Interventional News Issue 71

June

Issue

18 70

Embolization improves benign prostatic hyperplasia symptoms nearly as much as TURP does A randomised, open label trial published in the British Medical Journal (BMJ) in June suggests that the improvement in lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) seen 12 weeks after prostatic artery embolization (PAE) “is close to” the improvement observed after transurethral resection of the prostate (TURP).

H

owever, the investigators report that the noninferiority of embolization to TURP could not be established in the trial. “Prostatic artery embolization is associated with fewer complications than TURP but has disadvantages regarding functional outcomes, which should be considered when selecting patients,” they write.

Dominik Abt, consultant urologist and a team of colleagues from Kantonsspital, St Gallen, Switzerland that includes Lukas Hechelhammer, section chief of interventional radiology, set out to compare prostatic artery embolization with in the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia in terms of patient reported and functional outcomes.

the study was a change in international prostate symptoms score (IPSS) from baseline to 12 weeks after the procedure; a difference of less than three points between treatments was defined as non-inferiority for embolization and tested with a one-sided t test.

The secondary outcomes included further questionnaires, functional measures, magnetic resonance imaging findings, and adverse events; changes from baseline to 12 weeks were compared between treatments with two-sided tests for superiority.

The mean reduction in IPSS from baseline to 12 weeks was −9.23 points after embolization and −10.77 points after TURP. “Although the difference was less than three points (1.54 points in

favour of TURP, non-inferiority of embolization could not be shown (p=0.17),” the authors write.

“Before starting this trial, we did our sample calculations with assumed drop-out rates to correctly power this study.

Nevertheless, our standard deviations regarding the primary outcomes for both interventions were larger than assumed for the sample calculations. Therefore, this study is underpowered to show non-inferiority of prostatic artery embolization. On the other hand, it does not show that embolization is inferior,” Hechelhammer told Interventional News.

Further, none of the patient reported secondary outcomes differed significantly between Continued on page 2

Trial details

The investigators randomised 103 patients aged ≥40 years with refractory lower urinary tract symptoms secondary to benign prostatic hyperplasia to either receive embolization or surgery.

In the trial, 48 patients who were treated with embolization and 51 who were treated with surgery reached the follow-up endpoint 12 weeks after the procedure.

The authors report that embolization was performed with 250–400μm microspheres under local anaesthesia vs. monopolar TURP performed under spinal or general anaesthesia.

The primary outcome of

Dominik Abt (L) and Lukas Hechelhammer

Emprint Ablation System ™

POWERED BY THERMOSPHERE TECHNOLOGY ™

David Breen:

Renal ablation

Page 8

Jean Palussière:

Profile

Page 30

Novel technique to treat endometrial cysts is safe and effective

Catheter-based sclerotherapy is a safe and effective treatment for endometrial cysts and could help preserve fertility, according to a study published in Radiology.

E

ndometriosis is a common condition that affects about 10% of women of reproductive age. When endometriosis involves the ovaries, fluid-filled cysts called endometriomas may form, causing pelvic pain and abnormal uterine bleeding.

Surgery is a common treatment for endometriomas, but it carries risks, including the removal of healthy ovarian tissue, which can affect fertility. Needle-based sclerotherapy is a less-invasive option that involves inserting a needle into the cyst under ultrasound guidance and then withdrawing the cystic fluid through a needle.

The cyst is then washed with a solution of ethanol.

However, the needle-directed approach has limitations, said study co-author Man-Deuk Kim, professor at Severance Hospital, Yonsei University College of Medicine in Seoul, South Korea.

“Endometrial cyst content can be incredibly thick and sticky. A 16- or 18-gauge needle, which is commonly used for needle-directed sclerotherapy, is sometimes not large enough to completely evacuate the cyst,” he said. “This may reduce the efficacy of sclerotherapy and increase the possibility of needle displacement during aspiration.”

Kim and colleagues studied a sclerotherapy technique that replaces the needle with a catheter, a flexible tube used for removing fluid from cavities in the body. Along with draining cystic fluid more easily, a catheter allows for positional changes during the procedure, which helps Continued on page 2

MINIMALLY INVASIVE. MAXIMUM PREDICTABILITY.

© 2018 Medtronic. 18-weu-emprint-banner-interventional-news-2261247

18-weu-emprint-banner-interventional-news-2261247.indd 1

29/01/2018 15:17

2

June

Embolization improves benign prostatic hyperplasia symptoms nearly as much as TURP does Continued from page 1

treatments when tested for superiority; IPSS also did not differ significantly (p=0.31). At 12 weeks, embolization was less effective than TURP regarding changes in maximum rate of urinary flow (5.19 vs. 15.34 L/s; p<0.001), postvoid residual urine (−86.36 vs. −199.98mL; p=0.003), prostate volume (−12.17 vs. −30.27mL; p<0.001), and desobstructive effectiveness according to pressure flow studies (56% vs. 93% shift towards less obstructive category; p=0.003). Fewer adverse events occurred after embolization than after TURP (36 vs. 70 events; p=0.003).

“Improvement in lower urinary tract symptoms secondary to benign prostatic hyperplasia seen 12 weeks after embolization is close to that after TURP […] Further comparative study findings, including longer

Issue

18 70

Benign prostatic hyperplasia

follow-up, should be evaluated before embolization can be considered as a routine treatment,” the authors write in the BMJ. Defining the patient profile for embolization, Hechelhammer said: “Due to our results we believe that an ideal candidate for embolization is a man in whom the indication for intervention is primarily based upon symptoms; with a suitable vascular anatomy; and a reasonable volume of the prostate. Embolization can also be used for polymorbid patients not suitable for TURP. Since embolization is less effective at reducing obstruction after 12 weeks, TURP should be preferred in patients with bladder outlet obstruction (BOO) associated complications,” Hechelhammer added.

Novel technique to treat endometrial cysts is safe and effective Continued from page 1

maximise the ethanol’s effectiveness by enabling it to contact the cyst wall evenly.

The catheter also reduces the risk of spillage into the peritoneal cavity of the abdomen.

The researchers evaluated catheter-directed sclerotherapy with 95% ethanol in 14 women between the ages of 20 and 44 with ovarian endometriomas.

After about one year, the cysts had decreased on average from 5.8cm in diameter to 1.1cm. Pain was relieved in all patients, and blood tests indicated well-preserved ovarian function. There were no procedurerelated complications.

There were no endometrioma recurrences, even in patients with internal septation, or division, within their cysts. The multiple compartments of septated cysts can be difficult to puncture with a needle, which may lead to incomplete sclerotherapy.

In catheter-directed sclerotherapy, once the endometrioma is punctured, clinicians can manipulate the guidewire and catheter to break down internal septations, allowing for more effective treatment.

“In our study, the recurrence rate of catheter-directed sclerotherapy was 0%, which is very encouraging given that endometriomas measuring up to 13.5cm diameter or those that had internal septation were included in the study,” Kim said.

The results suggest that catheter-based sclerotherapy could lead to better short-term clinical outcomes in women with endometrial cysts while preserving ovarian function and improving future fertility, he noted. The researchers plan to conduct a study to see how catheter-directed sclerotherapy compares with surgery in terms of fertility, cyst recurrence and improvements in clinical symptoms.

Prostate artery embolization goes live from Lisbon to Dubai Tiago Bilhim and Daniel Torres (both from Saint Louis Hospital, Lisbon, Portugal) performed two cases of prostate artery embolization in patients with symptomatic benign prostatic hyperplasia (BPH) that were broadcast live to the 2018 Pan Arab Interventional Radiology Society meeting (PAIRS 2018, Dubai). Bilhim and Hicham Abada (Cleveland Clinic Abu Dhabi and chair of PAIRS 2019 Workshops Program) share the details.

and reviewed during the case. cone-beam CT was also performed after selective catheterisation of the right-side prostatic artery from the left radial access ensuring correct microcatheter position before embolization.”

Case 2

prostate arterial anatomy variants allowing precise treatment planning that helps to keep procedural times under one hour in most patients,” says Bilhim, while describing the cases.

“The second patient was 83 years old, with severely symptomatic BPH, on medication of Tamsulosin 0.4mg once daily. Pre-procedural CTA showed a prostatic artery arising from an aberrant obturator artery (from the inferior epigastric artery) on the left side and from the internal pudendal artery on the right side. Embolization was performed bilaterally using a femoral approach with the same size of microspheres as the first case. Balloonassisted embolization was performed using a balloonocclusion microcatheter in order to emphasise the potential advantages of this technique for the procedure. This method can reduce the risk of non-targeted embolization due to anastomoses or reflux and allows larger volumes of embolic material to be used.”

Case 1

“E

Tiago Bilhim

Hicham Abada

ach procedure lasted about an hour, with an overall live case session of three hours during which the indications, technique and expected outcomes of embolization for enlarged prostate were discussed. The featured procedures highlighted the role of radial access and balloon-occlusion for prostatic artery embolization,” Abada states.

“Pre-procedural CT angiography depicts all relevant

Editors-in-chief:

Professor Andy Adam Dr Brian Stainken

Publisher:

Stephen Greenhalgh

Head of Publishing: Amanda Nieves

Senior Editor:

Urmila Kerslake urmila@bibamedical.com

“The first patient was 70 years old, with severely symptomatic BPH under medication with Alfuzosin 10mg once daily. Pre-procedural CT angiography (CTA) showed a prostate artery arising from the superior gluteal artery on the left side and from the superior vesical artery on the right side. The patient preferred left radial over femoral access and the prostatic arteries were embolized with 300–500μm microspheres. There was a need to convert the radial access into femoral access during the embolization of the left prostatic artery due to catheter length restraints.

The need to convert a radial access into a femoral access is rare, but should be kept in mind due to catheter length limitations, especially in patients over 175cm in height.

Contraindications such as age above 75 years; radial artery size measured with ultrasound of less than 2mm; Barbeau test type D and technique for radial access were discussed

CTA

Both Bilhim and Abada note that the pre-procedural prostate artery anatomy study with CTA is vital to reduce fluoroscopy and procedural times, enabling prostatic artery embolization to be performed in under an hour.

Continued on page 6

London, UK SW6 5NR Tel: +44 (0) 20 7736 8788 Fax: +44 (0) 20 7736 8283

Write to us!

Susan Couch susan@bibamedical.com

Printed by:

urmila@bibamedical.com

Design

News or advertising queries:

Layout:

Published by:

Reprint requests and all correspondence regarding the newspaper should be addressed to the editor at the above address.

Editor

Advertising:

Suzie Marshall suzie@bibamedical.com

Shilpa Suthar shilpa@bibamedical.com

Editorial contribution:

Subscriptions:

Dawn Powell Zoë Öhman

David Reekie and Naomi Amorra Terry Hawes

Tel: +44 (0)20 7736 8788 BIBA Medical, 526 Fulham Road

linkedin.com/company/interventional-news/

Buxton Press

If you have comments on this issue or suggestions for upcoming editions, write to

Next issue: November 2018

© BIBA Medical Ltd, 2018 All rights reserved.

@in_publishing

www.interventionalnews.com

facebook.com/interventionalnews

4

Sept

Issue

18 71

Embolization

Embolization for trauma should be performed only by highly trained and experienced interventionalists Robert Morgan, St George’s University Hospitals NHS Foundation Trust, London, UK, discusses the role of interventional radiologists (IRs) in trauma embolization; and whether other clinical specialties with aspirations to perform these techniques should be involved in offering this treatment.

Working at a major trauma centre, Morgan, who sees between 100 and 200 traumatic haemorrhage cases a year, highlights the difficulty of the embolization techniques, and explains how important it is that only specialists with proper training should perform these procedures.

Robert Morgan

At the recent Global Embolization Cancer Symposium and Technologies (GEST) US meeting (9–12 May, Miami, USA), there was a discussion on the topic of embolization and turf.

What recent developments suggest that trauma embolization is the next battleground for IRs?

GEST (US) is a North American meeting, and it may be the case that there are more concerns about turf issues in embolization in North America than there are in Europe.

However, that is not to say that European IRs should be complacent about this. I think that there are potential issues regarding inadequately trained non-interventional radiologists performing embolization procedures, certainly in the trauma field. I am aware that this already occurs in some centres in Europe. In some European hospitals, non-IR trauma specialists advocate that they should be able to perform the full range of treatments for trauma, and that this should include embolization for haemorrhage. These individuals have stated that this approach would be better for patients, without any real evidence base for it.

From my point of view, I disagree with the view that embolization for traumatic haemorrhage is a technique that can be learnt relatively easily by other specialties with no formal training in catheter/guidewire/embolization techniques. I know that our vascular surgical colleagues perform some embolization procedures in connection with EVAR such as plug embolization of the internal iliac arteries and in a few European centres, embolization of endoleaks. However, I do not think that there is a growing enthusiasm from vascular surgeons to take this to the next level and perform embolization of haemorrhage using microcatheters. In the main, I do not see the likelihood of non-IRs performing embolization of haemorrhage as an imminent problem in the UK, and also probably in Europe. However, this is not to say that IRs should be complacent about their role in

embolization for haemorrhage.

In my opinion, it is difficult to say that certain specialists cannot perform specific procedures that other specialists do, such as embolization. We have already experienced turf issues between IRs and other specialties in terms of the endovascular treatment of lower limb peripheral vascular disease.

From this experience, I do not consider that it is productive to state that one specialty cannot do a procedure that another specialty does. We have to rely on best practice, and ask the question whether the person who wants to take on that procedure is trained to do it sufficiently well enough, according to published professional Standards of Practice guidelines for that specific procedure. It is evident from prior experience with other clinicians who want to perform procedures performed by IRs (for example, uterine artery embolization, or dialysis interventions) that this may not always be the case.

How important is embolization in treating trauma patients?

Embolization is very important for haemorrhage management in trauma. Certainly, not all cases of traumatic haemorrhage require management by embolization. However, there is a subset of patients with haemorrhage from certain abdominal organs, where the standard of care is focused on embolization rather than surgery. Therefore, embolization is integral to the management of some patients with traumatic haemorrhage.

In an interventional radiology list of seven to 12 cases, maybe one or two of those cases will be embolization procedures.

In terms of embolization for trauma, maybe one case in 30 to 50 cases. A typical scenario is the patient who has been involved in a road traffic accident and has sustained splenic trauma, usually in the middle of the night.

What constitutes adequate training to perform trauma embolization?

Trauma embolization is just one of the spectrum of cases that are treated by embolization. The procedures are often challenging, requiring endovascular access to small vessels in tortuous arterial territories. Therefore, you need to acquire the skills to be able to access the site of haemorrhage using standard catheters and microcatheters, and standard wires and microwires. You also need to have knowledge of the different types of embolic agents, in which situations to use them and the skills to be able to use them safely. These are not easy skills to acquire.

The catheter and guidewire skills necessary to manipulate catheters and guidewires around the relevant arterial territories take time to acquire, and are a considerable step up from the ability to manipulate catheters into relatively large visceral arteries such as

renal arteries. Some people never acquire these advanced skills. To master the smaller and more challenging tools that are used for embolization also takes a considerable time.

Embolization of haemorrhage is one of the most challenging tasks in vascular interventional radiology. In terms of how long these skills take to acquire, this will depend on the individual’s endovascular abilities. In terms of absolute numbers at least 50, and probably more than 100, embolization cases using microcatheters would be necessary to acquire the skills to perform embolization of haemorrhage, safely and effectively.

To maintain these skills once learned, you would need to be doing between three and five embolization procedures a month. It is not just the catheter and guidewire skills that are essential, it is also the pattern recognition skills of small and large vessel arterial territories on CT angiography and catheter angiography and also the appearance of haemorrhage on these imaging modalities that need to be acquired and maintained.

Finally, embolization for haemorrhage in major trauma patients needs to be done as quickly as possible. Trauma patients usually have skeletal or other injuries that may require urgent surgical management after the bleeding has been stopped by embolization.

Therefore, the interventionalist performing an embolization procedure in these critically ill patients needs to work under time pressures, with constant interruptions calling for the patient to be sent elsewhere for other procedures. In these situations, the interventionalist doing the embolization must be highly experienced and able to perform the procedure quickly and successfully under these difficult circumstances.

There is an understanding that non-IR specialties are undertaking simple embolization procedures, in some cases perhaps without adequate training...

I am aware that vascular surgeons undertake embolization in some abdominal arteries as a part of the EVAR (endovascular aneurysm repair) procedure and some surgeons also embolize endoleaks. Many vascular surgeons spend time working in interventional radiology departments, so that they are able to acquire the skills required in those situations. I would reiterate that I do not say for a minute that other specialties should not do those procedures, only that people need adequate training to do them safely and effectively.

As long as there is a recognition by doctors and also hospital administrators that certain procedures should be done by the specialty most suited in terms of training and experience to do them, embolization for haemorrhage will be performed successfully and with minimal procedural complica-

tions. In view of the extensive time that IRs spend in acquiring the skills required to use microcatheters and embolic agents, in the vast majority of hospitals IRs should be the specialists who are called upon to perform embolization for traumatic haemorrhage.

In many hospitals, the skills of interventional radiologists in trauma embolization are well-recognised and, as in my hospital, IRs are an important component of the protocols in place for the management of major trauma patients.

What are the key considerations when making the choice between embolization and surgery for traumatic haemorrhage? n The condition of the patient—the patient

may be in extremis and may be better off going straight to the operating room for surgery. The patient must be fit enough to come to the angiosuite for the embolization procedure, and anaesthetic support is usually required. Patients must be able to lie flat and immobile throughout the embolization procedure. n Time is important. You need to have enough time to do the embolization procedure—patients with very rapid bleeding need immediate haemorrhage control and should be treated surgically. n The area of haemorrhage that you want to embolize needs to be suitable for embolization, and not more suitable for treatment by any other cause; for example, somebody who is bleeding from a lacerated femoral artery requires surgery, and does not require embolization. Large vessel trauma requires surgery or endovascular stent grafting.

Therefore, there is only a small subset of patients with traumatic haemorrhage who are actually suitable for, or require, embolization. Most of these patients will have sustained solid organ abdominal trauma, most commonly the spleen. Pelvic trauma often requires embolization, and occasionally the liver and kidney.

