Romaric Loffroy

3-Bromopyruvate: A New Targeted Antiglycolytic Agent and a Promise for Cancer Therapy

The pyruvate analog, 3-bromopyruvate, is an alkylating agent and a potent inhibitor of glycolysis. This antiglycolytic property of 3-bromopyruvate has recently been exploited to target cancer cells, as most tumors depend on glycolysis for their energy requirements. The anticancer effect of 3-bromopyruvate is achieved by depleting intracellular energy (ATP) resulting in tumor cell death. In this review, we will discuss the principal mechanism of action and primary targets of 3-bromopyruvate, and report the impressive antitumor effects of 3-bromopyruvate in multiple animal tumor models. We describe that the primary mechanism of 3-bromopyruvate is via preferential alkylation of GAPDH and that 3-bromopyruvate mediated cell death is linked to generation of free radicals. Research in our laboratory also revealed that 3-bromopyruvate induces endoplasmic reticulum stress, inhibits global protein synthesis further contributing to cancer cell death. Therefore, these and other studies reveal the tremendous potential of 3-bromopyruvate as an anticancer agent.

Intraprocedural C-Arm Dual-Phase Cone-Beam CT: Can It Be Used to Predict Short-term Response to TACE with Drug-eluting Beads in Patients with Hepatocellular Carcinoma?

PURPOSE To investigate whether C-arm dual-phase cone-beam computed tomography (CT) performed during transcatheter arterial chemoembolization (TACE) with doxorubicin-eluting beads can help predict tumor response at 1-month follow-up in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS This prospective study was compliant with HIPAA and approved by the institutional review board and animal care and use committee. Analysis was performed retrospectively on 50 targeted HCC lesions in 29 patients (16 men, 13 women; mean age, 61.9 years ± 10.7) treated with TACE with drug-eluting beads. Magnetic resonance (MR) imaging was performed at baseline and 1 month after TACE. Dual-phase cone-beam CT was performed before and after TACE. Tumor enhancement at dual-phase cone-beam CT in early arterial and delayed venous phases was assessed retrospectively with blinding to MR findings. Tumor response at MR imaging was assessed according to European Association for the Study of the Liver (EASL) guidelines. Two patients were excluded from analysis because dual-phase cone-beam CT scans were not interpretable. Logistic regression models for correlated data were used to compare changes in tumor enhancement between modalities. The radiation dose with dual-phase cone-beam CT was measured in one pig. RESULTS At 1-month MR imaging follow-up, complete and/or partial tumor response was seen in 74% and 76% of lesions in the arterial and venous phases, respectively. Paired t tests used to compare images obtained before and after TACE showed a significant reduction in tumor enhancement with both modalities (P < .0001). The decrease in tumor enhancement seen with dual-phase cone-beam CT after TACE showed a linear correlation with MR findings. Estimated correlation coefficients were excellent for first (R = 0.89) and second (R = 0.82) phases. A significant relationship between tumor enhancement at cone-beam CT after TACE and complete and/or partial tumor response at MR imaging was found for arterial (odds ratio, 0.95; 95% confidence interval [CI]: 0.91, 0.99; P = .023) and venous (odds ratio, 0.96; 95% CI: 0.93, 0.99; P = .035) phases with the multivariate logistic regression model. Radiation dose for two dual-phase cone-beam CT scans was 3.08 mSv. CONCLUSION Intraprocedural C-arm dual-phase cone-beam CT can be used immediately after TACE with doxorubicin-eluting beads to predict HCC tumor response at 1-month MR imaging follow-up.

