Lipiodol as an intra-procedural imaging biomarker for liver tumor response to transarterial chemoembolization: Post-hoc analysis of a prospective clinical trial

BackgroundThe use of the ethiodized oil- Lipiodol in conventional trans-arterial chemoembolization (cTACE) ensures radiopacity to visualize drug delivery in the process of providing selective drug targeting to hepatic cancers and arterial embolization. Lipiodol functions as a carrier of chemo drugs for targeted therapy, as an embolic agent, augmenting the drug effect by efflux into the portal veins as well as a predictor for the tumor response and survival.PurposeTo prospectively evaluate the role of 3D quantitative assessment of intra-procedural Lipiodol deposition in liver tumors on CBCT immediately after cTACE as a predictive biomarker for the outcome of cTACE.Materials & methodsThis was a post-hoc analysis of data from an IRB-approved prospective clinical trial. Thirty-two patients with hepatocellular carcinoma or liver metastases underwent contrast enhanced CBCT obtained immediately after cTACE, unenhanced MDCT at 24 h after cTACE, and follow-up imaging 30-, 90- and 180-days post-procedure. Lipiodol deposition was quantified on CBCT after cTACE and was characterized by 4 ordinal levels: ≤25%, >25–50%, >50–75%, >75%. Tumor response was assessed on follow-up MRI. Lipiodol deposition on imaging, correlation between Lipiodol deposition and tumor response criteria, and correlation between Lipiodol coverage and median overall survival (MOS) were evaluated.ResultsImage analysis demonstrated a high degree of agreement between the Lipiodol deposition on CBCT and the 24 h post-TACE CT, with a Bland-Altman plot of Lipiodol deposition on imaging demonstrated a bias of 2.75, with 95%-limits-of-agreement: −16.6 to 22.1%. An inverse relationship between Lipiodol deposition in responders versus non-responders for two-dimensional EASL reached statistical significance at 30 days (p = 0.02) and 90 days (p = 0.05). Comparing the Lipiodol deposition in Modified Response Evaluation Criteria in Solid Tumors (mRECIST) responders versus non-responders showed a statistically significant higher volumetric deposition in responders for European Association for the Study of the Liver (EASL)-30d, EASL-90d, and quantitative EASL-180d. The correlation between the relative Lipiodol deposition and the change in enhancing tumor volume showed a negative association post-cTACE (30-day: p < 0.001; rho = −0.63). A Kaplan-Meier analysis for patients with high vs. low Lipiodol deposition showed a MOS of 46 vs. 33 months (p = 0.05).Conclusion3D quantification of Lipiodol deposition on intra-procedural CBCT is a predictive biomarker of outcome in patients with primary or metastatic liver cancer undergoing cTACE. There are spatial and volumetric agreements between 3D quantification of Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT. The spatial and volumetric agreement between Lipiodol deposition on intra-procedural CBCT and 24 h post-cTACE MDCT could suggest that acquiring MDCT 24 h after cTACE is redundant. Importantly, the demonstrated relationship between levels of tumor coverage with Lipiodol and degree and timeline of tumor response after cTACE underline the role of Lipiodol as an intra-procedural surrogate for tumor response, with potential implications for the prediction of survival.     

First clinical trial of a new superparamagnetic iron oxide for use as an oral gastrointestinal contrast agent in MR imaging

The authors report the results of preclinical testing and initial clinical application of a superparamagnetic iron oxide specifically prepared as a contrast agent for magnetic resonance (MR) imaging of the gastrointestinal tract. MR imaging was performed at 0.6 and 1.5 T in 15 volunteers. Images of the upper abdomen and pelvis were obtained before and after ingestion of the contrast material at doses of 22.5-225.0 mg of iron in 600-900 L. Two readers scored the images. Delivery of contrast material into the proximal and distal small bowel, with obvious loss of signal intensity (T2 enhancement), was achieved in all subjects. Enhanced images showed improved delineation of the head and tail of the pancreas, anterior margins of the kidneys, and paraaortic region. The contrast agent did not generate artifacts, an improvement over prototype formulations evaluated previously in animals. Except for a brief episode of diarrhea in five subjects, the agent was well tolerated. Use of this contrast agent improved the diagnostic quality of abdominal MR images by enabling the distinction of the bowel from nonbowel structures at concentrations that did not produce image distortion.     

