Lack of paediatric specific devices a glaring unmet need

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1 Issue 55 Lack of paediatric specific devices a glaring unmet need There is a compelling case for the medical community, including the device industry, to develop specific devices that are appropriate for paediatric patients. Paediatric interventional radiologists often have to make do and be creative in order to treat children whilst using devices that are designed for and tested on adults only. The need for appropriate devices for the paediatric population ranges from the common and simple, such as long-term feeding tubes and vascular access devices, to the expensive and biomechanically complex, such as bioabsorbable stent-grafts, say opinion leaders in the field There are many factors that make it difficult to tailor devices to paediatric patients (who range from neonates to teenagers) and who need devices that remain suitable and effective as the patients grow. Still, paediatric interventional radiologists see a real need for childrenspecific kits and are calling for incentives within the medical device industry to help drive testing and modifications for children, in order to improve patient care. Alex Barnacle, consultant interventional radiologist, Department of Radiology, Great Ormond Street Hospital for Children, London, UK, told Interventional News: There are almost no paediatric-specific interventional radiology devices available, other than Riccardo Lencioni: Future of IO Page 12 intravenous access devices. There is a modified paediatric version of a transjugular liver biopsy set available, which is still too large for use in small children, and a paediatric transjugular intrahepatic portosystemic shunt (TIPS) set, but otherwise most devices are only available in adult sizes. Daniel Sze, professor, Interventional Radiology with his colleagues Matthew Lungren, assistant professor and F Glen Seidel, clinical professor from the Lucile Packard Children s Suresh Vedantham: DVT updates Page 20 Hospital, Stanford University, Stanford, USA, said, There are very few devices specifically tailored for children, and this is a glaring unmet need for paediatric interventional radiology. However, there has been significant movement in the interventional marketplace to optimise intravascular devices for smaller and smaller size vessels as the demand increases in the adult interventional marketplace (ie. below the knee and retrograde revascularisation procedures, radial artery access); in fact, some basic interventional tools are already maximally miniaturised (needles, wires, microcatheters). For the most part, however, adult devices continue to be the only available devices for use in children, leaving few, if any, paediatric specific device options. Carlos J Guevara, Instructor of Radiology, Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, USA, echoes their views. Most devices are made for adult patients and therefore in Continued on page 3 Arterial embolization works to alleviate knee pain in mild to moderate osteoarthritis A small study conducted in Japan, published in CardioVascular and Interventional Radiology in July 2014, demonstrates that transcatheter arterial embolization is feasible and that it rapidly relieves pain associated with knee osteoarthritis and restores knee function Yuji Okuno José Ignacio Bilbao: Profile Page 26 The researchers reported in the paper that mild to moderate knee osteoarthritis that is resistant to treatment by nonsurgical options and that is not severe enough to warrant joint replacement represents a challenge in its management. They hypothesised that abnormal neovessels and accompanying nerves are possible sources of pain and that transcatheter arterial embolization can relieve pain associated with knee osteoarthritis by selectively occluding these abnormal neovessels, thus reducing pain and restoring knee function. Yuji Okuno, Department of Orthopedic Surgery, Edogawa Hospital, and colleagues, carried out the prospective study between June 2012 and December 2013 in Edogawa Hospital, Tokyo, Japan. The 14 patients (eight female; mean age, 65.2±8.3 years; range years) who were enrolled received explanations about various management modalities and the potential risks, benefits, and outcomes of transcatheter arte- Continued on page 4 Interventionalnews.com IN App

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3 Lack of paediatric specific devices a glaring unmet need Continued from page 1 many circumstances we have to get creative and use whatever tools we have available to us. I do not think there are enough adequate interventional radiology devices for use in paediatric patients and that includes common devices such as central vein catheters as well as more advanced devices such as transjugular biopsy needles and thrombolysis catheters, he said. Most needed devices While there are several different types of devices that need to be tailored to provide better care for paediatric patients, some of the most apparent ones include devices for central vein access, transvenous biopsy, enteral access, fluid drainage, and endovascular procedures. One of the biggest challenges is finding suitable long-term feeding tubes for small children. The small calibre gastrojejunal tubes needed in young children are simply not available, and this means that small children have to either continue to have uncomfortable nasojejunal tubes for several years or we have to place large calibre 16Fr feeding devices, which are really unsuitable for children who are only a few kilograms in weight, Barnacle pointed out. In Guevara s view, Two of the most common procedures done in paediatric patients are central line placement for venous access and drain placement for abscesses. Most of the catheters are designed for adult patients and the lines or catheters have to be positioned and covered so that they are not at risk from being pulled out inadvertently by children. In some instances there is a lot of redundancy of the device outside of the body which makes it difficult for the patient, the family, and the healthcare workers who have to work with the catheters. Sze and colleagues also make the case for low dose (high quality) fluoroscopy. Dose awareness has reached a peak in other modalities such as CT, but still lags somewhat in the interventional fluoroscopic suite. There are major advances on the horizon by the major manufacturers, who are close to achieving clinically advanced low-dose fluoroscopy and digital subtraction angiography without compromising image quality. For devices, one major area that the community hopes to see movement in is bioabsorbable medical device platforms, such as vascular stents. Other areas that need more attention include vascular access devices such as peripherally inserted central catheters (PICCs) and gastrostomy and gastrojejunal tubes. For vascular procedures, lower profile angiographic catheters of similar shapes and performance as adult models are needed, they outlined. Difficult patients Paediatric interventionalists expound that there are both inherent and external challenges to paediatric devices for example, the biology of growing bodies is a taxing environment for permanent implantable devices. In addition, available data in adult patients may not accurately predict outcomes in children. From a technical point of view, it is their small size that can be a challenge. The bodies of paediatric patients can be quite small and it can be challenging to adapt to carrying out a procedure in children for this reason. For example, some veins in children can be just a few millimetres wide and it can be difficult to get access. Also, since most of the equipment and devices are made for adults, this can add to the complexity of making these work when you have a small patient. For instance, when you have equipment that is designed for use in large adults (such as enteral access kits to place gastrostomy and gastrojejunostomy tubes), it is quite challenging to then use this same equipment for children, said Guevara. Another aspect to be considered is the type of anaesthesia needed to carry out interventional radiology procedures in children. Most interventional radiology procedures in adults are done using moderate sedation, and that is not possible for most paediatric patients. Anesthesia collaboration is necessary, which adds another layer of complexity, he continued. Barnacle agreed: Many children are frightened when they come into hospital and can be uncooperative because of fear or because of their limited level of understanding of what is happening to them. So paediatric units have to have far more capacity for sedation and general anaesthesia cases, and this is not always easy to achieve. Sze and colleagues point out that With very few exceptions, paediatric patients require dedicated specialty care, not simply for the procedure alone, but for the entire care experience; this often translates into more clinic visits and family meetings, tailored patient experiences for the children with dedicated paediatric or childlife specialty ancillary or support staff, paediatric trained sedation or anaesthesia practitioners, and availability of paediatric specific subspecialty services such as intensive care units, surgery, etc. In terms of the procedure itself, because the cases often require general anaesthesia, communication with patients during the procedure is not possible, and depending on the age, can be difficult or impossible before and after procedures. Small body sizes render much of our existing equipment disproportionate, clumsy, or even useless. Limitations on intravascular contrast and radiation exposure can restrict or severely limit which procedures can be performed. Finally, the disease processes in children are generally very different from those in adults. This compounds the issues already mentioned and makes many adult interventionalists very uncomfortable treating paediatric patients, even if the interventional techniques themselves are used routinely in adults. Formal training in paediatric interventional radiology, including sub-subspecialty fellowships, is becoming more recognised and available, but is currently still quite limited, they stated. Improvisation can make for better care Interventional radiology is characterised by its inventiveness and paediatric interventional radiologists are sometimes forced to apply this to their daily work in order to optimise devices for their patients. Sze and colleagues maintain that there is often improvisation needed in paediatric interventions, mainly in intravascular procedures. Cutting wires and catheters to length (with additional modifications on the table) is often needed, particularly in infants. Transjugular liver biopsies can be performed in infants with improvised percutaneous biopsy tools. Occasionally, cases are delayed or not feasible because of the lack of appropriately sized devices, which can sometimes be specially ordered or custom constructed, such as stent-grafts, but the FDA and local Institutional Review Boards may discourage improvisation that is perceived as risky, they explained. Sometimes paediatric interventionalists use miniaturised devices for other indications in order to proceed with the procedure. Renovascular hypertension is pretty rare in children but we have a relatively large cohort of patients in our centre. We commonly use 2.5 4mm coronary artery stents to treat their renal artery stenosis, as standard stents are too large for paediatric cases, Barnacle illustrated. Guevara draws attention to liver biopsy patients who are at a high risk of bleeding, or ascites that require that the biopsy be obtained via a transjugular approach. All the kits that are being manufactured are made for adults. If the patient is an infant, then these kits are too large. However in order to minimise the risk of bleeding, we sometimes have to use these large transjugular liver biopsy kits in small patients and be very careful not to injure the veins or to obtain a liver biopsy sample that traverses the liver out of the capsule, he noted. Guidance In May 2014, the US FDA released a guidance document stating that companies applying for premarket approval should also provide paediatric device use information. The document stated: Section 515A requires submitters to FDA of premarket approval applications (PMAs), supplements to PMAs, humanitarian device exemptions), and product development protocols for new devices to include readily available information about paediatric subpopulations that suffer from a disease or condition that the device is intended to treat, diagnose, or cure. The purpose of seeking this information, the US FDA said, was ultimately to use these data to determine unmet paediatric needs in medical device development. Once unmet needs are identified, the FDA will be better able to coordinate efforts of stakeholders, device manufacturers and FDA staff to promote new device development and proper labelling of existing medical devices for paediatric use. Medical technologies save lives, improve health and contribute to sustainable healthcare. Many of these products bring value to adults as well as children and newborns. In some cases, however, specific modified versions of the technology are developed to improve treatment outcomes or reduce adverse events. These range from diagnostic HIV-tests for foetuses over tracheostomy tubes for infants, to child-friendly blood-glucose meters. The medtech industry will continue to develop paediatric Paediatric devices Alex Barnacle Daniel Sze Carlos Guevara 3 and child-friendly technologies in those scenarios where we can bring more value to patients in doing so, noted MedTech Europe, an alliance of European medical technology industry associations European Diagnostic Manufacturers Association (EDMA) and Eucomed in a statement to Interventional News. Sze and colleagues point out that the paediatric device market is very small. Despite the fact that 25% of the US population is under 18 years of age, only about 5% of the overall healthcare expenses are applied to paediatric medical care. There is a developing consortium of interventionalists lobbying the governmental funding agencies and the device industry to invest in paediatric interventional tool development. Funding and profits are currently scant or nonexistent. We need to find a way to incentivise the development and manufacture of devices tailored for children. One possible strategy would be for the large children s hospitals to collaborate around key needs for paediatric medical device development and research, so as to be able to reach the economies of scale needed to move the industry and the field forward. The FDA has been a significant barrier to new device development in general, and the small size of the paediatric market makes it nearly impossible to recoup the investments required to bring new devices to market in this space. However, this is beginning to change since the FDA has begun to address the concern of a lack of innovation in paediatrics by instituting a Pediatric Consortia Grant Program, whose goals are to support the development of nonprofit consortia designed to stimulate projects which will promote paediatric device development. Additionally, the FDA has removed the profit prohibition for humanitarian device exemption (HDE) devices used to treat children, which may incentivise ventures into this space, they noted. Barnacle concurs. We should be taking our lead from the pharmaceutical industry, where there are often incentives for companies to extend trials into paediatric age groups. The same incentives do not seem to exist for devices, so most devices are not tested or modified for use in children, she said.

4 4 New developments Penile artery angioplasty safe and improves erectile function, first-in-man study shows A study from Taiwan, published in EuroIntervention in May and presented at the EuroPCR congress (20 23 May 2014, Paris, France), shows that penile artery angioplasty is safe and can achieve clinically significant improvements in erectile function in 60% of patients with erectile dysfunction and isolated penile artery stenoses at six months The authors Tzung-Dau Wang, Cardiovascular Centre and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei City, Taiwan, and colleagues, set out to assess the safety and feasibility of balloon angioplasty for isolated penile artery stenoses in patients with erectile dysfunction in this first-in-man study. Obstructive pelvic arterial lesions are highly prevalent in patients with erectile dysfunction and commonly located in penile artery segments, Wang and colleagues write. The researchers enrolled 25 patients with erectile dysfunction and isolated penile artery stenoses (unilateral stenosis 70% or bilateral stenoses 50%) as identified by pelvic computed tomographic angiography. From these, 20 patients (mean age 61 years [range, years]) underwent balloon angioplasty. Three of these patients had bilateral penile artery stenoses, Wang told delegates at EuroPCR. Wang and colleagues achieved procedural success in all 23 penile arteries, with an average balloon size of 1.6mm (range, mm). The average International Index for Erectile Function-5 (IIEF-5) score improved from 10.0±5.2 at baseline to 15.2±6.7 (p<0.001) at one month and 15.2±6.3 (p<0.001) at six months. Clinical success (change in the IIEF- 5 score 4 or normalisation of erectile function [IIEF-5 22]) was achieved in 15 (75%), 13 (65%), and 12 (60%) patients at one, three, and six months, respectively. There were no adverse events through follow-up. An accompanying editorial in EuroIntervention by Jason H Rogers, University of Califorina, Davis Medical Centre, Tzung-Dau Wang Sacramento, USA, notes: Erectile dysfunction is a complex, multifactorial psycho-physical condition. For interventionalists, it is tempting to look at an angiographic stenosis in an erectile-related artery in a patient with erectile dysfunction and attribute a cause-effect relationship. Rogers also writes that the results of the study from Taiwan had shown modest response to intervention as measured by IIEF-5 that could be explained by the placebo effect. Eighty five per cent of patients at six months still had an IIEF score of <22, which continues to meet the definition for some degree of erectile dysfunction. Longer term clinical follow-up will be required. Without any objective assessment of penile arterial inflow or imaging follow-up, it is not possible to describe what physiologic effect was achieved by performing angioplasty. Given the excitement to find an interventional solution for such a common clinical condition as erectile dysfunction, carefully controlled studies are required, he writes. Arterial embolization works to alleviate knee pain in mild to moderate osteoarthritis Continued from page 1 rial embolization as an alternative treatment for osteoarthritis-related knee pain. The patients then provided written informed consent to the procedure. The investigators included patients who had moderate to severe medial knee pain (visual analog scale [VAS] >50mm) resistant to at least three months of conservative therapies (antiinflammatory drugs, physical therapy, muscle strengthening, and intra-articular injection of hyaluronic acid). All patients were assessed by routine radiographs, and those with severe osteoarthritis changes (Kellgren Lawrence grade three or higher) were excluded because they were candidates for total knee arthroplasty. They excluded patients on the basis of local infection, malignancy, advanced atherosclerosis, rheumatoid arthritis, and prior knee surgery. Amine Korchi, Department of Diagnostic and Interventional Radiology, Geneva University Hospitals, Switzerland, a member of the research team, told Interventional News: Endovascular embolization of the musculoskeletal system is somehow limited compared to other fields of interventional radiology, and is mainly performed for bleeding in the context of trauma or after joint arthroplasty, for soft tissue vascular malformations and for pre-operative devascularisation of tumours. This study unveils a new and unconventional endovascular approach to treat resistant pain from knee osteoarthritis in a minimally invasive fashion. The results of this study at one year are encouraging, and this novel interventional radiology procedure seems promising. However, further larger and high quality trials are warranted to validate our findings and to depict the efficacy, safety and complication profiles of this procedure on a larger scale. Moreover, many interesting areas of research could arise from our study, such as the potential role of angio-mri in the detection of abnormal neovessels and thus in the selection of candidates for embolization, and also its role in the evaluation of outcomes. It could be also interesting to study the effect of embolic agent s size and type on clinical outcomes and occurrence of complications such as non-target embolization. Osteoarthritis is a common and major cause of pain and disability, and it is very exciting to see interventional radiologists stepping into this field, thinking outside the box and advancing research and knowledge. The researchers used imipenem/cilastatin sodium (in 11 patients) or 75µm calibrated Embozene microspheres (in three patients) as embolic agents. Imipenem/cilastatin sodium is approved as an antibiotic, is slightly soluble in water, and, when suspended in contrast agent, forms 10 70µm particles that exert an embolic effect, the researchers wrote. The embolic effect of Imipenem/cilastatin sodium is temporary and the inflammatory reaction is unknown. The mean volumes used in the study was a 2.5 ml/5ml suspension. The particle size of Embozene was calibrated at 75µm, its embolic effect is longer-term and inflammatory reaction low. The mean volume used in the study was ml/2 ml particle volume. The investigators then assessed adverse events and changes in Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores. Okuno and colleagues identified abnormal neovessels within soft tissue surrounding knee joint using arteriography. There were no major adverse events related to the procedures and transcatheter arterial embolization rapidly improved WOMAC pain scores from 12.2±1.9 to 3.3±2.1 at one month after the procedure, with further improvement seen at four months (1.7±2.2). WOMAC total scores changed from 47.3±5.8 to 11.6±5.4 at one month, and dropped further to 6.3±6 at four months. These improvements were maintained in most cases at the final follow-up examination at a mean of 12±5 months (range 4 19 months). NEWS IN BRIEF Charing Cross Symposium announces open call for abstracts and posters Following its successful inaugural abstract session in 2014, the Charing Cross Symposium has announced an open call for its abstract sessions, which run parallel to the main programme at the symposium (28 April 1 May 2015, London, UK). Senior and junior doctors are invited to submit an abstract or poster online to be considered for the CX Open Abstract Session. Abstract and poster submissions are invited in the following areas: carotid, aortic arch, thoracic aortic, juxta-renal aortic, abdominal aortic, peripheral, venous, vascular access and vascular imaging. The deadline for submission is 17 October Please visit to read the submission guidelines or submit your abstract. Abstracts or posters will be selected by the CX Programme Organising Board, and the authors of abstracts selected for presentation and authors of posters selected to be displayed at the congress will be notified by 1 December The registration fee will be waived only for junior doctors whose abstract/poster is accepted. Multinational CIRT registry to help assess SIR-Spheres therapy The CIRSE Registry for SIR-Spheres Therapy (CIRT) is a Europewide registry that aims to prospectively collect data on SIR-Spheres therapies. CIRSE notes that several medical centres use this therapy to treat liver tumours. While studies with small numbers of patients have shown that this treatment can have a benefit, the registry aims to investigate the safety, clinical outcome, and technical success of SIR-spheres on a much larger, multinational scale. The registry aims to assess the safety, clinical outcome, and technical success of the use of SIR-Spheres in the treatment of patients with primary and secondary liver tumours. CIRT will collect data prospectively from various medical centres in Europe that perform SIR-Spheres therapy and an announcement by CIRSE states that recruiting will start this year.

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6 6 Radiation protection Many interventionists take too many digital subtraction angiograms Interventional News spoke to two experts on the issue of radiation protection. James B Spies, chair and chief of service, Department of Radiology, Medstar Georgetown University Hospital, Washington, DC, USA, and president of the Society of Interventional Radiology (SIR) and Werner Jaschke, professor and director of the University Clinic for Radiology, Medical University of Innsbruck, Austria, and chairperson of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) Radiation Protection Subcommittee both emphasised that it is important for interventionists to practice radiation hygiene in a manner that is exemplary to others in order to create a safe radiation environment for both the patient and the staff How should leaders motivate the whole team to make radiation protection a priority? JS: Leaders should communicate and then re-communicate how important it is to maximise patient and staff safety, and that radiation hygiene is an important component of these efforts. Most nurses and technologists are dedicated to ensuring patient safety and will respond readily to the leadership of an informed interventional radiologist who is dedicated to radiation safety. The interventional radiologist should model the way and make radiation safety a point of discussion during every procedure. Creation of a radiation safety programme can begin with an in-service to remind everyone of the potential dangers of radiation, the simple steps to minimise radiation exposure to patients and staff, the need to avoid patient injury, and the desire of operators to be notified by the staff when certain dose thresholds are reached during procedures. To initiate such a programme should not be difficult unless the interventional radiologist reacts negatively to these dose threshold notifications. The interventional radiologists must realise that they set the tone in the procedural suite. WJ: Dose management is the way to go. You have to provide real-time data on applied doses and set up professional standards for procedures in order to promote radiation protection issues. In addition, you have to raise awareness of life-time risks of radiation exposure, such as radiationinduced cataracts. Sometimes adhering to the ALARA (As Low As Reasonably Achievable) principle conflicts directly with the desire of the operator to achieve and document a result. What is your advice? JS: In all cases, optimisation of image quality while minimising radiation dose should be the standard. Use of pulse fluoroscopy, minimising frame rates and duration of image acquisition during digital subtraction angiograms with attention towards the positioning of the image intensifier, and only including areas of relevance during image acquisition are the basic operational principles when using fluoroscopy and obtaining digital subtraction angiograms. Having an understanding of the principles that govern image quality and radiation dose exposure provides operators the foundation for employment of good radiation hygiene and should guide practice patterns during the process of achieving and documenting a satisfactory result. However, despite use of best practices, some procedures are associated with use James B Spies of higher radiation dose. These cases often involve technically challenging procedures or a difficult patient setting (patient with a large body mass index or with external fixation devices). Skin injury is the biggest short-term concern with radiation exposure and the SIR has set dose thresholds in an effort to provide guidance to minimise that risk. If a prolonged or difficult procedure results in a dose approaching those limits, it may be best to stop the procedure to avoid any potential radiation-induced injury. Reassessment of the risk-benefit ratio for the procedure and the need to reschedule a second attempt for the procedure for a later date is often prudent. Often, during a difficult procedure or during a repeat attempt, engagement of another colleague, especially one with more experience, may prove beneficial in achieving success. The only thing worse than failing to complete a procedure is failing and injuring the patient in the process. One of the hardest things for new interventional radiologists to learn is when a procedure is not likely to succeed and knowing when to stop a procedure. WJ: ALARA rarely interferes with real-life situations. If you want to perform a procedure safely and as quickly as possible, you do sometimes need the best quality image, even if this involves a higher radiation dose. Remember: radiation exposure correlates not only with tube output, but also with the duration of fluoroscopy. In addition, new technical developments have lowered doses and kept image quality high. The noise level of a flat-panel angiographic system is dramatically lower compared to an image intensifier-based angiographic system. Thus, very often we do not have to compromise on image quality. The best radiation protection, in my opinion, is when a skilled and experienced operator uses state-of-the-art equipment for a well-planned and medically indicated interventional treatment. Do you recall a powerful message on the dangers of radiation that you have heard? Werner Jaschke WJ: The threshold for the yearly exposure to the eyes of staff/patients has been lowered by public bodies to prevent radiationinduced cataracts. This clearly indicates that it is a concern worthy of our attention. JS: It is important to review the several published papers on the dangers of skin injury with fluoroscopic exposure. Demonstrating the pictures associated with these injuries should also be part of the in-servicing process. If such an incident has occurred at one s institution, a transparent quality assurance review should be undertaken and a learning exchange should occur between operators and staff. What practical information on radiation protection would you like to share? JS: There are three basic principles that come to mind. First, many interventionists take too many digital subtraction angiograms. These images should be limited to those that are needed for an accurate diagnosis, to guide therapy and to document a result. The frame rate during image acquisition, the positioning of the image intensifier, and the duration of image acquisition should be tailored to limit the radiation exposure. However, inadequate demonstration of the needed information may create a situation in which a repeat procedure becomes necessary. Therefore, the operator should understand the question being asked, and have the experience and knowledge of the anatomy being interrogated and what images are needed and why they are needed. Second, collimate the fluoroscopic images and place the image intensifier as close to the patient as possible. It is surprising how often anatomy irrelevant to the question being asked is included in the acquired images and the image intensifier positioned more than several inches above the patient, both resulting in unnecessary radiation exposure to the patient and staff and less than optimum images. Not only does collimation and optimising the subject to image intensifier distance reduce unneeded exposure, it has the added benefit of reducing scatter and improving the image quality. Third, reduce the fluoroscopic frame (pulse) rate. A frame rate of 30 frames per second (which is effectively cine fluoroscopy) is almost never needed. In many cases, use of 7.5 frames (pulses) per second during fluoroscopy is sufficient to guide treatment. If the area of interest is stationary or relatively free of movement, an even slower frame rate can be used. There are other basic principles of the safe use of image guidance, but these three are not always used by inexperienced interventionists and taken together, can dramatically reduce radiation exposure to the patient and staff. WJ: Do you see the risk? is the CIRSE slogan to promote awareness of radiation protection among members and the public. The risks of radiation can be successfully managed, as radiation can be easily measured and protective equipment is efficient. As pointed out above: keep fluoroscopy time short; and use state-of-the-art equipment and shielding. Initiatives from the societies In the Radiation Protection Pavilion at CIRSE s annual meeting in Glasgow, you will discover tips and tricks that address all three aspects of radiation protection. The best way to keep exposure as low as possible is: to carefully plan the procedure; to optimise the angiographic system by choosing imaging parameters best-suited for the procedure; and to adjust the shielding to reflect the operator s position during the procedure. For more information on the Radiation Protection Pavilion, please visit The Society of Interventional Radiology (SIR) has a long-term commitment to radiation safety and has taken a key role in measuring and assessing radiation dosage, developing educational programmes on radiation safety, radiation protection and reduction of skin dosage and promoting the safety of patients and healthcare professionals. Ongoing monitoring programmes are now a part of many interventional sections. In many radiology departments, radiation dose exposures that exceed SIR standards trigger a process for follow-up evaluation of the case, and an incident report is generated so that a further review can be conducted.