Quantitative and Volumetric European Association for the Study of the Liver and Response Evaluation Criteria in Solid Tumors Measurements: Feasibility of a Semiautomated Software Method to Assess Tumor Response after Transcatheter Arterial Chemoembolization

PURPOSE To show that hepatic tumor volume and enhancement pattern measurements can be obtained in a time-efficient and reproducible manner on a voxel-by-voxel basis to provide a true three-dimensional (3D) volumetric assessment. MATERIALS AND METHODS Magnetic resonance (MR) imaging data obtained from 20 patients recruited for a single-institution prospective study were retrospectively evaluated. All patients had a diagnosis of hepatocellular carcinoma (HCC) and underwent drug-eluting beads (DEB) transcatheter arterial chemoembolization for the first time. All patients had undergone contrast-enhanced MR imaging before and after DEB transcatheter arterial chemoembolization; poor image quality excluded 3 patients, resulting in a final count of 17 patients. Volumetric RECIST (vRECIST) and quantitative EASL (qEASL) were measured, and segmentation and processing times were recorded. RESULTS There were 34 scans analyzed. The time for semiautomatic segmentation was 65 seconds±33 (range, 40-200 seconds). vRECIST and qEASL of each tumor were computed<1 minute for each. CONCLUSIONS Semiautomatic quantitative tumor enhancement (qEASL) and volume (vRECIST) assessment is feasible in a workflow-efficient time frame. Clinical correlation is necessary, but vRECIST and qEASL could become part of the assessment of intraarterial therapy for interventional radiologists.

Evaluating tumors in transcatheter arterial chemoembolization (TACE) using dual-phase cone-beam CT

Abstract C-arm cone-beam computed tomography (CBCT) can be used to visualize tumor-feeding vessels and parenchymal staining during transcatheter arterial chemoembolization (TACE). To capture these two phases, all current commercially available CBCT systems necessitate two separate contrast-enhanced scans. In this feasibility study, we report initial results of novel software that enhanced our current CBCT system to capture these two phases using only one contrast injection. Novelty of this work is the addition of software that enabled the acquisition of two sequential, back-to-back CBCT scans (dual-phase CBCT, DPCBCT) so both tumor feeding vessels and parenchyma are captured using only one contrast injection. To illustrate our initial experience, DPCBCT was used for TACE treatments involving lipiodol, drug-eluting beads, and Yttrium-90 radioembolizing microspheres. For each case, the DPCBCT images were compared to pre-intervention contrast-enhanced MR/CT. DPCBCT is feasible for TACE treatments and the preliminary results show positive correlation with pre-intervention conventional CT and MR. In addition, the degree of embolization can be monitored. DPCBCT is a promising technology that provides comprehensive visualization of tumor-feeding vessels and parenchymal staining using a single injection of contrast. DPCBCT could potentially be used during TACE to verify catheter position and monitor the embolization effect.

Transcatheter Arterial Embolization in Patients with Kidney Diseases: an Overview of the Technical Aspects and Clinical Indications

Therapeutic embolization is defined as the voluntary occlusion of one or several vessels, and this is achieved by inserting material into the lumen to obtain transient or permanent thrombosis in the downstream vascular bed. There are a number of indications for this approach in urological practice, in particular for the patients with parenchymatous or vascular kidney disease. In this review, we present the different embolization techniques and the principally employed occluding agents, and then we present the principal clinical indications and we discuss other pathologies that may benefit from this non-invasive therapy. The complications, side effects and main precautions associated with this approach are also described.

A comparison of the results of arterial embolization for bleeding and non-bleeding gastroduodenal ulcers

Background Although some authors have advocated the practice of arterial embolization for angiographically negative acute hemorrhage from gastroduodenal ulcers, this technique remains controversial. Purpose To compare the results of arterial embolization for bleeding (BU) and non-bleeding (NBU) gastroduodenal ulcers. Material and Methods Transcatheter embolization was performed in 57 patients (39 men, 18 women, mean age 69.8 years) who experienced acute bleeding from gastroduodenal ulcers. At the time of embolization active contrast extravasation was seen in 36 of 57 patients, while in the remaining 21 patients embolization was based on endoscopic findings. Patient demographics, clinical success, need for re-intervention secondary to re-bleeding, and 30-day complication and mortality rates were reviewed and compared between the two groups by using statistical analyses. Results In the BU group, the gastroduodenal artery (GDA) was embolized in 31 patients (86.1%), the left gastric artery (LGA) in three patients (8.3%), and the left gastroepiploic artery (LGEA) in two patients (5.6%). In the NBU group, the GDA was embolized in 18 patients (85.7%), and the LGA in three patients (14.3%). Clinical success (61.9 vs. 75.0%, P = 0.30), need for re-intervention (38.1 vs. 27.8%, P = 0.42), and 30-day complication (9.5 vs. 5.6%, P = 0.57), and mortality (28.6 vs. 25%, P = 0.77) rates were not statistically different between the two groups. Embolization in patients in NBU group did not have impact on clinical success (OR, 0.54; 95%CI, 0.17–1.72; P = 0.30). Conclusion Arterial embolization in patients with angiographically NBU is as safe and effective as embolization in patients with BU.