In summary, interventional radiologists have the requisite training and experience for the embolization of traumatic arterial haemorrhage and should be an integral part of the team involved in the management of trauma. National government agencies involved in healthcare provision should ensure that sufficient interventional radiologists are in place at each hospital that manages trauma to provide a comprehensive embolization service for these patients.

Ensuring that there is sufficient cover by a well-staffed interventional radiology service is preferable to an ad hoc service provided by other non-IR clinicians, who seldom have the required skills, training or experience to perform embolization for these challenging and critically ill patients.

6

Sept

Issue

18 71

Augmented reality

New augmented reality system lets IRs “literally see through the patient” European Radiology Experimental has recently published a study on a new augmented reality system (Endosight) that is able to accurately guide interventional oncology procedures. A three-step experiment proves this system is precise and reliable enough to facilitate image guidance critical to the success of interventional oncology procedures.

U

sing a back-face camera and a tablet PC to visualise the patient, the system projects 3D images of body structures such as organs, lesions, and vessels on the video image of the patient. The projections are extracted from preoperative CT and/or MR scans, and 3D change angles depending on the corresponding camera direction of the tablet. It is a novel finding that the augmented reality system can guide procedures, as precise image guidance is critical to the success of procedures in interventional oncology. The authors concluded that their system is reliable and precise, as extremely high targeting accuracy (below 5mm) was achieved with experiments based on three models—an anthropomorphic trunk model, a porcine model, and a cadaver model. A thermal ablation procedure was simulated on these models, from which it followed that the projections of the augmented reality system very accurately depicted the location of the needle within the organs.

Luigi Solbiati (Humanitas University, Milan, Italy) speaks to Interventional News speaks about this new augmented reality system.

How does augmented reality work in the context of interventional oncology procedures?

After acquiring cross-sectional (CT or MRI) scans and performing 3D reconstruction, augmented reality allows physicians to visualise patient’s organs and targets just through a pair of googles, in an easy and straightforward way, without the need for any other imaging modality. Augmented reality also allows the precision targeting with conventional needles, electrodes, and antennas of any nodule previously detected by CT or MRI, at any distance from the skin.

What are the main advantages of using augmented reality in this way?

The main advantages of using augmented reality in interventional oncology are the following: Having the possibility to easily and precisely target the real centre of nodules, thanks to the 3D visualisation in real-time. This is particularly important for ablative procedures, in order to achieve homogeneously thick ablative margins all around the volume of nodules.

Significant shortening of the time needed to perform the procedure, compared to CT or MRI guidance.

Overcoming the limitations of ultrasound guidance: 2D visualisation, impossibility to visualise organs (lung, bones), difficulty or impossibility to visualise nodules located in critical areas (for example, tumours

in the liver dome).

Significant shortening of the learning curve of interventional procedures.

No risk of radiation for patients and operators.

Capability to let all the operators, fellows, students, and other users see exactly what the main operator sees and does, given that the images of the procedure can be simultaneously broadcast to an unlimited number of goggles in the same interventional room. This can be extremely useful in the teaching of how to perform interventional procedures.

Do you foresee the use of augmented reality becoming standard practice? If so, what do you think the challenges are with implementing this change?

As has always occurred in the history of medicine, it will take time to shift standard practice. There are many reasons for this lag in augmented reality becoming standard practice for the guidance of interventional procedures, such as the need for simplifying and refining the technology itself, and the traditional difficulty of convincing particularly skilled operators to abandon conventional guidance systems (based on 2D visualisation) and move to a totally new modality, based on 3D visualisation. There will certainly be a phase in which traditional guidance modalities will be used side by side with augmented reality in order to verify the precision of targeting before starting ablative procedures.

In my opinion, two completely different populations of users (opinion leaders and young operators particularly skilled in the use of new technologies) could lead the remaining majority of operators toward this change.

How do you see augmented reality systems changing interventional oncology?

Enabling a larger number of non-expert clinicians to safely and precisely perform interventional procedures, thus ultimately increasing the number of procedures performed throughout the world.

What are the clinical ramifications of the study published in European Radiology Experimental, concluding that the Endosight augmented reality system is safe, reliable and precise?

In our study, we decided to start testing the Endosight augmented reality system in a very challenging

Precise image guidance is critical to the success of interventional oncology procedures

environment at the Simulation Center of Humanitas University in Milan: targeting small hepatic metastases in a cadaver with a ventilator attached to the trachea to induce simulated respiration. We were able to target both metastases with a distance of the needle tip from their geometric centre ranging from 2.5 to 2.8mm. We should soon start a clinical study in human livers and, in addition, experimental studies in other moving organs (the lung) and non-moving organs (such as the prostate and neck), where we expect to run into fewer difficulties.

How does using augmented reality for interventional oncology procedures compare to the current standard practice involving other imaging technologies?

The biggest breakthroughs in the world of guidance modalities for interventional oncology procedures in the last 10 years have been image fusion of real-time sonography and pre-acquired CT or MRI and conebeam CT. However, the first suffers from the low spatial resolution of sonography and the lack of 3D representation, while the second from the risk of ionising radiation and the need for the use of contrast agents.

Augmented reality can overcome all these limitations.

What is the future for augmented reality systems in interventional oncology procedures?

This question is particularly challenging and the answer almost impossible: who could have expected only five years ago that we would have shortly been able to look into a patient by simply wearing a pair of glasses?

Prostate artery embolization goes live from Lisbon to Dubai Continued from page 2

“Both these patients had anatomical variants that had potential to increase procedural times.

One patient had the prostate artery arising from the posterior division of the internal iliac artery (superior gluteal artery) whereas in the other patient, it arose from a branch of the external iliac artery, outside the pelvic arteries (aberrant obturator from the inferior epigastric artery),” they say.

Follow-up

“Both patients were discharged around five hours after the procedure and reported no adverse events.

Both patients had significant improvement of their lower urinary tract symptoms (LUTS) due to BPH

after embolization and are very happy with the treatment results,” states Bilhim.

Commenting on the improvements in during follow-up, Bilhim reports: “For the first patient, the International Prostate Symptom Score (IPSS)/Quality of Life (QoL) score improved from 17/5 points to 3/2 points and the prostate volume reduced from 53mL to 30mL after one month.

“The second patient had an IPSS/QoL score improvement of 27/5 points to 13/3 points and the prostate volume reduced from 72mL to 64mL after one month. Both patients stopped their BPH medication with significant relief of the LUTS and experienced prostate volume reduction, highlighting

the potential for embolization in the management of patients with BPH. “PAE can be safely performed in an outpatient setting and is very well-tolerated by the patients, with very few adverse events that are usually mild and self-limiting. Patients can usually return to normal activities the following day with no pain, nausea or vomiting.

“The vast majority of patients has a significant improvement in LUTS with an overall improvement in the quality of life. The procedure compares favourably to conventional surgery as it has a much lower adverse event profile, with similar improvement in LUTS,” concludes Abada.

DESIGNED WITH PURPOSE

Concerto™ Detachable Coil System

All Concerto™ coils are designed with nylon or PGLA fibers to increase thrombogenicity and stop flow.1 Concerto™ fibered coils:

ACCELERATE THROMBUS FORMATION

241

%

HIGHER RATE OF THROMBIN PRODUCTION1*

NYLON/PGLA FIBERED COILS BARE COILS

MAXIMIZE THROMBUS FORMATION

80

%

INCREASE IN PEAK THROMBIN PRODUCTION1*

NYLON/PGLA FIBERED COILS BARE COILS

*Percentages are calculated from the average of nylon and PGLA fibered coils.

Reference 1 Girdhar G, Read M, Sohn J, Shah C, Shrivastava S. In-vitro thrombogenicity assessment of polymer filament modified and native platinum embolic coils. J Neurol Sci. April 15, 2014;339(1-2):97-101.

UC201901952aEE ©2018 Medtronic. All rights reserved.

Medtronic, Medtronic logo and Further, Together are trademarks of Medtronic.

All other brands are trademarks of a Medtronic company. 08/18

8

Sept

Issue

18 71

Ablation

Renal tumour ablation: Fighting for a place in the therapeutic armamentarium DAVID BREEN COMMENT & ANALYSIS What does it take to change a standard of care? David Breen, Southampton, UK, analyses the guidelines and uses the example of renal cancer to demonstrate how the threshold of evidence required to shift clinical practice appears to be different for ablation and surgery, with the former still being on the therapeutic sidelines despite having two decades of data behind it.

I

t is entirely correct that a new oncological intervention should demonstrate improved outcomes, ideally along with reduced patient morbidity and costs. The commissioning authorities, our colleagues within the field and most importantly, our patients are right to insist on nothing less. Over the years, interventional radiology has been slowly successful in this respect. An outstanding example that comes to mind is Andy Molyneux’s ISAT (International subarachnoid aneurysm trial) study that moved us, almost in single step, from clipping to coiling. Similarly, the EVAR1 trial fundamentally tipped the balance towards endovascular repair, at least out to the eight-year mark. More recently, Nigel Hacking’s UK ROPE (Registry of prostate embolization) registry has clearly convinced the UK commissioners that prostate artery embolization has a substantial role to play in the management of benign functional prostate disease. So what then of renal

tumour ablation where 20 years of practice have still failed to bring about a stepwise change in practice?

Radiological imaging is driving the appreciation of ever smaller cancers and is having a profound impact across the board on the epidemiology and presentation of malignant disease. Nowhere is this more apparent than in the arena of renal cancer. Some 75% of all renal cancers now presenting to our tumour boards are incidental and asymptomatic. All this begs the question whether disease best appreciated at cross-sectional imaging should not be targeted and treated by the same means. Whilst partial nephrectomy is held up as the standard of care, it remains variably practised and is not without significant risks of ipsilateral warm ischaemic injury and post-operative complications, in an often older age group.

To put it another way, the cure must not be worse than the disease. Many urological centres are suggesting that practice should

Figure 1: 44mm renal cancer before cryoablation

now migrate—at great expense—to robotic partial nephrectomy, without any clear evidence of its tangible benefits. Meanwhile image-guided ablation for small volume renal tumours has steadily evolved over the last 20 years into an effective alternative treatment option but remains on the therapeutic sidelines. Why? Dramatic changes in practice, rightly, need to be evidenced. There is a mass of single arm, non-randomised data testifying to the improved safety and equivalent renal cancer-specific mortality of ablation, cryoablation in particular. It must be acknowledged that there is a slightly higher local recurrence rate for ablation, but this is a remediable quality improvement issue that interventional oncology must bear down upon. There are now a good number of meta-analyses confirming the oncological equipoise achieved by renal tumour ablation. Of course Level 1 randomised data is the way to go, but to my knowledge at least two attempted, government-funded trials on this topic have collapsed through failure to recruit. We all know the issues as to why this occurs, despite perceived equipoise.

In the face of this Level 3 evidence—I would point out on which a lot of standard surgical practice is based—what do the guidelines say? In the last few years we have entered into an era of ‘Guidelines Wars’ on smaller renal tumours where at least seven major bodies have issued distinctly nuanced conclusions on the subject. These range from the European Association of Urology’s damning 2015 commentary: “Due to the low quality of the available data, no recommendation can be made on radiofrequency ablation and cryoablation” right through to the strikingly

different American Urological Association’s 2017 statement: “Physicians should consider thermal ablation as an alternate approach for the management of cT1a renal masses less than 3cm in size. For patients who elect thermal ablation, a percutaneous technique should be considered over a surgical approach whenever feasible to minimise morbidity”. These conclusions reached despite very similar reported literature-search methodology.

Returning to our original question: what does it take to change practice? Can we learn from some of those earlier pivotal studies and registries? To be sure registries such as EURECA (European registry of renal cancer ablation) and ARMOR (Ablation of renal masses outcomes registry) are in play and accruing data, but will they tip the balance? Should service commissioners now be asked to look at this from an independent cost-efficacy and morbidity standpoint? Are these not increasingly important outcome indicators in the setting of oncological equipoise for interventional oncological and surgical approaches? Is a drift towards robotic partial nephrectomy inevitable or even justifiable, or is this going to be a matter of attrition and increased public awareness of the options? The slow curve of changes in practice over decades is interesting to behold, but if interventional oncology drops the ball on such an outstandingly effective intervention as renal cancer ablation, it may well have implications for the ultimate role of interventional oncology as a whole.

David J Breen is a consultant abdominal radiologist specialising in interventional oncology at the University Hospital Southampton, Southampton, UK.

Figure 2: Post-ablation scan

EXCEPTIONAL INFLATION CONTROL

Q50 PLUS ®

Stent Graft Balloon Catheter

The aortic modeling balloon that offers the broadest diameter range with the lowest available profile.

merit.com

10

Sept

Awards

Interventional radiology depends on team work

Issue

18 71

Anna Maria Belli, a former president of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the British Society of Interventional Radiology (BSIR), retired in March 2018 after a long and successful interventional radiology career at St George’s University Hospitals NHS Foundation Trust in London, UK, where she impacted on so many patients’ lives. Belli, who will be awarded the 2018 CIRSE Gold Medal in Lisbon, Portugal, spoke to Interventional News about her work and research in the field.

In your view, what is the most important lesson from your career in the field?

One of your key research interests has been the treatment of trauma and obstetric haemorrhage by endovascular means. What changes in this field have you seen?

The most valuable learning has been that interventional radiology depends on team work. The whole team is critical to success and that has long been our approach at St Georges. Consultant interventional radiologists are not afraid to ask for help, or an opinion from other interventional radiologists (whether they are consultants or trainees). Our radiographers and nurses are crucial and valuable members of the team and are aware of that and the reliance we place on their dedication and expertise. This leads to effective team working and a constant approach to the widely varied interventional radiology procedures which has a knock-on positive effect on training, patient care and safety.

There is increasing awareness and acceptance of the advantages of interventional radiology over standard techniques. However, considering how long these techniques have been around, I am still astonished by the level of ignorance of non-interventional radiology colleagues of what interventional radiology can achieve.

Simultaneously, there is still a paucity of high-quality evidence surrounding much of what we do, for instance even for a procedure such as angioplasty. But we are getting better and newer interventional radiology procedures are undergoing more formal testing with trials. We will never get high-quality evidence for many procedures, such as those treating vascular malformations and lymphatic disorders, where there are very few therapeutic options. But even with obstetric haemorrhage where interventional radiology clearly saves lives, it is very hard, if not impossible, to get high-quality evidence.

With the benefit of your experience, what are three key priorities in interventional radiology?

The three priorities for interventional radiology are achieving clinical control; increasing the numbers of interventional radiologists; and boosting the attractiveness of interventional radiology to women.

Interventional radiologists treat patients and need to see them before, during and after their treatments just as any other clinician/surgeon does. This means seeing them in clinic, having inpatient beds and training juniors to take clinical control. The second priority is increasing the numbers of interventional radiologists. The job opportunities are great and young doctors should see this as a fantastic career opportunity. Thirdly, there is a real need to increase the attractiveness of interventional radiology to women because the majority of medical graduates are now women and, therefore, the future of the subspecialty depends on this.

You have a very interesting recent paper out in the journal, CardioVascular and Interventional Radiology (CVIR) on the results of a CIRSE survey on the gender gap in interventional radiology, co-authored with Tze Wah from Leeds, UK (see article on facing page). For you, what was the most striking finding from the survey?

What most surprised me was the ignorance surrounding radiation. Of course, radiation must be treated with respect, but the misinformation and lack of understanding surrounding it is preventing

Anna Maria Belli

women from either entering interventional radiology or participating fully in the interventional radiology team. Both of these are damaging.

In your accompanying editorial in the same journal titled “The Female Threat”, co-authored by Meridith Englander, from New York, USA, you write: “Interventional radiology is under threat, not just by competing specialties, but by its apparent lack of attraction to women.” What changes need to take place in order to attract and retain women in interventional radiology?

There needs to be better knowledge and understanding of radiation exposure during pregnancy and part-time training needs to be made available.

Also, there are plenty of role models but seeing more female interventional radiologists in key roles helps the next generation.

You have first-hand experience of being in a situation where interventional radiologists had to protect their turf from other specialties. Without going into the specifics, what learnings can you distil for others from this experience?

We should not apologise for our success and our ability to introduce new minimally invasive treatments and perform them to a high standard.

Interventional radiology is naturally innovative and attracts those who “think outside the box”. That some of these procedures will replace standard therapies is inevitable. The fact that other specialties may also want to perform them is also inevitable, and a measure of our success. While interventional radiology training and practice remains the gold standard, we cannot be complacent. Unless interventional radiologists take clinical responsibility and are helped in this by their diagnostic colleagues and hospital management, they will be weakened by clinicians who wish to compete for these same interventional radiology procedures and who can self-refer in preference, as they have clinical control.

This has the potential for unhealthy practice which can compromise patient care. As doctors, we are the patients’ advocate and must always stand-up for what we believe is best care.

SIR receives award for “IAmIR” diversity and inclusion campaign

The Society of Interventional Radiology (SIR) has been honoured with a 2018 ASAE ‘Power of A’ Silver Award for its “IAmIR” diversity and inclusion campaign.

A

SAE recognised the “IAmIR” campaign in the category of “The Power to Create a Competitive Workforce.” Through this effort, SIR is empowering members and helping to include more women and underrepresented minorities in the growing, cutting-edge medical specialty of interventional radiology.

“This award is a testament to our

members’ commitment to creating an interventional radiology workforce that reflects the diversity of the patients they treat,” says SIR executive director Susan E Sedory. “It is a powerful validation that our efforts to recruit and retain interventional radiologists from diverse backgrounds are resonating outside of SIR, with other associations who seek to make

a substantial, positive impact on the world every day.”

“IAmIR” combined traditional recruitment strategies with social media marketing and interactive experiences at the society’s 2018 Annual Scientific Meeting to generate broad enthusiasm for, awareness of, and engagement with interventional radiology among

medical students, residents, fellows and attending physicians of all backgrounds. “IAmIR” continues to serve as a unifying rallying cry for the interventional radiology community and the patients they serve through the application of minimally invasive, image-guided medicine, a press release from SIR states.

