Interventional News Issue 76 ROW

November 2019 | Issue 76 Kyaw Zay Ya:

Establishing IR in Myanmar Page 10

Steve Ferrara:

IR on the frontline

Ricardo García-Mónaco: Page 26

Interventional oncologists urged to embrace the clinical model at CIRSE 2019 To cement interventional oncology (IO) as the fourth pillar of cancer care, Govindarajan Narayanan (Baptist Hospital, Miami Cardiac and Vascular Institute, Miami, USA) proposed interventionalists embrace the clinical model and collaborate with oncology colleagues at all levels of organisation: from participating in multidisciplinary tumour board discussions, to engaging with international societies. He delivered his ideas on the future of IO in his Josef Roesch Lecture at the annual scientific congress of the Cardiovascular and Interventional Radiological Society of Europe (7–11 September, Barcelona, Spain).

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n his honourary lecture, “Pathways and challenges to innovation in interventional oncology”, Narayanan began by quoting Leonardo da Vinci: “Simplicity is the ultimate sophistication”. He explained: “IO has grown from an occasional procedure performed by an interventional radiologist on patients who have exhausted treatment options, to a specialty today that offers simple and elegant solutions to complex medical problems. It has the elements of surgery, medicine, and radiology, wrapped along with cutting-edge imaging technology and precision, impacting the lives of cancer patients in a positive way. An amazing transformation in just four decades, which has now made us the fourth pillar of cancer care, along with surgery, medical oncology, and radiation.”

A brief history of interventional oncologic interventions

Providing an overview of the history of IO, Narayanan selected a few key moments from the last four decades: 1978: First transarterial embolization for hepatocellular carcinoma (HCC) was performed by Ryusaku Yamada in Japan 1982: First ablation (with ethanol) for parathyroid mass was performed by Luigi Solbiati in Italy 1983: First ablation (with ethanol) for HCC was performed by Tito Livraghi in Italy 2002: TACE shown to be superior to best supportive care for unresectable HCC in a randomised controlled trial (RCT) from Jordi Llovet (Barcelona, Spain) et al and Chung-Mau Lo (Hong Kong, China) et al 2003: An RCT from Riccardo Lencioni (Pisa, Italy) et al concluded that radiofrequency ablation (RFA) is superior to percutaneous ethanol injection (PEI) with respect to local recurrence-free survival rates for the treatment of small HCC in patients with cirrhosis 2010: A meta-analysis from Giacomo Germani (London, UK) and colleagues showed that RFA improves survival compared to PEI for HCC, particularly for tumours larger than 2cm 2014: In a comparison of an IO procedure with a surgical technique, Konstantinos Katsanos (Patras, Greece) et al found that thermal ablation for the treatment of small renal tumours provided long-term oncologic outcomes similar to surgical nephrectomy,

Govindarajan Narayanan

but with a reduced complication rate and limited decline of renal function 2018: A systematic review and meta-analysis from Martijn Meijerink (Amsterdam, The Netherlands) et al, awarded the Cardiovascular and Interventional Radiology (CVIR) Editors’ Medal 2019, argues in favour of ablation over chemotherapy alone for the treatment of small, unresectable colorectal liver metastases, stating, “Further randomised comparisons of ablation to current-day chemotherapy alone should therefore be considered unethical”

Challenges to interventional oncology

“Growth of this kind has its own challenges,” Narayanan said, referring to this increase in procedural number and complexity, before going on to detail those challenges specific to IO. He expanded: “Our clinical goals have now become more ambitious. We started by managing cancer-related symptoms, offering palliative solutions, and then helping our colleagues to either bridge or downsize patients to surgery, and now we are looking at the potential for curing certain cancers.”

In light of these greater aspirations, he highlighted Continued on page 2

Profile

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Rebuttal from IR community as AUA continues not to recommend PAE outside of clinical trials The American Urological Association (AUA) has published guideline amendments in the September issue of The Journal of Urology, but has not changed its stance on prostate artery embolization (PAE). The AUA does not recommend PAE for the treatment of lower urinary tract symptoms/ benign prostatic hyperplasia (LUTS/BPH) outside the context of a clinical trial, a recommendation attributed to the expert opinion of a panel of urologists. This news is unwelcome to the interventional radiology (IR) community, which has been advocating for the procedure’s acceptance by the wider medical world. US interventional radiologists were awaiting these guideline amendments hopeful that new recommendations would better reflect the conclusion of multiple IR societies that PAE is a safe, effective, minimally invasive treatment option in select BPH patients.

THE GUIDELINES, AUTHORED by Harris Foster (Linthicum, USA) and colleagues, cite the following as their rationale: “High-level evidence remains sparse, and the overall quality of the studies is uniformly low.

Three randomised controlled trials (RCTs; n=247) with heterogeneous methods and results.

Concerns regarding radiation exposure, postembolization syndrome, vascular access, technical feasibility, and quality control at lower volume centres.

PAE should only be performed in the context of a clinical trial, comparing to sham will account for placebo effect.”

SIR urges AUA to reconsider their “unnecessarily restrictive” recommendation

This has sparked a response from US interventional radiologists. In May this year, 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) published a position statement in the Journal Continued on page 2

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Top stories

November 2019 | Issue 76

Interventional oncologists urged to embrace the clinical model at CIRSE 2019 Continued from page 1

investment as one of the specific challenges faced by interventional oncologists today. “Studies of any kind require investment,” he said, “and in today’s climate, this is quite a challenge around the world.”

Enrolment was another issue mentioned: “Our oncology patients usually do not belong to us, and are referred to us by surgical colleagues or medical oncology colleagues, which makes it difficult to enrol these patients when they have competing trials, so you would have to make a compelling case for them to enrol these patients into our trials.”

In addition, Narayanan pointed out that, unlike in medical oncology, where “a pill is the same across the world”, a lot of IO procedures are operator-dependent.

Indeed, he called standardisation the “Achilles’ heel” of IO: “If you take a TACE procedure, there is significant variation from country to country, and sometimes even within the same practice group”.

A further challenge faced by interventional oncologists is the rapid evolution of devices.

“Sometimes,” Narayanan said, “they evolve faster than what is required.” As an example, he recounted the shrinking of drug-eluting embolics in recent years.

When the PRECISION V randomised controlled trial—comparing the use of drug-eluting embolics and TACE with conventional TACE (cTACE) for the treatment of HCC—was started, the investigators were using embolics between 500–700µm. Whilst the RCT was still being conducted, interventionalists started using particles 300–500µm. This trend continued: from 300µm, to 75µm, to 40µm. Narayanan ultimately said: “While we [interventional oncologists] were getting to be familiar with the 75µm size, radio-opaque beads were already out.”

In the USA, many devices are approved by the US Food and Drug Administration (FDA)’s 510(k) pathway, which Narayanan described as “a blessing and a curse”. He elaborated: “A blessing, because it brings new technology to the market, but a curse because a lot of times the approvals are given without a specific indication, and that leads to a lack of reimbursement.

This leads insurance companies to deem some promising technologies as experimental, and sometimes could lead to an early demise of promising technologies.”

Lastly, Narayanan delineated challenges to the clinical model. “While we have made significant strides in bringing the clinical model into our day to day practice, we still face significant challenges,” he

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said. He explained how the clinical model pays low relative value units and reimbursement for time in clinic. There is also no reimbursement for time spent in tumour board: “It becomes a challenge to explain to our colleagues if you are in a multidisciplinary group with DR [diagnostic radiologists] that this is very important and key to improving our IO practice”. Drawing from his experience arguing for an IO clinic in his own institution, Narayanan described establishing the clinical model as an “uphill battle”, where “you have to explain in front of a committee of clinicians from various specialties as to why you need a clinic, because you are ‘just a radiologist’.”

Narayanan’s proposed solutions

“So how does IO compete with these challenges, stay relevant, and make progress?” Narayanan asked. He proposed the following solutions: Global collaboration: “This has been facilitated by our societies, SIR [Society of Interventional Radiology] and CIRSE. This should continue. When we collaborate with our colleagues from across the world, we can come up with bigger swathes of data, in a shorter period of time, and better understand the technology that we use.”

Standardising IO techniques: “While this has been shown to be difficult, it has been done, at least with Yttrium-90 (Y-90), and if we can do it there, I think we should make more of an effort to standardise our techniques across the globe.”

Coming up with meaningful endpoints in trials: “Overall survival is important, but a lot of what we do could also have other endpoints, such as quality of life.”

Registries: “A registry is a great tool, when it is properly planned, along with trials, where we can compare the devices that we use, or even collect data on a single device, to make sure that it delivers what it promises.”

Working with industry and regulatory bodies: “If we have an accepted IO clinical trials framework integrated into the regulatory and approvals process, that would help when we roll out new technology.

Having a controlled roll out of new devices, first studying the safety in a Phase 1 manner, and then following that with Phase 2 and Phase 3 studies.

Finally, partnering with industry for investment for well-planned registries.”

Explain the value of IO to the institution: “We bring a significant value to the clinical side, as opposed to our diagnostic colleagues, where we can influence the patient’s length of stay, there is a lot of downstream revenue attached to interventional radiology.”

Being part of a multidisciplinary tumour board: “I cannot stress enough the importance of tumour board participation, as IO is a team sport. We definitely need to work with our colleagues from other parts of oncology to have a successful practice.”

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Rebuttal from IR community as AUA continues not to recommend PAE outside of clinical trials Continued from page 1

of Vascular and Interventional Radiology (JVIR) concluding that current evidence supports the use of PAE for the treatment of LUTS for the symptoms of BPH in appropriately selected patients. The AUA has not accommodated this viewpoint in their latest guidelines amendments.

Speaking in her capacity as president of the SIR, Laura Findeiss (Atlanta, USA) provides this newspaper with the following statement: “The AUA’s recent guideline amendment to explicitly not recommend the use of PAE for the treatment of BPH outside of the context of a clinical trial fails to acknowledge the medical evidence supporting the safety and efficacy of this minimally invasive treatment option. It also fails to recognise the US Food and Drug Administration (FDA) approval of embolization devices for this use.

“SIR’s 2019 multisociety position statement on the application of PAE cites multiple randomised controlled trials and comparative studies of PAE versus the gold standard urologic treatment of LUTS caused by BPH—TURP, or transurethral resection of the prostate. These studies show that symptomatic improvement following PAE approaches are seen after TURP, while maintaining a superior safety profile. The multisociety statement’s authors cite dozens of other prospective and retrospective cohort studies and metaanalyses that also support the safety and efficacy of PAE as a treatment option for LUTS caused by BPH. “Due to the strong nature of the evidence supporting PAE, the societies endorsed PAE as ‘a definitive treatment option for multiple underserved patient groups, who may not have satisfactory urologic treatment options’. These patient groups include older patients with multiple medical conditions, patients with very large prostates, patients with bleeding from the prostate, patients with long-term bladder catheters, patients who cannot stop anticoagulation therapies, and patients who desire to preserve sexual function.

“Furthermore, the National Health Service (NHS) in the United Kingdom has also acknowledged the strength of the evidence and supports the use of PAE to treat BPH symptoms in appropriately selected patients.

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Urology guidelines

November 2019 | Issue 76

Rebuttal from IR community as AUA continues not to recommend PAE outside of clinical trials Continued from page 2

“AUA, however, has ignored the peer-reviewed data supporting PAE as appropriate for the sizeable population of men who are poor candidates for surgery and those who seek a nonsurgical, prostate-sparing option to treat their BPH symptoms. While AUA reasonably calls for increasing the level of evidence for the standard patient, the abundance of positive data moves PAE significantly beyond experimental. What is yet to be determined is where this therapy fits in the treatment algorithm. It is our hope that the urology community will partner with IR on behalf of patients in completing such recommended studies. Despite the AUA position, PAE is supportable as an evidence-based treatment modality that will remain available to men with LUTS secondary to BPH who seek this therapy.

“We urge the AUA to reconsider this recommendation, which is unnecessarily restrictive and is not founded in evidence. The SIR and the IR community stand ready to partner with urologists to ensure provision of the treatment that is most appropriate for each patient based on his clinical situation, risk tolerance, and priorities.”

While AUA calls for more Level 1 evidence, some interventional radiologists claim this is “an impossibility”

In April this year, an SIR Foundation-sponsored research consensus panel for PAE was convened with urologists from the AUA with the aim of positively establishing the procedure in the urology society’s guidelines. The meeting was chaired by Clifford Davis (Tampa, USA) and Jafar Golzarian (Minneapolis, USA). Davis informs Interventional News that since their conversation in the spring, where the AUA made it clear that it wanted additional Level 1 evidence, nothing has changed.

He is therefore “unsurprised” by the consistent recommendation of the AUA to not recommend PAE outside of the context of clinical trials, and is planning funding applications for a randomised controlled trial aimed at producing Level 1 data.

There are multiple barriers to an RCT involving PAE, however. Firstly, the research consensus panellists need to decide on a study design: PAE versus a sham, or PAE

Prostate artery embolization (PAE) is a minimally-invasive treatment for lower urinary tract symptoms attributed to benign prostatic hyperplasia (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 (LUTS) that impair their quality of life. This led Justin McWilliams (Los Angeles, USA) et al to call BPH and ensuing lower urinary tract symptoms a “significant health issue affecting millions of men” in the Journal of Vascular and Interventional Radiology (JVIR) in May this year. Here is a timeline of PAE recommendations over the last decade:

a surgical procedure”. A follow-up meeting to the April research consensus panel is to take place later this year to decide on which surgical procedure this may be.

“This sounds very simple”, Davis says, “but it is complicated because the patients that do best with PAE may have comorbidities for surgery. We feel that the patients who do best with PAE have bigger prostates in general, over 80g, which is not the typical patient seeking surgery. We have to compare PAE to a surgical technique that is generally accepted for a similar population. In my opinion, I think we should do an RCT [on either PAE] versus simple prostatectomy, or versus Holmium

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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.

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After initial reports on PAE in humans from João Pisco (Lisbon, Portugal) and Francisco Carnevale (Sao Paulo, Brazil), the AUA published guidelines in 2010 for the management of BPH, but failed to mention PAE.

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Continued on page 6

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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 PAE.

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In 2014, the SIR published a position statement, authored

by McWilliams et al, which concluded that “PAE for BPH is a novel and promising therapy that appears safe and efficacious based on short-term follow-up”, but that additional investigation was needed before PAE could be accepted into routine therapy.

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History of benign prostatic hyperplasia treatment recommendations

We urge the AUA to reconsider this recommendation, which is unnecessarily restrictive and is not founded in evidence.”

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Timeline

versus surgery. There are concerns with conducting a trial of PAE against a sham due to crossover issues.

Current guidelines from the AUA are based on RCTs with at least 12 months of data, and many had up to five years of follow-up. Patients randomised to a sham procedure or to PAE may move across to the opposite cohort before the 24-month mark, and could therefore cofound the data, but this would still be considered as low Level 1 evidence.

Furthermore, as RCTs are so expensive, Davis explains that “industry or our national associations [in the USA] cannot afford to fund them”. Instead, interventional radiologists are looking to the National Institutes of Health (NIH) for funding. Four years ago, following an earlier SIR-sponsored research consensus panel meeting, a decision was made to apply for NIH funding for a PAE versus sham study, but this was rejected. With this precedent in mind, Davis favours “building a large, multicentre RCT comparing PAE to

laser.” This latter option is a transurethral procedure that enucleates the prostate through the urethra, and is usually performed on men with larger prostates.

“I also think”, Davis elaborates, “an RCT trial with PAE should focus on patient satisfaction, including symptoms, quality of life, pain, and morbidity, and should not solely focus on flow rates and post-void residual (PVR) urine volumes, which are considered to be quantitative measures of surgical success. If PAE is found to be durable but less efficacious (regarding flow rates and PVR) but with fewer complications, lower costs and reduced hospital time compared to surgical options, then I would hope the AUA would reconsider it in its guidelines for certain populations.

“In all other RCTs of surgery versus a control group, there was noted a significant drop in International Prostate Symptom Score (IPSS) even without therapy.

This is a major argument of the urology community against our current data with small samples sizes and lack of long term follow-up.” In terms of data regarding the safety of radiation dose during PAE, Davis says that he and his team are currently working on publishing data from their centre in response to this concern raised by the PAE Research Consensus Panel.

Commenting on the status of the development of an RCT involving PAE, Ari Isaacson (Chapel Hill, USA), a co-author of the multisociety consensus document published in May, says: “The initial design and protocol and attempt to get funding [from the NIH] is underway, but it is a slow process. In the meantime,” he explains, “I think that a lot of urologists are going to feel handcuffed, because they do not feel that they can go against their society’s guidelines, and therefore there are going to be a lot of patients who either are not told about PAE or who are going to be dissuaded from pursuing it due to these guidelines.”

Even with funding, an RCT may not be feasible due to patient-driven issues with enrolment. Riad Salem (Chicago, USA), another co-author of the multisociety position statement and an outspoken advocate of PAE, explains to this newspaper why this is the case: “An RCT has been tried, and it has been rejected, not by the medical community, but by the patients that would enrol. The BEST trial, while initiated as an RCT, was subsequently revised to a prospective comparison to TURP, because patients are not willing to be randomised to TURP. Patients are looking for minimally invasive treatments—so an

Between 2014 and 2019, over 2,000 patients have been studied in PAE-pertaining publications, and there have been three RCTs comparing PAE to TURP. The longest duration of follow-up now exceeds five years.

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An FDA review in 2017 concluded that “the probable benefits outweigh the probable risks for this indication”.

Continued on page 6

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Benign prostatic hyperplasia

November 2019 | Issue 76

Rebuttal from IR community as AUA continues not to recommend PAE outside of clinical trials Continued from page 4

RCT randomising TURP versus PAE is effectively an impossibility. It is not feasible and not constructive to wait for this clinical trial that will never happen.”

Nabeel Hamoui, one of three physicians dualtrained in urology and interventional radiology in the USA (Brooksville, USA) agrees with Salem. Hamoui expands, “I have seen this in my own experience at Northwestern. If you sit a patient down and say ‘we can do this therapy called PAE, which has fewer side effects, where you most likely do not need a catheter for more than a day, if that, and your recovery time is essentially zero, and if it fails, you can always have the other treatment option’, it is going to be very difficult to enrol enough patients into the TURP or surgery arm of an RCT. How do you accumulate Level 1 data if the patient becomes the rate-limiting factor?”

However, Isaacson tells Interventional News that the AUA was unmoved by discussions with interventional radiologists concerning past attempts to get US RCT data on PAE. “We tried to suggest alternatives as far as what types of data we could get”, he explains, “but despite our, I think solid, arguments, the reply was that unless there is RCT data, the AUA will not consider PAE as part of their guidelines. I think this methodology is flawed—their unwillingness to look at studies of other types excludes most of the evidence available that shows PAE is safe, so I think their evaluation of the procedure is limited. In my view, this is narrow-minded.” This difficulty with accumulating Level 1 data on PAE, and the insistence of the AUA that interventional radiologists provide evidence from a US RCT investigating the procedure, has led to a “stalemate”, in Salem’s words.

Multidisciplinary cooperation called for to break the stalemate

As the US healthcare system operates on a fee-forservice model, one criticism levelled against either side in a dispute about procedural choice is that, instead of fighting for the best patient outcomes, individuals are fighting to protect their paychecks. Hamoui explains, “This is the reality of the US healthcare system. Unlike the NHS [in the UK], our system is

based on the intensivity of care, not outcomes per se.

As a urologist, if my practice is largely BPH-based, and I get paid to do surgery and treat them, then I am not going to want to give that up because that will affect my bottom-line. The opposite is also true: if an interventional radiologist aggressively markets PAE as the ultimate procedure, and recommends it over TURP and prostatectomy in a vast majority of cases, then they are doing so because they want money.”

However, Timothy McClure (New York, USA), a second dual-trained urologist/interventional radiologist in the USA and another co-author of the multisociety consensus position statement, says that urologists are acting solely on behalf of the patient: “I think the AUA is just being overly cautious, in part because of a lack of understanding of PAE. PAE is technically challenging, and they do not want problems arising in their patients.

The guidelines are established to protect patients, so the bottom line is that they are trying to protect patients from having a procedure done that either will not make a difference or will potentially harm people. In fact, most urologists I have spoken with think PAE is a good option

There is distrust in the USA, because in an RCT design by definition one specialty will lose patients.” for certain patient populations. I think their concerns stem from a lack of understanding of what PAE is and what interventional radiologists can do. They view this as a technically challenging procedure that requires a certain level of skill which may not be applicable to the entire IR community. PAE is a complex case but skilled interventional radiologists do complex cases on a daily basis. Their concerns over radiation, complications, and side effects suggest a lack of understanding of PAE. These concerns could have been addressed by having an interventional radiologist participate with the guidelines.

It is unfortunate that the AUA did not include a

representative from IR.” Davis likewise sympathises with the AUA guidelines committee, saying: “Some have negative feelings against the AUA; I feel differently. They hold their standards for their recommendations based on Level 1 data. They have held every other surgical procedure to that same level.

It is just more difficult to compare a procedure across specialties. There is distrust in the USA, because in an RCT design by definition one specialty will lose patients to the other, which could introduce subspecialty bias during patient selection into the trial.”

The AUA guidelines are not all based on Level 1 evidence, though. For example, they state that “Water vapour thermal therapy may be offered to eligible patients who desire preservation of erectile and ejaculatory function”. This is a conditional recommendation, based on Grade C evidence. Grade C means “Low quality evidence: observational studies that provide conflicting information or design problems (such as very small sample size).” However, Davis notes that, although the evidence is marked as Grade C for this recommendation, it is based on an RCT of a sham versus therapy with three months crossover, and that this trial now has follow-up to two years.

“PAE is not alone in having heterogeneous outcomes”, Salem says. “If you look at a lot of data in urology, that too is heterogeneous. Heterogeneity is unfortunately a reality in medicine. Per the AUA guidelines, urologists should only offer robotic prostatectomy if they possess the necessary skillset. Why could that recommendation also not be made for PAE?” Hamoui points to the urology procedure transurethral nuclear ablation, TUNA, highlighting its obsolescence.

“We ourselves have done procedures that are now in the dustbin of urology”, he comments. “Many of those procedures that people thought were cure-all, and that were advocated for by some of the more prominent names in urology and pushed by industry, were largely financially driven, had poor evidence, and in five to seven years completely failed. The nuclear ablation machine in the practice where I work is now collecting dust in the corner. We no longer use it due to bad outcomes, but when it was recommended, I do not think that was based on Level 1 evidence.”

Salem urges urologists to understand that PAE is not in competition with TURP or prostatectomy. “All interventional radiologists are saying,” he remarks, “is that PAE should be part of the discussion, and one of the Continued on page 8

Timeline

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In June 2017, 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.

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continued from page 4

The BSIR and the British Association of Urological Surgeons (BAUS) worked together to coordinate the UK ROPE study.

This compared embolization to conventional prostate surgery. The final results were presented at the 2017 annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 16–20 September, Copenhagen, Denmark), and found embolization provided a clinically and statistically significant

improvement in symptoms and quality of life for men with an enlarged prostate.

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In the UK, NICE determined in Spring 2018 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).

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In the USA, the AUA updated their guidelines in 2018, and briefly mentioned PAE: they did not recommend the procedure’s use outside of a clinical trial. The AUA called for additional sham trials to account for possible placebo effect. These guideline amendments were published in print in the September 2019 issue of The Journal of Urology (see page 1).

11 Tiago Bilhim (St Louis Hospital, Lisbon, Portugal) announced at GEST 2019 (Global Embolization Cancer Symposium Technologies; 9–12 May, New York, USA) 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.

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Prostate artery embolization

November 2019 | Issue 76

Rebuttal from IR community as AUA continues not to recommend PAE outside of clinical trials Continued from page 6

treatment options. Nobody is saying that anything should be replaced. Let the patient participate in the decisionmaking process. By urologists’ own admission, many of their treatments do not really work in glands over 80g. Most of their trials exclude glands larger than that volume. Glands this size or larger are the ideal candidate for PAE. So we are filling a niche, a treatment gap, that exists. To me, it is short-sighted to acknowledge there is a difficulty in treating larger glands, exclude them from urology studies, and then dismiss PAE.” That interventional radiologists wish PAE to exist within the current treatment algorithm is something many are eager to highlight. “The key thing that I want to get across is that PAE provides a great addition to the BPH treatment algorithm”, Isaacson articulates.

“It does not replace the current surgical therapies, but it does provide a nice alternative to certain patients: those with very large prostates, those on anticoagulation medication, or patients with surgical comorbidities.”

“PAE is radically different from any of the urologic treatment modalities”, Hamoui says. However, he explains that this can be a hindrance as well as a positive.

“In vascular surgery and IR, there is a huge overlap, so if vascular surgeons were to come up with new guidelines, they would have a lot of legitimacy because they understand IR procedures. For me, having the dual perspective [of urology and IR], I can understand that the treatment options sit alongside each other. I do not think urologists fully understand the benefits of the procedure.”

Hamoui believes urologist education about PAE is critical. He, alongside McClure, advocates for the involvement of interventional radiologists on the AUA

guidelines committee when discussing treatment options for BPH. Speaking at urology conferences is another method used by interventional radiologists to reach out across specialty borders. Salem gave a talk at a recent meeting of the Chicago Urologic Society, which reportedly helped diminish their scepticism of PAE, and aided the attending urologists’ understanding of which patients would and would not benefit from the procedure.

Publishing in urology-specific journals would also be an effective communication tool for interventional radiologists to communicate to urologists, suggests Isaacson. However, he reports that this is challenging: “We have attempted to [publish in a urology journal] several times; it is very difficult to get a PAE paper in a urology journal”. Salem, who is one of few US interventional radiologists that has published a PAE paper in a urology journal, supports this assertion, commenting, “In my 20 years of publishing over 330 papers, getting published in a urology journal was the most difficult, challenging, controversial process I have ever been through. The captious reviews were rude, insulting, and, worst of all, replete with emotional bias. We tried several

Until the loudest, most cynical voices are excluded from the discussion, this vitriolic debate will never end.”

First prostate artery embolization performed in Nigeria Hammed Ninalowo (Lagos, Nigeria) and Scott McLafferty (Columbus Radiology Corporation, Cincinnati, USA) performed the first prostate artery embolization (PAE) in Nigeria on 29 August 2019.

T

he patient was a 77-year-old man with a long history of benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS), according to Ninalowo and McLafferty, and was initially seen for a consultation in July 2019. Describing the patient’s condition prior to treatment, the interventionalists tell Interventional News that, “A few months prior, he had developed acute urinary retention, necessitating placement of a suprapubic catheter. Since that time, he had a significant worsening in his quality of life due to catheter dependence. The presence of the catheter caused him both significant physical and emotional distress, with the patient regressing into a state of depression, and refusing to have guests around his home. Due to a complex medical history including a prior coronary artery bypass surgery, prostate surgery was not an option.”

Ninalowo and McLafferty say they are “proud” to have performed the first

PAE in Nigeria, and to help this patient.

“At the time he was seen in clinic”, they recount, “it was clear he was desperate for a solution and prepared to leave Nigeria to find one. However, with [the] continued awareness of local physicians and the possibilities of interventional radiology, he was sent to us for consideration of minimally invasive PAE.” PAE is a minimally invasive treatment for LUTS secondary to BPH, and is frequently used to treat men who have failed traditional medical management.

Ninalowo and McLafferty explain that this is the story for a large number of older men in Nigeria, saying “many are desperate for a solution to improve their symptoms or be free of their catheter dependence”. However, they also state that local options have been limited, especially in high-risk, non-surgical candidates.

“Myriad Nigerian men suffered and did not have the means to seek PAE as a therapy locally”, they comment. “This

times, and finally got accepted into the fourth urology journal. This was a prospective, phase two, FDAapproved study, so it met all the high-level criteria, but it was still dismissed by many urology journals.”

As well as operating on the community level, many interventional radiologists have also expressed the need to start locally. “Where I work”, McClure says, “we have great collaboration with the BPH experts, and we have a good, collaborative, multidisciplinary approach to [treating] men with LUTS. Not every patient is a good candidate for PAE, and not every patient is a good candidate for TURP, so ultimately patients benefit when you have this cross-over between disciplines.”

McClure believes that urologists need to understand that interventional radiologists are clinicians and not just technicians, and that for this there needs to be a “collegial” relationship between the two specialties.

Hamoui, who mainly works as a urologist, thinks this is easier for him due to his dual training: “I am able to appreciate what interventional radiologists bring to the table”, he says, “so I can foster that by being friendly and receptive from the get-go, rather than being hostile and looking at them as competition. I think it is unfortunate to have PAE under such hostile attack. My own father, himself also a urologist, underwent PAE [performed] by Dr Salem and was happy with the results.”

