Reduced quality of life associated adverse events in intermediate hepatocellular carcinoma patients treated with PRECISION TACE with drug eluting beads: Results from the PRECISION V randomized trial : B-241

Purpose: To evaluate the extent of quality of life (QoL) associated adverse events (AEs) following PRECISION TACE with DC Bead compared with conventional transarterial chemoembolisation (cTACE). Methods and Materials: 201 intermediate HCC patients were treated with DC Bead (PRECISION TACE) or conventional TACE (cTACE) with doxorubicin in the PRECISION V clinical study. 93 patients were treated with DC Bead and 108 Patients with cTACE every 2 months and followed up for 6 months. AEs were classified according to the South West Oncology Group criteria. QoL associated AEs were defined as alopecia, constipation, nausea, vomiting, pyrexia, chills, asthenia, fatigue, and headache. Results: The biggest difference in QoL associated AEs was for alopecia: 2 patients (2.2%) for DC-Bead versus 21 patients (19.4%) for cTACE. For other clinical symptoms, constipation (n=10; 10.8% vs. n=13; 12%), vomiting (n=10; 10.8% vs. n=14; 13.0%), pyrexia (n=16; 17.2% vs. n=26; 24.1%), chills (n=1; 1.1% vs. n=5; 4.6%), and headache (n=2; 2.2% vs. n=8; 7.4%) showed lower incidence in the DC Bead group versus cTACE. Nausea, n= 15; 13.9% (n=15; 16.1%) and fatigue, n=6; 5.6% (n=13; 14.0%) were lower for cTACE. Total dose of doxorubicin was on average 35% higher in the DC Bead group. Conclusion: Although patients in the DC Bead group received a higher doxorubicin dose, less QoL associated AEs were reported for this group. Alopecia, the most obvious outward sign of toxicity, was only reported in a tenth of DC Bead patients. Thus, PRECISION TACE with DC Bead improves quality of life associated adverse events.

Repositioning precision of coronary arteries measured on X-ray angiography and its implications for coronary MR angiography.

BACKGROUND: To test the hypothesis that intervals with superior beat-to-beat coronary artery repositioning precision exist in the cardiac cycle, to design a coronary MR angiography (MRA) methodology in response, and to ascertain its performance. METHODS: Coronary repositioning precision in consecutive heartbeats was measured on x-ray coronary angiograms of 17 patients and periods with the highest repositioning precision were identified. In response, the temporal order of coronary MRA pulse sequence elements required modification and the T2 -prep now follows (T2 -post) rather than precedes the imaging part of the sequence. The performance of T2 -post was quantitatively compared (signal-to-noise [SNR], contrast-to-noise [CNR], vessel sharpness) to that of T2 -prep in vivo. RESULTS: Coronary repositioning precision is <1 mm at peak systole and in mid diastole. When comparing systolic T2 -post to diastolic T2 -prep, CNR and vessel sharpness remained unchanged (both P = NS) but SNR for muscle and blood increased by 104% and 36% (both P < 0.05), respectively. CONCLUSION: Windows with improved coronary repositioning precision exist in the cardiac cycle: one in peak systole and one in mid diastole. Peak-systolic imaging necessitates a re-design of conventional coronary MRA pulse sequences and leads to image quality very similar to that of conventional mid-diastolic data acquisition but improved SNR. J. Magn. Reson. Imaging 2015;41:1251-1258. © 2014 Wiley Periodicals, Inc.

Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study.