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8 8 Drug-eluting balloons Not all drug-eluting balloons are the same COMMENT & ANALYSIS Thomas Zeller, Bad Krozingen, Germany, analyses the results of two recent randomised controlled trials comparing drug-eluting balloons to angioplasty alone in femoropopliteal lesions Following successful first-in-man trials (THUNDER, FEMPAC) using the Paccocath/Cotavance coating technology (Bayer, iopromide & 3µg/m2 paclitaxel) two recently presented major pivotal trials confirmed the safety and efficacy of paclitaxel-eluting balloons in the endovascular treatment of femoropopliteal arterial disease. The IN.PACT SFA I & II trials using the IN.PACT Admiral device (Medtronic, urea & 3µg/m2 paclitaxel) enrolled overall 331 patients at 57 sites across Europe and the USA in a 2:1 randomisation scheme as well as the LEVANT 2 trial including 476 patients who had been treated with the Lutonix 35 balloon (Bard-Lutonix, polysorbate/sorbitol & 2µg/m2 paclitaxel). THOMAS ZELLER The pooled randomised multicentre IN.PACT SFA I & II trials revealed that clinically-driven target lesion revascularisation rates were significantly lower with the drug-eluting balloon as compared to those achieved with angioplasty (2.4% vs. 20.6%, p<0.001). Similarly, the primary patency rate achieved with IN.PACT Admiral was 82.2%, while the primary patency achieved with angioplasty was 52.45% (p<0.001). Primary patency at 360 days calculated by Kaplan-Meier survival estimates was 89.8% for the drug-eluting balloon group and 66.8% for the angioplasty group. In the LEVANT 2 trial, the primary patency at 12 months defined as freedom from both restenosis and target lesion revascularisation was 65.2% for the drug-eluting balloon which was superior to control angioplasty (52.6%, p=0.015) demonstrating superior efficacy. At 12 months, the freedom from clinicallydriven target lesion revascularisation in the Lutonix group was 87.7% compared to 83.2% in the control group (p=0.208). In both studies no device specific sideeffects were reported, no major amputation occurred. Thus, there was no safety concern regarding wash off of a part of the antiproliferative drug into the distal vasculature. Are both of the studies comparable? In brief, both studies enrolled only claudicants with femoropopliteal lesions. Lesions in the LEVANT 2 trial were slightly less challenging as compared to the IN.PACT SFA trial regarding mean lesion length (63mm vs. 89mm) and total occlusions (21% vs. 25.8%), and unlike prior femoropopliteal premarket approval studies, bailout stenting was not counted as a failure. Interestingly, the outcome of the control cohorts is almost identical regarding primary patency (52.6% in LEVANT 2 vs % in IN.PACT SFA) and freedom from target lesion revascularisation (83.2% vs. 79.4%). Thus, blinding for the treatment, as it was part of the LEVANT 2 protocol but not of the IN.PACT SFA protocol, did obviously not impact the trial outcome; blinding of the duplex physician or technician regarding the treatment modality which the patient received does hardly impact a decision regarding a reintervention in a non-invasive follow-up setting. Opposite to an invasive angiographic follow-up, where it is much more likely that the knowledge of the treatment modality might impact the decision for an ad-hoc target lesion revascularisation, the indication for a reintervention following a non-invasive diagnostic examination is most likely based on the patient s clinical symptoms. Thus, the differences in drug-eluting balloon performance regarding primary patency and freedom from clinically-driven target lesion revascularisation seem therefore to attribute to the different coating technologies. Already preclinical animal studies have shown that not each coating technique is equally effective. However, only a direct clinical comparison of both drug-eluting technologies could finally answer this question. The major message of the both peripheral interventional landmark trials is that a balloon based treatment approach for TASC II A & B femoropopliteal lesions achieves good clinical one-year outcomes regarding freedom from clinical-driven target lesion revascularisation which is the outcome patient and payers are mainly interested in. Of note, not every drugeluting balloon is alike; each single device deserves its own clinical efficacy and safety studies. Thomas Zeller is head, Department of Angiology at Universitäts Herzzentrum Freiburg-Bad Krozingen, Bad Krozingen, Germany Drug-eluting balloons closer to approval in the USA, new player debuts in Europe After the unanimous vote from the FDA Circulatory System Devices Advisory Panel in favour of approval for the Lutonix drug-eluting balloon (Bard), drug-eluting balloons are now closer to becoming available for the treatment of femoropopliteal artery disease in the USA. Medtronic, whose device has been available in Europe since 2009, anticipates an early 2016 US approval for its IN.PACT Admiral. Boston Scientific has recently launched the Ranger drug-eluting balloon in CE-mark countries Data from the LEVANT 2 trial comparing the Lutonix drug-eluting balloon with angioplasty alone in the treatment of peripheral arterial disease show that the primary endpoints of both safety and efficacy were met and superior efficacy and non-inferior safety of Lutonix compared to control angioplasty were demonstrated. Bard submitted the one-year results of LEVANT 2 study to the FDA advisory panel and on 12 June, the panel voted unanimously to recommend the approval of the device in the USA. The results of the LEVANT 2 trial have been submitted for publication in a peer-reviewed journal. In the LEVANT 2 trial, the primary efficacy endpoint for the Lutonix drug-eluting balloon was primary patency at 12 months defined as freedom from both restenosis and target lesion revascularisation. Primary patency for Lutonix was 65.2% which was superior to control angioplasty (52.6%, p=0.015) demonstrating superior efficacy. At six months, the primary patency rate was 92.3% for the drug-eluting balloon vs. 82.7% for angioplasty alone (p=0.003). The primary safety endpoint for Lutonix was freedom from perioperative death and 12-month index limb amputation (above and below the ankle), index limb re-intervention and index-limb related death. The primary safety endpoint rate for Lutonix (83.9%) was non-inferior to control angioplasty (79%, p=0.005). At six months, the rates were similar (94% vs. 94.1%). At 12 months, the freedom from target lesion revascularisation in the Lutonix group was 87.7% compared to 83.2% in the control group (p=0.208). Unlike prior femoropopliteal premarket approval studies, bailout stenting was not counted as a failure; a post-hoc analysis with procedural stenting counted as a target lesion revascularisation was conducted, and a higher freedom from target lesion revascularisation rate for Lutonix (85.3%) compared to control angioplasty (76.4%, p=0.017) was observed at 12 months. In a press release, Bard said that LEVANT 2 was designed to reduce bias in the results in order to accurately and scientifically assess and compare the long-term performance of key clinical measures. Two key aspects of the study design differentiate this trial from other recent superficial femoral artery studies. First, unlike some other trials, the LEVANT 2 clinical trial did not count bailout stenting as a primary patency or target lesion revascularisation failure. Second, to reduce the potential introduction of bias into the subjective clinical decision for revascularisation, the protocol required the clinical assessment to be performed by a physician who was blinded to the treatment group and the doppler patency measurement, the press release clarifies, the company stated. IN.PACT Admiral In June, Medtronic announced that it submitted the final module of its pre-market approval application for the In.pact Admiral device to the FDA. The application included data that demonstrated superior clinical outcomes compared with conventional angioplasty, with the lowest rates of repeat procedures (target lesion revascularisation) and the highest rate of uninterrupted blood flow (primary patency) at 12 months ever reported for the interventional treatment of peripheral artery disease. In April 2014, Medtronic released at the Charing Cross Symposium the one-year results of the IN.PACT SFA trial. In the study, the IN.PACT Admiral drug-eluting balloon was significantly superior to angioplasty. The primary patency rate achieve with the drug-eluting balloon was 82.2% and for angioplasty it was 52.45% (p<0.001). Freedom from clinically driven target lesion revascularisation was 97.6% with the drug-eluting balloon Continued on page 11

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10 10 Intravascular robotics We are exploring the scope of robotic catheterisation Barry T Katzen, founder and medical director of Miami Cardiac & Vascular Institute, Florida, USA, tells Interventional News that his team and other practitioners are gathering data on their early experience with intravascular robotics and trying to establish where in the workflow it offers the most benefit. Katzen urges other interventional radiologists or the best catheter jockeys out there to get involved and help evaluate the technology Could you provide some perspective on the use of intravascular robotics? We have been exploring the application of robotic catheterisation to identify clinical benefit to patients as a result of the technology. We are at the early stages of evaluation to understand which cases it might bring advantage to, and as a result we have used it in a very diverse group of clinical applications from renal embolization to carotid stenting to complex EVAR. Right now, we are exploring the scope of where robotic catheterisation can bring value. What are the most important benefits of using robotic navigation in interventional radiology procedures? There are several potential benefits, one of which is a less traumatic navigation through the circulatory system. Because of the robotic catheter s ability to be more centrally located and be less dependent on sliding against the side wall of a vessel, which is the way traditional way manual catheterisation works, there may be some clinical benefit there, although this might be difficult to prove. Saying that, in early animal work, there seems to be evidence that robotic catheterisation is actually less traumatic than manual catheterisation. The other important areas of potential benefit are reduction of radiation exposure for both the operator and the patient. One of the areas that we are currently exploring is in left to right crossover catheterisation in the iliac arteries. For example, if we have a patient who needs an embolization of a right hypogastric artery. Ordinarily, we would approach this with a catheter from the left groin going over to the right side. The operator would be working very close to the pelvis with a lot of scatter radiation, and frequently working with fingers and hands across the field. The use of a robotic catheter actually positions us away from the image intensifier, with significant dose reduction to the operator. If the catheterisation can be done more efficiently, then there is a potential dose reduction for the patient as well as for all the allied co-workers in the room, because people can stand back and away from the patient who is the big source of the X-ray scatter. For instance, we are evaluating use of the technology in endovascular aortic aneurysm repair (EVAR). If we can introduce the robotic catheter into the workflow so that we can reduce the number of catheter and wire exchanges, so that it can be all done with one device, then there can be a significant dose reduction to the patient as well. So the major potential benefits, I would say, are less trauma to the vessels, dose reduction to both patient and operator and possible increased chances of success in carrying out the procedure. For instance, with carotid stenting, if you place a sheath in the left common carotid artery, you would have to use a diagnostic catheter, a guidewire (may be one or two of those), make some exchanges and then although we wind up with a 6Fr sheath in the carotid artery for the carotid stent, with a robotic catheter you can do it all with one device, no catheter changes, put the stent in and then if you needed to go over to the other side you could do the same thing, all with the same device. Which procedures have you performed using robotic catheterisation? Where do you see the potential benefit? Barry T Katzen We have a very diverse group of procedures in which we are evaluating the value of robotic catheterisation including fenestrated EVAR and also conventional EVAR. In conventional EVAR, for instance, when we put the robotic catheter on first instead of a pig-tail catheter to be able to identify the renals for precise localisation. Instead, with a robotic catheter we can just direct it at the lowest renal artery with very small hand adjustments with 2 or 3cc of contrast during deployment, sparing the need for high volume and high flow injections of contrast. Once the body of the endograft is deployed, we can then use the same robotic catheter, bring it down and catheterise the contralateral gate, all with the same device. So introducing the robotic catheter early in the workflow seems to have more value. In other words, I do not think that using it to just catheterise the contralateral gate has a huge amount of value. To reiterate, introducing the robotic catheter early in the workflow seems to have more value. The other area that we have seen value for these catheters is in embolization procedures. We have used it in a variety of embolization procedures including contralateral hypogastric arteries, and renal artery aneuryms and renal embolization for renal tumour ablation. Additionally we have utilised the robotic system for carotid interventions. What are the limitations of robotic systems? I think the key limitations are the size of the device and cost. The company (Hansen Medical) has recently received USA FDA approval for the 6F device (catheter) which is shapeable. We have had some initial experience with the 6F catheter which offers a reduced size and the ability to do robotic assisted microcatheter procedures. The other aspect is cost, as investing in intravascular robotics represents a significant capital investment. It is not a device that you can do the entire procedure with (with the exception of carotid stenting and embolization, in which you can) using the robotic catheter and delivery system and those limitations would have to be addressed. What is the evidence to show that robotic catheterisation has any benefit? The value conferred by a procedure is defined as a combination of clinical benefit and financial cost. At this stage, we do not have a lot of evidence and are trying to accumulate data. There are two studies that are ongoing; one is the Rover Registry that is trying to capture all of the data related to all of the applications in which this device is being used. The question of whether it is a workhorse device or a unique application device remains to be proven. The one thing I can say anecdotally, on initial experience, is that there definitely have been patients in whom the robotic catheter has made possible things that would have been extremely difficult, or impossible with manual catheterisation techniques. However, being able to identify which patients would benefit most requires more data. We are working with other users to identify where the clinical benefit is and how is it measured. This may be technology that will help people who have lesser interventional skills or experience to carry out better catheterisations, but that remains to be proven. Interventional radiologists, the most skilled catheter jockeys in the world, need to evaluate and assess this technology in order to see if there is any meaningful value it can bring. Robot-assisted uterine artery embolization is feasible and safe, study finds A study published online ahead of print in July in the Journal of Vascular and Interventional Radiology (JVIR) provides a technical description of robot-assisted uterine artery embolization and investigates the safety and feasibility of using the Magellan system (Hansen Medical) robotic catheter in the uterus The study was a first-inwoman safety evaluation of the Magellan system in which five women, with a mean age of nearly 50 years, underwent robot-assisted bilateral uterine artery embolization over a 10-month period using the Magellan robotic catheter. Researchers Mohamad S Hamady and colleagues, Imperial College, London, UK, recorded demographic, clinicopathologic, and endovascular Uterine artery embolization performance metric data (fluoroscopy and cannulation times) associated with the procedure and short-term outcomes, after the procedure. The researchers found that robotic cannulation of bilateral internal iliac and uterine arteries was successful in all cases. Median right and left internal iliac artery cannulation and total fluoroscopy times were three minutes, two minutes, and 11 minutes. Median right and left uterine artery cannulation times were both 11 minutes. Hamady and colleagues report that technical success was 100% and that all patients were discharged on postoperative day one. There were no major or access site complications. Six months after the procedure, all patients reported significant improvement of symptoms, with a median increase in health-related quality-of-life score of 58%, the authors reported. Hamady told Interventional News: This safety and feasibility study shows the developing capabilities of robotic endovascular technology. It opens the door for further development in robot-assisted vascular intervention and sets the scene for more precise and efficient cannulation of complex arterial beds.

11 Drug-eluting balloons 11 Drug-eluting balloons closer to approval in the USA, new player debuts in Europe Continued from page 8 and 79.4% with angioplasty (p<0.001). This exciting milestone keeps us on track for FDA approval of the In.Pact Admiral drug-coated balloon in the USA in early FY16, said Tony Semedo, president of Medtronic s endovascular therapies business. The introduction of drug-coated balloons in the USA for the treatment of peripheral artery disease in the superficial femoral artery is highly anticipated as a new standard of care for this difficult to treat condition, especially due to the consistently strong clinical data we ve witnessed with In.Pact Admiral, says John Laird, co-principal investigator of IN.PACT SFA, and interventional cardiologist, UC Davis Medical Center, California, USA. The IN.PACT Admiral clinical programme has raised the bar for the industry, and may reduce the need for traditional interventions as first-line treatment, such as metal stents, which are not ideally suited for this dynamic artery. The In.Pact Admiral drug-coated balloon received the CE mark in 2009 but remains an investigational medical device in the USA. Stellarex Covidien s Stellarex drug-coated angioplasty balloon continues to be shown as safe and effective for treatment of peripheral arterial disease, according to new 24-month data released from the company s ILLUMENATE first-in-human study. The first-inhuman study results were reported at the EuroPCR congress (20 23 May, Paris, France). The ILLUMENATE first-in-human study is a prospective, multicentre, single arm study designed to assess the safety and effectiveness of the Stellarex drug-coated balloon. In the study, 58 superficial femoral and/or popliteal lesions in 50 patients were pre-dilated with an uncoated angioplasty balloon, followed by treatment with the Stellarex drug-coated balloon. When used to treat lesions in leg arteries, the Stellarex drug-coated balloon is intended to open narrowed or occluded vessels to restore blood flow and simultaneously deliver paclitaxel, the drug used in the balloon coating, to the vessel wall. This helps prevent restenosis after the artery has been treated. The study found the Stellarex drug-coated balloon to be safe, with durable results to 24 months, including: Primary patency (defined as the treated artery remaining open without further treatment required or renewed blockage detected by ultrasound scanning) was 82.3% at 24 months. Freedom from clinically-driven target lesion revascularisation at 24 months was 87.9%. This is the same rate observed at 12 months; no new events were reported demonstrating a sustained low rate of repeat treatment out to 24 months. No amputations or cardiovascular deaths We are very pleased with the study s promising results, as they support the use of an important emerging treatment for a painful and physically limiting condition that affects millions of people around the world, says Henrik Schröder, radiologist, Vascular Center-Jewish Hospital, Berlin, Germany, and principal investigator, ILLUMENATE FIH study. Good patency after two years, which translated into the absence of new clinically-driven target lesion revascularisations after one year and through the second year patient follow-up, demonstrates the durability of the Stellarex drug-coated angioplasty balloon. Ranger gets the CE mark Boston Scientific has received the CE mark for the Ranger Paclitaxel-Coated PTA Balloon Catheter. The Ranger Drug-Coated Balloon offers tremendous promise and will provide another important tool to treat both above-the-knee and below-the-knee lesions, said Dierk Scheinert, director, Center of Vascular Medicine, Angiology and Vascular Surgery at Park Krankenhaus, Leipzig, Germany. When using contemporary technologies, a significant amount of drug coating can be lost during the handling, insertion and delivery of the device. I am excited by the technology in the Ranger drug-coated balloon, which has the potential to reduce drug loss significantly while optimising both deliverability and the absorption of the drug in the targeted tissue. The Ranger DCB combines the deliverability of the market-leading Sterling balloon platform and the proven drug Paclitaxel with advanced technologies designed to address the delicate and often unstable nature of the coating associated with contemporary drug-coated balloons. The Ranger DCB features proprietary TransPax coating technology and an innovative loading tool designed to maintain drug-coating integrity and maximise drug-transfer efficiency resulting in consistent and predictable drug delivery.