Sept

Issue

18 71

Women in IR

Survey on gender gap reveals important perceptions of women working in IR TZE MIN WAH COMMENT & ANALYSIS Key findings from a Cardiovascular and Interventional Radiological Society of Europe (CIRSE) survey highlighting the perceptions and experiences of women in interventional radiology were published online ahead of print in the journal CardioVascular and Interventional Radiology (CVIR). “The survey was illuminating in quantifying the respondents’ perceptions of attitudes within interventional radiology,” writes Tze Min Wah, Leeds, UK, who distils the findings for Interventional News.

T

here is a global drive to increase gender diversity at the workplace in both private and public sectors.1 This is because gender diversity leads to a more empowered organisational culture, better talent retention rate and also increased financial revenue.2,3 In healthcare, there is published evidence to show that female physicians are providing better clinical care than their male counterparts.4,5 Given that more than 50% of medical graduates are female, this has prompted many clinical specialties to redesign their recruitment and training programmes in order to attract women into specialties that are traditionally perceived as the male-dominated, for example surgery.6 Obstetrics and gynaecology has been successful in increasing the intake of female trainees, e.g. 80% of current trainees are female.7 However, the uptake of female trainees in interventional radiology remains low at 10%.8 CIRSE has conducted a prospective online survey to understand the obstacles faced by female interventional radiologists and this has highlighted areas that we can all act upon to help to attract more women into the field.9

Key findings

An online questionnaire designed by the author and the CIRSE team was sent to 750 female and full junior members of CIRSE in the database. CIRSE is the largest interventional radiology society in Europe and its membership is representative of the specialty in Europe. The data were collected in August 2017 and facilitated by the CIRSE communication and publication team. The online questionnaire survey had the best CIRSE response rate to date which was 19.9% (n=149). Female interventional radiologists across 35 countries participated in the online survey where UK, Italy, Germany, Spain, Netherlands, France, Sweden, and USA accounted for the 65% of total response rate.

The demographics showed that the majority (91%) of the responders were between two major age groups: 31–45 years (56%) and 46–60 years (35%).

Most (83%) worked full time at a large university/tertiary referral institutions and expressed that they (69%) were a minority in the male-dominated interventional radiology department, where most of their superior/line managers were male (79%).

In addition, the majority (52%) of the female interventional radiologists had

no leadership role in their department and only 19% of them ever managed to participate in a senior leadership role either at local or national levels.

The survey was illuminating in quantifying the respondents’ perceptions of attitudes within interventional radiology.

A total of seven statements were used to enquire about their perceptions within their career in interventional radiology. ‘‘Interventional radiology is a less attractive career for women than other medical specialties’’ “Women are at a disadvantage when pursuing a career in interventional radiology’’ “Female interventional radiologists and radiologists are treated differently than my male colleagues by my superiors’’ ‘‘As a female interventional radiologist it is harder to get a promotion’’ “Female interventional radiologists are paid less than their male colleagues’’ ‘‘It is harder for female interventional radiologists to have both a fulfilled career and family life than for male interventional radiologists’’ ‘‘Interventional radiology is dominated by male networks’’ Apart from the last two statements, where a majority (67% and 77%) of the responders agreed with the statements, the majority of the female interventional radiologists disagreed with the first five statements. It is interesting to note that when the statements were interrogated against the four age groups (less than 30; 30–45; 46–60; over 60), the younger female interventional radiologists, i.e. those below 45 years of age, were more likely to agree with all the statements. Additionally, the vast majority (82%) of the female interventional radiologists had mentors/role models to guide and coach their career and overwhelmingly (72%) these mentors/role models were male.

Open responses from those who had agreed with the statements were usually centred on the five main themes: Radiation-related concern Pregnancy-related concern On call working pattern Difficulty in navigating interventional radiology with family life Male-dominated network It is reassuring to find that majority of the female interventional radiologists (67%) are

11

keen to take on leadership positions. They also feel that CIRSE could facilitate the progress and change the landscape to have more women in interventional radiology by providing the following: Guidance on radiation exposure to dispel the myth on radiation burden, particularly during pregnancy Guidance on structured and supportive training, e.g. flexible/part-time training Create a female mentors/role models programme for women in interventional radiology to promote female interventional radiologist through all stages of their career Promote female leadership at the faculty level in the congress and also at the editorial levels Promote interventional radiology at medical schools to raise visibility of the field as being a rewarding career option I would conclude with a quote from Elizabeth Broderick, former Sex Discrimination Commissioner, who said: “Gender equality isn’t a battle of sexes but a battle of equality, waged by women and men standing side by side”.

References 1. Company M. Women matter: gender diversity, a corporate performance driver; 2007.

2. Woetzel J, Madgavkar A, Ellingrud K, et al. The power of parity: how advancing women’s equality can add $12 trillion to global growth; 2015. https://www.mckinsey.com/ featured-insights/ employment-and-growth/how-advancing-womens-equality-can-add12-trillion-to-global-growth 3. Company, M. Women matter: reinventing the workplace to unlock the potential of gender diversity; 2016. https:// www. mckinsey.com/featured-insights/gender-equality/ reinventing-theworkplace-for-greater-gender-diversity 4. Tsugawa Y, et al. Comparison of hospital mortality and readmission rates for medicare patients treated by male vs female physicians. JAMA Intern Med. 2017;177(2):206–13.

5. Wallis CJ, et al. Comparison of postoperative outcomes among patients treated by male and female surgeons: a population based matched cohort study. BMJ. 2017;359:j4366.

6. Dageforde LA, Kibbe M, Jackson GP. Recruiting women to vascular surgery and other surgical specialties. J Vasc Surg. 2013;57 (1):262–7.

7. Jefferson L, Bloor K, Maynard A. Women in medicine: historical perspectives and recent trends. British Medical Bulletin 2015; 114 (1): 5–15 8. Clinical Radiology UK workforce census 2015 report.

London: Royal College of Radiologists; 2016.

9. Wah TM, Belli AM. The Interventional Radiology (IR) Gender Gap: A prospective online survey by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Cardiovasc Intervent Radiol 2018 Aug;41(8):1241–53.

Tze Min Wah is a professor and the lead for LTHT Interventional Oncology Program and a consultant interventional radiologist at the Diagnostic and Interventional Radiology Department, Institute of Oncology, St James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds, UK.

Scotland on red alert over shortage of interventional radiologists Interventional radiologists issued a red alert warning over staff shortages in Scotland as the only full-time specialists based in the Scottish Highlands step down. The Scottish Government has been urged to answer for “unacceptable failings”.

F

rom mid-August 2018, one health board will no longer have a substantive consultant interventional radiologist in post and plans to send emergency patients out of the area for treatment.

In a letter to local MSP Edward Mountain, the NHS Highland chair, David Alston, confirmed that there would be “no full time substantive consultant interventional radiologist based at Raigmore [Hospital in Inverness, Scotland] from the middle of August following a retiral and a resignation from the existing establishment of two consultants”.

Grant Baxter, Royal College of Radiologists in Scotland chairman, called on the government to boost the number of trainees to avert major problems after pledges were made for an extra 50 over five years.

Speaking to BBC Scotland, Baxter said: “We are on red alert. There is absolutely no doubt about this. If we do not address this issue now, there simply won’t be a service in the next three, four, five years. This situation is simply unsustainable and has resulted in thousands of studies currently lying around unreported, with all the safety issues that entails. Treatment regimens for cancer patients are almost entirely imaging based—therefore treatment decisions are being delayed.”

A spokeswoman for the health board explains that, for patients with immediate life-threatening conditions requiring intervention, there are arrangements in place to transfer to NHS Tayside or NHS Grampian.

There is an international shortage of radiologists, who are

in increasing demand. However, a locum is due to start in autumn and a retired radiologist will return one day a week from October.

A global recruitment drive was launched for nine boards across Scotland in February. Adverts in Western Europe, India, Australia, the USA and Canada sought to fill 32 radiologist vacancies.

Cabinet Secretary for Health Jeane Freeman said: “Despite an international shortage of radiologists affecting health services worldwide, since 2007 we have increased the number of clinical radiology consultants by 41% and increased radiography staff by 24.4%. We will also create an additional 50 specialist training places for clinical radiologists over the next five years.”

Sept

Issue

18 71

Embolization

13

ADVERTORIAL

Lipiodol and glue are better together for vascular embolization ROMARIC LOFFROY COMMENT & ANALYSIS Romaric Loffroy, Dijon, France, provides an overview of the technique and applications of vascular embolization with lipiodol and glue. Most of the complications related to the use of glue are avoidable with the use of proper technique, he writes.

N

-butyl cyanoacrylate (NBCA) is glue with a high adhesive strength that has been used in a wide variety of peripheral conditions. Certain properties of NBCA make it a potentially suitable agent for such applications. These properties include its high radiopacity when mixed with Lipiodol (Guerbet), quick time to embolization, low rate of same-vessel recanalisation, low viscosity for easy injection through small or tortuous catheters, and the ability to penetrate vascular beds in a flow-directed fashion. Same of the advantageous properties of NBCA can also lead to potential pitfalls. Although the list of such pitfalls and complications are long, the incidence is actually quite low in the periphery, when proper technique is used. NBCA glues, Trufill (Cordis, now Cardinal Health) and Histoacryl (B.Braun), have quite similar properties. Glubran 2 (GEM) is an NBCA glue combined with methacryloxysulpholane to produce a more pliable and stable polymer. Glubran 2 only has a European Conformity mark for intravascular use. The spectrum of peripheral applications for NBCA is wide: acute bleeding conditions, upper and lower gastrointestinal bleeding,

variceal bleed, haemoptysis, trauma, renal angiomyolipoma, type 2 endoleaks, varicocele, pelvic congestion syndrome, portal vein embolization and arteriovenous malformations.

Embolization technique

NBCA should be released under a fluoroscopic control mixed with Lipiodol. The mixture with Lipiodol also modulates the polymerisation rate.

Lipiodol is used for two reasons: first, to make the NBCA mixture radiopaque and, second, to dilute the NBCA to the desired concentration depending on how much the interventional radiologist wants to prolong the time to polymerisation. This allows the operator to control the degree of distal vessel penetration, allowing for occlusion at, or significantly beyond the catheter tip. A ratio of one part Lipiodol to one part NBCA (1:1) polymerises very quickly after coming into contact with ionic solutions, while a ratio of six parts Lipiodol to one part NBCA (6:1) will take longer.

Polymerisation of NBCA in contact with blood does not depend on coagulation parameters providing better haemostasis than other embolic agents, especially in bleeding patients with

Figure 1A

coagulopathy. The use of a coaxial catheter system is highly recommended when injecting all liquid embolic agents, especially glue.

NBCA is provided in small, sterile, 1mL containers. Our preferred method of preparing the Lipiodol/ glue mixture is to simply aspirate the glue out of its sealed container using a 5mL syringe. The glue is subsequently injected into a desired volume of lipiodol in a 5mL syringe through a three-way stopcock. The two components are then thoroughly mixed. Before injection of the mixture, the catheter is flushed thoroughly with 5% dextrose solution to completely clear its lumen from ionic solutions.

We prefer using 5mL syringes to inject the glue mixture. The syringe can be directly attached to the hub of the microcatheter to inject the desired volume of glue. Several factors impact the depth to which glue penetration occurs: the rapidity of flow passed through the catheter tip; ratio of NBCA to lipiodol; and injection technique are the most important. In vessels with rapid blood flow, more controlled injection of the glue mixture is necessary. For this reason, a lower ratio of lipiodol to NBCA may be chosen (1:1 or 1:2 ratio) to prevent penetration into the venous outflow and embolization to the pulmonary arteries. For distal embolization, a higher ratio (1:6) must be used to allow deep penetration. Once the injection is complete, the microcatheter is aspirated and withdrawn rapidly.

Pitfalls

Most of the complications related to the use of glue are avoidable with the use of proper technique. So, care must be taken to prevent them. Early polymerisation of glue can occur in the microcatheter leading to the occlusion of lumen and the potential loss of access.

Figure 1B

This is commonly due to contamination with ionic solutions and can be avoided by adequate flushing with 5% dextrose solution before the injection of glue.

If this occurs, it is recommended that the microcatheter be replaced. Excessive reflux around the microcatheter tip should be avoided. Reflux of polymerised glue around the microcatheter may adhere to its tip, increasing the risk of non-target embolization or catheter retention. If reflux is noted, the catheter tip should be pulled back sufficiently to free the tip before the glue polymerises.

Conclusion

Optimal use of NBCA requires adequate practical experience with this agent. As with other liquid embolic agents, there is a steep learning curve.

The marriage with lipiodol is absolutely mandatory. However, the advantages of using this class of agents in certain applications is worth the investment of time to achieve proficiency in their use.

Romaric Loffroy is professor and head of the Department of Vascular and Interventional Radiology, Center of Minimally Invasive Image-Guided Therapies, François-Mitterrand Teaching Hospital, University of Bourgogne/Franche-ComtÊ, Dijon, France. He is a consultant to Guerbet and GEM. Figure 1. Prophylactic arterial embolization of a large renal angiomyolipoma in an asymptomatic 36-year-old female. (A) Selective right renal arteriogram confirms the hypervascular angiomyolipoma. (B) After embolization of the two arteries supplying the lesion with a glue/Lipiodol mixture of 1:6 ratio, the arteriogram shows complete and selective exclusion of the angiomyolipoma. (C) Note the tumour uptake of glue/Lipiodol into the vascular bed on CT scan after embolization.

Figure 1C

14

Sept

Issue

18 71

Embolization

GEST 2018 US symposium underscores growing role for prostatic artery embolization

The burning issues in prostatic artery embolization were addressed by many of the physicians leading the research into this minimally invasive therapy at a mini symposium at the Global Embolization Cancer Symposium and Technologies (GEST US 2018; 17–20 May, Miami Beach, USA). The dedicated ‘symposium within a symposium’ in Miami in May featured a clinical forum and a technical forum, offering a focus on the crucial themes and the latest findings in this burgeoning field of therapy.

K

icking off the clinical forum, Christopher S Gomez (Miami, USA) shared the urology perspective with three presentations on the basics of benign prostatic hyperplasia (BPH). He looked at its epidemiology and pathophysiology, and introduced key terminology for BPH including benign prostatic obstruction (BPO) and lower urinary tract symptoms (LUTS), an all-encompassing term for urinary symptoms. In an overview of the medical management of male LUTS, he then discussed α1 antagonists, 5α-reductase inhibitors, phosphodiesterase 5 inhibitors, muscarinic receptor antagonists, and beta 3 receptor agonists. Then, focusing on surgical management of BPO, Gomez demonstrated that, although transurethral resection of the prostrate (TURP) remains the gold standard, its use is declining, and that bipolar TURP provides greater efficacy with less morbidity. Greenlight laser vapourisation can be used on patients who are on anticoagulants or taking aspirin, and in a comparison with TURP, he found both procedures gave similar short-term outcomes. However, the adverse event profile differed, with a greater bleeding rate following TURP and increased urinary incontinence after laser vapourisation. Gomez also pointed out that minimally invasive office-based techniques have decreased efficacy and had higher retreatment rates compared to TURP. He noted that robot-assisted surgeries may standardise results and decrease adverse events.

Jafar Golzarian (Minnesota, USA) then explored the features of the ideal candidate for embolization. He told delegates that the best patients are those who are either contraindicated for surgery or have had failed surgery. Patients with a very large prostate, and a low platelet count or a high risk of bleeding. Those who refuse surgery, have haematuria, or have had previous pelvic interventions, radiation or indwelling catheters should also be considered, he said.

Later in the clinical forum, Nigel Hacking (Southampton, UK) examined the significance of the results from the UK ROPE (Register of Prostate Embolization) registry published in August in BJU Int. He cited its multicentre, non-inferiority design as a strength, as well its funding by multiple stakeholders. The use of a postal questionnaire reduced bias, and physicians were free to choose embolics and catheters or microcatheters depending on their familiarity and expertise. But weaknesses included that this was nonrandomised data and that the study had a 12-month endpoint. Hacking concluded that ROPE data had contributed “arguably

Delegates at the GEST US 2018 meeting studying the prostatic arterial anatomy and its variants

very little” to the current evidence base, while praising its unbiased data, full urology and regulatory authority input, and the fact that it was instrumental in the procedure gaining approval from the National Institute for Health and Clinical Excellence (NICE).

“The news is out,” he said, “and prostatic artery embolization is here to stay.”

Meanwhile, in the technical forum, Tiago Bilhim (Lisbon, Portugal) made the case for pre-procedure imaging protocols.

He pointed out that finding your way in the pelvis is not easy, and that computed tomography angiography (CTA) prior to prostatic artery embolization is a beneficial planning tool to increase success rates. CTA images can be used to calculate the baseline prostate volume, and for intraprocedural anatomic guidance. Ideally, Bilhim said, the same physician reading the CTA should be performing the embolization. CTA, he said, allows confident identification of prostate arteries, promising: “If you do not see them on CTA, they are not there.”

Francisco Cesar Carnevale (São Paulo, Brazil) provided a guide to the Carnevale classification. His key take home messages were that an accurate knowledge of the male pelvic anatomy using a standard classification can help to standardise the procedure, recognise

anatomical variations, and reduce procedure time and radiation exposure, thus securing the best clinical outcomes safely and effectively, and minimising complications.

In a talk on erectile function, Shivank Bhatia (Miami, USA) presented the results from a meta-analysis and other studies, including this own retrospective review of 100 patients. The meta-analysis found that embolization has no effect on erectile function. In his review, Bhatia noted that it is associated with an improvement in erectile function.

He argued that embolization offers an excellent alternative to surgical options, such as TURP and photoselective vapourisation of the prostate (PVP), with a high rate of technical success and a favourable impact on sexual function.

He later returned to discuss an adjunctive role for embolization in the management of prostate cancer. He noted that a prostate artery embolization pre-prostatectomy can lead to superior surgical outcomes through a volumetric reduction of the prostrate and a reduction of vascularity to the prostate gland, and can be a useful alternative to hormone therapy, which has many side-effects.

Bhatia told delegates that, in his limited experience, embolization is safe and has

no impact on prostate cancer morphology.

Further, it has a potential role in improving the management of prostate cancer as an adjunct to current therapies, as well as a possible therapeutic role; and that it may improve quality of life by managing BPH in patients with advanced prostate cancer.