Transcatheter arterial chemoembolization (TACE) offers a survival benefit to patients with intermediate hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes administration of doxorubicin-oil emulsion followed by gelatine sponge-conventional TACE. Recently, a drug-eluting bead (DC Bead) has been developed to enhance tumor drug delivery and reduce systemic availability. This randomized trial compares conventional TACE (cTACE) with TACE with DC Bead for the treatment of cirrhotic patients with HCC. Two hundred twelve patients with Child-Pugh A/B cirrhosis and large and/or multinodular, unresectable, N0, M0 HCCs were randomized to receive TACE with DC Bead loaded with doxorubicin or cTACE with doxorubicin. Randomization was stratified according to Child-Pugh status (A/B), performance status (ECOG 0/1), bilobar disease (yes/no), and prior curative treatment (yes/no). The primary endpoint was tumor response (EASL) at 6 months following independent, blinded review of MRI studies. The drug-eluting bead group showed higher rates of complete response, objective response, and disease control compared with the cTACE group (27% vs. 22%, 52% vs. 44%, and 63% vs. 52%, respectively). The hypothesis of superiority was not met (one-sided P = 0.11). However, patients with Child-Pugh B, ECOG 1, bilobar disease, and recurrent disease showed a significant increase in objective response (P = 0.038) compared to cTACE. DC Bead was associated with improved tolerability, with a significant reduction in serious liver toxicity (P < 0.001) and a significantly lower rate of doxorubicin-related side effects (P = 0.0001). TACE with DC Bead and doxorubicin is safe and effective in the treatment of HCC and offers a benefit to patients with more advanced disease.

Reduced quality of life associated adverse events in intermediate hepatocellular carcinoma patients treated with PRECISION TACE with drug eluting beads: Results from the PRECISION V randomized trial

Purpose: To evaluate the extent of quality of life (QoL) associated adverse events (AEs) following PRECISION TACE with DC Bead compared with conventional transarterial chemoembolisation (cTACE). Methods and Materials: 201 intermediate HCC patients were treated with DC Bead (PRECISION TACE) or conventional TACE (cTACE) with doxorubicin in the PRECISION V clinical study. 93 patients were treated with DC Bead and 108 Patients with cTACE every 2 months and followed up for 6 months. AEs were classified according to the South West Oncology Group criteria. QoL associated AEs were defined as alopecia, constipation, nausea, vomiting, pyrexia, chills, asthenia, fatigue, and headache. Results: The biggest difference in QoL associated AEs was for alopecia: 2 patients (2.2%) for DC-Bead versus 21 patients (19.4%) for cTACE. For other clinical symptoms, constipation (n=10; 10.8% vs. n=13; 12%), vomiting (n=10; 10.8% vs. n=14; 13.0%), pyrexia (n=16; 17.2% vs. n=26; 24.1%), chills (n=1; 1.1% vs. n=5; 4.6%), and headache (n=2; 2.2% vs. n=8; 7.4%) showed lower incidence in the DC Bead group versus cTACE. Nausea, n= 15; 13.9% (n=15; 16.1%) and fatigue, n=6; 5.6% (n=13; 14.0%) were lower for cTACE. Total dose of doxorubicin was on average 35% higher in the DC Bead group. Conclusion: Although patients in the DC Bead group received a higher doxorubicin dose, less QoL associated AEs were reported for this group. Alopecia, the most obvious outward sign of toxicity, was only reported in a tenth of DC Bead patients. Thus, PRECISION TACE with DC Bead improves quality of life associated adverse events.

Liver, Gastrointestinal, and Cardiac Toxicity in Intermediate Hepatocellular Carcinoma Treated With PRECISION TACE With Drug-Eluting Beads: Results From the PRECISION V Randomized Trial.

OBJECTIVE. The purpose of our study was to evaluate hepatic, gastrointestinal, and cardiac toxicity after PRECISION transarterial chemoembolization (TACE) with drug-eluting beads (DEB) versus conventional TACE with doxorubicin in the treatment of intermediate-stage hepatocellular carcinoma (HCC).SUBJECTS AND METHODS. Two hundred twelve patients (185 men and 27 women; mean age, 67 years) were randomized to TACE with DEB or conventional TACE. The majority of patients (67% in both groups) presented in a more advanced stage. Safety was measured by rate of adverse events (Southwest Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed with left ventricular ejection fraction (LVEF) mainly on MRI or echocardiography.RESULTS. The mean maximum postchemoembolization alanine transaminase increase in the DEB group was 50% less than in the conventional TACE group (p < 0.001) and 41% less in respect to aspartate transaminase (p < 0.001). End-of-study values returned to approximately baseline levels but with greater variability in conventional TACE patients. Treatment-emergent adverse events in the hepatobiliary system organ class occurred in 16.1% of DEB group patients compared with 25% of conventional TACE patients. There were fewer liver toxicity events in the DEB group. There was a small but statistically significant difference in mean change from baseline in LVEF between the two groups of 4 percentage points for the conventional TACE group (95% CI, 0.71-7.3; p = 0.018).CONCLUSION. PRECISION TACE with DEB loaded with doxorubicin offers a safe therapy option for intermediate-stage HCC, even in patients with more advanced liver disease.

