Interventional News Issue 74 - ROW by BIBA Publishing

June

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19 74

IR community backs PAE and calls for close collaboration with urologists Current evidence supports the use of prostate artery embolization (PAE) as a safe, effective, and minimally-invasive treatment for the symptoms of benign prostatic hyperplasia (BPH) in appropriately selected patients. This is the conclusion of a multisociety consensus position statement on the use of PAE in the treatment of lower urinary tract symptoms attributed to BPH. The document has been published in the May edition of the Journal of Vascular and Interventional Radiology (JVIR) and outlines recommended standards of practice. The multisociety and multidisciplinary position statement comes from the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), Société Française de Radiologie (SFR), and the British Society of Interventional Radiology (BSIR).

Vincent Vidal: Emborrhoids

Page 12

Alex Tang:

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“The era of healthcare disruption is here”: IR unity urged in Dotter lecture

Interventional radiologists must work as a group to make the practice of medicine more patient-centric and efficient, said Alan H Matsumoto, professor and chair of the department of radiology and medical imaging at the University of Virginia, Charlottesville, USA, who delivered the Society of Interventional Radiology’s (SIR) 2019 Dr Charles T Dotter Lecture during SIR’s annual scientific meeting (23–28 March, Austin, USA).

Marc Sapoval presents at GEST 2019 during the PAE Symposium

owever, the interventional radiology (IR) community is still working to convince their urology colleagues to adopt the procedure as one treatment option. An SIR-sponsored research consensus panel for PAE has convened with urologists from the American Urological Association (AUA) to map a path towards PAE gaining acceptance in the urologists’ own guidelines. This meeting was chaired by Clifford Davis (Medical College of Virginia, Richmond, USA) and Jafar Golzarian (University of Minnesota, Minneapolis, USA). Golzarian informed Interventional News that one of the key takeaways from this meeting was understanding the importance urologists place on sham studies. Currently, a study comparing PAE with a sham procedure is underway; many in the IR community are hopeful that the publication of this data will support their case for the recognition of PAE as an effective, minimally-invasive procedure by urologists.

The recommendations of the multisociety consensus position statement

The multisociety release, penned by Justin McWilliams (David Geffen School of Medicine, Los Angeles, USA)

et al, advises PAE be used as a “valuable minimally invasive option for patients who cannot tolerate or who have failed medical therapy, and those who are poor surgical candidates or refuse invasive surgery.” The document makes the following eight recommendations: PAE is an acceptable minimally invasive treatment option for appropriately selected men with BPH and moderate to severe lower urinary tract symptoms. PAE can be considered as a treatment option in patients with BPH and moderate to severe lower urinary tract symptoms who have very large prostate glands (>80cm3), without an upper limit of prostate size. PAE can be considered as a treatment option in patients with BPH and acute or chronic urinary retention in the setting of preserved bladder function as a method of achieving catheter independence. PAE can be considered as a treatment option in patients with BPH and moderate to severe lower urinary tract symptoms who wish to preserve erectile and/or ejaculatory function. PAE can be considered in patients with haematuria of prostatic origin as a method of achieving cessation of bleeding. Continued on page 2

“BY PROVIDING TIMELY and accurate diagnoses and performing minimally invasive procedures with less morbidity and faster recovery times for patients, interventional radiologists are well positioned to address the triple aim of healthcare: better patient care, improving the health of populations and reducing per capita costs,” said Matsumoto. “We must have the will and fortitude to employ patience while we adapt and create mutually viable practice models for all members of our specialty. Interventional radiology can go so much further together, as one, in our efforts to grow the specialty and serve patients,” he said. “We must grow the relationship with patients to transition from being a doctor’s doctor to a patient’s doctor. Our patients can become some of our biggest advocates and allies, as long as we put them at the centre of our care models.” Matsumoto centred his lecture on four facts that he believes are impacting the practice of medicine and IR in the USA. In his words, these are: US healthcare is the most expensive in the world, yet ranks last amongst developed countries. Consumerism is starting to drive healthcare. Information is doubling every 73 days. Healthcare is changing so quickly, that being adaptable is now a requisite for health systems and providers. Elaborating on the expense and inefficiencies of the US healthcare system in his Dotter lecture, SIR Continued on page 6

June

Prostate artery embolization

IR community backs PAE and calls for close collaboration with urologists

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points. Just as importantly, PAE is very safe, with a low major complication rate and no change in erectile function. Ejaculatory dysfunction is still an open question; that was originally thought to be very uncommon, but some more recent studies have shown higher than expected rates of either reduced ejaculation or dry ejaculation. Radiation dose seems to be similar to other complex embolizations, such as gastrointestinal

haemorrhage or pelvic arteriovenous malformation embolization. In certain specific clinical scenarios, PAE is also effective. Definitely so in very large prostates, and catheter independence can be achieved in approximately 80% of patients with a Foley catheter. Haematuria of prostatic origin can almost always be stopped immediately.” Calling this “a landmark document”, Marc Sapoval (Hôpital Européen Georges-Pompidou, Paris, France), a co-author of the statement, voices his support to this newspaper: “At this point in 2019, we can say that PAE can be used safely and effectively in patients as an alternative to other treatments. This is strongly stated and supported by IR societies all around the world. I think this is very important for IR, to give us confidence in our support of PAE.” Speaking to Interventional News of the importance of these guidelines, Sandeep Bagla (Vascular Institute at Virginia, Woodbridge, USA), a co-author of the document, says: “We as a community are proud to have seen these guidelines come to fruition, after many years of having our initial guidelines out. It is a very difficult and tedious process to update a position statement. Along with many other important co-authors, including lead author Justin McWilliams, who really was the energiser behind this project, we were able to pull together a collaborative document representing the evidence-based view of many societies around the world. The value of this document is multi-fold. It is a rather big step for SIR to put forth this document with recommendations; it mirrors the actions of other large societies, such as the American Heart Association, where the guidelines are presented in a similar

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History of benign prostatic hyperplasia treatment recommendations

Prostate artery embolization is a minimally-invasive treatment for lower urinary tract symptoms attributed to BPH. More than 70% of men aged over 70 are affected by BPH, and a quarter of men over 70 have moderate to severe lower urinary tract symptoms that impair their quality of life. This has led McWilliams et al to

These recommendations are very supportive of PAE, and I think are reflective of the data and literature that are out there, with the endorsement of multiple international IR societies.”

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manner, based on level of evidence and the strength of recommendation. That is important, because many guidance documents just release recommendations based on panel agreement, not based on a review of data, and without using a universally accepted grading system, like we do in these recommendations.”

Continued from page 1

PAE can be considered as a treatment option in patients with BPH and moderate to severe lower urinary tract symptoms who are deemed not to be surgical candidates for any of the following reasons: advanced age, multiple comorbidities, coagulopathy, or inability to stop anticoagulation or antiplatelet therapy. PAE should be included in the individualised patientcentred discussion regarding treatment option for BPH with lower urinary tract symptoms. Interventional radiologists, given their knowledge of arterial anatomy, advanced microcatheter techniques, and expertise in embolization procedures, are the specialists best suited for the performance of PAE. In addition to the four societies that authored the guidelines, these recommendations are endorsed by the Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR; see page 45), the Canadian Association for Interventional Radiology (CAIR), the Chinese College of Interventionalists, the Interventional Radiology Society of Australasia, the Japanese Society of Interventional Radiology, and the Korean Society of Interventional Radiology. Speaking recently at GEST (Global Embolization Oncology Symposium Technologies; 9–12 May, New York, USA; see page 47), lead author Justin McWilliams addressed the audience on the status of international recommendations for PAE. “These recommendations are very supportive of PAE, and I think are reflective of the data and literature that are currently out there. With the endorsement of multiple international IR societies, my co-authors and I reviewed all articles published between 2010 and 2018 relevant to PAE—some 280 articles, which were whittled down to 67 after duplicate cohort, case reports and technical papers were excluded—and summarised their findings.” Of the 67 included articles, three were randomised controlled trials, a further three were non-randomised comparative trials, and 17 were unique cohort studies. There were also multiple reviews and meta-analyses, in addition to miscellaneous papers focusing on factors such as cost and radiation exposure. In total, over 2,200 patients from eleven countries were reviewed in these studies. “The overall findings were of no surprise to anyone in this room”, McWilliams said to the attendees of the GEST PAE Symposium, all interventional radiologists, “and are similar to the findings of prior meta-analyses. PAE is definitely effective; IPSS [International Prostate Symptom Score] improvement, depending on which study you look at, is between 10 and 18 points, and quality of life improvement ranges from two to four

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call BPH and ensuing lower urinary tract symptoms a “significant health issue affecting millions of men”. The lower urinary tract symptoms caused by BPH have historically been treated by medical and surgical methods. Medical therapies, such as α-1 blockers and 5-α reductase inhibitors, are the mainstay of treatment for mild to moderate lower urinary tract symptoms, while the more invasive transurethral resection of the prostate (TURP) and simple prostatectomy are considered the gold standards for patients with severe symptoms. After initial reports on PAE in humans from João Pisco (Lisbon, Portugal) and Francisco Carnevale (University of Sao Paulo Medical School, Sao Paulo, Brazil), McWilliams described the AUA as “unimpressed”, after their 2010 guidelines for the management of BPH failed to mention PAE. An initial review by the UK National Institute for Care Excellence (NICE) concluded in 2013 that more research was needed to establish the safety and efficacy of the procedure. McWilliams authored an initial SIR position statement in 2014, with multiple other interventional radiologists, though he says that “at that time, the data was not yet mature. We also concluded that additional investigation was needed before we could accept PAE into routine therapy.” However, “a lot has changed over the last five years”, he says. To date, more than 2,000 patients have been studied in PAE-pertaining publications, and there have been three randomised controlled trials comparing PAE to TURP. The longest duration of follow-up now exceeds five years. An FDA review in 2017 concluded

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June

Prostate artery embolization

IR community backs PAE and calls for close collaboration with urologists Continued from page 2

that “the probable benefits outweigh the probable risks for this indication”, and in June the same year, the indication of Embosphere microspheres (Merit Medical) was expanded through the FDA’s 513(f)(2) de novo classification to include PAE. In 2018, the product was approved for the same indication by a 510(k) pathway. Embozene microspheres (Boston Scientific) also gained an expanded indication in 2018, with the US FDA granting approval for its on-label use in PAE treatment in the USA via the 510(k) pathway. In the UK, NICE determined last year that the evidence on the safety and efficacy of PAE for BPH was adequate to support the use of this procedure on the National Health Service (NHS). This decision came after BSIR and the British Association of Urological Surgeons (BAUS) worked together to coordinate the UK ROPE study. The study compared embolization to conventional prostate surgery. It found embolization provided a clinically and statistically significant improvement in symptoms and quality of life for men with enlarged prostate. Also last year, in the USA, the updated AUA guidelines briefly mentioned PAE, where they did not recommend the procedure’s use outside of a clinical trial. During a debate at GEST on the topic this May, no one in attendance said they thought PAE should be restricted to clinical trials only. Indeed, during the PAE Symposium hosted by the conference, Riad Salem (Northwestern University, Chicago, USA), another co-author of these multisociety guidelines, said that, with the FDA approval of the Embosphere and Embozene microspheres, interventional radiologists “should not assume that PAE can only be performed as part of a clinical trial. In fact,” he added, “most cases are not. I think that is an important nuance.” However, he also said that “the most powerful data you can generate for your institution is the data generated internally”, and urged any audience members who performed PAE to collect data from their own patients. This is something done by an interventional radiologist attending the GEST PAE Symposim, who shared that he contacts all of his PAE patients one, three, six and 12 months’ post procedure. In the most recent guidelines from 2018, the AUA calls for additional sham trials to account for possible placebo effect, and, in McWilliams’ words, “remain unconvinced of the efficacy and safety of the technique”. Tiago Bilhim announced that he is working on a study that will compare PAE against a sham procedure, and that he hopes for the results to be published later this year. This work was started with his colleague Pisco, who passed away in March this year.

“We will have a lot more success if we collaborate with urology”

As NICE approved PAE in the UK in 2018, Tarun Sabharwal (Guy’s and St Thomas’ Hospital, London, UK), a co-author of the guidelines and a GEST panellist,

Prostate artery embolization

says that the collaboration between urologists and interventional radiologists in Britain acts as an example of how this relationship can benefit patients. He tells this newspaper: “These guidelines are significant in that they highlight to the American urological community what interventional radiologists can safely offer. Currently in the UK, with NICE approval for PAE, we have a good collaboration between urology and IR. We are able to

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by a few urologists that are personally very involved with urologic material development for BPH. Despite asking persistently, there was also no involvement of any IR society in the making of these guidelines [the most recent AUA guidelines, from 2018]. My strong recommendation is that SIR and AUA work handin-hand to identify which patients will benefit most from PAE. As a physician, our goal should only be to provide the best care for our patients; anything else is secondary.” Understanding the demand from the IR community for a closer collaboration with urology, one interventional radiologist who recently met with the AUA describes this conversation: “What we discussed

PAE Symposium panellists at GEST 2019

offer our patients a broad spectrum of choices for their prostate outlet obstructions that include embolization, so it is an alternative to surgery for them.” “For me, the issue I have with this therapy is that the response I get from urology is not a scientific response, it is an emotional response,” Salem tells the GEST audience during the PAE Symposium, speaking of the reaction he sees from urologists to PAE. “Even when you highlight the limitations of current therapies for BPH, and you highlight the tremendous work that has been done over the last ten years on PAE, the caliber of new studies that are being performed, the robustness of the findings, the attempts to recognise what you can and cannot do in a randomised setting, the post-hoc analyses, independent analyses by NICE—all the data triangulate to their being an important role for PAE in BPH. I think we have to get away from the emotionality of the subject.” This sentiment is echoed by Marc Sapoval (Hôpital Européen Georges-Pompidou, Paris, France) and Golzarian, also authors of these recommendations. Speaking to Interventional News, Sapoval comments: “I think this document demonstrates to urologists that IR is organised as an international community, and has an academic rigour equal to that of other specialties. We are taking PAE seriously, because we believe the evidence points to the procedure as a safe and effective one. I do not believe urologists are taking us seriously at this point, though I hope that changes—it is the patients who are currently missing out.” Golzarian adds, “PAE clearly works and helps patients—it is here to stay. In my opinion, the urologists’ guidelines are biased; they are mostly led

was the lack of level I evidence, [which is needed] for any therapy to make it into the guidelines. I think they [AUA] have a very strong stance on this. Having said that, they are not very rigid in terms of their guidelines, because, for example, they are flexible in using bipolar TURP or using GreenLight laser for large glands, which is not what the guidelines state. The guidelines only state [you should use] monopolar TURP or perform open prostatectomy, but that is not the standard of practice. “However, we do have an SIR [multisociety] position statement, which details when to use this procedure [PAE] in specific settings, but PAE is not in the AUA guidelines. The AUA guidelines are important in terms of reimbursement for the procedure.” Insurance coverage for PAE currently varies across the USA. In order to convince urologists that interventional radiologists are knowledgeable and skilled when it comes to PAE, Insausti Gorbea (Clínica Universidad de Navarra, Navarra, Spain), a panellist at the PAE Symposium hosted by GEST, stressed how important he believed it was to select patients carefully, saying “I think trials now should not be comparing PAE to surgery or TURP any longer; trials should be just to find out who are the good responders to this treatment. I think the technique is mature enough for this. Then we can say to urologists, ‘I know my limits’.” This comment was met with agreement by Bilhim, who added that for those first starting out performing PAE, they should begin with straightforward cases. Also in accordance, an audience member commented: “It does take some experience, so you should have five to seven years’ experience with basic embolization before moving on to PAE.”

June

Charles Dotter lecture

“The era of healthcare disruption is here”: IR unity urged in Dotter lecture Continued from page 1

Matsumoto quoted an international study from 2014 that looked at 11 different healthcare factors in developed nations, including efficiency, access, quality, and infant mortality, where the USA ranked last. “Despite that”, he said, “comparing the life expectancy amongst these 36 different developed countries, the USA ranks just 31st. Life expectancy in the USA is 78.6 years as of 2016. In 2018, it went down a little more.” He continued, “Despite the fact that our quality is lagging, and our life expectancy is below other developed countries, the cost of US healthcare is still going up. It is averaging US$12,000 per person, per year. What that translates into is that the cost of healthcare in the USA is more than two times the amount of that in any other developed country, which is about 3.3 trillion US dollars a year, which is about 8.8% of our GDP. Interestingly enough, that 3.3 trillion US dollars is more than the entire GDP of the UK.”

care when, where, and at the value that they want’. Price transparency and consumerism is really driving expectations relating to patients.” He went on to use the example of the cost of knee replacement surgeries for Californians: the average cost of this surgery was US$22,000 more, according to Matsumoto, on the Monterey coast than in the San Joaquin Valley. “This has led to the development of online shopping sites; this is driven by the consumers,” he told the SIR audience. Summing up all these difficulties, Matsumoto stated: “All of these headwinds in the healthcare industry are leading to disaggregation, failing practice, and hospital closures.”

“Consumerism is driving healthcare”

Speaking to Interventional News, Matsumoto expanded on the role of consumerism in driving healthcare. “Consumerism has hit the marketplace in healthcare. At the same time, industry has changed how it is approaching healthcare,” he said. “There is a lot of money in healthcare, so when the business sharks smell the blood in the water, they go to it. Retailers, payers, pharmacies, and venture capital groups are becoming more involved in the delivery of care. They are forming hundred billion, two hundred billion dollar corporations and partnerships to create vertically-integrated health system networks to affect where patients receive their care. Mega-mergers, acquisitions, partnerships and corporatisation of medicine are more commonplace, such that the era of healthcare disruption is here. We are in the middle of it. This disruption in healthcare and in medicine is causing many hospitals to close because they cannot compete.” Comparing the amount of money large, transnational companies have to the amount of individual hospitals, Matsumoto asked the audience to “Imagine the influence these companies can have on where our healthcare is going.” Showing a graph of changes in healthcare premiums between 1999 and 2015, he demonstrated that healthcare premiums had increased by almost 200%, whilst earnings had only increased by 56% in the same timeframe. Noting this, he said that “This divergence is creating a major problem for patients and employers, so many are choosing large deductible plans, and higher co-pays. “In addition, the growth in household spending between 2008 and 2016 has grown on average about 1.6%, yet if you look at the items like apparel, entertainment, housing and transportation, all of them have grown less than 1.2%. So what has made up that big difference? The effect in the spending is really [due to] healthcare. Out of pocket healthcare has grown by 5.6%, and health insurance itself has grown 8.4%. The healthcare costs have become so much, that patients are not able to pay their co-pays, and bad debt has also increased 500%, from to 1–5% over that same eightyear time period. It has led us to a situation where a decade of healthcare cost growth has really wiped out any significant income gains for the average family. This is what is driving consumerism. “It has led to many politicians and individual patients beginning to advocate for a single payer system. It has led the CEO of Walgreens to be quoted in The New York Times saying that ‘The patient as a consumer will expect, and have increasingly seamless access to,

Former SIR president Victoria Marx (L) and Alan Matsumoto. Photo credit: EPNAC.com

Information is doubling every 73 days

“In four years, we will be dealing with one million times the information we are dealing with today”, Matsumoto informed delegates. In 2005, computational capabilities started growing at an exponential rate, he said. “Companies took charge of that [growth], and, utilising not only the information, but other technologies, an inflection point took place in 2005.” He went on to list the launch of Android, YouTube, and Twitter around that time, as well as the subsequent appearance of virtual machine (VM) software— which made it possible to run multiple systems and applications simultaneously, and which eventually enabled cloud computing—and the emergence of

The era of healthcare disruption is here. We are in the middle of it, [and it is] causing many hospitals to close.” machine learning and artificial intelligence (initially from IBM Watson) as creating “a lot of turbulence in the world, and in medicine.” “The rapid pace of data generation and information sharing has made it difficult for systems and people to manage,” Matsumoto said. He urged patience of the listening interventional radiologists.

Being adaptable is a prerequisite of working in the US healthcare system: The opportunity for IR

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“Interventional radiologists should take the lead in the management of patients, and can no longer be so passive,” Matsumoto articulated. When asked how interventional radiologists can adapt to this changing environment, Matsumoto explained to this newspaper: “Because of the nature of our specialty, IR is well-positioned to help in managing this conversation on healthcare”. He cited a paper authored by Donald Berwick, a former administrator of the Centers for Medicare and Medicaid Services, and colleagues outlining the “triple aims of healthcare”. These were, in Matsumoto’s words, “Better health for patients, with improved quality, access, and outcomes; enhanced population health; and reducing the costs of healthcare—bending the costs, so to speak. “Interventional radiologists, because of our nature, being innovative and creative in doing minimallyinvasive procedures, can help address that component of the triple aim in medicine. However, things are changing so rapidly, and the disruption is creating essentially a tornado in healthcare that everyone has a sense of urgency to fix things. My message is: patience and patients. We need patients because they are our reason for being, and we should keep them as our “true north” as we think of solutions going forward. Interventional radiologists have the perfect opportunity to change from being a doctor’s doctor to being a patient’s doctor. That is again focusing on the patient’s well-being. We tend to have a high adaptability quotient. Most organisations and most people adapt on a linear scale to change. But with information accelerating so much, we are needing to adapt at an almost exponential phase. That can be even more fragmenting and disaggregating, so we need to exercise patience when we exercise our decisions and choices. Emphasising his take-home message, Matsumoto said: “The biggest message I have is unity and purpose [are essential] to not only our patients, but also to our specialty. With the fragmentation that is occurring in healthcare, if IR is disruptive, and people go off separately, our voice will become diluted, and policy makers, legislators, payers, health systems, and most importantly patients will not hear us. They will not recognise what we can bring to the table in this calculus of healthcare at this moment.” Ending on a positive note, he said to Interventional News: “I wanted to convey that you are much more likely to go further together than apart, and that the sum of the whole is greater than the individual parts. I ended the Dotter lecture with a proverb, pretty much to let folks take a thought home with them, and that is: if you want to go quickly, you go alone; if you want to go far, you go together.” The Dotter Lecture, supported by SIR Foundation, is an annual event named in honour of Charles T Dotter, considered universally to be the founding father of interventional radiology. SIR say that the annual lecture spotlights an outstanding interventional radiologist who has greatly contributed to the field and to the society. “Dr Matsumoto’s commitment to patient-centred care is representative of what the future of interventional radiology will be,” commented SIR president M Victoria Marx, an interventional radiologist at Keck Medicine of USC, and professor of clinical radiology and diagnostic radiology residency programme director at Keck School of Medicine of USC, Los Angeles, USA. “His call for unity and a shared purpose among interventional radiologists is a model for us to follow to make a change in the wider health care community.” A University of Virginia faculty member since 1991, Matsumoto has helped train ovr 200 diagnostic radiology residents and 100 vascular and interventional radiology fellows. he is a past-president of SIR and former programme chair of the annual scientific meeting; he has been involved with SIR for 31 years.

June

Issue

FAIR-Embo

FAIR-Embo hopes to spread safe, cheap embolization around the world Vincent Vidal (Marseille, France) and colleagues have demonstrated the in vivo feasibility of arterial embolization with permanent and absorbable suture fragments, leading them to propose what they have termed the “FAIR-Embo” concept to the wider interventional radiology (IR) community. Writing in Cardiovascular and Interventional Radiology (CVIR), they conclude: “Embolization by absorbable and non-absorbable suture is a feasible and effective treatment, which opens up the possibility of global use of this inexpensive and widely available embolization agent”.

peaking on this topic for the first time at GEST (Global Embolization Oncology Symposium Technologies; 9–12 May, New York, USA), Vidal presented the results of the preclinical study to attendees, calling this “the first step” towards his ambitions for the FAIR-Embo initiative. In this initial preclinical study, the investigators used a porcine model to test the feasibility and safety of arterial embolization with absorbable and non-absorbable suture fragments. Their publication reports that the embolization with these agents was a technical success. As described in the CVIR paper, an interventional radiologist embolized the target artery by inserting a suture fragment into the lumen of a 5ml syringe, and then pushing it through the catheter, along with contrast agent. Once a complete occlusion of the artery was achieved, the embolization was finished. The maximum suture fragment diameter corresponded with the inner catheter and microcatheter diameter: for example, when using a 4F catheter, the largest compatible suture fragment diameter was 0.9mm. Dubbing this method the “FAIREmbo technique”, Vidal and coauthors state: “The FAIR-Embo technique is similar to a torpedo gelatine embolization. In our study, the selective catherisation, along with an operator, has resulted in selective embolizations without any off-target embolizations.” They continue: “FAIR-Embo is a concept based on the hope [of using] interventional radiology in emerging countries, by the development of safe, available and cheap embolic material. “This work [the preclinical study] is a proof of concept of the feasibility and safety of the FAIR-Embo procedure, using homemade suture fragments—made from a globally available suture material—with the aim of making arterial embolization available in the greatest number of countries.”

FAIR-Embo ambitions

“Interventional radiology is very powerful for treating a vast range of different indications”, Vidal said at GEST. Showing an image of a wellkitted out angiography suite replete with multiple screens and bright, clinical lighting, he continued: “This is what we think when we think of interventional radiology in our country. In emerging countries, this is not the case.” Elaborating to Interventional News, he explained: “We have the knowledge, skill, and materials to save lives through interventional radiology, but these are unequally distributed around the world. In certain countries with emerging economies, physicians cannot perform embolizations, as they lack the embolic agents necessary. This can be for two reasons: firstly, the embolic agent may be too expensive; secondly, the material may not be available in that country, as the manufacturer does not distribute in that region. In both these cases, we can potentially offer a solution, if further testing proves that embolization with absorbable or non-absorbable sutures is safe and effective.”

Where FAIR-Embo started and next steps

The FAIR-Embo concept comes from Vidal, though he describes a conversation in Alexandria, Egypt, with Jafar Golzarian (University of Minnesota, Minneapolis, USA), a co-convenor of GEST, as catalytic. Allegedly, Golzarian and he were talking of many nations’ inability to afford the cost of materials for interventional radiology procedures. When asked about this conversation, Golzarian tells Interventional News: “We were talking about the cost of stents, and if it would be possible to create cheaper stents for use in countries that do not have much money. With this in mind, Vincent [Vidal] started to think about what we could do for embolization, and then he realised we have these absorbable and permanent suture materials that he could cut and use as an embolic agent. It

is very smart.” Currently, Vidal and his team are working on a second preclinical study. This will also use small fragments of sutures (non-spherical, noncalibrated particles, as in the first preclinical study presented at GEST and published in CVIR), but this time Vidal explains to this newspaper that the aim is to investigate their safety and efficacy when treating benign and malignant tumours. “That means we can have a range of embolizations, which is important”, he states. Vidal hopes to have completed this work and have the results before the end of the year. The next step will be to run a clinical study, where the feasibility of the FAIR-Embo technique can potentially be demonstrated in humans. Vidal informs Interventional News that, dependent on favourable outcomes in the second preclinical study, he hopes the clinical study can begin at the start of 2020. “We need to move as quickly as possible,” Vidal urges. “My goal is for everyone in the interventional radiology community to play their part; I want to give this idea to everyone. If we get good clinical results next year [2020], I would

He stresses that this is an opportunity to spread interventional radiology practices across the world, offering these minimally-invasive, image-guided procedures to all countries. The target regions are Africa, South America, South-East Asia, and some countries in the Middle East, such as Iran and Iraq. However, Vidal stresses that “it is important to understand that this community [of interventional radiologists] do not want to do the job for physicians in the emerging country.” He says: “We plan to provide the tools for them to do these procedures and build the interventional radiology practices themselves. This will give them the opportunity to do other kinds of interventional radiology procedures in the future.” The opportunities this endeavour represents for industry is something emphasised by multiple proponents of the FAIR-Embo initiative. Speaking with Interventional News, Golzarian said: “This certainly offers an opportunity to developing countries, in terms of physician education and patient outcomes, but also for industry. If these emerging countries start to perform embolizations, they will be able to attract more interventional

Top: Fragment of green suture (size 2) inserted into a 4 FR catheter. Middle: Fragment of purple suture (size 2) inserted into a microcatheter. Bottom: Blue particles roughly cut with scissors. Image courtesy of Vincent Vidal.

FAIR-Embo is a concept based on the hope [of using] IR in emerging countries by the development of safe, available, and cheap embolic material.” like to create a foundation to collect money to develop the FAIR-Embo project.”

An international effort

Ultimately, Vidal would like FAIREmbo to be an international effort, with interventional radiologists from developed countries working with those in more resource-poor settings to provide these cheaper, safe embolic agents.

radiologists, to train a younger group of physicians, and this will help grow interventional radiology and thus the market these companies operate in.” Marc Sapoval (Hôpital Européen Georges-Pompidou, Paris, France), co-convenor of GEST with Golzarian, lent his support to the project, enthusing: “If we could do fibroid embolization like this, it would be amazing”.

June

Issue

Uterine fibroid embolization

Uterine fibroid embolization safer and as effective as surgical treatment Uterine fibroid embolization (UFE) effectively treats uterine fibroids with fewer post-procedure complications compared to myomectomy, according to new research presented at the Society of Interventional Radiology’s 2019 annual scientific meeting (23–28 March, Austin, USA). Women who received this minimally-invasive treatment also had a slightly lower need for additional treatment than those who underwent surgery.

FE is a minimally-invasive treatment for uterine fibroids that is less painful, preserves the uterus, and allows women to get back to their lives sooner than surgical options. However, past research suggests US women, a majority of whom will experience uterine fibroids by age 50, are

largely unaware of UFE despite more than 30 years as an evidence-based treatment. “Women have options for treating their uterine fibroids. UFE and myomectomy are procedures with similar efficacy and durability for treating fibroids, but UFE has fewer complications and shorter hospital stays,” says Jemianne

Bautista-Jia, radiology resident at Kaiser Permanente (Los Angeles, USA) and lead author of the study. “There are important factors women should consider when choosing between the procedures. These factors include risk of bleeding, possibility of infections, and recovery time.” In the retrospective cohort study, researchers analysed treatment outcomes of 950 uterine fibroid patients from 1 January 2008 through to 31 December 2014. Half of the patients underwent UFE, a non-surgical treatment that eliminates the blood supply to fibroids, causing them to shrink or disappear. The other half were treated surgically through

UFE and myomectomy have similar efficacy and durability, but UFE has fewer complications.”

myomectomy, a procedure that removes existing fibroids. After an average seven-year follow up, the study found that women who underwent myomectomy had a higher rate of post-procedural complications, including a 2.9% rate of blood transfusion, which was significantly higher than the 0.9% rate for those who were treated using UFE. Patients in both treatment groups demonstrated a significant increase in haemoglobin one year after the initial procedure due to reduced bleeding. The two methods were comparably effective based on the rate at which secondary interventions— including UFE, myomectomy, and hysterectomy—were needed. Second interventions were completed in 8.9% of women who received an initial UFE compared to 11.2% for women who initially underwent a myomectomy. This study also showed similar rates of miscarriage for women who underwent either UFE or myomectomy. Future research should explore the impact of all uterine-sparing fibroid procedures on pregnancy, which remains still poorly understood.