An important issue in prostatic artery embolization is whether to use the transradial or femoral approach route. Ari J Isaacson (North Carolina, USA) highlighted the pros and cons for each. The femoral route, he pointed out, is a proven access point, with a shorter distance to the target vessel, and benefits from catheter and wire availability. But, it requires a longer recovery time, an increased time to ambulation, eating, and urination.

“There is a lower risk of access site haematoma in radial access; it is an easier approach for certain anatomies; and it is ideal for anticoagulated or coagulopathic patients, with a faster recovery overall.

However, longer catheters and wires are required, and there is potential for intracranial embolus. Room compatibility and radiation protection are also an issue, as is anatomy,” Isaacson noted.

Concluding, he advised familiarity with both methods, using an individual evaluation of each patient to inform the decision about which one to choose.

FV_BV

FV_BVS267918_Imperial_Advert_for_Biba.indd 1

06.09.18 15:30

16

Sept

Issue

18 71

Radial access

Setting up for prostatic artery embolization success with a radial-first approach “My approach is now ‘radial first’ for prostatic artery embolization and I believe that radial access is here to stay,” Shivank Bhatia, associate professor of Interventional Radiology and Urology, University of Miami Miller School of Medicine, Miami, USA, tells Interventional News.

Shivank Bhatia

What is your current experience with prostatic artery embolization?

My experience with the procedure began by observing cases with Francisco Carnevale at the University of São Paolo, Brazil, followed by an investigational device exemption trial in 2013 that compared embolization with transurethral resection of the prostate (TURP).

To date, I have performed over 350 prostate embolization procedures for a variety of indications including benign prostatic hyperplasia, urinary retention, chronic haematuria and as an adjunct in the management of prostate cancer. In benign prostatic hyperplasia, we are seeing an improvement of 60–80% in International Prostate Symptom Scores (IPSS) in over 90% of patients treated with embolization. The patients are pleased with these outcomes, which are similar to transurethral surgical procedures. The patients presenting with urinary retention are also doing well, with over 90% able to void without a catheter at one-month post procedure. However, we still need to evaluate the long-term durability of these outcomes.

along with the arterial tortuosity and variant anatomy deterred initial attempts at using the radial approach in this procedure.

We have been constantly looking at ways to improve patient experience and satisfaction with prostatic artery embolization. Offering radial access has been key to this. I started offering radial access for prostatic artery embolization in 2016, after attending a training course. Now, having treated over 230 patients using the radial approach, I believe this approach has led to improved patient satisfaction, reduced procedure time and overall improved procedure outcomes.

In our published experience, patients who received the procedure via radial access were compared with two sets of patients who had the procedure via transfemoral access (one group from early in the operator’s learning curve for embolization and the other, once the operator was familiar with the procedure). Radial access patients had decreased procedure times, fluoroscopy times, and total radiation doses when compared with all transfemoral access patients. No major complications occurred in any of these patients and there were no significant differences in minor complication rates when compared to both groups of transfemoral access patients.

Prior to selecting patients for radial access, collateral circulation must be adequate as determined using a Barbeau test (ie, a modified Allen’s test with a pulse-oximetry device).

Tools like ultrasound guidance for arterial access, use of tumescence around the artery, use of intraarterial drugs (we use a combination of 200mcg of NTG, 2000IU of heparin and 2mg Verapamil), and proper deflation protocols are key to establishing a successful radial practice with great patient satisfaction and outcomes. Our aim with every access is to ensure, as much as possible, that the vessel is patent for future interventions.

The exclusion criteria for using transradial access for prostatic artery embolization has been patient height (>6ft), type D Barbeau waveform, and radial artery diameter <2mm. My approach is now “radial first” for this procedure and I believe that radial access is here to stay.

Could you describe your room set-up?

After attending a radial course to understand the basics of radial access and gaining insight into the technique, our initial cases went very smoothly. I also quickly realised that room set-up for prostatic artery embolization using radial access could be accomplished by keeping the arm to the side of the patient, or at a 30 to 45-degree angle. I initially placed the monitor towards the head of the patient on the same side of the table, but this meant

my back was still very close to the radiation source. After some thought, I decided to place the patient’s arm outstretched at 90 degrees with the monitor on the opposite side of the table. This led to setting up the room in a similar fashion as for femoral access in terms of the monitor, the tray location, and the operator location (except that I was much further away from the radiation source).

This positioning also allowed me to perform the procedure with my dominant right hand as well. With the radial set-up I am using, there is significantly lower operator dose, due to distance from the field.

2D and 3D imaging capabilities

One of the most important aspects of radial access for prostatic artery embolization is a ceiling mounted angiographic system because it has enough “clearance” needed for optimal setup. Currently, we have full 2D and 3D capabilities with our system which is ideal for using these additional tools as needed. One of my initial concerns was the ability to perform cone beam CT during the procedure with this set-up. To my surprise, cone beam CT imaging resolution was excellent and it was actually much easier to perform with minimal manipulation. Currently, we are collecting data for a prospective study (NCT03164629) to evaluate the role of 3D angiography in prostatic artery embolization and perform all these procedures using radial access with the set-up I described.

What led you to using the radial access for this procedure?

Traditionally, prostatic artery embolization was performed via a transfemoral approach, but the transradial approach has increasingly garnered interest. Evidence suggests that access via the radial artery results in shorter post-procedure hospital stays, decreased accesssite complications, and an improved patient satisfaction. This method also allows patients to ambulate immediately after the procedure, which could facilitate urination. The distance from the forearm to pelvis

14390A_

14390A_IndigoSystem_PowerAspiration_wCATD_Ad_EU_forIntvNews_01Aug18.indd 1

8/3/18 2:53 PM

18

Sept

Issue

18 71

Embolization

All flow, some stick, and others are cohesive: The basics of handling liquid embolics Liquid embolics can be used to cast the nidus of arteriovenous malformations in the brain or periphery, treat type II endoleaks after endovascular aneurysm repair, occlude veins, stop bleeding, and close pseudoaneurysms. Delegates at GEST US 2018 (Miami, USA) learnt about handling various liquid embolics such as n-butyl cyanoacrylates (NBCA or glue; such as Glubran 2 [GEM], Trufill [Cordis, now Cardinal Health]), ethylene vinyl alcohol (EVOH) based agents (such as Onyx [Medtronic], PHIL [Microvention/ Terumo], Squid Peri [Balt] and Easyx [Antia Therapeutics]), alcohol, sclerosing agents (such as Varithena [BTG]) and other brand new embolics that will soon hit the market.

R

icardo Garcia-Monaco (Buenos Aires, Argentina), explained that glue is an adhesive liquid embolic agent that has a permanent (durable) embolic action. This is why, he said, gluetype agents are considered when you need to provide a definitive embolization.

Since NBCA polymerises immediately upon contact with any ionic solution or with the intima of a vessel, the delivery system must always be flushed with a nonionic solution (such as 5% dextrose) in order to avoid early polymerisation and occlusion of the catheter lumen, he exhorted. Garcia-Monaco also commented that the polymerisation time depends on the viscosity of NBCA and that this may be manipulated, and delayed, by mixing with Lipiodol (Guerbet). “The more Lipiodol you use in the mixture, the longer the polymerisation takes and the more distal the vessel occlusion is. NBCA is not radiopaque but mixing with Lipiodol makes it so,” he said.

EVOH copolymers

Robert Morgan (London, UK), while describing the basics and handling of EVOH-based agents, noted that these were cohesive agents.“These agents are non-thrombogenic and solidify on exposure to blood; they use dimethyl sulphoxide (DMSO) as a solvent and, therefore, must be injected through a DMSOcompatible microcatheter. EVOH-based agents contain radiopaque components to provide visibility; with Onyx and Squid, this is tantalum and with PHIL (precipitating hydrophobic injectable liquid), it is iodine,” he noted.

Morgan outlined that EVOH-based agents had specific handling requirements that were distinct from other liquid embolics. “Pain due to DMSO is a real issue–you should administer analgesia and sedation immediately before embolization,” he urged.

Delegates listen to a talk on embolics at GEST US

New agents

Marc Sapoval (Paris, France) emphasised that the best liquid embolic agent would need no preparation, be highly radiopaque with no artifacts on follow up-imaging (CT), be non-adhesive, have good cohesion capability and also possess a range of viscosity.

He gave a sneak preview of “newcomer” agents Easyx and Squid Peri, noting that that the time of the presentation, these agents had not yet received US FDA approval.

“Easyx is an iodinated polyvinyl alcohol ether dissolved in DMSO and available in three viscosities.

This agent can fill a small aneurysm, results in no toxicity to the arterial wall and mild artifacts on CT. It can fill the AVM [arteriovenous malformation] nidus well. The agent is being clinically evaluated in Europe via the Rebel European registry and the Easyx 1 prospective trial in France, which plans to enrol 50 patients,” Sapoval said.

Squid Peri is a non-adhesive liquid embolic agent indicated for peripheral embolization. It is composed of EVOH copolymer dissolved in DMSO with (suspended) micronised tantalum powder for radiopacity.

Alcohol

Sang Joon Park (Incheon, Korea) made the case for alcohol being an excellent embolic “in the right expert’s hands”. “Alcohol is cheaper than any other liquid embolic agents and has well-understood mechanisms of metabolism and excretion in humans. It is readily available and can be diluted. Further, it can be used a curative agent,” Park said.

“With alcohol, there is usually no recanalisation as seen with gelfoam, poly vinyl alcohol particles and tissue adhesives. With alcohol, it is also easier to control the level of occlusion and the agent can be administered in various ways such as by transarterial or transvenous means, or by direct puncture. It can also be combined with coils”, he explained.

Absolute ethanol is used in most cases and 80% ethanol diluted with nonionic contrast agent for superficial lesions near the skin. “Alcohol is a ‘most effective, yet most feared’ agent that needs mastering.

While using alcohol, it is necessary to use precautions such as Swan-Ganz catheter monitoring of pulmonary arterial pressure,” said Park.

Sclerosing agents

Michael S Rosenberg (Minnesota, USA), who introduced sclerosing agents, noted that these have a physical, chemical or biological effect that results in a controlled inflammatory response, which in turn leads to cell damage with fibroblast proliferation and eventually to sclerosis or fibrosis.

In the vascular world, sclerotherapy is used to treat varicose, peripheral and gonadal veins, vascular malformations and lymphatic disease. In the nonvascular world, it is used in the treatment of cysts, solid organs such as bone, lymphoceles, the gallbladder and animal models.

“Sclerotherapy forms a continuum with embolotherapy as it results in vascular occlusion; some embolic agents also create a sclerosant effect such as cyanoacrylate glue,” explained Rosenberg.

Gas embolotherapy generated microbubbles could provide vehicle for cutting off blood supply and delivering drugs Recently, scientists have explored another version of embolization, gas embolotherapy. During this process, the blood supply of cancerous tumours is cut off using acoustic droplet vapourisation (ADV), which uses microscopic gas bubbles induced by exposure to ultrasonic waves.

A

team of researchers from China and France has discovered that these bubbles could also be used as potential drug delivery systems. The researchers reported their findings this week in Applied Physics Letters.

“We have found that gas embolotherapy has great potential to not only starve tumours by shutting off blood flow, but also to be used as a source of targeted drug delivery,” says Yi Feng, associate professor of biomedical engineering at Xi’an Jiaotong University and first coauthor of the paper.

In gas embolotherapy, researchers

inject droplets, from tens to hundreds of nanometres in diameter, into feeder vessels surrounding the tumour. Microscopic gas bubbles are then formed from the droplets through ultrasound, growing large enough to block the feeder vessels. ADV is the process of transforming droplets into bubbles.

In previous work, the researchers expected to use ADV to starve the tumour by blocking blood flow in the arterioles. To their surprise, they found that the bubbles not only blocked the arterioles, but other gas bubbles entered the capillaries, resulting in vessel rupture and leakier microvasculature.

In their latest work, gas embolotherapy through ADV was performed to further explore the dynamics of the bubbles inside the capillaries. Testing was conducted ex vivo on rat tissue that attaches the intestines to the abdominal wall. It involved bubble formation in droplets of dodecafluoropentane containing a bovine serum which were injected into the blood flow.

Produced in the dodecafluoropentane through ultrasound, the bubbles accumulated as they lodged themselves in the capillaries.

At one point, the researchers observed a local vessel invagination (a pouchlike cavity), which they believe was caused by the interaction between the bubble and vessel and led to a capillary rupture.

Their findings could provide a one-two punch for cancer treatment—shutting off blood flow from the arterioles and delivering

drugs through the capillaries. In addition, chemotherapy drugs could be kept localised for longer periods of time because blood flow has been shut down, reducing drug dosage.

“In cancer therapy research, scientists are always interested in answering two questions: how to kill the cancer effectively and how to reduce the sideeffects of chemotherapeutic drugs,” says Mingxi Wan, professor of biomedical engineering also at Xi’an Jiaotong University and corresponding author of the paper. “We have found that gas embolotherapy has the potential to successfully address both of these areas.”

With an ultrasound imaging method in place, according to Feng, gas embolotherapy has a good chance of becoming a standard practice.

18-eme

PREDICTABILITY FOR YOU. OPTIONS FOR YOUR PATIENTS.

The Emprint™ ablation system powered by Thermosphere™ technology delivers that predictability. With three kinds of spatial energy control – thermal, field, and wavelength – it produces precise spherical ablation zones. It’s ablation you can count on. So the only thing to imagine is how it can transform your patients’ lives.

© 2018 Medtronic. All rights reserved. 18-emea-emprint-predictability-advert-2620225-1

18-emea-emprint-predictability-advert-2620225-1.indd 1

25/07/2018 14:48

20

Sept

Issue

18 71

Immunotherapy

IO4IO initiative: Advancing immuno-oncology Lambros Tselikas, Thierry De Baere, Frederic Deschamps, Steve Yevich and Aurélien Marabelle COMMENT & ANALYSIS Interventional oncology (IO) can contribute to the advancement of immunotherapy through several practical and innovative methods, write Lambros Tselikas, Thierry De Baere, Frederic Deschamps, Steve Yevich and Aurélien Marabelle, all from Villejuif, France.

I

mmunotherapy has quickly proved to have profound therapeutic effect for several cancer types. It is anticipated that it will radically change the standard of care for cancer treatments. In the past years, a phenomenal amount of preclinical and clinical data has been gathered on the effects of different immunotherapy agents. Despite treatment promise, severe toxicities have been reported and therapeutic results are often variable.

These inconsistencies appear to vary based on the cancer patients’ individual biology and possible cancer type, which underscore the incomplete understanding of the underlying mechanisms of action. IO can contribute to the advancement of immunotherapy through several practical and innovative methods.

Interventional oncology techniques can provide valuable access to tumour biology through minimallyinvasive image-guided tumor sampling. Primary resistance is a major limitation to immunotherapy. Roughly 70–80% of treated patients with solid cancer do not develop an objective response to monotherapies. Furthermore, secondary resistance has been reported in patients with progressing or relapsing tumours despite initial response.

The mechanisms for resistance are not well understood and require access to tumour biology. The acquisition of core needle samples before, during, and after treatment, allows the identification and development of preemptive biomarkers to predict tumour responses and better stratify treatment strategies for improved personalised patient care. Repeating sampling at relapse or toxicity can help to understand the mechanisms of acquired resistance and

treatment specific autoimmune toxicities.

In addition to diagnostic sampling, interventional oncology can help potentiate the immuno-oncology effects by stimulating a inflammatory response within a target tumour. Improved outcomes have been reported as the result of a combination of immunotherapy with targeted locoregional therapy of thermal ablation or endovascular embolization. The combination treatment can present a key mechanism to augment the response in patients with primary or secondary resistance to immunotherapy. As reviewed in a previous edition of Interventional News by Hickey et al., data shows that locoregional therapy can prime the systemic immune response for more effective outcome at the target tumour. While this locoregional response alone may not translate to immunotherapy effects at other tumours located distal to the targeted tumour site, the adjunctive administration of an immune checkpoint inhibitor can enhance the effects for an improved systemic response. Ongoing preclinical and clinical research is seeking to identify the optimal combination and administration sequence of immunotherapeutic agent, targeted locoregional therapy, and immune check point inhibitor to increase the objective response and duration.

Interventional oncology techniques also can provide delivery of the immunotherapeutic agent directly into the tumour. The agent can either be injected directly through a needle placed under image guidance into the tumor, or be injected through an artery supplying the tumour. The potential applications for this direct injection is to potentiate systemic anti-tumour immune responses

through local tumour inflammation, maximise delivery of immunotherapy to the tumour, and allow administration of a smaller dose to decrease side-effects. Thus, intratumoural administration could be more effective than systemic injections with dramatically decreased offtumour immune-related toxicities. As discussed in a recent review “using the tumour as the remedy”, five clinical trials are actively recruiting patients in our institution to evaluate direct intratumoural delivery of immunotherapy.

Lastly, interventional oncology can provide targeted locoregional treatment of any residual tumours or those that do not respond immunotherapies. For instance, not all tumours may respond sufficiently in patients with multiple metastatic locations. In patients with residual tumours after immunotherapy, IO can provide curative locoregional control through minimally invasive percutaneous techniques of thermal ablation. Alternatively, in the scenario of dissociated response, locally imagetargeted treatment could be offered to non-responding sites to maintain the patient on immunotherapy.

To summarise, IO is actively contributing to the advancement of immuno-oncology through four key methods. Minimally invasive tissue sampling provides key pathology specimens to evaluate underlying treatment effects and understand mechanisms of action. The addition of locoregional therapy can potentiate an inflammatory response to improve local and distant tumour response.

Direct delivery of immunotherapy into a target tumour can improve treatment effect, increase medication concentration within the tumour, and decrease systemic toxicities. Targeted curative IO therapies can also provide effective locoregional control in those patients that demonstrate a mixed response to immunotherapy.

Lambros Tselikas, Thierry De Baere, Frederic Deschamps and Steve Yevich are all from Interventional Radiology, Gustave Roussy, Villejuif, France. Lambros Tselikas and Aurélien Marabelle are affiliated to Laboratory of Translational Research in Immunology—LRTI, INSERM U1015 in Gustave Roussy. Marabelle is affiliated to the Drug Development Department, Gustave Roussy, France.