Precision of a new tool to measure visceral adipose tissue (VAT) using dual-energy X-Ray absorptiometry (DXA).

OBJECTIVE: A new tool to quantify visceral adipose tissue (VAT) over the android region of a total body dual-energy x-ray absorptiometry (DXA) scan has recently been reported. The measurement, CoreScan, is currently available on Lunar iDXA densitometers. The purpose of the study was to determine the precision of the CoreScan VAT measurement, which is critical for understanding the utility of this measure in longitudinal trials. DESIGN AND METHODS: VAT precision was characterized in both an anthropomorphic imaging phantom (measured on 10 Lunar iDXA systems) and a clinical population consisting of obese women (n = 32). RESULTS: The intrascanner precision for the VAT phantom across 9 quantities of VAT mass (0-1,800 g) ranged from 28.4 to 38.0 g. The interscanner precision ranged from 24.7 to 38.4 g. There was no statistical dependence on the quantity of VAT for either the inter- or intrascanner precision result (p = 0.670). Combining inter- and intrascanner precision yielded a total phantom precision estimate of 47.6 g for VAT mass, which corresponds to a 4.8% coefficient of variance (CV) for a 1 kg VAT mass. Our clinical population, who completed replicate total body scans with repositioning between scans, showed a precision of 56.8 g on an average VAT mass of 1110.4 g. This corresponds to a 5.1% CV. Hence, the in vivo precision result was similar to the phantom precision result. CONCLUSIONS: The study suggests that CoreScan has a relatively low precision error in both phantoms and obese women and therefore may be a useful addition to clinical trials where interventions are targeted towards changes in visceral adiposity.

High-precision U-Pb and 40Ar/39Ar dating of an Alpine ophiolite (Gets nappe, French Alps)

Coarse-grained gabbros from two different localities in the Gets nappe (Upper Prealps) have been dated by U-Pb and Ar-40/Ar-39 isotopic analyses. Zircons from both gabbros gave identical concordant U-Pb ages of 166 +/- 1 Ma (Fig. 4). Amphibole from one of them gave an Ar-40/Ar-39 plateau age of 165.9 +/- 2.2 Ma (Fig. 5). This concordance implies that 166 +/- 1 Ma is the age of magmatic crystallization of these gabbros. The Gets wildflysch with its mafic and ultramafic lenses is an ophiolitic melange, that we infer to come from a proximal part of the accretionary prism at the foot of the active SE margin of the Piemont ocean. In this position we can expect to find remnants of the oldest parts of the Piemont oceanic crust. These are the first high-precision dates using modern techniques from an Alpine ophiolite and are in excellent agreement with the following: 1) The few, somewhat younger, reliable ages on ophiolites from the probable continuation of the Piemont basin into the Apennines and Corsica; 2) Recent data on the age of the first supra-ophiolitic sediments (Late Bathonian to Early Callovian radiolarites); 3) The structural and stratigraphic evolution of the Brianconnais (s.s.) domain, the future NW margin of the Piemont ocean. We note a remarkable coincidence, in Late Bajocian time, between: (A) the end of tensile fracturing in the Brianconnais continental crust; (B) the beginning of its subsidence; (C) the age of the Gets ophiolites. This coincidence is consistent with an ocean opening mechanism based on a combination of subhorizontal extension and thermally driven vertical movements of the lithosphere.