12 12 Future of interventional oncology Lencioni issues a political call to arms for IO to actively seek recognition outside the interventional world At the 2014 European Conference on Interventional Oncology (ECIO, April, Berlin, Germany) Riccardo Lencioni, professor and director, Diagnostic Imaging and Intervention, University of Pisa School of Medicine, Pisa, Italy, who delivered the Honorary Lecture, summoned interventional oncologists to spread the word about what interventional oncology could offer and to build research data for the larger oncological world. After outlining the dramatic strides made by interventional oncology and pointing to the trials that will yield key evidence by 2020, he noted that there is still a lot of work to be done, as quite often, in the world of medical and surgical oncology, the discipline does not even have a seat at the multidisciplinary table In a lecture titled Twenty years of interventional oncology and future trends for 2020, Lencioni first outlined the vast leaps that interventional oncology had made since the 1990s when the discipline consisted of two homemade procedures: transarterial chemoembolization (TACE) and ethanol injection, one clinical application, hepatocellular carcinoma, and very little acceptance, if any, in the oncological world. He drew attention to the famous paper that appeared in the New England Journal of Medicine in 1995, that used questionable statistical assumptions to quickly discard the value of lipiodol chemoembolization in the treatment of hepatocellular carcinoma by stating that it often caused liver failure and did not significantly improve survival compared to no treatment at all. This sounded like a death sentence for TACE, but in reality the clinical practice was telling a different story, Lencioni said. He pointed out that some of his early research focused on analysing the prognostic factors for patients with hepatocellular carcinoma, those ineligible for surgery, who were treated with ethanol injection and that patients were offered intervention as a last resort. We gained knowledge from treating patients and understanding the disease and this knowledge was a key step in the development of a new chapter of interventional radiology. Then in the 2000s, interventional oncology was ready for randomised controlled trials such as the milestone TACE vs control (best supportive care) for unresectable hepatocellular carcinoma. With more experience, interventional oncology was ready to run randomised controlled trials with much more appropriate study design and better patient selection. In 2002, two landmark studies from Barcelona Riccardo Lencioni By 2003, trial results regarding TACE and radiofrequency ablation were sufficiently convincing for interventional oncology to be incorporated into clinical practice guidelines on hepatocellular carcinoma and Hong Kong, showed that chemoembolization was associated with better survival as compared to best supportive care, therefore establishing TACE as a valuable tool in the treatment armamentarium. By 2003, trial results regarding TACE and radiofrequency ablation were sufficiently convincing for interventional oncology to be incorporated into clinical practice guidelines on hepatocellular carcinoma. There was also a rapid evolution in interventional oncology with novel techniques and solutions becoming available so that the discipline began to look further afield than in the treatment of liver cancer. Today, interventional oncology has a variety of agents, energies, embolics and approaches in its armamentarium including embolic drug-eluting beads, radioembolization, heat-activated drugs, microwave ablation, tumour cryoablation, focused ultrasound, bone consolidation, metabolism inhibition, radiofrequency ablation, light activated therapy, immunotherapy, nerve root blocks, chemical ablation, chemosaturation, oncolytic viruses, chemoembolization, ultrasoundmediated drug-delivery and more. It also has a number of new clinical applications. It is unfair to focus entirely on liver cancer; there are many other cancers and several other diseases that we treat, including early stage non-small cell lung cancer, lung metastases from colorectal cancer and kidney cancer (where image-guided thermal ablation is truly challenging the results of surgical nephrectomy with significantly less morbidity from the procedure). We have also seen the significant developments of drug-eluting beads that now offer an improved pharmacokinetic profile, standardised delivery and less toxicity to patients and the Y90 beads with radioembolization pushing the boundaries of interventional techniques beyond the previous limits. Radioembolization is succeeding in bridging patients to resection and transplantation. Other novel technologies such as irreversible electroporation have also put pancreatic cancer within the scope of interventional oncology techniques and some centres, working in the setting of research protocols are using irreversible electroporation as a means to, downstaging unresectable patients with pancreatic cancer to resection this means the prognosis of the patient is dramatically altered. Another very important chapter has been the paradigm shift towards looking for new drug-carriers, and in the search for synergies between locoregional and systemic therapies. While the end results have been disappointing for trials such as HEAT, SPACE and others, Lencioni pointed out that a nuanced look at the results shows that some combinations such as TACE with sorafenib, or radiofrequency ablation with ThermoDox, hold potential. Lencioni then pointed to the new wave of randomised controlled trials that are ongoing, that will aim to truly try and change the standard of care, by 2020, (Figure 1) but cautioned that recognition of such progress outside the interventional world remains limited. Continued on page 14

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14 14 Future of interventional oncology Lencioni issues a political call to arms for IO to actively seek recognition outside the interventional world Continued from page 12 Where do we stand in clinical applications outside of liver cancer? What is the level of recognition and acceptance that we truly have outside the interventional community in the medical and surgical oncology community? asked Lencioni. Using the example of hepatic metastases from colorectal cancer, Lencioni noted that this was a very common area for our clinical practice. He reported that papers such as his own recent 2014 Journal of Vascular and Interventional Radiology publication put forward a proposed algorithm for the clinical management of patients with liver metastases from colorectal cancer and showed that interventional oncology could offer options for treatment including ablation as an option for limited disease, when resection is not indicated. [in the paper] We also suggest that those patients with liver only or liver-dominant disease should be considered for locoregional therapy such as irinotecan-loaded drug-eluting beads (DEBIRI) or Y90, potentially to downstage these patients for resectability, or in combination with systemic therapy. We also know that oncologists have different algorithms and guidelines, so it was no surprise that a recent publication in the European Journal of Cancer (van de Velde CJH et al. 2014) has no mention at all of any interventional oncology therapy. Highlighting that this document was framed as a multidisciplinary management and European consensus document on colorectal cancer, Lencioni commented that in the 33 pages of this document there is no [mention] at all of drug-eluting beads or Y90. There is one line on radiofrequency ablation stating that it might be considered as an alternative to stereotactic body radiation therapy (SBRT) for unresectable liver metastases. I think this is frankly unfair for ablation given that the rate of local tumour control for ablation is much higher than the best reported rates for local tumour control with SBRT, and on top of that we do have five-year data for radiofrequency ablation in the setting of metastatic colorectal cancer. However, I use this to make a different point, [ie. that the voice of interventional oncology is not being heard at multidisciplinary proceedings], he said noting that the publication was based on the proceedings of the first multidisciplinary consensus conference about colon and rectum that was held in December 2012 looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in the care of cancer patients with colon and rectal cancer and representatives of national colorectal registries including surgical oncologists, radiation oncologists, medical oncologists, pathologists, coloproctologists, diagnostic radiologists, nurses and patients everybody but us. We do not even have a seat at the table and frankly as a delegate for interventional radiology to the oncology community, I have to say that this is unfair, Lencioni stated. We should have a seat at the table and we should be able to come to a consensus that is truly multidisciplinary, he added. Time for action Lencioni hastened to tell delegates that he was not bringing up the publication where no mention of any interventional oncology therapies except a passing reference to radiofrequency ablation was made, to complain. I am showing this to illustrate that there still a lot of work to do. It is time for action in your hospital and in the tumour boards to show your referring physicians, your colleagues, your patients what interventional oncology can offer. It is time for action in research that produces more data, registries, and trials. We need to truly make an effort to get more recognition. It is time to do this, especially as there is an ongoing discussion in oncology on how to move the research forward in the area of clinical oncology. Lencioni pointed to a recent American Society of Clinical Oncology (ASCO) special article in the Journal of Clinical Oncology that has called for raising the bar for clinical trials, by defining clinically meaningful outcomes for common cancers. The paper describes the search for therapies that can combine an improvement in survival while at the same time maintaining the quality of life for patients; so there is a shift away from treatments that provide a marginal survival benefit at the price of major deteriortion in the quality of life. This is us this is what we do; it is minimally invasive interventional oncology and we should use this window of opportunity to produce more data. So this is a call to arms to you interventional oncologists to use these definitions to push all scientific organisations, working groups, funding sources and companies to move forward and produce the same effort as is currently ongoing in hepatocellular carcinoma. Let us fix the date, 2020, to truly establish interventional oncology as the fourth pillar of cancer care, he said.

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16 16 Interventional oncology My take on locoregional therapies for treatment of neuroendocrine tumours COMMENT & ANALYSIS Locoregional therapies in neuroendocrine tumours have been definitively incorporated as treatment options in non-surgical patients with progressive disease or symptoms refractory to medical treatment in many institutions. The best results are obtained in patients with liver neuroendocrine tumours from gastrointestinal origin, with less than 60% liver involvement and good clinical status (ECOG 0 1), writes Ricardo Garcia-Monaco Neuroendocrine tumours are rare neoplasms characterised by slow progression and an indolent biology. However, about 40% of patients with such tumours will develop metastasis during the course of their disease, mostly to the liver. The fiveyear mortality rate is as high as 80% in untreated patients with liver metastasis. Various locoregional therapies may be used in patients with liver metastasis from neuroendocrine tumours: ablation (using radiofrequenc or, microwave), transarterial embolization (TAE) or chemoembolization (TACE), and selective internal radiation therapy (SIRT) also called radioembolization. The main indications of locoregional therapies are non-surgical patients with progressive liver disease or refractory symptoms despite medical treatment (octreotide) and no contraindication to therapy. The best results are obtained in patients with liver neuroendocrine tumours from gastrointestinal origin, with less than 60% liver involvement and good clinical status (ECOG 0 1). In patients with liver metastasis from pancreatic neuroendocrine tumours and high Ki 67 index and mitotic rates systemic therapy is usually preferred and locoregional therapies are reserved for selected cases. It is important to emphasise that commitment to oncology patient care and involvement in the multidisciplinary follow-up is a cornerstone key message. Pre-procedure management Clinical consultation should be incorporated as a necessary activity of the interventional oncologist. The patient should be informed about the goal of treatment, the adverse effects, the potential benefits and complications. Clinical work up includes physical examination and clinical history to look for symptoms of hormone secretion and to rule out co-morbidities that could be especially encountered in neuroendocrine tumours (cardiopathy, hypertension, etc). Baseline contrast enhanced liver CT RICARDO GARCIA-MONACO or MR and tumour markers (serum cromogranin levels and others depending on the tumour type) are necessary to evaluate the treatment response at follow up. Scintigraphy with Indium111 labeled octreotide is recommended to rule out the existence of extra hepatic disease. Cardiac, liver and renal function should be tested, especially in advanced disease because impaired function is a relative contraindication to a locoregional aggressive treatment. In addition to the standard rules of pre-procedure management for locoregional therapies of any type of liver metastasis, pre-medication with octreotide is helpful to prevent complications related to sudden hormone release during or immediately after treatment Ablation therapies Percutaneous radiofrequency or microwave ablation are seldom used as sole treatment in neuroendocrine tumours because most patients not amenable to surgical resection have multinodular liver disease. Ablative techniques may be used in association with intra-arterial therapies or more commonly as adjuntive to surgical resection in the operating theatre. Bland embolization and chemoembolization As liver metastases from neuroendocrine tumours are hypervascular, intraarterial therapies are especially appealing for palliative treatments intended to reduce tumour burden and achieve symptom control. Both bland embolization and chemoembolization produce tumour necrosis due to ischaemic changes and also as a consequence of cytotoxic drug activity in the latter. Although there are non-randomised controlled trials, there is some low-level evidence that the combination of embolization and cytotoxic drugs provide a higher rate and durability of response. The most commonly used regimen of TACE (mixture of doxorubicin, lipiodol and an embolic agent) has shown efficacy and safety since the late 80s, and is also known as conventional TACE. Microspheres with loaded cytotoxic agents (so-called drug-eluting beads) without the need of lipiodol infusion, has been recently used as a new regimen for TACE and is also known as DEB- TACE. Special features As patients usually have a long survival, many sessions of TACE are performed during lifetime since diagnosis. The repetition of TACE may result in endothelial damage and vasculitis leading to intra hepatic arterial thrombosis. Thus, interventional oncologists should be aware that supply of liver neuroendocrine tumours from extra hepatic vessels is rather common. Examination of the phrenic, mammary, epiploic, intercostal and other potential collaterals of arterial liver should be considered in patients with previous procedures, especially if segmental vessels are not clearly depicted or tumours are not totally visible at angiography. The hepatic arteries in patients with carcinoid tumours are hyper-reactive and more prone to vasospasm and dissection when performing selective catheterisation compared to other types of liver tumours. The interventional oncologist should be cautious with catheterisation to preserve free flow embolization. Sudden release of hormonal peptides after treatment may occur and lead to disturbing symptoms (hypotension, hypertension, bronchoconstriction, etc.) even in presumably non functional tumours. Post-embolization syndrome is possible as in other types of tumour but may have in addition specific symptoms related to catabolite release as a consequence of tumour necrosis Contraindications are similar to those reported for other liver tumours, but cardiac failure is a specific condition that should be ruled out in patients with long-term carcinoid symptoms. Patients with a history of radical pancreaticoduodenectomy to resect the primary neuroendocrine tumours have an increased risk of infection after bland or chemoembolization because of the bilioenteric anastomoses. DEB-TACE Preliminary reports of DEB-TACE in neuroendocrine tumours have shown high rates of tumour response and very low rates of systemic drug toxicity. However, imaging and laboratory tests have shown a high rate of liver infarction and bile duct injuries, although most are asymptomatic. The technique of DEB-TACE is rather different from conventional TACE, notably with regard to the embolization endpoint. A more conservative embolization endpoint (limited embolization, not complete stasis) and the delivery of a limited amount of drug-eluting beads are recommended to avoid peribiliary plexus occlusion and decrease the likelihood of bile duct injuries. It is also important to remember that in DEB-TACE (as different from conventional TACE), free flow embolization is a must and over embolization should be avoided in order to spare non-tumoural liver tissue. Radioembolization Preliminary reports of Y90 liver infusion have shown excellent patient tolerance and promising results in terms of response and disease control. Patients with separate small tumour burden and large volume of spare liver tissue are not good candidates for this procedure. Provided that correct patient selection and correct application techniqueis applied, treatment complications and serious side-effects are uncommon. Mild fatigue may be a side-effect but postembolization syndrome does not occur The procedure may be performed with local anaesthesia and as an outpatient procedure thus providing more patient comfort compared to TAE/TACE. Repeated sessions are uncommon and this is a distinguishing feature from TACE. Due to better patient tolerance and uncommon side-effects and complications, the treatment results in an improved quality of life when compared to other intra-arterial therapies Conclusions Ablative techniques are not used as common as intra-arterial therapies to treat neuroendocrine tumours, except as an adjunct to surgical resection procedures. Conventional TACE is the most widely used intra-arterial technique, although TAE and DEB-TACE are being used by several interventional oncologists. SIRT with Y90 has shown impressive preliminary results in terms of response, patient tolerance and quality of life and is increasingly used in many hospitals. However, there is neither high grade evidence nor rdata from randomised controlled trials to assess which the best type of locoregional therapy is. The choice of a given technique is usually based on imaging findings, patient selection and also on available local expertise and experience. Locoregional therapies offer a high objective response rate (symptomatic, humoral, morphological) and disease control with a satisfactory durability of the response. Ricardo Garcia-Monaco is chairman and professor of Radiology, head of Vascular and Interventional Radiology, Hospital Italiano, University of Buenos Aires, Buenos Aires, Argentina. He has reported no disclosures pertinent to the article

17 Ablation Which primary lung cancer patients should receive which type of ablation? 17 COMMENT & ANALYSIS Although microwave ablation and cryoablation have yet to attain five-year results and the literature regarding these modalities is still premature in terms of patient numbers and uniformity, both have demonstrated comparable, even improved overall and cancer-specific survival and local control rates when compared with radiofrequency ablation at one, two and three years, writes Robert D Suh With over 224,000 new cases anticipated for 2014 (American Cancer Society 2014), lung cancer remains perched on the pinnacle of newly diagnosed cancer and cancer deaths in the USA. Despite relentless advances in surveillance and imaging and knowledge, the number of patients at initial presentation with surgically resectable local disease remains soberly small at under 30%, compounded by the realisation that many with resectable disease are rendered medically inoperable by comorbid disease. Although standard surgical lobectomy remains the gold standard for early stage non-small cell lung cancer, non-invasive and minimally invasive non-surgical measures for local control stereotactic body radiotherapy and image-guided tumour ablation, respectively, have been increasingly accepted and utilised for local control and cure for both medically inoperable but even medical operable lung cancer patients. For those with non-small cell lung cancer undergoing radiofrequency ablation, to date the most studied thermal ablation technique, the medical literature has focused on the high-risk, or medically inoperable population. Radiofrequency ablation, or image-guided tumour ablation, can be considered for those patients with locally recurrent cancer (oligorecurrent) after local or even systemic therapy or with synchronous or metachronous lung cancer, those with limited or low volume metastases particularly after a prolonged disease-free interval (oligometastatic) and those in need of palliative and now even salvage therapy. Although multiple methods for safe and effective local therapy are necessary, image-guided tumour ablation for non-small cell lung cancer is particularly poised for success, given it provides the best balance of comparable survival, superior cost and experiential use in the high-risk patient and other emerging patient populations, much of which was unfathomable a decade prior. Efficacy of ablation In 2007, Simon et al first published five-year long-term safety and efficacy data of radiofrequency ablation in 71 patients with stage I primary lung cancer. Overall survival was reported at 78% at one year, 57% at two years, 36% at three years and 27% at four ROBERT D SUH and five years. The authors re-emphasised that patients with treated cancers 3cm and smaller vs. cancers larger than 3cm demonstrated better overall survival at every annual time point; 83% vs. 45% at one year, 64% vs. 25% at two years, 57% vs. 25% at three years and 47% vs. 25% at four and five years. In addition, those patients with 3cm and smaller tumours showed significantly longer median time to progression, 45 months vs. 12 months. Although 27% five-year overall survival appears dismal at first glance, the study was quite remarkable in achieving this survival in the high-risk population, estimated up to 30% according to the Surveillance Epidemiology End Results (SEER) database in 2005, most therapeutically neglected due to their medical ineligibility before this time. Since 2007, at least three additional series in high-risk patients have shown comparable or better five-year overall survival; 24%, 25% and 61%, the last quite formidable and a testament to long-term operator experience and the benefits of lessons learned regarding patient and lesion selection. Although microwave ablation and cryoablation have yet to attain five-year results and the literature regarding to these modalities is still premature in terms of patient numbers and uniformity, both have demonstrated comparable, if not improved, overall and cancer-specific survival and local control rates to radiofrequency ablation at one, two and three years in some series with favourable complication profiles. Argued comparability Over the years, radiofrequency ablation has been unfavourably compared to sublobar resection and stereotactic body radiotherapy. However upon closer scrutiny, one major overlooked factor is that those patients treated with radiofrequency ablation were always the sickest, the radiofrequency ablation patients in most, if not all, studies demonstrating statistically significant poorer FEV1 (the volume exhaled during the first second of a forced expiratory manoeuvre) and older age compared to those undergoing sublobar resection. Moreover, when comparing patient demographics from the ACOSOG Z4033 and Z4032 and RTOG 0236 trials, those patients enrolled in the Z4033 were significantly older and held significantly lower diffusion capacity. Kwan et al recently argued comparable overall and lung-cancer specific survival between radiofrequency ablation and sublobar in SEER database patients when propensity scores were utilised to match patient subgroups. In many circles, stereotactic body radiotherapy has been largely hailed as the silver bullet against early stage lung cancer, setting new lofty standards for five-year overall survival and local recurrence ranging between 54 65% and 4 14%, respectively. Although certainly impressive, the results emerging from these and other similar series have not been free from criticism. Deeper analyses show that not all treated lesions were pathologically confirmed with many radiographically diagnosed. There was also a prevalence of more indolent tumours specifically adenocarcinoma in situ, and the treated population included both low-risk and high-risk patients. In fact, when parsing out the high-risk subgroup from the Onishi et al study in 2007, five-year overall survival drops from the overall reported 65% to 35%, similar to published five-year radiofrequency ablation results. Unlike radiofrequency ablation, moreover, stereotactic body radiotherapy s higher potential for collateral injury to healthy peritumoural lung may be detrimental in many high-risk patients with tenuous lung reserve. Will less equivalent local control be the death of radiofrequency ablation? In ascending order, local control improves when comparing radiofrequency, microwave ablation, cryoablation, stereotactic body radiotherapy and surgical lobectomy; however, despite enhanced local control, the rate of distant disease remains highly variable between studies whether comparing like or unlike therapies. Simply and most plausibly, this variability is the direct result of already microscopic disease at the time of treatment in some surgical series reported as high as 16% in 1cm apical cancers. In other words, even complete, or 100%, local control will have already microscopic locoregional and distant disease. This is further exacerbated in the high-risk population which may be ineligible for formal nodal staging through mediastinoscopy, left to complete reliance on medical imaging, specifically CT-PET. Ultimately, the rate of local and locoregional progression may not negatively impact overall survival. Specifically in 2012, Lanuti et al looked at locoregional recurrence in patients with stage I lung cancer initially treated with radiofrequency ablation, and despite retreatment with radiofrequency ablation, radiotherapy, chemoradiotherapy and chemotherapy, the authors found no significant difference in five-year overall and disease free survival in radiofrequency ablation patients without recurrence vs. those patients with treated recurrences. In some patients with advanced disease, Gu et al (2011) found that patients receiving cryoablation and gefitinib demonstrated significantly better survival at one-year than those patients receiving gefitinib alone. Similarly, Lee et al (2011) observed that even stage three and four lung cancer treated with radiofrequency ablation and chemotherapy demonstrated significantly longer median overall survival than those treated with only chemotherapy. In patients with localised recurrence after initial local or systemic treatment failure, radiofrequency ablation when added to a predetermined treatment regimen lengthened overall and progression-free survival. Cost benefit Although surgery showed overall survival superiority at one, two and three years, Alexander et al (2013) argued that this superiority came at a significantly increased median cost per months lived of 1.93 times from reimbursement rates from the study state. When compared with other modalities in the setting of oligometastatic non-small cell lung cancer, cryoablation appeared the most cost-effective, even when added to the cost of best supportive care or systemic regimens with an adjunctive cost-effectiveness ratio of US$49,008 87,074. Cryoablation was associated with very low morbidity and local tumour recurrence rates for all anatomic sites, and possibly increased overall survival. Although prospective cost-efficacy studies comparing image-guided tumour ablation and stereotactic body radiotherapy are non-existent with the exception of a single study utilising Markov modeling and older radiofrequency ablation data, global Medicare reimbursement in Rhode Island for radiotherapy was 4.25 times that of radiofrequency ablation at US$17,000 vs.us$4000. Whether or not the higher cost of radiotherapy for better local control and arguably better overall survival is justified remains to be seen in the high-risk population, particularly given the microscopic locoregional and distant disease rates and radiofrequency ablation s repeatability at lower cost. Advances in thermal energy devices and delivery have led to improved control. However, gains in survival will be limited for nonsmall cell lung cancer, given the limitations of radiographic staging and microscopic lymph nodal and distant disease at the time of therapy including ablation, rendering the need for adjuvant control in some situations. Additive local control even in those with advanced cancer appears to offer survival benefits in some patient subsets with recurrent or advanced disease. When critically compared to surgical resection and stereotactic body radiotherapy, image-guided ablation is an attractive option with an acceptable threshold for local control balanced with risk and cost without detriment to survival. Robert D Suh is professor, Department of Radiological Sciences, director, Thoracic Interventional Services and director, Diagnostic Radiology Education, David Geffen School of Medicine at University of California, Los Angeles. He has reported no disclosures pertinent to the article