Researchers chart the way ahead for immuno-oncology A key session at the World Conference on Interventional Oncology (WCIO; 7–10 June, Boston, USA) provided an update from early research into the use of immuno-oncology in interventional oncology, underlining its potential as future therapy. Investigations are being carried out with grants from the Society of Interventional Oncology (SIO) in an attempt to obtain an understanding of how interventional oncology can affect lymphocyte changes at the cellular level in cancer patients.

T

he session consisted of presentations from the first four successful grant recipients and included details of the impact of checkpoint inhibition (CI) and the abscopal effect. Checkpoint inhibitors are monoclonal antibodies generated against immunosuppressive portions of the immune system. They target these immunosuppressive pathways thus increasing the anti-tumour immune response and ultimately leading to a greater T-cell response. The abscopal effect is an infrequently observed

phenomenon in the treatment of metastatic cancer in which distant tumour regression occurs after localised irradiation.

Stephen Hunt (University of Pennsylvania, Philadelphia, USA) is exploring the immunobiologic treatment effects of embolization in a rat hepatocellular carcinoma (HCC) model. The study involves the insertion of LUMI beads (BTG) into a rat that has liver cancer to examine the effect of embolization with these beads on the immune system. It also aims to determine

any abscopal effect on tumours that have not been embolized, effects of combining embolization with checkpoint inhibitors, and whether it is possible to use any immune cells generated from embolization to create an anti-tumour response in another rat with cancer.

He cautioned that using cellular immunity to fight cancer is a “twoedged sword, because for every immune cell [reaction], there are both anti-tumourigenic, as well as protumourigenic factors”.

The investigating team has developed a lymphocyte grading system to measure high infiltration of tumour lymphocytes, and found “robust infiltration of T cells, which is marked with CD3 at 14 days after embolization”, Hunt said. “We can [soon] start teasing apart the different macrophage populations present within the cell.”

He predicted: “It is unlikely that

embolization or checkpoint inhibition alone are sufficient to generate an [effective systemic] immune response, but you can get neoantigenic expansion as a target for specific immune response.

There are, obviously, a lot of questions that remain. We have developed a phase I clinical trial combining embolization with checkpoint inhibition.”

Florian J Fintelmann (Massachusetts General Hospital, Boston, USA) outlined a pilot study of cryoablation combined with immune checkpoint inhibitor therapy in patients with PD-1 refractory metastatic melanoma.

The prospective clinical research is a phase II clinical trial of patients with either metastatic melanoma or lung cancer who have an acquired resistance to immune checkpoint inhibitor therapy. He explained: “The metastatic population which was the target of this trial is not suited for undergoing

Sept

Issue

18 71

Immuno-oncology

Take your pick from our transjugular liver access sets.

Stephen Hunt

Joseph P Erinjeri

surgery or a lot of invasive procedures.

These patients do not have other options. Interventional oncology is well suited to generate antigens to help stimulate the immune response, because we generate antigens by causing cell death.”

The intervention involves core needle biopsy of a site, with cryoablation at the same site, while continuing checkpoint inhibition therapy. A repeat core needle biopsy several weeks later looks for changes induced by the cryoablation to the tumour microenvironment.

Investigators follow the tumour burden using serial imaging, and evaluate overall survival, with specific attention paid to lesions untreated by cryoablation to harness the abscopal effect.

Fintelmann said that evaluating the mechanisms of resistance to checkpoint inhibition therapy at the time of cryoablation “is a really key question, because what we are after is enhancing checkpoint inhibitor therapy, so we need to have biomarkers and an understanding of what is going on at the time that these

following interventional oncology therapies, and looked at which of these techniques optimally stimulate the immune system.

The relationship between mutational load and neoantigen formation can predict survival; the more mutations that are present in a cancer, the more neoantigens are created, leading to greater clonal expansion of T-cells which has been shown to correlate with survival.

Erinjeri discussed the factors necessary to generate anti-tumour immunity, and whether it is possible to tell whether this immunity has been created using interventional oncology procedures. He also examined what T-cell clonality can reveal about the effects of interventional oncology procedures on the immune system.

“How would you know if you had enhanced tumour immunity after an interventional oncology procedure? It is hard to tease apart whether these are additive or synergistic effects. There may be lots of T-cells but they may not be

How would you know if you had enhanced tumour immunity after an interventional oncology procedure? It is hard to tease apart whether these are additive or synergistic effects Joseph P Erinjeri patients progress. There are not that many data points that are well established, so part of our effort is focused on generating data in that space.”

Rafael Duran (Lausanne University Hospital, Lausanne, Switzerland) updated delegates on an analysis of the immunobiology of hepatocellular carcinoma in patients undergoing Y-90 radioembolization, and told them that Y-90 radioembolization therapy has “matured the potential immunomodulatory abilities of radioembolization. We are confident that the results obtained from this investigation could be used to really design, rationalised future clinical trials.”

Joseph P Erinjeri (Memorial Sloan Kettering Cancer Center, New York, USA) delivered a talk on T-cell clonality and cancer neoantigen presentation

active, and the cytokines there may not be very specific,” Erinjeri queried.

The hypothesis of the study presented is that interventional oncology procedures expose the immune system to cancer neoantigens that stimulate clonal expansion of T-cells. The investigators aim to determine T-cell repertoire changes after interventional oncology procedures and discover which one stimulated the immune system the most.

Transarterial embolization works well in the liver because of the dual blood supply, and has been shown to increase the response against a panel of antigens, including HCC antigens, a process known as neoantigenic expansion. The release of tumour antigen in combination with checkpoint inhibition also generates an immune response.

Rösch-Uchida TRANSJUGULAR LIVER ACCESS SET

Includes solid trocar stylet and 10 Fr Flexor® sheath.

Ring TR ANSJ UG UL AR INTR AH E PATIC ACCE S S SE T

Includes hollow Colapinto needle and 9 Fr or 10 Fr Flexor sheath.

For more about these products and related physician training options, call your Cook sales representative or visit vista.cookmedical.com

MEDICAL

cookmedical.com © COOK 08/2016 IR-D28919-EN-F

21

22

Sept

Issue

18 71

Immuno-oncology

Interventional oncology has potential to energise the immune system Combining immune checkpoint blockade treatment with locoregional therapies to enhance the antitumour effects of immunotherapy may be the key to overcoming the limitations of either strategy alone, write Samdeep Mouli and Robert Lewandowski.

SAMDEEP MOULI ROBERT LEWANDOWSKI COMMENT & ANALYSIS

I

mmunotherapy has emerged as a novel treatment option for cancers that have historically failed conventional systemic agents. In the tumour microenvironment, cancer cells upregulate proteins that bind to specific T-cell receptors, resulting in immune escape or tolerance. Blockade of checkpoint proteins, specifically programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA4), have been shown to enhance antitumour activity in a variety of malignancies. This immune checkpoint blockade has gained approval for use in patients with advanced hepatocellular carcinoma (HCC); however, current approaches are limited by the strong intrinsic immune suppressive microenvironment within the liver. There is potential for interventional radiology procedures (eg, percutaneous ablation and/or intraarterial embolotherapy) to work synergistically with systemic immunotherapy to improve the outcomes of patients with HCC. Recent immunotherapy trials reveal the potential of immunotherapy. Nivolumab, a fully human IgG4 antiPD-1 antibody was studied in a phase I/II dose escalation and expansion trial in 214 patients with advanced HCC previously treated with sorafenib (Checkmate 040 NCT 01658878). Nivolumab was administered every two weeks in 214 patients with Child-Pugh A/B liver disease.

An objective response rate of 20% was observed based on RECIST v1.1 criterion, resulting in the conditional approval of Nivolumab for patients with advanced HCC failing sorafenib.1 A subsequent study comparing nivolumab to sorafenib as a first-line therapy in advanced HCC (Checkmate 459, NCT 02576509) is currently underway.

A similar study involving pembrolizumab, an anti PD-1 antibody, in BCLC B/C patients previously treated with sorafenib (Keynote 224 NCT 02702414) was recently reported at the 2018 Gastrointestinal Cancer Symposium of the American Society of Clinical Oncology (ASCO).

Patients received 200mg pembrolizumab every three weeks for two years, until disease progression or withdrawal from the study. The overall response rate

(by RECIST v1.1) was 16.3%, with approximately 94% of responders experiencing a response duration of six months or greater.2 This will be followed by the Keynote 240 trial, a double-blind placebo controlled phase III trial comparing pembrolizumab vs.best supportive care in advanced HCC. Other recent studies have reported initial results from combination systemic therapies. At ASCO 2018, results from a phase Ib study (NCT 02715531) combining atezolizumab (anti PD-L1) and bevacizumab (anti VEGF) in 26 patients with unresectable of metastatic HCC were reported. Preliminary results demonstrated a response rate of 62% by RECIST v1.1, suggesting synergistic activity of this treatment regimen.3 Results of this study led to the US FDA granting a breakthrough therapy designation for use of this combination therapy as a first-line treatment for patients with advanced or metastatic HCC. The phase III IMbrave150 study (NCT03434379) comparing the atezolizumab/ bevacizumab combination with sorafenib in the first line setting for patients with locally advanced or metastatic HCC is ongoing.

Despite the profound enthusiasm for immunotherapy for HCC, reported response rates thus far leave room for improvement. These results indicate that many patients remain unresponsive to therapy, probably secondary to the liver’s innate mechanisms of immunotolerance. While HCC may be a candidate for immunotherapy, liver immunology is very unique compared to other organ systems and poses a therapeutic hurdle. Due to its dual vascular supply, the liver receives numerous antigens from the gut through the portal vein. Thus, multiple mechanisms of immunotolerance exist to inhibit autoimmune liver damage. In chronic liver disease, dysregulation of these mechanisms leads to hepatic disease progression, and ultimately HCC. Dysregulation of inhibitory molecules, or immune checkpoints, have been implicated in HCC, specifically the PD-1 and CTLA-4 axes.

The key to improving immunotherapy efficiency in HCC may lie in improving immune cell influx and tumour antigen presentation. Combining immune

checkpoint blockade treatment with locoregional therapies to enhance the antitumour effects of immunotherapy may be the key to overcoming the limitations of either strategy alone. For example, both ablation and embolization have been shown to affect cellular immune function and induce a peripheral immune response. Once initiated, this immune response presents a potential avenue for synergistic treatment through immune modulating agents. A recent phase I/ II clinical trial utilised tremelimumab, an antibody to CTLA, in patients with intermediate and advanced HCC who were subsequently treated with either ablation or TACE. Overall a 26% partial response rate with a median overall survival of 12.3 months was seen.4 Similarly, radiation can also induce tumour-specific immune responses by increasing immune cell influx into tumour tissue. Given Y-90 radioembolization has demonstrated high tumour response rates and improved survival, potential synergies between radioembolization and immune checkpoint blockade requires study. Radioembolizations’ tumouricidal effects may be exploited to induce cell death and thereby release tumour antigens, which has been seen with other local therapies. In conjunction to immune checkpoint blockade, these antigens can be recognised by the immune system, ultimately resulting in a tumour-specific T-cell response. Studies exploring radioembolization in conjunction with ICB are ongoing (NCT 03033446 and NCT 03380130).

Developments in immunotherapy have led to exciting advancements in the treatment of cancer patients. There is tremendous opportunity for interventional radiologists to integrate loco-regional cancer therapies with immunotherapies to improve response rates, present antigen, and energise the immune system. Future studies should aim to better understand the immune response to ablative/embolic therapies to facilitate optimum combinations of these treatments.

Samdeep Mouli is at the Section of Interventional Radiology, Northwestern University, Chicago, USA. Robert Lewandowski is professor of Radiology, Medicine, and Surgery and director of Interventional Oncology, Department of Radiology, at the same institution. He is a consultant to BTG. References 1. El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet.

2017;389(10088):2492–2502.

2. Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab (pembro) in patients with advanced hepatocellular carcinoma (HCC): KEYNOTE-224 update. Journal of Clinical Oncology. 2018: 36:4_suppl, 209–209 3. Stein S, Pishvaian MJ, Lee MS, et al. Safety and clinical activity of 1L atezolizumab + bevacizumab in a phase Ib study in hepatocellular carcinoma (HCC). Journal of Clinical Oncology. 2018;36(15_suppl): 4074–4074 4. Duffy AG, Ulahannan SV, Makorova-Rusher O, et al. Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma. J Hepatol. 2017;66(3):545–51.

Involving interventional oncologists in gene therapies could cut their prohibitive costs Daniel Sze (Stanford University, Stanford, USA), presenting at the European Conference on Interventional Oncology Annual Meeting (ECIO; 22–25 April, Vienna, Austria), calls for a synergy between gene therapy and interventional oncology, saying that delivery efficiency can be improved by interventional oncologic procedures, cutting costs on treatments which can currently go up to US$1,200,000 per patient.

S

peaking in the session entitled ‘Immunotherapy in 2018’, Sze tells the ECIO audience: “Even after we have talked about this for 45 years, there are still few approved gene

therapies for human disease.” The first gene therapy to be approved was in 2003, when the drug Gendicine was granted clearance in 2003 to treat head and neck squamous cell carcinoma

(HNSCC). Since then, only a handful of gene therapies have been approved; most recently, in 2017, the US Food and Drug Administration (FDA) granted marketing authorisation to two CAR

(chimeric antigen receptor)-T cell wtherapies: Kymriah (Tisagenlecleucel, Novartis) for B-cell acute lymphoblastic leukaemia and Yescarta (axicabtagene ciloleucel, Kite) for diffuse large cell lymphoma.

“Even though interventional radiology is expensive, gene therapy is even more expensive”, Sze explains.

“For instance”, he continues, “those CAR-T cells that were approved

Sept

Issue

18 71

last year, Yescarta and Kymriah, cost US$500,000 per patient.

Strimvelis [another gene therapy; GlaxoSmithKline] is US$800,000, and Glybera [uniQure] costs US$1.2 million per patient to be treated. In fact, Glybera is going off the market right now, because in the six years since it has been approved, it has only been used to treat one patient, because only one patient could afford the cost.

“So we have to decide, as a field and as a society, where to spend the money.

There is the cost of manufacture of these genetic therapies, as well as the cost of administration.”

If, instead of pumping money into the manufacture, Sze argues, the financiers spend slightly more money on the treatment’s administration, then the overall cost of future gene therapy could be significantly reduced.

Currently, gene therapy is so expensive in part because scientists need to grow billions or even trillions of vectors to transfect the host cells and express the desired protein product. Transfection can occur either in vivo, where the patient is injected with the viral vector, or ex vivo, where host cells are removed, the viral vector is added, and the transgenic host cells are reintroduced to the patient’s body. Either method requires multitudinous vectors, which all need to maintain the ability to transfect cells, and if transfection occurs ex vivo, sterile, viable human cells need to be grown on a large scale.

“I propose we could spend a little bit more money on the administration. We could perhaps have the manufacturers manufacture a little bit less vector, and we inject it directly into the organ of interest. Likewise, we could have them grow a few fewer cells, and we could inject them into the region of interest,” Sze suggests.

Vector efficiency: “Let the experts have a crack at it”

“Delivery (in vivo); let the experts have a crack at it” read a slide behind Sze as he advises utilising the skills of interventional oncologists in improving

Immuno-oncology

Add LABS to your transjugular skill set.

The set includes a full complement of components for transjugular liver access and tissue biopsy.

Daniel Sze

engineering optimal vectors, the cancer biologists should focus on choosing optimal genes, but the interventional radiologists should work on the optimal delivery.”

Sze and colleagues have looked at some standard interventional radiology practices, and found that many are readily adaptable to gene therapies, and there are even some specificities for tumour cells over normal cells.

For instance, Sze used a wedged retrograde hepatic venous delivery in pigs and baboons of a non-viral vector encoding human factor IX, resulting in expression of the human gene, though the expression was not durable.

Writing recently in CardioVascular and Interventional Radiology, Oliver Pellerin and colleagues (Hôpital Européen Georges-Pompidou, Paris, France) provide an example of interventional oncologic methods applied to a gene therapy treatment.

They report the successful intra-arterial injection of a rabbit VX2 hepatic tumour with engineered mesenchymal stem cells. These cells are transgenic, possessing a gene that metabolises the prodrug cyclophosphamide 13 times better than the wild type. Following injection with the engineered cells, the investigators administered intravenous cyclophosphamide. While cyclophosphamide alone did suppress

Virologists should work on engineering optimal vectors, cancer biologists should focus on choosing optimal genes, but interventional radiologists should work on optimal delivery vector efficiency. A literature review in Anticancer Research cites a variety of possible routes for the administration of viral vectors: intravenous, intraarterial, intra-tumoural, intra-portal, intra-biliary, intra-splenic. Listing these, Sze says, “Of course, this is focusing on the liver, since the liver is the factory of the body. Of all of these, anyone can do intravenous, but these other types of administration are all in the purview of interventional radiology. So the virologists should work on choosing and

tumour growth, the addition of the genetically engineered mesenchymal stem cells helped to metabolise the drug and enhanced efficacy.

Sze concludes: “After nearly 50 years of study, only a few gene therapies are approved for human use, in part because multigenic diseases such as cancer are very challenging. Interventional oncologic methods, however, may improve efficacy and reduce toxicity, as well as reduce costs, due to locoregional delivery of reduced doses.”

View the LABS illustrated guide and animation at cookmedical.eu/LABS

LABS LIVER ACCESS AND BIOPSY SET

MEDICAL

cookmedical.com © COOK 05/2017

IR-D35279-EN-F

23

24

Sept

Liquid biopsy is an adjunct, but not an alternative, to needle biopsy Liquid biopsy does not replace percutaneous biopsy, particularly in the diagnostic setting, a session at the World Congress of Interventional Oncology (WCIO; 7–10 June, Boston, USA) has noted. However, liquid biopsy can be a useful adjunctive therapy to track clonal evolution and guide treatment, concluded Ryan Corcoran, Massachusetts General Hospital in Boston, US, during his presentation “Liquid biopsies: Are percutaneous biopsies becoming obsolete?”

H

Issue

18 71

Biopsy

e said: “There are still a number of reasons right now that percutaneous tumour biopsy is critical, and one of those is really for that initial diagnosis. To answer questions such as: ‘is this cancer?’ and ‘if so, what type of cancer, or what subtype of cancer?’ comes down to being able to look at the tissue under the microscope. And that is something that liquid biopsy, at least right now, cannot do.