A controlled clinical pilot trial to study the effectiveness of ice as a supplement to the exercise programme for the management of lateral elbow tendinopathy

Background

The use of ice as a supplement to an exercise programme has been recommended for the management of lateral elbow tendinopathy (LET). No studies have examined its effectiveness.

Objectives

To investigate whether an exercise programme supplemented with ice is more successful than the exercise programme alone in treating patients with LET.

Methods

Patients with unilateral LET for at least four weeks were included in this pilot study. They were sequentially allocated to receive five times a week for four weeks either an exercise programme with ice or the exercise programme alone. The exercise programme consisted of slow progressive eccentric exercises of wrist extensors and static stretching of the extensor carpi radialis brevis tendon. In the exercise programme/ice group, the ice was applied after the exercise programme for 10 minutes in the form of an ice bag to the facet of the lateral epicondyle. Patients were evaluated at baseline, at the end of treatment, and three months after the end of treatment. Outcome measures used were the pain visual analogue scale and the dropout rate.

Results

Forty patients met the inclusion criteria. At the end of treatment there was a decline in visual analogue scale of about 7 units in both groups compared with baseline (p<0.0005, paired t test). There were no significant differences in the magnitude of reduction between the groups at the end of treatment and at the three month follow up (p<0.0005, independent t test). There were no dropouts.

Conclusions

An exercise programme consisting of eccentric and static stretching exercises had reduced the pain in patients with LET at the end of the treatment and at the follow up whether or not ice was included. Further research to establish the relative, absolute, and cost effectiveness as well as the mechanism of action of the exercise programme is needed.     

Description and implementation of a quality control program in an imaging-based clinical trial

RATIONALE AND OBJECTIVES: The American College of Radiology Imaging Network is participating in the National Lung Screening Trial, a large, multicenter, randomized controlled trial, comparing multidetector helical computed tomography (MDCT) versus chest radiography (CXR) in screening for lung cancer. Because the threshold for detection of disease is an inherent function of image quality, and consistent image quality is necessary to track changes in suspicious findings, our purpose was to develop an image quality control (QC) program across all clinical sites for both modalities. MATERIALS AND METHODS: The primary goals of the QC program include standardization of imaging protocols, certification of imaging equipment, and ongoing, periodic evaluation of the equipment calibration and image quality. Minimum standards for equipment and standardized cross-platform acquisition protocols are achieved via radiologist and physicist attestation forms and web-distributed technique charts, respectively. Imaging equipment performance standards are implemented through an initial machine certification process that includes equipment calibration. Ongoing assessment of equipment performance and calibration, as well as adherence to established imaging protocols. is accomplished via periodic submission of calibration records and phantom images. Participant-specific image acquisition parameters are entered into a web-based centralized database and variations from established protocols are automatically flagged for review. Participant radiation dose can be estimated from the image acquisition parameters applied to the imaging equipment calibration measurements. A radiologist visual review committee also evaluates participant images for diagnostic quality. Data are collected from 23 independent centers, representing 14 models of MDCT scanners from four manufacturers, and CXR systems that include film-screen, computed radiography, and direct digital radiography systems. RESULTS: Widespread imaging protocol variation in extant clinical practice-as well as variability in equipment technology, image acquisition parameters, manufacturer terminology, and user interface-have required careful standardization as a prerequisite to trial participation and ongoing image QC. Acceptable ranges for image acquisition parameters have been refined to accommodate continuously evolving equipment platforms and the scope of participant size and body habitus. CONCLUSION: Standardization of imaging protocols is a critical component of image-based clinical trials, predicated on ongoing dialogue between sites and a centralized review committee.     