Salem is unequivocal in how he believes the debate should move forward: “The only way to break this stalemate is to engage individuals from both sides that can take a reasonable, tempered, non-emotional approach to this therapy. Get patients and get neutral physicians involved. Create a guideline that is tempered, recognises the limitations of the data we have, and incorporates PAE as one of the many treatment options for BPH. Until the loudest, most cynical voices are excluded from the discussion, this sensationalised and vitriolic debate will never end.”

is no longer the case. By offering this in Lagos, we create the first step towards improving access to care for these men.”

Nigeria is a country with a long history of its citizens traveling internationally for medical care. Five practising interventional radiologists today serve a country with a population of 200 million

By offering this in Lagos, we create the first step towards improving access to care for these men.”

people. Ninalowo is helping to lead the effort to establish greater access to interventional radiology for all Nigerians.

Following his own medical training in the USA, he founded the organisation IRDOCNIGERIA, which aims to train an additional 100 interventional radiologists in his home country over the next decade.

The first interventional radiology training programme in Nigeria also launches this month, with Ninalowo at its helm.

McLafferty expands on the importance of this work: “I think this model of a local physician trained in America repatriating his skills to his own people is the key to achieving a sustainable interventional radiology practice in a virgin country. His [Ninalowo’s] practice, IRDOCNIGERIA, currently offers highlevel interventional radiology procedures in Lagos, Nigeria.

“In addition, Ninalowo and I are managers with RAD-AID International’s IR4Nigeria effort to establish a sustainable IR training programme in Nigeria. With this, we have established a primary collaboration with the Nigerian Society of Interventional Radiology (NiSir), and also established a primary training site at the University College Hospital in Ibadan, Nigeria.

The enthusiasm of local radiologists to learn interventional radiology has been tremendous and we plan to continue to provide immediate access to simple and complex interventional radiology procedures and help build long-term sustainability.”

New PAE research

Issue 76 | November 2019

1,550-patient study indicates prostate artery embolization effective for a decade Prostate artery embolization (PAE) may become the standard of care procedure for the management of symptomatic benign prostatic hyperplasia (BPH), proposed Tiago Bilhim (CHULC, Saint Louis Hospital, Lisbon, Portugal), due to “good clinical results” presented at the 2019 annual meeting of the Cardiovascular and Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).

T

he investigators set out to evaluate the outcome of PAE for symptomatic BPH patients with moderate to severe lower urinary tract symptoms (LUTS). The single-centre, retrospective study examined data on 1,550 patients, prospectively-collected between March 2009 and February 2019.

“Subjective and objective parameters were assessed”, Bilhim said. The International Prostate Symptom Score (IPSS), quality of life (QoL) score, and international index of erectile function (IIEF-5) were categorised as subjective measures, whilst the investigators also calculated changes in prostate volume (PV) using trans-rectal ultrasound, peak urinary flow-rate (Qmax), post-void urinary residual (PVR), and prostate specific antigen (PSA) concentration. All of these were assessed before PAE, and

one, six, and 12 months after PAE, then yearly for up to 10 years.

Clinical outcomes

There was a statistically significant change from baseline in the evaluated parameters (p<0.001) across all time scales. In the short-term, defined as one to 12 months after PAE, the mean cumulative clinical success rate was 88.1% (range: 77.6–92.4%). In the medium-term, two to five years after the procedure, this was 85.1% (range: 71.3–93.1%), and over the long-term, from six to ten years post-PAE, the mean cumulative clinical success rate was 76.8% (range: 69.1–84.6%). Bilhim described the change in cumulative clinical success rate from short- to longterm—88.1% to 76.8%—as “not that much of a drop” over ten years.

Mean IPSS reduction was 13.5±6.9 in

Tiago Bilhim

the short-term, 14.1±7.3 in the mediumterm, and 13.9±8.7 in the long-term. Mean quality of life improvement was also consistent out to ten years: 1.8±1.2 in the short-term, 2.1±1.3 in the medium-term, and 1.7±1.5 in the long-term. Prostate volume reduction was also observed out to ten years, with the mean long-term reduction being 16.9±26.6cm3, and a short-term reduction of 18.3±27.9cm3.

From the 156 patients in acute urinary retention (AUR), 140 (89.7%) had the bladder catheter removed between two days and three months; 10 had repeated successful PAEs, and six had surgery.

For the 312 patients with prostates larger than 100mL, there was a high rate of clinical success: in 80.7% of patients (252 individuals) over the short-term; 77.6% of patients (242 individuals) over the medium-term; 75.3% of patients (235 individuals) in the long-term.

Bilhim reported three major

Balloon-occlusion PAE as effective as conventional microcatheter PAE Balloon-occlusion prostatic artery embolization (PAE) is as effective as conventional microcatheter PAE in the treatment of benign prostatic hyperplasia (BPH) with a potential to reduce non-target embolization, Tiago Bilhim (Saint Louis Hospital, Lisbon, Portugal) and colleagues report in the Journal of Vascular and Interventional Radiology (JVIR; doi:10.1016/j. jvir.2019.06.019 [Epub ahead of print]). However, the authors were surprised to note that there was no clear advantage of balloon-occlusion PAE over the conventional technique.

THE INVESTIGATORS SET out to compare the safety and efficacy of these two types of PAE. In this single-centre, prospective, randomised, single-blind clinical trial, 89 patients with symptomatic BPH were assigned to conventional microcatheter PAE (43 patients) or balloon-occlusion PAE (46 patients), and were treated between November 2017 and November 2018. All patients were embolized with 300–500µm Embosphere microspheres (Merit Medical), and were evaluated one and six months post-procedure.

All efficacy variables improved in both groups with statistical significance, with the exception of International Index of Erectile Function, which remained constant in both groups, and prostate-specific antigen levels, which decreased significantly in the conventional microcatheter PAE group (0.9nb/mL±2.22; p=0.01).

Assessments at six months after PAE showed mean International Prostate Symptom Score (IPSS) reduction from baseline was 7.58±6.88 after conventional microcatheter PAE, and 8.30±8.12 after balloonocclusion PAE (p=0.65).

Mean prostate volume reduction was 21.9cm3±51.6 (18.2%) after conventional microcatheter PAE and 6.15cm3±14.6 (7.3%) after balloon-occlusion PAE (p=0.05).

Additionally, Bilhim et al report no statistically significant difference in the average maximum pain reported within 24 hours after the procedure (0.74±1.31 and 0.93±1.70 in conventional microcatheter PAE and balloon-occlusion PAE groups, respectively; p=0.056).

Comparing the two PAE procedures, Bilhim and colleagues are surprised by their results, writing: “Balloon-occlusion PAE relies on the potential to prevent reflux and to reverse blood flow in the anastomoses between the prostate and surrounding organs. Thus, it would be reasonable to expect fewer adverse events in balloon-occlusion PAE and less need for protective coil blockage of the prostatic anastomoses. These assumptions were not proven here, as the overall rate of adverse events was not significantly different between the two groups.”

Indeed, no major adverse events occurred in either group, whilst minor adverse events occurred in 23 patients (53.5%) in the conventional microcatheter PAE group, and in 26 patients (56.5%) in the balloonocclusion PAE cohort. Penile skin lesions and rectal bleeding, which the study authors say can be due to nontarget embolization, only occurred in the conventional microcatheter PAE cohort: three patients (7.1%) had penile skin lesions and two (4.7%) had rectal bleeding.

Interpreting these findings, the investigators say that

9

complications: a bladder wall ischaemia, a perineal pain for three months without sequela, and a patient had expelled prostate fragments and AUR treated by trans-urethral resection of the prostate (TURP) without sequela.

Describing the technical outcomes, Bilhim reported that in 90% of patients (1,324 people), the interventionalist gained access to the vasculature through the femoral artery. Since 2016, interventional radiologists at Saint Louis Hospital in Lisbon, Portugal, have been using left radial access, so 10% of the cohort (148 patients) experienced this.

“This is our first-line approach”, he said of the technique, adding that now they are using it “more and more”.

Patient characteristics

Enrolled patients were 40 or older (with no upper limit on age; mean age: 65.1 years), and “severely symptomatic”, with an IPSS greater than 18 (mean IPSS: 21.8), a prostate volume greater than 30mL, and a peak urinary flow-rate less than 15mL per second. The prostate was larger than 100cm3 in 312 patients, and 156 patients were in acute urinary retention (AUR). In the initial phase of the trial, only patients failing medical therapy were accepted, meaning that 65% of the cohort were given medical therapy prior to PAE. However, Bilhim said that “a significant proportion” (35%) of patients had no medical therapy pre-PAE, as “they do not want the adverse events” attributed with the alpha-blockers and 5-alpha-reductae inhibitors, such as retrograde ejaculation.

“these observations are probably clinically relevant, as they represent indirect measures of non-target embolization”. They continue: “The lower rate of these adverse events [penile skin lesions and rectal bleeding] in the balloon-occlusion microcatheter PAE group (with no reported events) could be due to the protective features of balloon-occlusion. However, the wedged embolization technique used as opposed to a free-flow embolization and a low usage of protective coils (14%) could have led to a higher rate of non-target embolization in the conventional microcatheter PAE group (n=5; 11.9%).”

Bilhim and colleagues recommend that future trials comparing the two types of PAE procedures using radiopaque microspheres or macroaggregates, in an effort to clarify “any potential benefits related to reduced non-target embolization in particular”.

When enumerating the potential benefits of balloonocclusion PAE in comparison with conventional microcatheter PAE, Bilhim et al list reduced coil usage (as the placement of coils has been shown to increase procedural times and radiation exposure) and the establishment of an intraprostate negative pressure, which the authors claim “could likely allows the use of a larger amount of embolic volume”. If this latter benefit holds true, Bilhim and colleagues postulate that balloon-occlusion PAE “could lead to greater prostatic destruction, together with higher values of prostatespecific antigen in the 24 hours following embolization, and greater clinical relief”. However, this was not proven in the present study.

Furthermore, the authors note that their work corroborates earlier studies in showing that 5α-reductase inhibitors are not detrimental to the clinical outcomes after PAE. In fact, the present study “uncovered a potential positive interaction with PAE outcomes—that is, the use of 5α-reductase inhibitors before PAE may lead to better clinical outcomes”, according to Bilhim and colleagues.

10

IR in Myanmar

November 2019 | Issue 76

International collaboration has fuelled a decade of development for IR in Myanmar Collaboration, academic support, and hands-on training provided by the Singapore General Hospital, Singapore, have driven the small interventional radiology (IR) community of Myanmar to the international stage. As one of the organising members of the AsiaPacific Society of Cardiovascular and Interventional Radiology (APSCVIR), the group of interventional radiologists in Myanmar have been working more closely with members of the Society of Interventional Radiology (SIR) and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) to promote the specialty locally. Despite huge strides over the last decade in the number and complexity of IR cases being undertaken in the country, Myanmar faces several challenges, which Kyaw Zay Ya (an interventional radiologist based in Nyaung, Myanmar) summarised as the “three Ms: man, money, and materials”.

D

ue to a cancelled flight, Bien Soo Tan (Singapore General Hospital, Singapore) addressed delegates on behalf of Ya, speaking at the 2019 annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).

Myanmar is a large country in South East Asia with a population of 54 million, and a land area of 676,575km2.

In the late 1970s and early 1980s, a conventional angiography system with serial changer was installed for diagnostic purposes in Yangon General Hospital (Yangon, Myanmar). By the end of the 1980s, digital subtraction

angiography (DSA) was possible in the country, and some vascular and non-vascular interventional radiology (IR) procedures were performed in the early 1990s, though there was no proper training for interventionalists.

“At that time,” Tan said, “there were several very senior radiologists in Myanmar who were trained in Europe, in particular the UK, and when they went back [to Myanmar], they did introduce some of these procedures, […] primarily angiography and even chemoembolization.”

Following this informal introduction of IR to the country, Tan’s own institution, the Singapore General

Interview

Interventional radiologists welcome in Myanmar Kyaw Zay Ya caught up with Interventional News at the 2019 meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain) to discuss the opportunities and challenges Myanmar faces in developing its IR offering.

What is the status of IR in Myanmar?

My country is still developing, so IR in Myanmar is in the very initial phase. For me, I wanted to become an interventional radiologist after my radiology residency.

In 2002, I had the chance to apply for fellowship training in Singapore General Hospital (SGH) with Bien Tan Soo—he is my mentor. He helped me a lot, not only to get the training, but also to get continuing

Hospital, provided IR training to radiologists in Myanmar. This paved the way for the first two Myanmarese interventional radiologists to gradually start working in their home country in the early 2000s, with “very limited consumables available to them”.

Since then, IR has grown steadily in Myanmar. From 2008, interventional radiologists at Singapore General Hospital have trained one or two candidates, and have provided some of the required consumables. These are often consumables in Singapore which are close to expiry, as Tan explained: “They are not freely available; the distributors are not really bringing in these consumables, because there is not much volume in Myanmar itself.”

Today, Myanmar is one of the organising members of APSCVIR, and Tan told delegates that, increasingly, Myanmar is in contact with SIR, based in the USA, and CIRSE, in Europe. Indeed, earlier in the session, APSCVIR president Andrew Holden (Auckland, New Zealand) had praised the “very active outreach programme” in Myanmar; when CIRSE president, Robert Morgan (London, UK) visited the country in January 2019 to take part in said programme. Of this experience, he said: “I was struck firstly by how large Myanmar is as a country, and secondly by how beautiful it is as a country. The people are all very friendly, so I would certainly recommend anyone who wishes to go and visit to do so. I was impressed by the set-up in the hospitals there. I may have had pre-conceived ideas that things would be relatively primitive, but they were not, in fact; there were pretty good facilities in each of the hospitals I went to in Yangon and Mandalay. […] I think it was a very

interventional activities in Myanmar.

We interventional radiologists need to use so many advanced technologies and equipment, especially consumables—catheters, wires—that were very difficult to get at that time [early 2000s]. Anyhow, I requested that my colleagues at SGH get me some of the instruments and materials, and I tried to develop the interventional procedures in my country. At the same time, I tried to get the younger generation to get similar training like me in Singapore. I try to go to every conference in Singapore and took some of the consumables from SGH. From 2008, I got a chance to get the younger generation, my junior colleagues, training at SGH. One or two radiologists get that chance at SGH each year. Today, I have around 15 to 20 junior colleagues who perform interventional procedures in Myanmar.

Why is Singapore General Hospital a good collaborator?

SGH is very suitable for us. The case load and the instruments available make it the perfect place to train. When I first went in 2002, there were five interventional suites; nowadays, there are about 10 interventional suites in the department, and each and every day, there are at least 15 to 30 cases—on some days, there are 40 cases. Over a training period of one year, therefore, my colleagues can gain a lot of experience.

Primarily, we assist the interventional radiologists at SGH with their procedures. Later, when we [the

good venture for CIRSE to be involved in, and I am pleased that Afshin Gangi [CIRSE president since September 2019] will continue this in January next year.”

Speaking about convincing hospitals and governments to support the establishment and progression of IR, Tan commented: “For us [in Singapore], I think some of these arguments have been ongoing within our own institutions and national systems, but you can imagine that in Myanmar, the conversations are [at a] much earlier [stage], [as they] try to argue why IR should be supported.” On his presentation slide, Ya had outlined shorter hospital stays, money saving, reduction in transfusion requirements, better quality of life for patients, faster recovery times, and high intensity local treatments as convincing arguments supporting the development of an IR department.

“These advantages are all very clear to us”, Tan acknowledged to the CIRSE audience, while in Myanmar, he explained how the country’s interventional radiologists “have to start the conversation and lobby the hospital administrators, the ministry, to get more training, more equipment.”

Regaling the CIRSE audience with a personal anecdote, Tan shared: “I think one very telling story I have—I have visited Myanmar quite regularly for ten years now—when I went in 2009, they had an angiography unit installed in Yangon General Hospital that was quite new, I think it was two to three years old, but the tube had blown. So in 2009, there was no angiography available in Yangon General Hospital, which is the largest public hospital in the whole of Myanmar. When I went back over the next three to four years, they still had

trainees from Myanmar] are reliable, they give us the chance to do the procedures ourselves, under supervision. If there is a complication, they would come in and help, so it is very good training.

At the same time, Tan Soo and some of the other consultants at SGH not only help us with training and materials, but they also give us the chance to attend international conferences like CIRSE.

In 2010, Myanmar became a member of the Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR). Why is this important?

Due to being a member country, we have gained more international exposure. Every year, in January, we have an IR workshop in our country. It is an APSCVIR outreach programme, in collaboration with the Myanmar Radiology Society, in which there is a vascular and interventional radiology section. I am president of this section.

Due to these workshops, the interests of our clinicians and radiologists in IR has become bigger and has spread across the country. Next year, CIRSE president Afshin Gangi and Society of Interventional Radiology (SIR) president Laura Findeiss will come and teach, and help us to improve the status of IR. This collaboration has led to my attendance at CIRSE this year. This is a great opportunity for me to meet with industry and to discuss access to consumables in Myanmar. My aim at these conferences

IR in Myanmar

Issue 76 | November 2019 not got the money to buy the tube. Only about six or seven years later did they decide to junk the machine, and they got a new machine in. So these are the challenges that they are facing.”

Despite the difficulties with procurement, a “whole spectrum” of IR procedures are currently being conducted in Myanmar, tailored to the disease distribution seen in the country. There are six public centres and six private centres offering IR services. Between 2015 and 2019, in public centres across Myanmar, there have been, each year, on average: 612 transarterial chemoembolization (TACE) procedures (“one of the main treatments for inoperable HCC”, Tan told the audience, “they do not have the other modalities available, like Y90”), 721 guided biopsies, 67 percutaneous transhepatic biliary drainages (PTBD), 44 angioplasties, 21 intracranial arteriovenous malformations (AVM) treated, and three abdominal aortic aneurysms (AAA) stented. In the private sector, there is on average 352 TACE procedures, 35 guided biopsies, 23 PTBDs, and 18 angioplasties performed each year.

Remarking on the 21 intracranial AVMs treated in the public centre, Tan observed: “Very little neurointervention for such a huge population”.

These procedures have all been conducted by the small group of interventional radiologists working in the country. Modern-day Myanmar has 15 practicing interventional radiologists, trained at several institutions across Asia, including Singapore, Thailand, the Republic of Korea, Japan, and India.

There are two senior radiologists in the country with interventional training who have retired from public practice, but still work in the private sector. Twenty

Myanmarese trainees have received local training, and are preparing to move abroad to “gain more intense exposure”, in Tan’s words, to the discipline.

In addition to procurement difficulties and the low number of interventional radiologists, Myanmar faces other challenges in being able to offer IR services to its 54 million inhabitants. Access to adequate training stymies the discipline’s development.

Furthermore, awareness of IR among interventionalists’ clinical colleagues is low, according to Tan, “and therefore the referral system is not robust.”

However, he then said that the healthcare system is starting to invest in IR. “They [the Myanmarese healthcare system] are now starting to be vendors and distributors, gaining interest, but unfortunately, a lot of the interest is focused on cardiology, because that is where the money comes in, and less on IR.”

Ambitions for a more developed IR programme in Myanmar

Enumerating Ya’s aspirations for the development of IR in Myanmar, Tan listed the following: To have vascular interventional radiology (VIR) services in all tertiary hospitals To train more interventional radiologists To establish a 24-hour VIR service, especially for emergency cases To build up VIR clinics in all tertiary hospitals To train neuro-interventionalists To establish VIR sub-units in the radiology department of every teaching hospital To conduct up-to-date research within the specialty

is to get international contacts, and for my junior colleagues to receive training.

What message would you like to give to your IR colleagues in developed nations?

Our country is now open—politically, socially, and economically. IR is very quickly developing and, to ensure quality of care for our patients, we need international support. Because of the population of our country [54 million people], there is a lot of potential to develop a great IR specialty, but we still need some human resources and consumables.

I would like to invite interventional radiologists across the world to come to my country and help us in any way, through training or instrument support.

I hope I can improve the status of IR in Myanmar; within the next five years, it will become an international standard [of IR care].

We must dedicate our time and efforts to improving this valuable specialty.

KYAW ZAY YA: The first interventional radiologist in Myanmar, Ya has been instrumental to the development of the specialty in his home country. His message to the world is one of openness: “I would like to invite interventional radiologists across the world to come to my country”.

11

12

Genicular artery embolization

Preliminary results of first European prospective study find GAE reduces pain from osteoarthritis at three months Genicular artery embolization (GAE) is responsible for statistically significant improvements in pain scores from baseline out to three months, the preliminary results of the first European prospective study on the procedure show. Mark Little (University of Reading and Royal Berkshire NHS Foundation Trust, Reading, UK) presented these early results of the GENESIS study (geniculate artery embolisation in patients with osteoarthritis of the knee) at the Annual Scientific Meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).

WHILE CAUTIOUS ABOUT overinterpreting what he stresses are early data, Little is nonetheless optimistic about these positive results, telling delegates at CIRSE: “Musculoskeletal (MSK) embolization is the next frontier in embolotherapy”.

November 2019 | Issue 76 The GENESIS investigators report “excellent recruitment”, with 34 patients enrolled since the trial started recruiting. Little believes this reflects the fact that GAE is serving an unmet clinical need.

Osteoarthritis is a common condition with a growing prevalence due to an increasingly obese and elderly European population.

For those patients older than 45 years of age who have mild to moderate osteoarthritis that is resistant to conservative treatment, yet is not severe enough to warrant joint replacement, GAE is being hailed as a potential solution.

Detailing the scientific rationale for GAE, Little explained to the CIRSE audience that inflammation of the knee joint drives synovial angiogenesis through macrophage activation. “It Mark Little is hypothesised that angiogenesis contributes to structural damage and pain in osteoarthritis”, he explained, “and GAE can be used to treat this pain”.

The single centre, prospective GENESIS study (funded by Merit Medical and the National Institute for Health Research, NIHR) uses changes in pain measurements from baseline to post-procedural follow-up to assess the efficacy of GAE. Consultant interventional radiologists performed the procedure using 100–300micron Embosphere particles (Merit Medical) diluted in 20ml contrast.

I really want to stress how important it is to precisely measure patients’ pain.

We need to up our game in [...] MSK embolization.”

Tips to recognising genicular artery anatomy Sandeep Bagla Abin Sajan Comment & Analysis With an increasing number of interventional radiologists turning their technical and clinical expertise to musculoskeletal embolization, Sandeep Bagla and Abin Sajan believe it is important to have a thorough understanding of the anatomy specific to these procedures. Here, they detail the genicular artery anatomy, in the hope that increased physician familiarity translates into an increased ability to treat patients with challenging vasculature.

I

n an era of cutting-edge interventional procedures, genicular artery embolization (GAE) is a minimally invasive solution for patients with mild to moderate osteoarthritic (OA) knee pain.

The primary goal of GAE is to disrupt the inflammatory process by embolizing the hypervascular synovium causing the pain and disability. Successful preliminary results in pilot clinical

Pain is a complex multifactorial process and the GENESIS study protocol is using a number of novel tools to assess patient’s pain. Little’s research group at University of Reading, UK, is using neuropsychological assessments employing functional magnetic resonance imaging (fMRI) of the brain to map pain, in addition to measuring Visual Analog Scores (VAS) pain scores, and using the Knee Injury Osteoarthritis Outcome Score (KOOS), a validated questionnaire used throughout the orthopaedic literature on knee osteoarthritis.

Overall Visual Analogue Scale (VAS) decreased from baseline at both six weeks and three months follow-up: mean VAS was almost 70 pre-GAE, and just below 30 six weeks post-procedure.

VAS score was 33 at three months (p<0.005). Meanwhile, KOOS increased from baseline to one-year follow-up, representing a reduction in pain and symptoms. Mean KOOS was 39 at baseline, 62 (p<0.005) and 85 oneyear post-procedure.

There were two minor complications, observed in the 22 patients treated with GAE for this interim analysis— two cases of transient skin discoloration early on.

Explaining the significance of these results, Little tells Interventional News, “I really want to stress how important it is to precisely measure patients’ pain. We need to up our game in terms of accurate outcome measures in MSK embolization. We are very fortunate to have the Center for Integrative Neuroscience and Neurodynamics (CINN) at the University of Reading to carry out the pain assessments as part of the GENESIS study.”

Little reported that preliminary neuropsychology data reveal signals that may predict treatment failure.

“We are continuing to model the neuropsychological pain experiments with the ultimate aim of aiding patient selection”, he said. The triallists are instituting neuromodulation prior to the procedure to improve clinical outcomes.

studies have fostered a randomised control trial (RCT) at the Vascular Institute of Virginia and UNC Chapel Hill, which has finished recruitment and we hope to present our findings at the annual meeting of the Society of Interventional Radiology (SIR) next year (28 March–2 April, Seattle, USA).

As the popularity of GAE increases, it is important to have a thorough understanding of the genicular arterial anatomy. The success of GAE, as well as the prevention of non-target embolization, is associated with recognising patterns on the initial angiogram and anticipating potential obstacles during the procedure.

Possible anatomic challenges include variable presence of vessels, small sized vessels, acutely angled vessel origin, presence of atherosclerosis, and collateral supply. Familiarity with typical patterns and an understanding of angiographic relationships provide a dynamic foundation when presented with challenging anatomy.

We reviewed the angiographic patterns from our first two clinical trials to identify the basic arterial anatomy and review technical pearls for the procedure. We identified six main arteries: descending genicular artery (DGA), medial superior genicular artery (MSGA), medial inferior genicular artery (MIGA), lateral superior

genicular artery (LSGA), lateral inferior genicular artery (LIGA), and anterior tibial recurrent artery (ATR).

Since osteoarthritic knee pain can be lateralised to either the medial or lateral aspect of the knee, we present the anatomy using the same approach (Figure 1). Of note, other vessels, including the median genicular artery, contribute to the knee joint but were not included in our study.

The medial compartment of the knee is mainly perfused by the DGA, MSGA, and MIGA. The DGA originates from the distal superficial femoral artery and has a classic inverted “Y” appearance. It divides into a straight medial saphenous branch which courses superficially, and a more torturous lateral musculoarticular branch which courses deeper in the knee.

The MSGA arises from the proximalmid popliteal artery just above the medial femoral condyle and classically courses superiorly before travelling down to the medial knee joint. Although the MSGA is often difficult to visualise given its smaller calibre, we have noted that the luminal size of the MSGA is inversely related to the size of the DGA. The MIGA originates from the popliteal artery near the joint space and descends along the upper margin of the popliteus, before coursing anteriorly and superiorly, creating an angiographic “V” around the

Musculoskeletal embolization

Issue 76 | November 2019

Figure 1 (left) and Figure 2 (right): Angiography at the level of the upper and lower knee. Descending Genicular Artery (A) divides classically in to Saphenous Branch (G) and Articular Branch (H). The Superior Medial Genicular Artery (B) and Superior Lateral Genicular Artery (D) typically have a reversed curve origin from the popliteal artery. The Inferior Medial Genicular Artery (C) demonstrates its classic J shaped pattern and the Inferior Lateral (E) may arise at, or in this case, slightly below the joint. The Anterior Tibial Recurrent (F) originates from the proximal Anterior tibial artery as displayed.

medial tibial condyle. The MIGA arises adjacent to the sural arteries, which are distinguished by their steeper trajectory towards the gastrocnemius musculature.

The lateral compartment of the knee is mainly perfused by the LSGA, LIGA, and ATR. The LSGA arises from the mid-popliteal artery at the level of the lateral femoral condyle. Like the MSGA, it initially courses superolateral before travelling down to the lateral knee joint.

The LIGA originates around the joint space and courses laterally above the

may minimise the risk of non-target related cutaneous changes.

The most technically challenging aspect of GAE is catheterising the acutely angled vessel origins (Figure 2). Wire placement can be challenging in the first 3cm, and wires with a floppy tip may not allow ample support during catheterisation. In our experience, a 2.4F microcatheter was adequate in catheterising these arteries.

However, there is a role for pre-shaped microcatheters, especially in acutely

Understanding angiographic relationships provide[s] a dynamic foundation when presented with challenging anatomy.” fibular head before wrapping around the lateral tibial condyle, creating a “J” appearance. In addition, this reversecurved vessel may share a common trunk with the SMGA, making catheterisation more challenging. The ATR is the most inferior branch supplying the knee and originates from the very anterior tibial artery just beyond its origin.

Although the six arteries are typically present in all patients, absence of one or more arteries might suggest that another artery is more dominant in the affected compartment. Additionally, collateral supply can cross the joint space and embolizing in such cases can lead to non-target embolization of the asymptomatic side. Cutaneous branches often appear perpendicular to the main genicular artery and terminate at the skin surface. Skin purpura from embolizing these vessels is the most common side effect of GAE, and an attempt should be made to deliver particles distal to cutaneous branches, however this may be challenging given their ubiquitous presence. Ice-packs placed on the skin

angled vessel origins, most notably the SMGA and the SLGA. GAE is an exciting procedure that is leading the way for musculoskeletal embolization. We believe that a thorough understanding of the angiographic anatomy and knowledge of commonly encountered challenges will increase interest in GAE and promote future cutting-edge interventional procedures.