For the foreseeable future, the percutaneous biopsy business is here to stay.”

However, he described the potential of liquid biopsy as a noninvasive alternative as “very attractive”, and said it was emerging as “a very important complementary technology” to identify multiple resistant clones that may be present.

He outlined the concept of tumour heterogeneity and explained why liquid biopsies may offer an advantage: “There can be multiple resistant clones that occupy spatially distinct positions in this cancer, and if you perform just a single lesion tumour biopsy, you may get a limited view of what is

going on in the tumour to drive resistance. If you target what you find in this tumour, you may effectively take out that clone, but it may be inadequate to deal with the totality of the patient’s disease.”

Heterogeneity can be interlesional, where distinct metastatic lesions may have evolved independent resistance mechanisms, or intralesional, in which distinct tumour cell clones residing in the same lesion may harbour discrete resistance mechanisms. A biopsy needle inserted into a single region of one of many metastases may “vastly underestimate the degree of tumour heterogeneity, and the potentially actionable or problematic alterations that may exist”, Corcoran warned.

Liquid biopsy is defined as the detection and analysis of tumour-derived material in a bodily fluid. This typically refers to peripheral blood, although urine and cerebrospinal fluid (CSF) may also be used. Tumour-derived material can be viable circulating tumour cells or exosomes. But most commonly, investigators look for cell-free DNA, fragments

shed by dying tumour cells. These are easy to isolate and analyse, and testing for them has grown rapidly over the last few years.

Corcoran told delegates that physicians were starting to use liquid biopsy to rapidly adapt therapy “both by following the overall tumour burden using our clonal alterations and also by adapting therapies to target specific cell clonal populations that emerge with different therapies. As much as possible, we are trying to find therapies that can intercept a convergent point upon which several resistance mechanisms rely.”

He also pointed out that systemic therapy may not be the only option for targeting resistant clones. “We have started to work very closely with our radiation oncology colleagues and our interventional oncology colleagues to look at the role of localised therapy for problematic and progressing clones, particularly in the setting of oligometastatic progression.”

This local therapy, he suggested, could prolong the benefit of systemic therapy.

Summing up, he said: “Tumour biopsies provide critical information for diagnosis and analysis of protein, RNA, and immune markers which are currently not possible to do with liquid biopsy, and this is one of the reasons I think percutaneous biopsies remains critical. Single-lesion biopsies in the setting of resistance may not capture the heterogeneity that is present, missing alterations that might drive treatment failure.

Molecular profiling through circulating tumour DNA can be used to guide decisions, particularly when inadequate tissue is available. Liquid biopsy can effectively identify multiple heterogeneous resistance alterations and it can help drive treatment decisions.”

Biopsy sits front and centre of the interventional oncology armamentarium The opening plenary at the World Conference on Interventional Oncology (WCIO) put biopsy, which is considered a mundane procedure by some interventional radiologists, at the heart of cancer diagnosis and personalised treatment. Many experts see that doing a biopsy well could establish a fruitful collaboration with referring medical and surgical oncologists.

T

he session “Obtaining Tissue in the Age of Precision Medicine” highlighted biopsy as one of “the main inroads” for interventional radiologists to get into the oncology space.

Biopsy is seen as a gateway procedure by interventional oncologists. Once interventional oncologists get in the door and do a good job with biopsy, they can then offer other treatments to help manage the disease that was biopsied, delegates heard.

David C Madoff, professor of Radiology, vice chair for Academic Affairs, Weill Cornell Medicine, New York, USA, and programme chair of WCIO 2018, told Interventional News: “One of the most common image-guided procedures done by interventional radiologists is biopsy. Biopsy is seen as a bread-and-butter procedure that is considered by many practitioners as a routine one. Still, it may ultimately have the most impact on anything that we do in interventional oncology. One of the reasons that it is so important is that patients’ treatments are now reliant on the tissue obtained and its typing. It used to be that obtaining tissue was simply for diagnosis, and once a diagnosis was established, patients with a particular cancer would all be treated the same way in a one-sizefits-all manner. However, we know now that tumour tissue is very heterogeneous.

This can be within a tumour and there could also be heterogeneity between the primary tumour and metastases. So over the years, interventional radiologists are

asked to get much larger volume samples and many more samples in order to guide personalised treatment. With biopsy, interventional oncologists play a critical role in the diagnosis and management of patients with cancer.”

Speaking at the session, Stephen Solomon, chief, Interventional Radiology Service, Memorial Sloan Kettering Cancer Center, New York, USA and president of the Society of Interventional Oncology, noted that in the era of precision medicine, it is essential to provide reliable tissue biopsy. He noted “in-room pathology assessment will lead to improved results. Molecular imaging can provide improved targeting as it recognises tissue heterogeneity. New technology solutions can provide in-room assessment for all hospitals,” he said.

Interventional radiologists are held responsible for the collection of the biopsy sample and it is important to set appropriate expectations on the challenging biopsy, delegates at the session heard.

Alda Tam, associate professor of Interventional Radiology, MD Anderson Cancer Center, Houston, USA, speaking of the role of biopsy in oncology clinical trials said: “[Essentially] what we are looking for is an actionable mutation or an actionable immune biomarker so that a patient’s treatment for cancer can be individualised. In order to do that, biopsy plays a critical role. In addition to this, we are being held to a molecular adequacy

standard and what that means could be different for different trials.

“I think as interventional radiologists/ oncologists, we need to embrace the need for interventional radiology involvement in clinical trials at the level of which trials are being developed. So you need to write the protocol and review the protocol on how you sample the tissue. At MD Anderson, protocols do not go before the Institutional Review Board unless an interventional radiology collaborator has already signed on. We need communication tools amongst ourselves to ensure that we are in compliance about the number of samples that are being requested for each protocol.

Hopefully, at some level, we can move towards a standardisation of the sampling

David Madoff

requirements, beyond just the number of cores,” she noted.

Importantly, Tam noted that it was important to weigh the risks and benefits carefully before undertaking challenging biopsies.

“Be a clinician, weigh-in on the risk of the biopsy and lesion selection,” said Tam. “At the end of the day, you want that patient to go to the trial, but if they cannot, they cannot. We ought to be realistic as we are the only ones looking at the imaging and we are the only ones who know how much tissue is going to come out of the lesion being studied. Lastly, collaborate with pathology, because feedback is essential in order to improve quality and improve results,” Tam urged.

Alda Tam

AA6728

Go with Resin.

Make a difference

DISTRIBUTION 3 Natural flow-directed distribution for tumour coverage 3 Overlapping radiation clouds versus swiss cheese effect1 3 Glucose 5% provides increased patient comfort and a shorter administration time2

FLEXIBILITY AND CONTROL 3 One vial for all treatment strategies 3 Visualisation of the entire delivery process 3 Timing for preparation and application adaptable to needs

EVIDENCE AND EXPERTISE 3 The only SIRT with multiple RCTs3–6 3 Continuous training, support & advice 3 Over 86,000 doses sold in more than 40 countries and 1,160 centres

SIR-Spheres® is a registered trademark of Sirtex SIR-Spheres Pty Ltd

References: 1.

2.

3.

4.

5.

6.

Burrill et al., J Nucl Med Radiat Ther 2011, 2:1.

Ahmadzadehfar, H. et al. EJNMMI Research (2015) 5: 54.

Hendlisz A et al. J Clin Oncol 2010; 28: 3687–3694. van Hazel GA et al. J Clin Oncol 2016; 34: 1723–1731.

Wasan H et al. Lancet Oncol 2017; 18: 1159–1171.

Vilgrain V et al. Lancet Oncol 2017; 18: 1624–1636.

AA6728-Inteven-News-MAD-Ad-aw.indd 1

Sirtex Medical United Kingdom Ltd Building 3, Chiswick Park, 566 Chiswick High Road, London W4 5YA, United Kingdom www.sirtex.com

14/05/2018 11:11

26

Sept

Issue

18 71

Ablation

Top trends in ablation in 2018 ROBERTO IEZZI COMMENT & ANALYSIS Roberto Iezzi, Rome, Italy, provides an overview of what interventional radiologists can expect from ablation procedures in the near future.

I

n recent years, local ablative therapies have increased in clinical practice, playing an important role as a curative option in the treatment of localised primary and secondary cancers, and also as an alternative when palliation is desired, local control is needed, or surgical resection is not feasible, principally due to the longer survival of patients with metastatic disease.

In the above clinical scenario, thermal ablation technology has evolved rapidly with substantial technical and procedural improvements that can expand clinical indications, improve clinical outcomes and better safety profiles.

Future perspectives of ablation are based on the attempt to overcome ablation intrinsic limitations, mainly represented by the higher rate of local tumour progression (LTP) compared to surgical resection that can occur due to an incomplete ablation at the periphery of the tumour, and the absence of an ideal tool to precisely guide and monitor the ablative procedures. In detail, the creation of a larger ablation volume in a reasonable time frame without technical complexity is necessary to achieve a complete ablation, significantly reducing the rate of local tumour progression. This aim can be obtained using multiple electrodes to switch from monopolar to bipolar/multipolar modes, or by using different energy sources, including microwave, laser, high intensity-focused ultrasound (HIFU) and cryoablation. However, in the last few years the concept of combined treatment has strongly emerged (multimodality), such as in combined ablation and chemoembolization, and also to intermodality, a combination of ablative procedures, percutaneously or intra-arterially driven, with three-dimensional conformal radiotherapy (3DCRT). In detail, the development of three-dimensional conformal radiotherapy (3DCRT) has enabled high dose radiation to be directed to a tumour with a frank sparing of the nontumour surrounding liver parenchyma without restriction due to tumour topography and size,

presence of peri-tumourous satellite nodules, or associated segmental portal vein thrombosis.

Furthermore, the recent development of molecular-targeted agents in the treatment for hepatocellular carcinoma (HCC) has also prompted synergies between locoregional tumour ablation and systemic chemotherapy.

Other emerging technologies are represented by imaging-guiding modalities and assistive techniques for percutaneous treatment. In particular, recent technical advances of imaging fusion have enabled the overlay or side-by-side display of real-time ultrasound images combined with the established fusion of CT/MRI-acquired images, but also PET (Positron Emission Tomography) during an interventional procedure. Like fusion imaging, contrast-enhanced ultrasound increases radiofrequency ablation performance in terms of localisation and targeting of a tumour. Applying these techniques to tumour ablation enhances the identification of target lesions and the feasibility of the intervention.

Finally, there is a growing interest in combining immunotherapy with ablative strategies, but little data are available to guide if and how these modalities should be combined.

What is clear is that thermal ablation cannot be considered solely as a locoregional therapy.

The resultant inflammatory response, though at present limited and unpredictable, paves the way for an expanded role of thermal ablation as a stimulant to the immune system. Ablation, however, is a two-edged sword, and causes of and solutions to its oncogenic effects need to be investigated. What we strongly need is to optimise the timing of immunotherapy and thermal ablation; that is crucial for the creation of a curative therapy. Recent studies seem to demonstrate that a primed ablation protocol can enhance treatment response with a high tumour burden.

Also, as a result of mechanical and immunologic changes in the tumour microenvironment following local ablation, it seems to be a window of opportunity for employing immunotherapy, after which the ablation may actually limit the efficacy of immunotherapy. Sequential immunotherapeutic strategies after ablative therapies seem also to show a great potential for the prevention of post-ablation tumour recurrence and for generating durable and powerful antitumour immunity to achieve optimal tumour control. The prospect of manipulating the immune system toward the rejection of established cancers as part of the standard of care for patients is becoming closer to reality, even if more data are still needed to further verify its efficacy.

All these technical and procedural aspects will be discussed in the fourth edition of MIOLive 2019 (Mediterranean Interventional Oncology; 28â&#x20AC;&#x201C;29 January 2019, Rome, Italy). The meeting will be a forum for discussion for all those who are interested in interventional oncology, as well as locoregional treatments. It will be a practical interactive meeting based on live cases integrated by short presentations and lectures where professionals from various Mediterranean countries can share opinions, experiences, research projects and knowledge, under the guidance of several international experts. It is the best place for obtaining networking opportunities, listening to experts, and learning and sharing best practices.

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

AHEAD w i t h

C M O S

the comprehensive mobile hybrid solution 1

The Ziehm Vision RFD Hybrid Edition now comes with the latest CMOS technology. Requiring zero modifications to existing ORs, this mobile hybrid solution is ready to go â&#x20AC;&#x201C; anytime, anywhere.

Ziehm Vision RFD Hybrid Edition > Extend your cardiovascular surgical

Visit us at CIRSE or at www.ziehm.com/RFDHE

capabilities with a powerful 25 kW mobile C-arm > Take your OR to the next level with a mobile hybrid solution > Plug in and start your hybrid procedure with zero room preparation > Reduce exposure significantly with the next-generation SmartDose

MOSline represents a system configuration that is based on a Ziehm Imaging CMOS flat- C panel detector. 1 Ziehm Vision RFD Hybrid Edition represents a group of optional hardware and software that creates an option package on the device named Ziehm Vision RFD.

Zie-2155-Anzeige-CIRSE_225x153_RZ.indd 1

19.07.18 09:42

June

Issue

18 70

Ablation

27

CT-guided RFA a safe alternative to surgery Percutaneous CT-guided radiofrequency thermal ablation (RFA) is a safe and effective alternative treatment option in patients with pulmonary metastases from hepatocellular carcinoma (HCC) who cannot be considered candidates for surgery. This is the result of a retrospective study by Italian investigators, presented at the European Conference on Interventional Oncology (ECIO; 22–25 April, Vienna, Austria) by Giulia Lassandro (University Federico II, Department of Advanced Biomedical Sciences, Naples, Italy). could be treated with minimally invasive therapies like radiofrequency ablation, microwave and cryoablation, that preserve an effective lung parenchyma and have already been used in the treatment of lung lesions.

“In our experience, radiofrequency thermal ablation improves survival and quality of life in selected patients when used in addition to medical therapy.”

Fielding questions from the audience,

T

Giulia Lassandro

he investigators performed a retrospective evaluation of overall survival, local tumour progression, complication rates and early outcomes of percutaneous CT-guided ablation of pulmonary metastases from HCC. HCC is the most common primary tumour in the liver, representing about 90% of primary liver malignancy, and is the third leading cause of cancer-related mortality worldwide.

The most common site for HCC metastases is the lungs. In fact, Lassandro informed the ECIO audience that pulmonary metastases occur in 55% of cases via haematogenous dissemination to the pulmonary capillary network.

From February 2012 to September 2017, a total of 23 patients underwent CT-guided radiofrequency thermal ablation treatment as a first line therapy. There were 13 males and 10 females, with a mean age of 62 years.

There was a total of 38 lung lesions, treated in 36 CT-guided ablation sessions (two patients had two metastases treated during the same procedure).

Of the 23 patients treated in this study, overall survival observed at one year was 87%, 67% at three years, and 44% at five years. If HCC is untreated, the average survival rate is less than six months. The investigators also report a low complication rate for radiofrequency thermal ablation.

The most frequent complication observed in their patient cohort was subtle pneumothorax, which occurred in six of the 38 lung lesions (16%). Just one patient experienced a pneumothorax requiring pleural drainage tube insertion. The most dangerous complication observed was a relapse on a treated lesion, which occurred in one patient who died of extensive HCC occurrence in the liver.

Lassandro comments, “In general, patients with pulmonary metastases may benefit from surgical therapy, but current usual practice for metastasectomy is limited to a specific subset of patients, meaning that the vast majority of them are not suitable for resection. As an alternative, these patients

Lassandro was asked how she was able to convince the oncologists in her hospital to allow her to perform ablation in metastatic HCC patients. Lassandro answered: “I am very lucky, because at my centre we have a tumour board, including oncologists, pneumologists, gastroenterologists, diagnostic radiologists, interventional radiologists, and also a surgeon. Generally, we treat these type of patients—selected ones with no sign

of hepatic disease—with radiofrequency ablation. But it is not a rule for us, because generally oncologists want to treat them [metastatic HCC patients] with Sorafenib.

But we do not stop Sorafenib during the RFA treatment, so generally we accord with our oncologists to do this type of treatment in patients with continuous medical therapy.

So, we agree with each other on this type of treatment on our tumour board.”

28

Sept

Issue

18 71

Vascular access

Minimising arteriovenous graft infections and preserving vascular access using partial graft excisions The findings of a new retrospective review carried out by Suh Min Kim (Dongguk University Ilsan Hospital, Goyang, Korea) and colleagues that aimed to establish an appropriate treatment strategy for arteriovenous graft (AVG) infection have been published in the Journal of Vascular Access. The findings indicate that partial graft extension could be a treatment option to achieve both eradication of AVG infection and preservation of vascular access in selected patients.

T

he authors acknowledge that infection is a common complication in an arteriovenous graft (AVG); the reported infection rate being fivefold higher compared to an autogenous arteriovenous fistula. Prosthetic graft infections can lead to prolonged use of a catheter, a long duration of hospitalisation and life-threatening sepsis.

Both eradication of infection and vascular access salvage are important considerations—making treatment of AVG infection particularly challenging for vascular surgeons.

With regards to treatment, the authors write: “It is imperative to aim for balance between infection control and vascular access preservation, because of the limited anatomic options for vascular access creation.”

Traditionally, total graft excision (TGE) and the insertion of a central venous catheter are recommended until the infection is controlled. The authors report that previous studies suggest the use of a remnant cuff as a preferred method to reduce the morbidities of excision without an increased risk of recurrent infection. In addition to this, partial graft excision (PGE) with an interposition graft has been tried in order to preserve vascular access salvage in selected patients.

However, the Kim et al note the lack of data in relation to the clinical presentation and treatment outcomes in patients with an infected AVG. Furthermore, the extent of surgical excision to be performed for AVG

infection remains debatable.

Therefore, the authors aimed to report their experience regarding surgical treatment of an infection AVG for haemodialysis, to compare the results of PGE and TGE, and to establish an appropriate treatment strategy for both infection control and vascular access preservation.