Death due to an unrecognized groin abscess in a drug addict: A retrospective study

Intravenous drug injection persists despite health risks and medical complications. Venous thrombosis, septic thrombophlebitis, artery necrosis, arterio-venous fistula, mycotic aneurysm, dissecting hematoma, pseudoaneurysm formation, and soft tissues infections (i.e. abscesses, cellulitis, infected ulcers), are some of the major clinical consequences lives threatening. The aim of this work is to present this unusual autoptic case of a drug addict man died for an unrecognized groin abscess referred to the Institute of Legal Medicine, University of Chieti, causing femoral vein's erosion, and to analyse the most common patterns of vascular lesions among drug addicts.It could be stimulated a new scientific debate because groin injections and their vascular complications increase over years; while soft tissue infections may hide vascular lesions' diagnosis. So physicians should have a high index of suspicion for serious vascular problems, among intravenous drug users (IDUs): prevention for avoiding groin injection and a proper treatment are necessary.     

温敏药物缓释栓塞剂行兔肝动脉栓塞的实验研究

目的 探讨温敏药物缓释栓塞剂行肝动脉栓塞治疗的可行性与疗效.方法 选用新西兰大白兔15只,以自组包载"碘海醇"温敏缓释剂泊洛沙姆407(Pluronic F-127)行肝动脉栓塞术,术后随访4周,定期复查肝功能、DSA、CT及动物处死后组织病理检查.结果 术后丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)一过性增高,...     

A clinical and neuropathologic study of silk suture as an embolic agent for brain arteriovenous malformations.

PURPOSETo evaluate the safety and efficacy of silk suture as an agent for preoperative embolization of cerebral arteriovenous malformations.METHODSClinical and histopathologic results were analyzed in six patients who underwent embolization of cerebral arteriovenous malformations using silk suture in combination with other agents.RESULTSThree of the patients treated with silk hemorrhaged after embolization, and two of these patients died. Neuropathologic analysis of four patients showed acute perivascular inflammation, sometimes quite severe.CONCLUSIONSThe inflammatory response to silk may explain its effectiveness in producing vascular occlusion. However, a fulminate vasculitis theoretically can predispose to delayed hemorrhage. Other problems with silk include the pressure required to inject the agent and the inability to determine the final site of deposition of the silk. Although other embolic agents may share some of these potential difficulties, we feel that the disadvantages outweigh the advantages of silk as an embolic agent.     

The Japanese quail chorioallantoic membrane as a model to study an amphiphilic gradient copoly(2-oxazoline)s- based drug delivery system for photodynamic diagnosis and therapy research

Amphiphilic gradient copoly(2-oxazoline)s are widely researched in the field of drug delivery. They could be used as a transport system for hydrophobic drugs such as hypericin (HYP). We prepared six gradient copolymers (EtOx)-grad-(ROPhOx) by living cationic ring-opening polymerization of a hydrophilic comonomer 2-ethyl-2-oxazoline (EtOx) and a hydrophobic comonomer 2-(4-alkyloxyphenyl)-2-oxazoline (ROPhOx), with different composition ratio (88:12 and 85:15) and three different alkyl chain lengths of alkyl (R) substituents. As an experimental model, Japanese quail chorioallantoic membrane (CAM) was used. The effect of nanoparticles loaded with HYP was evaluated by the changes of fluorescence intensity during photodynamic diagnosis (PDD) monitored under 405 nm LED light before administration, and 0,1,3 and 24 h after topical administration. The effectiveness of photodynamic therapy (PDT) (405 nm, 285 mW/cm²) applied 1h after the administration of HYP-loaded nanoparticles was evaluated using vascular damage score and histological sections. Molecular analysis was done by measuring angiogenesis-related gene expression by qPCR. The application of nanoparticles unloaded or loaded with HYP proved to be biocompatible, non-toxic, and undamaging to the CAM tissue, while they successfully altered the HYP fluorescence. We observed a possible anti-angiogenic potential of prepared nanoparticles, which could present an advantage for PDT used for tumour treatment.     

