spherical microspheres, with small sizes down to 40 µm available. In this review, we describe the technical characteristics of these microspheres, analyze the scientific literature and hypothesize on the future perspectives.

Percutaneous thermal ablation of hepatocellular carcinomas located in the hepatic dome using artificial carbon dioxide pneumothorax: retrospective evaluation of safety and efficacy.

INTRODUCTION: The targeting of hepatocellular carcinomas (HCC) in the hepatic dome can be challenging during percutaneous thermal ablation (PTA). The aims of this study were (1) to evaluate the safety and efficacy of PTA of HCC in the hepatic dome that cannot be visualized under US, using artificial CO2 pneumothorax and CT-guidance and (2) to compare the results with US-visible HCC located in the liver dome treated under US-guidance. MATERIALS: Over a 32-month period, 56 HCC located in the hepatic dome were extracted from a prospectively maintained database. Twenty-eight cases (US-guidance group) were treated under US-guidance, while the others (n = 28, CT-CO2 group) were treated under CT-guidance using artificial CO2 pneumothorax after lipiodol tagging of the tumor. The primary technical success and complications rates of this technique were retrospectively assessed. Local tumor progression (LTP), intrahepatic distant recurrence (IDR), local recurrence-free survival (LRFS) and overall survival (OS) were also compared between both groups. RESULTS: Primary technical success was 100% in both groups. No major complications occurred. After a median follow-up of 13.8 months (range, 1-33.4 months), LTP occurred in 10.7% (3/28) in CT-CO2 vs. 25% (7/28) in the US-guidance group (p = NS). IDR occurred in 39.3% (11/28) in CT-CO2 vs. 28.6% (8/28) in the US-guidance group (p = NS). Death occurred in 17.9% (5/28) of patients in both groups. LRFS and OS did not significantly differ using Kaplan-Meier survival estimates. CONCLUSION: CT-guided PTA after artificially induced CO2 pneumothorax is a safe and efficient technique to treat HCC located in the hepatic dome.

Extended liver venous deprivation before major hepatectomy induces marked and very rapid increase in future liver remnant function.

OBJECTIVE: The aim of this study was to assess the safety and efficacy of extended liver venous deprivation (eLVD), i.e. combination of right portal vein embolisation and right (accessory right) and middle hepatic vein embolisation before major hepatectomy for future remnant liver (FRL) functional increase. METHODS: eLVD was performed in non-cirrhotic patients referred for major hepatectomy in a context of small FRL (baseline FRL <25% of the total liver volume or FRL function <2.69%/min/m2). All patients underwent 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) and computed tomographic evaluations. RESULTS: Ten consecutive patients underwent eLVD before surgery for liver metastases (n = 8), Klatskin tumour (n = 1) and gallbladder carcinoma (n = 1). FRL function increased by 64.3% (range = 28.1-107.5%) at day 21. In patients with serial measurements, maximum FRL function was at day 7 (+65.7 ± 16%). The FRL volume increased by +53.4% at 7 days (+25 ± 8 cc/day). Thirty-one days (range = 22-45 days) after eLVD, 9/10 patients were resected. No post-hepatectomy liver failure was reported. Two grade II and one grade III complications (Dindo-Clavien classification) occurred. No patient died with-in 90 days following surgery. CONCLUSIONS: eLVD is safe and provides a marked and very rapid increase in liver function, unprecedented for an interventional radiology procedure. KEY POINTS: • eLVD is safe • eLVD provides a marked and very rapid increase in liver function • After eLVD, the FRL-F increased by 64.3% (28.1-107.5%) at day 21 • After eLVD, the maximum FRL-F was obtained at day 7 (+65.7 ± 16%) • After eLVD, the FRL volume increased by +53.4% at 7 days (+25 ± 8 cc/day).

Software-based assessment of tumor margins after percutaneous thermal ablation of liver tumors: A systematic review.