Kim et al carried out a retrospective review, in which a total of 50 cases of AVG infection were treated between January 2005 and June 2016. The median age was 66.5 (range 29–84) years, with 33 men and 17 women. Thirty-seven (74%) had hypertension and 23 (46%) had diabetes mellitus. The median duration for which patients had been receiving haemodialysis was 37.5 months (range 2–432).

Reviewing medical records, the authors collected data pertaining to demographics, antibiotics, pathogens, types of AVG, the interval between AVG creation, or any intervention and surgical excision and complications.

The surgical methods used in the study were total graft excision (TGE; n=34), or partial graft excision (PGE) with an interposition graft (n=16). The choice of surgical methods was determined by three factors: the presence of fever (an indication for TGE), recent history of surgical manipulation mandating complete removal, and intraoperative findings. The latter was noted as a particularly important consideration, as infected prosthetic grafts

do not get encased in scar tissue—but this can be easily determined by experienced vascular surgeons.

The results of the study regarding clinical manifestations include that infection was noted at a puncture site in 22 cases, at a prior incision for surgery or endovascular therapy in 20, and abandoned (currently unused) grafts in five cases.

Additionally, infection occurred within one month after an AVG creation in only one case, while infection followed within one month of any intervention in 14 cases, and occurred more than one month after AVG creation or intervention in 35 cases. Simultaneous remote infection was identified in seven patients, two of whom underwent an operation for infective endocarditis and spondylitis.

In relation to the surgical outcomes of PGE, five patients (31.2%) having recurrent infection were treated with further graft excision; however, no patient showed lifethreatening complications.

After TGE, a central venous catheter (CVC) was inserted and used for a median period of 90 days. Among the 34 patients who underwent TGE, new vascular access was created in 18 patients at a median period of two months later, and 12 patients continued to use a CVC until last follow-up or death.

Taking into account the results of the study, the authors note some important clinical implications. As seven patients had simultaneous remote infection and two required major surgery due to it, this type of infection must be suspected if or when the patient develops sustained fever or bacteremia after graft extension.

Additionally, in 10% of the patients, infection involved an abandoned graft. As infection can occur at the site of abandoned vascular access, careful evaluation should

take place if the patient is being assessed for fever, the authors recommend.

The final clinical implication the authors point to is regarding the use of an endovascular approach in management of an infected graft. According to the authors, this approach could potentially cause septic emboli along with serious complications; meaning the possibility of infection should be evaluated when an endovascular procedure is planned for a thrombosed graft of pseudoaneurysm.

In relation to the limitations present in the study, the authors comment that they only analysed the outcomes in surgically treated patients, whereas information on the medically treated cases were not included.

An interposition graft was placed after PGE using only a polytetrafluoroethylene (PTFE) graft. However, the authors comment that it would be useful to study and compare the benefits of other types of grafts, such as cryopreserved veins. Furthermore, due to the small sample size, the authors could not compare results based on microbiological studies, such as Gram-negative species.

Irrespective of the current limitations, the authors conclude that PGE should be considered in selected patients in order to achieve both infection eradication and vascular access preservation. The presence of fever and a recent history of surgical intervention would commission the use of a TGE, while intraoperative findings of a well-incorporated graft would be an indication for PGE. Yet, the authors reiterate that due to a higher risk of recurrent infection after PGE, appropriate patient selection and sufficient surgical removal (until the surgeon encounters sterile segments) are essential factors for success.

Lastly, an extended courses of antibiotics and careful wound care is warranted for effective postoperative management.

Arteriovenous thigh graft access could be an option for haemodialysis patients A study published recently in the Journal of Vascular Access has indicated that the use of arteriovenous thigh graft access is viable as an alternative for patients who have exhausted all other access options.

D

enise Kim (Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada) and colleagues, including Charmaine Lok (pictured), performed a retrospective study of all thigh arteriovenous access grafts placed between 1995 and 2015. The clinical, demographic patient information and patency of each thigh graft was determined from the time of surgical creation placement until abandonment, transfer to other modality, or centre or end of study, and the reason for access failure documented.

The authors found that, in total, 44 patients received 49 thigh arteriovenous accesses. The average age was 60 years (13–79 years); half (53%) of the patients (n=24) were female and 61% of the patients (n=30) of arteriovenous accesses were left-sided. The cumulative proportion surviving (primary patency rates) at 12, 24, and 28 months were 43% (standard error=9%), 33% (standard error=9%), and 13% (standard error=9%), respectively.

The cumulative proportion of surviving grafts at 12, 24, and 48 months were 61% (standard error=8%), 58% (standard error=9%), and 31% (standard error=13%), respectively.

In total, 37 revisions were performed in 22 patients to maintain patency or eradicate infection. Infection occurred in 20 patients (39%) of thigh grafts requiring 16 patients (80% of those affected) to be removed; 14 patients had grafts (33.3%) that served as the lone haemodialysis arteriovenous access during the patients’ lifetime on dialysis.

Kim et al conclude that while arteriovenous thigh graft access is used infrequently, their study shows that they have an acceptable patency. They noted that some accesses require revisions and that they observed a high infection rate in their cohort of patients with arteriovenous thigh graft access. “Despite this, an acceptable proportion of leg grafts provide durable access for the dialysis lifetime of the patient,” Kim et al maintain.

Charmaine Lok

Proven Performance Through Innovative Design* The unique covered stent platform of the COVERA™ Vascular Covered Stent was designed to balance the flexibility and strength required for the tortuous venous outflow anatomy of the venous anastomosis.

In the AVeVA Clinical Study through 6 months, the COVERA™ Vascular Covered Stent demonstrated:

71% Target Lesion Primary Patency*

147

Days Between Interventions*to Maintain TLPP

*The AVeVA Clinical Study was a prospective, non-randomized, single arm multi-center study of the COVERA™ Vascular Covered Stent used to treat stenoses at the anastomosis of an arteriovenous graft and outflow vein. 110 patients were treated with the COVERA™ Vascular Covered Stent at 14 investigational sites in the US. Target Lesion Primary Patency (TLPP) of 71%, defined as the interval following the index intervention until the next clinically-driven reintervention at or adjacent to the original treatment site or until the extremity was abandoned for permanent access. AVeVA Clinical Study. Data on File.

Bard Peripheral Vascular Inc., Tempe AZ. Complications and Adverse Events associated with the use of the COVERA™ Vascular Covered Stent may include the usual complications associated with endovascular stent and covered stent placement and dialysis shunt revisions.

Please consult product labels and package inserts for indications, contraindications, hazards, warnings, cautions, and information for use. © 2018 BD. BD, the BD logo and all other trademarks are property of Becton, Dickinson and Company. Illustrations by Mike Austin. All Rights Reserved. BPV/SGF2/0618/0124

30

Sept

Issue

18 71

Interview

Profile

Jean Palussière

Following a one-year sabbatical in the equatorial forests of North Congo at the end of his residency, Jean Palussière returned to his University city of Bordeaux to work as a vascular radiologist. A pioneer in his field, Palussiére later worked in France’s first dedicated interventional radiology (IR) department, before launching his own interventional radiology unit at Institut Bergonié (Bordeaux, France), overseeing the installation of the first angiosuite in 1999. Here, he talks of the particular ambiance of performing emergency embolizations in the dead of night, the barriers to making radiofrequency ablation of the lungs common practice, and the importance of interdisciplinary integration in the running of a successful IR unit.

What made you choose IR?

Firstly, I like being in close contact with patients throughout their treatment, care and follow-up. I started IR with vascular procedures on dialysis access and peripheral arterial stenoses in the vascular radiology department, lead by professor Grenier. In dialysis access, there was no competition with surgeons, and there was good collaboration with nephrologists. It was remarkable then to propose using minimally invasive approaches, and to employ them to extend the lifetime of a dialysis access; at the time I understood how patients were dependant on percutaneous techniques. I also appreciated the innovative side of this field, with its many new technical solutions.

Later, in the oncologic field, I was enthused by the ability to treat patients at different stages of the disease, from intent to cure to palliation. Again, the collaboration with oncologists and other specialists through daily exchanges and tumour boards is a source of constant motivation. There is a great deal of trust and mutual respect between us that is beneficial for patients, and encourages us to go further in our therapeutic proposals.

What have you learned from your time in the intensive care unit before you embarked on a career in IR?

It was one of my first internships, and I had to be autonomous quickly. There were a lot technical skills to perform, such as intubation, deep venous access, drainages, right cardiac catheterism for pulmonary embolism, and bronchial fibroscopy. During the six month internship, I got the opportunity to learn all of them, and I realised that I really appreciated these kind of procedures without being completely aware of their future impact. When I chose radiology, I did not imagine how useful this learning would turn out to be.

Could you describe the energy and atmosphere of the first dedicated IR unit in France in Villejuif? How did this motivate and inspire you?

I spent six months in this service 20 years ago; this unit was entirely dedicated to interventional radiology in oncology. I met Alain Roche, who was the boss at the time, and Thierry de Baere. The unit was very well organised and progressive in many ways: physicians came to submit clinical cases, indications and advice were collegiateally discussed, and the patient was at the centre of the organisation, with consultations, follow-ups, and of course interventions. The patients were visited by both the interventioanl radiologists and technologists (the technologists were at the border betwee technicians and care-givers). There were no nurses in the department.

The different procedures were written and well coded. The anesthetists were very well integrated, participating in the unit’s development. They were responsible for deep venous access, and used interventional radiology facilities for that.

Everything was organised in a thoughtful way to maximise the empowerment of all involved.

Back in Bordeaux, I launched the interventional radiology unit. I kept very good relations with the department; I work with Thierry de Baere and his team to this day. In particular, we have shared a common database on lung ablation for more than 10 years, which is an exemplary tool for demonstrating the technique’s power.

What advice would you give to someone young who wants to practice interventional radiology?

Not to be obsessed by technology, but to be interested in patients in order to give the right treatment. To be a good radiologist before being an ace at the mechanical aspects of the job. Mastery of the technique will come. To be close to your patients. To participate in tumour boards and to discuss with other specialists in order to become familiar with different aspects of disease (for example, biology and genomics).

What are the main advances in ablation for lung cancer?

Lung ablation has demonstrated efficacy, safety, low invasiveness, high repeatability, and very good tolerance and acceptance in primary lung cancer and metastases. In primary lung cancer, two prospective multicentre studies (one US and one French) have demonstrated the potential of the technique in patients unsuitable for surgery. In this indication, stereotactic body radiation therapy (SBRT) is now the main proposed technique, despite the fact that besides good results, thermal ablation interventions also offer advantages such as the ability to biopsy and treat the lesion during the same intervention.

For lung metastases, thermal ablation remains a standard of care, with many advantages to the procedure. A limited metastatic disease could potentially become a future metastatic disease spread, and an opportune use of local therapy might prevent or delay widespread metastatic dissemination. In a more advanced stage of the disease, thermal ablation may also be proposed, especially when the metastatic disease is controlled by a systemic treatment. In a colorectal metastatic disease, although continued targeted drug therapy is preferred to increase the survival, the concept of a therapeutic pause or maintenance therapy has been tried out to improve patient quality of life. In this context, to propose a local treatment to good responders could be an option to delay more toxic treatment, or in other words to increase the time without chemotherapy. In this way, percutaneous thermal ablation that is well tolerated and repeatable has offered new therapeutic plans. The number of metastases that can be treated in a single session has increased. In the early days of this treatment option, it was thought that a maximum of five metastases could be treated in the same session. Now, it has been demonstrated that both lungs can be treated in the same session under some circumstances, and that a patient treated with 20 metastases in different sessions has no loss of lung function.

This high degree of tolerance, repeatability and flexibility of the technique are invaluable assets for patients.

What are the barriers to lung ablation being widely undertaken?

Some barriers are the lack of randomised studies. Without randomised studies, it is difficult to know how a local treatment in a metastatic disease can influence the overall survival. But it is difficult to conduct and to achieve randomised controlled trials in metastatic patients due to the variety of presentations. However, oncologists have integrated local treatment when discussing metastatic patients in the tumour board. Randomised studies and health-economic studies are needed to confront and compare different techniques of local treatment: surgery and SBRT. Again,

these studies are both costly and difficult to carry out.

A multicentre, prospective database exploring clinical questions around thermal ablation could be a good way to better define the place of thermal ablation, and as a result to improve the therapeutic strategy. Scientific societies like CIRSE (The Cardiovascular and Interventional Radiological Society of Europe) play a great role in disseminating the technique. In some institutions, the lack of anaesthetists may also be a brake on development.

Another research interest of yours is breast tumour ablation—in what type of cancer patients, with what treatment goals, and with which modalities would you carry out this procedure?

We have been proposing thermal ablation for elderly patients who are not surgical candidates for the last ten years. I have to mention that oncologists and surgeons at our institute were positive and helped us to launch this project. At the

Sept

Issue

18 71

beginning we treated with radiofrequency ablation, and now with cryotherapy. Cryotherapy has the advantage of being painless, and is performed under local anaesthetic only. Both techniques are efficient, with almost no complications. We have not extended the indications to younger patients, except in very rare cases (the presence of another primary cancer), so surgery remains the main treatment. Nevertheless, in the future, new strategies combining thermal ablation and immunotherapy may enlarge indications. Before mastectomy, a preoperative cryoablation combined with single-dose ipilimumab demonstrates favourable intratumoural and systemic immunological effects.

What is the current status of cementoplasty?

Cementoplasties have been developing for the last 25 years; in oncology, the added value is high. Alone or in addition to radiotherapy and/or surgery, it is a wonderful technique, not only to relieve pain, but also for mechanical stability. Thanks to therapeutic improvements, many metastatic patients live longer, and it is remarkable that some with evolving bone mets are able to walk or stand up thanks to a cementoplasty.

The technique is easy to perform and safe in experienced hands; it is also possible to re-treat some patients. Fifteen years ago, we were able to launch a multidisciplinary meeting on vertebral metastases with Vincent Pointillart, a spine surgeon who works at the university hospital in Bordeaux.

This board still exists and we are lucky to have discussions every week with an open-minded surgeon. The board has pushed us to enlarge our indications. This is one of the reasons for the big development of cementoplasties in our centre; it is the most commonly performed technique (40% of our activity), before thermal ablation. In Bergonié, almost half of our patients are treated for breast cancer—oncologists are very keen on this therapy. Alongside osseous metastatic

Interview patients, some patients presented multiple benign fractures during the course of a cancer disease that can be secondary to systemic treatments (chemical castration in prostatic cancer). Our aim is to give the right diagnosis and to propose vertebroplasty. Nowadays, adding screws to cementoplasty enlarges our possibilities for improved patient comfort.

31

Fact File

You have an interest in research on high HIFU and MR thermometry. What is your main message on these in 2018?

High intensity focused ultrasound (HIFU) may be a wonderful tool in the future for us interventional radiologists.

Despite over two decades of research, clinical application remains scarce. For some teams using MRI as a tool for treatment guidance, thermometry is the best. It remains challenging to provide communication between MRI and HIFU; nevertheless, it ensures remarkable safety during treatment.

The lack of available MRI for interventions is not an asset for the technique. It is essential to follow the advances of some high tech facilities like that of Afshin Gangi’s department in Strasbourg (France) to develop an interventional MRI. In oncology, currently prostate cancer and bone metastases are the main indications. Some teams have interesting results on pancreatic cancer. Following our experiences with RFA and cryotherapy on breast tumours, we have started to treat some patients with HIFU before surgical resection.

Which early technologies are you keeping an eye on?

The links between IR and Immunotherapy are an important line of work for the next few years. It is important for the IR community to engage in this way. Systemic immuno-targeted therapies based on checkpoint inhibitors have proven effective in many cancers. Some preclinical and clinical studies have shown that localised tumour ablation by thermal techniques can induce systemic T-cell–mediated anti-tumour immunity. Cryotherapy seems to be advantageous. The combination of thermal ablation and immunotherapy could be a way to reset the equilibrium between the tumour and the host immune system. It remains complex, but this association really deserves further investigation.

Other immunotherapy approaches, such as cancer vaccines and cell-based therapies, are used systemically or with local application. Interventional radiologists who are experts in image guidance for target selection, biopsies and local treatment delivery have a great role to play in these new therapeutic modalities.

Could you describe a memorable case?

There are many memorable cases. Most of them are cases with favourable evolution. During the period where I was more involved in vascular interventions, I will always remember emergency embolizations performed for postpartum and post-traumatic acute bleeding. They were often done in the night, and had this particular ambiance. You have to work rapidly, the patient’s status may be unstable, the conditions were not always the best compared to daytime activity, but at the end you saw life-saving results.

In oncology, too, there are memorable cases: some patients were totally relieved after a cementoplasty, while just a few hours before they had been unable to stand up. More recently, some patients treated with lung radiofrequency ablation for 15 to 20 lung metastases were able to stop chemotherapy for long periods.

Beside these successes, some memorable cases are also those with unforeseen complications, like a patient who suffered a major subcutaneous emphysema for ten days following a lung radiofrequency ablation for a primary cancer.

In the end, evolution was favourable after a percutaneous embolization of the pleural fistula.

What are your interests outside of medicine?

I am married with three children, and trips abroad with my family are a source of happiness. I am also an avid outdoors man, and could only be induced to leave the interventional radiology field by a life in the mountains; ski touring is one of my main passions.

Education

1980–1986 MD University of Bordeaux, Bordeaux, France 1986–1989 Intern, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France 1989–1991 Military service, Centre Hospitalier Universitaire Brazzaville, Brazzaville, Republic of Congo 1988 University diploma of tropical medicine, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France 1991–1992 MD Centre Hospitalier Universitaire Bordeaux, Bordeaux, France 1993–1995 Assistant to professor Grenier, Interventional Radiology Unit, Centre Hospitalier Universitaire Bordeaux, Bordeaux, France 1995 Assistant to professor Roche, Interventional Radiology Unit, Institut Gustave-Roussy, Villejuif, France 1996–Present Interventional Radiologist, Department of Interventional and diagnostic radiology, Institut Bergonié, Centre régional de lutte contre le cancer [Regional Centre for the Fight Against Cancer], Bordeaux, France

Research positions

1997–2007 Member, Molecular and Functional Imaging research laboratory, topic: High-Intensity Focused Ultrasound (HIFU), led by Chrit Moonen, University of Bordeaux, Bordeaux, France Present Member, IMOTION (Imagerie Moléculaire et Thérapies Innovantes en Oncologie; Molecular Imaging and Innovative Therapies in Oncology) research laboratory, University of Bordeaux, Bordeaux, France

Committee positions

2011–Present Member, Steering committee, TRAIL (Translational Research and Advanced Imaging Laboratory) project, University of Bordeaux, Bordeaux, France

CE Marked in EU as Class III device Loadable with 4 chemotherapeutic drugs : Doxorubicin, Idarubicin, Epirubicin and Irinotecan

• • • •

Wide range of drug loading options3 Enhanced suspension characteristics1,2 Tight calibration1,2 Syringe presentation

INTENDED USE/INDICATIONS: LifePearl Microshperes are indicated for embolization of blood vessels supplying primary-hypervascular tumors or metastases in the liver.