Use of 3.0-Tesla High Spatial Resolution Magnetic Resonance Imaging for Diagnosis and Treatment of Cystic Adventitial Disease of the Popliteal Artery

Cystic adventitial disease (CAD) of the popliteal artery is a rare vascular disease of unknown etiology in which a mucin-containing cyst develops in the adventitial layer of the artery. Early recognition and treatment of this condition will prevent progression of the popliteal thrombosis and critical ischemia. However, diagnosis of the condition is difficult. The combination of contrast-enhanced magnetic resonance (MR) angiography and the excellent soft-tissue resolution of MR imaging allow for detailed evaluation of patients with CAD and facilitate appropriate management decisions. We report the 3.0-Tesla MR imaging features of CAD in three patients and discuss the interest for this noninvasive imaging technique in such a setting.

Breathing motion compensated reconstruction for C-arm cone beam CT imaging: initial experience based on animal data

C-arm based tomographic 3D imaging is applied in an increasing number of minimal invasive procedures. Due to the limited acquisition speed for a complete projection data set required for tomographic reconstruction, breathing motion is a potential source of artifacts. This is the case for patients who cannot comply breathing commands (e.g. due to anesthesia). Intra-scan motion estimation and compensation is required. Here, a scheme for projection based local breathing motion estimation is combined with an anatomy adapted interpolation strategy and subsequent motion compensated filtered back projection. The breathing motion vector is measured as a displacement vector on the projections of a tomographic short scan acquisition using the diaphragm as a landmark. Scaling of the displacement to the acquisition iso-center and anatomy adapted volumetric motion vector field interpolation delivers a 3D motion vector per voxel. Motion compensated filtered back projection incorporates this motion vector field in the image reconstruction process. This approach is applied in animal experiments on a flat panel C-arm system delivering improved image quality (lower artifact levels, improved tumor delineation) in 3D liver tumor imaging.

Transcatheter arterial embolization for gastroduodenal ulcer bleeding: the use of cyanoacrylate glue has gained acceptance.