Interview Interventional News speaks to Jemianne Bautista-Jia about her research on uterine fibroid embolization (UFE). “Being in the same demographic as my patients allows me to realistically consider what I would want in their situation,” she says. Bautista-Jia calls for interventional radiologists to become better at marketing themselves, as she believes increasing awareness of the minimally-invasive possibilities offered by interventional radiology will foster the greater multidisciplinary collaboration necessary to best serve patients with uterine fibroids. She also acknowledges that more work needs to be done to collect data on the plausibility of pregnancy follower UFE.

What did you learn from this study?

Firstly, that UFE is safer than surgery with a lower rate of postprocedure blood transfusions. I think this is primarily due to the more invasive nature of the procedure [myomectomy], resulting in greater blood loss compared to UFE. Other studies corroborate our results such as the retrospective study published by Narayan et al in the Journal of Vascular and Interventional Radiology (JVIR) in 2010. One of our most surprising findings was that UFE resulted in a much higher rate of improvement in menorrhagia when compared with myomectomy. Seventy-five percent of patients in our UFE group reported an improvement in menorrhagia, versus only 50% in our myomectomy group— menorrhagia is the most common symptom that patients present with. Being a woman myself, I think that if I had symptomatic fibroids, I would rather have a procedure where you do not have a large incision, and you avoid the complications that can come with surgery such as blood loss and the development of adhesions which put you at risk for complications in the future.

Why do you think so many potential patients do not know about UFE, and what role can interventional radiologists play in spreading the word?

Firstly, a patient’s primary care physician is normally an internal medicine specialist or an obstetrician gynaecologist. Those are the doctors that patients see consistently, whereas interventional radiologists are specialists only seen by referral, at least in the USA. Those physicians are the gateway to get to interventional radiology, and may not be aware of this procedure. Maybe this lack of awareness is on us for not being more vocal about this procedure, and for publishing in journals that are specifically read by interventional radiologists. We need to be more proactive in letting other specialties know about this procedure, so they know it is an option to offer to their patients. Additionally, if patients are seeing obstetricians and gynaecologists for their problems, and obstetricians and gynaecologists are the ones performing myomectomies, of course they are more familiar with that procedure, and are probably more inclined towards keeping those patients and providing

comprehensive care. We also need to be more vocal about what our specialty is and what procedures we do, to reach patients directly, and to educate the wider public on what it is that interventional radiologists do. We have to be better at marketing ourselves and our procedures. Another reason may be, as studying fibroids is a relatively young branch of research, there is not enough data yet proving the safety of UFE in terms of pregnancy outcomes after the procedure. I think the most important thing interventional radiologists can do is to build a registry of patients who had UFE and who attempted to conceive following the procedure, so we can see whether it is safe or not. Being able to assuredly offer a minimally invasive treatment to patients with uterine fibroids who want to later get pregnant would be hugely valuable. We need to have more data for how UFE affects the plausibility of pregnancy postprocedurally. The late Dr. Pisco’s recent research in patients receiving conventional or partial UFE suggested that the procedure may actually aid in fertility. Particularly partial UFE in which only the arteries feeding the fibroids were embolised appeared to reduce the risk of infertility. These findings should be further explored.

Why do you think it is important to work with obstetricians and gynaecologists?

I think it is of the utmost importance, you have to have good relationships with all the physicians in your hospital, because of course everyone has something important and valuable to contribute to patient care. In specific situations, other specialities’ inputs and experiences may be more important for a patient and can help you to look at the situation from a different point of view. If any group is working in isolation, that is a disservice to the patient, because the treatment options are limited. However, many women are not receiving fibroid embolizations- a study published by NEJM found that, in the USA, just a few thousand patients receive UFEs each year, compared to around 200,000 who have hysterectomies. Some of these hysterectomy patients likely could have been treated with UFE and had their uteruses preserved, so the collaboration is clearly not as strong as it could be in an optimal scenario. We still have a way to go. Jemianne Bautista-Jia

June

Geniculate artery embolization

First geniculate artery embolization in the UK performed The first geniculate artery embolization (GAE) to take place in the UK to treat osteoarthritis pain in the knee has been performed by Mark Little at the Royal Berkshire Hospital in Reading, UK, where Little is a consultant interventional radiologist. Little is the lead investigator in the GENESIS study, investigating the use of GAE in UK patients, and is a visiting professor at the University of Reading, UK. A PREVIOUS JAPANESE study found a 75% reduction in pain over a four-year period. Yuji Okuno (Tokyo, Japan) and colleagues found that, in a small cohort of patients, GAE for mild to moderate knee osteoarthritis was feasible, rapidly relieved resistant pain, and restored knee function. Currently, in Europe, osteoarthritic patients are given painkillers, and knee-replacement surgery is conducted in severe cases. GAE is therefore posited as a potential minimally invasive alternative for patients with mild-to-moderate osteoarthritis pain for whom painkillers have not worked. Little, who is leading the study, comments: “If the results of this study and future studies confirm the Japanese data, then geniculate artery embolization is a potential game changer for the treatment of osteoarthritis. Performed under only local anaesthetic, the procedure takes about one hour and patients go home the same day. It is truly minimally invasive. If you can get patients off high-dose painkillers who are struggling with mobility and unable to work, it has a massive impact on their health and quality of life.” Speaking to Interventional News, Little elaborates about the ideal GAE patient: “Osteoarthritis of the knee is a hugely common problem. Whilst knee replacement is a good treatment, it is not a perfect treatment, and talking to orthopaedic surgeons, they do not want to operate on the patients who are 40 to 55 because they are young. Some of these patients have conservative treatment (physiotherapy, joint injections), and some will benefit from that for a period of time, but some will not. There is this real middle band of patients that have got significant symptoms from their knee osteoarthritis that are severe enough to affect their quality of life, but which are not severe enough to merit having knee replacement surgery. I think that is where GAE has a massive role to play, if it is proven long-term. As a scientist and as an interventional radiologist, I think we have to get together as a community and study this treatment, as we have done with prostatic artery embolization (PAE), and as we have done with uterine fibroid embolization (UFE). We need good quality data so we can say with decisiveness that this is a good option for our patients.” Against the backdrop of the current opioid epidemic, in both Europe and North America, Little further emphasises the positive role GAE may play in these patients’ lives by calling the procedure a “big opportunity” to lessen the dependence on painkillers. Whilst deliberate in not over-stating the present role of GAE in this regard, Little does say that “GAE has the potential to be game-changing”. More data are needed to confirm this hope. Through his work on GAE, Little has been working with orthopaedic surgeons. Of this experience, he says: “The multidisciplinary collaboration is very good. As these patients have failed conservative treatment, but are not suitable candidates for joint replacement, the orthopaedic surgeons are delighted to refer these patients. To be able to offer a potential new treatment for these patients is really very beneficial. There is a huge demand for a treatment in

Issue

up to two years, is being conducted in collaboration with the University of Reading, UK. It has funding from Merit Medical and support from the National Institute for Health Research (NIHR). An additional multicentre, randomised controlled trial investigating GAE against a sham procedure has been submitted by Little and collaborators for approvals in the UK through the Health Technologies Assessment (HTA) process, and an “ambitious international project” focusing on the procedure is underway (see page 11). Enthusing about the potential of this work, Little comments: “Interventional radiologists are great innovators, and we need to combine that creativity with performing very good, high calibre research. By doing that, musculoskeletal embolization and imageguided intervention may have a huge role to play in the future. There are certainly lots of patients out there, so we just need to prove that it works.”

The first GAE case in the UK: The patient response

Mark Little

As a scientist and an interventional radiologist, I think we have to get together as a community and study this treatment [GAE], just as we have done with prostatic artery embolization and uterine fibroid embolization.” this space—that is why we are having no trouble at all with referrals for the GENESIS study.” The GENESIS study has nearly completed enrolment, with 38 of 50 anticipated patients currently on board. Little reports a high patient referral rate for this study, and tells Interventional News that he anticipates enrolment to be complete within a few weeks of this newspaper going to press. Preliminary data will be presented at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 1–10 September, Barcelona, Spain), and Little says that though this will be based on “incomplete data”, and therefore will not provide “the full story”, he believes that “we will still be able to draw some early meaningful conclusions, as we have a number of patients already with up to six months’ follow-up”. The GENESIS study, which will follow all patients

The 65-year-old patient, Linda Skilton, underwent the procedure on 29 January, and reported positive results. Quoted in a press release from the Royal Berkshire NHS Foundation Trust, she says that before the procedure “I was having problems with my left knee; a lot of swelling, a lot of fluid, limited mobility. “I was given cortisone injections, which made it settle for a while, but it flared up again a year later when I was using some equipment in the gym. For the past couple of years, I have not been able stand for too long because it got so sore and swollen and I could not keep it bent or straight for any length of time either, which made sleeping difficult. She continues to describe the procedure: “I only felt the initial cut to get to the artery, which was no worse than a paper cut. I was expecting some feeling of pushing and pulling, but I did not feel anything at all. “Since the procedure, I can feel day-to-day that my knee is improving. I can easily walk up the stairs for the first time in years. I am delighted with the outcome.” Commenting specifically on this patient’s response to the procedure, Little says “Linda is clearly very active and if we can keep her playing golf, then that will have a profound impact on her social interactions with friends, improve her happiness, and wellbeing, and give her back her independence.” However, while he hopes that every patient has a reaction as positive as this, Little stresses that “n=1 does not mean that this is going to be the panacea. I will reserve getting carried away until we have data up to two years. Hopefully, we get consistently good results, but we need to take an analytical approach and compare all of our results before we can be categorical in our conclusions.”

The procedure

The patient is treated as a day case procedure. They have a pre-procedural contrast-enhanced MRI scan, where Little says the radiologist is “looking for synovitis and capsular enhancement”. During the procedure, in the majority of patients the interventional radiologist performs an antegrade puncture in the common femoral artery. The interventionalist then navigates the catheter under X-ray guidance down the affected leg into the geniculate arteries. Little says “We are looking for an abnormal contrast blush in the region of the degenerative change that correlates with the pre-procedural MRI scans”. Next, the IR uses angiography to select the vessels that correspond to those areas with abnormal vascularity. “Once we are in there,” Little says, “we will confirm through an on-table cone beam CT, and then once we are happy with everything, we will embolize the geniculate arteries. We use diluted Embosphere (Merit Medical) particles to embolize the abnormal regions”.

June

Issue

Musculoskeletal embolization

GAE registry will use artificial intelligence to predict patient outcomes Sandeep Bagla (chair of Interventional Radiology at the Vascular Institute at Virginia, Woodbridge, USA) presented the results of an initial clinical study detailing his positive experience treating 20 patients with geniculate artery embolization (GAE) for mild to moderate knee osteoarthritis and moderate to severe pain at the annual scientific meeting of the Society for Interventional Radiology (SIR; 23–28 March, Austin, USA) earlier this year. This is the prelude to a second, ongoing, randomised controlled trial focusing on GAE. A larger cohort has just been approved by the US Food and Drug Administration (FDA). With this wealth of data on the horizon, an embolization registry is being launched with the hope of utilising artificial intelligence (AI) to predict patient outcomes.

escribing the initial pilot study to Interventional News, Bagla believes the results are promising: “We found that the vast majority of patients were responders, so 19 out of 20 patients demonstrated a significant improvement in pain. The average reduction in pain was around 65%. The improvement in disability and the improvement in physical function paralleled the change in pain scores.” All 20 patients were followed up to six months post treatment, and were assessed for pain, disability, and physical function. Imaging was also compared before and after embolization. Sixty per cent of patients reduced their medications following the procedure. Bagla explains that “these patients were

on a variety of medication—NSAIDS or opioids—and as the majority of patients were able to reduce these, I think this could have a big impact on the opioid crisis.” “In terms of safety”, Bagla further comments, “there were a number of minor adverse events, the most common being transient skin discolouration, which occurs as a result of non-target embolization to cutaneous arteries. Two of our patients developed transient plantar numbness. Both of those patients were treated with a smaller sized particle, at 75 microns, so at that point we upsized our particle size to 100 microns, and we did not experience that [complication] further. Both of them resolved spontaneously in under two weeks, but they were eye opening in terms of us understanding what the potential

New interventional radiology treatment for lateral epicondylitis reduces pain and inflammation without surgery Lateral epicondylitis, otherwise known as “tennis elbow”, can be effectively treated through transcatheter arterial embolization (TAE), according to research presented at the Society of Interventional Radiology’s 2019 annual scientific meeting (23–28 March, Austin, USA). LATERAL EPICONDYLITIS IS a painful chronic condition caused by overuse and repetitive stress to the tendons and muscles around the elbow, and affects up to 3% of the US adult population. Possible treatments include nonsteroidal anti-inflammatory drugs, corticosteroid injections, extracorporeal shockwave therapy, sclerotherapy, growth factor treatment, stem cell treatment, and surgery. “Tennis elbow can be difficult to treat, leaving many patients unable to perform the simplest tasks, such

complications could be.” The investigators used a permanent embolic, Embozene (Boston Scientific), in this initial clinical study. Bagla says that this decision was informed by previous work in this space from Yuji Okuno and colleagues (see below) in Tokyo, Japan. Okuno et al used either the resorbable antibiotic imipenem/ cilastatin sodium or 75μm calibrated Embozene microspheres as the embolic agent in the transcatheter arterial embolization of 11 and three patients, respectively, suffering from mild to moderate knee osteoarthritis. “For us”, Bagla says, “the first natural step was to replicate and expand on what he had done, in terms of [using] a permanent embolic.” However, a second, follow-up study is underway, with enrolment just completed, that will use a resorbable embolic, Optisphere (Medtronic). This is a randomised controlled trial comparing GAE against a placebo, with a scheduled 12-month follow-up. Twenty-one patients are enrolled, with 2:1 randomisation—14 patients will undergo embolization, and seven will have a sham angiogram procedure with catheterisation. After one month, if the patients who received the sham procedure have reported no improvements, they will be allowed to cross over to the embolization arm of the study and be embolized. “As those seven patients can be unblinded and receive the treatment, in reality, all 21 patients could potentially receive the treatment”, explains Bagla. The US investigators have additionally recently received approval from the US Food and Drug Administration (FDA) for a much larger cohort study, which will roll out after the second study of 21 patients. Desiring to make best use of this imminent wealth of data focusing on

as picking up their children, cooking dinner, or even working on a computer. With this frustration, many patients turn to invasive major surgery after years of failed physical therapy and medication use,” comments Yuji Okuno, founder of the Okuno Clinic in Tokyo, Japan, and lead author of the study. “We were interested to see if this technique, already in use in other areas of the body, would be effective for this common, debilitating condition and help people immediately regain a range of motion that many of us take for granted in our everyday tasks.” Okuno and colleagues conducted a prospective study in 52 patients with lateral epicondylitis causing moderate to chronic pain for at least six months who did not find relief from conservative treatment through to 90 days. The patients received TAE between March 2013 and October 2017, and 48 patients were followed for four years after the treatment. According to the study investigators, the treatment is safe and effective and does not require physical therapy. No major adverse events were observed and no patients experienced bone marrow necrosis, obvious cartilage loss, or muscle atrophy. The researchers said they found statistically significant reductions from baseline in pain-rating scores at three, six, and 12 months post treatment. They used methods including the Quick Disability of the Arm, Shoulder and Hand scores (the median for this metric was 52.1 after one month, 5.6 at six months, and 3.7 at 12 months); visual analogue scale pain rating scores; patient-rated lateral epicondylitis evaluation scores; and pain-free grip strength. Additionally, MRI imaging in 32 patients two years after undergoing TAE showed an improvement in tendinosis and tear scores.

GAE and embolization as a whole, Bagla and his team are launching a global embolization registry. This registry will cover embolization for osteoarthritis as well as other forms, such as prostate artery embolization and uterine fibroid embolization. Bagla enumerates the benefits he believes a registry provides, saying that “Clinical trials can be criticised for their lack of ability to replicate the data in the real world. Many clinical trials are very well controlled, and have very strict inclusion and exclusion criteria, meaning that many patients are screened out. Registries allow practioners like myself, and others around the world, to collect real world data, so patients do not necessarily have to meet very strict criteria for enrolment and can be treated as part of their standard of care, where you are collecting information for all outcomes and adverse events. A registry also allows for large cohorts of patients. Now, you can get large cohorts of data from Asia, Europe, America, and pull the data together to perform more detailed analyses on subsets of patients. This enables you to determine which groups of patients do better.” He also hopes that data pooled in a registry will drive insurance coverage for the procedure. The registry will be sponsored by JiggleMed, a software company that Bagla heads as CEO. JiggleMed is partnering with the artificial intelligence company Surgeri to collect, annotate and analyse the data. “Ideally”, Bagla enthuses, “this data will help us to predict which patients will do better. The future of our field is to gather this data in one place, and to use it to predict how individual patients will do. Annotating the data is a timeintensive process, but it is a project we are dedicated to.”

The treatment can be completed in approximately one hour in an outpatient clinic, and requires access via the radial artery in the wrist under local anaesthesia. A catheter is moved through the wrist to the elbow where the inflamed blood vessels are embolized, preventing excessive blood flow to the affected part of the elbow. Okuno uses imipenem/cilastatin sodium as an embolic material. Okuno is an embolization pioneer, inventing the treatment. He has previously treated osteoarthritis in the knee using transcatheter artery embolization (see page 10 and the above story), and was the first in the world to use the procedure in the elbow. Both Sandeep Bagla (Woodbridge, USA) and Mark Little (Reading, UK) have cited Okuno as an “inspiration” for their work to Interventional News and, in Little’s case, that reading the published literature from Japan detailing the use of GAE in the knee had “piqued his interest”, and eventually led to his own work in the field. Commenting on embolization in the musculoskeletal system more generally, Little tells this newspaper: “I think musculoskeletal embolization is a slowly expanding area, but soon it will have a big role to play. Published data on interventional radiologists’ experiences in the shoulder and elbow, as well as with tendinopathy, indicate that these are areas where embolization seems to make a difference. Talking to my orthopaedic surgeons who specialise in shoulder surgery, for example, it is evident that there is a high demand for embolization: operating surgeons are reporting finding a mass of inflamed tissue and abnormal blood vessels in these diseased shoulders. They are desperate for us [interventional radiologists] to start a study looking at shoulder embolization, and maybe in the future we will do that.”

June

Emborrhoid

The emborrhoid technique in 2019: an outpatient option for patients in pain

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➔ 1

Vincent Vidal Comment & Analysis As a world-leading advocate of the “emborrhoid” technique—the embolization of the superior rectal arteries—and the lead author of the 2015 study demonstrating the procedure’s efficacy, Vincent Vidal provides an update four years on concerning the current status of the technique. In 1994 and 1998, EV Galkin (Krasnoyarsk, Russia) first described a potential interventional radiology treatment for chronic haemorrhoids complicated by haemorrhage. Published in Russian, the audience for these two papers was limited, and Vidal has been a pioneer for the furtherance of this work outside of Russia. With a randomised, comparative evaluation of the emborrhoid technique underway, Vidal hopes to confirm its place as a minimally-invasive, therapeutic alternative for treating patients with haemorrhoidal disease.

ith a prevalence of 4–35%, haemorrhoidal disease is the most common anorectal condition. One of the main chronic symptoms is rectal bleeding. Its recurrence can alter the quality of life and, more rarely, cause anaemia. Pain is less common, only occurring in the event of a complication (congestive exacerbation, external haemorrhoidal thrombosis, fissures). The most common treatment involves hygiene and dietary measures, phlebotonics and/or nonsurgical outpatient treatment (infrared photocoagulation, elastic band ligation). The haemorrhoidal arteriovenous network is a normal vascular formation. Internal haemorrhoids are now thought to result from an increase in arterial blood flow from the rectal arteries into the haemorrhoidal cushion (corpus cavernosum recti).1 Expansion of the vascular network of the anorectal submucosa initiates a negative vicious circle of progressive vascular dilation and venous insufficiency, leading to haemorrhoidal hyperplasia. This hyperplasia causes an increase in blood pressure, arterial inflow and anal pressure in the corpus cavernosum recti. The mechanical function of the corpus cavernosum recti is dependent on the influx of arterial blood from the branches of the inferior mesenteric artery, the superior rectal arteries, but also in 30 to 50% of patients from the unilateral or bilateral middle rectal artery. By contrast, the lower part of the rectum and the anal canal are supplied with blood by the inferior and

middle rectal arteries, both of which have origins at some distance from the inferior mesenteric artery (pudendal artery, iliac network).2 Ten years ago, proctologists developed a new concept of treatment: elective transanal Doppler-guided haemorrhoidal artery ligation (DGHAL). The DG-HAL technique involves the identification and ligation of the superior rectal arteries under transanal Doppler guidance. Ligation of the superior rectal arteries provides a significant reduction of arterial blood flow to the haemorrhoids, and is effective in treating haemorrhoid disease.3 We have suggested that arterial ligation can be performed with coils in the terminal branches of the superior and middle rectal arteries via the endovascular route. The advantages of emborrhoid and DG-HAL technique versus surgery are that it maintains the haemorrhoidal tissue in place, preserves anal continence, has no rectal wounds (meaning no local care is necessary), there is significantly less pain, and the complications of open surgery are avoided, thus allowing a faster return to activity. Emborrhoid embolization is performed using a right femoral route. The inferior mesenteric artery is catheterised using a Simmons or Sidewinder catheter. The superior rectal arteries are then catheterised with a microcatheter. Coils used for the embolization are 0.018’’, from 2–3mm

1. Opacification of the distal part of IMA showing superior rectal arteries (SRA) with right opacification of the corpus cavernosum recti (white arrow). 2. Embolization with coils. 3. Control after embolization of right and left superior rectal arteries: notice the small left SRA still patent. 4. Control after complete embolization.

in diameter. Distal opacification of the superior rectal artery may depict a direct anastomosis with a dominant middle rectal artery in 30 to 50% of cases. In this situation, the middle rectal artery should be also embolized after catheterisation of the anterior trunk of the hypogastric artery. The technical success of the emborrhoid technique has been reported to be up to 90%. Meanwhile, the clinical success is also impressive: the literature reports between 74 and 83% of patients treated with the emborrhoid technique as having no complications.2,6 The main advantages of emborrhoid technique are: Patients have absolutely no pain. No major complications have been related to the emborrhoid technique, and especially no ischaemic or continence complications. This technique is available in an outpatient setting. The patient can return to activity the day after embolization. Embolization does not close the door to a complementary treatment if mandatory. The technique is easy to perform in an hour or less, especially if there is no need for middle rectal artery embolization. There are many benefits of endovascular treatment, including the complete visualisation of all the branches of the superior rectal arteries and anastomoses with middle and inferior rectal arteries.7 With the DG-HAL technique, it is possible that not all arteries are detected, which can lead to incomplete treatment, especially if there are anastomoses. Obviously, embolization eliminates the risk of direct anorectal trauma. There are many patients who suffer

from haemorrhoids but do not complain to physicians because they refuse to have an endorectal treatment. If we can offer a treatment for outpatients without pain, we believe more patients will seek treatment for this condition. We have demonstrated that distal coil embolization of the superior and middle rectal arteries to stop chronic bleeding is safe and effective. Many clinical studies are ongoing in Europe, Asia and America. We are now building a randomised, comparative evaluation with DG-HAL to confirm the role of the emborrhoid technique as a minimally invasive therapeutic alternative for haemorrhoidal disease. Vincent Vidal is the head of the Interventional Radiology section in the Department of Medical Imaging at the University Hospital TIMONE in Marseilles, France. References 1. Aigner F, Bodner G, Conrad F, Mbaka G, Kreczy A, Fritsch H. The superior rectal artery and its branching pattern with regard to its clinical influence on ligation techniques for internal hemorrhoids. Am J Surg 2004; 187:102–108 2. Moussa N, Sielezneff I, Sapoval M, Tradi F, et al. Embolization of the superior rectal arteries for chronic bleeding due to hemorrhoidal disease. Colorectal Dis. 2016 Jun 24. doi: 10.1111/codi.13430. 3. Infantino A, Altomare DF, Bottini C et al. Prospective randomized multicentre study comparing stapler haemorrhoidopexy with Doppler-guided transanal haemorrhoid dearterialization for third-degree haemorrhoids. Colorectal Dis 2012; 14:205–211 4. Vidal V, Louis G, Bartoli JM, Sielezneff Y. Embolization of the hemorrhoidal arteries (the emborrhoid technique): a new concept and challenge for interventional radiology. Diagn Interv Imaging 2014 95:307–315 5. Vidal V, Sapoval M, Sielezneff Y, De Parades V, Tradi F, Louis G, Bartoli JM, Pellerin O. Emborrhoid: a new concept for the treatment of hemorrhoids with arterial embolization: the first 14 cases. Cardiovasc Intervent Radiol 2015; 38:72–8 6. X. Sun a, y, J. Xub, y, J. Zhang a, Y. Jina, Q. Chen. Management of rectal bleeding due to internal haemorrhoids with arterial embolisation: a single-centre experience and protocol. Clinical Radiology 2018; 73:985.e1-6. 7. Bilhim T, Pereira JA, Rio Tinto H, et al. Middle rectal artery: myth or reality? Retrospective study with CT angiography and digital subtraction angiography. Surg Radiol Anat 2013; 35:517–522

June

Irreversible electroporation

Preliminary results indicate IRE stimulates the immune response to improve survival in pancreatic cancer patients Hester Scheffer (Amsterdam, The Netherlands) advocates for the use of combined irreversible electroporation (IRE) and other immune stimulatory therapies to achieve greater overall survival in patients with pancreatic cancer. At the 2019 European Meeting on Interventional Oncology (ECIO; 8–11 April, Amsterdam, The Netherlands), Scheffer presented the preliminary results of the first clinical proof-of-evidence study for an IREinduced T-cell specific immune response in pancreatic cancer in humans.

he presented work was a small side study of the recently completed PANFIRE trial, with the investigators conducting immune monitoring on 10 patients. Scheffer told the ECIO audience that this meant this “pilot study was therefore not powered for statistical significance”, and that they had carried it out for “exploratory purposes”. However, she said that the results were “interesting” nonetheless, and illuminating for the direction of future research.

The problem: Pancreatic cancer can “escape the immune system”

Pancreatic cancer is particularly aggressive, Scheffer explained, due to its ability to “escape the immune system”. The cancerous tumour is capable of this evasion through two mechanisms: its suppression of the tumour microenvironment, and the rarity of spontaneous apoptosis in pancreatic cancer cells. Pancreatic cancer suppresses its microenvironment by releasing suppressive cytokines into the surrounding tissue, which upregulate immunosuppressive T cells (regulatory T cells and myeloid-derived suppressor cells [MDSCs]). These, in turn, downregulate effector T cells, which directly effectuate the immune response. The tumour is therefore not recognised by the immune system, and “T cell tolerance against the tumour develops”, Scheffer said. The second way in which a pancreatic tumour limits the immunogenic potential is due to the low spontaneous apoptosis rate amongst pancreatic cancer cells: when a cell undergoes apoptosis, it breaks up into immunogenic epitopes that are taken up by antigen-presenting cells and transported to the lymph nodes, where a systemic, adaptive anti-tumour immune response can be elicited. This does not occur in pancreatic cancer.