18 18 Interventional oncology The microenvironment of solid tumours matters COMMENT & ANALYSIS ARAVIND AREPALLY dependent upon pressure gradients, whereas the diffusion process is dependent on the density of the stromal matrix 1-3. Thus, the presence of elevated pressures impedes the convection process resulting in a markedly heterogeneous intratumoural distribution of therapeutic agents, which can result in reduced efficacy of drugs and radiotherapy 1. mean arterial pressure or the use of devices (such as balloons and anti-reflux systems) have begun to be utilised to overcome the interstitial pressures to further drive the therapeutic agent into the solid tumours 6, 7, 8. Conclusion Transvascular delivery of embolic agents has a unique opportunity to further improve from its current paradigm. As we further understand the interplay between the delivery of targeted therapeutics and its impact on tumour interstitial pressures, new device strategies should arise to broaden our approach to the treatment of solid tumours and provide an opportunity to significantly improve the outcomes of patients. Despite the rapid growth of imaging and treatment options in interventional oncology, one area that has been poorly understood and overlooked by the interventional community is the role of the tumour microenvironment and its impact on the delivery of therapeutic agents, writes Aravind Arepally The microenvironment of solid tumours is now well studied and more importantly has been shown to be a significant burden to the delivery of anti-cancer agents into tumour cells. Although the peritumoural stromal architecture seems markedly disorganised, there emerges a consistent configuration across solid tumours. This environment has been generally described as having poorly organised vasculature, a low ph, being hypoxic and elevated interstitial fluid pressures. Of all these features, elevated tumour interstitial pressure has gained interest from both a pharmacological and mechanical perspective as a common dominant feature of tumour biology and thus may have implications for targeted delivery of therapeutics. Origins of tumour interstitial pressure The origin of tumour interstitial pressure is multifactorial. Elevated tumour pressure arises from the abnormal permeability of tumour vasculature resulting in the leakage of fluids into the extracellular matrix. In addition the lack of normal lymphatic drainage along with the mechanical pressure of proliferating cells in a confined space heightens this process resulting in elevation of the pressure 1,2. Subsequently, elevation of tumour interstitial pressure releases peritumoral angiogenic features into the adjacent tissues resulting in angiogenesis and thus further aggravating this process 3. The movement of intravascular drugs and therapeutic agents is a multistep process. Initially, the agent has to reach the tumour via the vasculature, cross the vessel wall through the process of convection and finally, diffuse through the interstitial space to reach the target cells. Throughout this activity, the convection process across the vessel wall is highly Strategies to overcome tumour interstitial pressure Several strategies have emerged to modulate or overcome the elevated tumour interstitial pressure. Pharmaceutical approaches lower the tumour interstitial pressure through the use of vascular targeting agents such as vascular endothelial growth factor (VEGF) inhibitors that remodel or normalise the vascular flow to the tumour. The direct effect of this technique is to lower the tumour interstitial pressure, restore normal pressure gradients across the vessel wall and thus increase convection transport of therapeutic agents into the tumour. Thus anti-vegf inhibitors such as bevacizumab and sorafenib have been shown to significantly reduce tumour interstitial pressure 4,5. Further, the combination of anti-angiogenic drug with a cytotoxic agent has been shown to have improved therapeutic efficacy. Other physical methods such as irradiation, hyperthermia, hypothermia and photodynamic therapies have also been shown to reduce tumour interstitial pressure by mechanical processes such as cavitation and/or thermal effects on vascular permeability. Finally, transvascular approaches such as elevating the systemic References 1 Ariffin AB, Forde PF, Jahangeer S, Soden DM, Hinchion J. Releasing pressure in tumors: what do we know so far and where do we go from here? A review. Cancer Research. 2014; 74(10): Sheth RA, Hesketh R, Kong DS, Wicky S, Oklu R. Barriers to drug delivery in interventional oncology. Journal of Vascular and Interventional Radiology. 2013; 24(8): Jain RK, Stylianopoulos T. Delivering nanomedicine to solid tumors. Nature reviews. Clinical Oncology. 2010; 7(11): Raut CP, Boucher Y, Duda DG, et al. Effects of sorafenib on intra-tumoral interstitial fluid pressure and circulating biomarkers in patients with refractory sarcomas (NCI protocol 6948). PloS One. 2012; 7(2):e Tong RT, Boucher Y, Kozin SV, Winkler F, Hicklin DJ, Jain RK. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Research. 2004; 64(11): Irie T, Kuramochi M, Takahashi N. Dense accumulation of lipiodol emulsion in hepatocellular carcinoma nodule during selective balloon-occluded transarterial chemoembolization: measurement of balloon-occluded arterial stump pressure. Cardiovascular and Interventional Radiology. 2013; 36(3): Nagamitsu A, Greish K, Maeda H. Elevating blood pressure as a strategy to increase tumor-targeted delivery of macromolecular drug SMANCS: cases of advanced solid tumors. Japanese Journal of Clinical Oncology. 2009; 39(11): Arepally A, Chomas J, Kraitchman D, Hong K. Quantification and Reduction of Reflux during Embolotherapy Using an Antireflux Catheter and Tantalum Microspheres: Ex Vivo Analysis. Journal of Vascular and Interventional Radiology, (4): Aravind Arepally is with the Division of Interventional Radiology at Piedmont Radiology, Atlanta, USA. He receives a consulting fee from Surefire Medical and chairs the company s Scientific Advisory Board Personalised medicine important in oncology trials At the European Conference on Interventional Oncology (ECIO, April, Berlin, Germany), a session held jointly with the European Organisation for Research and Treatment of Cancer (EORTC) set out to provide interventional oncologists with the latest information needed in a rapidly changing landscape of oncology to run a clinical trial for patients with cancer EORTC has set out that moving the field of cancer treatment forward rests on interdisciplinary collaboration and the integration of pharmacology, molecular biology, tumour immunology, and imaging, as well as transversal problem solving beyond organ-based medicine that are gaining increasing importance. This has led to new therapeutic approaches, targeted therapy and an increasing focus on personalised medicine. Patrick Bourguet, professor of Nuclear Medicine, Centre Eugène Marquis, University of Rennes, Rennes, France, began by setting out the challenges of cancer clinical research in New knowledge of proteomics and genomics ( omics ) are completely changing the paradigm and revising the way that tumours are classified, making previous organ and pathology-based classifications somewhat historic, he said. Genomics and proteomics have revealed a large variety of tumours subtypes which can be defined by such characteristics as chemotherapy-resistance and radiotherapy-resistance, paving the way for personalised medicine. We are changing the way we search for leads and there is an increased focus on genomics. Ninety four per cent of the companies invest in personalised medicine, with 81% of companies having partnerships in personalised medicine. Fifty per cent of trials today involve the collection of DNA samples and 30% of companies require a biomarker for all compounds in development, and this has an impact on the design of clinical trials, as the new classification should have integration of genomics data to define the population of patients who can be included in trials, he told delegates. Bourguet highlighted that clinical research in oncology calls for a large amounts of data including physical examination, common tumour biology, results of omics, morphological and functional imaging. We need dedicated centres to carry out data harmonisation and standardisation. We need centralised management of data, so there is a place in clinical research for professional organisations, he said. Biostatistican Mureille Mauer, EORTC, Brussels, Belgium, described the methodology for conducting clinical trials, in which the gold standard is a randomised controlled tripleblind trial. Primary and secondary endpoints should represent a meaningful clinical benefit to the patient and should be uniformly and objectively measurable in all patients, she explained. Trial endpoints should be theoretically well-defined and equally defined if there are several groups and sensitive to the expected treatment effect. It is a bonus if it can be assessed blinded, she noted. Endpoints most important aspect of trials in interventional oncology Yasuaki Arai, National Cancer Centre, Japan, made the case for interventional oncologists to use endpoints that are recognised and accepted in the wider field of oncology for randomised controlled trials evaluating interventional oncology treatments. Arai also noted that undertaking randomised controlled trials of interventional oncology in the setting of palliative care was a challenging proposition. He reiterated that the endpoints of phase I trials are safety. Phase II trials should evaluate anti-tumoural efficacy and the modification of evaluation criteria should be allowed to take into account the special character of interventional oncology, Arai also said. He also noted that in phase III trials, which are comparative trials that are used to decide the standard treatment, common endpoints such as overall survival, progression-free survival quality of life must be used in clinical trials of interventional oncology in order to gain a wider acceptance of the results. To establish the status of interventional oncology firmly within oncology, interventional oncologists should learn the appropriate language of clinical trials in oncology and should use endpoints recognised by oncologists, he maintained.

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20 20 Deep venous thrombosis Interventional News Quick 4 New deep vein thrombosis guidelines: What you need to know Suresh Vedantham, professor of Radiology, Interventional Radiology Section, Washington University School of Medicine in St Louis, USA, spoke to Interventional News on the latest from the paper Quality improvement guidelines for the treatment of lower-extremity deep vein thrombosis with use of endovascular thrombus removal hot on the heels of its online publication in the Journal of Vascular and Interventional Radiology (JVIR) What prompted the need for new guidelines? The quality improvement guidelines for catheter-directed thrombolysis for deep vein thrombosis have been updated to reflect current practice, and have a substantially improved evidence foundation due to inclusion of information from new studies including two randomised trials. During the last decade, there have been major changes in the key pillars of clinical deep vein thrombosis practice. New oral anticoagulant classes have been introduced; the completed SOX trial (Compression stockings to prevent the post-thrombotic syndrome) has cast major doubt on the idea that compression stockings can prevent the post-thrombotic syndrome; and the practice of catheter-directed thrombolysis has evolved considerably to incorporate improved patient selection, technical refinements (including the frequent use of thrombectomy devices, stents, and retrievable caval filters), and longitudinal care by endovascular practitioners. Why is this paper important currently? A new study published in Journal of the American Medical Association (JAMA) (see page 21) observed a substantially higher risk of adverse safety outcomes in patients who received catheter-directed thrombolysis plus anticoagulation vs. anticoagulation alone in real-world US practice between 2005 and While this study s non-randomised methodology and reliance on administrative coding data likely introduced substantial bias into the comparison, physicians who offer catheter-directed thrombolysis should work hard to meet the high standard of safety that is being demanded by the medical community. We must not take for granted the risks involved in routinely offering thrombolytic therapy to patients with deep vein thrombosis who, after all, are being treated not in a life-saving capacity (as with myocardial infarction or stroke) but to optimise limb function and quality of life. What are the key updates in the revised guidelines? Key changes include: a) safety thresholds that are a little more stringent, reflecting the improved safety observed in catheter-directed thrombolysis studies between compared to before; b) a focus on ensuring longitudinal care to optimally assess the outcomes of therapy and to reduce unnecessary late risks such as those from long-term What the trials have taught us about aggressive therapy of deep venous thrombosis COMMENT & ANALYSIS Ongoing research and recently published studies are changing the treatment landscape for postthrombotic syndrome. Although current evidence in favour of catheter-directed thrombolysis for deep venous thrombosis may not be robust enough to allow for a shift in clinical practice, that may soon change with strict adherence to thrombolysis exclusion criteria, meticulous interventional techniques, and close treatment monitoring to minimise the risk of bleeding complications with catheter-directed thrombolysis, write Stephen T Kee and Adam Plotnik Deep venous thrombosis occurs in 3 600,000 patients per year in the USA, and is associated with significant rates of short (pulmonary embolus) and long-term morbidity (postthrombotic syndrome). Post-thrombotic syndrome has been reported to develop in over 50% of patients within two years following deep venous thrombosis despite standard therapy. The syndrome results from venous obstruction and inflammatory destruction of the valves. STEPHEN T KEE AND ADAM PLOTNIK Manifestations include chronic limb pain, swelling, heaviness, early fatigue, skin pigmentation and/or venous ulceration. Consequently, there is significant impairment on the patient s quality of life and the care required places a major economic burden on both the patient and healthcare providers. Conventional therapy Standard treatment of acute deep venous thrombosis is anticoagulation, Suresh Vedantham which prevents pulmonary embolus and the propagation of thrombus, but does not affect the outcome or severity of post-thrombotic syndrome. Historically the only treatment for post-thrombotic syndrome with level one evidence is compression stockings. Thrombolysis, initially published in 1994 by Semba and colleagues in Radiology, has also been used to treat extensive deep venous thrombosis, however, the data supporting its use to prevent post-thrombotic syndrome is inferior vena cava filter implantation; and c) sections that succintly summarise measures to prevent bleeding and pulmonary embolism during and after catheter-directed thrombolysis. How will this paper serve as a tool for local quality improvement programmes? This article offers physicians a template around which to design internal deep vein thrombosis quality improvement programmes. The authors ambition is for practicing physicians to build strong longitudinal care systems around deep vein thrombosis care, to ensure that patients can be provided catheter-directed thrombolysis as safely and as effectively as possible. This article represents the best consensus quality improvement tool we could develop within the bounds of existing catheter-directed thrombolysis studies, which are still quite limited in scope and methodology. We hope and expect that the next version of these guidelines will be created with the benefit of additional randomised trial data, including that from the National Institute for Health-sponsored, multicentre, randomised, assessor-blinded, ATTRACT (Acute venous thrombosis: thrombus removal with adjunctive catheter-directed thrombolysis) trial which has nearly completed patient accrual. limited. Ongoing research and recently published studies are changing the treatment landscape for this devastating disease. This article provides an update of this data. Data on thrombolysis and acute deep venous thrombosis A 2014 Cochrane review evaluating randomised controlled trials, with a total of 1103 patients from 17 studies, examined thrombolysis and anticoagulation vs. anticoagulation alone in the setting of acute deep venous thrombosis. They demonstrated significantly less post-thrombotic syndrome in those receiving thrombolysis compared with anticoagulation alone. However, it identified significantly increased bleeding complications (10% vs. 8%). Notably, most of these bleeding complications occurred in early studies (pre-1990), whereas recent adaptations in the standard practice of thrombolysis (lower dose rates and reduced concomitant heparin administration) should mitigate many of these issues. Only two randomised controlled trials have specifically compared catheterdirected thrombolysis with anticoagulation. Elsharawy and Elzayat (European Journal of Vascular and Endovascular Surgery, 2002) published data from 35 patients, half treated with catheter-directed thrombolysis and anticoagulation, half with anticoagulation alone. They found significantly less reflux and higher patency in the catheterdirected thrombolysis group although numbers were small and short follow-up

21 More bleeding with catheterdirected thrombolysis than with standard anticoagulation in deep venous thrombosis A study published in the Journal of the American Medical Association (JAMA) has found no difference in mortality rates between deep vein thrombosis patients treated with catheter-directed thrombolysis or anticoagulation alone. In the study, evidence of higher adverse events was noted in the catheter-directed thrombolysis group. The study was conducted by Riyaz Bashir, Temple University School of Medicine, Philadelphia, USA, and colleagues. Several small studies have suggested catheter-directed thrombolysis can reduce the incidence of post-thrombotic syndrome, which can impair quality of life for patients because of resulting pain, swelling and ulcerations. But catheter-directed thrombolysis is controversial with conflicting directives on its use because of inconclusive comparative safety outcomes, the authors write. The investigators examined in-hospital mortality, as well as secondary outcomes of bleeding complications, length of stay and hospital charges, in a group of 90,618 patients hospitalised for deep vein thrombosis from 2005 to 2010 as part of the US Nationwide Inpatient Sample database. They compared patients treated with catheter-directed thrombolysis plus anticoagulation with patients treated with anticoagulation alone. Of the 90,618 patients hospitalised for deep vein thrombosis, 3,649 (4.1%) underwent catheter-directed thrombolysis. The catheter-directed thrombolysis utilisation rate increased from 2.3% in 2005 to 5.9% in In-hospital mortality was not significantly different between the catheter-directed thrombolysis and anticoagulation groups (1.2% vs. 0.9%). However, rates for blood transfusion, pulmonary embolism, intracranial haemorrhage and vena cava filter placement were higher among patients treated with catheter-directed thrombolysis. Patients in the catheter-directed thrombolysis group also had longer average lengths of stay (7.2 vs. five days) and higher hospital charges (US$85,094 vs. US$28,164) compared with the anticoagulation group. Since our results are based on observational data, our findings could be subject to residual confounding, which further highlights the need for randomised trial evidence to evaluate the magnitude of the effect of catheter-directed thrombolysis on outcomes such as mortality, postthrombotic syndrome and recurrence of deep vein thrombosis, the authors wrote. Deep venous thrombosis 21 precluded evaluation of post-thrombotic syndrome. The other more significant randomised controlled trials was CaVent, a Norwegian study that included 209 patients. Half were treated with catheter-directed thrombolysis and anticoagulation, half with standard anticoagulation. Post-thrombotic syndrome was significantly lower in the catheter-directed thrombolysis group. Other observational studies have demonstrated improvement in long-term quality of life following catheter-directed thrombolysis, including Comerota in 2000 (54 patients) and Grewal in 2010 (42 patients). Despite this data, there continues to be widespread reluctance to change the paradigm of treatment for deep venous thrombosis, based mainly on the concerns regarding bleeding risks. Unresolved questions as to the benefits and risks of catheter-directed thrombolysis may be answered by an ongoing National institute of Health sponsored, multicentre trial, ATTRACT (Acute venous thrombosis: thrombus removal with adjunctive catheterdirected thrombolysis). Patients with an iliofemoral and femoropopliteal deep venous thrombosis are being stratified into catheter-based techniques of thrombolysis vs. anticoagulation alone. The primary endpoint is the development of postthrombotic syndrome at 24 months, and there will also be a cost-benefit assessment. Their study hypothesis targets a reduction in post-thrombotic syndrome of 33% in the lysis group, with hopefully, a low incidence of bleeding complications. Should this large multicentre randomised controlled trials result in clinical improvement with acceptable risk and an overall cost-benefit, it may shift the playing field in favour of aggressive thrombolytic therapy for deep venous thrombosis. Why are we not doing more thrombolysis? The challenge to incorporating catheterdirected thrombolysis into standard practice lies in the fact that post-thrombotic syndrome develops long after the patient s acute hospital admission for deep venous thrombosis. Many physicians dealing with the acute stage have a low-level of appreciation of the long-term sequelae. Data from trials clearly show a significant reduction in post-thrombotic syndrome with catheter-directed thrombolysis and AT- TRACT will hopefully demonstrate further improvement with the added inclusion of pharmacomechanical techniques, and cost-benefit data. Furthermore, with strict adherence to thrombolysis exclusion criteria, meticulous interventional techniques, and close treatment monitoring, the risk of bleeding complications can be minimised. Although current evidence in favour of catheter-directed thrombolysis for deep venous thrombosis may not be robust enough to allow for a shift in clinical practice, that may soon change. Stephen T Kee is associate professor of Radiology and section chief, Interventional Radiology, David Geffen School of Medicine at UCLA, Los Angeles, USA. Adam Plotnik is a radiologist at the same institution. The authors have reported no disclosures pertaining to the article

22 Venous news Study identifies key factors affecting catheter-directed thrombolysis for iliofemoral deep vein thrombosis 22 A study from Denmark has found that the most important factors to predict long-term competent veins after catheter-directed thrombolysis are symptom duration of less than two weeks and use of the pulse spray technique The study was presented at the European Venous Forum (26 28 June, Paris, France) by Pia Foegh, Vascular Clinic, Gentofte Hospital and Rigshospitalet, Copenhagen, Denmark, on behalf of the investigators. Foegh stated that many factors seem to influence the outcome of catheter-directed thrombolysis of deep thrombosis of the iliofemoral vein and explained that this study set out to identify the factors associated with long-term competent veins after catheter-directed thrombolysis. The investigators analysed data from 1999 to 2013, obtained from nearly 200 patients (over 200) limbs with iliofemoral involvement who underwent thrombolysis. They noted that the median follow-up was five years. The researchers obtained information on gender, age, side that treatment was carried out, inferior vena cava atresia, inferior vena cava thrombolysis, history of stenting, duration and type of lysis (infusion vs. pulse spray), duration of symptoms, and chronic lesions from the patient records. The study outcome was defined as competent vein (as a primary patent vein without signs of reflux on Pia Foegh ultrasound). They tested the association initially in a univariate survival model (Kaplan-Meier with log-rank test) and subsequently on a multivariate Cox proportional hazard model. The researchers found that univariate analyses revealed that gender, duration of lysis, stenting, duration of symptoms, type of lysis (infusion vs. pulse spray) and chronic lesions were significantly associated with outcome whereas age, side, inferior vena cava atresia and inferior vena cava thrombosis were not. The Kaplan-Meier model showed that the estimated per cent of competent veins was 79% after seven years. On the other hand, the multivariate Cox proportional hazard model revealed that symptom duration >2 weeks, infusion and chronic lesions were the only factors significantly associated with poorer outcome. This model also showed that stenting was more frequently reported in patients with a longer history of symptoms and this was not identified as a prognostic predictor. Niels Baekgaard, Vascular Clinic, Gentofte Hospital and Rigshospitalet, Copenhagen, Denmark, the senior author of the paper, told Interventional News: This study emphasises, for the first time, that the duration of symptoms prior to treatment has a great impact on the results after catheter-directed thrombolysis. This means that patients with more than two weeks of symptom duration will achieve inferior results with this treatment that are almost similar to anticoagulation and compression alone for this category of patients. The results of this study also show that physicians are able to rely on the accuracy of patient s memories with regard to the duration of symptoms. Perhaps, in the future, some of the newer imaging modalities in combination with patient history, will be able to estimate the thrombus age even more accurately and strictly in order to determine the best course of treatment. The researchers concluded that the most important factors for predicting long-term competent veins after catheter-directed thrombolysis are symptom duration less than two weeks and use of the pulse spray technique. This corresponds very well with the international definition of acute deep venous thrombosis (which is deep venous thrombosis less than two weeks), Foegh told delegates. She also noted that patients with chronic lesions distally to the iliac compression area seem to have poorer outcomes, perhaps because of previous subclinical episodes of former deep venous thrombosis. European Commission approves Eliquis (apixaban) for treatment of deep vein thrombosis and pulmonary embolism Bristol-Myers Squibb and Pfizer have announced that the European Commission has approved Eliquis (apixaban) for the treatment of deep vein thrombosis and pulmonary embolism, and the prevention of recurrent deep vein thrombosis and pulmonary embolism in adults. The European Commission approval applies to all European Union (EU) member states as well as Iceland and Norway. This approval broadens the clinical use for apixaban which is also approved for use in the EU for the prevention of venous thromboembolism (VTE) in adults who have undergone elective total hip or knee replacement surgery, and the prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors thromboembolism is a major public Venous health concern, and a burden to the UK and the NHS, commented Alexander T Cohen, Guy s and St Thomas Hospitals, London, UK In fact, the total cost of the management of venous thromboembolism is estimated to be between 340 and 640 million per year, placing a significant burden on the health system. In the AMPLIFY trial apixaban was shown to be effective in the treatment of venous thromboembolism, with the additional benefit of having a significantly lower risk of bleeds compared to current standard therapies, which is positive news for patients and healthcare professionals. This improved risk benefit profile will provide clinicians with confidence when considering prescribing this treatment and provide greater reassurance for patients. The fact it is an oral treatment that does not require INR monitoring has additional advantages in terms of convenience for patients with the additional potential to reduce hospitalisations. The marketing authorisation follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency, and is supported by two pivotal phase 3 clinical trials, AMPLIFY and AMPLIFY-EXT. The AMPLIFY (Apixaban for the initial management of pulmonary embolism and deep vein thrombosis as first-line therapy) study, was a randomised, doubleblind, multicentre, non-inferiority trial which evaluated apixaban therapy compared to standard of care. It included 5,395 patients (2,691 were randomised to apixaban and 2,704 were randomised to standard of care, which was initial enoxaparin treatment overlapped by warfarin therapy). The AMPLIFY-EXT (Apixaban after the initial management of pulmonary embolism and deep vein thrombosis with first-line therapy-extended treatment) study was a randomised, double blind, multicentre trial. It included 2,486 patients (842 were randomised to apixaban 2.5mg, 815 were randomised to apixaban 5mg and 829 were randomised to placebo). In this study, patients randomised had previously completed six to 12 months of anticoagulation treatment for deep vein thrombosis or pulmonary embolism and went on to receive apixaban therapy or placebo for a further 12 months. First varicose vein patient treated with FDAapproved Varithena BTG International has announced that the first varicose vein patient has been treated with Varithena (polidocanol injectable foam, 1%), the only FDA-approved foam for the treatment of incompetent great saphenous veins, accessory saphenous veins and visible varicosities of the great saphenous veins system both above and below the knee. Varithena improves symptoms related to or caused by varicose veins, and the appearance of varicose veins, and is proven to reduce the five symptoms patients consider most important heaviness, achiness, swelling, throbbing, itching (HASTI symptoms). Marlin Schul of the Lafayette Regional Vein & Laser Center in Indiana, USA, who conducted the first Varithena procedure, says, Varithena is a convenient, minimally invasive treatment and patients can return to normal activities shortly after treatment. Varithena is a uniform, low-nitrogen, polidocanol microfoam, dispensed from a proprietary canister device. The physician injects a small amount of Varithena into the malfunctioning vein through a catheter or a needle. It displaces the blood from the vein to reach and treat the vein wall; the diseased vein collapses and blood flow is diverted to healthy veins nearby. Varithena