We read with great interest the article by Mine et al. (1) recently published in Acta Radiologica and reporting outcomes of transcatheter arterial embolization (TAE) using N-butyl cyanoacrylate (NBCA) in patients with acute arterial bleeding from gastroduodenal ulcers. We have several comments. First of all, we would like to congratulate the authors for their study, which represents one of the most important series to date reporting results on TAE with NBCA glue as an embolic agent in such a setting. TAE has gained widespread acceptance for first-line treatment of acute upper gastrointestinal (GI) bleeding resistant to endoscopic therapy over the last decade (1–3). Coils have emerged as the currently preferred embolic agent for upper GI bleedings. However, higher rates of recurrent bleeding have been reported with coil embolization, especially in patients with coagulopathy (2). Indeed, we previously reported our experience with TAE used to treat refractory massive bleeding from gastroduodenal ulcers (2). Using coils alone to occlude the feeding artery and the presence of a coagulation disorder significantly predicted early rebleeding. Furthermore, no cases of rebleeding occurred in the 10 patients in whom NBCA was used alone for selective embolization of the bleeding vessel, and no cases of bowel ischemia occurred. High clinical success rate with the use of glue is confirmed in the present study, as recently reported in other studies (4,5), suggesting that this embolic agent has gained acceptance. So we absolutely agree with Mine et al. (1) about efficacy and safety of glue embolization in gastroduodenal ulcer bleeding. In our institution, selective TAE using NBCA glue as the only embolic agent has became the salvage treatment of choice of upper GI bleeding from gastroduodenal ulcers. We find the use of NBCA glue particularly interesting in hemodynamically unstable patients or in cases of underlying coagulopathy, because it provides faster and better hemostasis than other embolic agents, as described by the authors (1). However, we want to stress the fact that the use of NBCA requires training and considerable experience, given the risk of bowel infarction and glue reflux into other vessels. Reflux of NBCA may also result in its polymerization to the catheter tip. This bit of NBCA may then be stripped from the catheter during catheter retraction, resulting in non-target embolization. Prompt microcatheter removal after injection can significantly reduce this risk (2), but can be problematic because it gives up superselective vessel access before confirmation of adequate cessation of hemorrhage. A last drawback is the potential risk of bowel stenosis in the long term as suggested by Lang et al. (6) who reported a 25% duodenal stenosis rate in a study of 28 patients followed up for at least 5 years after TAE for bleeding duodenal ulcers. In the present study (1), follow-up endoscopic evaluations were performed only within 30 days of follow-up, after a mean delay of less than 10 days. Otherwise, evidence of arterial embolization-induced bowel stricture cannot be really appreciated on the long-term. In conclusion, our experience and recent literature suggest that TAE using cyanoacrylate glue in welltrained hands could be more effective in controlling bleeding from the upper GI tract than other embolic agents if used with great caution, and does not cause more ischemic complications. NBCA may be specifically useful in the setting of hemodynamic instability, coagulopathy, extreme vessel tortuosity, and narrowed vessels that are not amenable to distal embolization by microcoils. However, NBCA glue should not be used by interventional radiologists without a large experience with its use in other territories.

Letter to the Editor re: Superselective arterial embolisation with a liquid polyvinyl alcohol copolymer in patients with acute gastrointestinal haemorrhage

Sir, We read with great interest the article by Lenhart and colleagues recently published in European Radiology and reporting effectiveness of selective arterial embolisation using Onyx® in patients with acute gastrointestinal bleeding [1]. We have several comments. First of all, we would like to congratulate the authors for their study which represents the first series to date reporting results on arterial embolotherapy with Onyx® as an embolic agent in the gastrointestinal tract. Until now, the only available data on the use of this embolic material for peripheral applications came from case reports. Indeed, Onyx® is a new liquid embolic agent composed of ethylene-vinyl alcohol copolymer dissolved in dimethyl sulphoxide (DMSO), with emerging applications in neurovascular procedures, predominantly embolisation of cerebral aneurysms and arteriovenous malformations [2]. The main advantages of Onyx® are its nonadhesive properties, high radiopacity, and long solidification periods, which, compared with acrylic glues, make the embolisation procedure more controllable and predictable. However, the authors did not bring to attention several important disadvantageous characteristics of the use of Onyx®. First, DMSO can cause severe vasospasm if injected rapidly. This is most likely to occur early in the procedure and can be avoided by using no more than 0.2 ml of DMSO in the first minute of injection. Even if the authors reported a total injection time of DMSO and Onyx® of 10 min on average for their procedure, in our experience, the duration of injection is often much longer and varies depending on the amount of Onyx® used. Secondly, DMSO is volatile and is excreted via respiration and sweat. This has a typical smell not unlike that of diabetic ketoacidosis and may last a few days. The patient and ward staff should be warned to expect this. Lastly, the use of Onyx® has cost implications as it is much more expensive than alternative embolic materials and it requires specific DMSO-compatible microcatheters. The prohibitive costs of using Onyx® have led to its restricted use in neuroradiology in most of the institutions around the world. In conclusion, we think this embolic agent is very promising but the important cost aspect needs to be borne in mind when there are other cheaper alternatives that would be as effective and faster when used on an emergency basis.