PURPOSE: The purpose of this study was to make a systematic review of clinical studies evaluating software-based tumor margin assessment after percutaneous thermoablation (PTA) of liver tumors. MATERIALS AND METHODS: A systematic literature search was performed through Pubmed/MEDLINE, Embase and the Cochrane Library. Original studies published in English that reported on software-based assessment of ablation margins (AM) following PTA of liver tumors were selected. Studies were analyzed with respect to design, number of patients and tumors, tumor type, PTA technique, tumor size, target registration error, study outcome(s) (subtypes: feasibility, comparative, clinical impact, predictive or survival), and follow-up period. RESULTS: Twenty-nine articles (one multi-center and two prospective studies) were included. The majority were feasibility (26/29, 89.7%) or predictive (23/29, 79.3%) studies. AM was a risk factor of local tumor progression (LTP) in 25 studies (25/29, 86.2%). In nine studies (9/29, 31%) visual assessment overestimated AM compared with software-aided assessment. LTP occurred at the location of the thinnest margin in nine studies (9/29, 31%). Time for registration and analysis was heterogeneously reported, ranging between 5-30 min. Mean target registration error was reported in seven studies (7/29, 24.1%) at 1.62 mm (range: 1.20-2.23 mm). Inter-operator reproducibility was high (kappa range: 0.686-1). Ascites, liver deformation and inconspicuous tumor were major factors of co-registration error. CONCLUSION: Available studies present a low level of evidence overall, since most of them are feasibility, retrospective and single-center studies.

Small Steatotic HCC: A Radiological Variant Associated With Improved Outcome After Ablation.

Percutaneous thermal ablation is a validated treatment option for small hepatocellular carcinoma (HCC). Steatotic HCC can be reliably detected by magnetic resonance imaging. To determine the clinical relevance of this radiological variant, we included 235 patients (cirrhosis in 92.3%, classified Child-Pugh A in 97%) from a prospective database on percutaneous thermal ablation for <3 cm HCC. Among these patients, 52 (22.1%) had at least one steatotic HCC nodule. Nonalcoholic steatohepatitis was more frequent in patients with than without steatotic HCC (P = 0.057), whereas body mass index, diabetes mellitus, liver steatosis, and liver fat content did not differ between groups. Liver disease was less advanced in patients with than without steatotic HCC: lower total bilirubin ( - 2.1 µmol/L; P = 0.035), higher albumin (+0.8 g/L; P = 0.035), and lower Model for End-Stage Liver Disease score (-0.8; P = 0.014). Tumor phenotype was less aggressive in patients with steatotic HCC: lower alpha-fetoprotein (AFP) concentration (P = 0.019), less frequent AFP > 100 ng/mL (P = 0.045), and multifocality (P = 0.015). During the follow-up (median: 28.3 months), overall mortality (3.8% vs. 23.5%; P = 0.001) and HCC-specific mortality (0.0% vs. 14.2%; P = 0.002) rates were lower in patients with steatotic HCC. Early (<2 years) recurrence was also less frequent (32.7% vs. 49.2%; P = 0.041). The mean time to intrahepatic distant recurrence (16.4 vs. 9 months, P = 0.006) and the median time to recurrence and recurrence-free survival (32.4 vs. 18.6 months, P = 0.024 and 30.4 vs. 16.4 months, P = 0.018) were longer in patients with steatotic versus nonsteatotic HCC. The 3-year overall survival was 94.4% and 70.9% in steatotic and nonsteatotic HCC (P = 0.008). In multivariate analysis, steatotic HCC (hazard ratio = 0.12; P = 0.039) and AFP (HR=1.002; P < 0.001) independently predicted overall survival. Conclusion: Small steatotic HCC detected by magnetic resonance imaging is associated with a less aggressive tumor phenotype. In patients with such radiological variant, percutaneous thermal ablation results in improved outcome.

Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial.