Sandeep Bagla is the chair of Interventional Radiology at the Vascular Institute at Virginia, Woodbridge, USA. For his GAE clinical studies, Rachel Piechowiak and Ari Isaacson are coinvestigators.

Abin Sajan is a medical student at the State University of New York (SUNY) Downstate College of Medicine, New York, USA. He was awarded the SIR Dr and Mrs WC Culp Student Research Grant for his work on the “Cadaveric Classification of the Geniculate Artery Anatomy”. He is working with Maziar Sighary on the cadaveric studies.

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Endovascular thrombectomy

November 2019 | Issue 76

SIR publishes new training guidelines for endovascular thrombectomy The Society of Interventional Radiology (SIR) has published new training guidelines for endovascular stroke treatment. This is the first update since 2009, when the society released training guidelines for intra-arterial catheter-directed treatment of acute ischaemic stroke.

“OBVIOUSLY, THE WORLD of stroke intervention has changed tremendously since then”, lead author of the guidelines David Sacks (The Reading Hospital and Medical Center, West Reading, USA) tells Interventional News. At the time, catheter-directed thrombolysis was the only such therapy studied in randomised trials. In the intervening decade, mounting positive evidence for endovascular thrombectomy from randomised trials and meta-analyses, and the subsequent growth in the number of these procedures being performed each year, has led the SIR to believe that these new recommendations are timely and necessary.

The guidelines were authored by a diverse group of interventional radiologists, specifically-trained neurointerventionalists, endovascular specialists, and stroke neurologists, as well as academics and community hospital staff; they varied to being freshly out of training themselves, to having over 30 years’ experience of stroke interventions. Sacks explains to this newspaper: “We solicited people from a range of backgrounds so that we could have a diversity of opinion, experience and knowledge. We wanted to make sure that we were meeting the needs of people in many different environments, as well as meeting patients’ needs.”

However, no official representative of the Society of NeuroInterventional Surgery (SNIS) participated in the creation of these guidelines. Despite the SIR inviting various leaders and former leaders of SNIS to participate in the creation of these guidelines, “for various reasons those individuals declined”, Sacks reports. Several of the guideline authors are members of SNIS, though. Sacks also adds, “We [SIR and the guideline authors] have maintained lines of communication with the current leaders of SNIS, and we remain open to working with them in whatever ways would advance patient care for stroke interventions”.

“Interventional radiologists are seeking guidance as to how they should train”

Earlier this year, SIR, the Cardiovascular and Interventional Radiology Society of Europe (CIRSE), and the Interventional Radiology Society of Australasia published a joint position statement in the Journal of Vascular and Interventional Radiology (JVIR) outlining the role of interventional radiologists in acute ischaemic stroke interventions. Sacks, who was also the lead author of this joint statement, describes this as “an acknowledgement that interventional radiologists have an important role to play in stroke care”, but adds that “it was also cautionary, stating that interventional radiologists must be adequately trained”. These latest guidelines provide the training pathway alluded to in the earlier joint statement.

Sacks says that the new guidelines “make clearer what training and experience interventional radiologists are expected to have to be performing these [endovascular stroke] procedures”. He continues: “I think there are an increasing number of interventional radiologists already who are involved in stroke interventions, and like any kind of medical care, there will be a range of experiences and capabilities. We are trying to bring more uniformity at a high level of what that training and experience should be. I think there are already many hospitals that are turning to their interventional radiologists to help provide this care, and those interventional radiologists are seeking guidance as to

how they should train. They want to do a good job, and they need to know what the recommendations are for them to train to be able to do the good job they are committed to.”

Specific training requirements

The updated guidelines state: “The IR physician is expected to have baseline mastery in accordance with the Accreditation Council for Graduate Medical Education (ACGME) milestones of level 4 or higher of arterial access, selective vascular catheterisation, including microcatheters, and mechanical revascularisation, including thrombectomy and thrombolysis of extracranial vessels. The IR physician is also expected, as part of core training and certification in diagnostic radiology, to have experience with neuroimaging including CT, MRI, and perfusion imaging.”

minimum of six months of documented cognitive neuroscience training during or post-residency is necessary to become competent in the interventional care of patients with acute ischaemic stroke”.

Three training pathways are outlined in the document to highlight how this competency could be achieved.

Firstly, the new ACGME accredited IR/diagnostic radiology residency programme in the USA will provide trainees with at least two years of dedicated clinical and procedural training, with “motivated residents” able to access up to six months of neuroscience training.

Alternatively, practicing interventional radiologists could achieve competency to treat ischaemic stroke through a proctorship. The guideline authors elaborate: “Ideally, supervised training would include robust, hands-on training, not limited to interventional techniques but also workup prior to and management after thrombectomy”.

The final training pathway detailed in the guidelines is for physicians to enrol in an educational stroke course involving procedural simulations and potentially virtual reality to supplement stroke training.

The consensus of the guidelines’ authors is that a minimum of 10 procedures per year for each operator is recommended for maintenance of physician competence.

The onus also falls on institutions to provide appropriate infrastructure and support, according to Sacks and colleagues. They conclude: “Institutions performing stroke intervention must establish quality assurance programmes to optimise processes and outcomes, and both technical and clinical outcomes must be entered into a database or registry”.

Endovascular thrombectomy procedures on the rise

We wanted to make sure that we were meeting the needs of people in many different environments, as well as meeting patients’ needs.”

There is no requirement for full-scope neuroendovascular training through either a formal neurointerventional fellowship or near equivalent.

“However”, the authors note, “specific and rigorous training with demonstration of competence is required”.

Adequate training, according to Sacks et al, involves the following: Formal training that imparts the required depth of cognitive knowledge of the brain and its associated pathophysiological vascular processes, clinical syndromes, the full array of ischaemic stroke presentations, and pre-, peri-, and post-procedural care.

Procedural skill, including management of complications secondary to endovascular procedures, that is achieved by supervised training by a qualified instructor.

Diagnostic and therapeutic acumen, including the ability to recognise procedural/angiographic complications. This is achieved by studying, performing and correctly assessing an adequate number of diagnostic and interventional/endovascular procedures with proper tutelage.

In addition, the new SIR guidelines stipulate that “a

“I think the number of stroke interventions will continue to increase”, Sacks predicts. The current number of stroke interventions are vastly fewer than the number of patients generally acknowledged to be eligible. A 2018 survey from the European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN) and the Stroke Alliance for Europe (SAFE) investigated the access to and delivery rates of stroke care in 44 European countries— and found that over 65,000 stroke patients eligible for endovascular treatment were not provided with this intervention. On average, 1.9% (95% confidence interval [CI], 1.3–2.5) of all patients with an ischaemic stroke in Europe received endovascular treatment, while a recent UK study estimated that approximately 10% of stroke patients are good candidates.

The most common reason that stroke intervention was not performed on an eligible patient was the lack of adequately trained physicians, leading Sacks to argue that there is a need for well-trained interventional radiologists to perform these procedures. “Having more interventional radiologists who are adequately trained will allow more patients in total to be treated when it is appropriate to treat them”, he says.

In addition to the potential increase in stroke interventions caused by treating a greater majority of eligible patients, Sacks also believes the overall number of eligible patients will rise. “The estimates on which these articles are relying [for estimates of eligible patients] are based on the well-accepted indications: patients within six hours, patients with ICA-M1/M2 occlusions, and patients whose strokes are sufficiently severe but do not have large core [infarcts]”, he says.

“There are multiple trials underway looking at whether patients with mild strokes or patients with large core [infarcts] will benefit.

“I think that in the future, we are going to be treating increasing numbers of patients with a broader set of indications. Stroke patients will be treated at an increasing number of centres [in the USA] rather than [just at] the current number of thrombectomy-capable stroke centres. I think there will be more uniformity in the way people are training, and more uniformity in the expectations for outcomes.”

Stroke care

Issue 76 | November 2019

Adequately trained interventional radiologists should be performing endovascular thrombectomies to relieve stroke care burden David Sacks Comment & Analysis Thousands of eligible patients are not receiving endovascular thrombectomies after suffering a stroke due to a shortage of neurointerventionalists worldwide. In an effort to combat this, the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), and the Interventional Radiology Society of Australasia (IRSA) believe interventional radiologists must treat acute ischaemic stroke patients. SIR has published an update of its stroke guidelines, outlining the pathways to ensure adequate training for those performing the procedure. David Sacks, lead author of these guidelines and a physician who has been involved in stroke intervention since the original publication of the PROACT trial in 1999, here describes why involving interventional radiologists in stroke care is critical.

H

ow many patients with acute ischaemic strokes could be treated with emergency endovascular thrombectomy (EVT) but are not? Why is this happening? What can be done to help?

Worldwide access to stroke care

In the USA in 2015–2016, only 2.6% of stroke patients received EVT.1 A European survey on stroke care authored

by Aguiar de Sousa et al on behalf of the European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN), and the Stroke Alliance for Europe (SAFE) found that EVT was offered in 40 of 44 European countries.

On average across the continent, the procedure was offered for 1.9% of all strokes.2 The highest country rate was 5.6% of all strokes. Assuming that 5% is a reasonable goal, this means that 67,000 patients were clinically eligible for EVT but not treated.

Notably, the European survey considered 5% to be a conservative estimate. There is strong evidence from the DAWN and DEFUSE 3 trials3 to treat selected patients up to 24 hours after stroke onset. Furthermore, patients over 80 years of age have a similar odds ratio of benefit compared

to younger patients.4 Randomised trials are underway to evaluate the benefit of EVT for mild strokes, large core infarcts, and patients with moderate baseline disability. In one published national registry of current practice, 11% of treated patients had mild strokes, not currently included in treatment guidelines.5 Patients with large core infarcts are also likely to benefit.6 In the UK, it is estimated that about 10% of stroke admissions would be eligible for EVT, an estimate which does not include patients with mild strokes, large cores, baseline disability,

patients not being treated?

In the European survey, the most common reasons were lack of specifically trained personnel, lack of facilities, and costs. Multiple studies have demonstrated that EVT is a highly cost-effective intervention, but stroke interventions involve complex care, from ambulance staff to emergency department and radiology evaluation, patient transport, endovascular treatment, critical care management, stroke unit care, and rehabilitation. The resources to provide this care have not yet caught up with the recent proof of effectiveness of EVT. One way to provide additional personnel is to train vascular interventional physicians to provide EVT. In theory, this would allow EVT to be provided in locations where neurointerventional physicians are not able to provide 24/7 care, or not available at all. Hospitals that may not have sufficient volumes of cerebral aneurysms or vascular malformations to support multiple neurointerventional physicians may be able to provide EVT by sharing the EVT work with other endovascular colleagues. This raises a series of questions: can other interventional physicians be trained sufficiently to provide EVT such that outcomes meet international benchmarks? Might the learning curve for training be such that patients would be better off not being treated at all, or being transferred to another hospital with delayed treatment? If a hospital cannot provide 24/7 coverage by physicians specifically trained for neurointerventional procedures, might it also lack the infrastructure to provide all of the rest of the complex care that is necessary to achieve good outcomes? Might the treatment of stroke patients at many local hospitals lead to many low-volume centres with suboptimal outcomes compared to a few high-volume centres? Many of these questions will require trials for answers. In the meantime, patients with acute ischaemic strokes are being vastly undertreated with EVT.

The role of interventional radiologists Interventional radiology societies believe that appropriately trained

In the USA, 60% of primary stroke centres perform endovascular thrombectomy, and of these, 41% rely on interventional radiology physicians.” or time from stroke onset >12 hours.7 It is estimated that 30–46% of acute ischaemic strokes involve large vessel occlusions,8–11 and a recent commentary suggests that every stroke patient with an acute large vessel occlusion “should undergo thrombectomy unless the weight of evidence is strongly against treatment”.12

Why are more eligible

interventional radiologists can help address the manpower needs.

Interventional radiologists are currently active providers of EVT. The majority of the interventional physicians in The Netherlands who participated in the MR CLEAN trial and registry were interventional radiologists. The odds ratio for benefit in the MR CLEAN trial was the same as for the neurointerventional

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trial sites.13 The vast majority of the physicians providing EVT in the Czech Republic are interventional radiologists, and published results from the Czech registry are comparable to neurointerventional outcomes. In the USA, 60% of primary stroke centres perform EVT, and of these, 41% rely on interventional radiology physicians,14 and overall, 34% of EVT cases were performed by physicians who had not trained in dedicated neurointerventional fellowships.15 In a survey conducted

by SIR, approximately 25% of interventional physicians providing EVT at certified comprehensive or thrombectomy-capable stroke centres are interventional radiologists. SIR, CIRSE, and IRSA have published a joint statement on the role of interventional radiologists in acute stroke interventions.16 Working with neurologic and neurointerventional sister societies, SIR and CIRSE have published international benchmarks for EVT outcomes.17 A European pathway for training interventional radiologists in stroke interventions has been established.18 SIR has just published an update of its training guidelines (see page 14) written by multispecialty authors from interventional radiology, neurointerventional, combined interventional radiology and neurointerventional, stroke neurology, and endovascular neurosurgery backgrounds. The SIR training guidelines require a background of endovascular expertise supplemented with stroke specific imaging, cognitive, and technical training.

EVT is a powerful tool to reduce disability from acute ischaemic stroke.

There is strong evidence that eligible patients are not receiving EVT due to a shortage of EVT physicians.

IR physicians are currently working with our neurointerventional colleagues to provide this care with acceptable outcomes.

David Sacks is an interventional radiologist in the Department of Interventional Radiology at The Reading Hospital and Medical Center, West Reading, USA. References: 1. Stein et al, Journal of NeuroInterventional Surgery, doi:10.1136/neurintsurg-2019-015019 2. Aguiar de Sousa et al, European Stroke Journal 2019; 4:13–28 3. Nogueira et al, New England Journal of Medicine 2018; 378:11–21 4. Albers et al, New England Journal of Medicine 2018; 378:708–718 5. Goyal et al, Lancet 2016; 387:1,723–1,731 6. Asdaghi et al, Stroke 2019; 50:2,101–2,107 7. Panni et al, Stroke 2019; 50:1,164–1171 8. McMeekin et al, European Stroke Journal 2017; 2:319–326 9. Lakomkin et al, Journal of NeuroInterventional Surgery (JNIS) 2019; 11:241–245 10. Smith, Stroke 2009; 40:3,834–3840 11. El Tawil et al, European Stroke Journal 2016; 1:264–271 12. Nogueira and Ribo, Stroke, 50:2,612–2,618 13. Flynn et al, European Stroke Journal 2017; 2:308–318 14. Alberts et al, Interventional Neuroradiology 2017; 23:64–68 15. Kamel, Journal of the American Medical Association (JAMA) Neurology [Year]; [Issue; Pages] 16. Sacks et al, J Vasc Interv Radiol 2019; 30:131–133 17. Sacks et al, J Vasc Interv Radiol 2018; 29:441–453 18. European Board of Neurointervention.

Recommendations for acquiring competence in Acute Ischemic Stroke Intervention (AISI). Available at: https://ams3.digitaloceanspaces.com/ebnidocument-storage/68903e8bfc62bb742df0191935e 6f112/Standards-of-training-in-AISI-APPROVED.pdf

Neurovascular research

Issue 76 | November 2019

Novel embolization agent “promising” for the endovascular treatment of cerebral aneurysms in in vivo model

The first preclinical study of a novel embolization agent, GPX, reports its successful performance in a rabbit aneurysm model.

High rates of complete angiographic occlusion were achieved and maintained, said Ruben Mühl-Benninghaus (Saarland University Hospital, Homburg, Germany), presenting these “promising” results at the 2019 annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (7–11 September, Barcelona, Spain).

IN RECENT YEARS, liquid embolic agents have emerged for endovascular treatment of cerebral aneurysm. “There are multiple liquid embolics available right now”, Mühl-Benninghaus said, before describing the properties of the ideal embolic agent: “It should have good control and precision during embolic injection, it should not adhere to any adhesion or clumping within the catheter, and the penetration of the liquid embolic agent should always target the distal vessel, which is the aim of the occlusion. Ease of use is also very important, [to] minimise the preparation steps and minimise complications during preparation. Of course, no fragmentation and no reflux should be achieved in the optimal liquid agent.”

Introducing the CIRSE audience to GPX, he described it as a polymer in a hypersaline solution, which solidifies upon injection into the blood vessel

in response to a decreased sodium chloride concentration. The agent is prepackaged in a single, standard syringe and comes with an empty syringe.

The interventionalist connects the two syringes and needs to mix them 25 times before the agent is ready to use.

“Due to its waterborne composition, no specialised catheters are needed and no DMSO [dimethyl sulfoxide] and no vortexing prior to the procedure is required”, Mühl-Benninghaus explained.

In the present, pre-clinical study, the investigators set out to assess the in vivo performance of the GPX in a rabbit model.

To this end, elastase-induced aneurysms were created in 10 New Zealand white rabbits. Each aneurysm was embolized with low viscosity GPX using an Echelon 10 microcatheter (Medtronic) with balloon assistance. The mean aneurysm neck diameter, width, and height were

3.6±1mm, 3±0.8mm, and 7.4 injection from the new ±1.4mm, respectively. The embolic agent through the mean dome-to-neck ratio Echelon10 microcatheter. was 0.9±0.2.

Our impression was that Ninety per cent of there was a little varying aneurysms (nine of 10) visibility of GPX”. showed complete stagnation “Upon gross of intra-aneurysmal flow examination at 28-days, within 30 minutes of device tissue appeared normal”, deployment. One aneurysm he reported. Histological showed moderately examination of the diminished intra-aneurysmal Ruben Mühl-Benninghaus vessel wall, however, flow within 30 minutes due did reveal “evidence of to distal migration of GPX that still was some inflammation reaction”, but Mühlconnected to intra-aneurysmal embolic.

Benninghaus said that he did “not have This was assessed via digital subtraction the final results”. angiography (DSA), performed preCompared to stent-assisted coil deployment, as well as five, 10, and 30 embolization in the same model, MühlBenninghaus said that the occlusion rates achieved with GPX were similar. “We have also performed previously in the same model the same thing with onyx, and we did see less fragmentation with GPX. We did not use any remodelling balloon due to the cost of balloons. The remodelling balloons could provide better stability of the microcatheter. For further investigations, this might be an option.”

When concluding, he outlined some limitations of the present study. Namely, minutes post-deployment. the small study population, and the DSA was also performed one month outstanding final histological results. after the procedure in the eight surviving He summarised that while GPX was rabbits (two of the study animals did easy to use and did not require DMSO, not survive to one-month post-procedure). the agent’s viscosity needs improving, and All eight aneurysms were completely although it has the potential to achieve occluded. durable occlusion of cerebral aneurysms, “We did not see microscopically any its clinical relevance will have to be fragmentation of GPX, and we did not assessed in larger and longer-term studies. see any adhesion to the catheter or the “It looks to us to be a promising balloon”, Mühl-Benninghaus noted. embolic agent for neuro-intervention “We did observe some resistance during therapy,” he stated.

It looks to us to be a promising embolic agent for neurointervention therapy.”

Transvenous embolization should not be first-line treatment, study concludes A new study has found that transvenous embolization for brain arteriovenous malformations (AVM) may have a high rate of complete angiographic obliteration, but also a high rate of procedure-related morbidity and mortality, delegates attending a neurointerventions free paper session at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain) heard.

T

he results were part of a prospective, singlearm study that explored the surgical approach’s safety and efficacy in the treatment of ruptured AVMs as a last resort, delivered by Yingkun He (Henan Provincial People’s Hospital, Zhengzhou, China).

He et al sought to establish the safety and curability of the treatment as, owing to the limited reported data available, transvenous embolization is still considered an unproven salvage therapy. “Since there is only a limited number of cases reported using this approach, effectiveness and safety remain unclear,” He said. “In this study we tried to further validate this method.”

Over a two-year period, 21 consecutive patients with a ruptured brain AVM took part in the study.

Safety was evaluated by observing the procedurerelated complications occurring within one month, He observed, and the primary outcome of efficacy was complete angiographic obliteration of the AVM nidus on the six-month follow-up angiography.

Of the 21 patients, 19 (90.5%) were technically

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feasible while six (28.6%) had procedure-related complications. This included five haemorrhages and one infarction. “Fortunately, the permanent disability and death were one each,” He said.

Some 16 (84.2%) patients had immediate angiographic obliteration among the 19 technically feasible patients. The median angiographic follow-up for 14 patients was 5.5 (three to 15) months, and in 13 (92.9%) patients there was complete obliteration

Transvenous embolization can only be performed in highlyselected brain AVM with high complete obliteration rates.”

of the nidus conformed. “Among them, one patient in whom immediate angiographic obliteration was not achieved showed spontaneous obliteration at the 13-month follow-up,” He continued. “There were no recurrences during the follow-up period. The good functional outcome (mRS≤2) ratios improved from 57.1% (12/21) at pre-operation to 66.7% (14/21) at one-month follow-up and 100% (19/19) at six-month follow-up respectively.”

The study team reported comparable total occlusion rates with the literature: 93.3% versus 96% (90.5% versus 100% technically feasible). But they reported a high complication rate (28.6% versus 6% in the literature). This may be due to the fact the study included only patients with ruptured AVM as compared with the literature, He noted.

“Fortunately most of the patients with complications had good outcomes after receiving appropriate treatments,” He said.

The lead author drew attention to some of the limitations of the study: it called upon a small sample size, he said, and it was highly selective having been included as salvage procedures due to a lack of good microsurgical, transarterial and radiosurgical options, “which may imply greater propensity for procedural risk than in other studies”.

Overall, He concluded: “So transvenous embolization can only be performed in highlyselected brain AVM with high complete obliteration rates, improved functional outcome, and acceptable morbidity and mortality rates.

“But, more experience is needed to discern the role of this technique in the management of ruptured AVM and should not be considered as the first-line treatment.”

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Artificial intelligence

CIRSE puts artificial intelligence in the spotlight “Artificial intelligence [AI] is everything that includes the analysis of data in order to perform certain tasks,” Marc Sapoval (Hôpital Européen Georges Pompidou, Paris, France) told the audience at the 34th Annual Meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain). Along with Tobias Jakobs (Hospital Barmherzige Brueder Munich, Munich, Germany), Sapoval moderated an expert round table on AI, where panellists and participants from the floor discussed deep learning techniques, as well as augmented and virtual reality in interventional radiology (IR).

Machine learning: “Within the next few years, AI will absolutely give us superpowers”

“When we think of machine learning, often we think of pneumothorax detection, brain haemorrhage detection, automated diagnoses. That kind of thing is cool, but there are a really diverse set of things that machine learning can do for us—it can do really interesting things in interventional radiology far beyond that”, Kevin Seals (David Geffen School of Medicine at UCLA, Los Angeles, USA) promised at the start of his talk on applying machine learning to IR practice. “I think within the next few years, AI will absolutely give us super powers”.

Seals’ own work involves applying smart speakers to IR, starting with the idea that, when an interventional radiologist is in the angiosuite and has donned sterile attire, they “lose the ability to interface with technology to some degree”. He proposed that using smart speakers in this scenario is a solution to this problem, and would enable physicians to “really rapidly get information” without sacrificing sterility. He listed key features of smart speakers as being screen-less, sterile, fast, and intuitive.

“A huge problem in medicine now is doctors being buried behind a screen, not making eye contact with patients, so screen-less is a big deal”, he opined. “The rapidity of information [is important]—being able to ask the room a question and in a split second the answer materialises. Using conversation is super intuitive. There is almost nothing as intuitive as just saying ‘I want to know this’ and you get that information.”

Seals has also used this technology to work on device sizing (“building a tool that lets you say ‘I have this sort of stent, what size sheath do I need?’”), equipment cost (for example, “really rapidly determining how much is this wire compared to that wire”), and automated, preoperative calls (“a phone dialogue in an automated way using machine learning”).

“These things are cool and interesting, but they are baby steps towards the really, really cool things we will be able to do in the future”, Seals enthused. Enumerating possible uses of machine learning in the future that he finds exciting, he included inventory querying: “We often say ‘What stents do we have?’, and sometimes someone physically has to go to a storage room and they come back ten minutes later and it is ridiculously inefficient. Imagine if you could just ask the room, ‘What 5mm stents do we have?’ and just immediately get that information.”

He also believes that different types of electronic medical records (EMR) query will “be a big deal”.

For example, he imagined wanting to ask simple questions, such as if a patient has any allergies, but also more complicated ones: “Given that machine

November 2019 | Issue 76 learning can do sophisticated things, you can also ask complex questions, such as ‘How is this patient’s bowel structured?’. Say you are placing a G tube, you can get that information really quickly [using machine learning] by it digging through the chart and understanding language in an intelligent way.”

Another potential use of voice in IR, Seals suggested, is “wisdom of the crowd at scale”. He described how, as machine learning is increasingly used, the algorithm will be exposed to more cases. “You can imagine over time the machine learning algorithm seeing 10,000 cases—it could [use this data to tell the physician] what others might do. [For example,] ‘the particularly senior physician tends to use this approach at this particular time in the case, or this is what has worked historically’”.

Seals iterated how important he believes machine learning to be within the context of the burnout epidemic observed worldwide amongst physicians. He commented, “Some of these things seem like little perks and small little efficiency boosters, and like they are not necessarily that big of a deal, but physician burnout is a huge deal, and it is an epidemic at this point and a huge problem. Anything that makes our workflow a little smoother and our life a little bit easier is actually extremely valuable.”

All of these uses of machine learning in IR count as “friction reduction”, but Seals believes there are a lot of other potential utilities for this technology. He listed “analysis superpowers”, such as understanding a tumour “in a way that the human eye cannot; understanding that this particular tumour, with its subtle features and its texture, might respond to transarterial chemoembolization [TACE] or ablation, or something else. So extracting information from images that humans cannot see to guide our therapies”. A further example of how AI can be utilised in IR is through case curation: “You can imagine an algorithm crawling through the chart and automatically identifying filters that need to be removed, for example, either by detecting the filter in an image or just the text of an EMR and correlating that with different information to determine if the filter should come out, so passively we could build a large

Interventional radiology has always been at the forefront of medicine.”

list of filters that should be removed, creating both interesting cases and making sure that filters do get removed appropriately.”

Augmented reality: “Welcome to the future of medicine”

Miltiadis Krokidis (Addenbrooke’s University Hospital, Cambridge, UK) welcomed the CIRSE audience to “the future of medicine” during his talk on augmented reality (AR) at the congress. He defined AR as the superimposition of 3D images into reality, where the projections are integrated into the physician’s environment. This usually requires the use of a device, he said, such as specially designed glasses or goggles.

“For IR, AR might be helpful to explain complex procedures to patients, and would take our consent form, for example, to another level”, he postulated. Furthermore, Krokidis stated that AR “is definitely an excellent teaching tool”, and one which has been implemented in several schools already, particularly in the USA. An additional use of AR that Krokidis foresaw for interventional radiologists is the potential for radiationless navigation. He explained how AR could help increase procedural accuracy and, if integrated into routine clinical practice, could lead to “navigation of tools without the need for radiation or real-time imaging”.

He informed delegates that though this has not been done yet clinically, there have been successful cadaveric studies, and this is something he is “aiming” for.

“Interventional radiology has always been at the forefront of medicine”, he concluded, and the advent of AR is something he hopes will be embraced by his IR colleagues across the world.

When asked if they used AR in their practice, no audience member raised their hand. Responding to this, Gerard Goh (Monash University, Melbourne, Australia) commented from the floor that both AR and AI are already being used by most clinicians today: “Things such as a roadmap is AR. That is when we take an image and overlay it onto our image-intensification screen. We are also using things like AI: the X-ray tube automatically adapting for the kVp and milliamps on the X-ray tube is a form of AI. I think that, as this area expands, a lot of these tools will develop and we will use [them] in everyday practice. In fact, we are already using a lot of these things but we do not realise.

I think all these technologies will be things that, as interventional radiologists, we will not even think about them, because we will be so used to having these tools to help us in our daily practice.”

From L to R: Marc Sapoval, Rahil Kassamali, Kevin Seals, Ziv Haskal, and Miltiadis Krokidis

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MedTech Insights

November 2019 | Issue 76

Henry V can inspire us to develop innovative techniques for reducing radiation exposure During a session on radiation protection technologies at the 2019 Transcatheter Cardiovascular Therapeutics (TCT) meeting (25­–29 September, San Francisco, USA), Lloyd W Klein (Rush Medical College, Chicago, USA) said that Henry V led the heavily outnumbered English army to victory at the Battle of Agincourt (1415) because he “figured out how to use an old weapon in a new way”. He added that physicians needed to take a similar innovative approach to developing technologies for reducing radiation exposure.