The potential solution: shifting the balance “from immunosuppressive to immunostimulative”

Understanding these molecular machinations, Scheffer stated: “To improve the survival of pancreatic cancer patients, the cytokine balance needs to change from immunosuppressive to immunostimulative”. She and her colleagues hypothesised that IRE may be capable of altering this balance. As IRE reduces the tumour mass, it also leads to a reduction in the secretion of suppressive cytokines, which ultimately results in reduced T-cell tolerance. Additionally, the apoptosis induced by the IRE treatment triggers the sequence of events that stimulates the systemic, adaptive, anti-tumour immune response not otherwise witnessed in pancreatic cancer patients. Scheffer added that “hopefully, memory T cells will then induce anti-tumour immunity and delay or maybe even prevent the development of metastases. Through this way, IRE could in fact be a type of in situ tumour immunisation.” To test this hypothesis, Scheffer and colleagues sampled the venous blood of their patients three times: directly before IRE treatment, again two weeks after IRE treatment to investigate the immediate immune response, and then lastly three months post-IRE treatment, to investigate the durable immune response. White blood cells were isolated

immediately after blood sampling and cryopreserved for later analysis. None of the patients in the pilot study had received pre- or post-IRE chemotherapy. Speaking at the conference, Scheffer explained: “When we had collected the blood of all 10 patients, we broadly performed two different tests. In the first test, we determined the type, frequency and activation status of the circulating immune cells using flowcytometry. We investigated the MDSC and the T-cell subsets, and also activated PD-1 T-cells. But this only told us the number and the activation status of the circulating immune cells; it does not say anything about whether they were acting against the pancreatic tumour specifically.” To test the targeted immune response to the cancerous cells, the team performed tumour specific T-cell monitoring. They took the Wilms’ tumour 1 (WT1) epitope, which is expressed exclusively on the cell membrane of the pancreatic tumour, and coated it with an interferon-gamma (IFN-у) antibody so it could be detected. The investigators then combined the white blood cells collected from the patients with the Wilms’ tumour 1 epitope, and counted how many interferon-positive white blood cells—and thus Wilms’ tumour 1 positive white blood cells—there were. These represented tumour-specific T-cells, so tumour cells that were aggressive towards the pancreatic tumour. The Dutch researchers reported a significant and a nearsignificant decrease in the immunosuppressive cells (the regulatory T cells [p=0.03] and the MDSCs [p=0.09]) two weeks after IRE. Scheffer said: “We also found a nearsignificant increase in the immune-effector cells [p=0.08]. So, the observed reduced immune suppression did seem to allow for the effector T cells to develop, just as we hypothesised. “We also saw a significant de novo activation of PD-1 cytotoxic [p=0.04] and helper T-cells [p=0.01] two weeks after IRE, whereas the expression of the other immune checkpoints remained low and unchanged.” Turning their attention next to the tumour-specific T cell monitoring, the investigators found an immune response

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against the Wilms’ tumour antigen, and thus against the pancreatic tumour, in five out of the 10 patients. Scheffer elaborated: “This Wilms’ tumour 1 response correlated with the reduced immune suppression. Most interestingly, the patients who had a positive, tumour-specific T-cell response had a higher median overall survival than patients who did not have this Wilms’ tumour 1 response [p=0.055].” Scheffer summarised: “We found a temporary alleviation of the tumour-induced immune suppression, which created a window for anti-tumour T cell activation that was in turn associated with better overall median survival. These results advocate for the combination of IRE with other immune stimulatory therapies to further enhance this effect and achieve an even better overall survival.” Future work, Scheffer said, will look at the possibilities of further stimulating the immune response through a combination of IRE and immune modulatory therapies: this is the remit of the PANFIRE III trial. Ideas included performing a PD-1 blockade to additionally suppress regulatory T cells (as the investigators reported an upregulation of the PD-1 antigen), and the intratumoural delivery of Toll-like receptor ligands. According to Scheffer, the PANFIRE III trial will treat patients with oligometastatic pancreatic carcinoma— patients with between one and five liver metastases that are stable on four regimens of folforinox. “The patients will be randomised in three groups of six patients, and they will all receive PD-1 blockade, because we found upregulation of PD-1, so we think that is a very good thing to add,” Scheffer outlined. One arm will receive PD-1 blockade and IRE; one arm will receive PD-1 blockade and an intratumoural injection of Toll-like receptor ligand, and one arm will receive all three—PD-1 blockade, IRE, and the Toll-like receptor ligand. The PANFIRE III trial has just received full funding, and will begin recruiting patients in the coming months. Hugo Rio Tinto (Lisbon, Portugal), one of the panel moderators, said that this was “an interesting result”, commenting: “Maybe in the future we can regulate this immune response to a greater degree. Though I think the most important thing is patient selection”, something Scheffer agreed with. Rio Tinto also asked about the plausibility of predicting which patients would most benefit from this combined treatment, querying if Scheffer and colleagues will study factors that will predict patient outcomes, such as immune markers: “There are some immune types that are responding better to this therapy than others,” he said, “How will you identify these [possible] predictive factors?”. As half the patients showed the Wilms’ tumour 1 response, and half did not, Scheffer said at ECIO that this was something to consider. Speaking to Interventional News after the conference, Scheffer and Martijn Meijerink (Amsterdam, The Netherlands), panel moderator and senior author of the PANFIRE trial results, disclosed: “In our future study, we aim to perform NanoString sequencing and proteome analysis on pancreatic tissue pre IRE treatment. This will hopefully provide us with information about more than 700 oncogenes and just as many proteins and could possibly bridge the gap between cancer genome information, the observed cancer phenotype and the patient response to combined treatment with IRE and immunotherapy.” Fielding a question from the audience regarding whether or not the investigators were targeting the primary pancreatic tumour itself or the metastases, “which are more easy to puncture”, Scheffer said: “We are lowering the pulse protocol because we want to induce apoptosis as we want the antigen release, but we do not need to destroy the tumour completely, because obviously there are also metastases, so we will never achieve complete elimination. Hopefully we will not find any complications with this less invasive protocol. We chose the primary tumour because of the lymph drainage directly around it; the antigens have to be taken to the lymph nodes. For now, we think that will give the highest chance of a response, and if we only treat one metastasis, there might be fewer lymph nodes that can pick up the antigens. It is just a hypothesis, but we had to make a choice.”

June

Hepatocellular carcinoma

Y90 radioembolization in hepatocellular carcinoma: “Liver function is key” Jens Ricke (Department of Radiology, University Hospital LMU Munich, Germany) presented the latest evidence about Y90 radioembolization in hepatocellular carcinoma (HCC) at the 2019 European Conference on Interventional Oncology (ECIO; 8–11 April, Amsterdam, The Netherlands).

e outlined the latest recommendations from the European Society for Medical Oncology (ESMO) for treating HCC according to Barcelona Clinic Liver Cancer (BCLC) stage. “The figure summarising the treatment options has changed recently. What has changed is the position of radioembolization (selective internal radiation therapy; SIRT). In BCLC stages 0–A, SIRT is listed along with stereotactic radiation therapy (SBRT) and brachytherapy as alternative treatment. SIRT is also listed as an alternative treatment for BCLC stage B cancers, but not for BCLC C anymore.” A study by Salem et al in 2016 that compared conventional transarterial chemoembolization (cTACE) with Y90 radioembolization in a small group of patients with HCC of BCLC stages A or B found that Y90 treatment provided a significantly longer time to progression than cTACE. Ricke elaborated: “The response is probably totally similar between Y90 and TACE, but the time to progression is much better with radioembolization than with cTACE—this needs further validation.” The palliative substudy of the SORAMIC trial compared patients with advanced stage liver cancer treated with SIRT and sorafenib or with sorafenib alone. There was no significant difference in patients’ overall survival rates between the two groups but in some patient subgroups there were some possible survival benefits with the addition of SIRT. Ricke noted that “these are hypothesis-generating data and might affect how we treat these particular groups of patients in the future. We observed a survival benefit in patients with no cirrhosis (22 vs. 10 months, HR=4.46) and those with non-alcoholic aetiology (15 vs. 11 months, HR=4.63). We understand these results may be due to liver function. We also found a survival benefit

in patients younger than 65 years (18.5 vs. 11 months, HR=4.65).” To understand why younger patients might fare better, Ricke described albumin-bilirubin (ALBI) development in these patients: “We see that with the addition of Y90 to systemic treatment, in younger patients the ALBI score is fairly consistent, but in patients over 65 it gets out of hand.” In PP patients with Child Pugh points ≤6 and tumour size and lesions ≥7 (patients who are well compensated) overall survival with SIRT/sorafenib is 15 months vs. 11 months in patients treated with sorafenib (HR=4.82). Ricke compared this result with the same patients who were previously treated with TACE: “Liver function gets lost in the TACE group. If you apply Y90 after TACE you may therefore run a risk of losing the patient’s liver function early—somewhere between four and eight months.” A study by Chow in 2018 compared SIRT and sorafenib in patients with HCC and overall survival did not differ significantly between the two groups, though it initially looked better in patients treated with SIRT. Ricke explained, “Our hypothesis is that radiationinduced liver disease (RILD) is happening later than we are used to, so you lose those patients who are not well

[In the new ESMO guidelines] SIRT is listed as an alternative treatment for BCLC stage B cancers, but not for BCLC C anymore.”

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enough compensated or when there are no measures to prevent liver function. Liver prevention from RILD is key for radioembolization.” The preventive effects of a combined drug regimen (ursodeoxycholic acid, pentoxiphylline and enoxaparin) on focal radiation-induced liver injury (fRILI) in patients with HCC were illustrated by a 2014 study by Seidensticker et al. Patients underwent radiotherapy and one group was given the combined drug regimen. After six weeks, the combined drug group had a significantly higher minimal mean hepatic threshold dose than the no drug group (19.1Gy vs. 14.6Gy, p=0.011) and fRILI was found in 45.5% of patients in the combined drug group compared with 90.9% of the no drug group (p=0.022). Another study by Seidensticker et al in 2019 assessed the effect of RILD prophylaxis in patients with breast cancer. Ricke summarised the multivariate analysis, “The only post-therapeutic issue that would influence survival is intensified prophylaxis. The Kaplan Meier curves for survival analysis calculated from the date of radioembolization also show that intensified prophylaxis improves the probability of survival. This needs further validation but indicates that there is something we can do against RILD.” Ricke reported that a number of studies being carried out in intermediate-stage HCC combine immunooncology with something interventional such as Y90: “Some of these studies will have an arm with immunotherapy only in BCLC stage B.” The immunological impact of Y90-radioembolization was examined in a study by Chew in 2018. Ricke noted that “a prediction model applying the immune response after Y90 is the absolute best discriminator for overall survival. If you have immune response afterwards you will survive.” The AROMA study, which involves SIRT treatment of HCC, is collecting baseline biopsies and biopsies before a second intervention is given. Ricke explained, “you then have target tissue from abscopal untreated tumour four to six weeks after radioembolization. Four weeks after SIRT you can see extensive lymphocyte infiltration, which may be prognostically valuable. It is intriguing in terms of future combination with immunooncology.” Ricke concluded: “In SIRT, sequential and selective approaches must be mandatory—I urge you to be very selective, even in Y90—and strict patient selection must be carried out according to risk group definitions. Preventive measures need more validation but appear to be quite hopeful. In the future treatment will require combination with immuno-oncology.”

Smart speaker technology harnessed for hospital medical treatments

Smart speakers that are customarily used in your living room can be programmed to act as an aid to physicians in hospital operating rooms, according to new research presented at the Society of Interventional Radiology’s 2019 annual scientific meeting (23–28 March, Austin, USA). Smart speakers, such as the Amazon Echo and Google Home, offer a conversational voice interface that allows interventional radiology (IR) physicians to ask questions and retrieve information needed for their patient treatments without breaking sterile scrub. “DURING TREATMENT, IRs rely on nuanced medical information delivered in a timely manner. When you are in the middle of a procedure, you need to remain sterile, so you lose the ability to use a computer,” says Kevin Seals, a fellow in interventional radiology at the University of California, San Francisco (UCSF; San Francisco, USA) and lead author of the study. “This smart speaker technology helps us to quickly and intelligently make decisions relevant to a patient’s specific needs.”

The researchers at UCSF developed a device-sizing application for the Google Home smart speaker. The application processes questions from a human voice and provides recommendations on the precise sizing of medical devices. For example, if an IR needs to know what size sheath to use to implant a stent in a patient’s blood vessel, the smart speaker can quickly and accurately communicate the correct size based on the specific circumstances, which helps the physician in making a final decision.

“There are hundreds of devices, with more being introduced every day, making it difficult to determine the correct sizing or materials needed in every circumstance. This technology allows physicians to concentrate more closely on the care of their patients, devoting less time and mental energy to device technicalities,” explains Seals. In developing the application, size specifications were acquired using literature reviews for 475 IR devices, such as catheters, sheaths, stents, vascular plugs

and others. Natural language processing was implemented using Dialogflow, which extracted the information of interest from an input query. Logic operations and other data processing were performed using a Python script deployed to the cloud. The researchers plan to continue to build on this technology and expand its scope to include information on material costs and inventory databases. Having this information readily available will make treatments more efficient, cost-effective and beneficial to patients.

June

Issue

Interventional oncology

Call for IRs to standardise reporting of procedures to aid HCC patient outcome predictions The lessons learned from a recent research article were outlined in a presentation by interventional radiologist Maxime Ronot (Beaujon University Hospital, Paris, France) at the European Conference on Interventional Oncology (ECIO; 8–11 April, Amsterdam, The Netherlands). The article under scrutiny was ‘Development of a prognostic score for recommended TACE candidates with hepatocellular carcinoma: a multicentre observational study’, which was published by Wang et al in the Journal of Hepatology in 2019. TRANSARTERIAL CHEMOEMBOLISATION (TACE) is the standard of care for patients with Barcelona Clinic Liver Cancer (BCLC) intermediate stage B hepatocellular carcinoma (HCC) and for patients with unresectable BCLC stage A HCC. It can also be used as a bridge before liver transplant. When attempting to predict patient outcomes after TACE, Ronot reported, “individual factors have been described in many research papers as predictive of response to TACE, whether favourable or not, such as the size of the tumour, the number and location of lesions, and the way the tumour is enhanced or not after contrast injection. “You can also find many studies that try to include features and parameters about liver function or the status of the patient, and you end up with a lot of prognostic models with a lot of prognostic systems, and it is very hard to know which ones we should use, and how, and in which context,” he continued. Ronot also noted that, “most of these prognostic models have been described and derived from small series and from monocentric studies, and they lack external validation. Many are

also derived from cohorts of patients receiving TACE in a broader setting beyond the usual recommendations. This is where this paper comes in.” In their study, Wang et al included

had at least one measurable lesion >1cm. They screened 3,810 patients for eligibility. After exclusions, a total of 1,604 patients (87% male; 85% with hepatitis B virus) were randomised into training (n=807) and validation (n=797) cohorts in the study. “The authors’ first message,” said Ronot, “was that the patients’ median overall survival was rather high at more than 32 months and they explained that this was because of the strict inclusion/ exclusion criteria.” They produced two different models to see which was better at predicting patients’ overall survival: one with a simple addition of tumour size and number and a second which used an adjusted tumour size and number and included alpha-fetoprotein. Ronot stated that “the second model was not significantly better than the first model so they chose to stick with the first model.

For every scenario, they [the study authors] found the accuracy of their model was higher, and at the upper range of the discriminatory ability of all the models.” Maxime Ronot presenting at ECIO

patients receiving conventional TACE for HCC from 24 tertiary Chinese centres. They used strict inclusion criteria so their target population was made up of “recommended” or “ideal” candidates of TACE who were treatmentnaïve, had well preserved liver function with a Child-Pugh score of A5-B7 and

“The researchers proposed new criteria: the six–12 criteria, which we could use to stratify patients into three strata: the sum of the largest tumour and the number of tumours will be lower than six, between six and 12 or larger than 12. They showed how this could stratify in terms of patients’ overall survival in the derivation and validation

Virtual reality enables realtime, internal view of patient anatomy during treatment Immersive virtual reality (VR) may enable interventional radiologists to improve treatments using real-time 3D images from inside a patient’s blood vessels. New research presented at the Society of Interventional Radiology’s 2019 annual scientific meeting (23–28 March, Austin, USA) shows that the interactive technology could provide faster, more efficient treatment, with less radiation exposure and greater precision, ease and confidence.

“V

irtual reality will change how we look at a patient’s anatomy during an IR treatment,” asserts Wayne Monsky, a professor of radiology at the University of Washington (Seattle, USA) and lead author of the study. “This technology will allow physicians to travel inside a patient’s body instead of relying solely on 2D, black and white images.” The purpose of the study is to demonstrate the feasibility of using a catheter with electromagnetic sensors projected

onto a VR headset to see and steer the catheter through the anatomy to certain blood vessels. Using a CT angiography scan, researchers created a 3D-printed model and a holographic image of blood vessels in a patient’s abdomen and pelvis. They then guided hi-tech catheters through the 3D-printed model while the tracking system showed the image from the catheter through the VR headset. They compared the time taken to steer the catheter from the entry point of the femoral artery to three different

cohorts,” he explained. They then compared the performance and discriminative ability of this model with existing models. Ronot described how “for every scenario they found the accuracy of their model was higher, at the upper range of the discriminatory ability of all the models.” They also provided “a nice easy numbergram where you can plot the probability of one-, two- and three-year survival, as well as median survival, using the six–12 criteria. This is very useful and very easy to do.” Ronot outlined the strengths of the study, “which is clearly multicentric, as the data were from 24 centres, it has a clear endpoint of overall survival which is easy to understand, there is validation, the model was compared with other models and the model gives a continuous result.” He also noted some limitations: “As an observational study, the risk of bias is not completely absent, there was a high rate of HBV, as is common in Asia, and they did not look at the way treatment response reacted and changed with this model.” Ronot concluded that some important points can be taken from this study, “It underlines the importance of tumour burden that we frequently observe in HCC. It has demonstrated that survival can be quite long for patients at intermediate stage or with unresectable tumours—close to 33 months’ overall median survival is interesting. But most important for interventional radiologists, when I read this paper, I realised there was room for wide differences in the type of drug and dose used, whether gelatine sponge or polyvinyl alcohol foam particles were introduced, how tumour feeding vessels were embolized and so it is hard to believe that these differences will not have an impact on patient survival or response. I therefore believe that we need to start collectively working on a standardisation about the way we report procedures and the way we do the procedures.”

targeted vessels versus the time the process took using conventional fluoroscopic guidance, as well as time taken in similar real-life clinical angiographic procedures. In 18 simulated procedures, researchers found the mean time to reach the three targeted vessels using VR was much lower than in fluoroscopy, the standard practice that uses an X-ray image. In the first vessel, virtual reality took 17.6 seconds versus 70.3 seconds using the standard practice on the model and 171.2 seconds in the real-life procedure. With the improved efficiency, the researchers believe VR technology will create safer treatments by reducing the amount of radiation exposure to both patient and physician. They say it would also increase access to IR treatments. “Currently, the life-saving potential of IR is limited to hospitals and areas with the resources to invest in imageguided technology,” says Monsky. “There are three billion people worldwide in rural areas who do not have this access. This technology could allow for portability and accessibility so that these procedures are brought to rural areas using nothing more than a suitcase.” Researchers also surveyed the practitioners who had tried the technology, and they reported that VR improved the ease, precision and efficiency of the treatment. Additionally, the users said they felt more confident in their abilities.

June

SIR annual meeting highlights

Lumen morphology a “major factor” in determining clinical outcome of venous stenting in a challenging population Mahmood Razavi (Orange, USA) reported new data from a subanalysis of the VIRTUS trial, which set out to investigate the safety and efficacy of the Vici stent (Boston Scientific). The subanalysis forms part of the first prospective multicentre corelab adjudicated study that looked at correlates of clinical outcomes. It shed light on various baseline and procedural factors that are associated with clinical improvement as measured by Venous Clinical Severity Score (VCSS), one year after stenting. These included severity of patient symptoms before the procedure and lumen morphology after stent placement. “THE IDEA WAS to see who are the patients or the subpopulation of patients that actually do better with venous stenting, using the Vici stent system. We looked at multiple variables; both physiologically, in terms of patient characteristics, and anatomically, in terms of lumen shape before and after the stent placement,” Razavi tells Interventional News. The investigators performed both univariate and multivariate logistic regression analyses. Explaining their

methodology, Razavi says: “In terms of the threshold for significant improvement in clinical symptoms, we used both the traditional three-point drop in VCSS score, and the more stringent four-point drop in VCSS score. It turns out that when we use a three-point drop in VCSS score, one feature that was correlated to a significant improvement in clinical outcome was baseline VCSS score: the more symptomatic a patient was before the procedure, the greater the relief they experienced. The other two significant

Mahmood Razavi presenting at SIR 2019

factors had to do with the lumen morphology after stent placement. So, the lower the aspect ratio—that is a measure of how circular the vein looks after placement of the stent—and the lower the luminal area, [the better a patient fared]. The more circular a lumen looked, the better patients did clinically. Both [lumen aspect ratio and stent placement] were highly correlated to improve clinical outcome as measured by VCSS score.” When considering the four-point drop in VCSS score, which Razavi describes as “a much more stringent improvement”, two other features were also found to be significant. These were the aetiology of venous disease—

GEMS programme launches to promote diversity in IR specialty The Society of Interventional Radiology (SIR) announced the establishment of the Grants for Education of Medical Students (GEMS) programme at its 2019 annual scientific meeting (23–28 March, Austin, USA). Alan H Matsumoto, former SIR president, introduced the programme during his acceptance speech for the SIR Gold Medal Award (for which he was one of three recipients). The GEMS programme aims to support diversity within interventional radiology (IR) by providing travel grants for medical students participating in an IR clerkship outside of their home institution.

“W

ith IR now being recognised as its own medical specialty, we have a wonderful opportunity to engage medical students, whilst also focusing on the diversity within our specialty,” Matsumoto said. “We all know that once medical students are exposed to IR, they often fall in love with it. So it is really about giving them a chance to see and experience how IR really is early enough in their career so they can make the appropriate choice. “The purpose of the GEMS programme is to grow the diversity in IR by providing a travel grant to medical students who identify as either being from a gender, racial, or ethnic group underrepresented in IR, or who identify as LGBTQ, and who are seeking to be first generation physicians in their families, as well as students from a socioeconomically disadvantaged background, regardless of their gender or ethnicity, by providing them a travel grant as a way to encourage them to explore the specialty of IR as a career. Up to 10 US$15,000 travel grants per year will be awarded to medical students who have applied to participate in the GEMS programme, to participate in a four week IR clerkship outside of their home institution.”

The funding for the GEMS programme comes through donations from the Matsumoto family, the SIR Foundation, Boston Scientific, Cook Medical, Penumbra, Siemens Healthineers, and WO Gore. On the SIR Foundation’s website, the society state: “The clerkships to which the students are applying must devote at least 50% and up to 100% time to IR, with any remaining time devoted to diagnostic radiology (DR), nuclear medicine or a subspecialty area within DR. The clerkship must be at least four weeks in duration.” For IR programmes interested in participating, the SIR Foundation has said that it will “identify IR programmes from around the country” who are committed to assisting the eligible groups of medical students “to gain exposure to the field of IR” and will

The purpose of the GEMS programme is to grow diversity in IR.”

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thrombotic versus non-thrombotic—and stent location. Speaking of the former, Razavi says: “The difference in this trial versus the other three pivotal trials is that the thrombotics in this VIRTUS trial were only chronic occlusions; they were not acute thrombotic. Acute thrombotic patients were excluded, and chronic post-thrombotic patients had the worst outcome. That constituted 75% of patients in the VIRTUS trial. So chronic post-thrombotic versus non-thrombotic— there was a difference. “Also, stent location. When the inferior aspect of the stent extended into the common femoral vein and under the inguinal ligament, there seemed to be a correlation to outcome in those patients.” Describing the significance of these results to this newspaper, Razavi comments: “We have always assumed, or those of us who do a lot of venous intervention, based on our own experience, have thought that certain things are correlates to improved outcomes for patients in the patient population that we treat. By that, I mean both clinically and anatomically, such as patency and improvement in patient symptoms. But nobody had proven this. This is the first time that in a prospective, multicentre study, with corelab adjudication of data, we are actually looking at these variables, and to see which ones correlate with improved clinical outcome. These data were the correlates of improved clinical outcome, not patency; the patency analysis is coming—it is not complete yet.”

provide this listing on the SIR Foundation website. In his announcement speech, Matsumoto elaborated on the programme’s purpose: “The intent of the programme is to eliminate any financial barrier that might have prevented a medical student from exploring an IR clerkship. The rationale for encouraging students to participate in an IR clerkship different from their home institution is to provide them with the opportunity to be exposed to a different institution in an IR programme, to have a more personalised learning experience about the specialty of IR, to become more comfortable in a new environment, as a prelude to the residency application and interviewing process, and to potentially develop an early mentoring relationship in IR and broaden their professional network. “Not only does the programme offer opportunities for medical students, but hopefully will also encourage IR training programmes to contribute to the promotion of diversity in our specialty.” The GEMS programme began accepting applications from 1 April 2019. Matsumoto concluded: “It is really the goal and sincere hope of my family, Boston Scientific, Cook Medical, Penumbra, Siemanns Healthineers, Gore, the SIR and the SIR Foundation that the GEMS programme will help to expand the diversity of thought, and personnel of our specialty, so we may better serve the growing diversity of patients for whom we provide care.” This sentiment was echoed by then SIR president Victoria Marx (Keck School of Medicine of the University of Southern California, Los Angeles, USA), who commented: “SIR and SIR Foundation are incredibly grateful to Dr Matsumoto, his family and our inaugural industry sponsors—Boston Scientific, Penumbra, Siemens Healthineers, Gore and Cook—for supporting this important initiative to engage diverse groups of medical students in interventional radiology.”

June

Issue

Imaging

ADVERTORIAL SPONSORED BY GUERBET

The renaissance of Lipiodol in lymphangiography and lymphatic interventions Christof M Sommer, Thilo Hackert and Götz M Richter discuss the renaissance of Lipiodol-based lymphangiography following a decline in its use in lymphatic interventions at the start of the millennium. They cite this return to Lipiodol (Guerbet) as being directly connected to an increase in the number of patients suffering from lymphatic leakage caused by complex surgical procedures, labelling the contrast agent “indispensable” in a lymphatic interventions programme. The rise in Lipiodol usage is here to stay, they argue.

but also therapeutic, characteristics. Selective and persistent blockage of the diseased lymphatic vessels and sterile inflammation reactions with subsequent tissue scarring result regularly in the cure of lymphatic leakage. Lipiodol is also mandatory for second-line lymphatic interventions. Doxycycline- or ethanolbased sclerotherapy and EVOH (ethylene vinyl alcohol)-based liquid embolization show non-satisfying outcomes, especially in the setting of high-output lymphatic leakage, and therefore cyanoacrylate-based medical glue is regularly used instead. Not only for X-ray visualisation issues, but also for the specific adjustment of glue polymerisation time, Lipidodol is mixed with cyanoacrylate-based medical glue in different ratios.

Future directions

Christof M Sommer

Thilo Hackert

Introduction

The story of Lipiodol-based lymphangiography and lymphatic interventions starts in 1901, when the French pharmacist Marcel Guerbet synthesised Lipiodol, an iodinated poppy seed oil, today commercialised as Lipiodol Ultra Fluid. After the accidental discovery of lymphangiography during routine hystersalpingography by Charles Várady, an enormous amount of specific knowledge and skill accumulated. During the 20th century, Lipiodol-based lymphangiography was excessively used as a diagnostic procedure. Around the turn of the millennium, however, the numbers of patients undergoing lymphangiography decreased considerably, most likely since alternative noninvasive imaging modalities such as MRI became available. In the following years, interest in and competence to perform lymphangiography got lost in hospitals around the world. Interestingly, during the last decade, the pendulum swung back, and a high demand for diagnostic and therapeutic lymphangiography was noted. We believe that this phenomenon is directly connected to the increasing number of patients suffering from therapy-refractory lymphatic leakage caused by surgical procedures of great complexity. Today, Lipiodol is indispensable for all institutions with a lymphatic interventions programme.

Indications and outcomes

Lipiodol-based lymphangiography and lymphatic interventions can cure different types of highand low-output iatrogenic (for example, chylous ascites after ultra-radical lymphadenectomy) and spontaneous (for example, pulmonary lymphatic perfusion syndrome) lymphatic leakages. Typically, lymphangiography is performed either with the transpedal or intranodal application of Lipiodol under X-ray imaging, with the following outcome parameters: technical success rate of 90–100%, Lipiodol injection volume of 0.5–40ml, Lipiodol injection speed of 0.3–60ml/hour, complication rate of 0–22%, 30-day procedure-related morbidity and mortality rates of 0% and 0%, respectively, and clinical success rate of 51–100% for transpedal lymphangiography and 33–100% for intranodal

Götz M Richter

lymphangiography (according to the literature published between January 2007 and May 2017, and for patients suffering from post-operative therapyrefractory lymphatic leakage). Second-line lymphatic interventions, feasible on the same day as, or a few days after, Lipiodol-based lymphangiography, include many different procedures, such as interstitial embolization or thoracic duct embolization. Outcome parameters include technical success rate of 89–100%

Lipiodol unquestionably features not only important diagnostic, but also therapeutic, characteristics.” for interstitial embolization and 50–100% for thoracic duct embolization, Lipiodol/cyanoacrylatebased medical glue injection volume of 0.5–8ml, Lipiodol/cyanoacrylate-based medical glue mixing ratio of 1:2–20:1, complication rate of 0–22%, 30day morbidity and mortality rates of 2% and 0%, respectively, and clinical success rate of 80–100% for interstitial embolization and 90–100% for thoracic duct embolization.

Conclusions

Lipiodol plays a key role in lymphangiography and lymphatic interventions. For patients with iatrogenic and spontaneous lymphatic leakage, Lipiodol is the only pharmaceutical drug approved for radiological imaging of the lymphatic system. Following the application of Lipiodol, fluoroscopy, radiography and, in particular, computed tomography enable the precise visualisation of the different types of lymphatic leakages. Looking at published data, in conjunction with our long-standing experience at Stuttgart and Heidelberg—more than 600 transpedal lymphangiographies performed over the last three decades—it becomes evident that Lipiodol unquestionably features not only important diagnostic,

Lipiodol-based lymphangiography can be performed as a highly standardised and safe diagnostic and therapeutic radiological treatment. Second-line lymphatic interventions are associated with a higher degree of technical failure, complications, and morbidity, but also with a higher degree of clinical success. Currently, lymphangiography and lymphatic interventions are performed only in specialised centres, and not as nationwide primary care. This is the result of limited theoretical and practical knowledge in the radiological and referring community. Optimised radiological strategies, together with interdisciplinary consensus, should be published in the form of guidelines with the intention of promoting the best lymphatic care. The first steps towards achieving the strong evidence base have already been taken, with a prospective, randomised controlled multicentre trial currently being performed in South Korea, comparing interstitial embolization using Lipiodol and cyanoacrylate-based medical glue versus sclerotherapy in the management of symptomatic postoperative pelvic lymphocele. Nevertheless, the optimal pharmaceutical drug for second-line lymphatic interventions has not been developed yet. There have been speculations as to whether different versions of Lipiodol with even higher viscosity or a Lipiodol containing non-adhesive precipitating liquid embolic could further increase safety and efficacy. We have witnessed the successful renaissance of Lipiodol in lymphangiography; however, the reincarnation of Lipiodol in second-line lymphatic interventions is still an important objective. In the future, the number of patients with lymphatic leakage undergoing radiological treatment will dramatically increase, as soon as different problems (such as communication barriers between medical disciplines and the under-reporting of candidates) are solved. Christof M Sommer is an interventional radiologist at the Clinic of Diagnostic and Interventional Radiology and 1st Siemens European Reference Site for Interventional Oncology and Radiology, Klinikum Stuttgart, Stuttgart, Germany, as well as an assistant professor of radiology at the Clinic of Diagnostic and Interventional Radiology, Heidelberg University Hospital, Heidelberg, Germany. He has received a speaker honourary from Guerbet. Thilo Hackert is a professor at and deputy head of the Department of General, Abdominal and Transplantation Surgery, Heidelberg University Hospital and section chief at the European Pancreas Center, Heidelberg University Hospital, Heidelberg, Germany. He has no conflict of interest to report. Götz M Richter is a professor at and medical director of the Clinic of Diagnostic and Interventional Radiology and 1st Siemens European Reference Site for Interventional Oncology and Radiology, Klinikum Stuttgart, Germany. He has no conflict of interests to report.

June

Paclitaxel

While CX audience deems paclitaxel not dangerous, vascular pathologist says establishing “truth takes time” Delegates voted overwhelmingly against the notion that there was a demonstrable danger in any organ of the body attributed to circulating paclitaxel. These polling results, with a 67% majority, came after vascular pathologist Elena Ladich (Hollywood, USA) presented insights from new analysis on the effects of paclitaxel in the body. A Charing Cross (CX) Symposium Highlight Session (15–18 April, London, UK) explored the ramifications and possible resolutions four months on from the Katsanos et al meta-analysis published in the Journal of the American Heart Association (JAHA). The session was chaired by Roger Greenhalgh and moderated by CX Executive Board members Gunnar Tepe, Andrew Holden and Thomas Zeller. Experts, representatives of regulatory bodies (US FDA and UK MHRA) and other stakeholders scrutinised the current controversy surrounding paclitaxel-eluting devices over the course of four hours.