BACKGROUND: All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these studies did not use personalised dosimetry. We aimed to compare the efficacy of a personalised versus standard dosimetry approach of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with hepatocellular carcinoma. METHODS: DOSISPHERE-01 was a randomised, multicentre, open-label phase 2 trial done at four health-care centres in France. Patients were eligible if they were aged 18 years or older and had unresectable locally advanced hepatocellular carcinoma, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread (other than to the lymph nodes of the hilum, with a lesion <2 cm in size), and no contraindications to selective internal radiation therapy, as assessed by use of a technetium-99m macro-aggregated albumin scan. Patients were randomly assigned (1:1) by use of a permutated block method, with block sizes of four and without stratification, to receive either standard dosimetry (120 ±â€ˆ20 Gy) targeted to the perfused lobe; standard dosimetry group) or personalised dosimetry (≥205 Gy targeted to the index lesion; personalised dosimetry group). Investigators, patients, and study staff were not masked to treatment. The primary endpoint was the investigator-assessed objective response rate in the index lesion, according to European Association for the Study of the Liver criteria, at 3 months after selective internal radiation therapy in the modified intention-to-treat population. Safety was assessed in all patients who received at least one selective internal radiation therapy injection, and analysed on the basis of the treatment actually received (defined by central dosimetry assessment). The trial is registered with ClinicalTrials.gov, NCT02582034, and has been completed. FINDINGS: Between Dec 5, 2015, and Jan 4, 2018, 93 patients were assessed for eligibility. Of these patients, 60 were randomly assigned: 31 to the personalised dosimetry group and 29 to the standard dosimetry group (intention-to-treat population). 56 (93%) patients (28 in each group) were treated (modified intention-to-treat population). In the modified intention-to-treat population, 20 (71% [95% CI 51-87]) of 28 patients in the personalised dosimetry group and ten (36% [19-56]) of 28 patients in the standard dosimetry group had an objective response (p=0·0074). In the safety analysis population, a least one serious adverse event was reported in seven (20%) of the 35 patients who received personalised dosimetry, and in seven (33%) of the 21 patients who received standard dosimetry. The most frequent (ie, occurring in >5% of patients) grade 3 or higher adverse events were ascites (one [3%] patient who received personalised dosimetry vs two [10%] patients who received standard dosimetry), hepatic failure (two [6%] vs none), lymphopenia (12 [34%] vs nine [43%]), increased aspartate aminotransferase concentrations (three [9%] vs two [10%]), increased alanine aminotransferase concentrations (three [9%] vs none), anaemia (two [6%] vs one [5%]), gastrointestinal haemorrhage (none vs two [10%]), and icterus (none vs two [10%]). One treatment-related death occurred in each group. INTERPRETATION: Compared with standard dosimetry, personalised dosimetry significantly improved the objective response rate in patients with locally advanced hepatocellular carcinoma. The results of this study suggest that personalised dosimetry is likely to improve outcomes in clinical practice and should be used in future trials of selective internal radiation therapy. FUNDING: Biocompatibles UK, a Boston Scientific Group company.

Deportalization, Venous Congestion, Venous Deprivation: Serial Measurements of Volumes and Functions on Morphofunctional 99mTc-Mebrofenin SPECT-CT.

The objective was to assess the changes in regional volumes and functions under venous-impaired vascular conditions following liver preparation. Twelve patients underwent right portal vein embolization (PVE) (n = 5) or extended liver venous deprivation (eLVD, i.e., portal and right and middle hepatic veins embolization) (n = 7). Volume and function measurements of deportalized liver, venous-deprived liver and congestive liver were performed before and after PVE/eLVD at days 7, 14 and 21 using 99mTc-mebrofenin hepatobiliary scintigraphy with single-photon emission computed tomography and computed tomography (99mTc-mebrofenin SPECT-CT). Volume and function progressed independently in the deportalized liver (p = 0.47) with an early decrease in function (median -18.2% (IQR, -19.4--14.5) at day 7) followed by a decrease in volume (-19.3% (-22.6--14.4) at day 21). Volume and function progressed independently in the venous deprived liver (p = 0.80) with a marked and early decrease in function (-41.1% (-52.0--12.9) at day 7) but minimal changes in volume (-4.7% (-10.4-+3.9) at day 21). Volume and function progressed independently in the congestive liver (p = 0.21) with a gradual increase in volume (+43.2% (+38.3-+51.2) at day 21) that preceded a late and moderate increase in function at day 21 (+34.8% (-8.3-+46.6)), concomitantly to the disappearance of hypoattenuated congestive areas in segment IV (S4) on CT, initially observed in 6/7 patients after eLVD and represented 35.3% (22.2-46.4) of whole S4 volume. Liver volume and function progress independently whatever the vascular condition. Hepatic congestion from outflow obstruction drives volume increase but results in early impaired function.

Liver venous deprivation versus portal vein embolization before major hepatectomy: future liver remnant volumetric and functional changes.