23 Cyanocrylate embolization similar to radiofrequency ablation, a randomised FDA study finds A study presented at the European Venous Forum (26 28 June, Paris, France), by Nick Morrison from the Morrison Vein Institute, Scottsdale, USA, showed that cyanoacrylate embolization as compared to radiofrequency ablation demonstrates similar closure at three months (non-inferiority p-value <0.0001) Nick Morrison Principal investigator Morrison was reporting the results of a randomised, controlled, non-inferiority, FDA study comparing the safety and efficacy of cyanoacrylate adhesive embolization to radiofrequency ablation for closure of incompetent great saphenous veins. From March 2013 to September 2013, 222 patients with symptomatic great saphenous veins reflux at 10 US clinical sites were randomly assigned to treatment with either cyanoacrylate adhesive embolization using the VenaSeal Sapheon Closure System or radiofrequency ablation with the ClosureFast System (Covidien). Follow-up visits were arranged on the third day after the procedure, and at one and three months. Adjunctive procedures were not allowed until after the threemonth visit, Morrison said. The primary efficacy endpoint was complete closure of the symptomatic great saphenous veins at three months as measured by Doppler ultrasound and assessed by an independent core laboratory. The investigator at each site recorded CEAP classification at screening and three-month follow-up and Venous Clinical Severity Score (VCSS) at baseline, day three, and one and three months. Pre-specified procedure-related adverse events and patient-reported adverse events were recorded. The great saphenous vein closure results as judged by each site investigator were further reviewed by an independent vascular core laboratory with 100% agreement between the investigator sites and the core laboratory, Morrison clarified. There were 108 veins that were embolized. At one month 105 were evaluated and 100% showed complete closure (complete vein closure was defined as closure along the entire treated vein segment with no patency >5cm). At three months, 104 patients were evaluated and 103 (99%) were completely closed. In the group that received radiofrequency ablation, 114 veins were treated. At one month, 109 were evaluated and 94 showed complete closure (86.2%). At three months, 108 patients were evaluated and 103 (95.4%) showed completely closed. In both instances the non-inferiority p value (hypothesis 10%) was < The VCSS was not significantly different for both groups at all the time points during follow-up. The incidence of procedure-related adverse events and other adverse events throughout the study was similar between groups. Follow-up visits were arranged on the third day after the procedure and at one and three months. Adjunctive procedures were not allowed until the three-month visit Nick Morrison Venous news 23

24 24 Visceral aneurysms Interventional radiology techniques increasingly used in the treatment of visceral artery aneurysms than the known material in peripheral interventional radiology and need specific training which is not readily available. More collaboration between interventional community and industry is needed to develop instruments that are dedicated for peripheral use and tackle unresolved challenges in this field. MOHAMED HAMADY COMMENT & ANALYSIS Visceral artery aneurysms are an uncommon and usually asymptomatic vascular entity that frequently present as a life-threatening emergency. However, the increased use and widespread accessibility to non-invasive imaging modalities across the world (USS, CT, MRI), have improved the chances to diagnose asymptomatic cases and have created a more favourable environment to assess patients and map the disease from the cause to the treatment options. Although rare, these aneurysms have the potential to grow and rupture leading to catastrophic haemorrhage that could lead to death. The radiological findings have added precision that has allowed identification of the most common sites and the distinction between two major types, true and pseudoaneurysms. In order of frequency, splenic and hepatic arteries are the most common locations of visceral artery aneurysms. Aneurysms occur at a rate of 60 80% and 20% respectively at these locations. These aneurysm also occur in the renal arteries (15 22%) and mesenteric blood vessels, with the latter territory being the least common site (1 8%). It is important to differentiate between the two main types of visceral artery aneurysms, true aneurysms and pseudoaneurysms, as the natural history is likely to be different. The pseudoaneurysm has no proper wall and it is contained by either adventitia alone or by surrounding soft tissue while true aneurysm has three vessel layers. It is conceivable that pseudoaneurysm is at higher risk of rupture and subsequently carries higher risk of significant morbidity and mortality. The treatment approach should take into consideration the underlying cause of the aneurysm. The causes of true visceral artery aneurysms include; atherosclerosis, vasculitis and fibromuscular dysplasia. The false aneurysm can be secondary to trauma, infection, inflammation, vasculitis or iatrogenic injury. Ultrasound is useful modality for screening and follow up. Nevertheless, CT angiography and MR angiography are the most frequent modalities used to establish the features of the aneurysm including; shape, type, size, multiplicity, collateral vessels and status of surrounding tissues. Imaging can be crucial in deciding the most appropriate intervention tool and technical planning. The majority of visceral artery aneurysms are diagnosed incidentally. However, ruptured aneurysm may present with excruciating pain, haemodynamic instability and collapse. The clinical examination is usually unrevealing. Indications for intervention The natural history of visceral artery aneurysms is poorly understood. Therefore, there is no clear consensus or guidelines to dictate a clear set of criteria for intervention. Nevertheless, there is general agreement among experts that treatment is indicated in; 1) ruptured aneurysm 2) aneurysm size 2cm 3) growing aneurysm 4) aneurysms associated with pregnancy and arteritis and 5) psuedoaneurysms regardless of their size. Outcomes of open surgery versus endovascular intervention For long time, open surgery has been considered the gold standard treatment. The first surgery was performed in the 19th century. Since then, surgical techniques and measures to maximise the patient s physiology have significantly improved. Open or laparascopic surgical techniques entail aneurysm excision with re-establishment of blood flow or ligation with end organ removal such as splenectomy or nephrectomy. The reported results in the literature show good success rates and relatively low mortality and morbidity. However, the open approach carries several drawbacks such as invasiveness, prolonged hospitalisation and physiological trauma. Besides that, there are technical difficulties with accessing visceral artery aneurysms in hepatic and renal hilum in the presence of pancreatitis and a hostile abdomen. Yet the open approach remains the preferred option if possible in case of infected aneurysms as it allows for the washing of the vascular bed, debridement and vein graft. In the recent years, interventional radiology techniques have been increasingly used to treat visceral artery aneurysms. Several endovascular tools are available. These include; coils, stent -assisted coiling, covered stents, adhesive and non-adhesive liquid embolics, flow diverting stents, occlusion devices and thrombin injection. Regardless of the equipment used, the intervention must ensure complete isolation and thrombosis of the aneurysm with least damage possible in the end organ. The choice should be tailored to the patient s condition and aneurysm anatomy as well as operator s expertise. Due to the wide variety of interventional tools, interventional radiologists are required to familiarise themselves with these equipment in order to achieve the required success and overcome anatomical barriers and challenges that are still hindering more positive outcome in a reasonable number of cases. For example, dealing with aneurysm involving the bifurcation/trifurcation of renal artery at the hilar region without compromising the renal parenchyma is a recognised problem. The adaptation of some of techniques and tools known in neurointerventional radiology might expand the treatment option and increase safety. Flow diversion embolic devices, occlusive balloons, cage and coil that use retrievable stent are only examples of these techniques. However, currently, the high cost of equipment and the lack of adequate specific training is major inconvenience in their routine use. Those tools are much more expensive Outcomes of percutaneous intervention vs. open surgery The available evidence of treatment outcome, whether open or endovascular can be derived from case series or retrospective studies. There is lack of data from prospective, well-controlled case series or randomised trials. The endovascular approach shows slightly better positive outcomes when compared with open surgery with lower morbidity and mortality rates, comparable success rates and shorter hospital stay. The major drawback, however is the risk of reperfusion of aneurysms and a relatively high incidence of post embolization syndrome. This highlights the need for more technological refinement that would enable interventionists to improve their results. Also, interventionists should pay a great attention at sealing the inflow and outflow vessels together with packing the aneurysm sac. Interesting lessons can be learned from the experience of our colleagues in neuro-intervention. Pre-procedure planning and mental rehearsal of the team can add significant safety measures and enhance successful outcomes. Finally, the development of a central registry run and supervised by learned societies could help filling the gap of knowledge. This kind of registry should include all diagnosed patients with visceral artery aneurysms regardless of the final treatment; open, endovascular or medical so as to obtain comparative data between all treatment modalities. Analysing the registry data would allow for risk stratification and assessment of success rates, mortality and morbidity outcomes, data on patient quality of life as well as cost-effectiveness so as to advance practice based on the best evidence. A patient-tailored approach would be most suited achieving good care and this can be achieved through multidisciplinary collaboration involving interventional radiologists along with general surgeons, vascular and/or transplant surgeons. Mohamed Hamady is a consultant interventional radiologist and senior lecturer at Imperial College, London, UK. He has reported no disclosures pertaining to the article EmboCoh visceral aneurysm cohort registry idea outlined at GEST US 2014 EmboCoh is a structured international web-based channel, designed so that physicians can enter their data on embolization procedures. It will enable collaborative registrystyle data collection and analysis, particularly of uncommon embolization procedures, which would not be meaningfully possible from single-centre data due to the paucity of cases The first aim of the EmboCoh registry is to create the infrastructure to collate data on cohort studies involving embolization, and its first project is to collate international data on the embolization of visceral aneurysms, Marc Sapoval, Hôpital Européen Georges Pompidou (APHP) in Paris, France, told delegates at the Global Embolization Symposium and Technologies (GEST US 2014, 1 4 May, San Francisco, USA). EmboCoh is the brainchild of interventional radiologists Sapoval and Jafar Golzarian, Minneapolis, USA. Several international leaders in embolization such as Ziv Haskal, Charlottesville, USA, John Kaufman, Portland, USA, Michael Darcy, St Louis, USA, Kiego Osuga, Osaka, Japan, and Vincent Vidal, Marseille, France, are involved and the project is administered by Gert Andersen. The physicians believe that gathering data on uncommon embolization procedures and its analysis will eventually lead to a better standard of care for these procedures. EmboCoh will be opening soon under a limited release in Europe, the USA and Japan. It is in the proof of concept stage and more centres will be able to become involved, Sapoval stated.

25 New developments 25 He explained the rationale for launching EmboCoh with the aim of capturing data on the embolization of visceral aneurysms saying: There is currently little evidence on the best method to achieve long-term protection from rupture for visceral aneurysms. Sapoval also stated that other topics for which data could be collected in EmboCoh are embolization of varicoceles, pelvic congestion syndrome, conventional transarterial chemoembolization and transarterial chemoembolization with drug-eluting beads. An international prostatic artery embolization registry could also be developed, he noted. Sapoval also noted that the registry GEST US directors Marc Sapoval, Jafar Golzarian and Ziv Haskal could help centres to start a new intervention. For instance, scientific and ethical support could be provided for those who want to start prostatic artery embolization in a complex local environment. The registry could also serve as a channel to identify centres that are willing to enter into new multicentre collaborative projects, he explained. Sapoval told delegates that they had be aware of the relevant legal obligations that applied to data entry such as the Institutional Review Board approval in the USA and non-interventional study in Europe. Data entry are anonymous and follow-up information is mandatory, he outlined. Society of Interventional Radiology issues global call for research The Society of Interventional Radiology (SIR) has issued a global call for scientific abstracts covering all areas of vascular and nonvascular interventional radiology for its 40th Annual Scientific Meeting, which will be held 28 February 5 March at the Georgia World Congress Center in Atlanta, USA International practicing experts, early career professionals, research scientists, clinical associates and medical students in the interventional radiology field and related areas are asked to submit scientific abstracts for oral or poster presentation by 3 October, 5pm. (Eastern time, USA). Abstract categories include arterial interventions (aneurysm/dissection, angioplasty/stent placement and embolization); interventional oncology (ablation, biopsies, chemoembolization and radioembolization); venous interventions (angioplasty/stent placement, embolization, inferior vena cava filters and thrombolysis/thrombectomy); nonvascular interventions (abscess and fluid drainage, biliary, chest, gastrointestinal, genitourinary, gynecology, musculoskeletal and spine); dialysis interventions; education and training; practice management; health care policy; and quality improvement. All selected scientific abstracts will be published in SIR s flagship publication, the Journal of Vascular and Interventional Radiology, and on its website. Selected abstracts may be designated as Distinguished, Featured or Abstract of the Year. Additionally, US and international consumer and trade media report on SIR medical news; accepted research may also be discussed on SIR s social media sites. SIR will notify authors about the status of abstracts in November. SIR s International Scholarship programme provides physicians who are within 10 years of completion of training and who are practicing outside North America with the opportunity to attend and learn at the Annual Scientific Meeting. The scholarship also fosters professional networking through meeting participation, focused programming, and optional visiting observerships before or after the meeting. Accepted abstract presenters are not eligible for the International Scholarship. Research awards to support travel are also available through SIR Foundation for those medical students, residents and fellows whose abstract has been accepted for oral presentation at the Annual Scientific Meeting. SIR also offers two Annual Scientific Meeting scholarships for interventional radiologists-in-training: the SIR Medical Student Scholarship and SIR Resident-in- Training Scholarship. Information about both is on SIR s website ( sirweb.org/).

26 26 Interview Profile José Ignacio Bilbao Jaureguízar No matter what their future orientation, interventional radiologists involved in interventional oncology need to have a basic training in what is called general interventional radiology in order to be able to provide a uniform and standardised care, José Ignacio Bilbao Jaureguízar, professor and head of the Department of Interventional Radiology, Clínica Universitaria de Navarra, Pamplona, Spain, told Interventional News What drew you to medicine and interventional radiology? I am not sure about what drew me to medicine. At the age of 16 or 17, it is difficult to have certainities. I was a good student at the school and I had an idea about subjects that I did not want to pursue (economics, philosophy or law) however I was amazed with biology, history, art and maths, and found myself studying medicine. It is easy to understand that I was delighted to study human anatomy, histology and surgery. I then discovered radiology with its lines, shadows, volumes and mystery. Why interventional radiology? From the very begining of my residency (1980) I tried to combine morphology, surgery, care, devices and new horizons all the basic components of interventional radiology, so it was easy to choose. Who were your mentors and what wisdom did they impart to you? I have had many mentors from whom I have tried to learn and whose advice I have tried to follow. I want to single out Dr Francisco Lecumberri from whom I learned to analyse and observe during my residency. My first steps into interventional radiology were guided by Dr Luis Alonso de Santos and Dr Sidney Wallace (Houston, USA) and the foundations of my initial career came from Dr Ricardo Tobio (Madrid) and Dr Manuel Maynar (Canarias). I learned several concepts such as compromise, clinical orientation, teach and study from these luminaries and I can never forget them. As a recognised international expert on radioembolization, could you please identify three questions you would like to see answered about the procedure? The first is how to identify in which population the procedure could be performed in just one day, in order to avoid the need for two angiographic steps and the subsequent delay between the decision to treat and the treatment itself. The second is how to increase the accuracy of the intratumoural deployment of the treatment which is concerned with microvascular haemodynamics, particle characteristics and angiogenesis. A third question is to find out how we can confidently evaluate the response to the treatment at an early stage. Radioembolization should be incorporated in the guides and protocols which deal with the multidisciplinary approach to treat liver tumours. In the next two years there will be a lot of valuable information coming from ongoing studies that will help to back this up. At this moment, several series have demonstrated that radioembolization undoubtedly has an anti-tumoural effect with a demonstrated improvement in survival. Moreover, it should not just be seen as a useful therapy for refractory cancer, but also as first-line treatment or as a unique method for downstaging towards surgical treatment. Could you describe a memorable case that you treated by using radioembolization? As in many other circumstances of the life, I think that the most illustrative case is often the first one. It was September We evaluated the case of a cirrhotic patient with a hepatocellular carcinoma in the right lobe that did not respond to chemoembolization. The patient was not a candidate for liver transplantation. We then performed radioembolization to the right lobe of the liver with a subsequent excellent radiological response. In the following years, the patient did not present any tumoural recurrence and he was positively re-evaluated for receiving a liver transplant. Surgery was performed in January 2007 and the patient is now alive with excellent clinical conditions. What is the importance of adopting the multidisciplinary approach? Radioembolization is currently not just used for palliation but also with a curative intention on its own (tumoural ablation) or as downstaging/bridging to a curative treatment such as surgery (resection/transplantation). The interventional radiologist must work in conjunction with the other members of the multidisciplinary team in order to personalise, as much as posible, the procedure for the patient. It is obvious that any action made by the interventional radiologist such as coiling an artery during the procedure, might preclude a subsequent further surgical approach, resulting in a poorer outcome for the patient. Also radioembolization should not be approached as the only, and exclusive treatment that the patient will receive and similarly radioembolization may not be the first treatment that the patient has received. The latter situation might mean that patients could have previously received other treatments, such as antiangiogenics or surgery that can interfere with an interventional radiologist s technical planning of the procedure. Working closely in a multidisciplinary team can help specialties to work together in the best interests of the patient. You have extensive research in the area of transjugular intrahepatic portosystemic shunt (TIPS). What was the importance of this procedure? We, together with the team from Toulouse (Dr Rousseau, Dr Joffre, Dr Vinel), began to explore about TIPS in experimental models in around We initiated our clinical work in 1991 including some interesting modifications from those initially reported. Among them, the exclusive transjugular approach, the use of flexible, autoexpandable, prostheses and the ultrasound guidance of the procedure (vein catheterisation and portal puncture). We later participated in the study that demonstrated the usefulness of covered prostheses and explored the possibility to perform pecutaneous extrahepatic connections of vessels. The extensive amount of clinical research about TIPS has demonstrated its usefuness in a wide variety of conditions. TIPS has opened up the territory of the portal vein and the splachnic system allowing us to carry out a wide variety of procedures both for symptom alleviation and also for the amelioration of the venous flow and vascular patency which will allow

27 Interview 27 Fact File downstaging so that surgery (transplantation) can be performed. As the co-founder of the Spanish national society of vascular and interventional radiology, SERVEI, what are the key challenges that face the subspecialty in Spain? SERVEI (Sociedad Española de Radiología Vascular e Intervencionista) is one of the oldest national scientific societies specifically devoted to the promotion of vascular and interventional radiology in the world. Since its establishment in 1986, SERVEI (now with 250 members) has actively worked in the education of many Spanish (and South-American) specialists. However, and in spite of this, interventional radiology is not yet an independent recognised subspecialty and the administrative representation of Spanish interventional radiologists has to be performed, sometimes through indirect channels. Spanish interventionists perform all procedures of the specialty, but the implementation of interventional radiology across the country is still irregular. There are hospitals in which you can find a very high level in the quality of the care and others in which there is an important need for improvement and SERVEI is working towards assuring uniformity in the level of care. Our clinical collaboration with other specialists, such as vascular surgeons or cardiologists, needs to be restructured. Health managers must understand that the vascular system is an important area of activity for us and for the above mentioned groups, but this is not the only domain we work in. Recent interest in the creation of new groups having shared facilities and novel words/terms such as hybrid rooms or versatile teams must be counterbalanced with the fact that, for the benefit of the care, the education and the research, the future interventional specialist is not just a skilled provider in vascular solutions. So vascular disease, while an important part of the specialty is not the only area we work in and this should be widely recognised. Should vascular interventionalists pursue a different training pathway from those interested in interventional oncology? No matter what their future orientation, interventional radiologists involved in interventional oncology need to have a basic training in what is called general interventional radiology in order to be able to provide a uniform and standardised care. It has to be immediately understood that interventional radiologists who work in interventional oncology are not just highly skilled doers. We have to also promote their involvement in teaching, managing and research in oncology. Interventional oncology, for many of us and for many years, has been and is an important part of interventional radiology. Your question about specific training in interventional oncology has to be immediately linked with the concept of what is interventional oncology?. It could be understood that it consists of just carrying out percutaneous biopsies and tumoral ablations by precisely placing needles in the selected place (which in itself is not always an easy task!). This ability should also be accompanied with a profound knowledge of the morphologic and functional imaging peculiarities about the disease. Interventional oncology is much more than biopsies and ablations. Our specialists should be able to provide high-quality care to this specific group of patients with a detailed knowledge of the disease and as equal members of a multidisciplinary team. At this stage in your career, what is your basic approach to medicine? I feel young! As a physician I have been trained to deliver care to patients and as an interventional radiologists I use images, devices, imagination and time (a lot of time!) to do this so in that sense my motivation to pursue interventional radiology is somewhat unchanged. I spend many hours in my daily clinical practice trying to do my best for each patient, trying to be of help to my colleagues and trying to learn (one of my professors used to say: Everyday I see something that I have never seen before ). However, I realise that time passes (quickly) and that when you are almost 60 you must have a different approach to medicine. I am doing my best to teach what I have learnt to young people. I would like to increase my teaching involvement in our University s medical school. This is because I am delighted to transmit the attractiveness and importance of our specialty to young people. It is a big honour when a young interventional radiology colleague confesses that he/she has become infected by enthusiasm for interventional radiology by my teaching when they were a student of medicine. What are your interests outside of medicine? For years I have been very interested in history and Medieval art. I am delighted when I have the chance to be in a Romanic building, looking in complete silence at its stones and components and trying to understand their message. I also enjoy walking in the company of my family or good friends. It is very relaxing to spend a few hours walking surrounded by nature or old buildings. As every Basque (I was born in Bilbao) I try my best to be a reasonable cook and have achieved a degree of recognition of my skills within my family (including from my mother!) on my preparation of certain fish and vegetable dishes. Academic and hospital appointments ntitled professorship at Clínica Universitaria de Navarra (CUN), Pamplona, Spain (2007 present) n Head of Interventional Radiology (1991 present) Education n Graduate education, Doctor of Medicine (MD), Facultad de Medicina. Universidad de Navarra (1979) nresidency in Diagnostic Radiology, CUN ( ) Training ninterventional Radiology traineeship, MD Anderson Hospital and Tumor Institute, Houston, USA, with Professor Sidney Wallace (1982) Postgraduate education n PhD Cum Laude (awarded by CUN, 1989) Awards nspanish Society of Vascular and Interventional Radiology (SERVEI): Best Scientific Paper Awards in 1995, 1997, 2003, 2005 and 2007 nspanish Society of Radiology (SERAM): Gold Medal 2014 ncardiovascular and Interventional Radiological Society of Europe (CIRSE): Gold Medal (2013), Josef Rösch Lecture (2010), Best Article of the Year (2010) Best Scientific Paper (2002) nradiological Society of North America: Poster Awards in 1992, 1993, 1996, 1998 neuropean Association of Radiology (EAR): Diploma (2007) njournal of Vascular and Interventional Radiology Distinguished Reviewer ( ) Membership in professional societies nspanish Society of Vascular and Interventional Radiology (SERVEI): Founding member and president ( ) nspanish Society of Medical Radiology (SERAM): Executive committee ( ) ncardiovascular and Interventional Radiological Society of Europe (CIRSE): Executive committee ( ) and ( ) Congress co-chair (2004 and 2010) n Society of Interventional Radiology (SIR) n European Society of Radiology Executive committee ( ) and ( ) neuropean Congress of Radiology president (2013) n Radiological Society of North America nspanish Ministry of Health: National Committee of Diagnostic Radiology ( )