Elena Ladich

dditional polling at the close of the session revealed that 85% of CX delegates believed “no danger has been demonstrated in any organ of the body that is attributable to circulating paclitaxel”. This conviction was further consolidated when attendees were asked: “Have we established that there are substantial levels circulating in arteries used for reducing restenosis?”—68% of respondents said no. Ladich, whose presentation closed the session, spoke on the effects of paclitaxel on the artery wall, drawing from her practice with human autopsies. She explained that a proportion of the drug and excipient coating of paclitaxeleluting devices are known to embolize distally. While she said she “does not know the answer”, Ladich stressed the importance of asking whether or not we should be concerned with “the potential shower of drugs into the end organ”. In her experience, “rare case reports have described aneurysms, localised

hypersensitivity, downstream vasculitis and panniculitis following drug-coated balloon treatment”. However, she also noted that “to date, there are no published reports of autopsy findings or specific organ toxicity in humans treated with drug-coated balloons”. Additionally, to her knowledge there are “no causal links or mechanisms to explain the reported association of paclitaxel in the lower limbs and patient mortality”. Ladich clarified that despite this lack of evidence in both the literature and her experience, “this does not mean a potential damaging effect to organs does not exist”. The Highlight Session began with a

summary of the key messages from last month’s Vascular Leaders Forum (VLF; 1–2 March, Washington, DC, USA) by Gary Ansel (Columbus, USA). He told CX delegates that a central discussion point was whether a “protective benefit” with plain percutaneous transluminal angioplasty (PTA) could explain the higher mortality seen with paclitaxel devices in the meta-analysis. Ansel commented there was “no mechanistic signal to date” for such a benefit but, potentially, risk factors may be more frequently identified—and thus modified—in PTA patients because they are seen more often and undergo more interventions than those who receive

[There are] no causal links or mechanisms to explain the reported association of paxlitaxel in the lower limbs and patient mortality.”

Issue

paclitaxel devices. “This [peripheral arterial disease] population dies at a very high rate during the five years after a procedure. We should be focused on how we stop these patients from dying. From my standpoint, these patients should be followed much more closely for their general medical condition. We have to make sure these patients are not having infections or different oncology problems. We need to change this mortality rate with much more aggressive risk factor modification,” Ansel noted. The lack of mechanistic signal was one main criticism levelled at the Katsanos et al meta-analysis findings. Defending his methodology and conclusions, Konstantinos Katsanos (Patras, Greece) told CX delegates that the increased risk of death reported in the meta-analysis following the application of paclitaxel-eluting devices in the femoropopliteal artery was consistent and significant across multiple statistical analyses. “We are mathematically 99% certain of this significance”, Katsanos stated emphatically, pointing to results of a trial sequential meta-analysis. He added: “Every trial is only as good as its methodology. […] The key message here is not a smoking gun—it is the consistency of the findings. You see here the consistency of the mortality signal, and this I would say is the main takehome message.” Mårten Falkenberg (Gothenburg, Sweden), investigator of the SWEDEPAD registry-based randomised controlled trial, reported on the status of the trial which ceased enrolment in the wake of the JAHA metaanalysis. He told the CX audience that despite keeping up with the ongoing international conversation, the investigators were still trying to determine the best course of action, but no obvious consensus has emerged. Answering the question, “Do you agree with BASIL-3 and SWEDEPAD to recommend stop using paclitaxel products at this moment?”, a slight majority of 52% agreed. Furthermore, a similar split was seen as 53% voted for the motion “Do you suspect that the finding of Dr Katsanos is correct?”. Jonathan Michaels (Sheffield, UK), chair of the steering committee for the BASIL-2 and BASIL-3 trials, spoke about the halting of enrolment into the latter trial, which was set to expand on BASIL-2’s investigation of paclitaxel treatments for claudicants by examining the therapy in patients with critical limb ischaemia (CLI). However, BASIL-3 enrolment ceased following the Katsanos et al metaanalysis in order to review the ethics of continuing to treat patients with this drug. Michaels queried if there was an “innocent explanation” for the mortality signal. Like Ansel, he suggested a “plausible” reason for the observed increased mortality may be related to a greater follow-up frequency in patients treated with PTA, for whom potential comorbidities may be more likely to be

June

Issue

Paclitaxel believing the authorities were “reacting appropriately”. This result was quite decisive in comparison to the less unifying answers of previous polling.

Lessons from the paclitaxel pioneers and other disciplines

Marten Falkenberg and CX panellists

On the one hand, paclitaxel contributes to greater patency in the lower limbs, but on the other hand, there is an alleged increase in death.” diagnosed. Meanwhile, both Michaels and principal investigator Andrew Bradbury (Birmingham, UK) expressed their hopes to restart recruitment, although the unanswered questions surrounding paclitaxel present “serious challenges” for the triallists. Speaking from the floor, Bradbury further argued that a distinction “must be made” between claudicants and CLI patients as the risk profile varies drastically between the two. “For claudicants, treatment is about enabling the patient to walk further.” With CLI, Bradbury added, “the risk weigh-up” instead hinges on improving quality of life in end-stage peripheral arterial disease (PAD), for which effective treatment may be worth a potential increased late mortality risk. Responding directly to Bradbury’s comments concerning CLI, Zeller noted that teasing out an association of increased mortality would be more difficult in a CLI patient cohort, due to the “higher background noise” caused from greater overall mortality rate in this patient population compared to less ill patients. Bradbury further said: “We cannot assume that Katsanos’ findings apply to CLI patients.” Expressing his personal view, he told attendees that the BASIL and SWEDEPAD trials “represent a unique opportunity to settle the question with regard to CLI”. Indeed, speaking to this point, US FDA representative Misti Malone (Silverspring, USA) suggested that regulatory bodies may be able to make such a distinction between claudication and CLI, and pointed out that the FDA has currently not recommended the halting of paclitaxel trials. The methodology and statistical

validity of the meta-analysis outcomes were comprehensively described by statisticians and regulatory authorities. Overview of the meta-analysis’ statistical analysis was provided by Jon Deeks (Birmingham, UK), statistician of the BASIL-3 trial, and Sue Duval (Minneapolis, USA), one of the two independent, academic statistical advisors to the VIVA independent patient data (IPD) review. Deeks suggested that many of the studies used in the meta-analysis by Katsanos et al were “inadequate” in terms of the raw data, and that the reporting of the trials was “suboptimal”. However, Deeks acknowledged that “statisticians are never satisfied with the data”. Polling following this statistical discussion showed a slight shifting in favour of believing that there is statistical evidence currently indicating a real increased mortality from the use of paclitaxel on a balance of probabilities: 57% to 43%. Malone gave the FDA position, and announced the IPD review panel to take place on 19–20 June this year. This will be a meeting of the FDA’s Circulatory System Devices Panel of the Medical Devices Advisory Committee, and will take place from 8am to 5pm on the 19 June and 8am to 3pm 20 June in Gaithersburg, USA. Hazel Randall (London, UK) of the UK Medicines and Healthcare Products Regulatory Agency (MHRA) relayed the working process of the expert advisory group created last month, which is due to release its final recommendations for paclitaxel use “in the next few weeks”. Both regulatory bodies received considerable support from audience polling, with 68%

CX delegates heard from Ulrich Speck (Berlin, Germany), who spoke of his early work to enable the drug to coat the balloon, resulting in the plethora of devices available today. It was evident from Speck’s account that from the outset, the cell-killing effects of paclitaxel were known. “Of all the drugs tested in the swine model, none were as effective as paclitaxel”, Speck stated. Speaking on the pharmacokinetics of paclitaxel, Lindsay Machan (Vancouver, Canada) gave a description of the early application to stents, which was incorporated to address the issue of instent restenosis. The choice of paclitaxel was reliant upon its observed “powerful” ability to inhibit cytokineinduced migration of cartilaginous cells, which Machan explained cannot grow when more than 2mm away from a capillary. Providing an oncological perspective, Erica Mayer (Boston, USA) detailed the use of paclitaxel as a primary therapy in cancer care. Notably, Mayer referred to paclitaxel as “one of our most commonly used treatments” in breast cancer patients, and even reported its safe, effective use in the second and third trimester of pregnancy. “We think it is safe enough to give to our pregnant patients”, Mayer told the CX audience. Furthermore, she pointed to the significant difference in dosing: a higher-dose drug-coated balloon reportedly providing 0.55% of an average dose given in a weekly breast cancer regimen over 12 weeks. Finally, Bruno Scheller (Homburg/ Saar, Germany) outlined the lessons learned from paclitaxel use in coronary arteries, comparing the drug to its alternatives, sirolimus and everolimus.

Roger Greenhalgh and Gunnar Tepe

Referring to a similar controversy over a decade ago, in which a potential association with increased mortality was discussed for paclitaxel in the coronary arteries, Scheller said this 2006 “firestorm” is the “perfect blueprint” for the current paclitaxel debate. Ultimately, however, Scheller reported the coronary community concluded that the stent design and coating technology is “more important” than drug selection in these arteries, and drug-eluting devices are in continued use. Commenting on these lessons, Greenhalgh summarised that the early users of paclitaxel were “fully aware that the drug was cytotoxic, is has been used in oncology since”, iterating that its use in vascular applications was “always known to damage the artery wall in some way, which discouraged the restenosis process”. At this stage, 85% of the audience agreed with this sentiment, answering the poll: “Do you think that those who used paclitaxel in the early days were quite aware that paclitaxel kills cells?”. A follow-up question elaborated: “If you accept that the pioneers knew that paclitaxel would kill cells, do you think that they always aimed to have a balance between achieving less restenosis in the patients’ interest without increasing mortality?”. The result of this query was 72% in favour, capturing the audience support for the idea that there may exist a trade-off in the use of paclitaxel. “On the one hand,” Greenhalgh summarised, “paclitaxel contributes to greater patency in the lower limbs, but on the other hand, there is an alleged increase in death.” Extensive discussion followed on whether there exists a causative action as the drug circulates within the body, or whether this is “merely an association”. Overall, there was near unanimous support from speakers, the audience and the regulatory bodies on the position that while an association may exist, further investigation is required.

June

Endovascular options

Endovascular options gain ground in creation of haemodialysis lifelines Dimitrios Karnabatidis Konstantinos Katsanos Panagiotis M Kitrou Comment & Analysis Until recently, creation, maintenance and restoration of vascular access function was entirely performed by open surgical methods. However, it is becoming apparent that endovascular management is a valid treatment option and a comparable alternative to the open surgical one, write Dimitrios Karnabatidis, Konstantinos Katsanos and Panagiotis M Kitrou from Patras, Greece, who are organising the first EVA meeting on the topic from 21–22 June 2019, in Patras, Greece.

ascular access constitutes the “lifeline” for haemodialysis patients. Until recently, creation, maintenance and restoration of function (when thrombosis occurred) was performed by open surgical methods. However, it is becoming apparent, verified even in the most recent surgical and interventional guidelines for vascular access, that endovascular management is a valid treatment option and a comparable alternative to the open surgical one.1–3 In the last decade, there has been a continuous development of novel endovascular tools and devices (some of which were initially tested in the arterial vascular bed) that have made the endovascular approach faster and more appealing. Different types of wires and catheters, low profile devices, highpressure balloons, drug-coated balloons, scoring balloons and covered stents have improved patency rates, and in many cases circuit survival.4 Each of these devices offers an additional option to the operator. High-pressure balloons have revolutionised vascular access treatment, mainly because stenosis in this specific vascular field is characterised by an aggressive fibromuscular thickening that needs high pressures of up to 40atm, in many cases, to enable treatment. Drugcoated balloons have allowed for more extensive use of high-pressure balloons by decelerating the effect of restenosis.5,6 Covered stents offer a valid bail-out option in cases of persistent stenosis or elastic recoil; pseudoaneurysms; and ruptures—and there is Level 1 evidence supporting their use as a primary option for the treatment of venous graft anastomotic stenosis.7 When thrombosis occurs, endovascular

treatment with thrombolysis, thrombectomy or, in many cases, a mix and match of these procedures offers quick, safe and efficient ways of blood flow restoration. It also allows the patient to return immediately to

haemodialysis without the need for central venous catheter placement.8 Several thrombectomy devices are available on the market and there is already extensive clinical experience with these devices. An important benefit of endovascular treatment is that it offers the ability to perform, in the same setting, both declotting and treatment of the underlying stenosis, which in the majority of cases is the reason for thrombosis.

“EndoAVF” a major advancement

Lately, there has also been a major advancement in the vascular access field with the endovascular creation of arteriovenous fistulaes (AVF). This innovation occurs in a scenario where the gold standard (open surgery) has a failure rate of more than 50%. With two systems already available on the market (WavelinQ [BD] and Ellipsys [Avenu]) and with evidence detailing their benefits beginning to mount, patients will have the opportunity to have their fistula created without the need for surgical cut-downs, incisions and sutures, which are largely responsible for failure of maturation and future stenosis. Being available via a 4F radial or “wrist” access or under ultrasound guidance, these fistulas are created in the deep venous system. “EndoAVF” provides additional vascular access creation sites (two when WavelinQ is used and one when Ellipsys is employed) and could conceivably become the primary option for fistula creation. The reason for this is that “endoAVF” does not implicate the

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superficial venous system, which is the system used in the open surgical fistula creation. Additionally, in case of failure, conditioning of the superficial outflow veins of the arm may occur, facilitating faster surgical fistula maturation. Even though there is a growing role for endovascular vascular access management, centres performing these procedures remain low. We believe it is important for all specialties involved to understand the benefits that endovascular approaches provide to haemodialysis patients. Meetings on the specific subject remain highly “open surgery oriented and those with broader audiences sometimes combine vascular access treatment with venous disease. We feel that there is a need to help disseminate education and awareness in this area, particularly among nephrologists on the endovascular pathway/service they can provide to their patients. Endovascular therapists, either interventional radiologists, vascular surgeons or interventional nephrologists, would also gain from staying current with developments in the field, with a view to improving the care available to haemodialysis patients. In light of the current developments in this field, hospital multidisciplinary team meetings should involve endovascular specialists and congresses on the specific subject should be geared towards a multidisciplinary approach. It is in this context that the EVA (Endo Vascular Access) Meeting was created—its content is specifically designed to focus on the treatment options that the endovascular approach offers to haemodialysis patients. From EndoAVF, trial updates and treatment of symptomatic central venous stenosis to central venous catheters and background development, the EVA Meeting presents a multidisciplinary faculty of physicians from around the globe. The first EVA Meeting will be held in Patras, Greece on 21–22 June 2019. Dimitrios Karnabatidis is a professor of interventional radiology, Patras University Hospital, Patras, Greece. Konstantinos Katsanos and Panagiotis M Kitrou are assistant professors of interventional radiology. They are also directors of the EVA Meeting.

It is becoming apparent, verified even in the most recent surgical and interventional guidelines, that endovascular management is a valid treatment option and a comparable alternative to the open, surgical one.”

References 1. Dariushnia SR, Walker TG, Silberzweig JE, et al. Quality improvement guidelines for percutaneous image-guided management of the thrombosed or dysfunctional dialysis circuit. J Vasc Interv Radiol. 2016;27(10):1518–30. 2. Ibeas J, Roca-Tey R, Vallespin J, et al. Spanish clinical guidelines on vascular access for haemodialysis. Nefrologia. 2017;37 Suppl 1:1–191. 3. Schmidli J, Widmer MK, Basile C, et al. Editor’s Choice – Vascular Access: 2018 Clinical practice guidelines of the European Society for Vascular Surgery (ESVS). Eur J Vasc Endovasc Surg. 2018;55(6):757–818. 4. Kitrou P, Papasotiriou M, Katsanos K, et al. Recent developments in endovascular interventions to sustain vascular access patency in haemodialysis patients. Nephrol Dial Transplant. 2018. 5. Trerotola SO, Lawson J, Roy-Chaudhury P, Saad TF, Lutonix AVCTI. Drug coated balloon angioplasty in failing AV fistulas: A randomized controlled trial. Clin J Am Soc Nephrol. 2018;13(8):1215–24. 6. Kitrou PM, Papadimatos P, Spiliopoulos S, et al. Paclitaxel-coated balloons for the treatment of symptomatic central venous stenosis in dialysis access: Results from a randomized controlled trial. J Vasc Interv Radiol. 2017;28(6):811–7. 7. Haskal ZJ, Trerotola S, Dolmatch B, et al. Stent graft vs. balloon angioplasty for failing dialysis-access grafts. N Engl J Med. 2010;362(6):494–503. 8. Kitrou PM, Katsanos K, Papadimatos P, et al. A survival guide for endovascular declotting in dialysis access: Procedures, devices, and a statistical analysis of 3,000 cases. Expert Rev Med Devices. 2018;15(4):283–91.

June

Issue

0.018-inch drug delivery platforms are as effective as 0.035-inch devices

Interventionists can confidently use lower profile drug delivery platforms, based on data that show 0.018-inch guidewire devices are noninferior to 0.035-inch guidewires. In a Podium 1st presentation at the Charing Cross Symposium (CX; 15–18 April, London, UK), Andrew Holden (Auckland, New Zealand) said: “At 90 days, we can see that the 0.018inch IN.PACT Pacific device is certainly noninferior to the [0.035-inch] IN.PACT Admiral device—the device with so much five-year follow-up data. What this means is we can have confidence transposing all the published data from 0.035-inch technologies to these newer low-profile 0.018-inch devices.” RANDOMISED CONTROLLED trials and real-world registries have established a patency advantage in the femoropopliteal segment for drug coated balloons (DCBs) with an 0.035-inch guidewire compatible platform. But Holden pointed out: “There are a lot of clinicians who would like to use lower profile, 0.018-inch guidewirecompatible devices,” and he listed the clinical advantages. “The profile is smaller and that reduces access sheath size and bleeding risk,” he said. “And that is often very relevant, particularly in elderly female patients with small calibre vessels. Lower profile means we have better deliverability and crossing ability, and we can just use one guidewire to cross lesions above and below the knee.” Researchers created arterial injuries in swine models using angioplasty and stenting, and treated 30 days later with a DCB or drug-eluting stent. They then

Andrew Holden

Drug delivery platforms assessed restenosis rates using quantitative vessel analysis (QVA) and optical coherence tomography (OCT) imaging at 60, 90 or 120 days post-treatment, and also measured tissue levels of drug at the terminal timepoint. Firstly, the performance of two 0.035inch compatible guidewire devices, the IN.PACT Admiral (Medtronic) and the Stellarex (Phillips), were compared: “At various timepoints, both 60 and 90 days, there is a significant reduction in restenosis with the IN.PACT Admiral compared to the Stellarex, and this is not surprising given the higher input dose with the IN.PACT Admiral. The tissue concentrations that were obtained at the terminal timepoint also showed that there was higher tissue dose of paclitaxel with the IN.PACT Admiral.” The investigators also looked at two 0.018-inch guidewire compatible devices—the Pacific (Medtronic) and the Ranger (Boston Scientific); this comparison extended the timepoint to 120 days. “The Pacific was trending towards a lower restenosis rate with QVA and OCT compared to the Ranger at 60 and 120 days. It did not reach statistical significance, but there was a positive trend.” Holden told Interventional News that the lower stenosis rates found with Pacific compared to Ranger could also be explained by the higher input dose for the Pacific balloon. The dissolution rates with paclitaxel for all the devices are pretty much the same so if you have a higher input dose at the start you are likely to see a pronounced, more prolonged restenosis effect. However, “both platforms performed extremely well in terms of preventing restenosis,” Holden said. A comparison between the IN.PACT Pacific and the IN.PACT Admiral—the 0.018-inch and the 0.035-inch devices from the same company—by QVA and OCT found comparable performance in terms of restenosis. Holden said: “This implies that the data we have from the 0.035-inch database can be translated to the 0.018-inch platform.” He concluded: “We certainly could show that the 0.018” guidewire devices were noninferior to the 0.035” devices. Although this is a preclinical study, it is one that really does have clinical relevance.”

June

Peripheral interventions

Ambulatory treatment can be offered to high-risk patients too Office-based lower extremity arterial interventions are feasible, safe, and costeffective, and provide high levels of patient satisfaction. Enrico Ascher (Brooklyn, USA) presented data that “challenge the dogma that high-risk patients should not be offered office-based endovascular infrainguinal arterial procedures”. He was providing a US perspective on ambulatory interventions at the 2019 Charing Cross Symposium (15–18 April, London, UK). ASCHER CITED STUDIES that show patient satisfaction levels with outpatient care of 99%, and listed its other advantages as improved physician efficiency, due to multitasking, better reimbursement levels, and increased independence for practitioners because hospital administrators are “cut out of the equation”. He also highlighted his own data series, collected from 2014–2018 and based on 8,336 cases. There were no procedure-related deaths, and only one case required

an emergency transfer. The complication rate was 1.3%, and death rate at one month was 0.15%. Among the patients excluded were those who weighed >180kg, had advanced chronic obstructive pulmonary disease (COPD), disabling spine stenosis (and therefore could not remain supine), and unstable psychiatric patients. From 2014–2018, there were 576 arterial interventions, with zero cases of embolization, retroperitoneal bleed, and acute stenosis, and six cases of puncture site stenosis. A review of the arterial patient selection criteria revealed that lesion type or location did not play a factor in patient selection, and that eligible patients were given a choice to have their procedure done in the office or in the hospital. Ascher pointed out: “You would think that we would select patients with easy lesions, but that was not true.” The data were then further evaluated by comparing findings in high-risk patients with those of more average risk. The risk factors analysed were age ≥80

[These] procedures in high-risk patients should be further validated by a large multicentre prospective randomised study.” years old, serum creatinine ≥2mg/dL or end-stage renal disease, ejection fraction (EF) ≤39%, and American Society of Anaesthesiologists (ASA) classification of 3 and 4. For patients who were ≥80 years old, the reintervention rate at one year was 21% vs. 38% in the younger group (p=0.04). Of these, 18% were office-

Europe needs guidelines for outpatient endovascular repair European guidelines should do more to promote the use of ambulatory endovascular peripheral interventions and to support physicians wishing to set up an outpatient centre, Yann Gouëffic (Nantes, France) told the Charing Cross Symposium (15–18 April, London, UK).

“D

RGs [device-related guidelines] should be revised to promote outpatient [care], and guidelines should be released to help vascular interventionists to organise their practice in the most appropriate and safe conditions,” he said. And he echoed Enrico Ascher’s conclusions, pointing out: “Outpatient management is safe and efficient. We know that it works.” Gouëffic presented the European perspective on how ambulatory treatments are moving on in the field of arterial disease, outlining how practice differs across different European nations,

Yann Gouëffic

“according to the type of DRG [device related guideline] in each country, and according to type of vascular interventionist”. He described the growth of office-led intervention in the USA as “amazing”. In France, the rate of ambulatory treatment for peripheral arterial disease (PAD) using endovascular repair was about 11% in 2018. In the UK, almost 30% of procedures for the same indications are performed in an outpatient setting. European guidelines, in place since 2003, recommend overnight observation after a percutaneous transluminal angioplasty (PTA) procedure. The French Society of Vascular and Endovascular Surgery (SCVE) in 2019 released the first guidelines for outpatient management in France, providing help to physicians on

Issue

based and 1.4% were hospital-based for older patients, compared to 29% office-based (p=0.03) and 4% hospital-based reinterventions (p=0.18) among those of a younger age. No patients required a bypass. A comparison between those with renal impairment and those with adequate renal function found a reintervention rate of 12% among high-risk patients, and 36% in the lower-risk group (p=0.01). All patients at higher risk had the repeat procedure performed in hospital, while only 4% of patients with adequate renal function were hospital-based (p=0.21); 14 of the 297 reinterventions in the low-risk group required bypass. Reintervention rates for patients with impaired cardiac function—defined as an EF ≤39%—was 31% compared to those with adequate function at 34% (p=0.44). Only one of five reinterventions was officebased for those with impaired cardiac function, versus 84 of 105 cases among lower-risk patients (p=0.22). Two patients with EF ≤39% had a bypass vs. 12 of those with EF function ≥39%. Outcomes for patients with an ASA classification of 3 and 4 were compared to those with a classification of 2, and found a reintervention rate of 12% among those at higher risk vs. 34% among the lower-risk group (p=0.44). Numbers of bypasses were the same in each group as for those among the high and low-risk cardiac function patients. The mortality rate was zero and there were no major amputations among any of the groups selected for comparison. Limitations of the data analysis were that it was retrospective and single-centre, and based on a single surgeon performing >15,000 endovascular arterial procedures. However, Ascher concluded: “Appropriately selected high-risk patients can benefit from office-based endovascular arterial procedures,” adding, “ideally, office-based arterial endovascular procedures in high-risk patients should be further validated by a large multicentre prospective randomised study.”

how to deal with legal issues. Concerns about how to deal with complications is one of the issues that may be affecting the development of outpatient endovascular intervention, he suggested. Other factors are economic and clinical. Economic factors, he said, may be related to regulatory issues, but also to the need to demonstrate societal costeffectiveness. Clinical issues relate to the need to demonstrate the safety and efficiency of ambulatory management, the benefits of different devices, and whether it is possible to perform manual compression. Gouëffic said: “Further evidence is required to ensure the clinical, legal, and medical economic value of outpatient management.” He described three trials that are aiming to do so. One, the Freedom registry, has been set up to demonstrate the feasibility of same-day discharge after manual puncture point compression in patients treated for PAD by endovascular technique with a 5Fr sheath femoral approach. So far, 111 of the 150 patients to be included in the trial have been recruited. A second, the STEP study, is a randomised trial comparing two arterial devices to assess their value in outpatient management. At the time of the presentation, only one patient remained to be enrolled, with 229 of the required 230 patients already recruited. Gouëffic also outlined details of a medical economics study, the AMBUVASC trial, which has finished recruiting patients. This is a French

We have no medical economic study available to assess the cost-efficiency of outpatient [treatment].” multicentre randomised controlled trial to evaluate the efficiency of outpatient versus hospital PAD intervention. “We have no medical economic study available to assess the cost-efficiency of outpatient [treatment]. The objective of AMBUVASC is to compare the utility cost of conventional hospitalisation versus ambulatory hospitalisation using an arterial closure device.” The primary endpoint of the study is the incremental cost-effective ratio (ICER). This describes the extra cost per one additional unit of patient outcome, and consists of a cost utility and a costeffectiveness analysis. Quality adjusted life years (QALYs) are also used to measure ICER. Secondary endpoints include safety, complication rates, functional improvements, and time taken to return to employment. A vote at the end of the audience discussion that followed indicated that 63% among the audience would recommend ambulatory treatment for their own patients with PAD.

June

Issue

Peripheral interventions

New MIMICS-2 trial data show helical stents provide durable treatment of diseased femoropopliteal arteries New data from the MIMICS-2 trial show the BioMimics 3D stent, which mimics natural vascular curvature, remains safe and effective for patients with symptomatic atherosclerotic disease of the femoropopliteal arteries two years after implantation. PRINCIPAL INVESTIGATOR Timothy Sullivan (Abbott Northwestern Hospital, Minnesota, USA) presented the two-year findings at this year’s Charing Cross Symposium (CX; 15–18 April, London, UK) in a Podium 1st session. He explained: “We know that swirling flow creates increased wall stress in the arterial wall, which is atheroprotective, and this is especially important in the superficial femoral artery where, under normal circumstances, shear stress is quite low. The use of a helical stent produces swirling flow and increased wall shear stress.” MIMICS-2 is an international investigational device exemption (IDE) study to evaluate the safety and efficacy of the BioMimics 3D stent system (Veryan Medical) in patients undergoing endovascular intervention to relieve obstructive or occlusive disease in the femoropopliteal artery. The three-year, prospective, single-arm trial is tracking outcomes in 271 subjects with a mean age at baseline of 68.4 years, across 43 sites in the USA, Germany and Japan. About 50% of patients had diabetes mellitus, and the majority were in Rutherford categories 3 and 4: “These were patients with significant clinical symptoms related to lower extremity arterial claudication and a baseline ankle-brachial index of 0.7, representing patients that we all would treat in our clinical practice, typically with lower extremity intervention following a trial of exercise therapy.” Device and technical success was 100%. The primary safety endpoint of freedom from major adverse events (death, major amputation, or clinicallydriven target lesion revascularisation [CD-TLR]) at 12 months was achieved for 99.6% of subjects. At 24 months, freedom from CD-

Timothy Sullivan

TLR was 84.2% and “compares quite favourably to that at 12 months, which was 89%,” said Sullivan. “The [KaplanMeier] curve really starts to flatten out at about 360 days, without much loss in clinically driven-TLR.” This performance at two years is similar to that of drug-eluting stents (DESs) and drug-coated balloons (DCBs), despite the MIMICS-2 subject cohort including a greater proportion of challenging cases than those in pivotal DES/DCB trials. Imaging confirmed there were no cases of stent fracture in any of the MIMCS-2 subjects, including those who have reached three-year follow-up. Sullivan concluded: “Swirling flow with this BioMimic stent creates increased shear stress at the vessel wall, which is atheroprotective without the use of an antiproliferative drug.” The positive outcomes were achieved independent of lesion complexity—at the start of MIMICS-2, 45.9% of subjects had moderate to severe legion calcification. The Kaplan-Meier estimate of survival from CD-TLR at 24 months for those in this group was 85.5%. Sullivan told Interventional News: “What these data tell me is that, in complicated patients with very calcified lesions […] when a device becomes available for general clinical use in the USA, I will be using it for long or calcified lesions, […] in which I might otherwise have used one of the other treatment algorithms, with the confidence that restenosis is going to be minimal. The results shown are pretty amazing after two years.” The other MIMICS-2 principal investigators are Thomas Zeller (Bad Krozingen, Germany) and Masato Nakamura (Tokyo, Japan).

June

Endovascular interventions

Appropriate follow-up of patients after endovascular procedures Marianne Brodmann Comment & Analysis Marianne Brodmann outlines follow-up and surveillance protocols after endovascular treatments for peripheral arterial disease (PAD), arguing for a standardised approach to ensure best practice for patients who have gone through peripheral endovascular procedures.

ndovascular procedures have become a key element of treating patients with PAD, either with intermittent claudication or critical limb ischaemia. Nevertheless, there is currently no standardised approach and no general- or guidelines-derived recommendation for how to do this. The follow-up after these procedures is often dependent on facility resources, such as available manpower and equipment, or geography (urban versus rural).