HE EXPLAINED THAT, at the Battle of Agincourt: “The French had the best weapons, the best armour; they had the best everything. They [the English] were outnumbered seven to one. And yet, 7,000 French troops died during the battle versus a few hundred English. How did Henry V do this?” According to Klein, the answer is not the “great motivational speech” that Shakespeare gave him (“probably the best speech ever written in the English language”) but Henry V’s innovative military tactics.

“Henry figured out that the French armour could be used against them.

So, he made them charge through a muddy field. And then to take further advantage, he figured out how to use an old weapon in a new way— the longbow [more than 80% of the English army had longbows]. The longbow made the heavy armour obsolete,” Klein said. He added that physicians were “now looking for our longbow” in terms of innovation to reduce radiation exposure.

Klein made clear that there is a need to reduce radiation exposure, outlining the damaging side effects of exposure to patients, operators and staff. He stated that the side effects could be related to the radiation itself (deterministic injuries and stochastic injuries) and/ or to having to wear lead-lined aprons to protect against exposure (musculoskeletal injuries). Therefore, Klein said, it was “time for a safer environment”.

While he did acknowledge that technologies for reducing radiation exposure were already available, he said that they had limitations. The Zero-Gravity radiation protection system (Biotronik), for example, was “cumbersome” and the CorPath robotic angioplasty system (Corindus Vascular Robotics) gave “less procedural control than we would like”. Concluding, Klein said: “If the same level of commitment to innovation that has been applied to other fields of interventional medicine was transferred to workplace

safety, then the career of the interventionalist and their staff would undoubtedly be more comfortable”.

Jennifer A Tremmel’s (Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, USA), who was speaking at the same radiation protection technologies session as Klein, agreed that there was a need to reduce radiation exposure and that current technologies have limitations. “The downside to many radiation reduction techniques is that they take effort. You have to push a button, move yourself or a device, or learn a new technique.

Ideally, a system would reduce

via eye-tracking (ControlRad View). Tremmel reported, based on the results of a 2016 study, that this leads to a “75% or greater radiation reduction from Lloyd Klein whatever dose you would have been getting”.

“Radiation risk is a real concern for operators, staff, and patients.

It is our responsibility to minimise that risk. This includes getting our administrators to pay for equipment that keeps everyone safe. Technology is increasingly

Radiation risk is a real concern for operators, staff, and patients. It is our responsibility to minimise that risk.” radiation for us and our patients automatically without interrupting our workflow.” She then proposed that ControlRad was such a system.

Tremmel explained that ControlRad worked on the principle that peripheral vision was not as important as central vision.

“Peripheral vision has value but there is no need to have the same image quality, [and thus] the same amount of radiation, over the entire field of view. Instead, it would be better to limit the radiation only to the area we are focusing on (which is 5% of our visual field), but keeping the periphery visible.”

According to Tremmel, ControlRad focuses on the operator’s area of interest while maintaining the peripheral view. It attenuates radiation (and image quality) for the peripheral view by using dynamic semi-transparent filters. The system can be integrated into existing fixed and mobile C-arm units, and the operator identifies the area of interest via a tablet (ControlRad Trace) or

offering us solutions—those that require minimal learning and do not affect our workflow will be easier to adopt,” she concluded.

Following Tremmel, Jean-Michel Paradis (Québec Heart and Lung Institute, Québec, Canada) spoke about the Newton system. He explained that it was a “double suspension system” that was designed to support the weight of the leaded aprons of two operators, adding that the system could be used “with your personal radiation protection apron, with virtually no motion restriction”. Furthermore,

BIBA Briefings

Paradis commented, the Newton system could potentially allow you to choose “a thicker/heavier garment” to improve your radiation protection because you did not have to support the weight of your apron.

In contrast to Paradis, both James A Goldstein (Department of Cardiovascular Medicine, Beaumont Health System, Royal Oak, USA) and Amir Belson (Neoguide Systems) spoke about technologies that were designed to eliminate the need for radiation protection.

Goldstein reviewed the Protego system, describing it as a shield that provided “comprehensive total body exposure protection” but one that did not “interfere with procedural performance”. In his talk about an “innovative robotic shield device” (Radiaction), Belson commented: “It is deployed to encapsulate the imaging beam. The system blocks scattered radiation at its source—the patient and the table, and it provides 360-degree, full-body protection”.

During the discussion following the talks on the new technologies, Klein called for action to better protect operators against the dangers of radiation exposure. He said: “Our [interventional] societies should come together to demand technologies that reduce radiation exposure. We need to be clear that this [the current situation] is something we are no longer OK with; change is something we should insist on. It is time for us to say that this is no longer acceptable.

We do not want to have to live our lives like this.”

BIBA Briefings is an online platform (www.bibamedtech.com/bibabriefings) that gives an in-depth analysis of the latest market intelligence from BIBA MedTech Insights (www.bibamedtech.com). It also reviews the latest industry news and pipeline developments.

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Interventional oncology

Issue 76 | November 2019

Digitised IR examination increases candidate numbers The European Board of Interventional Radiology (EBIR) examination has been fully digitised, allowing greater numbers of participants to sit it at once. The examination was introduced by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) nine years ago, though Maria Weren, head of Certification and Accreditation at CIRSE, tells Interventional News that the society has “constantly been developing and adapting it according to the requirements and advancements of this specialty”.

T

he new examination format, launched in autumn 2019, is divided into two sections. The first is a Clinical Case Scenario Examination, which presents candidates with a series of questions that reflect the decisions faced by interventional radiologists when handling a clinical case. This section replaced the oral component of the examination. The second part is a General Clinical Practice Examination, similar to the old multiple-choice examination.

Explaining the ramifications of digitising the examination, Weren says, “Previously, we were limited to examining only 30 candidates, a number which hardly met the demand anymore because we saw a significant increase in applications over the years.

This September, 65 candidates sat the examination at once!”

Indeed, Raman Uberoi, EBIR Examination Council chairperson (Oxford, UK) has said that “In their new format, examinations can be attended by significantly more candidates, at least 70–80 per sitting”.

In addition to allowing more participants to sit the exam at once, these changes mean that the tests can take place over one day, rather than two. Uberoi explained: “This will give the candidates more time to attend the conferences that the EBIR is scheduled around.”

Exams can be attended by significantly more candidates.”

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Lipiodol “clinically feasible” imaging biomarker, study concludes Lipiodol (Guerbet) can be used as a clinically feasible imaging biomarker for doxorubicin kinetics after conventional transarterial chemoembolization (cTACE), a study presented at the Symposium on Clinical Interventional Oncology (CIO; 11–13 October, Miami, USA) concluded. The data were presented by Todd Schlachter (New Haven, USA), who also concluded that larger enhancing tumours are associated with higher overall systemic doxorubicin exposure.

SCHLACHTER AND HIS coinvestigators set out to compare the pharmacokinetic profiles of doxorubicin and its metabolite after lobar versus selective cTACE, and to identify surrogate markers for high systemic drug exposure.

An interim analysis of their single centre, phase 1, prospective study included 30 patients treated with lobar or selective cTACE. Those treated with cTACE were given 50mg doxorubicin and 10mg mitomycin-C mixed 1:2.2 with Lipiodol followed by Embospheres (Merit Medical). The primary endpoint was the concentration of doxorubicin and doxorubicinol in peripheral blood samples, measured with a standard, non-compartmental pharmacokinetic analysis, and the secondary endpoint was the absence of treatment-related toxicity within three to four weeks post-cTACE. Peak concentrations of doxorubicin and doxorubicinol were higher after lobar than

selective cTACE stratified according to Lipiodol distribution, Schlachter reported.

In addition, cTACE of one segment (“tumour-on-a-stick”, as Schlachter put it) achieved significantly less non-target Lipiodol deposition in the liver than multi-segmental or lobar cTACE. Clinical and laboratory adverse events were generally rare and mainly mild to moderate, Schlachter said. “Clinical toxicity occurred more often after lobar than selective cTACE, despite the smaller number of patients with statistical significance regarding the event of fatigue [p=0.044],” he detailed.

However, Schlachter did acknowledge that this was a relatively small patient cohort, which included both primary and secondary liver cancer. Only 21 of 30 patients received the full doxorubicin dose, but dose normalisation was performed.

This presentation was awarded CIO’s runner up for best abstract.

Conference coverage

Issue 76 | November 2019

“The opportunity is enormous”: CIO attendees experience thyroid ablation case in virtual reality

The 11th Symposium on Clinical Interventional Oncology (CIO; 11–13 October, Miami, USA) hosted a virtual reality (VR) case presentation, where delegates placed their smartphones into a provided cardboard headset and watched Auh Whan Park (UVA Health, Charlottesville, USA) perform a prerecorded thyroid ablation as though they were in the operating room.

This case presentation followed a series of talks discussing state of the art thyroid intervention, versing the audience in the current mainstay of thyroid cancer treatment.

SPEAKING IN HIS capacity as panel moderator, Ziv Haskal (UVA Health, Charlottesville, USA) introduced the live case: “I have had the great fortune and pleasure of being involved in this meeting for ten years, and they have tolerated a lot of the things I have done.

There is a certain atmosphere here—maybe it is the Miami meeting or the southern Florida meeting that just makes it a cool and hip way to learn things—and I think, at least for me, things just stick better when you can meet faculty and talk to them and see things that

CIO attendees using the VR headsets

might be defining. I will never forget the first time I saw a live EVAR [endovascular aortic repair] case at ISET [International Symposium on Endovascular Therapy] a few decades ago. No matter how many papers you had read beforehand, seeing that live was transforming. It was several years before I did my first case, so there is sort of an inertia, but [witnessing that live case is nevertheless] a marked event.

“What we are going to do here is try to give you a little bit of that cool by putting you in that intimate, close-up seat, in the room, where you can watch Dr Park do a thyroid ablation. The purpose is to take something that probably none of you have done, and show you that […] you can actually do this: this is something you can learn and put into your practices. The opportunity

[We are] putting you in that intimate, close-up seat, in the room, where you can watch.”

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is enormous. This will happen in the USA; whether it is going to be interventional radiologists (we all have experience with ablation, after all), or endocrine surgeons [is to be decided]—it is going to be performed by whoever is going to bring it [to institutions], and whoever is going to do it well.”

Prior to the session, Ziv Haskal attendees downloaded a free application to their smartphones, and then used this to stream the case. By placing a smartphone into the cardboard headsets provided, attendees were transported to Park’s operating room, where they watched a 15-minute thyroid ablation case. Haskal provided commentary throughout, describing operator decisions and drawing the audience’s attention to certain technical aspects of the case. Turning around whilst wearing the VR headset, session participants could see a presentation slide outlining the procedural steps.

The case

The patient was a woman with two benign nodules in the right thyroid lobe, which had been growing for two years prior to the procedure. Her preprocedural thyroid function tests were normal. The patient had opted for radiofrequency ablation (RFA) over a thyroidectomy to preserve her singing voice.

The procedure was a success, with Park reporting: “She [the patient] is now really happy. She sent me a thank you letter to say that she had an invitation to perform at a concert, she is a jazz singer, so she is really happy and grateful.”

Miami Beach hosts the biggest Symposium on Clinical Interventional Oncology yet The Symposium on Clinical Interventional Oncology (CIO) returned to the Eden Roc/Nobu Hotel, Miami, USA, on 11–13 October 2019 for its 11th annual meeting. This was CIO’s debut as a standalone meeting, having separated this year from the International Symposium on Endovascular Therapy (ISET), which took place 27–30 January 2019 (Hollywood, USA).

T

he three-day CIO meeting covered key updates in the world of interventional oncology, with event organisers enthusing: “As the field of interventional oncology [IO] rapidly expands, so must the premier arena for practical IO education. Renowned for its originality, practicality, and focus on improving patient care, CIO is the mustattend symposium for those looking to learn concise, efficient applications from the experts.”

CIO founder Barry Katzen (Baptist Cardiac and Vascular Institute, Miami, USA) adds: “Importantly, because of the growth of IO and the need to integrate multidisciplinary oncology faculty, after 11 years of evolving from the ISET content, CIO became its own meeting. As with all of our activities, the programme directors ensure that our attendees leave with new and useful information that will help their practice immediately, along with information that may shape their practice in the short-term future.”

Expanded this year, the meeting played host to more than 40 faculty members, with delegates having the chance to listen to and discuss more than 80 presentations over the course of the weekend.

The meeting kicked off with a pre-conference session covering IO fundamentals, bringing audience members who may be new to IO up to speed with a 90-minute programme devoted to the basics of oncology terminology, hepatocellular carcinoma (HCC) diagnosis, staging, and treatment, chemoembolization, radioembolization, ablation, and palliative care.

Next, lead programme directors Ripal Gandhi and Constantino Peña (both Miami Cardiac and Vascular Institute, Miami, USA) moderated a session entitled “Year in Review: Update on Liver Therapy”. This afforded delegates the opportunity to reflect on research published within the last year, and to discuss the status of HCC and liver metastatic disease management today.

Barry Katzen

Demonstrations in the exhibition space

Underlining the importance of crossdiscipline collaboration to interventional radiologists’ work, audience members heard from a medical oncologist and surgeon, in addition to their IO colleagues. The session concluded with a series of cases and panel discussion.

Throughout the meeting, there were several other case discussions. Most notably, Ziv Haskal (University of Virginia Health System University Hospital, Charlottesville, USA) chaired the presentation of a prerecorded thyroid ablation using virtual reality (VR) headsets (see below). Commenting on this, Katzen enthuses to this newspaper: “The field test of VR was a first in the USA, fully aligned with our interest in bringing innovation into the educational space.”

Additional cases examined lung and renal ablations, where top operators discussed important elements of the case from beginning to end, highlighting case selection, practical planning, cutting-edge techniques, and real-world follow-up.

New to this year, the meeting featured hands-on workshops on ablation and embolization, a session focused on complications and saves, and the opportunity to engage with operators as they discussed important elements of a case from beginning to end.

In partnership with the Miami Cardiac and Vascular Institute and the Miami Cancer Institute, CIO is endorsed by the Society of Interventional Radiology (SIR) and IO Learning, the official news source for the symposium.

Advances in IO

Issue 76 | November 2019

Temporary protective embolization of non-target liver vessels before Y-90 reduces radiation exposure in healthy tissue

Using degradable starch microspheres (DSM, Embocept) to perform selective temporary protective embolization (TPE) of non-target branches of liver vessels before hepatic radioembolization “markedly reduces” PET-activity in the non-target-volume, and therefore radiation exposure to the normal liver, an animal study has found.

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aul Sieben (Uniklinik RWTH Aachen, Aachen, Denmark) presented the results on behalf of the investigators at the annual scientific meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain).

He outlined why physicians might consider performing a temporary protective embolization prior to Y-90 (Yttrium 90) radioembolization: “Non-target embolization may lead to adverse effects. This is why […] we perform the MAA [microaggregated albumin] test injection, with coiling of hepatic and hepatofugal vessels prior to the Y-90 embolization. Also, there may be a challenging intrahepatic vascular anatomy, which may lead to the accidental deposition of Y-90 in healthy liver tissue, with a side-effect of

radiation […] and less activity deposited inside the tumour. Temporary protective embolization may help to avoid this, by preventing effectively the accidental deposition in healthy liver tissue, while at the same time, because of its temporary nature, maintaining arterial blood supply in the healthy liver parenchyma.”

Y-90 is a high-energy β-radiation emitter, traditionally assessed using Bremsstralhen SPECT to measure intraand extrahepatic post-procedure activity.

However, its accuracy is reduced by its low spatial resolution. For that reason, the researchers used Y-90 PETCT, which uses background positron emission of Y-90 decay. “This helps us to better assess the intrahepatic or potential extrahepatic Y-90 deposition,” explained Sieben, “because of the higher spatial resolution.”

Sieben and colleagues aimed to

demonstrate the safety and efficacy of TPE of arterial vessels supplying nontarget (non-tumour-supplying) branches of liver tissue using DSM. A standard left lobar Y-90radioembolization was performed in seven female mini-pigs who were considered to have a challenging vascular anatomy. In four of the animals, vessel branching was judged to be too close to the microcatheter’s embolization position, and these vessels were selectively embolized using DSM before radioembolization. TPE was not performed in the remaining three subjects, allowing comparison between the two groups, with non-TPE the control group.

Positron emission tomographycomputed tomography (PET-CT) scans, using the positron-decay of Y-90 as the PET-signal source, were used to evaluate intrahepatic activity distribution. Volumes of interest of target-volume (left-sided liver) and non-target-volume (right-sided liver) were calculated using cone-beam CT obtained during intervention to assess Y-90 activity distribution. Left-sided paraspinal muscles were measured as a reference. PET-activity was a metric for Y-90 deposition and thus, for intrahepatic radiation dose, and was compared between the groups: with TPE versus without TPE. Volume of interest was calculated in averaged counts per cubic metre over a period of 30 minutes, which was the duration of the PET-CT scan.

Initial results say transarterial chemoperfusion is safe and effective for treating pleural mesothelioma Transarterial chemoperfusion treatment is safe, and has a promising disease control rate in patients with malignant pleural mesothelioma, Bela Kis (Moffitt Cancer Center, Tampa, USA) reports at the 2019 scientific annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).

IN THEIR PROSPECTIVE study, the investigators set out to evaluate the disease control rate, overall survival, and adverse event portfolio of transarterial chemoperfusion treatment with cisplatin, methotrexate, and gemcitabine in patients with relapsed, unresectable, malignant pleural mesothelioma.

Twenty-three patients were enrolled between March 2016 and May 2018. All had transarterial chemoperfusion treatment every four weeks with 35mg/m2 cisplatin, 100mg/m2 methotrexate, and 1,000mg/m2 gemcitabine delivered via the ipsilateral internal mammary artery and/or descending aorta. All patients had received prior chemotherapy. In addition, four patients had also received radiation therapy, and three patients had a pleurectomy.

“So far, we have performed 128 treatments,” Kis shared, “84 via the radial artery, 24 via the femoral artery.” He reported no transarterial chemoperfusion-related mortality.

The major complication rate was 1.6% (one fever, which Kis said he was “not sure this was related to the treatment”, and one ischaemic stroke, which related to the angiography technique, and from which the patient fully recovered).

There were 100 minor complications: 52 events of chest pain during gemcitabine injection, and 20 events of nausea.

Malignant pleural mesothelioma is not a common indication for interventional radiologists to treat. Kis therefore contextualised these positive results. Malignant

pleural mesothelioma, he said, is associated with asbestos exposure, and was considered a very rare disease until 50 years ago, when industrialised nations started to use asbestos, mostly for insulation. The median latency between asbestos exposure and disease onset is 44.6 years, and the projected peak incidence is expected to be around 2020. Indeed, approximately 2,400 new cases are reported each year in the USA. It has an “extremely poor” prognosis, Kis informed delegates, with a median survival of less than one year for stage 3 and 4 disease. Currently, the only curative option is surgical resection for stage

Transarterial chemoperfusion treatment with triplet chemotherapy [...] is safe.”

1 and 2 mesothelioma, though 85–90% of patients are considered unresectable at diagnosis. “Treatment options for unresectable mesothelioma are radiation therapy and chemotherapy, which are largely ineffective”, Kis said.

Then, in 2013, Thomas Vogl (Johann Wolfgang Goethe University, Frankfurt, Germany) et al published a paper in

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Sieben said: “As expected, there was similar activity in the target volume of both groups [121.3±29.01 counts/ ccm with TPE vs. 147.1±28.44 counts/ ccm without TPE]. On the other hand, there was greatly reduced PET activity in the non-target-volume group, where it was reduced by a factor of around five by protective embolization using the degradable starch microspheres [3.35±1.08 in the TPE group vs.

40.7±6.18 counts/ccm in the non-TPE group]. Also as expected, there was next to no PET activity in our reference [0.12±0.096 counts/ccm with DSM vs.

0.17±0.19 counts/ccm without DSM], which shows that the procedure was technically a success.”

The investigators concluded that TPE with DSM markedly reduced PET activity, and thus irradiation of nontarget liver parenchyma, which in turn may prevent potential adverse reactions.

Sieben added: “Y-90 PET-CT is, by virtue of its superior spatial resolution, an interesting alternative to Bremsstralhen SPECT. This procedure may be especially interesting in patients with compromised liver function, or in cases where the Y-90 radioembolization is used as a ‘bridge to resection’, where you do not want to have any adverse reactions in the fugitive remnant and you need to be extra careful to protect it.”

Accordingly, TPE led to a reduction of PET-activity in the non-target liver volume by a factor of 4.9, without compromising the Y-90-dose in the target volume.

Radiology concluding that “Transarterial chemoperfusion may have the potential to yield positive results and response in the treatment of recurrent and/or unresectable pleural mesothelioma”. Vogl and colleagues directly injected the chemotherapy into the artery supplying the tumour, giving a much higher concentration to the tumour compared to intravenous (IV) administration. This more invasive approach yielded positive results, with a mean survival time of 14.2 months (range: 2.1–33.1 months), “which is excellent in these patients”, according to Kis. “Based on this publication, we designed our prospective study”, Kis explained. The open label, single-arm, phase 2, prospective study enrolled patients with progressive disease who had had at least one line of chemotherapy.

The disease control rate was 70%, which Kis described as “excellent” in this group of heavily pretreated patients with mesothelioma. The median overall survival in this initial report was 7.9 months, which Kis said is less than for Vogl et al. “But,” Kis added: “this study is still ongoing, and several of our patients are still alive.”

Detailing one specific “star patient”, Kis described how, after 12 months of treatment, there was a significant decrease in tumour size. Showing images taken at baseline, after 12 months of treatment, and again after a three-month break from treatment, Kis remarked on the positive outcomes, saying: “He [the patient] felt excellent after 12 months of treatment. He wanted to travel, so he was off treatment for three months. When he came back, after three months, you can see [on the images] that the tumour is starting to come back. So he continued the treatment. So far he has received 27 treatments, and he is still alive three and half years after the initial treatment.”

Whilst the work is still ongoing, these positive, initial results led Kis to conclude that “Transarterial chemoperfusion treatment with triplet chemotherapy every four weeks is feasible and safe, with minimal side effects.”

The enrolment goal is 32 patients, with final results expected in one year.

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IR in the austere environment

November 2019 | Issue 76

Interventional radiology beyond the water’s edge Steve Ferrara Figure 2: Steve Ferrara with a patient on board the USNS Mercy

Comment & Analysis “The steady drumbeat of natural and manmade crises resulting in human suffering fuels an insatiable need for selfless and talented volunteers”, writes Steve Ferrara. Reflecting on the lessons he has learned through a medical career with the US Navy, he describes what it is like to perform interventional radiology procedures in austere environments, and how physicians preparing for their first experience providing either humanitarian assistance or disaster relief should know that these two types of support are challenging in fundamentally different ways. As established “out of the box” thinkers, Ferrara posits that interventional radiologists are ideally placed to offer help in resource-limited settings.

T

hanks to breakneck innovations in fields such as transportation and communication, the world continues to become an ever smaller place. The relative ease and economy of moving people and information across vast distances has connected the global community in ways that were

class is more demanding of government, which improves the prospects for retaining existing gains and advancing new ones (Figure 1).

It is appropriate that we recognise this progress and salute the efforts of so many who have done yeoman’s work for decades to make it possible. It is also

Figure 1: Number of people who are poor, vulnerable, middle class, and rich worldwide

difficult to imagine just 20 years ago.

This compression of time and space has come with astounding benefits, such as the liberalisation of economies that have lifted more people out of poverty in the past generation than any previous epoch in human history. In September 2018, a milestone was reached—hopefully a tipping point, where, for the first time in 10,000 years of historical record, the majority of humankind was no longer poor or threatened by poverty. In fact, by purchasing power parity, more than 50% of the population are considered “middle class” or “rich.” This is significant since a robust middle class creates a virtuous cycle of greater market opportunities to buoy continued economic mobilisation; yet, perhaps more importantly, the middle

an important contextual marker for the responsibility that increasing wealth brings; the incumbent duty embedded into the social contract is for those who have escaped poverty to care for those who have yet to do so. The medical community has a strong, centuries-old tradition of honouring this social contract, caring for the sick and needy within our communities regardless of ability to pay, and often at tremendous personal risk from contagion or strife. In 2019, our communities extend well beyond our neighborhoods, villages, or towns. Our “community” is no longer defined or delimited by our shoreline, but instead by our inspiration.

Natural disasters and armed conflict continue to wreak indiscriminate havoc around the world, and while economic

Figure 3: Aceh province, Indonesia, following the 2004 tsunami

advancements provide the greatest bulwark against the scourges of Mother Nature through public health and physical infrastructure improvements, in 2015 there were still 22,773 deaths due to natural disasters. This is largely because the geographic distribution of economic benefit remains quite disparate, and there is a correlation between economic leftbehinds and extreme natural phenomena, resulting in vast, highly vulnerable populations.

The continued prevalence of global income inequality and the ongoing destruction and suffering secondary to natural disasters and political conflict present a continuing need for medical assistance in the form of both humanitarian assistance (HA) and disaster relief (DR) throughout the foreseeable future. While traditional models of medical relief missions emphasised public health and primary care interventions, experience over the past 15 years has shown the practicality and substantial value of imaging and image-guided interventions in austere environments.

Having surpassed the “proof of concept” phase, the opportunities to perform image-guided interventions in remote environments continues to grow. Due to its obvious substantial logistical capabilities and unique mission, the US military continues to lead and innovate in both the humanitarian assistance and disaster relief environments. The opportunities for civilians to participate in HA/DR missions is also rapidly growing, thanks to a number of organisations, such as RAD-AID, a unique non-governmental organisation specifically dedicated to imaging and image-guided intervention.

As opportunities to deliver interventional radiology (IR) services in the HA/DR environment grow, it is helpful to understand that there are fundamental differences in these two

missions. Cognisance of these differences will inform more realistic expectations and facilitate both the planning and execution phases of the mission.

Humanitarian assistance

Humanitarian assistance missions typically involve going to developing nations that are in a “status quo” environment: for example, they are resource-limited, but not acutely affected by a natural or political trauma. These missions typically emphasise capacity-building, with an important but lesser role of primary care and public health augmentation.

Capacity-building is best achieved and most durable through education. This can be in the form of didactic and hands-on offerings as well as by way of introduction to continuing resources, such as online journals and search engines. For example, in 2015 I was part of an official US Navy delegation to Vietnam commemorating the 20th anniversary of normalisation of relations between the two nations.

In addition to collaborating in direct patient care in the IR suite over several weeks, I gave approximately 20 hours of lectures on modern IR techniques. In the course of one of the lectures I referenced PubMed. Much to my surprise, my Vietnamese colleagues were fascinated by the reference and probed me to further explain this magical resource known as PubMed. It became quickly apparent that introducing them to PubMed was far more valuable and enduring than anything I could provide in a typical lecture.

Further, it is always important to be mindful of political and cultural sensitivities, especially in the HA role. As an invited guest, the goal is not to highlight weaknesses or comparative deficiencies in the local healthcare system, but to offer practical and realistic strategies of healthcare empowerment that will translate into better outcomes for everyday patients.

IR in the austere environment

Issue 76 | November 2019 This may involve peripherally inserted central catheter (PICC) line placement or wound care education. During an HA mission to a war-ravaged city in the Horn of Africa in 1997, I introduced basic debridement and wet-to-dry dressing change techniques to the surgical team who were treating a ward full of patients with non-healing wounds. Many of these patients also had HIV/AIDS, and while an alternative lecture outlining the latest HIV drug therapy may have seemed useful, the wound care education provided immediate and reproducible benefits to their patients.

HIV drug therapy was so economically out of reach to this community to render it theoretical. Its discussion would have robbed precious time away from practical education and had the pernicious effect of undermining the community’s trust and confidence in their own medical providers.

Disaster relief

Disaster relief is an entirely different paradigm to humanitarian assistance.

Whether in a developed or developing world, the status quo has been completely disrupted and chaos often rules the day.

The medical acuity and complexity is high and often complicated by disruptions to public health and infrastructure.

There may be shortages of clean water, electricity, transportation, and communication. Further, there could be a loss of professional expertise to remedy the deficits and manage the crisis.

Following the massive Asian tsunami in 2004 that killed an estimated 230,000 people across 14 countries, Aceh province on the Indonesian island of Sumatra was hardest hit with 167,000 deaths. When the USNS Mercy arrived in Aceh, we found every hospital and healthcare provider had been lost to the disaster (Figures 2, 3).

No local expertise could be recruited to assist in the relief effort and all treatment plans were influenced by the knowledge that patients could not obtain follow-up once relief personnel departed the region.