28 28 Key updates The promise of chemical renal denervation COMMENT & ANALYSIS The sobering results from SYM- PLICITY-HTN 3 trial, 1 which found that Medtronic s Symplicity system was not associated with significant reductions in blood pressure compared with a sham procedure, have left some casual observers sceptical about the promise of renal denervation as a means to manage resistant hypertension. However, more sophisticated experts in the field have begun to shed light on the root cause of the trial s failure. It has become increasingly clear that the major problem with radiofrequency-mediated renal denervation is poor efficacy caused by incomplete and inconsistent sympathetic nerve injury and, consequently, inadequate denervation. Non-responders are not necessarily unresponsive to renal sympathetic denervation they are just not adequately denervated. Radiofrequency-based burning from the intima, in a point by point, or even multipoint array suffers from the two main limitations. Firstly, it provides inadequate depth of nerve kill, with porcine studies and a recent human autopsy report 2 showing that the maximum depth of nerve injury is as little as 2mm from the intimal surface (even less in diseased TIM A FISCHELL arteries); therefore, a radiofrequencybased system may potentially miss more than half of the sympathetic nerves. Secondly, with radiofrequency-based burning, there is a lack of circumferential nerve kill as each point burn creates only an about degree arc of damage. Thus, with only 4 5 burns (as was typically done in the US trial), one can only attain at best a degree arc. With both a lack of depth and a lack of circumferential effects, it is likely that 4 6 burns would only achieve 15 30% denervation in many cases. The anatomical challenges related to renal denevation with the radiofrequency-based approach are have also been suggested in a recent analysis of the SYMPLICITY-HTN 3 data by David Kandzari. 3 This analysis showed a dose-response to radiofrequency, such that patients receiving 4 6 burns have essentially no blood pressure lowering effect vs. the sham group. Blood pressure lowering was not observed until one performed 8 9 burns per artery. That a certain number of burns has to be achieved if radiofrequency renal denervation is to be effective may pose a major challenge to the radiofrequency spiral burning concept; there are very few patients (<15%) who have the 4 5cm long renal arteries needed to safely achieve this threshold number of burns. Chemical renal denervation using micro-doses of dehydrated alcohol (ethanol) is a potential alternative to radiofrequency-based renal denervation. It has been evaluated in preclinical and early clinical studies, and has the potential to overcome many of the serious limitations of radiofrequencybased denervation. For example, the Peregrine infusion catheter (Ablative Solutions) has been extensively tested in a porcine model to deliver micro-doses of ethanol to the adventitia. 4 The device s three needles are deployed simultaneously at 120 degree one to another at a depth of about 3.5mm measured from the intima. At this depth, the needle tips are located in the adventitia and thus in very close proximity to the sympathetic nerve fibres. Ethanol doses of 0.3ml and 0.6ml consistently achieve about 85 92% nerve inactivation, as evidenced by drops in renal parenchymal norepinephrine measurements, and by histopathological evaluation 4.Histopathology demonstrates 360 degrees of nerve kill at depths of 8 12mm from the intimal surface. In the early human experience (18 patients treated in a first human use study), there were consistent and significant blood pressure reductions in all patients in the face of a significant reduction of antihypertensive medications. The delivery of 0.3ml of ethanol to the adventitia in these patients was also essentially painless, which offers a major advantage over treatment with radiofrequency catheters. There have been no adverse events at six months of follow-up. Complete analysis of these data will be presented in a peerreviewed publication. Conclusion Chemical renal denervation using ethanol may have numerous advantages over energy-based burning technologies, including: Its ability to achieve 360 degrees of nerve kill at substantial depth to achieve rapid, complete and predictable denervation even in short (<1cm long) renal arteries Its ability to target the nerves where they are located (in the adventitia), sparing injury to the media That it provides essentially painless denervation It does not require for expensive capital equipment. Additional clinical evaluations are underway to better define the safety and efficacy of this promising next generation technology for renal sympathetic denervation. References 1. Bhatt et al. N Engl J Med Epub 2. Vink, et al. Nephrol Dial Transplant 2014; 0: Zoller. Cardiology News 2014 (report on Kandzari data presented) 4. Fischell et al. EuroIntervention 2013; 9: Tim A Fischell is professor of Medicine, Michigan State University, East Lansing, USA. He is also CEO and chief medical officer of Ablative Solutions Embolizing the liver tract a priority to improve outcomes for percutaneous transhepatic interventions Research presented at the Global Embolization Symposium and Technologies US (GEST US meeting, 1 4 May, San Francisco, USA) meeting suggests that patients undergoing transhepatic interventions should have tract embolization performed to prevent haemorrhagic complications Stephen Goode, Sheffield Vascular Institute and the University of Sheffield, UK, presented the study that was designed to identify the incidence of postprocedural haemorrhagic complications in patients undergoing percutaneous transhepatic cholangiography and to further assess the impact of using a dedicated liver tract embolization closure method on patient outcomes. Clinically significant post-procedure haemorrhage occurred in 12% of the cohort who did not undergo embolization for liver tract for closure. Following the incorporation of a dedicated targeted and expanding gelatine foam embolization method for tract closure, we demonstrated a significant decrease in bleeding complications, Goode told delegates. Explaining the background to the study, Goode noted: Increasing numbers of percutaneous transhepatic interventions are being performed worldwide. Recently published results of the British Society of Interventional Radiology Biliary Drainage and Stent Registry showed very high mortality and haemorrhage rates. The researchers conducted a retrospective analysis of all patients undergoing percutaneous transhepatic cholangiography and biliary stent insertion between October 2010 and June 2011 (n=101) to identify rates of complications and death. They then further analysed results of procedures performed between November 2011 and November 2012 after a new dedicated liver tract embolization closure method for percutaneous transhepatic cholangiography and biliary stent insertion was initiated (n=119). Goode and colleagues found that the vast majority of interventions were done for malignant disease (95%). In the cohort that did not undergo dedicated tract embolization, there was a 12% haemorrhage rate. Dedicated liver tract embolization closure was performed in 119 patients and resulted in a significantly decreased haemorrhage rate of 3% (p=0.03). There was also a significant decrease in postprocedural haemoglobin drop in this cohort (p=0.04). Stephen Goode Goode told Interventional News: These data provide a significant step forward for percutaneous transhepatic procedures. We have shown that utilising a targeted and expanding gelatin foam pledget (Hunter Biospy Sealing Device, Vascular Solutions) for embolizing and essentially closing the liver tract following percutaneous transhepatic procedures, we can decrease haemorrhagic complications associated with these procedures. This is via decreasing the overall rate of arterial haemorrhage but also the subclinical venous bleeding (from portal vein and hepatic venous branch injuries) leading to decrease in haemoglobin post procedure. In our institution we perform all our percutaneous liver work utilising this methodology including percutaneous transhepatic cholangiography and biliary stenting and also portal vein embolization procedures. We hope that these data and liver tract embolization methodology that we have presented will go some way to improving outcomes for percutaneous liver procedures and improving safety and clinical outcomes for patients undergoing these high risk interventions.

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30 30 New horizons Selective catheterisation of occluded fallopian tubes is safe and effective A study from Lublin, Poland, that set out to evaluate the results of selective catheterisation of occlusions in the proximal fallopian tubes and its effect on fertility, was presented at the Global Embolization Symposium and Technologies US (GEST US, 1 4 May, San Francisco, USA) meeting The research has found that the procedure can be considered a safe and effective procedure for tubal recanalisation, and that it is highly acceptable for patients. Malgorzata Szczerbo-Trojanowska and team, Department of Interventional Radiology, Medical University of Lublin, Lublin, Poland, noted that since selective catheterisation is an effective and relatively inexpensive procedure, it should be considered as the first step in the treatment of infertility due to tubal occlusion. Fallopian tube recanalisation has emerged as an excellent, patient-friendly, less-invasive and cost-effective alternative to tubal microsurgery and in vitro fertilisation in the treatment of proximally obstructed fallopian tubes in well-selected patients, Szczerbo-Trojanowska told Interventional News. The method would particularly be useful for couples who have ethical or religious concerns that do not allow for in vitro fertilisation and embryo transfers, she added. In the single centre study, 128 patients with bilateral tubal occlusion, as confirmed by hysterosalpingography underwent non-invasive transcervical tubal recanalisation using endovascular equipment under fluoroscopy. The patients were treated between 2011 and 2012 and the investigators evaluated the effectiveness of the treatment (follow-up, 3 9 months). Other items assessed were procedure time of the recanalisation, the radiation dose used, and the level of pain accompanying the procedure, said Krzysztof Pyra, who presented the study. Results The researchers found that the recanalisation rate was 86%. Among the patients in whom tubal patency was restored, 23 became pregnant, yielding an effective 21% pregnancy rate. The average execution time of Malgorzata Szczerbo-Trojanowska Krzysztof Pyra recanalisation was 26 minutes, and the average dose of radiation used during the procedure was 73 mgy. The complication rate was 2.8%, including extravasation of contrast agent into the myometrial venous plexus (2%) and fallopian tube perforation (0.8%), Pyra said. First patient treated using incisionless system for symptomatic uterine fibroids Gynesonics has announced the first treatment of a patient in Cologne, Germany, using the new VizAblate system. According to a press release from the company, VizAblate is the only medical device to integrate ultrasound imaging with radiofrequency ablation in a single handheld device for the treatment of fibroids. The system is minimally invasive and is inserted through the cervix without any need for incisions. Thomas Röme and Ralf Bends performed the first procedure with the system at Evangelisches Krankenhaus Köln-Weyertal ggmbh in Cologne, Germany. The intrauterine ultrasound imaging made the navigation and radiofrequency ablation extremely efficient. The entire system can be mastered with a very achievable and short learning curve. This system may produce a paradigm shift in the way patients are treated for symptomatic uterine fibroids, a press release from the company said. The procedure was straightforward thanks to the unique and improved design of the new VizAblate System, Bends added. The new VizAblate System has been designed to improve ease-of-use, increase ultrasound resolution, and streamline the graphical user interface. The incisionless procedure preserves the uterus, does not involve laparoscopy or hysteroscopy, and features the industry s first, exclusive graphically-based ablation sizing guide and safety margin indicator. Procedures that are amenable to an outpatient setting and have short procedure times. VizAblate can ablate larger and deeper fibroids that are not treatable by other transcervical methods. Based on our experience, the Gynesonics VizAblate System, which does not require an incision, offers an exciting and less invasive treatment for symptomatic uterine fibroids, said Römer. Bariatric Embolization: The first image-guided therapy targeting obesity Bariatric Embolization is the first image-guided transvascular procedure targeting obesity. By anatomically and functionally isolating a specific portion of the stomach via particle embolization, bariatric embolization has the potential to provide a minimally invasive alternative to bariatric surgery. This is an extremely promising new procedure, researchers say, but they maintain that further clinical studies need to be validated before this technique can be used routinely in humans Speaking at a session at the Global Embolization Symposium and Technologies (GEST) US meeting (May 1-4, San Francisco, USA), Aravind Arepally, Division of Interventional Radiology at Piedmont Radiology, Atlanta, USA, outlined the future directions for bariatric embolization, a procedure that is lower risk, and potentially cheaper than more invasive weight loss interventions such as gastric bypass and laparoscopic approaches. Defining the procedure for delegates, Arepally said bariatric embolization was a minimally invasive image-guided therapy targeting the functionality of the stomach. The procedure involves a targeted delivery of embolics used to defunctionalise specific portions of the stomach in order to impact mechanical functionality by impairing hormonal production in the stomach, he noted. Arepally drew attention to the BEAT Obesity (Bariatric embolization of the arteries for treatment of obesity) clinical trial that has just commenced recruiting (August 2014). Jointly undertaken by two centres in the USA, Johns Hopkins Medical Institution in Baltimore and Mount Sinai in New York City, the trial is designed to determine if bariatric embolization is a safe and viable option to traditional gastric bypass surgery for treating obesity. The BEAT trial is a phase I study that will evaluate the feasibility, safety and efficacy of bariatric embolization in morbidly obese patients with follow-up for one year post embolization, said Arepally. The primary endpoints of this study are weight loss (percentage of total body loss) and 30 day adverse events. Although there are over 40 hormones that limit food intake, there is only one hormone, ghrelin that has been shown to stimulate food intake. Bariatric embolization aims to impair the production of is ghrelin. Arepally told delegates that ghrelin is the most potent appetite stimulant, and majority of the hormone is produced in the gastric fundus. The levels of ghrelin rise before meals; its levels fall after eating and rise with dieting. He also reported that the procedure could also affect hormones such as GLP-1, which is associated with type-2 diabetes. Bariatric embolization in not without side-effects. Endoscopy in the animal studies reveal that there are ulcers seen in 2/6 (33%) of treatment animals. There is also a relatively high incidence of non-target embolization and gastritis seen in all animals. Arepally pointed out that future directions for basic science regarding the procedure would involve maximising the precision of delivery.

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33 Canada lags on adoption of interventional radiology Global IR 33 The findings from a report commissioned by the Canadian Interventional Radiology Association (CIRA) and carried out by the Millennium Research Group (MRG) indicate that Canada lags behind other industrialised countries in the G7 such as Europe, USA and Japan in the adoption of interventional radiology treatment. Canada received formal recognition of interventional radiology as a clinical subspecialty in 2013 lower-than-average adoption of interventional The radiology in Canada is problematic for the Canadian healthcare system, because interventional radiology has been shown to reduce patient hospital stays, reduce the need for follow-up, and reduce patient costs, the report finds. The report also points out that there is significant room for improvement in Canada in terms of adoption of interventional radiology procedures and finds that the lag in adoption is due to a multitude of factors including healthcare funding, lack of physician resources and lack of awareness about interventional radiology procedures. MRG analysed eleven key therapy areas in interventional radiology to determine the value that treatment brings to both patients and the healthcare system. Additionally, a cost analysis of minimally-invasive interventional radiology therapy relative to the surgical alternative was conducted for three therapy areas including: lower extremity peripheral arterial disease, abdominal aortic aneurysm repair, and interventional oncology for hepatocellular carcinoma. For the cost analysis, US Medicare claims records were analysed for hospital charges, as well as patient metrics such as lengths of stay, complications and mortality. an active role in the development of the subspecialty in Canada through interventional radiology-based education and training. MRG further recommended that CIRA should partner with other physician groups to drive patient and physician awareness of interventional radiology. The Canadian government and healthcare facilities should make efforts to take advantage of interventional radiology s value in order to reduce financial strain and improve patient care, the report concludes. Factors hindering adoption Based on the results of the research, MRG analysed that healthcare funding in Canada dissuades the adoption of interventional radiology. The Canadian government and hospital administrators should revise the system of budget allocation towards interventional radiology procedures by providing separate funding for these treatments, they recommended. They also found that interventional radiologists are overworked, but must dedicate more time to improving their clinical practice. In order for this to take place, MRG recommended that Canadian hospitals should increase interventional radiology support staffing. Another key area identified by the report was that more interventional radiologists should be trained and hired to keep up with the current and future demands on the interventional radiology departments of Canadian hospitals. In order to meet this requirement, the awareness of interventional radiology must improve and CIRA should continue to play

34 34 Comment and analysis Optimising radiation protection in 2014 COMMENT & ANALYSIS Optimisation is one of the key goals of the new imaging modalities and image acquisition protocols. The manufacturers have made an impressive effort in the last years to the hardware and in post-processing tools to reduce patient doses, while maintaining or even improving image quality, write Gabriel Bartal and Eliseo Vano Interventional radiology is a rapidly evolving, relatively young field of modern medicine and is based on providing image-guided (mainly fluoroscopy-guided) minimally invasive procedures. The core imaging modality for the vascular interventionist is still good old angiography. The hazards of ionising radiation to patients and personnel are well-known and require very special means of intelligent dose management and active radiation protection. CT angiography and cone beam CT are an integral part of any imaging work-up and involve a great clinical benefit, but contribute to an additional radiation burden on the patient s cumulative dose. Patient and staff dose management and radiation protection are particularly challenging in below the knee interventions, haemodialysis access management and hybrid procedures performed in Interventional Radiology suite or operating rooms (the so-called hybrid rooms). We believe that the emphasis should be on protecting patients (subsidiary account being taken of the radiation detriment from the exposure of the radiological staff and of other individuals) so that physicians have to justify medical procedures and optimise radiation protection. Optimisation is one of the three GABRIEL BARTAL ELISEO VANO fundamental principles of the radiological protection structure promoted by the International Commission on Radiological Protection (ICRP) and is applicable to both patient exposure as well as personnel exposures. Diagnostic reference levels should be used to help in optimisation of protection during medical imaging. These indicate whether, in routine conditions, the level of patient dose from a specified imaging procedure is unusually high or low for that procedure. Then, a local review should be initiated to determine whether protection has been adequately optimised or whether corrective action is required. Justification and optimisation criteria should be the key components considered in the update of the radiation protection aspects of the quality assurance programs when medical facilities introduce new technology (including new software) involving relevant changes in patient doses or image quality. In 2001, the ICRP advised application of diagnostic reference levels in interventional radiology with the suggestion of taking into consideration not only the usual clinical and technical factors, but also the relative complexity of the procedure. Following the ICRP recommendation to reduce the personnel dose limit to the lens of the eyes and its adoption by international and European Basic Safety Standards, the measurement and follow-up of staff lens doses should be part of the quality programs in any Interventional Radiology practice. Optimisation is one of the key goals of the new imaging modalities and image acquisition protocols. The manufacturers have made an impressive effort in the last years to improve the hardware and post-processing tools to reduce patient doses, while maintaining or even improving image quality. The introduction of digital systems allows for the collection and archiving of dosimetric and demographic data of all the imaging procedures as part of the Digital Imaging and Communications in Medicine (DICOM) headers, or using other DICOM services. Clearly, analysis of departmental results needs to be subjected to quality control. European regulations requiremeasurement and recording of patient doses from interventional radiology procedures. The SIR Standards of Practice Committee published Quality Improvement Guidelines for Recording Patient Radiation Dose in the Medical Record for Fluoroscopically-Guided Procedures in the Journal of Vascular and Interventional Radiology in January This paper states that ideally, all available patient radiation dose data should be recorded and recognises that in the future, this may become an automatic process, as the FDA has expressed an intention to establish requirements for CT and fluoroscopic devices to provide radiation dose information for use in patient medical records or a radiation dose registry. These guidelines also suggest adequate recording of different dose metrics for all interventional procedures requiring fluoroscopy including skin dose mapping, should be carried out. It also suggests establishing thresholds to prompt reviews. We have seen that the use of medical simulators for basic as well as advanced training have proved to improve the operator s skills and consequently to reduce fluoroscopy time. Dose management and radiation protection training should become an integral part of simulator-based individual and team procedure training. Diagnostic reference levels (DRLs) have proved to be a very useful tool in the optimisation of fluoroscopy-guided interventional procedures. Appropriate optimisation shall be undertaken whenever DRLs are consistently exceeded and appropriate corrective action shall be applied. We expect more advice from ICRP to clarify some aspects of optimisation strategies that would comprise not only stochastic, but also deterministic (tissue reactions) effects. As complete patient individual doses distribution becomes available, other optimisation options could be considered and implemented (ie. decreasing high dose tails in the distributions and discriminating individual high dose values for clinical follow-up). Clearly, adoption of the above listed dose management and patient radiation protection strategies will ultimately reduce personnel exposure. Gabriel Bartal is director, Department of Medical Imaging and Interventional Radiology at Meir Medical Center, Kfar Saba, Israel. Eliseo Vano is professor of Medical Physics at the Complutense University of Madrid and head of Medical Physics Service, San Carlos University Hospital, Madrid, Spain. The authors have reported no disclosures pertaining to the article A rough guide to implementing a radiation protection culture COMMENT & ANALYSIS EFSTATHIOS EFSTATHOPOULOS Radiation protection culture is a dynamic process that needs continuous evaluation and update. It should be an integral part of clinical routine and demands deep knowledge of radiation risks, safety rules and active participation of all stakeholders, writes Efstathios Efstathopoulos Culture is one of the two or three most complicated words in English language. The most attractive one for the purpose of this article is that culture is the total range of activities and ideas of a group of people with shared traditions, which are transmitted and reinforced by members of the group. According to the International Radiation Protection Association (IRPA), radiation protection culture is defined as The combination of knowledge, values, behaviours and experience of radiation protection in all its aspects for patients, workers, population and enviroment, and in all exposure situations, combining scientific and social dimensions. In other words, radiation protection culture is the assembly of attitudes, strategies and practices among staff and leaders that emphasise in radiation protection safety. The number of interventional radiology and interventional cardiology examinations have almost doubled in the last decade. Interventional procedures deliver effective dose to the patients ranging from 5 to 70mSv and contribute about 8% to collective dose. Due to the high radiation doses that patients and staff are exposed to, the establishment of radiation protection culture is important in every interventional radiology department. Continued on page 36

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36 36 Radiation protection A rough guide to implementing a radiation protection culture Continued from page 34 In interventional radiology, the radiation protection culture is primarily oriented towards patient and staff dosimetry, and staff education. The objectives of radiation protection culture are to provide a safe working enviroment, promote knowledge of radiation risks, minimise unsafe practices, control radiation risks, share responsibility among workers and improve the quality of an already existent radiation protection programme. According to IRPA, the radiation protection culture principles, include the well-established justification, optimisation and dose limitation principles, but also include the sharing of competence by training and education. In order to establish radiation protection culture in an interventional radiology department, three main factors play the key role: The leader and the other interventionalists have to demonstrate absolute commitment to safety Decision-making procedures should reflect safety first A quality assurance programme should be running in the routine work of the department But how we can achieve the development and implementation of radiation protection culture in a department? How easy is it to apply a radiation protection culture in clinical routine and who should be involved in this? The establishment of radiation protection culture requires: Continuing education of the staff and professional development with the organisation of training courses, workshops, seminars and e-learning systems. Creation of a positive, supportive and motivating work environment which will ensure trust between managements and employees and leadership among workers. Stakeholder engagement: effective communication among stakeholders of all levels including health authorities, researchers, medical staff, manufacturers and patients. In practice, there are simple and effective ways to achieve the implementation of a radiation protection culture in a department including rewarding of good and conviction of unsafe practices, guidelines and recommendations, radiation doses according to ALARA principle, special attention to radiation protection of children, optimised protocols, quality assurance programmes and personnel dosimetry. In addition, less-invasive procedures and reduction of radiation exposure are crucial for the development of a radiation protection culture. The implementation of a radiation protection culture is being driven from the highest level. Managers, medical professionals, health professionals and workers are directly involved and have a key role in the execution of such a culture in every department. Radiation protection experts enhance safety culture, provide leadership, develop relationships with the administration and the employees and are responsible for the staff training and the constitution of guidelines and recommendations under the guidance of radiation protection associations such as the IRPA. Radiation protection culture is a dynamic process that needs continuous evaluation and update. It should be an integral part of clinical routine and demands deep knowledge of radiation risks, safety rules and active participation of all stakeholders. For the successful establishment of a strong radiation protection culture programme, authorities, professionals, workers, patients and general public must fully understand the role of radiation protection culture and fill the gap between theory and practice. Efstathios Efstathopoulos is an associate professor of Medical Radiation Physics, 2nd Department of Radiology, Medical School, University of Athens, Greece. He has reported no disclosures pertaining to this article ADVERTORIAL Long-term experience shows enduring favourable results for multi-use balloon expandable Advanta V12 stent The Advanta V12 stent (MAQUET) is the company s proprietary balloon-expandable covered stent technology. Richard G McWilliams, Radiology Department, Royal Liverpool University Hospital, Liverpool, UK, spoke about his centre s experience with the Advanta V12 McWilliams said the Advanta V12 is used in his unit, the in-patient centre in an arterial network in the UK National Health Service (NHS) which has a long history of recognised excellence in vascular surgery and intervention. There are 10 vascular surgeons and seven full-time, consultant interventional radiologists at the centre. We were the first centre in the UK to start using fenestrated grafts. At the beginning we often used uncovered stents, depending on the amount of infrarenal neck in the FEVAR cases, but as we progressed to shorter and shorter necks, we needed more often to use a covered stent. When the Advanta V12 came out we started using it early in our experience and we now use it routinely. There are a wide range of applications for the Advanta V12 stent, including FEVAR. Because our experience has been so good we extrapolated this and have had the confidence to use the Advanta V12 at other sites where we had traditionally used uncovered stents, comments McWilliams. Other indications include: supraaortic branches (such as the subclavian artery) and common carotid ostial lesions and mesenteric ischaemia for coeliac access and SMA stenotic disease. Referring to Gustavo Oderich s (professor, Vascular and Endovascular Surgery and Vascular Center, Mayo Clinic, Minnesota, USA ) study in which the primary patency at 36 months for covered vs. bare metal for chronic mesenteric ischaemia for the primary intervention arm was 92% vs. 52%, McWilliams says it supports their empirical decision to use the stent with good evidence. The Advanta V12 RX system is also applicable in other visceral arteries to treat renal artery stenosis and renal artery aneurysms (if stenting is used rather than liquid embolics) and hepatic artery pseudoaneurysms. McWilliams says, at his unit, the Advanta V12 has also been employed in aortic trauma and aortic stenosis and in CERAB (Covered Endovascular Reconstruction of Aortic Bifurcation) procedures treating aortoiliac occlusive disease. McWilliams notes that they are very pleased with the CERAB technique with the three stent approach with one placed in the aorta and two in the common iliacs to create a new aortoiliac bifurcation. He says they are very happy to do this percutaneously. Usman Shaikh is the lead for CERAB at Royal Liverpool University Hospital. He says the benefits of using the Advanta V12 are that there is a good range of sizes to fit different anatomies, it is covered inside and outside which avoids snagging of J-tip guidewires and makes repeat access uncomplicated and, in a post-dilation setting, it can be flared at the level of the fenestration to lock it and facilitate subsequent access. He notes that restenosis and occlusion rates, at his unit, are very low. The best data on this is the COBEST (Covered vs. Bare Metal Stent) trial from Perth, Australia, which rounds things off nicely as Perth is the home of fenestrated grafting and that is where our initial driver for using the Advanta V12 for fenestrated came from. Further use of the stent is supported by the COBEST study, noted McWilliams. Richard McWilliams The COBEST study was published in the Journal of Vascular Surgery in It showed that covered stents performed best for TASC C and D aortoiliac lesions in long-term patency in clinical outcome. McWilliams added to this saying that, from their clinical results using the Advanta V12 in FEVAR at 10 years, there were no recorded Advanta V12 stent occlusions. We are looking forward to some further data in the future on the Advanta V12 vs. Bare Metal Stents in the iliac system from ongoing studies. Our experience with the stent is very positive and combined with modern, flexible sheaths we are able to deliver this stent everywhere. We have no fears about reaching for an Advanta V12 stent.