Lys-plasminogen as an adjunct to local intra-arterial fibrinolysis for carotid territory stroke: laboratory and clinical findings

To improve the efficacy of local intraarterial fibrinolysis (LIF), we compared different fibrinolytic drugs in a cerebral circulation model in the laboratory. The technical efficacy of fibrinolysis, defined as the clot volume lysed per unit time, was found to be optimal with r-tissue plasminogen activator (TPA) activated lys-plasminogen (=plasmin). Subsequently, 20 patients with stroke due to carotid artery territory occlusion were treated by local intrarterial fibrinolysis using the plasmin regimen. The angiographic data and clinical outcome of these patients were compared with those of 40 patients who received plasminogen activators (urokinase or r-TPA) only. Laboratory and clinical data confirmed that plasmin lysis is superior to treatment using only plasminogen activators.     

Analysis of a new fluoroquinolone derivative (Q-35) in human scalp hair as an index of drug exposure and as a time marker in hair

Summary Scalp hair samples were obtained every month for three months after administration from healthy male volunteers who participated in the phase I study of a new antimicrobial fluoroquinolone derivative (Q-35). Hairs were cut into 1 cm long pieces successively from the scalp end. Corresponding pieces of 5 hair strands were dissolved in 1M NaOH and assessed for Q-35 by HPLC. The drug was detectable in the hairs of all subjects taking either a single (400 mg,n = 6) or repeated oral doses of Q-35 (400 mg/day for 6.5 days, total 2600 mg,n = 6). The hair portions containing the drug were shown in most subjects to move outwards along the hair shafts month by month in proportion to the hair growth rate of about 1 cm/month. Q35 (600 mg/day) was also given to 6 healthy male volunteers for 6.5 days (total 3900 mg) and hair samples were obtained 1 and 3 months after administration. When Q-35 was analyzed along a single hair shaft, the drug was detectable only in 1–2 consecutive 1 cm long pieces, which were also shown to move outwards along the hair shaft with time. A detailed analysis revealed that the drug was contained only in 2–4 consecutive 2.5 mm long pieces of a single hair collected after 3 months, showing that there was no significant axial diffusion of the drug along the hair shaft with time. These findings indicate the utility of measuring this fluoroquinolone derivative in human scalp hair as an index of drug exposure and as a time marker for analyzing other drug(s) in hair.     

Gadolinium-ethoxybenzyl-DTPA as a hepatobiliary contrast agent for use in MR cholangiography: results of an in vivo phase-I clinical evaluation

The purpose of this study was to investigate the time course of contrast enhancement in bile ducts and the gallbladder (GB) after injection of gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA). In a clinical phase-I study, MR imaging at 1.5T was performed in 16 healthy volunteers with four different doses of Gd-EOB-DTPA (10, 25, 50, and 100 μmol/kg b. w., four volunteers per dosage). The study protocol comprised a heavily T1-weighted fast multiplanar gradient-echo (GE) sequence before and at increasing intervals for up to 360 min after injection of Gd-EOB-DTPA. The signal enhancement was evaluated in extra- and intrahepatic bile ducts as well as in the GB. In all 16 volunteers the common bile duct showed intense signal enhancement beginning 5–16 min after injection (mean 10 min) and persisting for at least 120 min in 4 subjects and for 360 min in 12 subjects. The duration of signal enhancement was significantly (p < 0.05) longer for higher doses (50, 100 μmol/kg) than for lower doses (10, 25 μmol/kg). Intrahepatic bile ducts were hyperintense as compared with liver parenchyma in all subjects receiving 10 μmol/kg from approximately 50–120 min after contrast agent application. Intrahepatic bile ducts were not displayed using the higher doses, probably because of the strong enhancement of the liver parenchyma. Gallbladder contrasting was achieved in all cases beginning 7–33 min after injection (mean 19 min) and remained visible for up to 360 min in 94 %. Hyperintense visualization of normal extrahepatic bile ducts as well as the GB is regularly achieved with the hepatobiliary contrast agent Gd-EOB-DTPA. The dosage for hyperintense visualization of intrahepatic bile ducts is 10 μmol/kg. Received 6 December 1995; Revision received 21 March 1996; Accepted 25 March 1996