BACKGROUND: We previously showed that embolization of portal inflow and hepatic vein (HV) outflow (liver venous deprivation, LVD) promotes future liver remnant (FLR) volume (FLR-V) and function (FLR-F) gain. Here, we compared FLR-V and FLR-F changes after portal vein embolization (PVE) and LVD. METHODS: This study included all patients referred for liver preparation before major hepatectomy over 26 months. Exclusion criteria were: unavailable baseline/follow-up imaging, cirrhosis, Klatskin tumor, two-stage hepatectomy. 99mTc-mebrofenin SPECT-CT was performed at baseline and at day 7, 14 and 21 after PVE or LVD. FLR-V and FLR-F variations were compared using multivariate generalized linear mixed models (joint modelling) with/without missing data imputation. RESULTS: Baseline FLR-F was lower in the LVD (n=29) than PVE group (n=22) (P<0.001). Technical success was 100% in both groups without any major complication. Changes in FLR-V at day 14 and 21 (+14.2% vs. +50%, P=0.002; and +18.6% vs. +52.6%, P=0.001), and in FLR-F at day 7, 14 and 21 (+23.1% vs. +54.3%, P=0.02; +17.6% vs. +56.1%, P=0.006; and +29.8% vs. +63.9%, P<0.001) differed between PVE and LVD group. LVD (P=0.009), age (P=0.027) and baseline FLR-V (P=0.001) independently predicted FLR-V variations, whereas only LVD (P=0.01) predicted FLR-F changes. After missing data handling, LVD remained an independent predictor of FLR-V and FLR-F variations. CONCLUSIONS: LVD is safe and provides greater FLR-V and FLR-F increase than PVE. These results are now evaluated in the HYPERLIV-01 multicenter randomized trial.

Multimodal Percutaneous Thermal Ablation of Small Hepatocellular Carcinoma: Predictive Factors of Recurrence and Survival in Western Patients.

BACKGROUND: To identify the predictive factors of recurrence and survival in an unselected population of Western patients who underwent multimodal percutaneous thermal ablation (PTA) for small Hepatocellular Carcinomas (HCCs). METHODS: January 2015-June 2019: data on multimodal PTA for <3 cm HCC were extracted from a prospective database. Local tumor progression (LTP), intrahepatic distant recurrence (IDR), time-to-LTP, time-to-IDR, recurrence-free (RFS) and overall (OS) survival were evaluated. RESULTS: 238 patients underwent 317 PTA sessions to treat 412 HCCs. During follow-up (median: 27.1 months), 47.1% patients had IDR and 18.5% died. LTP occurred after 13.3% of PTA. Tumor size (OR = 1.108, p < 0.001; hazard ratio (HR) = 1.075, p = 0.002) and ultrasound guidance (OR = 0.294, p = 0.017; HR = 0.429, p = 0.009) independently predicted LTP and time-to-LTP, respectively. Alpha fetoprotein (AFP) > 100 ng/mL (OR = 3.027, p = 0.037) and tumor size (OR = 1.06, p = 0.001) independently predicted IDR. Multinodular HCC (HR = 2.67, p < 0.001), treatment-naïve patient (HR = 0.507, p = 0.002) and AFP > 100 ng/mL (HR = 2.767, p = 0.014) independently predicted time-to-IDR. RFS was independently predicted by multinodular HCC (HR = 2.144, p = 0.001), treatment naivety (HR = 0.546, p = 0.004) and AFP > 100 ng/mL (HR = 2.437, p = 0.013). The American Society of Anesthesiologists (ASA) score > 2 (HR = 4.273, p = 0.011), AFP (HR = 1.002, p < 0.001), multinodular HCC (HR = 3.939, p = 0.003) and steatotic HCC (HR = 1.81 × 10-16, p < 0.001) independently predicted OS. CONCLUSIONS: IDR was associated with tumor aggressiveness, suggesting a metastatic mechanism. Besides AFP association with LTP, IDR, RFS and OS, treatment-naïve patients had longer RFS, and multi-nodularity was associated with shorter RFS and OS. Steatotic HCC, identified on pre-treatment MRI, independently predicted longer OS, and needs to be further explored.

[Interventional radiology of liver tumors]. / Prise en charge des tumeurs malignes du foie en radiologie interventionnelle.

Interventional radiology (IR) has considerably grown since the 90s and has currently a central position in the management of patients suffering from cancer. The aim of this paper is to describe the principle, indications, technique and results of three common hepatic oncologic IR procedures: preoperative portal vein embolization, transarterial chemoembolization and radioembolization. Portal vein embolization is performed before a right hepatectomy in order to increase the left liver volume and functional capacity to ensure adequate liver function of the future remnant liver and to prevent the post-hepatectomy liver failure. It is a proven, well-tolerated and effective technique, allowing most of patients to undergo surgery. Transarterial chemoembolization consists of an injection of a chemotherapeutic agent and an embolic agent into the hepatic artery to locally act on liver tumors. It is the standard of care for BCLC stage B hepatocellular carcinoma and is also recommended for the liver metastases treatment, mainly from neuroendocrine tumors. Radioembolization is an IR procedure on the rise that consists of the injection into the hepatic artery of Yttrium 90 loaded microparticles, which will preferentially deliver high dose on the tumors, sparing the adjacent hepatic parenchyma. Radioembolization is recommended for the palliative treatment of HCC and for colorectal cancer liver metastases resistant to treatment. It is a very well tolerated intervention which place has yet to be defined in the management of neuroendocrine tumors liver metastases and unresectable cholangiocarcinoma. IR is a constantly evolving discipline with proven techniques playing a major role in the oncological management of liver tumor patients. In oncology, IR is now the 4th patient management linchpin alongside oncology, surgery and radiotherapy.