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38 38 Global IR The 11th Scientific Meeting of the Chinese Society of Interventional Radiology successfully held in Changsha The 11th Scientific Meeting of the Chinese Society of Interventional Radiology (2014 CSIR) was held from June 2014 in Changsha, China. The Chinese Society of Interventional Radiology writes this report for Interventional News The 2014 CSIR conference provided an opportunity for interventional physicians to exchange views with their peers in academic circles both at home and abroad, enhancing the influence and reputation of the society. It was supported by the Chinese Society of Interventional Radiology, Hunan Provincial Hospital, and the Third Affiliated Hospital of Sun Yat-sen University. There were over 3,500 participants from China (including Taiwan), USA, Japan, Singapore, Korea, India and other countries and regions. Compared with previous CSIR meetings, this year s event hosted the largest number of participants. There were around 265 lectures scheduled for discussion on hot topics in five main fields, including neurointervention, peripheral vascular intervention, oncological intervention, paediatric intervention, and musculoskeletal intervention. As chairman of CSIR, Hong Shan, Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, hosted the opening ceremony. The conference then commenced with the Plenary Speech delivered by Xu Ke, Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China, who lectured on Seizing opportunities, meeting challenges, and continuously upgrading the strength and status of the medical imaging department. Then, Gaojun Teng, Department of Radiology at Zhong-Da Hospital, Southeast University, Nanjing, China, gave a lecture on The importance and practice of multidisciplinary multicentre randomised controlled trials for the development of interventional radiology. Shan then presented on Interventional radiology technology promotes the development of precise medicine followed by Jie Tian, Institute of Automation, Chinese Academy of Sciences, who spoke on The future of interventional operation based on optical molecular imaging. Guest speakers included Brian Stainken, Roger Williams Medical Center, Providence, USA and Society of Interventional Radiology past president, David Kumpe from University of Colorado, Denver, USA, Shozo Hirota, Hyogo College of Medicine, Japan, Osamu Matsui Xu Ke Hong Shan Brian Stainken receives honorary membership from Gaojun Teng from Kanazawa University Graduate School of Medical Science, Japan, were invited to give lectures. Stainken and Matsui were granted the Honorary Members Award given to international experts who have made great contribution to the development of interventional radiology in China. Several dedicated academic activities were held during the conference. One of these was the English Papers Report Grand Prix for young interventional radiologists. Forty four contestants were first put into four groups to present their own previously prepared slideshows. Three participants from each group were then selected into the final. During the final, four groups of three participants were formed by lottery, and each participant was given an article selected by the board of judges. Participants were given one and a half days to prepare a reading report on the designated article in the form of slideshows for presentation. Their performance was then scored by both the judges and the audience, weighing 70% Opening ceremony and 30%, respectively. One champion, two second awards, and three third awards were given based on their score. The winner was provided a scholarship to attend the 2014 CIRSE conference. The best young interventional radiologists from the country applied for the competition, and during the final, with the limited amount of time given, each participant was able to organise a wellstructured presentation. In addition, the interventional nursing forum was the first of its kind in China and the Interventional Development Forum was another highlight, during which directors of more than 100 major local medical centres in the Hunan Province were invited to listen to special lectures on hospital management and development. Flow 2014 meeting turns spotlight on Interventional Radiology in India The 16th annual conference of the Indian Society of Interventional Radiology, ISVIR 2014, was held 3 6 April in Mumbai, India. The theme of the meeting was flow of ideas, progress, and of course, as physicians who spend a lot of time opening blocked arteries, of blood to the feet! The organisers, Gireesh Warawdekar and Vimal Someshwar, arranged a three and a half day meeting with daily themes of venous interventions, peripheral vascular interventions, aortic interventions, oncology, and neurointerventional radiology. The meeting was attended by over 320 registrants all over India and the world. International faculty from the UK, the US, Japan, Korea, Greece, Germany and Singapore participated. Two keynote addresses were offered by John Kaufman, Dotter institute, Portland, USA, whose lecture Interventional Radiology: the first 50 years Highlights of the Flow meeting focused on the great strides we have made toward achieving Charles Dotter s vision. Chander Mohan then offered a National Oration, summarising the state of interventional radiology in India and noting the opportunities at hand to take charge of the field s future. Other meeting highlights included an inspiring early morning group walkathon that included several patients treated for peripheral vascular disease who shared inspirational stories of how interventional radiology solutions had helped them become mobile again. There was also an exciting competition among the interventional radiology fellows at leading institutions throughout India, and a groundbreaking session on training opportunities in interventional radiology that focused all on the great need for more training to meet demand in this populous country. As the meeting wound down with a rousing Bollywoodthemed party, Someshwar said: A well-rounded scientific programme, an extensive exhibition and enjoyable evening functions were well appreciated by attending interventional radiologists.

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40 40 Peripheral arterial disease Women have similar procedural success as men after peripheral interventions, despite more severe disease Women could be at higher risk for adverse outcomes than men, but overall they have similar procedural success compared with men despite higher complications rates, data from a study published in Journal of the American College of Cardiology in June suggests In the study, outcomes of lower extremity peripheral vascular interventions in women were associated with a higher rate of vascular complications, transfusions, and embolism, but there were no differences observed for in-hospital death, myocardial infarction, stroke or transient ischaemic attack. Elizabeth Jackson, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, USA, and colleagues set out to examine sex-related differences in outcomes related to peripheral vascular intervention procedures since percutaneous peripheral vascular interventions are frequently performed to treat peripheral arterial disease. However, little is known about sex-related differences related to peripheral vascular intervention procedures, the authors write, explaining why they undertook the study. The investigators assessed the impact of sex among 12,379 patients (41% female) who underwent lower extremity peripheral vascular interventions from 2004 to 2009 at 16 hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium Peripheral Vascular Interventions registry. They carried out a multivariate propensity-matched analyses to adjust for differences in baseline characteristics, procedural indications, and comorbidities on the basis of sex. We found that women had excellent outcomes compared to men, even though they were older and had more severe disease, said senior study author P Michael Grossman, an interventional cardiologist at the University of Michigan Frankel Cardiovascular Center and director of the cardiac catheterization laboratory at the Veterans Administration Ann Arbor Healthcare System. Compared with men, women were older at the time of the procedure and have multilevel disease and critical limb ischemia. In a propensity-matched analysis, female sex was associated with a higher rate of vascular complications, transfusions, and embolism. No differences were observed for in-hospital death, myocardial infarction, or stroke or transient ischemic attack. Technical success was more commonly achieved in Elizabeth Jackson women (91.2% vs. 89.1%, p=0.014), but because of a higher complication rate, the overall procedural success rates were similar in men and women (79.7% vs. 81.6%, p=0.08), Jackson and colleagues wrote. In a press release from University of Michigan Health System, the researchers noted that it was surprising to observe no gender-related differences in procedural success considering that women experienced more transfusions, vascular complications and embolisms. The authors therefore concluded that women represent a significant proportion of patients undergoing lower-extremity peripheral vascular interventions, have P Michael Grossman a more severe and complex disease process, and are at increased risk for adverse outcomes. Despite higher complications rates, women had similar procedural success compared with men, making peripheral vascular intervention an effective treatment strategy among women with lower extremity peripheral arterial disease. The data suggests women may benefit to a greater degree with an invasive percutaneous strategy for the management of peripheral arterial disease, particularly if complications can be avoided, said study author Elizabeth Jackson, cardiologist and director of the University of Michigan Women s Heart Program. Angioscopy system used to guide wiring in chronic total occlusions Daisuke Kamoi, Nagoya Kyoritsu Hospital, Nagoya, Japan, reported on the first-in-man experience of angioscopy-guided chronic total occlusion techniques in peripheral arterial lesions at the EuroPCR congress (20 23 May, Paris, France). The system used in the study was the I-Light angioscopy system from iheart Medical Kamoi told delegates that chronic total occlusions remain one of the most challenging lesions in interventional medicine, especially in longer and complicated peripheral arterial disease lesions. Recently, in order to improve the revascularisation success rate, we investigated the efficacy of using an angioscopyguided technique to penetrate the true lumen of chronic total occlusions, he said. He explained that the angioscope is positioned proximally to the chronic total occlusion lesion, and the luminal observation of chronic total occlusion entry was achieved for 60 to 80 seconds with single balloon occlusion and saline flushing. After visually identifying the centre of chronic total occlusion entry, the wire is inserted through the balloon and tip lumen to penetrate the lesion. Then the wire drilling is monitored by angioscopic and cineangiography screen simultaneously, to ensure the wire is in true lumen. Furthermore, the stiffer wire is determined after the chronic total occlusion entry is confirmed by angioscopy. Kamoi then presented the first-in-man cases with the system. In the first, a superficial femoral artery chronic total occlusion lesion, the main artery chronic total occlusion entry was confirmed by angioscopy. After the soft wire penetrated the core, a stiffer wire passed the true lumen easily. In the second case, the retrograde wire was viewed by angioscopy, and the two wires were in the same lumen. Then the retrograde wire was inserted into the antegrade sheath. We performed eight cases until February 2014, with 100% success. The new technique using angioscopy to guide wiring in chronic total occlusion lesions was safe and efficient. To further enhance the user friendly procedure, a new delivery catheter of double wires is under development, Kamoi said. He added, This forwardlooking visual technology enables strategic selections of chronic total occlusion crossing methods from the characteristic observation of the entrance. Kamoi also noted that the system has limitations: it is difficult to observe the orifice of the superficial femoral artery, and it required pre-dilatation for the bulky device to pass the lesion prior to chronic total occlusion. SCAI publishes recommendations for treating arterial disease below the knee The third paper in the series, published online on 18 July 2014 in Catheterization & Cardiovascular Interventions, outlines recommendations for treating infrapopliteal, or arterial disease below the knee Bruce H Gray, professor of Surgery/Vascular Medicine, University of South Carolina School of Medicine, and lead author of the consensus paper said: Depending on the patient s condition, open surgery, an endovascular intervention or amputation are considered an appropriate course of action. These new recommendations aim to help guide physicians to make the best care decisions when an endovascular approach is appropriate. The expert panel reviewed scientific data on each critical limb ischaemia treatment option, including balloon angioplasty, stents, atherectomy, as well as experimental therapies such as drug-coated balloons. The recommendations state that patients with severe disease, those with pain at rest and those with minor or major tissue loss should be considered for revascularisation, with either surgery or endovascular treatment to prevent amputation or improve healing fol- Continued on page 42

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42 42 New studies OVER analysis: Endoleak does not predict reduced long-term survival, but is associated with less sac shrinkage An analysis of the OVER trial presented at the Society for Vascular Surgery Vascular Annual Meeting (SVS, 5 7 June, Boston, USA) shows that endoleaks were common in patients treated with endovascular aneurysm repair (EVAR) in the study, with an incidence of 31% Wei Zhou, professor of Surgery, Stanford University and VA Palo Alto Health Care System, Stanford, USA, who presented the results of the analysis, said that 53% of the endoleaks seen in the trial resolved spontaneously. The OVER trial randomised 881 patients at 42 Veteran Affairs centres in the USA and 439 of the patients received successful EVAR. The study showed a lower perioperative mortality rate for EVAR (0.5%) vs. open repair (3%, p=0.004), but there was no significant difference in mortality at two years (7% vs. 9.8%, p=0.13). The objective of the analysis presented at the SVS meeting was to identify risk factors and long-term outcome of endoleaks in patients who received successful EVAR in the OVER cohort. In the analysis, logistic regression SCAI publishes recommendations for treating arterial disease below the knee Continued from page 41 lowing amputation. Currently there is insufficient evidence to support treatment in those with asymptomatic disease. Intervention to treat infrapopliteal arterial disease can be challenging because the patients comorbidities, the anatomic variables, and the limitations of our techniques. Clinical scenarios based on anatomic and clinical variables are presented. Recommendations regarding intervention (appropriate care, may be appropriate care, rarely appropriate care) are made based on best evidence), the authors write while introducing the recommendations. Critical limb ischaemia is the predominant clinical indication for treatment of infrapopliteal arterial disease and occurs when arterial perfusion is reduced below a critical level resulting in ischaemic pain and/or skin breakdown. Prompt revascularisation is aimed at symptom relief with improved limb salvage and ulcer healing. Multilevel disease is more common than isolated infrapopliteal disease, and a systematic approach to achieve straight-line flow from the iliac to pedal arch with complete revascularisation is necessary to optimise outcomes. Percutaneous transluminal angioplasty is the current standard for endovascular therapy for clinically significant infrapopliteal disease. Bailout bare metal and drug-eluting stents in the tibial arteries should be considered for failures of balloon angioplasty. Studies are currently enrolling patients to address the use of combined strategies (ie. atherectomy and drug-coated balloons). Further data are needed regarding the utility of atherectomy devices, drug-coated balloons, drug-eluting stents, and bioabsorbable stents in infrapopliteal interventions. However, until these results are available, given the increased costs of other modalities (eg. cutting balloons, cryoplasty, laser, orbital, rotational, and directional atherectomy catheters), and the lack of comparative data to support their efficacy, balloon angioplasty should remain the initial endovascular therapy for most infrapopliteal disease, the document concludes. was used to identify predictors for endoleaks and secondary interventions. Of the total of 439 patients treated with EVAR, 134 (31%) developed 187 endoleaks over a mean follow-up of 62±2.4 years and five aneurysms ruptured. Zhou, speaking on behalf of the OVER Study Group, noted that the results showed that there was no difference in survival between patients who developed endoleaks and those who did not. She explained that the 187 endoleaks included 76% type II leaks, 12% that were type I, 3% that were type III, 3% that were type IV and 6% that were indeterminate. Age >75 years predicted the presence of endoleaks on univariate analysis, but did not show significant on the multivariate model. Neck length and angulation Large real-world experience shows positive results with Zilver PTX in challenging patient population A post-market surveillance (PMS) study of the Zilver PTX drug-eluting stent (Cook Medical) conducted in Japan has shown positive results with the device in the treatment of femoropopliteal lesions. According to the investigators, the results confirm the benefit of the Zilver PTX technology. The 12-month results, which were presented at the EuroPCR congress (20 23 May 2014, Paris, France), show no safety concerns and no increased thrombosis with the device. Hiroyoshi Yokoi, Department of Cardiovascular Medicine, Fukuoka Sanno Hospital, Fukuoka, Japan, who presented the results on behalf of the investigators, explained that the Zilver PTX clinical programme included pre-market studies (a randomised controlled trial and a single-arm study) and post-market studies such as the Japan PMS study of 907 patients. Yokoi said that, in comparison to the pre-market studies, the Japan PMS study treated more complex patients and lesions as it was all allcomers study with no exclusion criteria used to eliminate patients from enrolment. The Japan PMS were not associated with the development of endoleak in the OVER cohort with relatively good anatomy. The presence of endoleak was significantly associated with less sac shrinkage (p<0.001). Fifty three per cent of endoleaks resolved spontaneously. Of those that did not resolve Medtronic s endograft appeared to have less than half (35) the endoleak rate of Cook Medical (74) and Gore (76), but the time from endoleak detection to resolution was not significantly different among the endografts. The initial aneurysm size independently predicted a need for secondary intervention (p<0.001), and 32% of patients with endoleak received secondary intervention (10% of all patients), Zhou said. She added, Delayed type II endoleak (detected more than one year following EVAR) was significantly associated with sac enlargement compared to type II endoleak detected early. There was no difference in aneurysm size or length of survival between type II and other types of endoleaks. Hiroshi Yokoi patients were older and had a higher prevalence of diabetes and renal disease, he said. In addition, the lesions were more complex they were longer, with more in-stent restenosis and fewer patent runoff vessels and patients had significantly greater incidence of critical limb ischaemia, twice the incidence reported in the pre-market studies. At EuroPCR, he presented 12-month follow-up results that were available for 802 patients. In 58% of them, he said, patency was assessed by ultrasound if this was the standard of care. He told delegates that freedom from target lesion revascularisation was 97.3% at six months and 91.4% at 12 months, similar to the rates seen in both pre-market studies, and that the rate of thrombosis/occlusion was 3.2% at 12 months. Summarising the results, Zhou stated that endoleaks were common and did not affect long-term survival, and that the presence of endoleaks was significantly associated with less sac regression; large aneurysms predicted future secondary interventions; type II endoleaks had similar effects on aneurysm size over time compared to other types; and delayed type II endoleak was significantly associated with late sac enlargement. She explained that the analysis had some limitations: endoleak detection and classification were not centrally adjudicated, there was no randomisation between devices, and the decision for endoleak interventions was made by individual surgeons. In conclusion, Zhou told delegates at the SVS meeting, The presence of an endoleak does not predict reduced long-term survival, but negatively impacts sac regression. In addition, delayed type II endoleaks behave more aggressively than their earlier counterparts. Long-term surveillance is essential. The 12-month thrombosis/occlusion rate from the Japan PMS was low and similar to the rates seen in the ZILVER PTX randomised controlled trial (1.9%) and the singlearm study (2.7%). It is also similar to the rates seen with the Zilver bare metal stent in the randomised controlled trial (3.6%) and to bare metal stent periprocedural rates in the literature (2 5%), he stated. The primary patency rate as assessed by duplex ultrasound (n=469) was 84.4% at 12 months, and this rate was similar to the rates seen in both pre-market studies. Yokoi said that the Japan PMS study results were positive and confirmed the benefit of this paclitaxeleluting technology. There is a large amount of clinical data available for Zilver PTX, ranging from carefully controlled level I evidence to large, global, real-world experience. As expected, the patient population and lesion characteristics become more challenging in real-world, all-comer studies. The consistency seen across studies provides added assurance of the performance of the Zilver PTX drug-eluting stent, he concluded.