PRECISION V: Randomisierte Phase II-Studie mit Drug Eluting Beads (DEB) zur Behandlung des hepatozelluläre Karzinoms (HCC) mittels transarterieller Chemoemblisation [PRECISION V: Randomized Phase II-Study with Drug Eluting Beads (DEB) for the Treatment of Hepatocellular cancer (HCC) using transarterial Chemoemblisation.]

Zielsetzung: Vergleich von Drug Eluting Bead (DEB)-TACE mit konventioneller TACE bei der Behandlung von ,,intermediate stage-HCC bei Patienten mit Zirrhose. Material und Methodik: 212 Patienten (185 ♂, 27 ♀; mittleres Alter, 67 Jahre) mit Child-Pugh A oder B Leberzirrhose und großem und/oder multinodulärem, irresektablen HCC wurden randomisiert, um das Therapieansprechen nach der Behandlung mit DEB (DC Bead; Biocompatibles, UK) beladen mit Doxorubicin oder konventioneller TACE mit Doxorubicin zu vergleichen. Die Randomisierung wurde nach Child-Pugh Status (A oder B), Performance Status (ECOG 0 oder 1), bilobärer Erkrankung (ja/nein) und frühere kurative Behandlung (ja/nein) stratifiziert. Der primäre Studienendpunkt war das 6-Monats-Tumoransprechen. Eine unabhängige verblindete MRT-Studie wurde durchgeführt, um das Tumoransprechen nach den RECIST Kriterien zu beurteilen. Ergebnisse: DEB-TACE mit Doxorubicin zeigte eine höhere Rate an komplettem Tumoransprechen, objektivem Ansprechen und Tumorkontrolle im Vergleich zur konventionellen TACE (27% vs 22%; 52% vs 44%; and 63% vs 52%; P>0.05). Patienten mit Child-Pugh B Zirrhose, ECOG 1 Performance Status, bilobärer Erkrankung und Rezidiven nach kurativer Behandlung zeigte einen signifikanten Anstieg des objektiven Ansprechens (p = 0.038) im Vergleich zur Kontrollgruppe. Bei Patienten, die mit DEB-TACE behandelt wurden, konnte eine deutliche Reduktion der gravierenden Lebertoxizität erreicht werden. Die Doxorubicin-Nebenwirkungsrate war in der DEB-TACE Gruppe deutlich geringer (p = 0.0001) als in der konventionellen TACEGruppe. Schlussfolgerung: DEB-TACE mit Doxorubicin ist sicher und effektiv in der Behandlung von ,,intermediate-stage HCC und bietet einen signifikanten Vorteil bei Patienten mit fortgeschrittener Erkrankung.

High-precision satellite positioning system as a new tool to study the biomechanics of human locomotion.

New Global Positioning System (GPS) receivers allow now to measure a location on earth at high frequency (5Hz) with a centimetric precision using phase differential positioning method. We studied whether such technique was accurate enough to retrieve basic parameters of human locomotion. Eight subjects walked on an athletics track at four different imposed step frequencies (70-130steps/min) plus a run at free pace. Differential carrier phase localization between a fixed base station and the mobile antenna mounted on the walking person was calculated. In parallel, a triaxial accelerometer, attached to the low back, recorded body accelerations. The different parameters were averaged for 150 consecutive steps of each run for each subject (total of 6000 steps analyzed). We observed a perfect correlation between average step duration measured by accelerometer and by GPS (r=0.9998, N=40). Two important parameters for the calculation of the external work of walking were also analyzed, namely the vertical lift of the trunk and the velocity variation per step. For an average walking speed of 4.0km/h, average vertical lift and velocity variation were, respectively, 4.8cm and 0.60km/h. The average intra-individual step-to-step variability at a constant speed, which includes GPS errors and the biological gait style variation, were found to be 24. 5% (coefficient of variation) for vertical lift and 44.5% for velocity variation. It is concluded that GPS technique can provide useful biomechanical parameters for the analysis of an unlimited number of strides in an unconstrained free-living environment.