Radiation Exposure During Transarterial Chemoembolization: Angio-CT Versus Cone-Beam CT.

INTRODUCTION: Cone-beam computed tomography (CBCT) has been developed to improve reliability of many interventional radiology (IR) procedures performed with Angio system, such as transarterial chemoembolization (TACE). Angio-CT has emerged as a new imaging technology that combines a CT scanner with an Angio system in the same IR suite. The purpose of our study was to compare Angio system with CBCT capability and Angio-CT in terms of patient radiation exposure during TACE procedures. MATERIALS AND METHODS: Consecutive TACE procedures performed between January 2016 and September 2017 with the two imaging modalities (Artis Zeego defining the CBCT group and Infinix-i 4D-CT defining the Angio-CT group) were reviewed. TACE and patient's characteristics and patient radiation exposure parameters were collected. Dose-area products (DAP) and dose-length products (DLP) were converted into effective doses (ED) using conversion factors. Accuracy of tumor targeting and response was retrospectively assessed. RESULTS: A total of 114 TACE procedures in 96 patients were included with 57 procedures in each group. The total ED in the Angio-CT group was 2.5 times lower than that in the CBCT group (median 15.4 vs. 39.2 mSv, p < 0.001). Both 2D ED and 3D ED were lower in the Angio-CT group than in the CBCT group (5.1 vs. 20 mSv, p < 0.001, and 7.4 vs. 17.9 mSv, p < 0.001, respectively). There was no significant difference neither in terms of classes of tumor targeting (p = 0.509) nor in terms of classes of tumor response (p = 0.070) between both groups. CONCLUSION: Angio-CT provides significant decrease in patient effective dose during TACE procedures compared to Angio system with CBCT.

Transarterial Chemoembolization of Hepatocellular Carcinoma with Idarubicin-Loaded Tandem Drug-Eluting Embolics.

: Objective: To describe the responses, toxicities and outcomes of HCC patients treated by transarterial chemoembolization (TACE) using idarubicin-loaded TANDEM beads. Materials and Methods: Seventy-two consecutive patients (mean age: 71 years (58-84 years)) with HCC were treated by TACE using idarubicin-loaded TANDEM in a first line, over a five-year period. Most patients (89%) had liver cirrhosis classified as Child-Pugh A (90%). BCLC B classification applied in 85% of cases. Baseline tumor burden was limited to one to three nodules in 92% of cases, unilobar in 88% cases, with a median tumor diameter of 55 mm (range: 13-150 mm). Toxicity was assessed using NCI CTC AE v4.0. Response was assessed using mRECIST criteria. Time-to-treatment failure (TTTF) and overall survival (OS) were also calculated based on Kaplan-Meier method. Result: Of 141 TACE sessions performed with bead sizes of 100 and 75 µm in 42 (29.8%) and 99 (70.2%) sessions, respectively. In 78% of all TACE sessions, the full dose of idarubicin-loaded beads was injected. Grade 3-4 AE were observed after 73 (52%) sessions, most of them being biological. Multi-organ failure was observed three days after the first TACE in a Child B patients, unfortunately leading to death. Overall, the best objective response rate (ORR) was 65%. Median follow-up lasted 14.3 months (95% CI: 11.2-18.8 months). Median TTTF and OS were 14.4 months (95% CI: 7.2-24.6 months) and 34.6 months (95% CI: 24.7-not reached) respectively. Conclusion: In this retrospective study involving well-selected HCC patients, high ORR and long TTTF and OS are observed after TACE using idarubicin-loaded TANDEM. A randomized trial is needed.

Radiofrequency Ablation of Liver Tumors: No Difference in the Ablation Zone Volume Between Cirrhotic and Healthy Liver.