For physicians accustomed to caring for patients in resource-rich America, this created a novel set of challenges apart from the obvious clinical ones.

While the interventional radiologist’s efforts in the HA environment focuses on capacity-building, diagnosis, and low-complexity intervention, the DR environment demands high-complexity therapeutic interventions such as embolization, IVC filter placement, and drainage catheter placement. The common thread between HA and DR, however, is how vitally important the cognitive and technical expertise of IR is in each setting.

From a purely cognitive standpoint, the IR mindset is uniquely well-suited to this “out-of-the-box” environment. In contrast to some medical specialties, interventional radiologists are intensely solution-focused. The nature of doing high-level therapies such as aortic repair through a percutaneous access demands both creativity and optimism. We are a stubbornly practical field that thrives on repurposing devices and techniques—an enormously valuable mindset in resourceconstrained, austere environments. From a technical standpoint, minimally-invasive therapies with quick recovery times are

immensely better-suited to environments where follow-up care is low-tech, limited, or nonexistent.

In 2009, a simple procedure shifted the landscape of battlefield medicine and catapulted IR to the forefront. A local Afghan man presented ill from an empyema. He could not stay in our NATO hospital in Kandahar, and the local facility lacked the expertise to manage a surgical tube thoracostomy. We placed a pigtail drainage catheter and improvised with an IV bag and tubing since we did not have a proper drainage bag system at the time.

This simple procedure provided the “proof of concept” necessary to win the hearts and minds of the US military medical establishment and ushered in the era of

IR as an integral component of combat casualty care.

A world without the need for humanitarian assistance or disaster relief is aspirational, but distant. The steady drumbeat of natural and manmade crises resulting in human suffering fuels an insatiable need for selfless and talented volunteers. Continuous improvements in imaging technologies such as ultrasound and digital radiography have made them more portable and higher quality than ever. Advancements in portable energy generation and storage capacity further potentiate the ability to deploy advanced imaging modalities such as CT and C-arm fluoroscopy. Most importantly, however, is the recognition of IR’s value to the HA/

27

DR paradigm. Our relentless focus on practical and innovative solutions is ideal for resource-constrained settings. While a medical mission is not for the faint of heart—be prepared to be challenged, and frequently outside of your comfort zone—it is also amongst the most gratifying and impactful professional and personal experiences possible. For an interventional radiologist, that sounds like a great day at the office.

Steve Ferrara is an interventional radiologist and retired US Navy Captain.

He was formerly the Navy’s chief medical officer, and during his 25-year service he deployed with the Army, Navy, and Marine Corps.

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Interview

November 2019 | Issue 76

Profile

Ricardo García-Mónaco

Establishing the first Interventional Radiology department in Argentina, Ricardo García-Mónaco is a pioneer of minimally invasive, image-guided therapies in South America. Looking back on a career that spans more than three decades, he discusses how establishing interventional radiology (IR) as a clinical discipline rather than a technical one is crucial for the field’s survival and success, and recalls a particularly memorable case where IR intervention in a two-day-old baby saved the patient from amputation and enabled her to go on to become the healthy, active teenager she is today.

What initially attracted you to interventional radiology (IR)?

When I was in my second year of residency in radiology, in 1985, my hospital incorporated digital subtraction angiography equipment, the first of its kind in my country.

Before that the Radiology departments in Argentina did not have vascular suites. I was selected by the chair of Radiology to join the new Angiography Unit (at the time the unit only performed diagnostic examinations), in addition to the regular residency curricula. I was very happy with the patient commitment I could get in radiology through this subspecialty, and started reading about the subject in the radiology journals that we had at the time in Argentina: American Journal of Roentgenology (AJR) and Radiology. I was rapidly fascinated by the possibilities of therapeutic angiography, as it was then called. I foresaw the tremendous future of the endovascular approach as a proper tool to treat different diseases, especially through embolization procedures that were not recognised or regularly performed at that time in my country. Except for cardiologists performing angioplasty procedures, there were not many physicians interested in vascular procedures, and I realised it was a great opportunity to develop my career in what was a rather “unknown” area in Argentina at the time.

Who have been important mentors for you throughout your career?

I was very lucky to have important mentors in my career, who positively marked my professional and personal pathways. First of all, during my residency, Eduardo De Santibanes, an outstanding young liver surgeon at the time, introduced me to the importance of clinical commitment and patient follow-up—not very common amongst radiologists. He always encouraged me to be in the operating room while surgery was being conducted on any of my angiography patients, and then to go to the pathology department to observe the specimen resected.

He was very keen to explain every detail of the surgery to me, and to elucidate the correlation with the imaging studies I had performed preoperatively.

Years later, when I went to France to train in vascular and interventional radiology, I was lucky enough to meet two outstanding mentors: Pierre Lasjaunias and Alain Roche. Knowing them and incorporating their ways of practicing IR was a breakthrough in my career. They were top IR physicians ahead of their time, and they developed the foundations of many of the clinical and technical interventions still performed to this day worldwide.

Indeed, both of them were mentors for a whole generation of interventional radiologists, and many that trained with them are now successful professionals at different international facilities.

Which innovations have most influenced your career, and how?

As I have been in IR for 30 years, I have seen many innovations, including technical developments, material refinements, new devices, new interventions, new indications of IR treatments, and improvements in equipment and software. But what has most influenced my career has been the conceptual shift from IR being

a technical speciality to becoming a clinical, patientcentred one. Indeed, this “innovation” is increasing IR recognition among other clinical and surgical specialties, allowing interdisciplinary interactions to offer IR as a solution to the patient as it occurs with medical or surgical therapies. A nice example of innovation in this setting is the recent development of interventional oncology, now regarded as the forth pillar of cancer care, joining medical, surgical, and radiation oncology.

What were the biggest challenges and rewards in establishing Argentina’s first interventional radiology department?

Argentina being a rather conservative country, one of the biggest challenges was overcoming the disbelief that a radiologist could have a therapeutic role and run an interventional department. As radiologists are commonly regarded as physicians who only work with images and who do not interact with patients, both patients and doctors were unaware of the possibilities of IR. I remember in my early days back from France, every indication and every procedure I performed were like tests, because my results were under constant scrutiny from other physicians.

Demonstrating that IR training differs a lot from that of diagnostic radiology and that we are specifically trained to treat certain diseases, along with our positive results, minimised this reluctance. Another big challenge was to organise all the staff, including nurses and technicians, as the path to success is dependent on paramedical staff as well as IR. Doing so many procedures requiring specific materials for the very first time in my country (such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), transjugular intrahepatic portosystemic shunt (TIPS), and venous stenting), I had to explain the advantages of IR to the hospital administrators and payers, as these were initially regarded just as additional costs. Indeed, this challenge still continues today with procedures recently introduced to my country, such as radioembolization, cryoablation, and venous deprivation.

On the other hand, establishing an Endovascular Therapy and Interventional Radiology department was very rewarding. Developing a single department performing all types of image-guided therapies regardless of the organ (except for the heart) prevented other specialties from developing these types of procedures in their own domain. This was different to other hospitals, where neurointerventions, peripheral angioplasty, aortic aneurysm grafts, vertebroplasty, and many other procedures were being performed by other specialities.

A single, broad department allowed not only important clinical activity, but also enabled educational endeavours, evidenced by the number of young Latin American interventional radiologists trained at our facility. Being recognised as one of the best teaching centres in Latin America and the high quality standards advocated by the Joint Commission is one of the biggest rewards for me.

As a founding member of the Argentine College of Vascular and Interventional Radiology (CARVI), what are your ambitions for the society?

I was the first president of this recently created society.

The main goals are to foster education in IR and to work with the national government to recognise IR as a true speciality. Additionally, it is a facilitator for physicians interested in the subject and wanting to pursue an IR career. It is also a professional and juridical way to interact with other medical specialities and the minister of health from an official position.

What is the most exciting research coming from South America in IR right now, in your opinion?

The expenditure on research in South America is very low compared to other regions. However, some exciting research has originated from South America, such as the introduction of stent grafts to treat aortic aneurysms (albeit developed by a vascular surgeon), or the first prostate arterial embolization (together with Portugal). The latter, developed by Francisco Carnevale in Brazil, is probably the most relevant research to come out of South America in recent years. The same group is still performing additional work on the matter, and we have studied the macro- and microvascular anatomy of the prostate and its implications for embolization. The field of interventional

Interview

Issue 76 | November 2019

29

Fact File

volleyball and dancing. This made me very happy, especially considering she risked amputation as a newborn, and this was not done thanks to our IR decision.

What do you think the future of IR will look like?

IR has a bright future, because innovations and improvements in imaging capabilities are constant.

However, IR needs to become a true clinical specialty, just like surgery or paediatrics. IR has not yet found the correct pathway to succeed and survive.

Should it be a subspecialty of radiology, or should it run separate and by itself?

Should the medical community or payers accept IR as a self-specialty, or as a therapeutic technique inside a broad specialty (as is the case with “interventional neurosurgery”, performed by neurosurgeons, and “endovascular surgery”, performed by vascular surgeons)? Of course I do not have the answer, but new generations of interventional radiologists should consider that clinical competence is as important as technical skill.

IR procedures will continue to grow, because in my view the number of open surgeries being performed will continue to fall, and ultimately these will be replaced by minimally invasive or medical options, except for in a few indications.

What is the biggest challenge in IR today?

oncology is very exciting, and we are part of some international randomised controlled trials, including RETNET, the first study to compare bland embolization versus conventional TACE versus DEBTACE in neuroendocrine liver tumours.

Would you describe a particularly memorable case?

I have many memorable cases—some due to amazing, positive results, and others that have saved patients’ lives or much improved their quality of life. Among these, maybe the most memorable was a newborn with a life-threatening condition due to multi-organ haemorrhages and congestive heart failure, secondary to a giant right lower limb tumour (Kaposiform Hemangioendothelioma). The patient was so critically ill, despite medication, that amputation of her right leg was considered to stop the irreversible coagulopathy caused by the tumour. Instead, we intervened to embolize the tumour early on the second day of life—a challenging intervention in this 3kg, decompensated newborn—which lead to a dramatic and total recovery.

Most memorably, I met the patient recently, now a teenager with a normal life, practicing several sports, including

Atomisation of the specialty by other disciplines could jeopardise the future of IR. The most notorious examples are neurointerventional procedures that in many countries are performed by neurosurgeons, or endovascular interventions performed by vascular surgeons. Interestingly, in some countries there is a trend for surgical departments to establish a “percutaneous surgery unit” that performs drainage of fluid collections, gastrostomy, bile duct interventions, and even tumour ablations. I think this is one of the biggest challenges in IR at the moment; strategies must be built accordingly.

Fortunately, SIR, CIRSE, and many other IR societies are aware of this and are currently facing this problem.

What are your hobbies and interests outside of medicine?

I am a family man, so enjoy spending time with my family, watching soccer games with my son or daughter in stadiums, and seeing my son play in the Argentinian Rugby Union tournament. I love sports, and played rugby in the first division during my youth. More recently, I have been coaching young rugby teams for several years. I used to ski with the family every winter and like to fly cast in Patagonia lakes and rivers in the summer. I also like to cook a typical Argentine meal called “asado” on Sundays, a kind of firewood grilled beef, and to watch movies or TV series at night, or dine with friends and family.

Current positions 1992–Present

2005–Present

Head of Interventional Radiology and Endovascular Therapy, Hospital Italiano, University of Buenos Aires, Buenos Aires, Argentina Head of Vascular and Interventional Radiology, Hospital Italiano, University of Buenos Aires, Buenos Aires, Argentina

Previous positions 2005–2018

1991–1992

1991

1990

1990

1988–1992

1987–1988

1983–1987

Chair of Department of Radiology, Hospital Italiano, University of Buenos Aires, Buenos Aires, Argentina Medecin Consultant, Radiologe Interventionelle, IGR, Villejuif, France Medecin Assistant a Titre Etranger, Bicêtre Hospital, University of Paris, Paris, France Visiting Fellowship, Toronto Western Hospital, Toronto, Canada Visiting Fellowship, New York University, New York, USA Training in Angiography and Interventional Radiology, Bicêtre Hospital, University of Paris Senior Chief Resident, Hospital Italiano, University of Buenos Aires, Buenos Aires, Argentina Residency in Radiology, Hospital Italiano, University of Buenos Aires, Buenos Aires, Argentina

Society positions 2016–2018

2014–2018

2006–2008

2000–2006

President of the International Society of Radiology (ISR) President and founding member of the Argentine College of Vascular and Interventional Radiology President of Inter-American College of Radiology (CIR) President of the Argentine Society of Radiology (SAR)

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Vascular access

November 2019 | Issue 76

A thumbnail sketch of haemodialysis access: Past, present, and future in the USA Bart Dolmatch Comment & Analysis Bart Dolmatch gives an overview of the history of haemodialysis access in the USA, and balances the pros and cons of current access options. He outlines his hopes for the increasing role he believes interventional radiologists should play in the management of end-stage renal disease patients, and how innovation is helping physicians achieve better clinical results.

WHILE THE INCIDENCE of endstage renal disease (ESRD) in the USA has reached a plateau over the past few years, prevalence continues to climb due to lower mortality rates.1 ESRD is treated with renal replacement, but it is costly and places a growing financial burden upon Medicare participants. Medicarepaid claims for ESRD, including renal replacement, represented over 7% of all Medicare payments and exceeded US$35 billion in 2015–2016.2 Renal replacement can be performed with a kidney transplantation, peritoneal dialysis, or haemodialysis. For many people, transplantation may be the best option, but due to the ongoing shortage of donor organs, fewer than 3% of people with ESRD received a preemptive transplant. Peritoneal dialysis, conveniently performed at home by most people, accounted for only 9.7% of all renal replacement. Haemodialysis accounted for renal replacement for nearly 90% of the ESRD population in the USA.1 Haemodialysis is simply the process of cycling a person’s blood through a filtration system, removing toxins while balancing fluids and electrolytes, and returning the blood back to the patient’s circulatory system. Efficient cycling of

blood requires a way to both remove and replace blood, typically through one of three methods: a dual lumen catheter; an arteriovenous graft (AVG); or an arteriovenous fistula (AVF). An AVG is a surgically interposed conduit between an artery and vein that is accessed for haemodialysis. An AVF is the direct connection of an artery to vein, where the venous side of the circuit serves as the access site. Both an AVG and AVF are accessed for haemodialysis using two-needle cannulation—one for cycling blood to the dialyser, the other to return blood to the patient.

All three types of vascular access have pros and cons. Catheters are convenient but have the highest morbidity rates compared to AVGs and AVFs.3,4 AVGs had a high rate of usability, but up to 75% failed in their first year.5 Once an AVF is ready for repeated successful haemodialysis, it is often an excellent long-term vascular access solution with better durability than an AVG. However, up to 60% of AVFs were not ready for use within four to five months after surgery, and many were abandoned before any attempt to salvage.6 While there are problems with all forms of haemodialysis access, the

AVF remains the preferred modality and accounts for about two-thirds of haemodialysis access in the USA.5 For more than 50 years, creation of an AVF was the purview of surgeons. However, in 2018, two catheter-based systems were cleared for percutaneous AVF creation by the US Food and Drug Administration (FDA)—BD’s WavelinQ and Avenu Medical’s Ellipsys. The hope is that percutaneous AVFs, created without pre-operative delay, will have high rates of early unassisted usability and remain functional. So far, data are encouraging.6,7 AVGs and AVFs often develop stenoses that reduce dialysis efficiency and can lead to thrombosis. Percutaneous transluminal angioplasty (PTA) has been used for decades, though with varying durability. We have learned that bare metal stents do not improve durability over successful PTA.8–10 However, covered stents from BD such as the Flair, Fluency, and Covera, as well as

The hope is that percutaneous AVFs, created without preoperative delay, will have high rates of early unassisted usability and remain functional.

So far, data are encouraging.”

Gore and Associate’s Viabahn, reduce restenosis rates. These covered stents have demonstrated superior outcomes in prospective clinical trials when compared to PTA.11–15 In addition, BD’s Lutonix drug-coated balloon also confers improved outcomes compared to PTA.16 The past few years have seen great strides in creating and maintaining haemodialysis access. We now have new ways to achieve better results, with the hope that through ongoing innovation

IN.PACT AV access trial meets primary safety and effectiveness endpoints The first results from the IN.PACT AV access clinical study, comparing the investigational IN.PACT AV drug-coated balloon (DCB; Medtronic) to percutaneous transluminal angioplasty (PTA) in patients with de novo or non-stented restenotic arteriovenous (AV) fistulae lesions, were presented at the Cardiovascular and Interventional Radiology Society of Europe (CIRSE) annual meeting (7–11 September, Barcelona, Spain). The study met all primary safety and effectiveness endpoints.

“T

hese results demonstrate the promise of IN.PACT AV DCB to not only address these critical issues, but to potentially improve the quality of life of patients undergoing dialysis,” says Andrew Holden (Auckland, New Zealand).

The IN.PACT AV access study is a randomised controlled trial (RCT), which has enrolled 330 subjects

at 29 sites in the USA, Japan, and New Zealand. The primary effectiveness endpoint was defined as freedom from clinically-driven target lesion revascularisation (CDTLR) or access circuit thrombosis measured through six months post-procedure and the primary safety endpoint was defined as the serious adverse event rate involving the AV access circuit through 30 days post-procedure.

and comparative prospective clinical research, we can improve the lives of patients with ESRD. Bart Dolmatch is an interventional radiologist at The Palo Alto Medical Foundation and El Camino Hospital, Palo Alto, USA. References 1. 2 018, United States Renal Data System Annual Report, End-Stage Renal Disease, Chapter 1, https://www.usrds. org/2018/view/v2_01.aspx, Accessed 15 August, 2019 2. 2018, United States Renal Data System Annual Report, End-Stage Renal Disease, Chapter 9: Healthcare Expenditures for Persons with ESRD, https://www.usrds. org/2018/view/v2_09.aspx, Accessed 15 August, 2019 3. Charmaine E Lok and Robert Foley, Vascular Access Morbidity and Mortality: Trends of the Last Decade, Clinical Journal of the American Society of Nephrology (CJASN), 2013; 8 (7):1,213–1,219 4. Gürbey Ocak, et al, Haemodialysis catheters increase mortality as compared to arteriovenous accesses especially in elderly patients, Nephrology Dialysis Transplantation, 2011; 26(8):2,611–2,617 5. 2018 United States Renal Data System Annual Report, End-Stage Renal Disease, Chapter 3: Vascular Access. https://www.usrds.org/2018/view/v2_03.aspx, Accessed 15 August, 2019 6. Charmaine Lok et al, Endovascular Proximal Forearm Arteriovenous Fistula for Hemodialysis Access: Results of the Prospective, Multicenter Novel Endovascular Access Trial (NEAT), American Journal of Kidney Disease, 2017; 70(4):486–497 7. Jeffrey E Hull, William C Jennings, Randy I Cooper, et al, The Pivotal Multicenter Trial of UltrasoundGuided Percutaneous Arteriovenous Fistula Creation for Hemodialysis Access, Journal of Vascular and Interventional Radiology, 2018; 29(2):149–158 8. Quinn S F, Schuman E S, Demlow T A et al, Percutaneous transluminal angioplasty versus endovascular stent placement in the treatment of venous stenoses in patients undergoing hemodialysis: intermediate results. Journal of Vascular and Interventional Radiology, 1995;6(6):851–855 9. Beathard G A, Gianturco self-expanding stent in the treatment of stenosis in dialysis access grafts, Kidney International, 1993;43(4):872–877 10. Hoffer E K, Sultan S, Herskowitz M M, Daniels I D, Sclafani S JA, Prospective randomized trial of a metallic intravascular stent in hemodialysis graft maintenance. Journal of Vascular and Interventional Radiology, 1997;8(6):965–973 11. Haskal ZJ, Trerotola S, Dolmatch B, Schuman E, et al, Stent Graft versus Balloon Angioplasty for Failing Dialysis-Access Grafts, 2010, New England Journal of Medicine, 2010;362:494–503 12. Haskal ZJ, Saad TF, Hoggard JG, Cooper RI, et al, Prospective, Randomized, Concurrently-Controlled Study of a Stent Graft versus Balloon Angioplasty for Treatment of Arteriovenous Access Graft Stenosis: Two-Year Results of the RENOVA Study, Journal of Vascular and Interventional Radiology, 2016 Aug;27(8):1,105–1,114 13. Falk A, Maya ID, Yevzlin AS, and RESCUE Investigators, A Prospective, Randomized Study of an Expanded Polytetrafluoroethylene Stent Graft versus Balloon Angioplasty for In-Stent Restenosis in Arteriovenous Grafts and Fistulae: Two-Year Results of the RESCUE Study, Journal of Vascular and Interventional Radiology, 2016; 27(10):1,465–1,476 14. Vesely T, DaVanzo W, Behrend T, Dwyer A, Aruny J, Balloon angioplasty versus Viabahn stent graft for treatment of failing or thrombosed prosthetic hemodialysis grafts. Journal of Vascular and Interventional Radiology, 2016 Nov;64(5):1,400–1,410 15. Covera Vascular Covered Stent Instructions for Use, Bard Peripheral Vascular, B05872 Rev.3/05-18. https:// www.accessdata.fda.gov/cdrh_docs/pdf17/P170042D. pdf, Accessed August 15, 2019 16. Scott O Trerotola, Jeffrey Lawson, Prabir RoyChaudhury and Theodore F Saad; for the Lutonix AV Clinical Trial Investigators, Drug-Coated Balloon Angioplasty in Failing AV Fistulas: A Randomized Controlled Trial, Clinical Journal of the American Society of Nephrology (CJASN), 2018; 13(8):1,215–1,224

The study enrolled a patient population who had been undergoing dialysis for an average of 4.3 years. Overall, the IN.PACT AV DCB group demonstrated clinical benefit compared to the PTA control group.

Per Kaplan-Meier estimates, the primary patency rate of the target lesion at 180 days was 86.1% in the IN.PACT AV DCB group compared to 68.9% in the PTA control group (p<0.001). At 210 days, this was 81.4% in the IN.PACT AV DCB group compared to 59% in the PTA control group (p<0.001). Patients in the IN.PACT AV DCB group required 56% fewer reinterventions to maintain target lesion patency through 210 days compared to those in the PTA control group A low rate of access circuit-related serious adverse events, with 4.2% in the IN.PACT AV DCB study group compared to 4.4% in the PTA control group through 30 days. Additionally, the Kaplan-Meier estimated freedom from all-cause death through 360 days was 90.6% in the IN.PACT AV DCB study group and 90.4% in the PTA control group.

Arteriovenous fistulas

Issue 76 | November 2019

e-PTFE-covered stent demonstrates “significantly better” target lesion primary patency than angioplasty at one year The results of AVeNEW, the first level 1 clinical study dedicated solely to the use of a covered stent designed to treat stenosis in the arteriovenous (AV) fistula access circuit, show that the Covera vascular covered stent (Bard) demonstrates “significantly better” target lesion primary patency compared to percutaneous transluminal angioplasty (PTA) at six months, with the difference sustained in the 12-month data. Also, better access circuit patency was maintained at 12 months.

L

ead investigator Bart Dolmatch (The Palo Alto Medical Foundation, Mountain View, USA) recently presented this “first look” at the 12-month results of the AVeNEW study at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain).

Dolmatch and colleagues describe AVeNEW as a prospective, international, multicentre randomised controlled clinical trial, designed to assess the Covera vascular covered stent compared to angioplasty for the treatment of stenotic lesions in the venous outflow of upper extremity AV access circuits in patients dialysing with an autogenous fistula.

The Covera stent, which received US Food and Drug Administration (FDA) approval in July 2018, is described on the FDA website as “an expandable,

flexible, metal [nitinol] tube covered with a material called expanded polytetrafluoroethylene [ePTFE].”

Dolmatch and colleagues comment that AVeNEW is “the first level 1 clinical trial dedicated solely to the use of a covered stent graft designed to treat stenosis in the AV fistula access circuit,” and they conclude that the covered stent group demonstrated “significantly better” target lesion primary patency compared to the PTA group at six months, with the difference sustained at 12 months. Access circuit primary patency was numerically different at six months, and “statistically better” for the stent graft group at 12 months.

The investigators enrolled 280 patients with stenosis ≥50% in the venous outflow of the AV access circuit, and with clinical or haemodynamic evidence of fistula dysfunction, at 20 centres across the USA, Europe, Australia, and New Zealand.

They detail that patients received either PTA alone or PTA followed by covered stent placement.

The primary endpoints were six-month target lesion primary patency and 30-day safety. Secondary outcomes included target lesion primary patency at 12 months, and access circuit primary patency at six and 12 months.

The majority of patients included in the study were Caucasian (68.6%) with a mean age of 63±12.4 years, and most patients were male (61.8%). Patients included in the study had multiple risk factors for renal dysfunction, including diabetes mellitus (69.6%) and hypertension (97.1%). Lesions were restenotic in 73.2% of cases, were on average 29.3±17.2mm long

31

(diameter stenosis: 72.5±12.5%), and 53% were in the cephalic vein arch.

The proportion of patients free from a primary safety event with the covered stent (95%) was non-inferior to PTA (96.4%) at 30 days (p=0.002, significant for non-inferiority). Target lesion primary patency was significantly better for the covered stent group (78.7%) versus the PTA group (47.9%) at six months (Kaplan-Meier analysis) and remained statistically significant at 12 months (57.5% vs.

21.2%, respectively; p<0.001). Access circuit primary patency at six months numerically favoured the covered stent (50.7%) group compared to the PTA group (43.8%) while at 12 months the difference was statistically significant (28.9% vs. 17.7%, respectively; p=0.016).

The investigators summarise that the results of the AVeNEW study have shown that the covered stent conferred more than a 30% improvement in patency at the target lesion compared to PTA at both six and 12 months. Furthermore, the covered stent group had statistically superior access circuit patency at 12 months. “Clinical follow-up is ongoing,” they comment, “and will continue out to three years”.

Covera stent (BD)

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Peripheral interventions

November 2019 | Issue 76

No evidence of increased mortality with paclitaxel-based devices in German claim database through 11 years A real-world safety analysis of paclitaxel-based devices in peripheral arteries, recently published in the European Heart Journal, showed no evidence for increased mortality over a period of 11 years. “In summary,” the authors remark, “our analysis found the use of drug-eluting devices to be safe for endovascular therapy of the lower limbs”.

ELABORATING ON THE findings, they comment that “Particularly with regard to long-term mortality, neither drug-coated balloons nor drug-eluting stents was associated with increased risk compared to non-drug-eluting devices”. Furthermore, they say the analysis “exemplarily demonstrates the significance of health claims data for assessing urgent safety concerns without undue delay”.

In 9.2 million insurants of the German BARMER Health Insurance, Eva Freisinger (University Hospital Münster, Germany) and colleagues retrieved data on the application of paclitaxelbased drug-eluting stents (DES) and drug-coated balloons (DCB) from their introduction on the market in 2007 until present.

They then indexed all patients with first endovascular revascularisation

between 2007 and 2015 and followed them until 31 December 2017.

Freisinger and colleagues included each subsequently applied DES, DCB, bare-metal stent, and uncoated balloon in further analysis.

Multivariable Cox regression analysis considered potential non-linear time-dependent hazard ratios of DES and DCB over 11 years. The authors identified 64,771 patients who underwent 107,112 endovascular revascularisation procedures using 23,137 drugeluting devices.

The investigators report that this analysis showed paclitaxel-based DES not to be associated with increased long-term mortality for over 11 years past application (all p>0.057). DCB was associated with decreased longterm mortality for the first year past application (HR 0.92; p<0.001), and

indifferent correlation in the years thereafter (all p>0.202).

Addressing the significance of the study, the authors remark: “Our study debilitates current safety concerns resulting from previous findings,” referring to recent data which have indicated a two-fold increase in long-term mortality among patients treated with paclitaxel-based drug-eluting devices.

While drug-eluting devices represent a well-established therapy being widely used for endovascular revascularisation for peripheral vessels, the authors note, these safety concerns affected international regulatory authorities to call for several alerts for further application of drug-eluting devices.

“Compared to the meta-analysis by Katsanos et al that resulted from smallsized selected cohorts of the underlying RCTs,” Freisinger and colleagues continue, “our data reflect the unselected real-world patient collective to which the

Our data reflect the unselected realworld patient collective to which the devices actually apply.”

Novel paclitaxel-nano-coated balloon achieves less restenosis than plain angioplasty at two years Two-year results of EffPac—a randomised controlled trial to assess the safety and efficacy of a novel drug-coated balloon (DCB) with a nanotechnology coating—have been announced. The investigators, Ulf Teichgräber (University Hospital Jena, Germany) and colleagues, report that use of the DCB in question, iVascular’s Luminor, resulted in a significantly lower incidence of binary restenosis compared to percutaneous transluminal angioplasty (PTA).