What is the rationale of surveillance after endovascular procedures?

It is important to accurately implement preventative strategies to avoid other

cardiovascular events and disease progression in a patient cohort with a high risk of morbidity and mortality, while also avoiding recurrence of symptoms and the need for repeat revascularisation. The importance of this is amplified by the fact that we are facing an increasing disease burden of PAD patients needing treatment. In 2008, >98,000 endovascular procedures and >86,000 surgical revascularisations were performed for lower limb arterial disease in Germany alone, illustrating the burden of peripheral revascularisation interventions in Europe. For a standardised approach to surveillance, we need to discuss several questions. What should we offer and how

should we do it? Is follow-up with anklebrachial index (ABI) alone enough, or should we also perform duplex ultrasound? What are the timeframes to do this? Another important question is, who should perform the follow-up? One simple key element is the clinical follow-up. This also means that we should create awareness among patients about the symptoms that occur in revascularisation failure, and when immediate contact to vascular specialists is indicated. With regards to imaging techniques, which help us to detect restenosis either in the immediate or long-term follow-up, duplex ultrasound is the most applicable. It is non-invasive and widely available, and can be repeated over time to detect subclinical abnormalities. It has therefore become the first-line technique for follow-up. Duplex ultrasound surveillance has been reported to predict severe in-stent restenosis with a specificity of >90%. Functional tests such as ABI or toebrachial index (TBI) can further help to optimise surveillance of the lower limbs. Computed tomography angiography (CTA) and magnetic resonance angiography are mostly limited to the confirmation and investigation of duplex ultrasound findings, but can be performed straight away in urgent cases. In cases of recurrent claudication, the treadmill test with post-exercise ABI can assess the functional severity. However, ensuring follow-up after endovascular procedures will also serve

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to prevent disease progression. Regular monitoring for risk factor modification, exercise training and medical therapy is a must. Even in patients with intermittent claudication, disease progression to chronic limb threatening ischaemia may be underestimated. In a meta-analysis of studies conducted between 1990 and 2015, 21% of patients with intermittent claudication were diagnosed with chronic limb-threatening ischaemia during a five-year follow-up period, and 4–27% of them suffered amputations.

How often should we do it?

There should be an immediate postprocedural follow-up the day after the procedure, to gain insight into the procedural success achieved. To detect early restenosis, the next follow-up should be performed one month later, and thereafter in a six month period up to one year. Long-term follow-up should be performed annually. As for who should carry out the followup, this should be performed by the people taking care of patients with vascular disease, whether they are general practitioners or cardiovascular specialists, such as cardiologists, vascular physicians or vascular surgeons. The appropriateness of who carries this responsibility will vary according to the management of patients in different countries. Marianne Brodmann is a vascular specialist at the Medical University of Graz, Austria.

ACTION trial finds ACT-guided heparinisation increases patient safety Implementing a method of heparinisation guided by activated clotting time (ACT), with a goal of 200–220 seconds, provides a “promising” increase in safety and may decrease risk of thromboembolic events, while not increasing bleeding complications. Presenting the findings of the pilot ACTION trial, Arno Wiersema (Amsterdam, The Netherlands) stated he and his colleagues “believe it is time to upgrade one of the foundations of vascular surgery to optimise patient care and to prove that ACTguided heparinisation results in far fewer thromboembolic complications.”

“T

he success of open and endovascular arterial interventions depends on a delicate balance between coagulation and anticoagulation”, said Wiersema in the first Aortic Podium 1st session at the Charing Cross Symposium (CX; 15–18 April, London, UK). “Ever since its introduction in clinical practice 70 years ago, unfractionated heparin has been administered during these non-cardiac arterial procedures to prevent thromboembolic complications. A major disadvantage of this use of heparin is that it could increase bleeding complications, as extensive surveys have shown that almost all vascular surgeons and interventional radiologists use a standardised bolus of 5,000IU of heparin during non-cardiac arterial procedures.” This is in sharp contrast to cardiac interventions, noted Wiersema, where heparin is used in higher dosages. “As surprising as it may seem, only one randomised controlled trial (in 1996) has been performed on the benefit of heparin,

comparing a group with heparin to a group without heparin as prophylactic antithrombotic.” The fact that no other study has since been performed on this subject despite the wide uptake of heparinisation is, to Wiersema and his colleagues, reportedly “astonishing”. For this reason, the ACTION trial was designed to examine the benefits of heparinisation guided by ACT, with the

the actual ACT.” He added that a protocol was instituted for the use of protamine at the end of the procedure, to decrease the incidence of bleeding complications. In terms of the results, “ACT-guided heparinisation ensured the vast majority of the patients of adequate and safe anticoagulation. Almost all patients reached an ACT of more than 200 seconds after the first bolus.” The mean dose of

It is time to upgrade one of the foundations of vascular surgery to optimise patient care.” hypothesis that less thromboembolic complications and no increase in bleeding complications would be observed. “The final goal of ACT to strive for”, commented Wiersema, “was set at 200 to 220 seconds. To reach those ACT values, a starting bolus of 100 units per kilogram was used and additional doses were set at 60 or 30 units, depending on

heparin needed to maintain this optimal anticoagulation was roughly twice the bolus of 5,000 units. While the incidence of bleeding complications was not increased, a “promising trend” of decrease in thromboembolic complications was observed, falling from 11% to 6%. Wiersema emphasised the importance of establishing the added value of ACT-

Arno Wiersema

guided heparinisation “once and for all”, stating: “We are on the verge of receiving a large grant to perform an international randomised controlled trial. This trial is starting in The Netherlands, Hamburg (Germany) and Copenhagen (Denmark), and we are more than happy to include other major vascular centres around the world. We need only 748 patients in five years to prove a reduction for the combined incidence of thromboembolic complications and mortality from 19% to 11%. If this method is proven to be better during open aortic aneurysm repair, it can be directly incorporated for all our other procedures.” Concluding, Wiersema said “the ACTION pilot showed that ACT-guided heparinisation increases patient safety and looks very promising as a method to decrease thromboembolic complications, without a relevant rise in bleeding complications.”

June

Interview

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Profile

Alex Tang

“Deep in my heart, I knew interventional radiology (IR) had a tremendous future,” Alex Tang tells Interventional News. Looking back at his career, Tang talks of setting up IR services in his native Malaysia, and, as the convenor of the Asia-Pacific Congress of Interventional Oncology (APCIO), details the myriad opportunities and challenges interventional radiologists in the Asia-Pacific region face.

What first drew you to interventional radiology?

I joined as a radiology trainee at the National University of Malaysia in 1991. This was an unexpected opportunity: a nurse happened to drop the application for radiology training on to my desk during the peak of the outpatient rush. The chances of enrolling into radiology training 29 years ago were as slim as winning the lottery. I was mesmerised by my radiology counterparts, who were able to biopsy the liver percutaneously in a trauma case, in one instance saving a patient with a massive post-biopsy bleed—this was done by my senior using the frightening Vim-Silverman needle. I then obtained a place on a postgraduate training course to eventually become a specialist; the places were full, but the phrase “I want to do interventional radiology” during my interview secured me the training post. Back then, I was not yet aware of how wide-reaching and interesting the field of IR was.

Have you had important mentors throughout your career? What have they taught you?

My training in IR started in the Hammersmith Hospital, The Royal Postgraduate School University of London, UK, under the guidance of Ann Hemingway and James Jackson, from 1997 to 1998. During my fellowship training, I was also seconded to the Guy’s Hospital, London, UK, where I worked under Andreas Adam. Ann Hemingway created the fellowship opportunity for me despite working around a very busy schedule. James Jackson taught me complex, state-of-art techniques in embolization. Andreas Adam completed my training in the various non-vascular interventions. In addition, Richard Edwards and John Moss were very important mentors to me, because they exposed me so much to various endovascular revascularisation techniques in the Gartnavel General Hospital, Glasgow, Scotland. I have obtained strong technical skills from all of these mentors. These hands-on training opportunities shaped me to become an all-rounder within IR by the time I returned to Malaysia to start the IR services in my home country. To those who have shaped me to be who I am today, I sincerely thank and appreciate you from the bottom of my heart.

As the convener of APCIO, why did you feel the need for a meeting in the AsiaPacific region?

Modern oncology is among the fastest growing fields in medicine. Interventional Oncology (IO) being the fourth pillar of cancer care, it is one of the most rapidly evolving sub-specialties. The practice of IO in the Asia Pacific region is extremely variable; we have to take into consideration the varying standards of care, technologies and availability of services, as well as the diverse geographies, ethnicities, socio-economic backgrounds and skills in each and every country. With the theme “Interventional Therapy in Modern Oncology: Technological Integration Beyond Boundaries”, APCIO 2019 is multidisciplinary and multinational. The meeting aims to establish a regular platform from which to discuss ways of continually improving medical expertise, while also ensuring

the delivery of best ethical practices in oncological patient care. APCIO 2019 enrols almost every country in the Asia-Pacific region, with the primary aim of developing even greater interest in the next generation of interventional radiologists. APCIO 2019 also wishes to strengthen intersocietal collaborations, with associations such as the Society of Interventional Radiology (SIR), the Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR), the Cardiovascular and Interventional Radiology Society of Europe (CIRSE), the Society of Interventional Oncology (SIO), the Asia Pacific Primary Liver Cancer Expert group (APPLE), the Asian Pacific Association for the Study of the Liver (APASL), the local oncology society and many more.

How has the APCIO changed over the last six meetings?

APCIO was first established in 2010 in Beijing, China, by the Asia Pacific Society of Interventional Oncology (APSIO). It is a biennial meeting of interventional radiologists from the Asia-Pacific countries. The last five meetings were held in Beijing, China, 2010; Hangzhou, China, 2011; Guangzhou, China, 2013; Miyayaki, Japan, 2015; and New Delhi, India, 2017. The sixth meeting will be held in Kuala Lumpur, Malaysia, 2–5 October 2019. With the premise of providing a multidisciplinary approach and fostering intersociety collaborations, APCIO 2019 is establishing a collaborative platform in interventional oncology in the region. We see positive steps in having non-interventional radiologists coming forward to collaborate with and to support the meeting. This is a very encouraging and favourable development. With IO being the fourth pillar of modern oncology, it is vital that we work with the other three pillars to offer more holistic and multidisciplinary care in the best interest of cancer patients. Moving forward, future APCIO meetings will see a greater symbiosis with our clinical counterparts in surgical oncology, medical oncology, radiation oncology, immunology, stem cell medicine, modern pathology, palliative care and various support groups in the modern oncology field.

What are the challenges and triumphs of interventional radiology specific to the Asia-Pacific region?

Asia Pacific countries are geographically, ethnically and financially diverse. The standard of care in medicine, especially in the field of interventional radiology, varies throughout the region. The disease spectra, presentations and incidences also vary regionally, and are different from in western countries. Whilst numerous procedures are performed to the best achievable local standards, they frequently have suboptimal outcomes, especially in the economically under-privileged countries. Procedures are also performed in diverse ways, and optimal endpoints for the best result may not have been reached. One example is conventional transarterial chemoembolization (cTACE) in hepatocellular carcinoma (HCC): the technical approach, patient selection and outcomes are extremely variable. Skill level, equipment availability, and financial constraints—notably a lack of national healthcare

High quality research and clinical evidence in IO and IR treatment techniques are still lacking, and are needed.” financing—present daily challenges. There is a huge need for streamlining the standard of care, procedural techniques and skills, regional availability of necessary equipment for procedures—from the very basic to the most advanced—and the training of young interventional radiologists across the region. This should be our priority. APCIO wishes to do this by gathering everyone under one roof on a regular basis, with the hope of strengthening the regional IO/IR fraternity. To this end, 80 young investigator awards are given out at the meeting. These are strongly supported by the industry, with the hope of bringing delegates from financially restricted countries, as well as providing individual benefit to the recipients. Two US$3,000 training scholarships are also provided.

June

Issue

Interview

Fact File in Radiology has proved the safety of this new and highly effective treatment. A 100% complete remission rate using the ablative chemoembolization protocol has been reported; a very encouraging development. In my personal experience, TEE/ACE offer numerous advantages and has fewer side effects. It is highly efficacious in controlling the tumour, especially if it is injected super selectively into the tumour. Ethanol has the property of instigating immediate cellular coagulation; hence, it achieves an immediate tumour necrosis, especially if a concentration of more than 66% is used during the procedure.

As president of the MYSIR, what are your goals for the society?

The Malaysian Society of Interventional Radiology (MYSIR) is a young society, established in 2013. Our main goals are: to establish a more streamlined standard of care in IR/IO, to train more young blood, to promote IR services locally, and to enhance our presence in the daily clinical workflow. MYSIR is working collaboratively with multiple disciplines to gain greater clinical acceptance of the newer IR technologies and treatment modalities. We are organising more multidisciplinary team meetings, among them the Multidisciplinary Oncology Symposium Malaysia (MOSM) and APCIO 2019. MYSIR is an organisational member of the Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR), and we are looking forward to having a greater presence both regionally and internationally, and to establishing a more cohesive collaboration with larger societies, such as SIR, CIRSE, Society of Interventional Oncology (SIO), ACTA, APPLE and APASL, to promote IR services and to conduct training workshops for local IRs and trainees.

What is the biggest challenge for IR at the moment?

What is the most exciting research coming from the Asia-Pacific region in interventional oncology, in your opinion?

The paper from the Chinese University of Hong Kong, on the “Ablative chemoembolization for hepatocellular carcinoma: a prospective phase I case-control comparison with conventional chemoembolization”, by Simon Yu et al. It was published in Radiology in April 2018. The management of giant HCC, an endemic disease in the Asia-Pacific region, has been a great challenge to all of us. Treating and completely controling a giant HCC in a non-resectable candidate with cTACE or DEB TACE is frequently futile. The use of transarterial ethanol injection (TEE) in the embolization of liver cancer was first attempted in the 1970s in Japan. This treatment technique was abandoned because of multiple technical failures. Technical improvisation and improvements in safety have optimised this procedure, and Yu et al published a paper in the Journal of Vascular and Interventional Radiology in March 2009 detailing their positive experience of TEE. Ever since, TEE has been gaining momentum, with more interventional radiologists using this new treatment modality in the management of intermediate stage HCC. Yu has attempted to further advance the treatment for HCC by adding an element of chemotherapy (cisplatin) into the formulation of TEE, to develop what he calls ablative chemoembolization (ACE). His study published

The public awareness of the availability of IR treatment techniques is still low, especially in some Asia-Pacific countries. Similarly, in the medical fraternity, many doctors are unaware of the availability of the state-ofthe-art options IR offers in the management of diseases. Clinical acceptance of the new IR techniques is also a big challenge for us, as many of the clinicians prefer to opt for more conventional means. Evidence-based medicine and clinical outcomes remain the most important determinants of our daily practice. High quality research and clinical evidence in IO and IR treatment techniques are still lacking, and they are needed to justify our clinical presence and in offering best medicine for the best interests of our patients.

What do you anticipate being the most practice-changing technology in IR over the next 10 years?

Artificial intelligence (AI), especially machine learning (ML), is expected to play a primary role in the future of IR. This is especially true for minimally invasive tumour therapies performed by interventional oncologists. The overwhelming amount of disparate clinical, laboratory, and imaging data derived from clinical research is beyond anyone’s ability to digest, and thus cannot be systematically applied in the everyday clinical setting. This results in institutional and individual variabilities in multidisciplinary decision-making involved in daily patient management. The growing need for more patientcentred and individualised care necessitates a more systematic and unbiased approach for determining case stratification, treatment protocols, outcome predictions and, most importantly, avoiding those treatments that are not (or less) effective. AI solutions can use ML algorithms in precise planning, and may help make sense of the potentially nonsensical. This will cause a paradigm shift for interventional oncologists, improving clinical outcomes to the extent that it will be the mainstay of IR practice.

Current positions

Present: Senior consultant vascular & interventional radiologist and head of Clinical Radiology, Subang Jaya Medical Centre, Subang Jaya, Malaysia Present: Founding member, Asia Pacific Society of Interventional Oncology 2018–2020: President, Malaysian Society of Interventional Radiology 2008–2020: Council member, Asia Pacific Society of Vascular & Interventional Radiology (APSCVIR) 2018–2020: Council member, College of Radiology, Academy of Medicine of Malaysia 2019: O rganising chair and course director, Asia Pacific Conference on Interventional Oncology (APCIO 2019) 2019: Organising chair, 2nd Multidisciplinary Oncology Symposium Malaysia (MOSM)

Previous appointments 2017:

O rganising chair and faculty, MOSM 2013–2016: Vice president, Malaysian Society of Interventional Radiology 2009–2011: Committee member, Independent Ethic Committee, SDMC 2008–2010: President, Asia Pacific Society of Cardiovascular & Interventional Radiology 2008: Organising chair, 8th Asia Pacific Congress of Cardiovascular and Interventional Radiology Symposium (APCCVIR), Kuala Lumpur, Malaysia 2007–2014: C ommittee member, Specialist Credentialing Board, Ministry of Health, Malaysia 2006–2008: Honorary secretary, College of Radiology, Academy of Medicine, Malaysia 2004–2012: Council member, College of Radiology, Academy of Medicine of Malaysia 2001–2017: Visiting consultant in interventional neuroradiology, University Malaya Medical Centre

June

Critical limb ischaemia

The reactive and repetitive multidisciplinary CLI team Jihad Mustapha Comment & Analysis It is imperative that every medical institution has an interdisciplinary CLI team, argues Jihad Mustapha. Here, he exhorts the benefits of working in such a multidisciplinary team, and outlines how the circle of care concept can be applied to reduce rates of unnecessary major amputation.

he most effective critical limb ischaemia (CLI) multidisciplinary team structure is comprised of multiple layers or groups of providers from a variety of areas, including surgical and endovascular revascularisation, podiatry, wound care, endocrinology, primary care, orthopaedics, cardiology, infectious disease and physical medicine. The action of each group is reactive to the immediate need of the CLI patient. The course of action in the treatment cascade is not linear; instead, it is both repetitive and reactive. To transform the potentially catastrophic event of a CLI diagnosis into a patient with a successful outcome, the team must act in harmony and initiate the reactive cycle of therapy when a CLI patient receives treatment at the level that is most critical at any single point in time (Figure 1). A provider will refer the CLI patient to the next most critical continuum for the secondary issue to be addressed (cascade of care). The CLI team must always be aware of and acknowledge that the CLI

patient’s therapy is not conclusive, and that the chance of recurrent disease is high. Therefore, heightened awareness and strict follow-up evaluation are required. Once a recurrent CLI event is discovered, the repetitive cycle must be initiated. For a patient with active CLI disease, there should never be a period of time where no form of therapy is being delivered. The average time it takes for a CLI patient to receive any type of first treatment or diagnostic testing has been reported to be nine days. This is unacceptable. Too much can happen in nine days to result in a poor outcome for a CLI patient. Therefore, the repetitive phase must be initiated as early as possible. Any member of the CLI team can and should trigger the repetitive treatment cascade in the presence of: Recurrent rest pain Absent doppler pulse Occluded target vessel and lack of progression of wound healing Regression of wound healing

New global guideline on critical limb-threatening ischaemia finalised, awaiting publication The long-awaited Global Vascular Guidelines for chronic limb-threatening ischaemia have been finalised, with the comprehensive guideline set to be published shortly. The news was announced by the Society for Vascular Surgery, one of the societies participating in the international effort to produce the document. THE JOURNAL OF VASCULAR Surgery is publishing the guideline, with 113 specific recommendations, as a supplement to the June edition, which at the time this newspaper went to press has not yet been released. The guidelines were made available online in late May.

Infection or sepsis. Note: Amputation is not always the answer here. Revascularisation and intravenous antibiotics must be tried first, unless the patient is in shock and the limb is not salvageable. Only then should amputation be performed without an attempt at revascularisation. Once a CLI patient has been treated and has reached a stable form of the disease, such as wound healing, rest pain resolution and/or return to activity, the preventive phase of CLI therapy (in the circle of care) should be initiated by the CLI team. The CLI team members must each provide their recommended medical treatment based on their specialty. Most importantly, the circle of care (preventive phase) should never be stopped. In fact, prevention should be started in the pre-CLI phase for patients who are Rutherford 1–3. Any form of peripheral arterial disease (PAD) should be preventively treated as early as possible to prevent the catastrophic outcomes that we know can happen to those patients that reach the CLI phase. Hence, there is an extreme need for a multidisciplinary CLI team to exist in every institution in

[The final document is] a unique practice guideline, reflecting the spectrum of the disease seen worldwide.”

the USA and around the globe. CLI centres are a new concept, and have adopted the strategies discussed above. The success of any CLI centre is dependent upon the harmony of the members of the multidisciplinary CLI team. CLI centres’ outcomes have been shown to produce excellent outcomes with impressive reductions in major amputation.1,2 The future of effective CLI therapy lives in a cohesive and functional multidisciplinary team. Jihad A Mustapha is the associate clinical professor of Medicine at Michigan State University COM, E Lansing, USA. He is also the CEO of Advanced Cardiac and Vascular Centers for Amputation Prevention, Grand Rapids, USA. References 1. Mustapha JA, Saab FA, Diaz-Sandoval LJ, Beasley R, McGoff T, Finton S, Heaney C, Adams G. The Peripheral RegIstry of Endovascular Clinical OutcoMEs (The PRIME Registry): Interim Analysis of the First 328 Subjects With Critical Limb Ischemia. Vascular Disease Management. 2017;14(3): E55-67. 2. Raymond Dattilo, Alexandra Dattilo, Shawn Colby. Outcomes of Patients Treated for Critical Limb Ischemia in an Outpatient Endovascular Center. Vascular Disease Management 2018;15(6):E49-E52.

CLI Patient presents with CLI disease and enters the Cascade of Care at the point of entry per the specialist who initiates care. Here the patient receives all necessary care until reaching wound healing or resolution of rest pain. Once in remission, the CLI patient remains in the Circle of Care indefinitely. The patient must be closely evaluated to prevent recurrent of active CLI disease to maintain Amputation Prevention.

The Society for Vascular Surgery (SVS) reports the guidelines “creates a new conceptual framework for treating chronic limb-threatening ischaemia, the end-stage of peripheral arterial disease. The document encompasses nomenclature, disease staging and a platform for evidence-based revascularisation that will allow for future evolution and quality improvement in the field.” Furthermore, a notable change is a purposeful move from the term critical limb ischaemia (CLI) to chronic limb-threatening ischaemia (CLTI): a name which the authors explain is a better reflection of the full spectrum of the disease. Michael Conte of the Society from Vascular Surgery, Philippe Kolh of the European Society for Vascular Surgery and Andrew Bradbury of the World Federation of Vascular Societies co-edited the guidelines document, with close to 60 additional authors. All specialties treating CLI were represented among the authors, the SVS notes, with participants from six

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CLI Patient

Cascade of Care

Circle of Care

continents. Highlighting the thorough and methodical work of the writing group, the finalised document is “a unique practice guideline, reflecting the spectrum of the disease and approaches seen worldwide,” Conte told the SVS. The SVS further discloses that major recommendations will cover the need for comprehensive assessments in patients with suspected CLTI; optimal medical therapy, including a variety of treatments for CLTI patients; and prompt and effective revascularisation for patients with advanced ischaemia and limb threat. The document also outlines the importance of an individualised approach to improve patient care and reduce limb loss. Other significant changes include a standardised classification system with endorsement of the SVS Threatened Limb Classification System based on grading wound, ischaemia and foot infection (WIfI) in the affected limb, as well as introducing the Global Limb Anatomic Staging System (GLASS) to stratify patterns of arterial occlusive disease. “Perhaps most notably, the guideline supports a structured approach to decision-making regarding revascularisation based on Patient risk, Limb severity and ANatomic complexity (PLAN), in that order of priority,” Conte comments in the SVS announcement. “The guideline seeks to provide a new foundation for practice but also for data collection to support evidenced-based revascularisation in CLTI.”

June

Issue

BIBABriefings

MedTech Insights

FDA letter may lead US physicians to use fewer drug-coated balloons Following a letter from the US Food and Drug Administration (FDA) that advised against the use of paclitaxel devices in most patients with peripheral arterial disease, according to a new survey, most (68%) US-based physicians think that they will use fewer drug-coated balloons this year than they did last year. A previous survey, conducted just after the Katsanos et al meta-analysis was published (December 2018), found that only 55% of US-based physicians thought that they would use fewer of these devices.

Source: BIBA MedTech Insights

fter the publication of the Katsanos et al meta-analysis (December 2018), the FDA performed a preliminary analysis of the long-term follow-up data of FDAapproved paclitaxel devices. As reported in the FDA letter (published March 2019), this analysis showed higher mortality in patients who were treated with paclitaxel-coated devices than those treated with uncoated devices. Furthermore, the letter says: “For most patients, alternative treatment options to paclitaxel-coated balloons and paclitaxel-eluting stents should generally be used until additional analysis of the safety signal has been performed”. However, it says physicians may believe that the benefits of paclitaxel devices outweigh the apparent risks “for some individuals at particularly high risk for restenosis”. Subsequent to this letter, BIBA MedTech surveyed 275 physicians about their anticipated use of paclitaxel devices in the femoropopliteal arteries this year (versus their actual use last year). Of these, 60% were from Western Europe, 17% were from North America, and 23% were from other regions. Overall, 45% of respondents anticipated using fewer drug-coated balloons this year compared with how many they used last year. However, when the results for the subgroup of US respondents were reviewed, the proportion who reported that they anticipate using fewer drug-coated balloons increased to 68%. A similar trend was seen with drug-eluting stents—66% of US-based physicians believe they will use fewer stents this

Source: BIBA MedTech Insights

year compared with 39% of respondents overall. Among Western European respondents, 50% think they will use fewer drug-coated balloons and 42% say they will use fewer drug-eluting stents.

Impact of the Katsanos et al meta-analysis versus impact of the FDA letter

In early January 2019, as reported in the last issue of Interventional News, BIBA MedTech conducted a survey of 107 physicians to determine the immediate impact of the Katsanos et al meta-analysis. In this survey, 46% of physicians were from Western Europe, 25% were from North America, and 29% were from other regions. The number of US physicians in this first survey who thought they would use fewer drug-coated balloons was considerably lower than in the second survey: 55% versus 68%, respectively (see Figure 1). Similarly, the proportion of US physicians who think their use of drug-eluting stents will go down this year was lower in the first survey: 36% for the post Katsanos et al survey versus 66% for the post FDA survey. Of note, for Western European physicians, their anticipated use of both drug-coated balloons and drug-eluting stents remained relatively stable between the two surveys: 49% versus 50% for drug-coated balloons and 40% versus 42% for drug-eluting stents, respectively. Between the Katsanos et al metaanalysis being published and the FDA letter being released, several companies shared patient-level data for their paclitaxel devices and various conferences held special sessions reviewing the safety of paclitaxel devices. In particular,

a highlight of the 2019 Charing Cross Symposium was the “Paclitaxel: The last word” session (see pags 20–21). Therefore, the increase in the number of US physicians anticipating a drop in the number of paclitaxel devices that they use could be the result of several factors. However, that such an increase was not observed among Western European physicians does suggest that the FDA letter has had an influence on the attitudes of the US physicians (given that the FDA only regulates the US device market). Of note, this does not mean that the FDA letter has not had any influence on Western European physicians. In fact,of respondents who think that they will use fewer paclitaxel devices this year (in the second survey), 68% of US physicians and 74% of Western European physicians say that their decision is a “direct result” of the FDA letter. Furthermore, only 43% and 60%, respectively, say that the Katsanos et al meta-analysis directly affected their anticipated use of devices this year.

Alternatives to paclitaxel

In the post FDA letter survey, if they stated they would use fewer paclitaxel devices, respondents were asked what

they would use as alternative treatments. Of 95 respondents overall, most (68) said that they would use plain balloon angioplasty rather than drug-coated balloons. The remaining respondents said that they would use speciality balloons (10), bare metal stents (eight), interwoven nitinol stents (six), and other methods (3; see Figure 2). Regarding alternatives to drug-eluting stents, of 72 overall, 38 would use bare metal stents, 21 would use interwoven nitinol stents, five would use plain balloon angioplasty, three would use speciality balloons, and five would use other methods.

68% of US physicians and 74% of Western European physicians say that their decision is a ‘direct result’ of the FDA letter.”

BIBA Briefings BIBA Briefings provides in-depth analysis of the latest market intelligence from BIBA MedTech Insights, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America. The platform also reviews data and news. For more information about BIBA Briefings or BIBA MedTech Insights, please contact Merveille Anderson merveille@bibamedical.com

June

Access to IR services

Patients deserve improved access to IR services Trevor Cleveland Comment & Analysis In the wake of the recent joint statement from the British Society of Interventional Radiology (BSIR) and the Royal College of Radiologists (RCR) advocating for the increased provision of interventional radiology services in the UK (see below), and in anticipation of the publication of the Provision of Interventional Radiology Services (POIRS) document in the summer of 2019, BSIR president Trevor Cleveland writes about why patient access and awareness of interventional radiology (IR) procedures is crucial. IT IS IMPORTANT to improve the provision of IR (image guided surgical) procedures across a range of emergency and elective, adult and paediatric services, because they have the ability to treat people with reduced morbidity, and generally have a quicker recovery time. IR as a specialty has evolved within what was originally a diagnostic service, with the expertise in image interpretation as a cornerstone to its effectiveness and success. The situation now is that IR procedures are the “go to” option in a number of emergency and elective scenarios, offering treatment for patients who previously needed more invasive open surgery, or were considered too high risk for those treatments. In many ways, image-guided procedures complement the open options, and extend the range of people who can have effective treatment (including cancer treatments). In other scenarios, the minimally invasive

nature of IR procedures has meant that some open surgical side effects and complications can be avoided. By its very nature, a new specialty develops in a relatively uncoordinated way, with pockets of enthusiasm and expertise being developed. The time has come, and the clinical need exists, for IR to come out of those shadows and be recognised for the specialty that it is, and the great things it can offer patients. The POIRS and RCR Census tell us that we need more interventional radiologists in training, and that we need to use our current capacity more effectively. We also know that trainees and consultants can be discouraged in taking on IR procedures because of the high emergency commitment (so we need to make that more acceptable to work life balance), the higher risk of litigation, and the low level of recognition of the specialty.