PURPOSE: The "oven effect" theory assumes that radiofrequency ablation (RFA) would be more efficient on tumors of cirrhotic livers. The aim of the study was to compare the size and volume of the ablation zone following RFA on tumors of cirrhotic versus healthy livers. METHODS: One hundred and eleven patients who underwent RFA from 2011 to 2013 for the treatment of 140 liver tumors (83 hepatocellular carcinomas developed on a cirrhotic liver, i.e., "cirrhosis group," and 57 tumors developed on a healthy liver, mainly liver metastasis, i.e., "healthy liver group") using the same RFA device were retrospectively selected. The diameter and volume of the ablation zone were compared between groups at the end of the procedure (FU0), at first (FU1) and second follow-up (FU2) performed 1.6 months (± 19 days) and 4.7 months (± 40 days) post-RFA, respectively. RESULTS: No differences in the size or volume of the ablation zone were found between groups at FU0 (36.5 ± 12 mm vs. 34.3 ± 10 mm, p = 0.5; and 28 ± 16 mm3 vs. 26.5 ± 16 mm3, p = 0.6, respectively), FU1, or FU2. Similarly, no differences were found at FU0, FU1, or FU2 in the subgroups of tumors treated using a single radiofrequency application. The mean volume of the ablation zone decreased over time, by 33.3% at FU1 and 48.5% at FU2, without any difference between groups. CONCLUSION: In contradiction to the "oven effect" theory, RFA achieves ablation zones of a comparable size and volume in cirrhotic and healthy livers.

Challenging TIPS in Liver Transplant Recipients: The Pull-Through Technique to Address Piggyback Anastomosis.

PURPOSE: The hepatic vein access during transjugular intrahepatic portosystemic shunt (TIPS) can be challenging in liver transplant recipient patients, especially when piggyback anastomosis was performed. We described a modified technique and reviewed the clinical outcomes of TIPS in transplanted patients. MATERIALS AND METHODS: From 2015 to 2016, 8 patients with history of liver transplantation using a three-hepatic vein piggyback technique for venous anastomosis underwent a TIPS in our institution. Indications were refractory ascites (n = 7) or variceal bleeding (n = 1). When the hepatic vein access failed via the standard jugular route, a pull-through technique was used: After puncturing the right hepatic vein under ultrasound guidance, a guidewire and a vascular sheath were advanced, then the guidewire was snared in the inferior vena cava and retrieved though the jugular access, and the hepatic vein was catheterized along the guidewire. The safety and technical success rates of this technique and the clinical outcomes of the study population were retrospectively assessed. RESULTS: Seven of 8 patients (87.5%) required the pull-through technique to access a hepatic vein. No complications of the percutaneous access of the hepatic vein were found at the one-day and one-month ultrasound Doppler examinations. Among 7 patients who had refractory ascites, 3 had complete resolution of ascites (43%), and one had moderate improvement. One patient with refractory infected ascites on severe graft failure and one with massive bleeding died soon after the procedure. CONCLUSION: A pull-through technique following percutaneous puncture of a hepatic vein is a safe technique for performing a TIPS in liver transplant recipients with piggyback anastomosis complicated by acute hepatic vein angulation.

[Portal vein embolization: Present and future]. / Embolisation portale préopératoire : présent et futur.

Portal vein embolization consists of occluding a part of the portal venous system in order to achieve the hypertrophy of the non-embolized liver segments. This technique is used during the preoperative period of major liver resection when the future remnant liver (FRL) volume is insufficient, exposing to postoperative liver failure, main cause of death after major hepatectomy. Portal vein embolization indication depends on the FRL, commonly assessed by its volume. Nowadays, FRL function evaluation seems more relevant and can be measured by 99mTc labelled mebrofenin scintigraphy. Portal vein embolization procedure is mostly performed with percutaneous trans-hepatic access by using ultrasonography guidance and consists of embolic agent injection, such as cyanoacrylate, in the targeted portal vein branches with fluoroscopic guidance. It is a safe and well-tolerated technique, with extremely low morbi-mortality. Portal vein embolization leads to sufficient FRL hypertrophy in about 80% of patients, allowing them to undergo surgery from which they were initially rejected. The two main reasons of non-resection are tumor progression (≈15% of cases) and FRL insufficient hypertrophy (≈5% of cases). When portal vein embolization is not enough to obtain adequate FRL regeneration, hepatic vein embolization may potentiate its effect (liver venous deprivation technique).