T

he new data, presented for the first time at the annual scientific meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE 2019; 7–11 September, Barcelona, Spain), also showed a significant clinical and haemodynamic improvement from baseline, similar to the level of improvement achieved with PTA, but with considerably fewer repeat revascularisations. The investigators found no difference to PTA regarding safety.

The EffPac (Effectiveness of paclitaxel-coated Luminor balloon catheter versus uncoated balloon catheter in the arteria femoralis superficialis) trial was designed to assess the safety and efficacy of the Luminor paclitaxel drug-eluting balloon in inhibiting restenosis and in ensuring long-term patency. The investigators compared the DCB catheter to noncoated PTA in stenotic or occlusive lesions of the femoropopoliteal artery.

Between September 2015 and December 2016, the investigators enrolled 171 subjects across 11 German study centres. Eighty-five of these patients were randomised to DCB angioplasty, with the remaining 86 being assigned to the PTA group. They note that before the 24-month mark, analysis was discontinued

devices actually apply.”

Commenting on the patient cohort, they say it is “representative compared to other large epidemiological studies in terms of age, sex, cardiovascular risk burden, and LEAD [lower extremity artery disease] severity,” referring directly to studies by Olinic et al and Fowkes et al.

While the authors stress that the present analysis covers a “large and comprehensive” database of unselected real-world patients, they admit that it is limited by the “general constraints” in the use of secondary healthcare data. Specifically, they note, real-world administrative data do not provide information on the underlying reason for DED treatment, representing a potential selection bias.

Luminor DCB

for 25 patients in the DCB group and 30 patients in the PTA cohort.

The primary endpoint of the study was defined as late lumen loss at six months. The secondary endpoints at six, 12, and 24 months included primary patency, target lesion (TLR) and vessel (TVR) revascularisation, quality of life—assessed by the EQ-5D—change of RutherfordBecker classification (RBC), ankle-brachial index (ABI), and major and minor amputation rates, among others.

Eva Freisinger

The authors comment that 12 months into the study, the investigational DCB catheter proved “highly effective and safe in inhibiting restenosis,” and demonstrated a walking improvement in change of RBC compared to PTA. Twelve-month results of the safety and efficacy of the Luminor device had been released prior to the CIRSE 2019 presentation. The authors detail that at six months, the late lumen loss was on average 0.92mm lower in the DCB group than in the PTA group (95% confidence interval [CI]: -1.36mm to -0.49mm, p<0.001). Significantly more patients showed a walking improvement after DCB treatment at six months (p=0.021).

Looking now at the 24-month results, Teichgräber and colleagues reveal that primary patency (the rate of freedom from restenosis) was 90.2% (95% CI: 80.4–95.2) in the DCB arm, compared to 94.7% (95% CI: 86.4–98) at 12 months. The corresponding figures for the POBA cohort were 62.7% (95% CI: 50–73) and 71.3% (95% CI: 59.4–80.3).

Freedom from TLR in the DCB group was 97.2% (95% CI: 89.1–99.3) at 24 months, compared to 98.7% (95% CI: 91.1–99.8) at 12 months. In the PTA group, the figures were 78% (95% CI: 66.5–86) and 81.6% (95% CI: 71–88.7), respectively.

In both groups, patients were of similar age. While the DCB cohort was 68±7.5 years old, on average, the PTA group was 68.1±8.8 (p=0.979). There were slightly fewer male patients in the DCB group (60%) than in the PTA group (69.8%; p=0.239), and also slightly fewer diabetic patients in the DCB group (36.5%), compared to 40.4% in the PTA group (p=0.681). There were fewer current smokers in the PTA group than among DCB patients (40.5% vs. 43%; p=0.856). There were just over double the number of patients with critical limb ischaemia in the DCB group (3.6%) than there were in the PTA group (1.2%; p=0.929).

Endovascular interventions

Issue 76 | November 2019

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THIS ADVERTORIAL IS SPONSORED BY BOSTON SCIENTIFIC

Endovascular intervention for the treatment of femoropopliteal lesions: ELUVIA is safe and effective Boston Scientific leads the largest clinical programme investigating drug-eluting therapy for the treatment of peripheral arterial disease (PAD), in an effort to capture safety and efficacy data, and to help physicians make informed decisions. PAD affects an estimated 27 million adults in Europe and North America, and is associated with significant morbidity and mortality, as well as impaired quality of life and lower-extremity functioning over time.

Boston Scientific’s ELUVIA® drug-eluting stent is a safe, effective option for these patients, writes Yann Gouëffic, MD, PhD (Paris, France).

E

ndovascular intervention for the treatment of femoropopliteal lesions is established as a first-line strategy. In the 2000s, self-expandable stents showed superiority over percutaneous transluminal angioplasty (PTA), but in-stent restenosis rates were still high (19–37%). Paclitaxel-coated balloons have been shown to successfully prevent intimal hyperplasia, but the use of scaffolding appears to be a more effective option to reduce restenosis.

In 2011, Michael Dake (Tucson, USA) et al evaluated a polymer-free, paclitaxel-eluting stent (ZILVER® PTX®, Cook Medical), and showed that it was superior to balloon angioplasty in terms of patency and reintervention, with provisional stenting. However, there was still room for improvement, notably in terms of controlled drug release: ZILVER® PTX® does not utilise a polymer to release paclitaxel, and delivers approximately 95% of the total drug load within 24 hours of deployment. Paclitaxel levels are sustained in the artery wall for 56 days. However, in-stent restenosis predominantly occurs a year after nitinol stenting in the femoropopliteal segment, so the kinetics of paclitaxel release by ZILVER® PTX® do not match the kinetics of restenosis at the femoropopliteal level.

ELUVIA® is characterised by its nitinol platform (INNOVA®), low paclitaxel loading (0.167µg/mm2 dose density), and use of polymer to control drugelution. The amount of paclitaxel is much lower for ELUVIA® compared with other drug-eluting devices.

The polymer is similar to the polymer used in coronary paclitaxel-eluting stents, and, as a result, its safety and biocompatibility have been well studied.

The polymer is composed of a dual layer. The primer layer (poly n-butyl methacrylate) promotes adhesion of the active layer (poly[vinylidiene fluoridehexafluoropropylene]) to the stent, while the active layer controls the release of paclitaxel.

After promising preclinical studies, ELUVIA® was first evaluated in humans in the MAJESTIC registry. In MAJESTIC, 57 patients were treated for femoropopliteal lesions with an average length of 70.8mm±28.1. The primary patency at one year reached 96.4% (KaplanMeier [KM] estimate). Subsequently, a randomised (2:1) controlled trial was launched comparing ELUVIA® to ZILVER® PTX® for femoropopliteal lesions: IMPERIAL.

through one month, major amputation of the target limb through 12 months, or target lesion revascularisation (TLR) through 12 months. Additionally, a prespecified post-hoc superiority analysis for the primary efficacy endpoint was included within the statistical analysis plan. A duplex ultrasound core laboratory and a clinical events committee were involved to assess the primary endpoints.

Between December 2015 and February 2017, 309 patients were included in the ELUVIA® group and 156 in the ZILVER® PTX® group. The mean age of participants was 68.5 and 67.8 years old, respectively, and 42–44% of the patients were diabetic. The mean length of the treated lesions ranged from 81.8–86.5mm.

Non-inferiority was shown for both efficacy and safety endpoints at 12 months. Primary patency was observed for 231 (87%) of 266 patients in the ELUVIA® group, and for 106 (82%) of 130 patients in the ZILVER® PTX® stent group (difference 5.3% [one-sided lower bound of 95% CI –0.66]; p<0·0001).

Moreover, statistical superiority was met in the post-hoc analysis of 12-month primary patency in the full cohort analysis. Among the secondary endpoints, the rates of thrombosis in the ELUVIA® and ZILVER® PTX® groups were 1.7% and 4%, respectively (p=0.20).

One year TLR rates were 4.6% for ELUVIA® and 8.1% for ZILVER® PTX® (p=0.0142). This statistically significant difference is maintained out to two years, with TLR rates of 12.9% and 20.5% for ELUVIA® and ZILVER® PTX®, respectively (p=0.0472).

Prespecified subgroups at high risk of restenosis and reintervention, namely chronic total occlusion (CTO), high calcium lesion, diabetes, and long lesions, were analysed in the IMPERIAL dataset. Lesions at high risk of restenosis demonstrated a consistent two year TLR rate (Figure 1).

In the ELUVIA® group, non-CTO lesions had a higher average one-year primary patency (90.6% vs. 83.9%).

Of the 193 lesions considered to have moderate or severe calcifications, a primary patency rate of 89.2% was recorded at one-year compared to lesions with no or mild

calcification, which had a patency of 87%. In diabetic patients, ELUVIA® showed primary patency results of 87.4%, consistent with the overall cohort, and in comparison to 80.2% with ZILVER® PTX® at one-year.

Lastly, the 50 long femoropopliteal lesions in IMPERIAL (mean length 162.8mm) had an 87.9% primary patency rate at one year (KM estimate). These data are in line with a previous long femoropopliteal lesion ELUVIA® registry. At one-year, the primary patency rate was 87% (KM estimate). There is remarkable consistency in efficacy across all lesions at high risk of restenosis for this device.

Paclitaxel-coated devices under scrutiny, but benefits outweigh risks

In December 2018, a meta-analysis showed a late mortality signal with certain paclitaxel-coated devices compared to non-coated devices. Notably, the ELUVIA® stent was not included in this. Recently, a new meta-analysis was presented at the FDA Panel in June 2019, though, again, ELUVIA® was not part of these contributing datasets.

However, during this June meeting, additional data were released regarding the comparison between ELUVIA® and coronary drug-eluting stent designs.

Interestingly, the polymer release design principles are similar between both, but paclitaxel concentration is higher in coronary paclitaxel-eluting stents. Over 4,000 patients have been included in randomised clinical trials comparing paclitaxel-eluting coronary stents versus bare metal stents, and no all-cause mortality signal has been observed in a meta-analysis, negating the hypothesis of a systemic effect of paclitaxel delivered by this method.

The FDA highlighted “that for individual patients judged to be at particularly high risk for restenosis and repeat femoropopliteal interventions, clinicians may determine that the benefits of using a paclitaxel-coated device outweigh the risk of late mortality”.

Boston Scientific has developed the largest clinical programme regarding drug-eluting therapy for PAD. The EMINENT RCT is recruiting 750 patients to compare ELUVIA® to bare-metal stents. To ensure long-term data capture both IMPERIAL and EMINENT, follow-up has been extended to five years. SPORTS, an investigatorsponsored study, is an RCT with three arms (total 222 patients) to compare a bare metal stent, a paclitaxeleluting stent, and a paclitaxel-coated balloon (SeQuent Please®, from B Braun) for long femoropopliteal lesions.

Data from this clinical programme, as well as from other ongoing drug-eluting device trials and analyses, should provide further information to help physicians with patient-centric decision-making in the endovascular treatment of femoropopliteal disease, and in particular the treatment of lesions at high risk of restenosis.

Yann Gouëffic, MD, PhD, is affiliated with the department of vascular and endovascular surgery, Hôpital Paris St Joseph, Paris, France.

The IMPERIAL trial

The IMPERIAL trial was designed as a non-inferiority study, including patients with Rutherford category 2–4, with lesions that range from 30–140mm in length. Sixtyfive centres were included to enrol 465 patients. The primary efficacy endpoint was primary vessel patency at 12 months, defined as a binary endpoint based on a duplex ultrasound peak systolic velocity ratio of 2.4 or lower at the 12-month follow-up visit in the absence of clinically-driven target lesion revascularisation or bypass of the target lesion.

The primary safety endpoint was the occurrence of major adverse events, defined as all causes of death

Figure 1. As presented at FDA Panel in June 2019. BSC Data on File. As-treated ELUVIA patients. Abbreviations: CTO, chronic total occlusion; RCT, randomised controlled trial.

Chronic total occlusions

Issue 76 | November 2019

The retrograde approach to CTOs: What, who, when, where, why, and how Lorenzo Patrone Comment & Analysis Lorenzo Patrone talks to Interventional News about retrograde access to lower limb arterial chronic total occlusions (CTOs).

What?

The retrograde approach to lower limb arterial chronic total occlusions was originally described more than thirty years ago but is still sometimes considered taboo.

Who?

I strongly believe that every operator should master the retrograde approach to lower limb arterial CTOs. I routinely run workshops on advanced lower limb recanalisations at my institution, which are open to motivated vascular surgeons and interventional radiologists. The retrograde approach is one of my main focuses during the course, offering the possibility to learn tips and tricks from my recorded and live cases.

When?

The retrograde approach to CTOs should be used sooner rather than later during the procedure in order to increase the recanalisation success rate, thus avoiding having to reschedule the patient for another endovascular procedure/bypass.

I personally use the retrograde approach in 30–40% of my cases, when I struggle more than five to 10 minutes in re-entering into the distal true lumen or when I perforate the vessel during the recanalisation attempt from the antegrade access. The recanalisation success rate using this approach is extremely high.

Furthermore, it allows you to preserve the distal landing zone of the occluded artery with the potential subintimal dissection just limited to the occluded arterial segment.

Where?

The distal superficial femoral artery, proximal anterior tibial artery, dorsalis pedis artery and posterior tibial artery are the preferable choices but any artery can potentially be punctured in a retrograde fashion.

Why?

The retrograde access has almost always been described as a bailout solution after failed standard antegrade approach. The recently published C-TOP classification

has shown how the on-table morphology of the plaque can already predict if patients could benefit from a retrograde approach. This could then be used as the first approach to treating the CTO (a higher rate of successful intraluminal recanalisation from the retrograde approach is described by Fanelli et al when compared to the antegrade one), or to increase the chances of final success by reconnecting with the antegrade wire in the middle of the occluded artery.

The retrograde access is almost always used to exteriorise the wire from the antegrade access. In very rare cases it can be used as the main or even only access from where to introduce balloons or stent.

How?

Retrograde access can be obtained by ultrasound or fluoroscopic guidance, depending on the skill set of the operator and the location/anatomy of the chosen artery. The distal SFA, dorsalis pedis artery and distal posterior tibial artery are usually easily accessible under ultrasound. This approach presents the advantages of better accuracy, real time visualisation of the needle (particularly important in case of patient under local anaesthesia), and avoids radiation exposure to the operator.

The fluoroscopic guidance is, on the other hand, easier to manage for any operator and preferable for retrograde access through a peroneal or proximal anterior tibial artery puncture. Proficient use of fluoroscopic filters can minimise the radiation exposure to the operator.

In this method the needle needs to be advanced at 45 degrees to the skin while keeping it completely in line with the artery to minimise the chance of missing the artery.

The very vast majority of retrograde accesses do not require the insertion of a sheath, and an 0.018’’ wire and a compatible catheter are usually sufficient to cross the occlusion. The actual outer diameter of the sheath is always 2Fr bigger than the indicated size, so by going sheath-less one avoids greater trauma to the punctured vessel.

Angioplasty alone at the level of the retrograde access site is enough to obtain haemostasis in the majority of cases.

Ten tips and tricks

1. The bigger the vessel, the easier the puncture. I think that the distal SFA is probably the most suitable target for someone who wants to start practising in retrograde punctures. If the operator feels comfortable with ultrasound, a good trick could be to scan the patient’s distal thigh by ultrasound before starting the operation and mark on the skin at the level of a possible entry point (remember, however, that if the same distal SFA will be punctured under fluoroscopic guidance the access site will significantly change, being more medial). To have a sterile window already prepared before starting with the recanalisation reduces the effort in getting the access at a later stage.

2. When puncturing under fluoroscopic

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suggest you to keep at least 7–8cm between your puncture site and the distal occluded vessel, in order to achieve sufficient stability once the wire needs to be inserted and the recanalisation starts.

7. Always avoid surgical exposure of the vessels at the level of the ankle, especially in critical limb ischemia patients. The ultrasound approach for these vessels is usually relatively easy and the percutaneous access avoids possible difficult wound healing in already arterially compromised patients.

8. There are different ways to externalise the wire advanced from the retrograde access. One is to try to pass it into a catheter advanced from the antegrade access (6F for the above-knee vessels and 4F for the below-knee ones); the other one is to use a snare, inserted from the antegrade access, to grab it.

In my practice, I now approach all the long SFA occlusions with an initial

Figure 1 a) Distal SFA puncture b) Distal AT puncture c) Proximal AT puncture d) US guided access at the level of the distal PT

guidance, try to zoom in on your potential retrograde access site to increase your accuracy.

3. The needle which I routinely use is the 21Gx7cm one which is part of any micropuncture kit. I then use a 21Gx15cm Chiba needle when the body habitus of the patient suggests to me that the distance to the distal superficial femoral artery, proximal anterior tibial artery, or peroneal artery is longer than in the majority of patients.

4. Always use a 0.018”x300cm long wire, which has to be passed through the needle as soon as the puncture is made because you will benefit from all its length once the wire is through the antegrade and the retrograde access.

5. There is never the need to position the patient prone for a distal SFA/popliteal access. A moderate extrarotation of the knee permits to reach the distal SFA and the proximal popliteal artery in the vast majority of the cases under ultrasound or fluoroscopic guidance. If needed, the tibioperoneal trunk and the distal popliteal artery can be punctured under fluoroscopic guidance through the interossea membrane.

6. Always remember that, when puncturing a deep vessel as the distal superficial femoral artery, the proximal anterior tibial artery, or the peroneal artery under fluoroscopic guidance, you will hit the vessel roughly 4–5cm above your skin entrance. I therefore

over the hill common femoral artery access in order to facilitate grabbing a wire inserted through a retrograde approach by withdrawing my sheath/ catheter to the level of the external iliac artery.

9. Another important trick, useful for patients who need to be punctured distally under fluoroscopic guidance and are not under general or spinal, is to avoid the local anaesthesia before the retrograde puncture. It will be easier and quicker to puncture the distal vessel without getting movement artefacts due to the stinging of the local anaesthesia which can then be easily provided once the retrograde access is secured by the insertion of the wire.

10. Finally, when puncturing distal vessels under fluoroscopic guidance, remember to use one hand to advance the needle and the other one to simultaneously hold the foot. In case the patient moves between the angiogram and the puncture, you can always align the vessel to your reference image again with small controlled movements of the foot.

Lorenzo Patrone is a vascular and interventional radiology consultant at the West London Vascular and Interventional Centre (Northwick Park Hospital, London, UK).

All references for this article are online at www.interventionalnews.com.

Venous thromboembolisms

Issue 76 | November 2019

Updated VTE treatment guideline for patients with cancer revealed

by ASCO An updated guideline on the prophylaxis and treatment of venous thromboembolism (VTE) in patients with cancer has been unveiled by the American Society of Clinical Oncology (ASCO) in its Journal of Clinical Oncology. An expert panel convened by ASCO reviewed evidence—including randomised controlled trials (RCTs) and meta-analyses of RCTs—from the period between 1 August 2014 and 4 December 2018, before providing a list of findings and recommendations.

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atients with cancer are at a higher risk of developing VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), than those without cancer, and have higher rates of VTE recurrence and bleeding during VTE treatment. Consequently, VTE is an “important cause of morbidity and mortality” among cancer patients.

According to the review, two RCTs of direct oral anticoagulants (DOACs) for the treatment of VTE in cancer patients confirmed the efficacy of edoxaban and rivaroxaban, but found they could be associated with an increased risk of bleeding compared to low-molecularweight heparin (LMWH). Two additional RCTs underlined the potential benefits and side-effects of DOACs for thromboprophylaxis in ambulatory cancer patients at a higher risk of VTE. Co-chaired by Nigel S Key (Chapel Hill, USA) and Anna Falanga (Bergamo, Italy), the panel’s systematic review included a total of 35 publications (26 meta-analyses and nine RCTs) on VTE prophylaxis and treatment, and 18 publications on VTE risk assessment (six included multiple types of cancer, while 12 focused on individual cancer types).

In addition to Key and Falanga, 15 additional authors worked on the project.

Speaking to Interventional News about the importance of these guidelines, Key

updated ASCO guidelines reflect the new evidence from clinical research showing the efficacy of new anticoagulant drugs for VTE management in oncology.

The addition of some DOAC to our armamentarium to prevent and treat cancer-associated VTE expands our choice and allows the possibility to personalise treatment based on patient characteristics and type of cancer.”

The updated guideline addresses six clinical questions:

Should hospitalised patients with cancer receive anticoagulation for VTE prophylaxis?

Should ambulatory patients with cancer receive anticoagulation for VTE prophylaxis during systemic chemotherapy?

Should patients with cancer undergoing surgery receive perioperative VTE prophylaxis?

What is the best method for treatment of patients with cancer with established VTE to prevent recurrence?

Should patients with cancer receive anticoagulants in the absence of established VTE to improve survival?

What is known about risk prediction and awareness of VTE among patients with cancer?

In response to the first clinical question,

This iteration of the ASCO guidelines on VTE prevention and treatment reflects an evolving evidencebased set of recommendations.” comments, “This iteration of the ASCO guidelines on VTE prevention and treatment reflects an evolving evidencebased set of recommendations on a common problem in a challenging patient population. Perhaps the greatest advances are the recommendations to consider certain oral direct factor Xa inhibitors for the treatment of VTE and for VTE prevention in higher risk cancer patients.”

Falanga is in accordance, adding, “The

“Should hospitalised patients with cancer receive anticoagulation for VTE prophylaxis?”, ASCO’s guideline states that hospitalised patients who have active malignancy and acute medical illness, or reduced mobility, should be offered pharmacologic thromboprophylaxis in the absence of bleeding, while patients with active malignancy but no additional risk factors may be offered pharmacologic thromboprophylaxis. However,

Anna Falanga

pharmacologic thromboprophylaxis should not be offered to patients admitted for minor procedures or chemotherapy infusion, nor patients undergoing stemcell or bone marrow transplantation.

On the subject of whether ambulatory patients with cancer should receive anticoagulation for VTE prophylaxis during systemic chemotherapy, a new addition to the guideline is that high-risk outpatients with cancer may be offered

37

preferred. Patients with active cancer, including those with metastatic disease or persons receiving chemotherapy, should receive anticoagulation with LMWH, DOACs, or vitamin K antagonists (VKAs) beyond six months.

Responding to expert opinion in the absence of randomised trial data, uncertainty towards short-term benefits, and evidence of long-term harm from filters, ASCO has recommended against the insertion of a vena cava filter for patients with established or chronic thrombosis. Additionally, the guideline asserts that filter insertion has no role for primary prevention or prophylaxis of PE or DVT, though a vena cava filter may be offered as an adjunct to anticoagulation in patients with progression of thrombosis.

Incidental PE and deep vein thrombosis should be treated in the same manner as symptomatic VTE, according to ASCO. Answering the question of whether patients with cancer should receive anticoagulants in the absence of established VTE to improve chances of survival, anticoagulant use is not recommended to improve survival in patients with cancer without VTE. Finally, the guideline addresses what

The addition of some DOAC to our armamentarium to prevent and treat cancer-associated VTE expands our choice and allows the possibility to personalise treatment based on patient characteristics.” thromboprophylaxis with apixaban, rivaroxaban or LMWH. Patients with multiple myeloma receiving thalidomide or lenalidomide with chemotherapy should be offered pharmacologic thromboprophylaxis, according to the guideline.

For cancer patients undergoing surgery, it is recommended that all persons with malignant disease undergoing a major surgical intervention receive perioperative VTE prophylaxis with either unfractionated heparin (UFH) or LMWH, unless they present a high bleeding risk or other contraindications.

Prophylaxis should be commenced preoperatively and continue after surgery for at least seven to 10 days, while extended prophylaxis with LMWH, for up to four weeks, is recommended for cancer patients undergoing major open, laparoscopic abdominal or pelvic surgery.

Regarding the best method of treating cancer patients in order to prevent VTE recurrence, a number of recommendations are included in the guideline. Initial anticoagulation may involve LMWH, UFH, fondaparinux, or rivaroxaban, though LMWH is preferred over UFH for the initial five to 10 days of anticoagulation for patients with newly diagnosed VTE. For long-term anticoagulation of six months, it is stated that LMWH, edoxaban, or rivaroxaban are more effective and therefore Nigel S Key

is known about risk prediction and awareness of VTE among patients with cancer, recommending they be assessed for VTE risk initially and periodically, particularly when starting systemic antineoplastic therapy or at the time of hospitalisation. At the same time, individual risk factors do not reliably identify patients with cancer at high risk of VTE. ASCO argues that oncologists should educate patients regarding VTE, particularly in settings that increase risk such as major surgery and hospitalisation.

Future of IR

Issue 76 | November 2019

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A glimpse of the future: The next decade of interventional innovations Interventional News speaks with Atul Gupta about the future of interventional radiology (IR). As chief medical officer for ImageGuided Therapy, Philips, he enthuses about the possibilities of radiation-free interventional procedures, and a medical world advanced by augmented reality and artificial intelligence solutions.

How has IR changed over the course of your career?

I have been practicing for about 20 years, so when I first started my career, it was simple: just X-ray and a device.

Procedures are becoming increasingly complex. When I do an intervention today, it is no longer just X-ray and device—I have to analyse data from a whole bunch of sources: haemodynamic data, electronic health records, 2D and 3D live imaging, intravascular ultrasound (IVUS) and ablation data.

I have also seen a change in the types of procedure that we do. My entryway to the human body used to be the femoral artery, but now, as we do things like uterine fibroid embolization (UFE), prostate artery embolization (PAE), transarterial chemoembolization (TACE), peripheral vascular disease (PVD) work, and even biliary procedures, we have several different access points: radial, pedal, femoral, jugular, transabdominal. I want to be able to rapidly image wrist to wrist, from head to toe, and I need to be able to do it very quickly and with great image quality.

That is the biggest change I have seen in the last 20 years, the increased complexity of these procedures. Fortunately, technology now exists to help us make these procedures a lot more efficient.

What are the challenges for today’s interventional radiologists, and how can these be overcome?

At CIRSE 2019 [the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe; 7–11 September, Barcelona, Spain], we heard a lot about how we as a specialty have an identity crisis. Not just with patients, but also with other physicians. It is well understood that cardiologists treat the heart, neurologists treat the brain—but what do interventional radiologists treat?

Put simply, everything, everywhere. What other field can treat a liver blockage, a stroke patient, a trauma patient, a prostate patient, kill a kidney tumour, and drain from the lungs, all in one day? We do it all, and that is a challenge. But there are three ways I think you can overcome this identity issue.

Firstly, education in the impressionable years. Any individual specialist knows us for our procedures specific to them: gynaecologists know us as the UFE expert, trauma doctors know us for doing splenic embolization, and geriatricians know us as the people who perform kyphoplasties. They are amazed to hear of all the things that we do outside of their specialty. At CIRSE, the society's

Students Programme brought 350 medical students to the congress. Not all of those 350 are going to go into IR, but they will be IR ambassadors for us, as they learn about all the things that we do.

Secondly, interdisciplinary congresses such as VIVA, ISET, CX, and CIRSE, where all these specialists from across disciplines gather, are important.

Finally, social media, which gives us interventional radiologists the opportunity to get the word out, is playing an increasing role.

Live guidance of a thrombectomy procedure performed with Philips Azurion

What technological developments do you think will be most disruptive in IR?

Lots of things! That is the cool part of the job, I get a glimpse of the future and help define what the next five to ten years of innovation are going to be, and the world that I and my colleagues are going to work in. Philips is an innovation company, so we are very much about creating technology, but it is very important to remember that it is not just about the technology. We are not here to push technology for technology’s sake—technology is the enabler to help physicians do a procedure better.

I think we are going to be working increasingly in a radiation-less, or maybe even radiation-free, world. We are going to be using ultrasound instead of X-ray.

We [at Philips] have technology called TrueView, where I can photo-realistically render 3D ultrasound on the fly, so I can guide a device using ultrasound and see it in 3D, maybe even see it in a hologram in the world of augmented reality (AR).

In addition to sound, we are going to be using light to navigate our devices instead of X-ray. Philips is developing devices using technology called FibreOptic RealShape (FORS), which lets me visualise wires and catheters in 3D using light, instead of X-ray; this was presented to the world through first-in-human cases shown at the 2019 Leipzig Interventional Course (LINC; 22–25 January, Leipzig, Germany), the International Symposium on Endovascular Therapy (ISET; 27–30 January, Hollywood, USA), and the Charing Cross Symposium (CX; 15–18 April, London, UK). Philips acquired EPD Solutions last year, and we now have a new technology called dielectric imaging, which lets you visualise not just the device, but the anatomy, in high definition and 3D, without X-ray. If we can do all this imaging without X-ray, and support it with artificial intelligence (AI), this is, I think, going to be massively disruptive, not just for IR, but for all interventionalists.