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However, it is clear that IR procedures offer great short and long term benefits for patients, to which they deserve to have access in a timely fashion, and for these to be performed by well trained, well-practiced and fresh doctors.

after a procedure, to ensure optimised aftercare, to manage any difficulties or complications, and it is essential that interventional radiologists are made aware of outcomes, and are able to record these for audit and quality purposes.

Interventional radiologists must take primary responsibility in the patient pathway

BSIR is addressing challenges facing IR in the UK

It is important that interventional radiologists take primary responsibility in the patient pathway. The techniques, work up, follow up and audit of IR procedures, like all interventions, carry with them benefits and risks unique to the procedures and to individuals. It makes sense for patients and interventional radiologists to meet, discuss and address questions and expectations. Indeed, it is a requirement from the General Medical Council (GMC) that these facilities exist. Perhaps, in the past, where simple imaging was “ordered”, the situation was different. But as the complexity, and the potential risk:benefit analysis becomes more complex, such a situation is not tenable. It can be a very difficult balance, because there are a number of high volume procedures, which are relatively straight forward, and mandating direct face-to-face IR input may result in delay in treatment. There are two potential ways to address this. One is to have very clear information for patients and other clinical teams, with specific training designed to allow for delegated responsibilities along the consent process. This at least reduces the time pressures required of interventional radiologists directly. The other approach is to significantly increase the IR capacity. Of course the latter is the ideal, but difficult to achieve, particularly in the short term. It is vital that these two strategies run concurrently, to ensure the highest quality service to patients possible. Alongside this, it is important that patients have the opportunity to have a review with an interventional radiologist

One of the challenges for IR, which BSIR is trying to address, is the general lack of understanding of what IR is, and what we can offer. This level of misunderstanding exists in many areas, including amongst patients, commissioners, general practitioners and even fellow hospital clinicians. BSIR has established a communications team, which includes interventional radiologists alongside communications experts. We have been leveraging a number of areas to try to raise the knowledge and profile of IR, including social media, web site information, newsprint (including Interventional News) and through direct involvement in parliamentary groups. In addition, BSIR has recognised for a number of years that medical students and junior doctors often have not been exposed to, or understand, IR procedures. To address this, we support a series of essay and case study applications, which, if successful, give the opportunity (with expenses support) for both groups to attend the BSIR annual scientific meeting (13–15 November, Manchester, UK), where there are specific events for them, in addition to the main programme. We also support local meetings of interested groups, as well as training events. These are aimed at increasing the awareness of IR, as well as trying to encourage suitably minded trainees to join the IR specialty. Trevor Cleveland is an interventional radiologist at the Sheffield Teaching Hospitals NHS Foundation Trust and the Sheffield Vascular Institute, Sheffield, UK.

BSIR and RCR joint statement supports increased provision of interventional radiology procedures The Interventional Radiology Committee of the Royal College of Radiologists (RCR), in collaboration with the British Society of Interventional Radiology (BSIR), have released a statement for interventional radiology (IR) service provision in the UK to supplement the existing Provision of Interventional Radiology Services (POIRS) document. This supports both longitudinal care and ownership of patients by interventional radiologists, and has been met with approval from the IR community.

n a document entitled “The clinical role of interventional radiology (image guided surgery) in patient care”, the two bodies write: “The Provision of Interventional Radiology Services (POIRS) has been revised, and the second edition is due to be published this summer (2019). This statement has been released by the Royal College of Radiologists (RCR) and British Society of Interventional Radiology (BSIR) to introduce the POIRS document, identify the benchmarks for interventional radiology and to highlight the competencies of interventional radiologists in patient management, both in an inpatient and outpatient scenario, obtained as part of their subspecialty training.” Speaking to Interventional News about how this joint statement will affect interventional radiologists in

the UK, BSIR president Trevor Cleveland (Sheffield, UK) comments: “IR has changed considerably, even between the 2013 version of this document and today. Interventional radiologists are using increasingly complex techniques and treating more complex clinical situations, often in an emergency environment. This includes acute bleeding (associated with trauma and iatrogenic injury) in a number of organ systems. The treatment of sepsis, whilst to some degree a core radiology skill, in more complex situations requires more advanced techniques. As such, interventional radiologists have become essential to the effective functioning of many acute services. This is in addition to an expanding range of elective treatments, including oncology, as well as the more established IR procedures, such as angioplasty

and stenting, and more recently stroke treatment and prevention. These are delivered across both adult and paediatric populations. “Yet there remains a relatively small number of interventional radiologists who can provide this service, in an environment where the emergency commitment is increasing for this group. The POIRS update provides current information, informed by both the BSIR membership and the RCR Census survey, on the present service delivery, and the numbers that need to be included in the workforce planning going forward. “Key to this is delivering a timely service for patients (making the best use of the IR skills that we have now, including ensuring that IR skills are not unnecessarily lost as a result of the reconfiguration processes and/

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or an imbalance of emergency commitment) and future planning. Trainees are our future, and we must ensure that we have an environment that encourages enthusiastic young doctors, and the capacity to meet the expanding needs. Add to this the likely loss of IR skills as some of the present community reach retirement (which is compounded by the pension tax laws which mean that, like in General Practice, experienced doctors are being effectively encouraged to leave or to reduce their activity).” As an “essential part of modern medicine”, the BSIR and RCR joint statement introducing the anticipated POIRS document outlines how interventional radiologists can act to widen the provision of IR services in the UK. There are four conclusions: IR is a subspecialty of clinical radiology requiring an additional year of training, compared to diagnostic radiology (six years total) to be certified by the General Medical Council (GMC) IR Certificate of Completion of Training. IRs receive training appropriate to their scope of practice, enabling them to clinically manage patients under their direct care, throughout the patient pathway, and provide clinical advice for patients under the care of other clinical specialties. To deliver this clinical care, IRs require appropriate clinical time, infrastructure and support from their employing organisations, including access to outpatient clinics and inpatient beds. Trusts should be supportive of IRs who wish to deliver high quality longitudinal care on a par with many fellow specialists. Commenting on these conclusions, and the ramifications she envisages they will have for British IR, Clare Bent, an interventional radiologist at The Royal Bournemouth and Christchurch Hospitals, Bournemouth, UK, says: “The IR benchmarks and a focus on the development of a subspecialty IR curriculum are both key to the provision of a

Access to IR services robust, competent IR workforce who can deliver comprehensive, longitudinal, high quality care in both an inpatient and outpatient setting. Ward rounds, outpatient clinics, and admitting privileges with adequate and appropriately trained support staff are all integral factors in the optimisation of patient centred care for the IR specialty.

The diverse nature of IR service provision and continual innovations in the specialty mean that trained interventional radiologists are best placed to provide information and consent for such minimallyinvasive procedures.” She continues: “The diverse nature of IR service provision and continual innovations in the specialty mean that trained interventional radiologists are best placed to provide information and consent for such minimally-invasive procedures—which in turn improves patient experience, understanding, and confidence. Formalising the IR clinical role will bring clarity to the doctor-patient relationship for the IR speciality, establish a standardised IR management pathway and will allow allocation of appropriate funding streams. The less invasive approach that IR offers allows rapid recovery, reduced in-hospital stay and reduced morbidity and mortality, with a profound impact on healthcare economy.

“This interim statement is a step forward in supporting interventional radiologists, as clinicians, to deliver high quality patient care to the UK population.” Cleveland is in accordance, explaining how the document, which “represents a close collaboration between BSIR and RCR”, provides “as representative a statement as possible, including engagement from Members and Fellows of both organisations.” He goes on to explain that, as such, “it provides a framework for change and development, and serves as guidance to the wider healthcare community including interventional radiologists, radiologists more generally, commissioners, NHS England and Health Education England. We hope that it will act as a useful support for the real and effective changes that need to take place to ensure a high quality and equitable service, which patients deserve.” In advance of the publication of the POIRS document this summer, Cleveland stresses its significance: “The POIRS document is an enormously important one, which provides information on IR procedures, and guidance for future planning. It seems highly likely that the attractiveness, for patients and healthcare services alike, of IR procedures will result in a continued expansion. Innovation and equipment development are also likely to continue, with further techniques and applications being identified on a regular basis. Key to these is the expert interpretation and training in imaging that IRs have. Whilst it may be appealing to split off some of these activities for short-term reasons, IRs offer a skill set that extends across a wide range of clinical scenarios and teams. The major challenge facing us at the moment is delivering an emergency service, in a timely equitable fashion, whilst maintaining and developing a sustainable workforce. This requires an elective practice that underpins the emergency service. The issues raised and recommendations made in the POIRS document are key to achieving this for NHS patients.”

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Stroke

Training IRs to perform thrombectomies maintains quality of stroke care and improves access Training interventional radiologists to perform endovascular thrombectomies results in positive outcomes for patients experiencing stroke, according to a study presented at the Society of Interventional Radiology annual scientific meeting (23–28 March, Austin, USA). Expanding access to this treatment provides patients timely access to this gold-standard treatment.

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here is a limited availability of thrombectomy providers in the USA,” says Kelvin Hong, associate professor and division chief of interventional radiology at Johns Hopkins University, Baltimore, USA. “Patients do not plan where and when they have a stroke. Our model of training board-certified interventional radiologists can expand access to quality, evidence-based care, and reduce the lifelong disability associated with stroke.” Thrombectomy increases the survival rates among those suffering an acute ischaemic stroke, reduces the likelihood of resulting disabilities, and speeds function recovery. However, to gain these benefits, thrombectomies must be initiated and performed quickly. Many hospitals do not have providers available to perform these treatments and must transfer patients to a facility where they can get this care, losing valuable time. To determine an efficient and sustainable way to expand access to thrombectomy, researchers from Johns Hopkins University developed an interventional radiology stroke team at Suburban Hospital, a community hospital in Montgomery County, Maryland, a suburb of Washington, DC. The

team consisted of four interventional radiologists who were specially trained by a neurointerventional radiologist for six months. The entire team was available 24 hours a day, seven days a week with the neurointerventional radiologist helicoptered to the hospital for every case during this training period. “We looked to change the dynamic in stroke care, where instead of transporting medically fragile patients, we brought in a specialist to perform this care and build the infrastructure necessary to provide this treatment to a community with limited stroke care resources,” comments Ferdinand Hui, a neurointerventional radiologist and associate professor of radiology and radiological science at Johns Hopkins University. “In a situation where every minute counts, we wanted to design our programme to provide the training and organisation necessary to bring twenty-four-seven highly trained stroke interventionalists online as quickly as possible.” Once the interventional radiologists were conducting the treatments independently, researchers measured the technical success of the thrombectomies performed by the newly trained physicians in 35 stroke cases using the Thrombolysis in Cerebral

Infarction (TICI) scale, and found no significant differences compared to the 2016 HERMES meta-analysis of endovascular thrombectomy outcomes performed by other practitioners, such as neurointerventional radiologists and neurosurgeons. Additionally, 14% mortality in the first 90 days after the procedure was similar to 15.3% 90-day mortality among patients at stroke centres evaluated through the Journal of the American Medical Associationpublished HERMES trial. The median interval from symptom onset to the point when blood flow was restored was 325 minutes, compared to 285 minutes in previous research. Researchers plan to further evaluate the technical outcomes and time metrics in a second-year study with a goal of further reducing the time to treat each patient by improving efficiency and optimisation year over year. A limitation of the study may be in whether hospitals of varying sizes and resources can reproduce the programme with the same outcomes, the study authors accede. The research team plans to re-evaluate the programme after two years of data collection.

CX audience votes against neurointerventionists exclusively performing intracranial thrombectomy In the closest debate of the Acute Stroke Challenges session that took place on the first day of the Charing Cross (CX) Symposium (15–18 April, London, UK), Jan Kovac (University Hospitals of Leicester NHS Trust, Leicester, UK) and Andrew Clifton (St George’s University Hospitals NHS Foundation Trust, London, UK) discussed whether intracranial thrombectomy should be limited to neurointerventionists. KOVAC, A CARDIOLOGIST, whose proposition was that intracranial thrombectomy should not be limited to neurointerventionists, won the debate with 57% of the vote, but a substantial minority (43%) supported Andrew Clifton’s arguments that the procedure should be limited to neurointerventionists. While Clifton argued that experience and proper training leads to “appropriate patient selection [and] faster, safer procedures with fewer complications”, Kovac said that, given the magnitude of the potential clinical and economic benefits of mechanical thrombectomy, a “collaboration of various interventional specialists is desirable to deliver this therapy to a wider population”. Kovac argued that “Mechanical thrombectomy is the best evidencebased therapy for acute ischaemic stroke if provided in a timely manner by an experienced, multidisciplinary team.” He went on to say: “There is currently a hiatus between evidence and its implementation into practice across the world, with practice

varying significantly within and between countries. For several logistical, practical and economic reasons, collaboration of various interventional specialists is desirable to deliver this therapy to a wider population.” Indeed, he concluded that, “Given the magnitude of the potential clinical and wider economic benefits from mechanical thrombectomy, it should now be a key priority to address the substantial infrastructure and workforce obstacles impeding rapid and widespread implementation in the UK, Europe and beyond.”

Intracranial thrombectomy

The debate on intracranial thrombectomy was part of a whole session dedicated to the procedure. Hugh Markus (Cambridge, UK), who was chairing the session, called intracranial thrombectomy “one of the huge advances in stroke care at the moment”. Outlining its significance, he said “for every three patients we treat, we can cure

Acute Stroke Challenges session during the CX Symposium

one, so it is a massive treatment effect. It has transformed stroke care.” In a keynote lecture, David Hargroves (Kent, UK) reviewed what thrombectomy trials “really tell us”, and how the findings can be implemented into routine clinical practice. In light of the DAWN and DIFFUSE-3 trials, he said that there is a strong evidence basis for thrombectomy and that this treatment should be available to all patients. Additionally, Hargroves posited that regional and countrywide networks are required to deliver and achieve its 10% potential reach. However, he said, caution is needed when reorganising stroke services, so as

Intracranial thrombectomy is one of the huge advances in stroke care at the moment.”

not to destabilise the ‘core’ business and therapeutic benefit of organised care, closest to home.

Virtual reality for training purposes may elucidate “who can do the procedure”

Thomas Liebig (Munich, Germany) looked at the use of virtual reality in thrombectomy training. He described his own training as similar to that of learning to drive a car, and contrasted it with the simulator experiences of pilots who must demonstrate their competencies in a virtual environment. Liebig pointed out that skilled performance is difficult to characterise, and then outlined his work with University College Cork (Republic of Ireland) to develop surrogate parameters for performance metrics that can be used in a simulator. The findings, he said, “have the potential not only for training purposes” but, in a nod to the earlier debate on intracranial thrombectomy, could also allow us to “discriminate between a person who can do the procedure and those who should be doing something else”.

June

Stroke

Novel thrombectomy system aims to remove the clot with a single first pass Acknowledging that current methods used to remove clots to treat stroke can leave up to 20% of targeted material, Vasotorq, a medical device company based in Clyde Hill, USA, have recently patented a nitinol stent with distal protection designed to remove distal emboli from vasculature with greater efficacy. Speaking to Interventional News, co-founder and CEO of Vasotorq, interventional radiologist Joseph M Eskridge, outlines how Vasotorq’s thrombectomy system differs from those currently used, and discusses the company’s plans for the future.

What was your rationale behind developing Vasotorq’s thrombectomy system?

Current stent retrievers can require up to seven to 10 passes through the clot to remove all of the clots. Many physicians give up after three attempts. We aim to remove the clot with a single first pass. Many stent retrievers used in current practice today leave behind distal emboli

in 10–20% of cases according to the operating surgeon. One study indicated that surgeons are missing even more distal emboli when the case was reviewed by an independent third party physician.

How does the Vasotorq thrombectomy system improve on previous generations of stent retrievers?

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Vasotorq's next-generation stent adds an expandable distal protection umbrella that keeps the clot intact and in one piece, as well as catches emboli before they can break away and travel downstream.

How does the Vasotorq thrombectomy system improve on previous generations of stent retrievers?

Outside of stroke, Vasotorq's nextgeneration stent can be used in the coronary arteries during myocardial infarctions, the pulmonary arteries during pulmonary embolic showers and in the peripheral arteries in chronic total occlusions.

Are you currently working on any other projects at Vasotorq?

We are also working on the software for a mobile app that uses artificial intelligence to diagnose distal embolic occlusions in the left brain dominant hemisphere for expressive speech, receptive language, right arm and leg motor, and sensory functions. This helps the surgeon determine if pursuing distal breakaway emboli justifies the additional risk to the patient.

Joseph M Eskridge

What are the next steps moving forward?

We are currently seeking National Institute of Health grants and accredited investor funding and plan to seek additional indications once we achieve brain and stroke approval. Joseph M Eskridge is an interventional radiologist in Seattle, USA.

Interventional radiologists achieve similar clinical outcomes to published data for complex stroke cases Appropriately trained interventional radiologists performing endovascular thrombectomy in technically complicated stroke cases achieve similar reperfusion and clinical outcomes to those reported in the published literature. This is the conclusion of Andrew Hines, an interventional radiologist at Northeast Charlotte Radiology, Charlotte, USA, presenting his data at the annual meeting of the Society of Interventional Radiology (SIR; 23–28 March, Austin, USA).

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here is a lot of political pressure right now amongst other subspecialties, and they feel that we are not appropriately positioned to perform stroke thrombectomies, so it is even more important for those of us in this room to make sure that our data is extremely robust,” he said to SIR attendees. Hines said that, although he believes interventional radiologists are doing a good job at demonstrating their technical ability at performing M1 occlusions, the most common type of large vessel occlusion, they must demonstrate that capability in more technically challenging stoke cases to assuage “critics of interventional radiology”. Tandem occlusions are occlusions of the internal carotid artery in addition to occlusions of some of the inter-cerebral vessels and, according to Hines, there is very little literature focusing on gauging how well interventional radiologists are performing these procedures specifically. “Interventional radiology is not new to this [stroke cases]”, he informed delegates; “75% of the patients in the MR CLEAN study were performed by interventional radiologists, and that was actually the first of the five landmark trials, so we certainly have been here since the beginning.” The other four “landmark” trials he

mentioned are ESCAPE, EXTEND IA, SWIFT PRIME, and REVASCAT. Comparing published studies looking at tandem occlusions specifically, Hines said that “they all have a low patient sample size, ranging from two patients to about 100”. He also noted that both the technical outcomes and the TICI 2B/3 [Thrombolysis In Cerebral Infarction scale; an evaluation of angiographic

75% of the patients in the MR CLEAN study were performed by interventional radiologists, and that was the first of the five landmark trials, so we certainly have been here [performing stroke care] since the beginning.”

intracranial flow] varied widely, both “from 50 to 100%”. Several of the investigators from the five “landmark” trials have conducted subanalyses of their data to look at tandem occlusions. Showing the SIR audience an ESCAPE trial subanalysis, Hines said “In this series, in their tandem occlusions the TICI 2B/3 was 69% for technical success in revascularisation, and their mRS 0–2 at 90 days was 60%. So this sets the bar, I think, as to what we interventional radiologists should be trying to achieve.” Turning to his own data, Hines then asked the question “So, how well did we do?”. Going through his results, he explained, “With tandem occlusions, we achieved a TICI 2B/3 of 86%—that is almost as good as our M1 data. Our mRS 0–2 at 90 days was 43%, compared to 48.7% [in his M1 data]. Importantly, our complication rate was only 2.7%, and our mortality rate was 24%. “If you squeeze this data into the various retrospective series”, he continued, “you can see that we are definitely in the top quartile of all of the published series, especially when you look at the series that have more than 30 patients.” The key takeaway Hines stressed to the audience was that, when appropriately trained, interventional radiologists are proficient at performing these complicated procedures, and that the clinical outcomes are comparable with published data from other specialties who perform these tandem occlusions as part of stroke care.

June

Biopsy

Could selective liquid biopsy drive the oneshot treatment of melanoma? Bruno Damascelli Vladimira Tichà

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Comment & Analysis Within the context of liquid biopsy’s rising clinical application, Bruno Damascelli and Vladimira Tichà propose a means of improving this analytical technique through selective venous sampling. They argue that by drawing blood from a site nearer to the area affected by the malignancy, the sensitivity and specificity of the diagnosis would be enhanced. They present two illustrative cases that, according to the authors, “reinforce the interest for liquid biopsy”, a procedure they describe as “an important tool for the molecular definition of cancer and for its precise treatment”.

ncidence rates for malignant melanoma are currently rising more than those of any other malignancy. Predisposing factors are not fully known, except for the phenotype with fair complexion and light hair and eyes. A family history of melanoma accounts for 10% of all cases. Diagnosis is difficult because melanoma presents as a pigmented lesion, usually in a person with several cutaneous nevi. Electronic dermatoscopy has improved melanoma diagnosis, but excision of the skin lesion is normally conservative because staging is post-surgical unless there are distant lymph node metastases. Clinicalpathological staging is based on excisional biopsy, wide local excision, and sentinel lymph node biopsy. The American Joint Committee on Cancer (AJCC) melanoma committee strongly recommends sentinel lymph node biopsy because of the great difference in five-year survival rates in patients with negative lymph nodes. The sentinel lymph node must be removed for lesions with a Breslow thickness of 0 or >1mm, and those with spontaneous ulceration or with a mitotic rate of 1/ mm2. This means planning at least three separate procedures: (1) excisional biopsy, (2) wide excision, and (3) selective lymphadenectomy (SLN). It is now known that the DNA released by tumour cells (ctDNA) can be detected in blood even in an early stage of disease. This analytical technique, known as liquid biopsy, is increasingly finding clinical application. The limitation of liquid biopsy lies in the minimal amount of tumour DNA, which is masked by the prevalent amount of cell-free DNA (cfDNA)

produced by the body’s normal tissue turnover. One or more mutations related to a certain tumour confirms the diagnosis with some certainty, as is the case when circulating tumour cells (CTCs) are found in blood samples. If blood is sampled in proximity to the venous drainage of the area affected by the malignancy, it is possible that a larger amount of tumour DNA will be obtained, with an increase in the sensitivity and therefore of the specificity of the liquid biopsy. Two cases presented here by way of example suggest that selective venous sampling should be considered in early-stage melanoma.

Case one

Fifty-three-year-old man with nevus on left arm and a diagnosis on excision of superficial melanoma, with a Breslow thickness of 0.7mm, Clark level 3, nonbrisk tumour-infiltrating lymphocytes (TILs), no ulceration or regression, mitotic rate of 2/mm2, no vascular and perineural invasion, and negative lateral and deep margins. The indication for SLN was marginal. Peripheral liquid biopsy was negative. Selective liquid biopsy via transfemoral catheterisation of the left subclavian vein showed fragmented circulating DNA with a

Figure 1: 53-year-old man—Histological examination of melanoma on left arm (see text). Figure 2: Intraparenchymal metastasis, diameter 1mm, in sentinel lymph node. Figure 3: Seventy-nine-year-old man—Pigmented nevus on left arm, suspected melanoma. Figure 4: Right transbrachial catheterisation of left subclavian vein for selective liquid biopsy blood sampling. Figure 5: Wide local excision of nevus. Figure 6: Sentinel lymph node identification at time of wide local excision.

p.Y1021S mutation in codon 1,021 of the PiK3CA gene. No mutations were found in the KRAS, BRAF and NRAS genes. On SLN, melanoma metastases were found in one of two sentinel lymph nodes in the left axilla, as well as two intraparenchymal micrometastases, the larger measuring 1mm (Figures 1 and 2). Radical lymphadenectomy with 27 lymph nodes was negative, as was two-year follow-up of the patient.

Case 2

Seventy-nine-year-old man with nevus on left arm, suspected to be melanoma (Figure 3). Selective liquid biopsy with sampling from the left subclavian

The AJCC melanoma committee strongly recommends sentinel lymph node biopsy because of the great difference in five-year survival rates in patients with negative lymph nodes.”

vein (Figure 4) at the same time as peripheral sampling was suggested. Mutation p.Q61R of the NRAS gene in exone 3 was found, leading to a diagnosis of melanoma and wide excision (Figure 5) with sentinel lymph node lymphoscintigraphy and biopsy (Figure 6). Histological diagnosis confirmed melanoma with horizontal growth, no vertical growth, Breslow thickness of 0.9mm, Clark level 3, non-brisk TIL, no ulceration or regression, pigmentation present, mitotic rate 0, no perineural invasion, associated nevus present, and negative lateral and deep margins. Molecular tissue analysis confirmed the NRAS gene mutation. SLN biopsy was negative, as was liquid biopsy molecular analysis six months after surgery. Bruno Damascelli and Vladimira Tichà are interventionalists at the Department of Interventional Oncology EMO GVM Centrocuore Columbus in Milan, Italy. Their work is sponsored by the Falciani Foundation. The authors report no disclosures pertaining to this article.

June

Issue

Biopsy

Biopsy alternative: ‘Wearable’ device captures cancer cells from blood A prototype wearable device, tested in animal models, can continuously collect live cancer cells directly from a patient’s blood. Proposed as an alternative to biopsy, the system allows for the analysis of larger blood volumes, leading its developers to write in Nature Communications that “this technology could potentially be used to analyse larger number[s] of circulating tumour cells to facilitate translation of analytical information into future clinical decisions”.

eveloped by a team of engineers and doctors at the University of Michigan (Ann Arbor, USA), it could help doctors diagnose and treat cancer more effectively. “Nobody wants to have a biopsy. If we could get enough cancer cells from the blood, we could use them to learn about the tumour biology and direct care for the patients. That is the excitement of why we are doing this,” says Daniel F Hayes, the Stuart B Padnos professor of breast cancer research at the University of Michigan Rogel Cancer Center and senior author of the Nature Communications paper. Cancerous tumours can release more than 1,000 circulating tumour cells (CTCs) into the bloodstream in a single minute. These have become an established biomarker for prognosis in patients with various carcinomas, with elevated levels of CTC isolated from a single blood draw being indicative of metastatic breast, colorectal, prostate, or lung cancers. Current methods of capturing CTCs from blood rely on samples from the patient—usually no more than a tablespoon taken in a single draw. Some blood draws come back with no cancer cells, even in patients with advanced cancer; an average 7.5ml sample from a patient with metastatic breast cancer contains no more than 10 cancer cells, identified within the context of billions of erythrocytes and millions of leukocytes. Over a couple of hours in the hospital, the new device—a portable aphaeretic system—could continuously capture CTCs directly from the vein, screening much larger volumes of a patient’s blood. In animal tests, the cell-grabbing chip in the wearable device trapped 3.5 times as many cancer cells per millilitre of blood as it did running samples collected by blood draw. “It is the difference between having a security camera that takes a snapshot of a door every five minutes or takes a video. If an intruder enters between the snapshots, you would not know about it,” explains Sunitha Nagrath, associate professor of chemical engineering at the University of Michigan, who led the development of the device.

The uses of CTC evaluation

Research shows that most cancer cells cannot survive in the bloodstream, but those that do are more likely to start a new tumour. Typically, it is these metastases that are deadly, rather than the original tumour. This means CTCs captured from blood could provide better information for planning treatments than those from a conventional biopsy. Indeed, the investigators of the present proof-of-principle study hypothesised that “CTC evaluation might be used for early detection of malignancy, if an assay with sufficient sensitivity and specificity could be developed.” The team tested the device in dogs at the Colorado State University’s Flint Animal Cancer Center (Fort Collins, USA) in collaboration with Douglas Thamm, a professor of veterinary oncology and director of clinical research there. They injected healthy adult animals with human

cancer cells, which are eliminated by the dogs’ immune systems over the course of a few hours with no lasting effects. For the first two hours’ post-injection, the dogs were given a mild sedative and connected to the device, which screened between 1–2% of their blood. At the same time, the dogs had blood drawn every 20 minutes, and the cancer cells in these samples were collected by a chip of the same design.

The device

The device shrinks a machine that is typically the size of an oven down to something that could be worn on the wrist and connected to a vein in the arm. For help with the design, the engineering team turned to Laura Cooling, a professor of clinical pathology at the University of Michigan and associate director of the blood bank, where she manages the full-size systems.

Daniel F Hayes

heparin injector, and a CTC capture module that contains a microfluidic CTC capture chip. The investigators developed protocols for mixing the blood with heparin, to prevent clotting, and sterilisation methods that killed bacteria without harming the antibodies on the chip. Kim also packaged some of the smallest medical-grade pumps in a 3D-printed box with the electronics and the cancercell-capturing chip. The chip itself is a new twist on one of the highestcapture-rate devices from Nagrath’s lab. It uses the nanomaterial graphene oxide to create dense forests of antibody-tipped molecular chains, enabling it to trap more than 80% of the cancer cells in whole blood that flows across it. The chip can also be used to grow the captured cancer cells, producing larger samples for further analysis.

The next steps

In the next steps for the device, the team hopes to increase the blood processing rate. Then, led by Thamm, they will use the optimised system to capture cancer cells from pet dogs that come to the cancer centre as patients. Chips targeting proteins on the surfaces of canine breast cancer cells are under development in the Nagrath lab now. Hayes estimates the device could begin human trials in three to five years. It would be used to help to optimise treatments for human cancers by enabling doctors to see if the cancer cells are making the molecules that serve as targets for many newer cancer drugs. “This is the epitome of precision medicine, which is so exciting in the field of oncology right now,” says Hayes.

Sunitha Nagrath

It is the difference between having a security camera that takes a snapshot of a door every five minutes or takes a video. If an intruder enters between the snapshots, you would not knowabout it.” “The most challenging parts were integrating all of the components into a single device and then ensuring that the blood would not clot, that the cells would not clog up the chip, and that the entire device is completely sterile,” comments Tae Hyun Kim, who earned his doctorate in electrical engineering in the Nagrath Lab and is now a postdoctoral scholar at the California Institute of Technology (Pasadena, USA). Each component of the device is integrated into a compact 3D printed, portable structure, and is controlled through a custom built mobile application via wireless communication. The system consists of four major parts: a micro-controller, peristaltic pump,

The wearable device measures roughly 2x2.75x1 inches, with the cancer-cell-capturing chip mounted on top. The catheter connecting to the patient runs through the hole in the top left corner. Credit: Tae Hyun Kim

Inside the wearable device, the blood pump sits in the upper left corner while the heparin injector runs the length of the near side of the box. The green circuit boards control the blood pump, heparin injector and provide display data.