Precision of tibial tunnel placement under arthroscopic control alone in posterior cruciate ligament reconstruction: A radiological study

Introduction: Accurate and reproducible tibial tunnel placement minimizing the risk of neurovascular damage is a crucial condition for successful arthroscopic reconstruction of the posterior cruciate ligament (PCL). This step is commonly performed under fluoroscopic control. Hypothesis: Performing the tibial tunnel under exclusive arthroscopic control allows accurate and reliable tunnel placement according to recommendations in the literature. Materials and Methods: Between February 2007 and December 2009, 108 arthroscopic single bundle PCL reconstructions in tibial tunnel technique were performed. The routine postoperative radiographs were screened according to previously defined quality criterions. After critical analysis, the radiographs of 48 patients (48 knees) were enrolled in the study. 10 patients had simultaneous ACL reconstruction and 7 had PCL revision surgery. The tibial tunnel was placed under direct arthroscopic control through a posteromedial portal using a standard tibial aming device. Key anatomical landmarks were the exposed tibial insertion of the PCL and the posterior horn of the medial meniscus. First, the centre of the posterior tibial tunnel outlet on the a-p view was determined by digital analysis of the postoperative radiographes. Its distance to the medial tibial spine was measured parallel to the tibia plateau. The mediolateral position was expressed by the ratio between the distance of the tunnel outlet to the medial border and the total width of the tibial plateau. On the lateral view the vertical tunnel position was measured perpendicularly to a tangent of the medial tibial plateau. All measurement were repeated at least twice and carried out by two examiners. Results: The mean mediolateral tunnel position was 49.3 ± 4.6% (ratio), 6.7 ± 3.6 mm lateral to the medial tibial spine. On the lateral view the tunnel centre was 10.1 ± 4.5 mm distal to the bony surface of the medial tibial plateau. Neurovascular damage was observed in none of our patients. Conclusion: The results of this radiological study confirm that exclusive arthroscopic control for tibial tunnel placement in PCL reconstruction yields reproducible and accurate results according to the literature. Our technique avoids radiation, facilitates the operation room setting and enables the surgeon to visualize the anatomic key landmarks for tibial tunnel placement.

Liver, gastrointestinal and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial : B-240

Purpose: To evaluate the toxicity focussing on hepatic, gastrointestinal and cardiac parameters following PRECISION TACE with DC Bead? versus conventional transarterial chemoembolization (cTACE) in the treatment of intermediate-stage hepatocellular carcinoma (HCC). Methods and Materials: This prospective, randomized, multicentre study was conducted under best practice trial management and authorized by local institutional review boards. Informed consent was obtained. 212 patients (185 men/27 women; mean: 67 years) were randomized to be treated with DC Beads? or cTACE. The majority of both groups presented in a more advanced stage. Safety was measured by rate of adverse events (South West Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed by means of left ventricular ejection fraction (LVEF) in MRI or echocardiography. The results of the two groups were compared using the chi-square test and Student`s t-test. Results: Mean maximum alanine transaminase increase in the DC Bead group was 50% in the cTACE group (p < 0.001) and 59% for aspartate transaminase (p < 0.001). For bilirubin, mean increase was 5.30±15.13 vs. 13.53±73.89 µmol/L. Concerning gastrointestinal disorders, 120 adverse events (AEs) occurred in 57/93 (61.3%) patients in the DC Bead group vs. 114 in 49/108 (45.4%) in cTACE. Concerning hepatobiliary disorders, serious AEs occurred in 8/93 (8.6%) vs. 11/108 (10.2%) patients. LVEF showed an increase in the DC Bead group by +2.7±10.1 percentage points and a small decrease by -1.5±7.6 in the cTACE group, p=0.018. Conclusion: PRECISION TACE is safe, even in more advanced HCC patients. Serious liver and cardiac toxicity were significantly lower in the DC Bead group.