Atul Gupta

The Microsoft Hololens 2 AR headset

What can other medical disciplines learn from IR?

like ISET and Vascular InterVentional Advances (VIVA), we also see multiple specialties coming together. None of us work in a vacuum, and so crossing over to approach patient care is extraordinarily important, not just for physicians, but also for industry. Collaboration leads to the very best in innovation.

I think that collaboration is the most important thing that interventional radiologists bring to the table. We know that no two patients are the same, and so we are often asked by other specialities to solve very unique problems, and that lets me as an interventional radiologist be creative. Interventional radiologists are the innovators; we are always inventing new ways of treating patients. That is a hot topic every year, from the annual meeting of the Society of Interventional Radiology (SIR) to CIRSE. By

How are you working to shape the future of IR?

This is the part of my job that I like the best, the innovation piece. The process of how we innovate and co-create with physicians is both extraordinary and

I get a glimpse of the future and help define what the next five to 10 years of innovation are going to be.” collaborating with industry and with other physicians, the procedures that we develop disseminate into other fields.

I think that other medical disciplines love interventional radiologists’ passion for innovation and creativity, but most importantly for collaboration. If I fast forward 10 or 15 years, I would not be surprised to see a blurring of lines between specialties, because a lot of the procedures that we do are increasingly overlapping. What specialist today is the expert in critical limb ischaemia (CLI), or AAA, or venous disease?

Many people: cardiologists, surgeons, and interventional radiologists. I think that we are starting to see physicians meet across specialties. I saw vascular surgeons, cardiologists, and radiologists attending CIRSE 2019. At conferences

fascinating, because you never want to just push technology out, everything has to start with the end-user and patient.

Recently, we brought teenagers into our innovation centre, and allowed them to sit in an interventional suite and start playing with it. These adolescents were born after the iPhone was introduced in 2007, and they are going to be the physicians of the future. Their insights are tremendous. So the process starts early on, but we also work with the world’s leading interventionalists to help us improve our devices, imaging, and software.

Atul Gupta is chief medical officer for Image-Guided Therapy, Philips.

He is also a practicing interventional radiologist in Philadelphia, USA.

Vertebroplasty

Issue 76 | November 2019

Percutaneous vertebroplasty safe and effective only in patients with acute fractures A meta-analysis, recently published in Osteoporosis International, has found that the application of percutaneous vertebroplasty is safe and effective only in patients with acute osteoporotic vertebral compression fractures (OVCFs) having persistent and severe pain.

The investigators recorded no benefits among patients with older fractures or those bearing non-severe symptoms.

A

ccording to the authors, S Lou (The First Affiliated Hospital of Harbin Medical University, Heilongjiang, China) and colleagues, OVCFs are common in the elderly population and are often treated using percutaneous vertebroplasty. However, the effectiveness of percutaneous vertebroplasty reported by various randomised controlled trials (RCTs) is inconclusive. This study therefore aimed to analyse, from published literature, the efficacy and safety of percutaneous vertebroplasty for OVCFs. Lou and colleagues conducted searches in Medline, EMBASE, and Cochrane Libraries since their respective inceptions on 1 January 2019 for RCTs of OVCFs treated with percutaneous vertebroplasty compared with nonoperative treatment. The primary outcomes were pain relief at one to two weeks, one to three months, and six to 12 months. The secondary outcome was the rate of occurrence of

new vertebral fractures, and the metaanalysis was performed using a random effect model.

The investigators included a total of 12 RCTs, comprising 1,624 patients, in the analysis. For the blinded studies, they found statistical differences between percutaneous vertebroplasty and the sham injection group for the three primary outcomes in the subgroup of the VAPOUR (Vertebroplasty for acute painful osteoporotic fractures) trial. Although pain scores were similar between the percutaneous vertebroplasty group and the sham injection group for the VAPOUR trial at each period, the effect size of percutaneous vertebroplasty increased over time.

They found that in the open label studies, percutaneous vertebroplasty significantly reduced pain at all the time points, and that the risk of the new vertebral fractures was similar between the percutaneous vertebroplasty groups

Preventive vertebroplasty effective for the long-term consolidation of vertebral metastases

Preventive vertebroplasty is a long-term, effective means of consolidating vertebral metastases, Frédéric Deschamps (Gustave Roussy Cancer Campus, Villejuif, France) told a spinal interventions free paper session at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain). But the quality of injections matter, suggesting techniques that improve both the quantity and quality of cement diffusion with vertebral metastases require development, he said.

THE STUDY AIMED to evaluate the long-term consolidation of the metastases after the procedure and to report on the risk factors of pathological fractures despite it having been performed.

The spine being the most common site of bone metastases, pathological fractures can result in a

and control groups.

Due to certain limitations of the meta-analysis, Lou and colleagues warn that the results should be “interpreted cautiously”. They note, for example, methodological limitations in the quality of the original studies, such as the unclear random method, the unclear concealment of the treatment allocation, and the inadequate blinding.

In addition, the possibility of publication bias might exist because of the ongoing and unpublished trials, although no statistical evidence for this was detected.

They also note that while the baseline of pain scores and duration of fracture might be key factors affecting the percutaneous vertebroplasty, there might be other clinically relevant but unreported confounding factors, such as the types

Followup longer than 12 months is necessary for further studies to demonstrate the long-term therapeutic effects of percutaneous vertebroplasty.”

significant deterioration in a patient’s quality of life.

In order to measure tumour-related instability, the research team used the spine instability neoplastic score (SINS), which adds together six components: location of the metastases, mechanical pain, spinal alignment, bone lesion type, vertebral body collapse, and posterolateral involvement. With a score of six or lower, there is no instability, Deschamps said; seven to 12 is considered indeterminate, while 13-plus indicates high instability, with surgery required.

“Vertebroplasty is a technique that can be used to restore the vertebral body strength in order to prevent pathological fractures, pain, and neurological complications,” he explained. “It consists of the injection of cement in the vertebral body but also within the metastases.”

Furthermore, Deschamps continued, measurement of cement injection quality involved assessment of the cement’s contact with both endplates, a vertebral filling score (Saliou score), and the metastases filling.

The researchers performed a single-centre, retrospective review of patients who underwent vertebroplasty between January 2005 and January 2016.

A total of 573 patients were enlisted, with 473 excluded owing to follow-up of less than a year, receiving the procedure for palliation of pathological or osteoporosis fractures as well as for consolidation of benign tumours.

Among the 100 who were included, there was a mean age of 54, with 61 female participants and 39 male, and the primary cancer being breast (35%).

The research team enumerated 215 vertebral metastases at the time of the procedure (T0): 138 were considered at risk of pathological fracture (treated metastases) and 77 were not considered at risk (untreated metastases), Deschamps explained.

They compared the metastases’ characteristics using SINS at T0 and the rate of pathologic fracture at one, two and three years between the treated and untreated

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of patients, the degree of bone mineral density, and the types of percutaneous vertebroplasty techniques. Moreover, owing to the limited number of studies, whether the baseline of pain scores and duration of fracture truly affect the percutaneous vertebroplasty “still needs to be determined by further trials”.

Considering the direction of future research, the investigators suggest that it should “focus more on [patients with acute OVCFs and experiencing severe pain] and use more consistent inclusion criteria”. They suggest, for example, that each study should add the confirmation of OVCFs with magnetic resonance imaging (MRI) to the inclusion criteria and use the same threshold of the baseline scores for patient eligibility.

Lou and colleagues also suggest that, since they determined that the baseline information could affect the effect of percutaneous vertebroplasty, further studies “should clearly report the baseline information, such as the duration of back pain, the baseline pain scores, the methods of nonoperative therapy, the PMAA volume, the baseline T-scores, and other clinically relevant factors, to find the association between these factors and percutaneous vertebroplasty.”

Finally, they indicate that a longer follow-up—more than 12 months— with a large enough sample size is “necessary for further studies to determine the long-term therapeutic effects of percutaneous vertebroplasty”.

metastases.

Deschamps outlined the results: “Despite a lower SINS value at T0 (4.5 vs. 5.8; p<0.001), the rates of pathological fracture at one, two and three years were significantly higher among untreated-vertebral metastases compared to the treated-vertebral metastases (p<0.005). Major risk factors of fracture among treatedvertebral metastases were: SINS value ≥8 (OR: 6.3; p=0.012), mechanical pain (OR: 11.295; p=0.001), osteolytic lesion (OR: 8.280; p=0.033) and metastatic vertebral body involvement >50% with no collapse (OR: 12.325; p<0.001), Saliou-score <9 (OR: 8.334; p=0.008), vertebral metastasis filling with cement <50%

My personal advice is to perform at least bipedicular access if you want to perform good consolidation.”

(OR: 7.396; p=0.007), and the absence of cement’s contact with vertebral endplates (OR: 4.876; p=0.014).”

The appropriate selection of vertebral metastases can be done based on the SINS value: if the score is eight or higher, Deschamps said, vertebroplasty should not be performed. “You can do it for pain but for consolidation it is not appropriate and you probably have to discuss consolidation through surgery. If less than eight, vertebroplasty is of great value, meaning a Saliou score of nine or more.”

Deschamps added: “My personal advice is to perform at least bipedicular access if you want to perform good consolidation, and also to consider other techniques such as kyphoplasty or stentoplasty for this purpose.”

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IR outreach

Interventional radiology TED talk raises awareness of image-guided, minimally invasive medicine

November 2019 | Issue 76 vertebroplasty. Lastly, she spoke of a liver cancer patient who could undergo “potentially curative” microwave ablation or chemoembolization in order to avoid either liver transplant and a lifelong immunosuppression, or a long course of chemotherapy with its attendant side effects: infection, bleeding, hair loss, fatigue, and stomach pains.

Reaching an audience of millions, TED talks are an effective means of communicating with large swathes of the general public. This accords with one of SIR’s key mission statements, to reach “around the world and out to partners across corporate, public, and private

Oleksandra Kutsenko, a radiology resident at Upstate Medical University, Syracuse, USA, and Society of Interventional Radiology-Resident Fellow Student (SIRRFS) advocacy chair, has given a TED talk expressing the possibilities of minimally invasive, image-guided medicine.

FOCUSING ON THE “science-fiction”-like capabilities of interventional radiology (IR), Kutsenko began her talk by describing three case studies where patients were not treated with IR procedures, but could have potentially received better treatment if they had been. In the first example, she detailed how a woman who had a hysterectomy could have been saved an invasive surgery, a long recovery time, and her fertility if she had been treated with a uterine fibroid embolization. In the next example, she detailed how a young veteran treated for back pain with opioids could have been spared his resultant painkiller addiction through original treatment with nerve ablation and

Oleksandra Kutsenko

Popular TED educational videos can increase awareness about IR far beyond single hospitals [or] cities.”

sectors to ensure the story of interventional radiology is spread through a range of communication channels”.

In addition to public outreach, SIR advocates on behalf of its members and interventional radiology as a whole before Congress, insurance carriers, and other key decision-makers.

Improving the public awareness of interventional radiology procedures was central to Kutsenko’s talk. “It seems that interventional radiology has been the best kept secret of medicine”, she told the audience. “So let us change this”.

Speaking to Interventional News, Kutsenko comments, “Interventional radiology covers a broad spectrum of minimally-invasive procedures that diagnose and treat almost every organ in the body; we work with physicians in nearly every specialty of medicine and provide some of the best healthcare value and outcomes, and yet our specialty is strikingly unknown among other physicians, legislative bodies, and, most importantly, patients.

“To change this, we need to reach out to large masses of people in the general population and spread the word about the treatment options we have to offer. TED is one of the greatest media platforms that is doing exactly that.

Extremely popular TED educational videos can increase awareness about IR far beyond single hospitals, cities, or even countries. As a result, the information on value of minimally invasive, image-guided procedures can be delivered to large populations, and through them further influence hospital and national policies. The voice of our patients will be heard, and we all should make sure that their health decisions are based on understanding new technically-advanced, IR-inclusive, better medicine.”

After sharing her TED talk on Twitter, Kutsenko was quickly the recipient of much praise from other interventional radiologists on the platform. Replying on the site, aspiring interventional radiologist Alex Sher (Mount Sinai, New York, USA) wrote: “Great talk and thanks for spreading the word about interventional radiology!”

Public view of IR

Issue 76 | November 2019

Public outreach for IR procedures: Is it nice or necessary?

Theresa Caridi Comment & Analysis Theresa Caridi is an interventional radiology advocate, and believes passionately in spreading awareness of minimally invasive, imageguided procedures to both potential patients and referrers. In July 2019, Caridi appeared on ABC 7 News WJLA, an ABC affiliate covering national and local news in Washington, DC, USA, where she talked about uterine fibroid embolization for Fibroid Awareness Month. Here, she describes why it is important for interventional radiologists to market themselves, and how individuals, as well as organisations like the Society of Interventional Radiology (SIR), can best spread their message about what interventional radiology has to offer.

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nderstanding interventional radiology (IR) as a specialty and descriptor has been a topic of much discussion over the last two decades, if not for even longer.1–5 The name itself has been questioned for its reductive nature, in that the term “interventional radiology” fails to explain the complexity and value of what we do.1 We interventional radiologists cannot always describe the type of doctor we are, so it is easy to see how our patients and referrers have a gap in understanding in what IR is and how we can help. It has even been speculated that IR cannot be easily understood because both the specialty and term are in the forefront of true

interdisciplinary medicine—specifically the blending of image, body, and physician.1 Public outreach in the form of speaking/lectures, radio, media, or print marketing may help to provide clarity to both patients and referring physicians on treatment options provided by IR. Additional factors play an important role in the lack of awareness of IR. As interventional radiologists, we may become involved in a patient’s treatment plan later than a primary specialty. Once the traditional specialties have offered what they can and failed, or are ruled out as an option due to a patient’s advanced disease, a referrer may think to involve an interventional radiologist, or a patient

may ask for other options. Due to the diverse nature of our specialty, we lack the longstanding relationship that begins early in a patient’s life, such as that seen with a primary care physician or obstetrician/ gynaecologist. Furthermore, interventional radiologists have knowledge of and treatments for the entire body, and are sometimes lost in the treatment algorithm because we are not the first specialty that comes to mind for a specific organ system.

Lastly, there are many different types of IR practices, and the patient or referring physician may only be familiar with one—and this practice model may not be the one they are looking for.

A good marketing tool is one that derives traction from both patients and colleagues. One of the most effective ways that I have found to reach patients and referrers is through educational videos that demonstrate a physician’s knowledge, but perhaps more importantly also their character and disposition.

When a patient comes in for consultation after having watched one of my educational videos, I get a sense that it has accelerated their comfort level and also their ability to speak about sensitive issues—this tends to be pretty valuable in a women’s health-focused practice where a woman has spent her lifetime building a relationship with her gynaecologist, but has never met her interventional radiologist. This is one of the many challenges that we face.

Podcasts, particularly with video, can have a similar beneficial effect. Any type of video allows viewers to see the physician’s human side and allows for nuances that cannot be demonstrated in a social media snippet. It also seems a bit more credible than the average social media post. This is not to diminish the effect of social media, which has been shown to improve the transparency and accessibility of medicine.6 Social media can be very useful in promoting speaking engagements, radio, traditional media, or

SIR launches new award to celebrate those who champion women in IR The Society of Interventional Radiology (SIR) Women in IR section has launched the Women in IR Champion Award to recognise an individual who has consistently made a significant contribution to the advancement of women in interventional radiology (IR). The award will be presented each year at the society’s annual meeting, with the first honoree receiving the award at the 2020 Annual Scientific Meeting (28 March–2 April, Seattle, USA).

ACCORDING TO THE SIR website, the significant contribution towards women in IR can be in “sponsorship, mentorship, teaching, promotion, advocacy, and recruitment”. The nominee must be a member of SIR for at least 10 years after completing their training, and must be an actively practicing interventional radiologist.

Calls for nominees opened on 9 September 2019, and will be conducted through to 31 October 2019.

Individuals can self-nominate or be nominated by a peer. The SIR website details that all nominations must be accompanied by two letters of support (three if it is a self-nomination) outlining how the nominee has contributed to the advancement of women in IR and a copy of the nominee’s CV. Aneesa Majid, an interventional radiologist based in Chicago, USA, and founder and president of No

Limits Radiology, expands on why she believes this award is so important: “Currently, approximately 8% of interventional radiologists are women. While we have had amazing women interventional radiologists achieve great things and lead the society, we are still a minority.

Advancement requires advocacy, and recognising those who promote women in IR is important in helping to grow the community of IR to be more inclusive of women interventionalists.”

Majid also tells this newspaper why this award is timely: “Gender equality in the workplace is the topic now, and the focus of gender equality in medicine is front and centre in the discussion. There is not a day that goes by on social media and #medtwitter where this topic is not discussed. It is important for us to join that conversation and highlight those who are active in working to achieve that equality within our field.”

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print marketing. But social medial must be used appropriately. Information that could identify a patient must be removed, including age and specifics about disease.

Further, one must be careful not to give medical advice outside of suggesting a person get evaluated by a physician.7 I think most would agree that promoting IR in this manner is necessary, but it is time consuming. It takes institutional infrastructure and often an eager physician to get follow through.

Fortunately, the Society of Interventional Radiology (SIR) has launched a national awareness and education campaign this fall—the Vision to Heal, Together— which takes a multipronged approach, with aspects that promote IR to patients and elements that market the discipline to referrers. SIR members can access campaign materials online at sirweb.org/ vthresources, which can be shared with your institution’s marketing team. Do not be afraid to ask them for help or to learn from an IR colleague who already has a successful marketing plan in place.

Theresa Caridi is an interventional radiologist at MedStar Georgetown University Hospital, Washington, DC, USA. References: 1. Iwai YA, Erinjeri JP, What’s in a Name: Is “Interventional Radiology” too Reductive? Journal of Vascular and Interventional Radiology (JVIR), JID—9203369.

2. Becker G.J: Interventional radiology 2000 and beyond: back from the brink. JVIR 1999; 10: pp.681–687.

3. Baerlocher MO, Asch MR, Puri G, Vellahottam A, Myers A, and Andrews A: Awareness of interventional radiology among patients referred to the interventional radiology department: A survey of patients in a large Canadian community hospital. JVIR 2007; 18: pp.633–637.

4. Baum RA, and Baum SB: Interventional radiology: A half century of innovation. Radiology 2014; 273: pp.S75–S91.

5. Baerlocher MO, and Asch MR: The future interventional radiologist: Clinician or hired gun? JVIR 2004; 15: pp.1,385–1,390.

6. Pershad Y, Hangge PT, Albadawi H, Oklu RA, Social Medicine: Twitter in Healthcare. LID—E121 pii [LID— 10.3390/jcm7060121 doi]. Journal of clinical medicine JID—101606588 PMC—PMC6025547 OTO—NOTNLM. 7. Ahmed O, Jilani S, Ginsburg M, Hadied O, Tasse J, Loanzon R, et al. You Are What You Tweet: Navigating Legal Issues in Social Media for Interventional Radiologists. JVIR JID—9203369.

The future of interventional radiology will be more gender inclusive, Majid enthuses. “We are already seeing female medical students and residents learning about IR early in their training, showing interest and pursuing it as their field of choice,” she says. “Data have shown that being gender inclusive results in better performance than single gender teams, provides a wider talent pool, offers different perspectives, which sparks greater creativity and innovation, enhances collaboration, improves staff retention, is a better reflection of the patient population we serve, improves

It is important for us to [...] highlight those who are active in working to achieve [...] equality.” recruitment and reputation, and [leads to] greater profitability. Thus, I look forward to seeing many more amazing innovations from female interventional radiologists, particularly in the areas of womens’ health and womens’ health services that are consistently ignored. I also look forward to seeing strong interventional departments that break the myth that IR is not a profitable field.”

Young interventional radiologists

Issue 76 | November 2019

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Inspiring medical students and junior doctors: Reflections on the first UK National Interventional Radiology Symposium Yiwang Xu Comment & Analysis

An interactive learning environment at NIRS 2019

Yiwang Xu gives an account of the first National Interventional Radiology Symposium (NIRS), detailing why it is so important to educate and inspire the next generation of interventional radiologists. Through reflecting on the successes of NIRS 2019, he hopes to provide a blueprint of how best to access and inform medical students and junior doctors about an interventional radiology (IR) career.

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IRS) 2019 was held at the Royal Free Hospital, London, UK, on 21 September 2019 with support from the British Society of Interventional Radiology (BSIR). It was the first dedicated interventional radiology conference in the UK for medical students and junior doctors, and served to inspire those with limited prior exposure, as well as to share insights with those already expressing career interest.

On behalf of the NIRS 2019 organising committee, I would like to share our experience for the wider interventional radiology (IR) community to build upon, and to stress the importance of outreach activities targeting medical students and junior doctors.

Enthusiasm from across the country

NIRS 2019 reached over 8,000 potential attendees via its social media platforms, and many more via medical school and hospital education centre bulletins.

The event was further promoted via a number of senior interventional radiologists with educational roles in

Delegates at NIRS 2019

their local deanery, and rapidly sold out.

Within just three weeks of registration opening, all 80 tickets had sold, with the majority of attendees travelling from outside of London, and dozens more on the waiting list!

We were also glad to see a mixed audience, with different expectations and prior exposures. Two thirds of attendees were foundation year or more senior doctors (at a career crossroad), and a third were medical students (for an early taster). A third rated themselves as “moderately exposed” prior to the event (i.e. having experience from an elective, a student-select component, a taster week, or similar); another third said they were “less exposed” (i.e. medical school rotation, briefly observed), and the final third were “never exposed”.

Feedback on NIRS 2019

We tailored our talks and workshops and grouped our attendees according to their previous exposure to IR. To increase the variety of IR subspecialties and provide insights into different stages of an interventional radiologists’ career,

we invited speakers ranging from senior fellow to the head of service, covering subspecialties including vascular, nonvascular, paediatric IR, and interventional neuroradiology—an average of 97% of delegates found the talks “engaging” and “informative”.

Purposefully designed mini-curricula with specific learning outcomes were incorporated into the workshops, including:

It is important for outreach events to provide a relaxed environment for prospective trainees.”

1. Safe endovascular navigation using Mentice simulators 2. Effective learning and assistance of IR procedures following common device demonstrations 3. Experience in interdisciplinary collaboration through the ‘Scalpel and Beam’ surgical radiology tutorials 4. Taster of hand-eye coordination from ultrasound-guided phantom model biopsy 5. Advanced knowledge of aortic stent graft procedure—an average of 91% of delegates enjoyed the contents and organisation of the workshops The endovascular simulation was the most popular session, and we thank our industry partner Cardinal Health—the hands-on experience provided to our delegates would not have been as realistic and insightful without their expert technical and equipment support.

In addition, more than 90% of delegates enjoyed the ‘Scalpel and Beam’ tutorial. It was originally an award-winning, eight-hour-long surgical radiology course, condensed to the most representative cases where collaboration and communication between surgery and (interventional) radiology significantly altered patient outcomes. Indeed, this unique session highlighted the interdisciplinary nature of IR work—an essential yet not very well demonstrated

aspect for non-radiology trainees.

Overall, 99% of attendees gained new insights in IR, 97% found the NIRS 2019 well organised and enjoyable, and 77% would consider a future career in IR. Outreach events provide much needed career insights and guidance for prospective trainees. From previous studies, we already know about the suboptimal level of IR exposure during undergraduate and foundation training.

In my opinion, it is as important for outreach events to provide a relaxed environment for perspective trainees to seek career guidance and to network with each other, as to supplement knowledge and skills through lectures and workshops. At NIRS 2019, we gratefully had senior interventional radiologists available to answer any delegate questions, and portfolios from recent specialty trainees were on display.

We can see from attendees’ feedback that they really appreciated these informal opportunities to seek career guidance— this is truly insightful for future event organisers. The overall experience led to 10% more delegates seriously considering IR as their future career.

Such a self-selected cohort of attendees can also help the IR community to pinpoint the attraction of a career in IR. This knowledge can help to target certain aspects of undergraduate and foundation training, in turn allowing us to cultivate prospective IR applicants more effectively—the findings from our survey will be shared in due time.

During NIRS 2019, we also provided the highly motivated audience a lot of information on portfolio and career development, and promoted essay competitions for BSIR Annual Meeting bursaries. Especially in the light of IR potentially becoming a separate specialty in the UK, it is crucial to inform those who are about to make career choices early and adequately.

Yiwang Xu is a radiology registrar at the London Imperial scheme, London, UK, and is the lead organiser of NIRS 2019. He was formerly a foundation year representative for the BSIR Trainee committee, and is a keen advocate of IR among medical students and junior doctors.

Conference coverage

Issue 76 | November 2019

Fifth edition of MIOLive is coming: What have the last five years of IO taught us?

Roberto Iezzi Comment & Analysis With the fifth MIOLive meeting in Rome, Italy, approaching, Roberto Iezzi discusses the most important lessons from the last five years of interventional oncology. He highlights the importance of interventional radiologists having clinical ownership of their patients, and enthuses about personalised medicine. MIOLive 2020 will feature live cases and lectures covering new developments in the field, and will take place 20–21 January 2020.

OVER THE LAST five years, interventional oncology (IO) using image-guided procedures has increased its role in cancer care management, improving technical capabilities, developing new procedures, and becoming generally preferred over more invasive alternatives. IO plays a critical role in cancer diagnosis, therapy, and symptom palliation, and is considered the fourth pillar of modern oncology care. Its aim is to provide minimally invasive procedures tailored to individual patient characteristics, developing more personalised procedures able to identify cancer cells, selectively reach and treat them, and to assess drug delivery and uptake in real-time in order to perform adjustments in the treatment, on the basis of procedure feedback, with the possibility to predict response. In addition to improving overall survival, these percutaneous or intra-arterial treatments can also be focused on maintaining

quality of life, which is critical in managing patients with cancer.

New technical capabilities have been introduced into clinical practice, allowing individualised treatments, with procedural improvements that can expand clinical indications and improve clinical outcomes and safety profiles.

There are also new tools to precisely guide and monitor IO procedures. All of these technological improvements have the potential to offer curative treatments, reducing the rate of residual response or local tumour progression, and may be used in association with systemic treatments, providing integrative and multidisciplinary solutions.

Furthermore, in the last few years, the concept of combined treatment has strongly emerged. This not only refers to multimodality, such as combining percutaneous and intra-arterial approaches, but also to intermodality: combining ablative procedures,

Foundation trainees’ perception of interventional radiology “poor”

Foundation trainees’ perception of interventional radiology (IR) is “generally poor due to a lack of adequate knowledge”, a recent survey from the Radiology department of the Pennine Acute Hospitals NHS Trust, Manchester, UK, reports.

MARAWAN EL FARARGY, Khalid Bashaeb, L Watkins, and Aws Alfahad, all from said institute, set out to assess perceptions of the specialty amongst foundation trainees, with the simultaneous aim of exploring the means by which these perceptions could be addressed, “with the overall outcome of encouraging junior doctors to consider a career in this advancing sub-speciality.”

El Farargy et al distributed a physical copy of an anonymised survey to a total of 79 students in the first and second year of their foundation course (FYs), all of

percutaneously or intra-arterially driven, with three-dimensional conformal radiotherapy (3D-CRT). The development of 3D-CRT has enabled high-dose radiation to be directed to tumours with a frank sparing of the non-tumourous tissue of the surrounding liver parenchyma.

The last five years have also seen the application in clinical practice of the combination of immunotherapy and IO strategies, paving the way for an expanded role of these procedures as a stimulant to the immune system, potentially preventing post-treatment tumour recurrence and generating durable and powerful antitumour immunity to achieve optimal tumour control.

We now also have increased scientific evidence supporting the use of IO in cancer care, with the introduction of these approaches into international cancer care guidelines or recommendations— even if usually with a low level of evidence. It means that, together with biotechnologies, new devices, new indications, and new treatments, we need clinical trials or registries that could

IO plays a critical role in cancer diagnosis, cancer therapy, and cancer symptom palliation.” demonstrate all the advantages of using IO techniques, and could justify the need for locoregional treatments from a costeffectiveness point of view.

However, despite all these new opportunities and technological improvements, the most important lesson from the last five years has been this: in order to provide a high-quality service in oncology, interventional radiologists need to be both highly technically competent, and have a clinical responsibility for

whom responded. Forty-five per cent (34 of 79) were introduced to IR within their prescribed training posts, and 38% (29 of 79) were “interested enough to learn more through self-directed reading”. Approximately 28% (22 of 79) had heard of IR during medical school rotations, and six trainees (of 79) were exposed to the specialty during elective placements.