June

Vertebroplasty

Response: The ASBMR taskforce report is “dangerous” and “shameful” Douglas Beall Comment & Analysis A recent taskforce report charged by the American Society for Bone and Mineral Research (ASBMR) concluded that current evidence does not support the routine use of vertebroplasty for the treatment of pain from vertebral fractures. However, as someone who strongly believes the evidence supports the use of this procedure to alleviate pain, Douglas Beall has significant concerns about the impact this report will have on patient numbers.

he article published in the Journal of Bone and Mineral Research (JBMR) is dangerous and puts patients at an increased risk of morbid injury and death. The manuscript focuses on recommendations by a task force from the American Society for Bone and Mineral Research (ASBMR). Most of the taskforce do not even perform the procedure they are writing about (vertebral augmentation) and the ones that do it still do it after writing negative articles about it. I would never continue to do a surgery or procedure that I found to be ineffective, but it is well documented that authors of this trial do. One can only conclude that either they do not believe their own recommendations, or that they perform the procedure for reasons other than clinical effectiveness. I would also never write any article, especially a highly

They would like to ban a procedure that is demonstrably life-saving.” critical one about a technique that I did not personally do, but the taskforce is filled with authors from the departments of Internal Medicine, Clinical Sciences, Epidemiology and Human Metabolism that have never seen the inside of an operating room in their current professional positions. So what is dangerous about these recommendations? The task force says there is insufficient evidence to recommend vertebral augmentation. This will assuredly decrease the number of patients treated. This situation has been seen previously after two vertebroplasty versus sham trials were published in the New England Journal of Medicine

(NEJM) in 2009. What happened afterwards was recently described by Kevin Ong (Philadelphia, USA) et al who documented the decreasing number of patients treated and estimated that 75,452 patients were at higher mortality risk and that 6,814 lives were lost due to the downward trend in treatment. The inevitable increase in patient morbidity and mortality has not even been addressed by the taskforce despite the fact that this has been studied by many authors from many countries in the USA, Europe and Asia. If the ASMBR taskforce has their way, they would like to ban a procedure that is demonstrably life-saving and life prolonging. The taskforce states that there is “insufficient evidence to support kyphoplasty over non-surgical management, percutaneous vertebroplasty, vertebral body stenting or Kiva” but is apparently unaware of a large kyphoplasty randomised control trial (RCT)—the Fracture Reduction Evaluation (FREE) trial, published in 2009—that provided Level 1 evidence supporting kyphoplasty over non-surgical management, and a recent meta-analysis by Ioannis Papanastassiou (Rimini, Greece) that showed prominent pain, function and quality of life improvements with vertebral augmentation. The meta-analysis examined 1,587 articles in the English language including 27 Level 1 or 2 articles compared to the taskforce’s five articles. Why only five articles? They only examined the vertebroplasty versus sham trials. Despite this severely limited dataset this did not stop the taskforce from making recommendations about implant augmentation and kyphoplasty which has been shown to be highly effective. The taskforce incorrectly stated that “a sham procedure means that local anaesthetic was administered to the skin and the procedure was simulated”, which is only true for one of the positive trials, not the three negative ones. The negative studies use a sham that

involved injecting anaesthetic onto the bone in the location of the medial branch of the dorsal ramus, a technique that has Level 1 evidence supporting its efficacy in significantly decreasing back pain. Not only is this not a sham, it is an active treatment that significantly decreases back pain. This active treatment, called a sham by the authors of VERTOS IV, decreased the pain by a massive 4.75 points on the numerical rating scale. So how does this rate? If you account for their calculations for significance, this is better than spine injections, radiofrequency ablations, cervical discectomy, total hip arthroplasty and virtually everything we do in medicine. Yes, even the gold standards in spine and orthopaedic surgery—the cervical discectomy and fusion and the hip arthroplasty—are nowhere close to as good as the fake surgery for the authors of VERTOS IV. The fundamental problem is that by comparing mean pain scores, as was inadvisably done in VERTOS IV, the authors created an impossibly high benchmark for comparison that almost nothing significantly outperforms, except for, ironically, kyphoplasty. In the largest clinical trial ever done on kyphoplasty with 354 patients, the pain decreased by an average of 6.3. The world’s largest registry recently completed in the USA showed real-world results on data collected from sites around the country and featured a mean pain score reduction of 6.7 points and a median pain reduction of 9 points. These two data sources are the largest realworld post-market data sources globally for vertebral augmentation but were not even mentioned by the ASBMR taskforce. The bottom line is that we know better than to produce recommendations like this that are completely divorced from the reality of today’s treatment of vertebral compression fractures and we know better to recommend something that has been shown to result in increased morbid suffering and death. The best way I can describe these recommendations is that they are shameful. Douglas Beall is the chief of Radiology Services at the Clinical Radiology of Oklahoma in Oklahoma City, USA. Disclosures Consulting: Medtronic, Spineology, Merit Medical, Lilly, Johnson & Johnson, SpinTech, Imaging3, IZI, Medlantis, Techlamed, Consultant, Peterson Enterprises, Medical Metrics, Radius Pharmaceuticals, Halyard, Vertiflex, Sollis Pharmaceuticals, Simplify Medical, Stryker Research Funding: Medtronic, SpinTech, Medical Metrics, Avanos, Relievant, Vertiflex, Stryker, Sollis Pharmaceuticals, Simplify Medical Advisory Board: Medtronic, Imaging3 Board Member: SpinTech, Nocimed Stock Holder: Metactive, Sophiris, Eleven Biotherapeutics, Radius Pharmaceuticals, Flow Forward Editorial Support: Thieme, Springer, Humana References 1. Kallmes DF, Comstock BA, Heagerty PJ, Turner JA, Wilson DJ, Diamond TH, Edwards R, Gray LA, Stout L, Owen S, Hollingworth W, Ghdoke B, Annesley-Williams DJ, Ralston SH, Jarvik JG. A randomized trial of vertebroplasty for osteoporotic spinal fractures. N Engl J Med 2009; 361:569–579. 2. Buchbinder R, Osborne RH, Ebeling PR, Wark JD, Mitchell P, Wriedt C, Graves S, Staples MP, Murphy B. A randomized trial of vertebroplasty for painful osteoporotic vertebral fractures. N Engl J Med 2009; 361:557–568. 3. Firanescu CE, Vries J, Lodder P, et al Vertebroplasty versus sham procedure for painful acute osteoporotic vertebral compression fractures (VERTOS IV): randomized sham controlled clinical trial. BMJ 2018;360:k1551. http://dx.doi.org/10.1136/bmj.k1551 4. Beall DP, Tutton SM, Murphy K, Olan W, Warner C, Test JB. Analysis of Reporting Bias in Vertebral Augmentation. Pain Physician. 2017 Nov;20(7):E1081–

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E1090. 5. Ong KL, Beall DP, Frohbergh M, Lau E, Hirsch JA. Reply to “At what price decreased mortality risk?”. Osteoporos Int. 29(8), 1929–1930. 2018 May 3., doi: 10.1007/s00198-018-4551-4. 6. Edidin A, et al. Mortality Risk for Operated and NonOperated Vertebral Fracture Patients in the Medicare Population. JBMR, 2011: Feb 9. DOI: 10.1002/jbmr.353 7. Chen AT, Cohen DB, Skolasky RL. Impact of nonoperative treatment, vertebroplasty, and kyphoplasty on survival and morbidity after vertebral compression fracture in the Medicare population. J Bone Joint Surg Am. 2013 Oct 2;95(19):1729–36. doi: 10.2106/JBJS.K.01649. 8. Zampini JM, White AP, McGuire KJ. Comparison of 5766 vertebral compression fractures treated with or without kyphoplasty. Clin Orthop Relat Res. 2010 Jul;468(7):1773–80. doi: 10.1007/s11999-010-1279-7. 9. Park J, Park S, Lee HJ, Lee C, Chang B, Kim H. Mortality following benign sacral insufficiency fracture and associated risk factors. Arch Osteoporos (2017) 12: 100. https://doi.org/10.1007/s11657-017-0395-3 10. Lange A, Kasperk C, Alvares L, Sauermann S, Braun S. Survival and Cost Comparison of Kyphoplasty and Percutaneous Vertebroplasty Using German Claims Data. Spine 2014;39:318–326 11. Edidin AA1, Ong KL, Lau E, Kurtz SM. Morbidity and Mortality after Vertebral Fractures: Comparison of Vertebral Augmentation and Non-Operative Management in the Medicare Population. Spine (Phila Pa 1976). 2015 May 27. 12. Kanis JA, Oden A, Johnell O, et al. Excess mortality after hospitalisation for vertebral fracture. Osteoporos Int 2004;15:108–112 13. Lin JH, Chien LN, Tsai WL, et al. Early vertebroplasty associated with a lower risk of mortality and respiratory failure in aged patients with painful vertebral compression fractures. Spine J 2017 14. Niemi-Nikkola, Ville,; Saijets, Nelli; Ylipoussu, Henriikka; Kinnunen, Pietari; Pesälä, Juha; Mäkelä, Pirkka; Alen, Markku; Kallinen, Mauri; Vainionpää, Aki, Long-term Posttraumatic Survival of Spinal Fracture Patients in Northern Finland, Spine: December 1, 2018 – Volume 43 – Issue 23 – p 1657–1663. doi: 10.1097/BRS.0000000000002687. 15. Wardlaw D, Cummings SR, Van Meirhaeghe J, Bastian L, Tillman JB, Ranstam J, Eastell R, Shabe P, Talmadge K, Boonen S. Efficacy and safety of balloon kyphoplasty compared with non-surgical care for vertebral compression fracture (FREE): a randomised controlled trial. Lancet. 2009. PubMed PMID: 19246088. 16. Papanastassiou ID, Phillips FM, Meirhaeghe JV, et al. Comparing effects of kyphoplasty, vertebroplasty, and nonsurgical management in a systematic review of randomized and non-randomized controlled studies. Eur Spine J DOI 10.1007/s00586-012-2314-z 17. Noriega DC, Rodrίguez-Monsalve F, Ramajo R, Sánchez-Lite I, Toribio B, Ardura F. Long-term safety and clinical performance of kyphoplasty and SpineJack procedures in the treatment of osteoporotic vertebral compression fractures: a pilot, monocentric, investigator-initiated study. Osteoporos Int. 2019 Mar;30(3):637–645. doi: 10.1007/s00198018-4773-5. Epub 2018 Nov 28. 18. Wilson DJ, Owen S, Corkill RA. Facet joint injections as a means of reducing the need for vertebroplasty in insufficiency fractures of the spine. European radiology 2011;21:1772–8. 19. Im TS, Lee JW, Lee E, Kang Y, Ahn JM, Kang HS. Effects of Facet Joint Injection Reducing the Need for Percutaneous Vertebroplasty in Vertebral Compression Fractures. Cardiovasc Intervent Radiol 2016;39:740–5. 20. Nath S, Nath CA, Pettersson K. Percutaneous lumbar zygapophysial (Facet) joint neurotomy using radiofrequency current, in the management of chronic low back pain: a randomized double-blind trial. Spine 2008; 33:1291–7. 21. Tekin I, Mirzai H, Ok G, Erbuyun K, Vatansever D. A comparison of conventional and pulsed radiofrequency denervation in the treatment of chronic facet joint pain. Clin J Pain 2007; 23524–9. 22. Lakemeier S, Lind M, Schultz W, Fuchs-Winkelmann S, Timmesfeld N, Foelsch C, Peterlain CD. A comparison of intraarticular lumbar facet joint steroid injections and lumbar facet joint radiofrequency denervation in the treatment of low back pain: a randomized, controlled, double-blind trial. Anesth Analg 2013; 117:228–235. 23. Fischgrund, J. S., Rhyne, A., Franke, J., Sasso, R., Kitchel, S., Bae, H., et al. (2018). Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study. European Spine Journal, 1–11. 24. Manchikanti L, Cash KA, McManus CD, Pampati V. Fluoroscopic caudal epidural injections in managing chronic axial low back pain without disc herniation, radiculitis, or facet joint pain. J Pain Res. 2012;5:381– 90. doi: 10.2147/JPR.S35924. 25. Kapural, Leonardo, Cong Yu, Matthew W Doust, et al “188 Randomized Controlled Clinical Trial Evaluating the Safety and Effectiveness of 10 KHz HighFrequency and Traditional Low-Frequency Stimulation for the Treatment of Chronic Back and Leg Pain.” Anesthesiology Pain Med Newly Published on 07 2015: doi:10.1097/ALN.0000000000000774 26. Rolfson O, Dahlberg L E, Nilsson J A, Malchau H, Garellick G.Variables determining outcome in total hip replacement surgery. J Bone Joint Surg Br 2009; 91(2): 157–61. 27. Beall DP, Chambers MF, Thomas SM, et al Prospective and Multicenter Evaluation of Outcomes for Quality of Life and Activities of Daily Living for Balloon Kyphoplasty in the Treatment of Vertebral Compression Fractures: The EVOLVE Trial. J of Neurosurgery 0:1–11, 2018 DOI:10.1093/neuros/ nyy017. 28. Beall DP, Shonnard NH, Berven SH, Anderson PA, Norwitz J, Wagoner D, Khor S. Registry Outcomes of Cement Augmentation for Osteoporotic Vertebral Compression Fractures. (Abstract Accepted) Society of Interventional Radiology, Austin, USA, 23–28, 2019.

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Obituary

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In memoriam

Professor João Bexiga Martins Pisco (1941–2019) Tiago Bilhim remembers Professor João Bexiga Martins Pisco, who passed away on 26 March 2019, during the annual meeting of the Society of Interventional Radiology (Austin, USA): “He was very accessible and kind, fond of teaching and enthusiastic about all types of minimally-invasive image-guided interventions.” Bilhim reflects on the “legacy” Professor Pisco leaves behind, following a lifetime of pioneering research.

rofessor Pisco was a renowned physician, both in his home country of Portugal and worldwide, and was especially esteemed amongst the radiology and interventional radiology community. He leaves behind a legacy, his work a major influence within the Portuguese radiology community. Professor Pisco had an immense interest in imageguided interventions, and his career tracked the evolution of interventional radiology from its beginnings in the 1970s until the end of his life in 2019, by which time he was a landmark figure for interventional radiology throughout the globe. He graduated in medicine in Coimbra, Portugal, and completed the radiology residency in Lisbon, Portugal (1972–1975). Between 1975 and 1976 he undertook a fellowship in cardiac radiology at the National Heart Hospital in London, UK. Afterwards, he continued his international career as a fellow, instructor and consultant radiologist at the University of Louisiana, Lafayette, USA (1977–1980). These three years in the USA had a profound effect on his whole career, shaping the way he approached medicine and patient care. He decided to pursue interventional radiology, embracing teaching and scientific research simultaneously. Those who learned from him knew his very practical and “American” way of working: “See one, do one, teach one”. He was very accessible and kind, fond of teaching and enthusiastic about all types of minimally-invasive image-guided interventions. With this in mind, Professor Pisco returned to Portugal in 1980, and became one of the great pioneers in interventional radiology. During his further 40 years of practice in Portugal, he was responsible for the dissemination of interventional radiology within our country. He was the director of the Radiology Department of the Santa Marta Hospital between 1980 and 1998. Later, he was the director of the Radiology Department of the Pulido Valente Hospital from 1998 through to 2005. He then became head of the Interventional Radiology Unit at Saint Louis Hospital in Lisbon, a position he held from 1998 until his death. Those who knew him experienced his enthusiasm for all interventional radiology procedures, and how he

always highlighted the huge impact they had on patients’ lives; offering many different treatment options, alternatives to surgery with lower morbidity and mortality. He was responsible for the implementation of many different interventional radiology techniques within Portugal, such as: percutaneous transluminal angioplasty; intra-arterial fibrinolysis; arterial and venous stent placement; arterial embolization; intra-arterial chemoembolization; inferior vena cava filter placement and sclerotherapy of varicocele and pelvic venous

urologists in the last decade that came in to learn about prostatic artery embolization (Figure 1). During his lifetime’s work at Saint Louis Hospital, we performed over 2,100 uterine fibroid embolizations and 1,500 prostatic artery embolizations, with a huge impact in all of these patient’s lives. He was married to Beatriz (Figure 2) and they had a daughter, Joana, who is following Professor Pisco’s passion for interventional radiology (Figure 3). Besides these clinical activities, Professor Pisco was a dedicated teacher and scientific researcher. He completed his PhD thesis in interventional radiology at the Nova Medical School in 1990 (Figure 4). His chosen research topic was the vasa vasorum changes following percutaneous transluminal angioplasty and stent placement in experimental arterial stenoses in a canine model; this was published in the Journal of Vascular and Interventional Radiology (JVIR) in 1993 and 1994. Many of the publications and scientific research in the 1980s and 1990s included case reports and retrospective cohort studies of the

congestion syndrome. He became known worldwide for his scientific research regarding arterial embolization for pelvic tumours in the 1980s at the Santa Marta Hospital, but is mainly recognised for the research he developed at Saint Louis Hospital on uterine fibroid embolization from the late 1990s and, since 2009, on prostatic artery embolization. He truly put Saint Louis Hospital in Lisbon on the map from the perspective of the interventional radiology community. This small hospital received hundreds of interventional radiologists and

first patients treated in Portugal with percutaneous transluminal angioplasty, stent-placement and arterial or venous embolization. From 2008, most of the work developed at Saint Louis Hospital in uterine fibroid embolization and prostatic artery embolization started to appear in all of the major international radiology journals, including Radiology, European Radiology, JVIR and Cardiovascular and Interventional Radiology (CVIR), amongst others. He published over 200 research manuscripts, participated in over 400 presentations during scientific meetings,

published six books and 78 book chapters, and received many awards for his scientific research in prostatic artery embolization (Figure 5). He was a devoted teacher, becoming the head of the Radiology Department at the Nova Medical School from 1997 to 2011. He taught all medical students during that time period, introducing them to the fundamental role of radiology in medicine and of interventional radiology in patient care. He would invite the best medical students to pursue interventional radiology, letting them perform the simplest procedures first, and guiding them through many subsequent interventions. He was also responsible for the postgraduate courses in radiology and interventional radiology that were held in Lisbon every other year; 22 overall (Figure 6). He would have national and international renowned faculty and approximately 200–300 attendants. Through all of this exhausting work, he shaped the present and future of radiology and interventional radiology not just in Portugal, but worldwide. Professor Pisco kept his “American”

1. Professor Pisco (centre) and the interventional radiology team from Saint Louis Hospital in Lisbon, Portugal. Left to right: Nuno Vasco Costa, Keith Pereira (visiting from the USA to learn about prostatic artery embolization), João Pisco, Tiago Bilhim, Lúcia Fernandes. 2. Professor Pisco with wife Beatriz and daughter Joana. 3. Professor Pisco daughter Joana after finishing a uterine artery embolization procedure. 4. Professor Pisco after completing his PhD.

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influence and was an entrepreneur and pioneer. He always tried to maintain the bond between clinical practice and scientific research, and his constant eagerness for new studies and publications made him a frequent participant in all European and American interventional radiology meetings (in particular the annual meetings of the Cardiovascular and Interventional Radiological Society of Europe [CIRSE] and the Society of Interventional Radiology [SIR]). During the last 20 years, one can finger-count the number of CIRSE or SIR meetings where Professor Pisco was not there presenting the most up-to-date results from our group on uterine fibroid embolization and prostatic artery embolization. He was very active during the latest CIRSE meeting in Lisbon (22–25 September 2018), and was present at the last SIR in Austin, USA (23–28 March 2019). Those who knew his passion for interventional radiology meetings are not surprised that he passed away during one—this was his “home away from home”. He died after a full day of prostatic artery embolization

6 5. Professor Pisco and Tiago Bilhim before receiving an award from Bial in Portugal in 2014, one of the most prestigious awards in medicine from his native country. 6. Professor Pisco (at the speaker’s podium) in the opening ceremony of the last post-graduate radiology course he organised in Lisbon, Portugal.

sessions, where he participated both as presenter and commenter. Late in the afternoon he received an award from the JVIR regarding one of our group’s publications from 2018; he was notably happy (Figure 7). Professor Pisco loved the recognition from his peers, loved SIR and CIRSE, and received three prizes from the JVIR during his last 10 years in the field of prostatic artery embolization. This was a perfect ending—already in the clouds after receiving another award even before passing away. He left us, certain that future generations touched by his

Obituary

passion for interventional radiology will keep alive all minimally-invasive, image-guided therapies—embolization and angioplasty—as alternative treatment options to surgery. For all of the patient’s lives that he helped to save, all of the medical students he taught, all of the radiologists and interventional radiologists that he taught—thank you! I hope to see you again someday. Tiago Bilhim is an interventional radiologist in Lisbon, Portugal.

7 7. Professor Pisco (third from right) receiving an award from JVIR 2018 editor’s honourees clinical studies. Photo taken a few hours before he passed away during the 2019 annual meeting of the Society of Interventional Radiology (SIR), on 26 March in Austin, USA. Photo credit: EPNAC.com

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Issue

IR in the Asia Pacific

“IR education and science have no borders”: APSCVIR 2019 meeting round-up The 14th Annual Scientific Meeting of the Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR) took place in Bali, Indonesia earlier this year (21–24 February), with 420 registrants from the Asia-Pacific region and beyond.

total of 143 free papers including 43 oral papers, 77 e-posters and nine walking posters were presented during the meeting. APSCVIR president Andrew Holden (Auckland, New Zealand) tells this newspaper that “The meeting was extremely well planned by [presidentelect] Prijo Sidipratomo [Jakarta, Indonesia] and his organising committee, and continued the proud tradition of an excellent academic programme combined with wonderful social occasions in an exotic location. The four-day schedule involved plenary and concurrent sessions, involving 120 world-class international and regional experts covering a wide range of vascular, oncology and other interventions.” In a press release, the society stated: “APSCVIR enjoyed the commitment and support by various global interventional radiology societies including CIRSE [Cardiovascular and Interventional Radiological Society of Europe], SIR [Society of Interventional Radiology], SIO [Society of Interventional Oncology], SPIR [Society for Paediatric Interventional Radiology] and ISVIR [Indian Society of Vascular and Interventional Radiology] that brought together world-renowned leaders in the different subspecialties of interventional radiology at the meeting, galvanising the bonds with these societies. “The above academic pursuits would not have been possible without the continued generous support from our 20 industry partners who contributed nine educational sessions during the meeting.” Holden iterated this, saying: “Strong industry support provided a busy trade display area and excellent interaction during session breaks.” During the awards ceremony held at the Cultural Fest Gala Dinner, three society members received the 2019 APSCVIR Gold Medallist Award: Abdul Samad Bin Sakijan (Kuala Lumpur, Malaysia), Gao Jun Teng (Nanjing, China), and Masatoshi Okazaki (Fukuoka, Japan). Jim Reekers (Amsterdam, the Netherlands), Ziv Haskal (Charlottesville, USA), and Brian Stainken (Stamford, USA) were also presented APSCVIR Honourary Memberships “for their long, untiring support and outstanding

contributions to [the] field of cardiovascular and interventional radiology”. Speaking to Interventional News, Haskal refers to the Honorary Membership as a “career highlight”, adding: “I have been a decades-long attendee and supporter of the APSCVIR, firm in the belief that it brings together a unique group of attendees, ones with

Immediately above: APSCVIR president Andrew Holden (L) and CIRSE president Robert Morgan. Immediately left: Young interventional radiologist sponsorship award recipients. Below: Andrew Holden (L) helps pour drinks.

The Asia Pacific society for IR covers a very broad area and has a great diversity in members.” expertise that has always broadened my interventional practice and approach. Things are simply different in different parts of the planet, and diversity creates new ideas, opportunities and advances. I think the APSCVIR is one of the most important IR societies, and I would encourage all interventional radiologists to put its meetings firmly on their potential travel calendars.” Echoing these sentiments, Reekers comments: “The Asian Pacific society for IR covers a very broad area and has a great diversity in members. Additionally, in Asia interventional radiology is a fast growing medical specialty. It is a great honour to be recognised as somebody who has contributed to the development, growth and spread of interventional radiology, also in the Asia

Pacific part of the world. It only shows that interventional radiology is truly an international specialty and that IR education and science have no borders. Many of the APSCIVR members visit the CIRSE annual meetings, and it is always a great pleasure to interact there in many ways. Therefore, the honorary membership of APSCIVR means a lot for me personally and I am very grateful for my election. The fact that I have always been a great lover of the Asia Pacific region makes it even more valuable for me to be in this position. I am sure that my ties to this group and region will even be more strengthened.” Additionally, 15 interventional radiologists below the age of 40 received the young interventional radiologist sponsorship awards, and were provided

with a grant to assist with travel. Holden says this continues “the tradition of supporting young interventionalists from developing countries in our region to attend the meeting”. He adds: “We look forward to welcoming you to the 15th APSCVIR in 2020 in Taipeh, Taiwan—an event that is sure to carry on the fine traditions of our Annual Scientific Meeting”.

June

Issue

Interventional radiology

Best of GEST 2019 The 2019 GEST (Global Embolization Oncology Symposium Technologies) Symposium took place on 9–12 May in New York, USA, with a new focus this year on trainees and fellows, representing, as co-convenors of the conference Marc Sapoval (Hôpital Européen Georges-Pompidou, Paris, France) and Jafar Golzarian (University of Minnesota, Minneapolis, USA) tell Interventional News, “the future of interventional radiology (IR)”. THIS FOCUS WAS manifested in an increase in trainee attendance and engagement, with 150 medical students from across the globe. New this year, a specific programme dedicated to career development, starting outside the usual conference hours at 7am, was packed. Sapoval enthused about the youth turnout, saying it was “striking to have a room full of people, with an average age of around 25, turning up at that time”. GEST 2019 also played host to a series of case competitions aimed at medical students and trainees. An evening session entitled “Future Meets the Present (…Almost the Past)” saw established interventional radiologists giving their advice to the younger cohort. Justin McWilliams (David Geffen School of Medicine, Los Angeles, USA) spoke about how to approach the first year in practice; Brian Stainken (Stamford Health, Stamford, USA) noted three things he would do differently in his early career were he to start over; Donna D’Souza (University of Minnesota, Minneapolis, USA) outlined her experience of being a successful woman in IR; and Michael Darcy (Mallinckrodt

Far left: Plenary Hall at GEST. Left: Jafar Golzarian. Above: Marc Sapoval and GEST faculty hosting a Masterclass.

Institute; Washington University, St Louis, USA) detailed what a work/ life balance should look like. These activities and the positive response prompted Golzarian and Sapoval to describe the meeting as “a push for the future” of the specialty. In addition to an increase in youth turnout specifically, there was a more general increase in attendance this year: a rise of 20%, according to Sapoval. This included approximately 50 new faculty members, meaning the meeting had a faculty more than 150 strong in total. GEST 2019 saw 180 abstracts submitted, and 90 accepted posters. Three of the abstracts received financial prizes, as did the three best posters. There were also three prizes awarded in the case competition aimed at trainees. The global nature of IR was reflected in the international cohort who attended and organised the GEST meeting. Fortyseven percent of the nearly 1,100 attendees were international (from outside of the USA), and the four committees that help organise the conference programme comprised of a diverse group of volunteers. These committees—focused on research,

interventional oncology, training, and workshops—are entirely volunteer-led, and Golzarian and Sapoval thank all those who have invested their time and efforts into GEST 2019: “Their involvement made this meeting our best yet”. The sessions dedicated to prostate artery embolization (PAE) and portal intervention were attendee favourites. At the end of the PAE Symposium, audience polling revealed that 100% of voters wanted to see the session return next year. Speaking to Interventional News, Golzarian claimed that GEST was “the only meeting that covers these two topics to this degree of detail”. The focus on PAE is a stalwart fixture of the meeting, which has featured a dedicated PAE day since 2012. Sapoval also spotlighted the flow dynamics session as a high point of the conference, saying: “It was an amazing session”. This was only open to registrants, and, in Golzarian’s words, “covered a lot of ground, including what we need to know but do not yet understand”. He said that flow dynamics was an “important topic” as “it is so essential to what we do in embolization”.

Radiology trainees’ exposure to invasive procedures is in decline As interventional radiology evolves as a distinct specialty from diagnostic radiology, the central and ongoing role of diagnostic radiologists in performing certain invasive radiological procedures could have important patient access implications. A recent study, published online in the Journal of American College of Radiology (JACR), characterises longitudinal changes in radiology trainees’ exposure to invasive image-guided procedures.

“U

sing national Medicare claims data over two decades as a surrogate measure of the changing relative distribution of services rendered by radiology trainees overall, we observed that radiology trainees now spend a smaller fraction of their overall work effort performing invasive procedures than in the past,” says Andrew Rosenkrantz, professor and director of health policy in the department of radiology at NYU Langone Health (New York, USA) and a Neiman Institute affiliate research fellow (Reston, USA). “Previously, a variety of invasive procedures accounted for approximately one third of radiology trainees’ relative work effort. Trainees’ relative invasive procedural work effort has now declined to approximately one half of that.” Rosenkrantz and team used Physician/Supplier Procedure Summary Master Files from 1997 to 2016,

and identified Medicare services performed by radiology trainees in approved programmes by extracting information on services billed by diagnostic radiologists and interventional radiologists reported with “GC” modifiers. Services were categorised as (1) invasive procedures, (2) non-invasive diagnostic imaging services,

Radiology trainees now spend a smaller fraction of their overall work effort performing minimally-invasive procedures.”

New this year was the “GEST stress test”, based off the American “Shark tank” or the European “Dragon’s Den” concepts, where three innovative interventionalists presented their novel research ideas to a group of expert panellists, who then judged the entrants’ projects. This sparked “excellent debates” and showcased three very different projects, Sapoval comments. “I think it really helped the investigators to focus on their research and hone in on how they could improve their current projects”, he said. James Spies (MedStar Georgetown University Hospital, Washington, DC, USA) comments: “GEST continues as the premier embolization meeting in the world. It is unique in the breadth of faculty experts, the detailed review of the tools of embolization and the quality of the presentations. The panel discussions have been expanded, where real life cases and questions can be addressed by the leaders in the field. I never fail to learn new things at GEST and it remains my favourite meeting of the year.” GEST will return to New York, USA, on 14–17 May 2020.

or (3) clinical evaluation and management services. Relative category trainee work effort was estimated using service level professional work relative value units. Nationally from 1997 to 2016, invasive procedures declined from 34.2% to 14.3% of relative work effort for all Medicare-billed radiology trainee services. Radiology trainees’ non-invasive diagnostic imaging services increased from 65.1% to 85.4%. Clinical evaluation and management services remained uniformly low (0.7% to 0.3%). Diagnostic radiology and interventional radiology faculty supervised 81% and 19%, respectively, of all trainee invasive procedures in 1997, versus 68.3% and 31.7%, respectively, in 2016. Despite declining relative procedural work, trainees were exposed to a wide range of both basic and complex invasive procedures in both 1997 and 2016. “Radiology trainees’ relative invasive procedural work effort has declined over time as their work increasingly focuses on CT and MRI,” states study senior author Richard Duszak, professor and vice chair for health policy and practice in the department of radiology and imaging sciences at Emory University (Atlanta, USA) and senior affiliate research fellow at the Neiman Institute. “As diagnostic radiology and interventional radiology/diagnostic radiology residency curricula begin to diverge, it is critical that both diagnostic radiology and interventional radiology residents receive robust training in basic image-guided procedures to ensure broad patient access to these services.”