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44 44 Market watch Product News FDA IDE approval for Vici venous stent system Veniti has announced that it has received approval from the US FDA for an investigational device exemption to begin the VIRTUS trial of the Vici venous stent system. The Vici venous stent system was designed from inception to be compatible with the unique anatomy and pathophysiology of the venous system. Until recently, the only treatment options available for lower-extremity venous disease patients involved the use of repurposed vascular stents originally designed for use in the arterial system. Co-principal investigators for the VIRTUS trial are William Marston, chief, Division of Vascular Surgery, professor, Department of Surgery, UNC Department of Surgery, Chapel Hill, North Carolina, and Mahmood Razavi, director for Clinical Trials & Research at the Heart and Vascular Center, St Joseph Hospital, Orange, California, USA. Obstruction of the iliac veins and vena cava have been identified as a frequent cause of severe venous disease resulting in major disabling symptoms including leg swelling, pain, and ulceration, said Marston. He added, The development of stents specifically designed for the unique characteristics of the venous system provide the potential to reduce these debilitating symptoms for patients, while improving the cost-effectiveness of interventional treatment for venous obstruction. Razavi commented, This is an important landmark for Veniti and patients with deep venous disease. Due to the absence of vein-specific stents, physicians have thus far been using stents that were not designed for veins. We look forward to the completion of this important study and availability of optimal stents to treat our patients with deep vein obstructive lesions. The trial has commenced in Europe, with first patients enrolled and treated by Marta Ramirez Ortega, at Hospital Madrid Monteprincipe in Madrid, Spain. It is important for my patients to be able to be treated with a stent specifically designed for the venous anatomy and for them to have their data collected so that future patients can benefit from knowing how well venous stenting works, says Ramirez. Teleflex receives FDA clearance for Arrow-Clark Vectorflow chronic haemodialysis catheter Teleflex has announced it has received FDA 510(k) clearance to market its Arrow-Clark Vectorflow chronic haemodialysis catheter. The catheter features a symmetrical tip design that allows ease of placement. The Arrow-Clark Vectorflow catheter was designed by Timothy Clark, Associate Professor of Clinical Radiology, Department of Radiology, University of Pennsylvania Health System, Philadelphia, USA. The unique design of this catheter is that it has helically-shaped distal lumens, which deflect the vector of blood entering Vici venous stent and leaving the catheter to minimise recirculation and provide improved flow characteristics, Clark told Interventional News. Arrow-Clark Vectorflow is the only catheter with an innovative tip designed to produce a helical, three-dimensional transition of blood entering and leaving the catheter, a press release from the company says. Spectranetics announces FDA clearance of peripheral laser atherectomy devices for instent restenosis Spectranetics has announced receiving US FDA 510(k) clearance of their peripheral atherectomy products, Turbo-Tandem and Turbo Elite, for the treatment of in-stent restenosis. FDA clearance comes on the heels of the EX- CITE ISR (Excimer laser randomised controlled study for treatment of femoropopliteal instent restenosis) study s clinical findings. The study, which is the first multicentre, randomised, prospective trial conducted for the treatment of in-stent restenosis, demonstrated highly superior safety and efficacy of laser atherectomy with adjunctive percutaneous transluminal angioplasty compared with angioplasty alone. The trial shows a 94% procedural success rate using laser atherectomy with angioplasty vs. 83% with angioplasty alone. With mean lesion length at 20cm, approximately one-third of the patients being re-treated for in-stent restenosis and also approximately onethird with total occlusions, EXCITE represents a very sick, real-world patient set, said Eric Dippel, Genesis Heart Institute, Davenport, USA. The highly superior outcomes for both safety and efficacy and the delta in procedural success rates between the two arms of the trial are compelling. Given that a significant number of patients today are treated with percutaneous transluminal angioplasty alone with very poor outcomes, EXCITE ISR demonstrates a proven treatment algorithm that physicians and their patients need. Complete results from the EXCITE trial have been submitted to a peerreviewed medical journal, the release states. Liver tumour ablation more predictable with Emprint Overcoming a significant roadblock to predictable ablation of soft tissue, Covidien has unveiled an advanced ablation system Arrow-Clark Vectorflow catheter that offers physicians predictable results regardless of the target location or tissue type. The Emprint ablation system with Thermosphere technology is designed to precisely heat and destroy diseased soft tissue (including liver, lung and kidney), and non-resectable liver tumours. Covidien is dedicated to improving patient safety and simplifying procedural options, and this innovative technology enables physicians to deliver precise ablation directly to soft tissue, including liver tumours, says Chuck Brynelsen, president, Early Technologies, Covidien. By providing predictable spherical ablation zones, this technology gives physicians more choices in terms of approach, further simplifying needle placement and saving planning and procedure time. The Emprint ablation system provides clinicians three kinds of spatial energy control thermal, field and wavelength to create predictable and spherical ablation zones regardless of target location, tissue type, or changes in tissue properties during a procedure. Covidien s advanced ablation system can be used in three different procedure settings including non-surgical procedures directly through the skin, minimally invasive surgery and open surgery. Covidien received US Food and Drug Administration 510(k) clearance for the Emprint ablation system with Thermosphere technology in April Covidien launches next generation Trellis peripheral infusion system Covidien has announced the commercial launch of its next generation Emprint ablation system Trellis peripheral infusion system. The redesigned system continues to be the only pharmacomechanical thrombolysis device that enables focused treatment of blood clots that lead to post-thrombotic syndrome. This latest Trellis system has been optimised to enhance drug delivery and the removal of the dissolved clot. The Trellis system provides a way for physicians to dissolve acute thrombus and intervene on deep vein thrombosis before it advances to post-thrombotic syndrome. The system is comprised of an overthe-wire catheter with two occlusive balloons to close off the treatment area and block drug release to other areas of the body; an infusion zone to deliver the lytic drug; and an oscillation drive unit that disperses the drug to dissolve the clot. The updated Trellis system features enhanced drug delivery and increased amplitude of the dispersion wire to better distribute the drug throughout the clot. Additionally, the new system features a larger aspiration window than the previous version, which allows for better removal of the drug and the dissolved clot. The Trellis peripheral infusion system is currently available in the USA, Europe and Canada. Zilver PTX drugeluting stent selected as a top emerging health technology in Canada The Canadian Network for Environmental Scanning in Health (CNESH) has selected Cook Medical s Zilver PTX drugeluting peripheral stent as a top 10 game-changing health technology for The CNESH top 10 list is designed to encourage the adoption and use

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46 46 Market watch Product News of effective, safe health technologies in Canada and was announced at the 2014 Canadian Agency for Drugs and Technologies in Health (CADTH) symposium. Zilver PTX is the first self-expanding, drug-eluting stent available to help treat peripheral arterial disease in the superficial femoral artery in Canada. Approximately 800,000 Canadians have peripheral artery disease. According to CADTH, the disease occurs in 4% of Canadians older than 40, increasing to 20% in individuals over the age of 75. Worldwide, recent reports have shown that has reached epidemic levels in developed countries, with 38 million new cases reported in the last 10 years. Now that we have over four years of clinical data showing a long-term drug effect compared to uncoated stents, the advantage of treating superficial femoral artery blockages with drug-eluting stents is clear, said Mark Breedlove, vice president and global leader of Cook Medical s Peripheral Intervention division. It is fantastic to see CNESH highlight technologies that positively impact patient outcomes and healthcare costs by reducing the number of repeat procedures. Zilver PTX entered the European market in August 2009, the US market in November 2012, and is the first drug-eluting stent indicated to treat peripheral arterial disease in the superficial femoral artery in Canada. Since its release, the stent has been used to treat more than 25,000 patients in Europe, Asia, South merica, Australia, New Zealand and India. Vascular Solutions launches Gel-Bead bioresorbable embolization spheres Vascular Solutions has announced the US market launch of its Gel-Bead embolization spheres for the treatment of hypervascular tumours. Gel-Bead embolization spheres are precisely sized, bioresorbable beads of gelatin that are absorbed by the body over time, providing physicians with a treatment option for hypervascular tumours in cases when a permanent embolic agent is not desired. Gel-Bead, which received 510(k) clearance from the US Food and Drug Administration in April, will be sold to interventional radiologists who currently embolize hypervascular tumours with microspheres, polyvinyl particles, and gelatin foam slurries. Gel-Bead is supplied in 20ml syringes, each containing 1ml of gelatin spheres suspended in 5ml of saline. Gel-Bead is available in four sizes of sphere diameter ( microns, microns, microns, and ,000 microns), each identified by a different coloured syringe plunger. Aorfix receives regulatory approval in Japan for treatment of abdominal aortic aneurysms Lombard Medical has announced that its lead product, Aorfix, an endovascular stent graft to treat abdominal aortic aneurysms, has received approval from the Japanese Ministry of Health, Labour and Welfare. Commercial sales will follow reimbursement approval, which the company anticipates receiving in September Aorfix will be exclusively distributed by Medico s Hirata, one of Japan s leading suppliers of vascular products with proven expertise in building significant market share for abdominal aortic aneurysms stent grafts. Japan is the world s second largest, standalone EVAR market. Aorfix is the first and only endovascular stent graft approved in Japan to treat abdominal aortic aneurysms in patients with aortic neck angulations up to 90 degrees, commonly considered to be challenging cases. Aorfix is currently approved to treat patients with neck angles up to 90 degrees in the USA and Europe. Lombard Medical s chief executive officer, Simon Hubbert comments, Japan is a substantial EVAR market, both strategically and financially, and the approval of Aorfix is a significant milestone for the company. We are confident that, through Medico s Hirata s experienced and established sales force, we will be able to realise the full potential of Aorfix in this growing market. We look forward to providing Japanese physicians with our uniquely differentiated stent graft approved to address the significant population of patients with complex anatomies who, until today, had no onlabel minimally invasive treatment option. First clinical cases in USA with Magellan 6F robotic catheter announced Hansen Medical has announced the successful completion of the first clinical procedures in the USA using the Magellan 6F robotic catheter. Alan Lumsden, treated two patients with the catheter at Houston Methodist Hospital in Houston, USA. The cases included an endovascular aneurysm repair (EVAR) to treat an abdominal aortic aneurysm and a lower extremity intervention for the treatment of peripheral artery disease. The procedures at Houston Methodist follow the completion of the world s first clinical procedures using the Magellan 6F robotic catheter at Hôpital Européen Georges Pompidou in Paris, France. The Pompidou procedures were part of an ongoing, 25-patient study to assess the use of the new Magellan 6F catheter in a variety of embolization procedures. The 6F catheter is the latest addition to the family of catheters for use with the Magellan Robotic System. The 6F catheter s design provides for precise robotic navigation and control in a single, 6F outer diameter catheter; enabling use of the Magellan Robotic System in smaller vessels in the peripheral vasculature. Aorfix Magellan 6F catheter Philips expands interventional oncology portfolio with EmboGuide to see, reach and treat tumour lesions Philips has announced the launch of EmboGuide, its latest innovation in interventional oncology, to treat difficultto-reach tumours or tumours in patients who are deemed unsuitable for surgery. EmboGuide is a live 3D image guidance tool that supports the increasing number of minimally-invasive procedures in oncology. It is designed for use in conjunction with Philips interventional X-ray system to perform tumour embolization procedures. Developed in collaboration with leading clinicians and partners such as BTG, an innovator in interventional oncology, EmboGuide addresses the need for an enhanced 3D imaging solution to make interventional oncology procedures more effective and easier to perform, and ultimately improve patient outcomes. It offers interventional radiologists the ability to visualise and characterise tumour lesions and plan and execute interventional procedures. A specific example of a tumour embolization procedure is transarterial chemo-embolization (TACE). We can only treat what we see, yet the embolization of all blood vessels that feed the liver tumour lesion is key for an effective TACE procedure, says Shiro Miyayama, Department of Diagnostic Radiology, Fukuiken Saisekai Hospital, Japan. EmboGuide s live 3D image guidance helps to improve the technical success of the procedure, as it can automatically identify the small tumour-feeders that are difficult to detect with conventional 2D angiographic imaging methods. EmboGuide leverages the ultra-low X-ray dose settings of Philips AlluraClarity interventional X-ray system and the fast, high quality imaging of the abdomen of XperCT Dual. XperCT Dual s enhanced imaging technique (multiphase cone beam CT) offers high quality 3D images of lesions, with proven detection accuracy superior to conventional 2D angiographic imaging. It offers clinicians a better view of the treatment targets for informed decision making while performing the procedure. XperCT Dual is comparable to MRI, which is considered to be the gold standard. EmboGuide helps to define the tumour lesions and features automatic identification of blood vessels that feed the lesions. It detects more than twice as many tumour feeding arteries compared to conventional imaging methods (Digital Subtraction Angiography (DSA). This allows interventional radiologists to optimize the catheter locations for embolization and plan a route to them. During the administration of the embolization agent, EmboGuide accurately superimposes the planning information onto the interventional X-ray system s live images to monitor the treatment progress and determine its endpoint. In the treatment of intermediate hepatocellular carcinoma, the integrated use of our embolic device with image guidance is vital for successful treatment, says Mike Motion, BTG general manager, Interventional Oncology. As a leader in interventional oncology, we invest to improve the safety and efficacy of the procedure. Partnering with Philips has strengthened our ability to further develop this cohesive approach using DC Bead and Philips EmboGuide with the ultimate objective of advancing interventional oncology. EmboGuide is currently not available in the USA.

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48 48 Company news Industry News Terumo obtains regulatory approvals for marketing MicroThermX in additional countries BSD Medical Corporation reported that Terumo Europe NV (Terumo) has obtained approvals to market and import the MicroThermX Microwave Ablation System in South Africa, Dubai, Qatar, and Jordan. These approvals are part of Terumo s comprehensive marketing strategy to expand MicroThermX distribution outside of Western Europe, a press release from BSD Medical states. The company s exclusive, multimillion dollar agreement with Terumo covers distribution of the MicroThermX in more than 100 countries, including Europe, Western Asia and Africa, with a market potential that exceeds US$1 billion. Terumo is implementing a well-planned marketing strategy for the MicroThermX aimed at geographic expansion, said Sam Maravich, vice president of International Sales and Marketing of BSD Medical. We are gaining sales traction in the Western European countries. Terumo is an exceptional partner for BSD, making substantial investments in sales and marketing of the Micro- ThermX. Cook Medical begins two studies on inferior vena cava filters Cook Medical is engaged in two clinical studies that will provide additional data on the safety and effectiveness of inferior vena cava filters. The first study, the Cook Inferior Vena Cava Filter (CIVC) study, will add to Cook s existing clinical data on its commercially available inferior vena cava filters. This includes three previous studies including more than 1,300 patients treated with Cook inferior vena cava filters. CIVC will also address filter safety concerns expressed in the 2010 and 2014 safety communications from the US Food and Drug Administration (FDA). The study s primary endpoints will be technical placement success and one-year freedom from new symptomatic pulmonary embolism, and one-year freedom from major adverse events. CIVC will collect additional safety and effectiveness data on Cook s permanent and retrievable filters. Enrolment in the CIVC study began in March Up to 470 patients at up to 40 international sites will be enrolled in the study. The second study, the PRESERVE study, will involve collaboration between Cook, the Society for Vascular Surgery, the Society of Interventional Radiology, the FDA, and other filter manufacturers, and will enrol patients in the USA only. ROADSTER trial completes patient enrolment Silk Road Medical has announced the completion of enrolment in its pivotal ROADSTER study. The trial is the first of its kind to study the treatment of carotid artery stenosis by placing a stent via direct access to the common carotid artery in the neck in an entirely new minimally invasive procedure. The device under study is the company s Enroute transcarotid neuroprotection system which incorporates proven surgical principles to protect the brain from a stroke during carotid angioplasty and stenting, and features a mechanism to divert dangerous debris away from the brain by temporarily reversing blood flow. Data from the trial will be used to support 510(k) clearance of the Enroute transcarotid neuroprotection system as well as pre-market approval of the Enroute transcarotid stent system. The Enroute transcarotid neuroprotection system was designed to reduce the excess stroke risk of a carotid stent procedure, while at the same time minimising the surgical risks of an open carotid artery surgery known as carotid endarterectomy, says Sumaira Macdonald an expert in the field of carotid artery disease and Silk Road Medical s chief medical officer. Until now, carotid stents were typically placed via the femoral artery approach, which is about three feet from the culprit carotid stenosis, and requires navigation of catheters and other instruments through often hostile territory, increasing the risk of stroke during or immediately after the procedure, she says. We know that carotid stents are effective in preventing strokes in the long term, but we need a safer way to deliver them. The Silk Road procedure moves the access point to within inches of the stenosis to avoid at-risk steps and provides a surgically-inspired method of protecting the brain throughout the simplified procedure. EKOS initiates study in patients with chronic deep vein thrombosis and post-thrombotic syndrome EKOS Corporation has announced the start of patient enrolment for the Accelerated thrombolysis for EkoSonic Endovascular System post-thrombotic syndrome using the EkoSonic endovascular system (ACCESS PTS) study. The ACCESS PTS study is a prospective, single-arm, multicentre trial, designed to evaluate the safety and efficacy of ultrasound accelerated thrombolysis using the EkoSonic endovascular system with standard infusion of a thrombolytic drug for post-thrombotic syndrome and chronic venous occlusions. The study will enrol up to 200 subjects over a period of 12 months at approximately 30 study sites across the United States. Subjects will receive clinical follow-up for 12 months. Clinical effectiveness will be evaluated using the Villalta score (measurement of the severity of PTS) at baseline compared to 30 days post-ekosonictreatment. Success will be defined by 50% or more of the subjects achieving at least a 4 point reduction in the Villalta score, which represents a significant improvement in the symptoms of post-thrombotic syndrome. Potential study subjects will be between 18 and 75 years of age with lower extremity deep vein thrombosis who have: Been objectively diagnosed via imaging as having persistent deep vein thrombosis for at least six months A Villalta score 8. Failed three months of conservative treatment including compression stockings and anticoagulation drugs. BIOLUX 4EVER trial commences Biotronik has announced that the first patient has been enrolled in the investigator-initiated BIOLUX 4EVER trial. Given the positive results from each of the previous drugeluting balloon and self-expanding stent trials, investigators were interested in exploring the combined use of the Pulsar-18 selfexpanding stent and Passeo-18 Lux drug-eluting balloon to see if the outcome could be improved further. BIOLUX 4EVER will follow the study design of the previously completed, investigator-initiated 4EVER trial, which examined the efficacy of the Pulsar-18 self-expanding stent in the treatment of superficial femoral artery lesions, but this time adding the Passeo-18 Lux drug-eluting balloon to the treatment. The study will enrol 120 patients treated with both products, with the primary endpoint of primary patency at 12 months. Studying these two devices in combination is a novel idea, explains principal investigator Marc Bosiers, St Blasius Hospital, Dendermonde, Belgium. Previous studies of each device have yielded encouraging results, but we wanted to go one step further. Now, patients will be treated with both the Pulsar-18 stent and the Passeo-18 Lux, hopefully pushing the results off the charts. ArtVentive announces positive clinical results and expanded enrolment in OCCLUDE I post-market surveillance study ArtVentive has announced positive clinical results in conjunction with expanded enrolment in the ArtVentive Endoluminal Occlusion System (EOS device) OCCLUDE I post-market surveillance study. The Department of Interventional Radiology and Neuroradiology, Medical University of Lublin, Poland, has reported successful results for eleven cases over a two-day period. Tomasz Jargiello served as the primary investigator and Malgorzata Szczerbo-Trojanowska, head of the Department, Krzysztof Pyra and Michal Sojka each participated in the study. In conjunction with the study, four female patients were treated for pelvic congestion syndrome and seven male patients were treated for varicocoeles using the ArtVentive EOS device. The ArtVentive EOS device performed extremely well and met expectations in a clinical setting, Jargiello stated. I was able to deliver the device with ease to the desired site and I was impressed with its simple deployment. The device provided instant and complete occlusion of the target site. This is an improvement over other currently available occlusion devices and provided our team with confidence that the desired embolization was achieved. Full two-year Mimics data confirm long-term patency protection with BioMimics 3D stent Full two-year data from the Mimics study, presented for the first time at the 15th Annual New Cardiovascular Horizons (NCVH) Conference (28 30 May, New Orleans, USA), have confirmed that BioMimics 3D provides a significant improvement in long-term patency compared to a straight nitinol control stent in patients undergoing femoropopliteal artery intervention. BioMimics 3D, a nitinol stent with unique three-dimensional helical geometry, has been developed by Veryan, based on pioneering research by Colin Caro at Imperial College London, UK, into the link between blood flow mechanics and vascular disease. The Mimics study is a prospective, randomised, multicentre controlled trial conducted at eight German investigational centres and supported by an independent core lab. A total of 76 patients were enrolled and randomised 2:1 (50 Bio- Mimics 3D v 26 Control) in patients undergoing femoropopliteal artery intervention. Mimics investigators compared the safety, efficacy and vascular haemodynamics of the Bio- Mimics 3D stent to straight nitinol stents (24/26 control subjects were treated with C R Bard s LifeStent). The final 24-month data for the BioMimics 3D stent confirm that the flow effects produced by its helical design are contributing to an improved outcome compared to that achieved with the straight control stents. The results of the Mimics study show a significantly greater freedom from loss of primary patency with BioMimics in the 24-month Kaplan Meier

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50 50 Company news Industry News survival analysis, comments Zeller. Importantly, there was no change in the rate of clinically-driven target lesion revascularisation in the 12 and 24 month follow-ups for BioMimics 3D and this longer-term benefit appears to correlate with a trend to lower peak systolic velocities. Overall, these data suggest that a biomimetic stent with 3D helical curvature may provide a new performance benchmark in femoropopliteal stenting. Veryan has received CE mark approval for the BioMimics 3D stent and plans to commercialise the stent later this year. Volcano Corporation announces agreement to acquire AtheroMed Volcano Corporation has announced that it has signed an agreement to acquire AtheroMed, a September CIRSE 2014 Cardiovascular and Interventional Radiological Society of Europe Annual Meeting Glasgow, Scotland W privately-held company that has developed the Phoenix Atherectomy System used in the treatment of peripheral artery disease. Under terms of the agreement, Volcano will pay US$115 million in cash at closing. In addition, Volcano will make a US$15 million milestone payment if a Phoenix device currently before the FDA receives clearance by 15 November Spectranetics completes acquisition of AngioScore Spectranetics has announced that it has completed the acquisition of AngioScore, a leading developer, manufacturer and marketer of cardiovascular, specialty balloons, for US$230 million in cash, along with additional contingent commercial and regulatory milestone payments. Calendar of events October The Best of WCIO 2014 Buenos Aires, Argentina E info@wcioargentina.com W October CiDA 2014 Controversies in Dialysis Access AngioScore, based in Fremont, California, USA, develops and markets the AngioSculpt scoring balloon technology platform, which is a differentiated, comprehensive portfolio to treat blockages in the coronary and peripheral vasculature. Boston Scientific announces definitive agreement to acquire Bayer s Interventional Division In a move to expand its portfolio of leading solutions for peripheral interventions, Boston Scientific has entered into a definitive agreement to acquire the Interventional Division of Bayer AG for US$415 million in cash, including fees for transitional services. The company expects to close the transaction in the second half of 2014, subject to customary closing conditions. Salt Lake City, USA E registration@ccmcme.org November BSIR 2014 British Society of Interventional Radiology Annual Meeting Liverpool, UK T +44 (0) The acquisition is expected to improve Boston Scientific s access to a number of attractive segments in the peripheral space, including the growing atherectomy and thrombectomy categories. In 2013, Bayer Interventional generated sales of approximately US$120 million. Bayer Interventional offers a number of innovative technologies designed to treat coronary and peripheral vascular disease. The transaction includes the AngioJet Thrombectomy System and the Fetch 2 Aspiration Catheter, which use endovascular techniques to remove blood clots from blocked arteries and veins, and the JetStream Atherectomy System, a minimally invasive device used to remove plaque from diseased peripheral arteries. Will Medtronic s proposed acquisition of Covidien go through as it stands? At the time of this newspaper going to press, questions still surrounded Medtronic E meeting@bsir.org W November Synergy 2014 Miami, USA E umcme@med.miami.edu W 28 February 5 March 2015 SIR 2015 Society of Interventional Radiology Annual Scientific Meeting Atlanta, USA and Covidien s announcement on 15 June 2014 that they have entered into a definitive agreement under which Medtronic has agreed to acquire Covidien in a cash-and-stock transaction valued at US$93.22 per Covidien share, or a total of approximately US$42.9 billion. The proposed acquisition has garnered some controversy regarding the deal s structure as a tax inversion. Medtronic has stated that Covidien deal has little to do with tax benefits and more with expansion of its product pipeline. The corporate tax rate in the United States is 35% the highest nominal rate in the world, leading a number of companies to move their headquarter to low-tax nations such as Ireland and other countries. With the Obama administration coming down on tax inversion, there has been some reporting to suggest that Medtronic is expected to modify its offer for Covidien and that the acquisition deal is likely to be completed by early E annualmeeting@sirweb.org W March 2015 ECR 2015 European Congress of Radiology Vienna, Austria W 28 April 1 May 2015 Charing Cross International Symposium London, UK T +44 (0) W Interventional News team Editors-in-chief: Professor Andy Adam Dr Brian Stainken Publisher: Stephen Greenhalgh Head of Publishing: Marcio Brito Editor: Urmila Doraswami urmila@bibamedical.com Design: David Reekie Layout: Tim Parker Advertising: Shilpa Suthar shilpa@bibamedical.com Subscriptions: Sue Couch subscriptions@bibamedical.com Please contact the Interventional News team with news or advertising queries Tel: +44 (0) Published by: BIBA Medical, 526 Fulham Road, Fulham, London, SW6 5NR, UK Tel: +44 (0) Printed by: Buxton Press Reprint requests and all correspondence regarding the newspaper should be addressed to the editor at the above address. BIBA Medical Ltd, 2014 All rights reserved. Write to us! If you have comments on this issue or suggestions for upcoming editions write to urmila@bibamedical.com Sign up for a free subscription Please visit Make sure you get your copy of Interventional News Next issue November 2014

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