“The findings of the present survey are indicative of the poor general knowledge of FYs regarding IR,” the authors surmise, “and highlights that IR is not introduced appropriately to undergraduates” They continue: “The Royal College of Radiologists has already made recommendations regarding the embedding of clinical radiology as a whole in medical education. Interventional radiologists must take a leading role in the education of both undergraduate and junior doctors to address the apparent lack of interest in radiology of newly qualified doctors. In addition, universities and societies should ensure that a basic level of general radiology and IR knowledge is obtained by medical students prior to graduation.

“Despite reasonable awareness of the IR subspeciality, 75% of FYs (59 of 79) stated that they were not willing to consider a career in IR, and around 11% were unsure about pursuing a career in IR,” the authors write. “Of those who did not wish to consider IR as an

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the patient they treat. Specifically, an interventional radiologist needs to be well trained for tumour board discussions, particularly in their oncological knowledge, to fully inform patients of the spectrum of therapeutic options that can be provided, to establish treatment plans, and implement them under the care of other clinical specialties.

This requires interventional radiologists to consult with patients in an outpatient setting in the preprocedural period, for assessment and discussion of the potential outcomes, clinical benefits, and complications of the procedure.

In addition, interventional radiologists should also follow their patients longterm to assess outcomes, recurrence, or development of new problems.

All these technical, procedural, and organisational aspects will be discussed in the fifth edition of MIOLive 2020, which will be held in Rome 20–21 January 2019. The meeting will be a forum for discussion for all those who are interested in interventional oncology and locoregional treatments.

It will be a practical, interactive meeting based on live cases punctuated by short presentations and lectures, where professionals from various countries in the Mediterranean area can share opinions, experiences, research projects and knowledge, under the guide of international experts. It is the best place for obtaining networking opportunities, listening to experts, and learning and sharing best practices. During the conference, there will also be a session (“Five-year results from MIOLive 2015: how indications changed”) dedicated to reviewing live cases performed during MIOLive 2015, highlighting how indications to procedures have rapidly changed in the last five years, and focusing on new therapeutical opportunities.

Roberto Iezzi is an interventional radiologist at the Fondazione Policlinico A Gemelli IRCCS, Rome, Italy.

option, 53 of 59 lacked general interest in radiology and 13 out of 59 felt they did not have enough information about this career option”.

While almost all respondents demonstrated awareness that IR is both an elective and an emergency specialty, over 45% did not know that attending clinic is part of the consultant role. Citing an American study by Julia Fielding (University of North Carolina, Chapel Hill, USA) et al that found that less patient contact discourages medical students from selecting radiology as a speciality, El Farargy and colleagues say, “it is understandable that inadequate knowledge of the typical IR consultant job plan may dissuade junior trainees from pursing interventional radiology as a future career”.

Market watch

Issue 76 | November 2019

Industry News Boston Scientific closes acquisition of BTG

Boston Scientific has announced the completion of its acquisition of BTG, pursuant to the previously announced scheme of arrangement. BTG develops and commercialises products used in minimally invasive procedures targeting cancer and vascular diseases, as well as specialty pharmaceuticals.

BTG has three key businesses, the largest of which is its highlydifferentiated interventional medicine portfolio that encompasses interventional oncology therapeutic technologies for patients with liver and kidney cancers, as well as a vascular portfolio for treatment of deep vein thrombosis, pulmonary embolism, deep venous obstruction, and superficial venous disease.

“The addition of the BTG interventional medicine portfolio reinforces our category leadership strategy and enables us to offer best-inclass technologies, unparalleled clinical evidence, and a strengthened commercial infrastructure to support physicians treating some of the most challenging diseases impacting patient health around the world,” comments Mike Mahoney, chairman and chief executive officer, Boston Scientific. “Leveraging the employee talent and clinical and commercial expertise of these two highperforming organisations will generate continued innovation and access so that we may advance patient care in ways that neither company could do alone.”

In addition to the interventional medicine product lines, the BTG portfolio also includes a specialty pharmaceutical business comprised of acute care antidotes to treat overexposure to certain medications and toxins, and a licensing business that receives royalties related to BTG intellectual property and product license agreements.

Upon the effectiveness of the scheme of arrangement, BTG became a whollyowned subsidiary of Boston Scientific, and BTG shares no longer trade on the London Stock Exchange. Under the terms of the previously announced transaction, holders of BTG common shares will receive 840 pence in cash per share.

Boston Scientific expects to complete the previously announced sale of its global embolic microspheres portfolio—comprised of Embozene, Embozene Tandem, and Oncozene brands—to Varian Medical Systems in due course, a transaction entered into in connection with obtaining the antitrust clearances required to complete the BTG transaction.

In addition, the company is initiating a process to explore the divestiture of the royalty stream associated with BTG’s Zytiga licensing arrangements and anticipates closing this divestiture

Physician driving CorPath GRX

by the end of 2019.

The transaction is expected to be immaterial to adjusted earnings per share in 2019 as a result of the BTG transaction closing later than originally anticipated, the divestiture of the Boston Scientific embolic microspheres portfolio, and the treatment of the licensing business as an asset for accounting purposes and its intended divestiture. The transaction is expected to be four to five US cents accretive in 2020 on an adjusted basis, and increasingly accretive thereafter. On a GAAP basis, the transaction is expected to be less accretive, or more dilutive as the case may be, due to amortisation expense and acquisition-related net charges.

robotic-assisted coronary, peripheral, and neurovascular procedures,” says Michel Therin, president of advanced therapies at Siemens Healthineers. “The acquisition of Corindus, combined with Siemens’ strong advanced therapies portfolio, will help further advance the growth of vascular robotics. The integration of our technologies could lead to reduced variability, improved efficiency, expanded access to care, and ultimately improved patient outcomes. We look forward to welcoming the Corindus team to Siemens Healthineers.”

Corindus Vascular Robotics’ CorPath is the first US Food and Drug Administration-cleared medical device to bring robotic technology to percutaneous coronary and vascular procedures.

Siemens Healthineers is a multibilliondollar healthcare technology company.

Michael Jaff joins Boston Scientific to drive innovation in peripheral technologies Michael R Jaff is to be vice president, clinical affairs, innovation and technology, peripheral interventions of Boston Scientific by January 2020. In this role, a press release reports, Jaff will lead clinical and medical affairs strategies to support the development and commercialisation of the company’s peripheral vascular medical device portfolio, and drive engagement with external stakeholders to advance technologies that deliver strong clinical value and enable patient care.

Siemens Healthineers has acquired Corindus Vascular Robotics

Siemens Healthineers has acquired all issued and outstanding shares of common stock of Corindus Vascular Robotics, Corindus announced.

The cash transaction is US$4.28 per share, resulting in an aggregate purchase price of US$1.1 billion

by Siemens Medical Solutions, a subsidiary of Siemens Healthineers, according to Corindus.

“We are pleased to have reached this agreement with Siemens Healthineers,” comments Mark J Toland, president and CEO of Corindus, in the news release. Speaking before the acquisition took place, he said: “We believe the transaction will deliver immediate, compelling, and certain value to all Corindus stockholders, as well as substantial benefits to our customers. The combination of Siemens Healthineers’ advanced, highquality imaging, digital and artificial intelligence tools with Corindus’ precision robotics platform has the potential to transform the way healthcare is delivered to those suffering from cardiovascular or peripheral disease. The tremendous technology synergies and shared vision between both companies should allow us to achieve a seamless integration between our businesses.”

“Corindus has established a leading position in vascular robotics with a compelling technology platform for

Michael Jaff

The press release adds that Jaff is currently president of Newton-Wellesley Hospital (part of the Partners Healthcare system in Massachusetts), “where he has been instrumental in the hospital’s growth since 2016”. Previously, he was responsible for process improvement efforts to redesign healthcare delivery at Massachusetts General Hospital and led its Fireman Vascular Center.

With more than 25 years of experience as a vascular clinician, his research has been published in more than 300 peer reviewed medical journals. Jaff is also the founder of VasCore, which is the world’s largest core laboratory for non-invasive vascular imaging and clinical trials.

Furthermore, he is currently professor of medicine at Harvard Medical School and has served on multiple professional society and hospital boards of directors.

Jaff says: “I have had the privilege of collaborating with Boston Scientific

49

over the course of my career and have participated in numerous clinical trials investigating the company’s devices. The Boston Scientific culture of innovation, dedication to the highest ethical approach to interventional therapies, and commitment to bringing forward solutions that improve the care of patients made this the best decision for the next phase of my career.”

Jeff Mirviss, senior vice president and president, peripheral interventions, Boston Scientific, comments: “Michael’s experience as a clinician, researcher, and hospital administrator will bring a unique perspective in our efforts to help solve complex healthcare challenges and support our customers in advancing the care of patients suffering from debilitating vascular diseases and conditions. We are looking forward to Michael joining our Boston Scientific team.”

International Cardio begins first-in-human trial of its high-intensity ultrasound system

International Cardio Corporation (ICC) announced that it has achieved the first human use of its high-intensity focused ultrasound (HIFU) system designed to treat peripheral vascular disease (PVD).

The Minneapolis-based company said its HIFU Synthesiser system is undergoing a 15-patient safety study in The Netherlands to investigate its feasibility and safety for the treatment of atherosclerotic plaques. The system uses high-intensity ultrasound to noninvasively treat vulnerable and occlusive plaques in peripheral arteries to reduce stroke mortality and improve the quality of life for those suffering from PVD. “The potential for noninvasively ablating and stabilising vulnerable vascular plaques is a compelling opportunity to both reduce stroke risk and deliver better outcomes with higher patient safety than current treatment options for patients suffering from PVD,” says ICC chief operating officer David Lee in a news release.

The safety study is the first step toward achieving the CE mark and US Food and Drug Administration (FDA) approval HIFU Synthesiser.

On The Netherlands Trial Register website, the investigators summarise their study: “Current treatment of lower extremity peripheral arterial disease consists of risk factor modification, exercise therapy, and pharmacological treatment initially, but intervention is frequently needed when patients are significantly disabled. Interventional treatment is invasive, either surgical or endovascular. This study investigates a new noninvasive technique that uses high-intensity focused ultrasound to treat atherosclerotic arterial disease.”

The primary endpoint of the study is the 30-day major complication rate, which is a composite endpoint that includes 30-day major adverse limb event rate and 30-day mortality rate. Secondary outcomes assessed include a range of technical, MRI, echo-duplex, clinical, and quality of life parameters.

Market watch

Issue 76 | November 2019

First patient enrolled in Cook Regentec’s clinical trial of investigational therapy for critical limb ischaemia

Clinical News

Martin Funovics presenting at CIRSE 2019

New data show high chronic outward force causes significantly more restenosis

Twelve-month results of the BIOFLEX COF trial have demonstrated that the implantation of stents with low chronic outward force (COF) was associated with less neointimal hyperplasia, consequently resulting in less restenosis.

Patients treated with BIOTRONIK’s low COF Pulsar stent showed significantly lower restenosis rates than patients treated with the high COF LifeStent implant. Martin Funovics (Medical University of Vienna, Austria), presented the full cohort primary endpoint data at the annual scientific meeting of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE; 7–11 September, Barcelona, Spain).

BIOFLEX-COF is the first randomised controlled trial (RCT) to investigate differences in clinical outcomes of nitinol stents with high versus low COF in de novo superficial femoral artery occlusive arterial lesions.

The low-COF Pulsar stent had a mean restenosis rate of 26%, while the highCOF LifeStent implant showed 35%, as measured on CT angiography at one year (p<0.001, t-test and Mann-Whitney U test).

“We initiated the BIOFLEX COF trial to close the gap on how COF impacts the human neointima,” explains principal investigator Funovics. “These RCT data support our hypothesis that high COF leads to increased neointimal hyperplasia, which causes restenosis and increases the risk of repeat interventions for the patient. Our results suggest that COF impacts clinical outcomes and should therefore be an important factor in the choice of the stent.”

Self-expanding nitinol stents must be oversized by at least a minimal amount to ensure contact with the vessel wall and prevent migration. Once the stent is deployed, it exerts a continuous force upon the vascular wall, termed COF. While an animal study has found increased neointimal hyperplasia, inflammation and injury scores in vessels treated with high COF stents, human data were not available until now.

The investigator-initiated BIOFLEXCOF RCT enrolled 83 patients with

symptomatic peripheral arterial lesions eligible for endovascular stent implantation. The patients were randomised 1:1 to either a high COF group or a low COF group. The trial’s primary endpoint is the amount of instent restenosis at one and two years, as assessed by contrast-enhanced CTA. “At Biotronik, we develop our technologies to continuously improve patient outcomes,” comments Alexander Uhl, senior vice president of Corporate Marketing at Biotronik. “With its unique design, Pulsar stent offers the benefits of a low COF stent and thin struts while resisting crush force: the optimal balance of radial forces keeps the vessel open, increases blood flow and reduces stress to the vessel wall. This helps to decrease patients’ risk of restenosis and need for re-interventions.”

Cook Regentec has announced enrolment of the first patient in an international clinical trial evaluating the HemaTrate Blood Filtration System to treat patients with critical limb ischaemia (CLI) due to peripheral arterial disease (PAD). To treat CLI, the HemaTrate system produces an autologous, peripheral blood-derived total nucleated cell (TNC) concentrate for intramuscular injection into the ischaemic limb.

“Critical limb ischaemia is the final stage of peripheral arterial disease and is associated with major morbidity and mortality despite current medical and surgical treatment,” noted Bijan Modarai, the study’s principal investigator, who treated the first enrolled patient at Guy’s and St. Thomas’ Hospital in London, UK. “Circulating nucleated cells are thought to stimulate vascular repair and regeneration and are of growing interest as a potential therapeutic option for these patients.”

The HemaTrate CLI (HT-CLI) trial is an international, multicentre, randomised controlled study that will enrol up to 350 patients. Subjects with Rutherford class 4 or 5 CLI will be randomised to receive a series of three intramuscular injection treatments of TNCs or saline, six weeks apart. The primary endpoint is clinical benefit through 12-month follow-up, defined as freedom from reintervention, major amputation or death. Following the 12-month study period, all patients will be offered TNC treatment for both study and non-study limbs. Patients will be followed for a total of 24 months.

“Patients with PAD-associated CLI

Cook Regentec HemaTrate

Marianne Brodmann presenting TOBA III data

51

who are poor candidates for surgical or endovascular procedures require alternative treatment options that deliver improved long-term outcomes,” said Brad Shirley, business leader at Cook Regentec. “We are excited that patients enrolled in our global CLI trial will begin to receive HemaTrate as treatment for this often-devastating condition.”

Bijan Modarai is a principal investigator of the HemaTrate CLI trial, and a paid consultant of Cook Regentec.

Intact vascular announces positive one-year data from TOBA III clinical trial

Intact Vascular has announced the positive one-year results of its Tack Optimised Balloon Angioplasty (TOBA) III clinical trial, successfully achieving both primary and secondary endpoints. Marianne Brodmann, head of the Clinical Division of Angiology, Medical University of Graz, Austria and principal investigator of the TOBA III trial, presented the data during the high impact clinical research session of the 31st Transcatheter Cardiovascular Therapeutics (TCT) meeting (25–29 September, San Francisco, USA), the annual scientific symposium of the Cardiovascular Research Foundation.

This multicentre, single-arm, prospective study was conducted in Europe and investigated the combination of the Tack endovascular system with Medtronic’s IN.PACT Admiral drugcoated balloon as a treatment in the superficial femoral (SFA) and/or proximal popliteal (PPA) arteries. The study enrolled 201 patients, including 169 patients with arterial lesions ≤150mm in length and a subset of 32 patients with long arterial lesions (>150 and ≤250mm).

All patients suffered from peripheral arterial disease (PAD) and underwent balloon angioplasty, consequently experiencing at least one dissection requiring repair.

Results from the 169 patient standard lesion cohort (≤150mm) demonstrated 97.7% complete dissection resolution, 95% Kaplan-Meier (KM) vessel patency and 97.5% K-M freedom from clinically-driven reintervention at 12-months. This was accomplished with a 0.6% bailout stent rate. These results add to the body of clinical evidence supporting the use of the Tack system for post-PTA dissection repair and further demonstrate the long-term effectiveness of the technology.

“I am extremely pleased with the clinically compelling results of the TOBA III study,” comments Marianne Brodmann. “The Tack system provides a safe and effective solution for treating post-angioplasty dissections. I believe this new therapeutic paradigm will change the standard of care for abovethe-knee interventions.”

The observational data from the long lesion subset (>150 and ≤250mm) was analysed separately. Results from these 32 patients notably demonstrated 98.8% complete dissection resolution and 89.3% K-M vessel patency, with 96.8% K-M freedom from clinically-driven reintervention at 12-months and a 0% bailout stent rate.

Market watch

Issue 76 | November 2019

Product News light-weight yet strong and has a high resistance to chemical attack from commonly used cleaning products.

MagicTouch PTA sirolimuscoated balloon granted breakthrough device designation Adept Medical Antegrade IR platform and ArmSure

Adept Medical launches the Antegrade IR platform

Adept Medical has launched its Antegrade IR platform, which provides a work surface for antegrade femoral approach during interventional radiology vascular procedures. The device sits within the company’s existing range of access and patient positioning devices designed for interventional radiology, cardiology and vascular procedures.

Designed to provide a stable, radiolucent, height- and lengthappropriate work surface for supporting light-weight equipment during the antegrade femoral approach, the Antegrade IR Platform offers clinical benefits to the current practice of laying procedural equipment on the mattress and patient, a press release states.

The narrow portion of the Antegrade IR Platform extends alongside the patient towards the femoral artery, offering a steady platform for the clinician to rest their wrists on during wire manipulation. It can be set up at two different lengths and at various heights according to the patient and procedure, providing flexibility.

“Having the Retrograde IR Platform in market now for a few years gave us deeper insights into the requirements surrounding femoral artery access and that product was the conversation starter for the Antegrade IR Platform”, Adept Medical’s product development manager Matt Lazenby comments.

“It became a common request when promoting at congress meetings and we worked closely with director of Medical Imaging, Marcus Mykytowycz of Western Health (Melbourne, Australia), with iterations of prototypes before widening our trial sites. Lower leg interventions for ischaemia is going through a rapid upsurge due to the increase in diabetes cases and we felt that the timing was right to release a specific platform for facilitating antegrade femoral access with all the same benefits as our existing retrograde platform.”

Ideally used in conjunction with the Adept Medical Drape Support and ArmSure, these two products offer drape management, patient comfort and security during interventional radiology procedures.

Crafted from carbon fibre composite and high-performance engineering plastics, the Antegrade IR Platform is

Concept Medical has been granted breakthrough device designation from the US Food and Drug Administration (FDA) for its MagicTouch percutaneous transluminal angioplasty (PTA) sirolimus drug-coated balloon (DCB) catheter, used in the treatment of peripheral arterial disease (PAD) in infra-popliteal lesions.

The first breakthrough device designation received by Concept Medical was on 30 April 2019 for its MagicTouch sirolimuscoated balloon, for the treatment of coronary arterial disease (CAD) in patients with in-stent restenosis.

Concept Medical has pioneered the sirolimus drug delivery platform technology (Nanolute Technology), which has been used in more than 30,000 patients worldwide. The MagicTouch PTA sirolimus-coated balloon is developed using this Nanolute Technology for use in PAD. In an ongoing clinical study (XTOSI), associate professor Edward Choke, principal investigator of the trial and chief of Vascular Surgery, Sengkang General Hospital, Singapore, said, “XTOSI study is the world’s first pilot study to investigate the safety and efficacy of novel MagicTouch PTA sirolimus drug-coated balloon in the treatment of below the knee arterial lesions in addition to femoropopliteal lesions. The majority of patients enrolled had major comorbidities (diabetes and end stage renal failure) and the indication for angioplasty was for severe critical limb ischaemia (more than 90% had the most severe Rutherford scores of 5 or 6).

The extent of peripheral arterial disease treated was also severe, and about 80% of patients did not have any patent below the knee arteries before angioplasty.

“I am very encouraged by the excellent results so far in this challenging cohort of patients. Device and technical success were both 100%. Freedom from device and procedure related mortality was 100%. Limb salvage rate at 30 days was 97%. At six months, freedom from clinically driven target lesion revascularisation (TLR) was 91%; and primary patency, independently and blindly assessed by duplex ultrasound, was 82%. I did not encounter any distal embolization or ‘slow flow phenomenon’ after application of sirolimus-coated balloon in below the knee vessels.”

Sahil Parikh, an interventional cardiologist and associate professor of Medicine and director of Endovascular Services at the Columbia University College of Physicians and Surgeons (New York, USA) says, “The breakthrough designation demonstrates

how important it is for us to have new technologies for below the knee intervention. Patients with critical limb ischemia (CLI) represent an enormous burden to our healthcare system and comprehensive care for these patients begins with effective revascularisation.

The MagicTouch PTA will hopefully bring us closer to our goals of reducing amputations in the USA and the world.”

According to a press release, this breakthrough device offers Concept Medical an opportunity to interact with the FDA’s experts through several different programme options “to efficiently address topics as they arise during the premarket review phase, which can help manufacturers receive feedback from the FDA and identify areas of agreement in a timely way”.

Manufacturers can also expect prioritised review of their submission. Under the programme, the FDA will provide Concept Medical with priority review and interactive communication regarding device development and clinical trial protocols, through to commercialisation decisions.

Cook Medical launches new 2.6Fr CXI support catheter

Cook Medical recently released the second generation of the 2.6Fr CXI support catheter with platinum-iridium marker bands. The CXI catheter is used in small-vessel anatomy or superselective anatomy for diagnostic and interventional procedures, including peripheral use.

“We strive to offer physicians the tools they need to provide the best possible outcomes for patients,” comments Mike Williams, director of global vascular programmes. “Physicians frequently asked for the 2.6Fr CXI support catheter to have the same visibility as smallersized CXI catheters. Platinum-iridium marker bands were added in response to these needs.”

This second-generation CXI catheter provides clinicians with better visualisation under fluoroscopy because of the platinum-iridium marker bands.

The catheter comes with additional tip configurations and a new 135cm length. Its stainless steel braid provides responsive torque and pushability, and the 2.3Fr and 2.6Fr sizes can fit coaxially in the 4.0Fr size to increase the amount of support.

The new design of the 2.6Fr platform is available in Europe, the USA and Canada.

New PreludeSYNC EVO radial compression device commercially available

Merit Medical have announced the commercial launch of the PreludeSYNC EVO radial compression device in the USA. The PreludeSYNC EVO is a sterile, single-use, disposable device used to assist in gaining haemostasis of the arterial percutaneous access site following catheterisation procedures.

Merit Medical’s launch of the PreludeSYNC EVO follows nearly two decades of innovation in haemostasis band products, the company asserts.

The PreludeSYNC EVO was designed

53

to provide operators improved clarity, safety, and patient comfort. According to a press release, the clear balloon and curved backer plate provide optimal visualisation of the puncture site, facilitating easy placement. The band, which is easily adjustable and fits securely around a patient’s wrist, comes in two sizes (24cm and 29cm). The device also features the new Slip-n-Lock Connection for safe and easy inflation and deflation.

“A core part of Merit Medical’s mission is to continually evolve and improve our product offerings, including in the area of access and hemostasis,” says Fred P Lampropoulos, Merit Medical’s founder, chair, and CEO. “Accordingly, the PreludeSYNC EVO is a needed solution that elevates the radial compression experience for operators and their patients. The Merit leadership team is excited to put the EVO in the hands of specialists across the USA.”

Merit Medical announces Torpedo gelatin foam for embolization of hypervascular tumours

Torpedos and Introducer

Merit Medical has announced the commercial launch of Torpedo, a proprietary gelatin foam indicated for use in the embolization of hypervascular tumours. The Torpedo provides physicians a pre-shaped gelatin foam loaded into a cartridge with an optional blunt stylet, removing the need for manual foam shaping and providing fast and easy attachment to the catheter for delivery, a press release describes.

The Merit Torpedo is easy to prepare and use, requiring only hydration with a 50:50 saline-to-contrast mixture. The product is available in two diameters (2.5mm and 5mm) and two lengths (10mm and 20mm), and is designed for use with a catheter with an inner diameter large enough to allow delivery of the Torpedo to the target vasculature via syringe injection. The gelatin foam in the Torpedo is biocompatible, hydrophilic, and resorbable.

“In the operating room, time and consistency are crucial,” comments Fred Lampropoulos, chair and CEO of Merit Medical. “The Torpedo device, which includes embolizing gelatin compressed into a cylindrical shape and pre-loaded into a cartridge, will save physicians valuable time and improve material delivery with precision and predictability by eliminating manual

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Market watch

November 2019 | Issue 76

Philips and B Braun launch Onvision needle tip tracking: Real-time ultrasound guidance for regional anaesthesia

Product News cutting and shaping. The Torpedo’s launch exemplifies Merit’s commitment to ongoing innovation in the field of embolotherapy, and we look forward to bringing physicians even more groundbreaking technologies soon.”

The Torpedo’s commercial launch follows the recent 510(k) clearance of Merit’s EmboCube. The EmboCube offers uniformly cut cubes of gelatin foam preloaded into a syringe, specifically designed to save time and avoid inconsistent particle sizes associated with manual preparation of gelatin foam sheets. Torpedo and EmboCube, the newest additions to Merit’s suite of microcatheters and embolic products, together address an important market need: reducing surgical time without compromising quality of care.

MRI Interventions reaches ClearPoint milestone

MRI Interventions said its ClearPoint Neuro navigation system has been used in 3,000 neurosurgical procedures.

The milestone procedure was completed at the University of California, San Francisco, USA, according to the vendor.

“This milestone is a testament to the value surgeons are placing on precision guided therapy, especially in neurosurgery where the stakes are the highest,” comments Joe Burnett, president and CEO of MRI Interventions. “Although the timing is coincidental, we were thrilled to share this success with the team at the University of California, San Francisco, who have partnered with us for the last decade in refining our platform and ensuring the voice of not only the doctor, but also that of the patient, is included in every improvement. It is also important to note that not only did UCSF perform the 3,000th case using ClearPoint, they also performed the 3,001st case that same day. UCSF is among the now ten centres scheduling two cases per day utilising the same MRI scanner, which has been a strategic push for us in the past year.”

Onvision probe needle

Philips and B Braun have announced the launch of Onvision, a breakthrough ultrasound guidance solution for realtime needle tip tracking in regional anaesthesia. Available on the latest version of the B Braun and Philips Xperius ultrasound system, Onvision gives anaesthesiologists the confidence to accurately position the needle tip inside the body. The introduction is part of a multi-year strategic alliance

between Philips and B Braun to innovate in ultrasound-guided regional anaesthesia, a rapidly growing alternative to general anaesthesia.

Onvision was launched at the 38th Annual Conference of the European Society of Regional Anaesthesia and Pain Therapy (ESRA) in Bilbao, Spain (11–14 September).

“Regional anaesthesia is a rapidly growing alternative to general anaesthesia and has the potential to improve patient outcomes as well as increase workflow efficiency in the hospital,” says Bert van Meurs, chief business leader, Image Guided Therapy at Philips.

Together, B Braun’s Stimuplex Onvision needles and Philips’ Onvision needle tip tracking technology indicate the position of the needle tip in relation to the ultrasound viewing plane to an accuracy of better than 3mm, a press release reports. A sensitive microsensor placed on the needle, combined with advanced signal processing and visualisation techniques on the Xperius system, indicate the real-time location of the needle tip in relation to the 2D ultrasound viewing plane. According to the release, the solution provides greater flexibility in needle trajectory and can reduce procedure times.

Calendar of events 13–15 November British Society of Interventional Radiology (BSIR) Annual Meeting 2019 Manchester, UK

21–22 November Future of Interventional Radiology Expert Panel Marseille, France

22–25 January International Symposium on Endovascular Therapy (ISET) Hollywood, USA

www.fire-congress.org

www.iset.org

14–15 November Embolotherapy 2019 Buenos Aires, Argentina

5 December Vascular Anomalies Special Interest Group Forum 2019 London, UK

31 January–3 February Society of Interventional Oncology (SIO) Annual Scientific Meeting 2020 New Orleans, USA

www.embolotherapy.com.ar

www.bsir.org

www.SIO-Central.org

15–17 November Evolution Miami 2019: The Future of Interventional Therapy: Today Miami, USA

18–21 January Spectrum Miami, USA

28 March–2 April Society of Interventional Radiology (SIR) Annual Scientific Meeting 2020 Seattle, USA

www.bsir.org

www.cvent.com

www.the spectrumconference.org

21–24 April 2020 Charing Cross (CX) Symposium London, UK www.cxsymposium.com

26–29 April European Conference of Interventional Oncology (ECIO) 2020 Nice, France www.ecio.org

14–17 May Global Embolization Cancer Symposium Technologies (GEST) US New York, USA www.gestweb.org

www.sirmeeting.org

Mar

Issue

19 73

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