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Market watch AuntMinnie.com’s SalaryScan survey on medical imaging compensation.

Industry News Cook Medical releases patient-level data from Zilver PTX paclitaxel-coated balloon study

Cook Medical has released deidentifiable patient-level data from a clinical trial of its Zilver PTX peripheral paclitaxel-eluting stent. The move comes a month after the US Food and Drug Administration (FDA) said that its preliminary review of longterm follow-up data found a “potentially concerning signal” of increased longterm mortality in people with peripheral artery disease who were treated with paclitaxel-coated devices compared to those treated with bare devices.

Zilver PTX

Cook Medical said that it was releasing the data to encourage further collaboration with researchers to improve treatment of peripheral arterial disease. The company website states: “In the spirit of full transparency, Cook Medical is providing our extensive long-term data on Zilver PTX, our drug eluting stent. Zilver PTX is a paclitaxel-coated stent that was approved by the FDA in 2012 through the premarket approval process.” The Zilver PTX randomised, controlled trial followed 479 patients over five years in the USA, Germany and Japan. Cook Medical touted that it is the first company with paclitaxel devices to make its de-identifiable patient-level data publicly available. “We will continue to support our customers and their patients by sharing what we have discovered from our research and data in the area of paclitaxel,” vascular division vice president Mark Breedlove said in a press release. Last September, Cook Medical said that it won FDA approval for a smallerdiameter version of its Zilver PTX peripheral drug-eluting stent.

Global registry to collect realworld data on liver lesions ablated with the Neuwave microwave ablation system launches A new global registry from Ethicon (part of Johnson & Johnson medical device companies) has been launched to collect and analyse real-world data on patients

with soft tissue liver lesions ablated with the company’s Neuwave microwave ablation system. Ethicon announced this registry at the Society of Interventional Radiology (SIR) annual meeting (23–28 March, Austin, USA). The multicentre, observational registry will follow approximately 1,500 patients worldwide for a total of five years from the date of their first liver ablation procedure with the Neuwave system. Real-world data will be collected from up to 30 centres throughout the world on the technical aspects of the procedure, including ablation time under varying liver tissue and lesion conditions. Efficacy and other outcome data will also be documented and assessed at various time points over the course of the study. “The goal of the registry is to systematically and comprehensively develop ablation parameter guidance for the microwave ablation of liver lesions with the Neuwave system,” says Paul Laeseke, an interventional radiologist at the University of Wisconsin School of Medicine and Public Health (Madison, USA), who consulted on the design of the registry. “Microwave ablation is an important treatment option that is increasingly being utilised throughout the world, and this data may provide new insights into factors that are critical for successful outcomes across a range of patients, clinical settings and health care providers. The registry will be an important contribution to our understanding of microwave ablation and support its further adoption.” The registry will also include data from consenting patients enrolled in other Ethicon-sponsored studies on microwave liver ablation with the Neuwave system in Korea and China, as well as a multicentre study that is evaluating the device using Neuwave’s ablation confirmation software, which, according to a press release, helps physicians identify ablation targets, assess appropriate probe placement and confirm the technical success of each procedure. The Neuwave system, which Ethicon claim is the microwave ablation market leader in the USA, is a minimally invasive system that enables physicians to effectively tailor ablations for lesions of varying shapes and sizes with consistency and control. A press release states that studies have shown microwave ablation has strong efficacy and a favourable complication profile, with most patients leaving the hospital the same day with a bandage at the probe insertion site.

Interventional radiologists earn higher salaries than diagnostic radiologists

Interventional radiologists earned higher salaries in the USA in 2018 than their colleagues in diagnostic radiology, according to the latest data from

Neuwave system

With an average annual salary of US$411,345, interventional radiologists had higher annual compensation than diagnostic radiologists, regardless of the latter's modality subspecialisation, according to the SalaryScan data. The top salary for diagnostic radiologists was for those who subspecialise in computed tomography (CT), with an average annual salary of US$396,907, followed by magnetic resonance imaging (MRI) subspecialists at US$395,328. The lowest paid radiology subspecialty was mammography, with an average annual salary of US$375,514. The survey also broke down salaries by region in the USA. Radiologists living in the US West North Central region had the highest average annual salary, at US$445,945, compared with an average annual salary of US$394,034 for North American radiologists of all experience levels, organisation types, and modality specialisations. The second highest earners were radiologists living in the US West South Central region, with an average annual salary of US$424,061. The lowest salaries were pulled in from radiologists working in the US New England region, with an average annual salary of US$363,264. For radiologic technologists, the salary hierarchy by subspecialty was slightly different. Interventional radiology technologists earned an average base salary of US$79,368 per year, compared to an average base salary of US$72,351 a year for technologists with no subspecialisation. Nuclear medicine technologists were the best compensated, with an average annual salary of US$80,779, and mammography technologists earned the lowest average annual salary, at US$69,382.

SIR 2019 Gold Medalists exemplify outstanding achievement in interventional radiology

The Society of Interventional Radiology (SIR) presented its highest honour, the SIR Gold Medal, to Alan H Matsumoto (see page 1), Daniel Picus and James B Spies during its 2019 annual scientific meeting (23–28 March, Austin, USA). These awards acknowledge distinguished and extraordinary service to SIR or to the discipline of interventional radiology. “The 2019 Gold Medallists exemplify the innovative and collaborative spirit

of interventional radiology through their research, mentorship, dedication to the advancement of the quality of medicine and patient care," says SIR 2018–2019 president M Victoria Marx, interventional radiologist at Keck Medicine of USC, and professor of clinical radiology and diagnostic radiology residency programme director at Keck School of Medicine of University of Southern California (USC), Los Angeles, USA. Matsumoto is professor and chair of the department of radiology and medical imaging at the University of Virginia, Charlottesville, USA, where he has been on faculty since 1991 and helped train more than 200 diagnostic radiology residents and 100 vascular and interventional radiology fellows. He developed and ran the core lab for the trial that led to the first US Food and Drug Administration (FDA)-approved abdominal aortic stent graft in 1999. A past-president of SIR and programme chair of the 2004 SIR Annual Scientific Meeting, Matsumoto has also served as an American Board of Radiology examiner, in committee and council chair positions at the American Heart Association, and as a member of the American College of Radiology Council Steering Committee and Board of Chancellors. Picus is a professor of radiology and surgery at the Mallinckrodt Institute of Radiology (MIR) at Washington University School of Medicine, St Louis, USA. There he established the interventional radiology section, serving as its first chief from 1987–2000. He then took on the role of division chief for diagnostic radiology until 2018. During his career, Picus became a member of the American Medical Association’s Current Procedural Terminology (AMA CPT) Editorial Panel. He delivered the Dr Charles T Dotter Lecture at the 2013 SIR Annual Scientific Meeting and has served SIR as Education and Annual Meeting Councillor, first editor of the Society of Cardiovascular and Interventional Radiology (SCVIR, now SIR) newsletter, and first deputy editor and second editorin-chief of SIR’s Journal of Vascular and Interventional Radiology. Spies is a professor of radiology at Georgetown University School of Medicine and chair of the department of radiology at MedStar Georgetown University Hospital in Washington, D.C, USA. Spies is recognised as an international authority on uterine artery embolization (UAE) for fibroids. He maintains an active UAE clinical practice, has performed extensive research in that area and continues to actively research outcomes from a range of fibroid therapies. He has published more than 100 scientific studies and given more than 400 invited presentations. In addition to serving as a trustee of the American Board of Radiology (ABR) for interventional radiology since 2016, Spies has served SIR in many roles, including SIR president from 2014–2015, SIR Foundation chair from 2006–2008, and as a member of numerous SIR committees.

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Market watch

Clinical News Peregrine catheter demonstrated 100% procedural success in postmarket clinical trial

Peregrine infusion catheter

The Peregrine System infusion catheter (Ablative Solutions) has demonstrated 100% procedural success in the Peregrine post-market clinical trial, new data presented during a late-breaking session at the 2019 Cardiovascular Research Technologies (CRT) meeting (2–5 March, Washington, DC, USA) attests. The Peregrine post-market study is a European multicentre, openlabel trial that evaluated the safety and performance of the CE marked Peregrine System infusion catheter using alcohol as a neurolytic agent in 45 patients with systemic hypertension. The efficacy endpoint of the study was met, with a reduction in mean systolic 24-hour ambulatory blood pressure of 11mmHg (±14 mm Hg, p<0.001) at six-month follow-up. Additionally, the average reduction in systolic office blood pressure was 18 mmHg (±21 mmHg, p<0.001). Antihypertensive medications were unchanged in 73% and reduced in 23% of patients at six months. The study demonstrated 100% procedural success, and the safety endpoint was met in 96% of patients. Two patients had major adverse events of periprocedural access site pseudoaneurysms, with major bleeding in one patient. There were no deaths or instances of myocardial infarction, stroke, or transient ischaemic attack. “The Peregrine post-market study showed efficient nerve ablation with the CE marked Peregrine catheter, resulting in significantly sustained reduction in both systolic and diastolic blood pressure at six months, with the vast majority of patients not requiring an increase in the number of antihypertensive medications during this time,” says Felix Mahfoud, of Saarland University Hospital, Homburg, Germany. The Peregrine system infusion catheter has received a Certificate of Conformity and has been CE marked for the infusion of a neurolytic agent (for example, alcohol) to achieve a reduction in systemic blood pressure in hypertensive patients.

Designed to be performed in a short and straightforward procedure with minimal sedation required, the Peregrine catheter is engineered to target nerves known to influence the body’s regulation of blood pressure. The delivery of a neurolytic agent—dehydrated alcohol in this study—directly to the space outside of the renal artery is intended to block the overactive signalling of the sympathetic nerves, a press release explains. The investigational Peregrine kit, which includes the Peregrine system infusion catheter (Peregrine catheter) and Ablative Solutions dehydrated alcohol, will be investigated in the TARGET BP clinical programme, which comprises two clinical trials. The global TARGET BP I trial in centres in the USA and EU is a blinded, randomised, sham-controlled study which will evaluate the safety and efficacy of the Peregrine kit in the treatment of patients with uncontrolled hypertension and who are taking two to five anti-hypertensive medications. Patient enrolment in the Target BP I trial is anticipated to begin soon. The recently initiated TARGET BP OFF-MED trial in Europe is a proof-ofconcept, blinded, randomised, shamcontrolled study evaluating the safety and effectiveness of the Peregrine kit for the treatment of patients with uncontrolled hypertension who are not taking anti-hypertensive medications. “Based on early clinical results using the CE-marked Peregrine catheter, we are excited to be embarking upon the pivotal TARGET BP I Clinical trial of the investigational Peregrine kit to evaluate safety and efficacy when used in the treatment of patients with uncontrolled hypertension in conjunction with antihypertensive medications,” says David Kandzari, coprincipal investigator of the TARGET BP I trial, and director of Interventional Cardiology and chief scientific officer at Piedmont Heart Institute in Atlanta, USA.

Mentice donates IR simulators to Rad-Aid

Endovascular therapy training provider Mentice has signed an agreement to donate its virtual reality-based simulators to humanitarian organisation Rad-Aid for use in interventional radiology (IR) procedure training in various resource-constrained regions of the world. Under the agreement, the Gothenburg, Sweden-based Mentice pledges to contribute simulator software, hardware and expertise to RAD-AID IR educational teams. Commenting on the agreement, Mentice CEO Göran Malmberg says “RAD-AID is doing an amazing job bringing the benefits of IR to

disadvantaged communities around the world. It is a great honour and a privilege to be working with RAD-AID helping improve patient care access and outcomes in these underserved communities.” Launched in 2008, RAD-AID is a 501c3 non-profit organisation committed to bringing radiology and imaging technologies and solutions to developing countries and medically underserved communities. “It is easy to forget,” adds Malmberg, “that for many people, even relatively cost-effective X-ray imaging remains a luxury. We at Mentice can make a real contribution by helping improve access and IR performance.” RAD-AID is active in over 30 countries worldwide, and encompasses over 10,000 volunteers from 100 countries, 73 universitybased chapter organisations, and an annual conference on global health radiology. “RAD-AID programmes are multidisciplinary and bring together innovative technology, infrastructureplanning, and educational initiatives. Such multidisciplinary cooperation is essential, and by working with Mentice, we can help bring effective IR programs to some of the world’s neediest patients,” says Daniel Mollura, founder and CEO of RAD-AID International.

Simulation software

FDA grant approval to initiate NanoKnife DIRECT clinical study

The US Food and Drug Administration (FDA) have approved AngioDynamic’s investigational device exemption (IDE) application for NanoKnife Irreversible Electroporation “Direct IRE Cancer Treatment” clinical study (DIRECT). The DIRECT Study supports a proposed expanded indication for the NanoKnife system in the treatment of stage III pancreatic cancer. In January 2018, the FDA granted the company’s NanoKnife system a breakthrough device designation under the 21st Century Cures Act.

NanoKnife

According to a press release, the NanoKnife system is a next-generation ablative technology that physicians have identified as an innovative treatment for pancreatic cancer. AngioDynamics state that this is evidenced by the 42 publications that document more than 800 patients who have been treated for stage III pancreatic cancer with NanoKnife technology from 2012 to 2019. The NanoKnife system received 510(k) clearance from the FDA for the surgical ablation of soft tissue in 2008. Unlike other ablative technologies, the NanoKnife system utilises lowenergy, direct-current electrical pulses to permanently open pores in target cell membranes and does not rely on thermal effects, the press release explains. These permanent defects in the cell membranes result in cell death. The treated tissue is then removed by the body's natural processes in a matter of weeks, mimicking natural cell death. AngioDynamics state that their DIRECT study will feature a “comprehensive data collection strategy” that will provide meaningful clinical information to healthcare professionals, support a regulatory indication for the treatment of stage III pancreatic cancer, and facilitate reimbursement for hospitals and treating physicians. The study is classified as a Category B IDE by the FDA, allowing participating sites to obtain coverage for procedures performed as well as related routine costs. The DIRECT study comprises a randomised controlled trial at up to 15 sites and a real-world evidence, next-generation registry (RWE) at up to 30 sites, each with a NanoKnife system treatment arm and a control arm. AngioDynamics expects each NanoKnife arm to consist of approximately 250 patients with an equal number of control patients. The primary endpoint of the study is overall survival. The randomised controlled trial component of the DIRECT study will illustrate the promise of the NanoKnife system by isolating variables in a controlled setting, says the press release. Recognising that results from a hyper-controlled setting do not always translate to clinical practice, the study also includes a RWE component to provide clinicians, patients, and payers with data generated in a real-world setting.

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Market watch

Product News Merit’s Embosphere microspheres receive expanded indication to control haemorrhaging in the peripheral vasculature The FDA has cleared an expanded indication of Embosphere microspheres (Merit Medical) for the embolization of blood vessels to occlude blood flow in the peripheral vasculature to control bleeding or haemorrhaging.

Embosphere microspheres (Merit)

The Embosphere microspheres are the first spherical embolic devices to be cleared for this use. According to Merit Medical, Embosphere microspheres have now received more indications for use than any other spherical embolic on the market. With this approval, Embosphere microspheres are now indicated for use in embolization of arteriovenous malformations, hypervascular tumours, symptomatic uterine fibroids, prostatic arteries for the relief of symptoms related to benign prostatic hyperplasia, and for controlling bleeding or haemorrhaging in the peripheral vasculature.

designed to longitudinally fracture plaque at lower inflation pressures compared to standard PTA and may allow for more controlled plaque fracture and less vessel recoil, even in calcified lesions. With the addition of the 0.014” guidewire platform, the device is available in both 0.014” and 0.035” solutions with sizes ranging from 2mm to 8mm in diameter and up to 300mm in length. “The deliverability, ease of use and expansion of the vessel with UltraScore Focused Force PTA Balloon are excellent,” commented William Bachinsky, director of the Cardiac and Vascular Interventional Program at UPMC Pinnacle. “The addition of UltraScore 014 Focused Force PTA Balloon will fit right in with our treatment algorithms for popliteal and infrapopliteal lesions.” Both UltraScore 035 and UltraScore 014 devices are CE-marked and have received 510(k) clearance by the US Food and Drug Administration (FDA).

Guerbet receives CE mark approval for SeQure and DraKon microcatheters for interventional imaging

SeQure and DraKon (Guerbet), two novel microcatheters for peripheral embolization procedures, are set for commercial launch in Europe. The devices have received the CE mark for the delivery of intra-arterial therapy and embolic materials into all peripheral vessels.

BD announces launch of UltraScore 014 focused force PTA balloon

BD has announced the launch of their UltraScore 014 Focused Force percutaneous transluminal angioplasty (PTA) Balloon. This marks the first scoring balloon with sheath compatibility as small as 4F on the US market. The UltraScore balloon is intended to dilate stenoses in the iliac, femoral, ilio-femoral, popliteal, infra-popliteal and renal arteries and for the treatment of obstructive lesions of native or synthetic arteriovenous dialysis fistulae. This device is also recommended for post dilatation of balloon expandable stents, self-expanding stents, and stent grafts in the peripheral vasculature. UltraScore is

Standard and anti-reflux catheters (Guerbet)

UltraScore 014 PTA balloon (BD)

The SeQure microcatheter is a reflux control microcatheter that, according to a press release, uses flow dynamics to create a fluid barrier designed to deliver more treatment to the target vessel and reduce the risk of non-target embolization, for less potential damage to surrounding tissue. It consists of side slits specifically sized to allow the outflow of contrast media, Guerbet describe, creating a fluid barrier around

the microcatheter to reduce microspheres reflux and assist delivery to the target vessel. The DraKon peripheral microcatheter is the same as SeQure but without the side slits. A press release claims it has been designed to optimise “pushability, flexibility and torqueability for improved trackability and highest performance standards”. Guerbet obtained both microcatheters as part of their acquisition of Israeli company Accurate Medical Therapeutics, announced in January 2018. The SeQure and DraKon microcatheters received FDA clearance on January 26, 2018 and are currently commercialised on the US market. They are also registered in Hong Kong, New Zealand and Thailand. The registration plan includes Australia, China, India, Japan, Korea, Singapore and Vietnam within the next two years. SeQure and DraKon are class IIb medical devices intended for use by interventional radiologists and interventional oncologists for the infusion of contrast media into all peripheral vessels and for drug infusion in intra-arterial therapy and infusion of embolic materials. They should not be used in cerebral vessels.

SIRT approved for routine commissioning on the NHS

National Health Service (NHS) England have announced that selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) microspheres will now be routinely commissioned for NHS patients with advanced colorectal cancer that has spread to the liver and is not responding to standard chemotherapies. The use of SIRT in the NHS was assessed by NHS England from January 2014 to March 2017, as part of their Commissioning through Evaluation (CtE) scheme and the results of the assessment were published by the National Institute of Care Excellence (NICE) and NHS England in October 2017. The findings were also published online as a scientific paper in the Journal of Clinical Oncology by consultant radiation oncologist Ricky Sharma (chair of radiation oncology, University College London, London, UK) and his colleagues in September 2018, which confirmed that the real-world experience of SIRT in the NHS is consistent with the published literature. Since 2017, NHS England has been considering the case for routine commissioning of SIRT, and they have reached the conclusion that the evidence base on SIR-Spheres resin microspheres (Sirtex) is sufficient to offer SIRT as a routine treatment for patients with colorectal cancer that has spread to the liver who meet certain criteria. In the Clinical Commissioning Policy paper: Selective Internal Radiation Therapy (SIRT) for chemotherapy refractory/intolerant metastatic colorectal cancer (adults), NHS England recommends that adults with chemotherapy refractory or chemotherapy intolerant unresectable, liver-only metastatic colorectal cancer that meet all of the eligibility criteria

will be able to be treated with SIRT using Y-90 microspheres.

SIRT microspheres

Patients with advanced bowel cancer will have to meet certain criteria to be eligible for the treatment on the NHS. Specialist liver centres in England which satisfy the criteria specified by NHS England will be able to routinely offer this procedure. “The decision by NHS England to locally commission SIRT from April [2019] is an enormous relief for patients with bowel cancer that has spread to the liver. These patients often need disease control within the liver and have limited treatment options. As long as patients meet NHS England’s clinical criteria for SIRT, treated in expert liver centres— there is likely to be benefit in controlling the liver spread,” comments Harpreet Wasan, consultant in medical oncology, Imperial Hammersmith Academic Health Trust, London, UK. Wasan was co-chief investigator for the FOXFIRE trial of SIRT in liver metastases. The liver metastases should be inoperable, and the disease should not be responding to standard chemotherapies. For patients with other cancers that may benefit from SIRT, such as primary cancers of the liver, the policy proposals are still being reviewed. Patients who do not qualify for this treatment by the NHS criteria may be able to receive SIRT by participating in a clinical trial, by submitting individual funding requests via their oncologist, or pay for it privately. “In specialist centres we have the possibility to treat patients with innovative treatments such as SIRSpheres Y-90 resin microspheres. It is great news that we now have the possibility to discuss this treatment option during the multidisciplinary team meetings for all patients who could benefit from it (meeting eligibility criteria)” states Jon Bell, consultant interventional radiologist at the Christie NHS Foundation Trust, Manchester, UK. Sharma says: “We are delighted by this announcement. Our study has confirmed that the real-world experience of SIRT as a cancer treatment in the NHS is consistent with the published data from other countries. There is still scope for improving access to this specialist treatment for patients with a variety of cancers, not just bowel cancer, and across all the nations of the UK, not just England.” “Patients in England with liver cancer that has spread from their bowel and who have exhausted other treatments, now have access to a therapy which can extend their survival,” says Vanessa Hebditch, director of policy at the British Liver Trust.

June

Market watch

Product News Biotronik expands peripheral portfolio with a new treatment tool for interventions in complex lesions

Biotronik has launched the Carnelian support catheter, designed to improve the access for treatment of tortuous and highly calcified lesions. Carnelian support is indicated for the exchange and support of guidewires into peripheral vasculature. Up to 40% of patients with symptomatic peripheral artery disease present with a chronic total occlusion (CTO), a press release states. If just a guidewire is used to cross the CTO, the release continues, there is a risk it will buckle once it encounters resistance by atherosclerotic plaque, stopping it from advancing further. Carnelian support is designed to prevent this buckling by enhancing guidewire control and allowing CTO crossing.

Carnelian support comes in five models and has a low tip profile of 1.6 and 1.8 French. Its tungsten braided shaft and platinum marker contribute to high kink resistance and excellent radiopaque visibility. According to the company, the catheter’s multisegment shaft design provides a smooth transition from the soft distal tip allowing trackability to the stiffer proximal part that ensures additional push. “I was impressed by the Carnelian support and Japanese crossing technique that enable the treatment of very complex lesions, as I recently had a chance to demonstrate in live cases at CLIC 2019,” explained Marco Manzi, (Policlinico Abano Terme, Italy). “The Carnelian support catheter is the right tool to tackle the most challenging crossings even in below-the-ankle arteries.” This product launch marks the start

Carnelian support catheter

of a partnership between Biotronik and Tokai Medical Products.

FDA grants 510(k) clearance to software suite for molecular imaging and molecular radiotherapy dosimetry

The US Food and Drug Administration (FDA) has granted 510(k) clearance to the company DOSIsoft to market its Planet Onco Dose software, for its oncology and Yttrium-90 (Y90) microsphere selective internal radiation therapy (SIRT) 3D dosimetry components.

www.etconference.org

22–25 July The Society of NeuroInterventional Surgery (SNIS) 16th Annual Meeting Miami, USA www.snisonline.org

8–10 August SOBRICE 2019: Brazilian Society of Interventional Radiology and Endovascular Surgery São Paulo, Brazil www.congressosobrice.com.br

7–11 September Cardiovascular ad Interventional Radiological Society of Europe (CIRSE) Annual Meeting 2019 Barcelona, Spain www.cirse.org

23–27 September ESVS: European Society for Vascular Surgery annual meeting Hamburg, Germany www.esvs.org

11–13 October The Symposium on Clinical Interventional Oncology (CIO) Hollywood, USA

31 October–2 November Aortic Summit 2019 Lugano, Switzerland www.aorticassociation.org

4–7 November VIVA: Vascular Interventional Advances Las Vegas, USA www.vivaphysicians.org

13–15 November British Society of Interventional Radiology (BSIR) Annual Meeting 2019 Manchester, UK www.bsir.org

www.interventionaloncology360.com

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ed for increas are calling n computer Clinicians and betwee engineers collaboration biomedical ists as machine scientists, oncolog more to play a interventional radiology is posited learning role in interventionalg the initial prominent ures, from informinselection (IR) proced through to patiente. In a diagnosis, cedural guidanc Journal The gy and intrapro published in tional Radiolo Forum recent primer Leaders Wang and r and Interven at the Vascular of Vascula Letzen, Clinton School of Panellists Leaders Forum (JVIR), Brian , all of the Yale outline the of the Vascular hosted floor the USA, n DC, USA), FDA peaking from Julius Chapiro e learning New Haven, (VIVA), March, Washingto Advances (VLF; 1–2 Medicine, of JAHA paper, tions of machinwhere c review Interventional has “reviewed most ing In the original conducted a systemati a future by Vascular clinical applica , who trials investigat the al visualise -coated Katsanos et randomised controlled Donna Buckley, ded them to be approved” (AI) enables , for IRs, and or paclitaxel first 28 investigator intelligence In angioplasty and recommen perspective: “Our analysis of ne to become artificial to these devices body’s e of -coated balloon popliteal arteries. of the discipli the regulatory ysis was, I think, similar ss, paclitaxel in the femoral and/or nt claudication) were elevation ’s words, “the epitom explained Nonethele stents meta-anal metal the bit surprised. seriously.” (89% intermitte in Chapiro was all-cause response to medicine”. were a little very all, 4,663 patients safety measure points. “Risk else’s: we personalised n that we took primarily everybody time The primary outline their informatio

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g different analysed. AGUES learning with a random analysed at it was compellinFDA evaluation is focusingwith data the g machine AND COLLE patient death, differences were pooled trials integratin LETZEN The ongoing ent, AI can risk d controlled in IR: “By wrote. preliminary ratios and randomise evidenced vision of AI , treatment, and managem uality the authors on US-based can validate. The FDA’s reported by trials have the highest-q effects model,” body ed controlled signal significantly into diagnosis s to provide that meets regulatory the mortality said the FDA’s physician Previous randomis balloons and stents lesion confirmed efficient manner Whereas empower -coated and target at VLF, Buckley (PMA) trials evaluation care in an that paclitaxel of vessel restenosis al. Speaking t approval tal clinical practice. personalised ysis interventions. Katsanos et rates pre-marke of modern on incremen extremity ed of five US reduce the it [the meta-analall after lower the demands traditionally focused (28 randomis own analysis to where we feel like for a new has d between revascularisationall-cause patient death t we still have , AI allows medicine was similar research, has “converge a statistical glitch—bu rapidly analysed vs. all the statistical At one year, not 4,432 patients) hypothesis-based‘big data’ can be have arms (2.3% n as well with findings] is trials with and control where us informatio years controlled that may otherwise paradigm -coated devices death at two this incongruo have gone through.” new insights USA) called was , trials.” paclitaxel ng All-cause 17 ve we uncoveri risk of death). trials with 2,316 patients) of prospecti the data analysis that Peter Schneider (Honolulu of 2.3% crude g to review the Society vs. control required decades Also at VLF, ed controlled is undertakin paclitaxel meeting of year features deaths (12 randomis in case of that the FDA and spot on”. [SIR] this The annual vs. 3.8% [35 the process tly increased providers Radiology interventional rward patients] ional significan healthcare straight-fo 1,397 eeded-to, in to Intervent a letter deaths in number-n “judicious learning IR summit FDA issued evaluating the “recent (7.2% [101 risk of death, Long-term its first machine and the BOLD-A Indeed, the long-term it was CI: 19–59]). patients] crude April, New ed session, stating that for increased - in 919 NYU (24 patients [95% years (three randomis oncology in January the potential or paclitaxel [NNH]: 29 Stanford and five in y and ethical by to balloon harm up n regarding further regulator initiated death informatio increased paclitaxel-coated pliteal artery for will tackle risk of all-cause with 863 patients) for AI research. on page 4 following York, USA) in 529 patients] mortality” trials in the femoropo(PAD). The agency g to data use Continued deaths out controlled treatments of death, (14.7% [78 issues pertainin crude risk eluting stent arterial disease FDA case of paclitaxel in 334 patients] peripheral ongoing, the treated deaths patients with the data review was vs. 8.1% [27 ce” for patients [95% CI: 9–32]).that meta-regression 2 that said that whilst d surveillan in the letter on page NNH: 14 patientscolleagues wrote ds “continue body stated for Continued recommen Katsanos and . The regulatory to outweigh the risks” with paclitaxel continue the “benefits indications. it believes within their approved devices

According to a company press release, Planet Onco Dose is a comprehensive software platform dedicated to medical diagnosis aid, therapy response assessment aid, contouring for radiotherapy, and internal dosimetry computation, using molecular imaging modalities. It is a modular software suite comprised of two main elements: an oncology module (Planet Onco) and a dosimetry module (Planet Dose). The former, the oncology module, has the core system features: comprehensive reviewing of multimodal molecular image series (CT, MRI, PET, SPECT), fusion and registration, automatic and semi-automatic contouring of regions of interest, tumour segmentation, quantification, tumoural activity monitoring, and therapy response assessment. The dosimetry module includes 3D personalised voxelbased internal dosimetry computation dedicated to molecular radiotherapy (MRT). CE marked since 2016, Planet Onco Dose is the first fully integrated imaging and personalised 3D dosimetry platform for radionuclide-based therapies.

Calendar of events 26–29 June European Conference on Embolotherapy (ET) 2019 Valencia, Spain

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