Note: LifePearl® can be loaded with chemotherapeutic drugs. When used for drug loading, drug loading should be done under a physician’s direction, choice and responsibility, based on type and dose of drug most beneficial to the patient.

Lifepearl Microspheres are not available for sale in all countries. This information is provided only in respect to markets where this product is approved or cleared. The use of the LifePearl® device in combination with drugs is not cleared or approved in the U.S.A. by the Food and Drug Administration. Lifepearl Microspheres are not approved in Canada. Please contact your Terumo local sales representative for more information.

MICROVENTION is a registered trademark of MicroVention, Inc. Lifepearl Microspheres are a trademark of Terumo, Inc. Scientific and clinical data related to this document are on file at MicroVention, Inc. Refer to Instructions for Use for additional information. ©2018 MicroVention, Inc. MM683(i° EMEA) 1 2

IS510GB1217ITIX

3

De Baere et al J Vasc Interv Radiol 2016.

Perreira et al. Anti-Cancer Drugs 2016.

LifePearl Instructions for use - December 2017

www.terumo-europe.com

Manufacturer MicroVention Europe 30 bis, rue du Vieil Abreuvoir 78100 Saint-Germain-en-Laye France Tel: +33(0)1 39 21 77 46 Fax: +33(0)1 39 21 16 01

Distributed by: Terumo Europe N.V. Interleuvenlaan 40 3001 Louvain Belgique Tel: +32 16 38 12 11 Trademark ® Registered Published by Terumo Europe NV

Sept

Issue

18 71

Peripheral arterial disease

33

Bayer announces new licensed indication for use of Xarelto in patients with coronary or peripheral arterial disease Xarelto, co-administered with aspirin, is indicated in the EU for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral arterial disease (PAD) at high risk of ischaemic events.

T

he European Commission (EC) has approved a combination of Xarelto (rivaroxaban) 2.5mg twice daily plus low dose aspirin (acetylsalicylic acid/ASA) once daily for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral arterial disease (PAD) at high risk of ischaemic events.

The EU approval is based on data from the COMPASS study, the largest phase III study with rivaroxaban (27,395 patients), which showed that the rivaroxaban vascular dose, 2.5mg twice daily, plus ASA 100mg once daily reduced the risk of the composite of stroke, cardiovascular (CV) death and heart attack by 24% (relative risk reduction, ARR: 1.3%) compared with ASA 100mg once daily alone in patients with CAD and/or PAD. Derek Connolly, consultant interventional cardiologist at Birmingham City Hospital (Birmingham, UK) and COMPASS trial investigator, comments: “Cardiovascular diseases are one of the leading causes of death in the

UK, and coronary artery disease and peripheral artery disease represent a major public health burden—despite many advances in the area of cardiovascular care, CAD and PAD have remained an area of unmet need.

Even with currently available treatments for secondary prevention, patients remain at an unacceptably high risk of thrombotic events, which can lead to disability, loss of limb and death. This was the biggest study of rivaroxaban to date, and now that it is licensed for these conditions, it provides UK clinicians with a new option for treating CAD and PAD.” Lars Bruening, CEO Bayer UK & Ireland, says: “The story and momentum behind the COMPASS data continues to grow—from the study being stopped one year early for overwhelming efficacy, the presentation of the results themselves at the European Society of Cardiology congress last year, and now to this exciting news from the European Commission.

Ten years ago this October saw Bayer just starting

out on the Xarelto journey with the first indication in orthopaedics—and this year we welcome our eighth indication for the management of patients with CAD and PAD in the UK. It is especially exciting to see the continuing impact that Xarelto will have on patients with PAD, most of whom have concurrent CAD, as it has been many years since a new medical therapy has been proven in this high risk patient population.”

Following the licence approval across Europe, the new indication will be submitted to the National Institute for Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC) for review for routine reimbursement across the UK. Xarelto

Worth an arm and a leg: Revascularisation bests amputation on all fronts in critical limb ischaemia treatment Recent data, published in the Journal of the American Heart Association (JAHA), demonstrate the significant clinical and financial burden that critical limb ischaemia (CLI) poses to the US healthcare system. While primary treatment selection is still controversial, the study found that patients with more advanced peripheral artery disease had worse survival and generated higher healthcare costs when major amputation was performed as a first-line treatment. Revascularisation, both endovascular and surgical, in contrast, had improved long-term survival rates.

I

n a propensity score-matched analysis of 9,942 Medicare beneficiaries initially diagnosed with critical limb ischemia (CLI) in 2011, four-year survival rates were 38% with endovascular revascularisation as the first-line strategy, 40% with surgical revascularisation, and 23% with major amputation (P<0.001 for both versus amputation). The study investigators were able to stratify the clinical outcomes and costs on the basis of initial treatment strategy using procedural codes for each method.

Lead author Jihad Mustapha (Advanced Cardiac & Vascular Amputation Prevention Centers, Grand Rapids, USA) and colleagues found that subsequent major amputation rates over the follow-up period were 6.5% for endovascular revascularisation, 9.6% for surgical revascularisation, and 10.6% for primary major amputation (P<0.001 for all comparisons).

Additionally, total health costs per patient per year totalled US$49,200 for endovascular revascularisation, US$49,200 for surgical revascularisation, and US$55,700 for amputation.

The propensity-matched analysis of 9,942 individuals represented a subset of

the Medicare beneficiaries diagnosed with CLI in 2011. The study authors also looked at every individual Medicare beneficiary diagnosed with CLI in 2011, totalling 72,199 patients. For this unmatched analysis, the patient population demonstrated 46% survival over four years, and 87% freedom from major amputation.

The mortality rate was considerably higher in the matched patients versus the unmatched patient cohort. Notably, in the unmatched population, 25% of patients presented with gangrene. In the propensitymatched population, 66% had gangrene.

“Primary major amputation portends a poor prognosis even when adjusting for demographics, medical history, and disease severity. Compared with revascularisation, primary major amputation is associated with shorter survival time, increased risk of second major amputation, and higher healthcare costs. These results were generally consistent regardless of patient characteristics and clinical presentation,” the authors write.

“Survival following CLI diagnosis is lower than that of heart failure, stroke, and most cancers. Given that CLI is underdiagnosed, increasing in prevalence,

and responsible for significant risk to life and limb, considerable efforts are needed to raise disease awareness, refine diagnostic algorithms, and establish evidence-based treatment pathways,” they continue.

While according to Mustapha et al longterm survival and cost in CLI management is comparable between revascularisation techniques, it remains controversial which revascularisation method to opt for (open surgical or endovascular) when selecting an initial revascularisation strategy. In an analysis of 7,900 CLI patients from the Vascular Quality Initiative, three-year survival was lower with endovascular versus surgical revascularisation strategies (90% vs. 78%), whereas in the present study there was no significant difference of four-year survival. In the First-Line Treatments in Patients with Critical Limb Ischaemia (CRITISCH) registry of 1,200 patients, no difference in one-year mortality or major amputation between revascularisation methods was identified, in accordance with these most recent JAHA findings.

Additionally, the randomised BASIL (Bypass versus Angioplasty in Severe Ischaemia of the Leg) study also found no differences in long-term mortality or major amputation when comparing endovascular versus surgical revascularisation. The study authors look to the BEST Endovascular Versus Surgical Therapy for Patients with Critical Limb Ischaemia (BEST-CLI) trial in the hope of a more definitive answer to the revascularisation question. This is due for completion in 2019, and includes 2,100 participants.

There are a number of limitations to

the present study, however, which muddy the results. Most significantly, the authors note that there is a susceptibility to bias caused by the influence of confounding variables. Despite the use of propensityscore matching to adjust the selection bias among major treatments, the authors note that there is a possibility of unmeasured patient characteristics being different among treatment groups, which may have influenced outcomes. Additionally, the rationale for treatment decisions cannot be determined from this research. For example, although primary major amputation was performed in 6% of patients, whether amputation was performed because of standard institutional practice, extensive gangrene, inability to ambulate, or otherwise is unknown.

Writing in an accompanying JAHA editorial, Javier Valle and Stephen Waldo (both University of Colorado, Denver, USA) write: “The authors should be commended for bringing additional attention to CLI, and attempting to investigate its clinical outcomes and financial costs across treatment modalities. However, the findings underscore some of the significant challenges in studying this population.” Valle and Waldo cite the significant clinical overlap of different billing codes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]) as a source of difficulty when stratifying the data by treatment option using administrative data alone.

However, the editorialists note that the adoption of new billing codes (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM]) will improve the granularity of the data.

34

Sept

Issue

18 71

Medtech insights

BIBABriefings

Most operators can use their device of choice for peripheral interventions

D

ata from the 2017 Peripheral Usage and Attitudes Survey (BIBA MedTech Insights) indicate that 95% of operators performing peripheral interventions in Western Europe are able, at least in the majority of cases, to choose which device to use for peripheral intervention procedures (see Figure 1). This finding is despite 85% of those surveyed (149 overall) working in a public institution (71% in a public teaching/university hospital and 14% in a public community hospital), where cost is more likely to influence choice of treatment.

The survey also shows, over the next 12 months, that drug-coated balloons will increasingly be

used to treat lesions in the superficial femoral artery. During 2017, on average, survey respondents reported that they used drug-coated balloons to treat short lesions (<15cm) in just over a quarter (27%). However, when asked which devices they thought they would use over the next 12 months, the respondents predicted that drug-coated balloons would be used in 35% of short lesions (in the superficial femoral artery). This increase in use of drug-coated balloons correlates to a decrease in the use of percutaneous transluminal angioplasty—on average, 37% of such procedures in 2017 vs. 28% this year (predicted).

The move from percutaneous transluminal angioplasty to drug-coated balloon was seen in all types of superficial femoral artery lesions surveyed: long lesions (>15cm), in-stent restenosis, and chronic total occlusions.

In particular, according to the survey respondents, drug-coated balloons will be used more frequently for long lesions in 2018 than percutaneous transluminal angioplasty will be (see Figure 2). In 2017, respondents reported using percutaneous transluminal angioplasty in 26% of cases and drug-coated balloons in 21% of cases. But their predicted use of these devices for 2018 was 19% and 29%, respectively.

Boston Scientific corners lion’s share of radiofrequency ablation market in top five EU countries

T

he BIBA MedTech Insights Interventional Oncology Ablation Monitor shows that of 6,069 radiofrequency ablation procedures performed between 1 January and 31 March this year in Western Europe, 58% were with the LeVeen probe (Boston Scientific). The second most used probes were Cool-tip/Osteocool (Medtronic), which were used in 16% of procedures overall.

However, in the microwave ablation market, HS Hospital Service,

Healthronics, and Endocare—who jointly distribute the Amica probe (in different territories)—had the greatest market share. The probe was used in 46% of microwave ablation procedures performed (1,719 of 3,775 overall).

The Ice Probe (BTG/Galil Medical) is, by far, the most used cryoablation device in Western Europe; it was used in 72% of cryoablation ablation procedures (2,384 overall).

Polyphenol-coated angioplasty balloon to be developed

the Journal of Biomedical Materials Research, in which they state the drugs on the nanoparticle “showed excellent biocompatibility with limited cytotoxicity,” and the nanoparticle “released the two drugs only very slowly over 10 days”.

R

esearchers at Louisiana State University (Louisiana State University, Baton Rouge, USA) are developing a nanoparticle that contains the polyphenols resveratrol and quercetin—both of which are found in red wine—as an alternative drug-coated balloon for peripheral arterial disease.

According to a Louisiana State University press release, Tammy Dugas discovered that the two polyphenols, in combination, may work well as a treatment for peripheral arterial disease without causing some of the side-effects seen with current treatments. She then asked Cristina Sabliov (a biological and agricultural engineering professor at Louisiana State University) to develop a nanoparticle to contain the two drugs.

Once developed, the nanoparticle will be used to coat an angioplasty balloon—which would then be delivered into the peripheral arteries as a typical drug-coated balloon. The idea is for the novel balloon to provide the benefits of a stent (i.e. vessel healing) without the sideeffects. Sabliov comments: “There are places where the stent is not suitable. You cannot have a stent in the part of the leg that bends. You want the artery to stay open

BIBA Briefings

but without a stent, so what do you do? With these new drugs, the aim is to stop the artery cells from growing back and causing the artery to re-narrow.”

However, there have been some challenges, including ensuring that the drugs are combined in the optimal ratio, that the nanoparticle was “nano” enough, and that drugs have a positive charge. “We did not want the drugs to kill the cells. We just wanted them to prevent the cells from growing back,” Sabliov says.

Dugas and Sabliov have written about their work in

BIBA Briefings is a new platform that provides in-depth analysis of the latest market intelligence from BIBA MedTech Insights, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America.

The aim of each report is to give an overview of the key information affecting the medical device industry, enabling those working in the industry to keep abreast of the latest developments and make knowledgeable decisions.

For more information about BIBA Briefings or BIBA MedTech Insights, please contact: sales@bibamedical.com

AV1643

AV1643EN1.VTRTCX.AD.245x342.indd 1

03.08.17 15:17

36

Sept

New developments

Study shows novel sensor can accurately measure blood flow in real time

Issue

18 71

There exists an unmet need to answer the question of whether a particular intervention has re-established enough flow to the target tissues to address patients’ symptoms. A pilot study of 100 patients with peripheral arterial disease shows that a novel method of measuring blood flow can give accurate real-time intraprocedural as well as follow-up information on the status of limb blood flow, writes Mahmood Razavi, Orange County, USA.

MAHMOOD RAZAVI COMMENT & ANALYSIS

A

ccurate vascular evaluation of the lower limbs is essential in the proper management of patients with peripheral arterial disease.

Noninvasive diagnostic tools such as duplex ultrasound and ankle/toe brachial indices (ABI/TBI) are the current standard of care for screening and follow-up of patients. Prior studies, however, have shown that ABI is an unreliable measure for patients with critical limb ischaemia.

Furthermore, these measurements only provide information at a single point in time and are impractical for use in continuous monitoring. During a procedure, interventionists have no

adequate tool for real-time assessment of flow to a target area and vascular function outside of angiography. There exists an unmet need to answer the question of whether a particular intervention has re-established enough flow to the target tissues to address patients’ symptoms.

Laser Associated Sciences has developed the FlowMet-R, a non-invasive optical probe that acts as a continuous monitor of vascular status. The device can clip onto any of the digits (fingers or toes) and plot measurements of the flow rate of blood through the digit. The underlying technology of the FlowMet-R is based on dynamic light scattering, a technique

that uses coherent laser illumination and a sensor to observe interference changes caused by moving blood cells.

In a clinical pilot study, the FlowMet-R device was validated against existing standard of care metrics by calculating the correlation between sensor output and ABI, TBI, and Rutherford classification.

Patients were seen at an outpatient vascular laboratory, where the Rutherford-Becker classification was assessed based on clinical history and physical examination, as well as bilateral ABI/TBI measurements. Following noninvasive assessment, FlowMet-R probes were placed on the toe, and blood flow data was recorded for a few seconds. The blood flow value and waveforms were then analysed and correlated to patients’ clinical status and ABI/TBI. A predictive model based on paramteric regression was generated and statistical correlation and p-values were calculated between the model and ABI/ TBI. The study showed that all flow parameters had significant p-values when conducting a hypothesis with ABI and TBI. In classification of critical limb

ischaemia, the TBI showed superior performance over ABI, which agrees with prior literature, while the parametric flow model showed superior sensitivity and specificity to both TBI and ABI. Intraprocedural evaluation of FlowMet-R has also confirmed the results of the outpatient study indicated above.

Based on this early experience in 100 patients, it appears that FlowMet-R is an accurate means for outpatient diagnosis and follow-up of patients with peripheral arterial disease. It can also be a critical intraoperative or intraprocedural tool to guide physicians as to the adequacy of revascularisation procedures. The simplicity of FlowMet-R may also allow for effective home monitoring of patients with critical limb ischaemia by avoiding unnecessary doctor visits and catching early signs of recurrent vascular compromise.

Mahmood K Razavi is director, Department of Clinical Trials, St Joseph Heart & Vascular Center, Orange, USA. He is a consultant to Laser Associated Sciences.

NICE draft guideline casts shadow over EVAR for unruptured aneurysms The UK’s National Institute for Health and Care Excellence (NICE) has issued draft guidance on abdominal aortic aneurysm (AAA) diagnosis and management. The most notable recommendation within the guideline is related to repairing unruptured aneurysms, where the guideline states that patients should not be offered endovascular repair (EVAR) if open surgical repair is suitable.

T

his latest draft guideline issued in May is for consultation, and will update NICE technology appraisal guidance 167, published in February 2009.

According to NICE, the guideline aims to improve care by helping people who are at risk to get tested, specifying how often to monitor asymptomatic aneurysms, and identifying when aneurysm repair is needed and which procedure will work best.

On monitoring the risk of rupture, NICE recommends that patients with an asymptomatic AAA be offered surveillance with aortic ultrasound every three months if the AAA is 4.5–5.4cm or every two years if the AAA is 3–4.4cm.

When it comes to repairing unruptured aneurysms, the guideline suggests that physicians should consider aneurysm repair for people with an unruptured AAA if it is symptomatic, asymptomatic and 5.5cm or larger, or asymptomatic, larger than 4cm and has grown by more than 1cm in one year. But add that patients meeting these criteria should be offered surgical repair unless there are anaesthetic or medical contraindications.

As for EVAR for repairing unruptured aneurysms, the instructions in the draft guideline are clear: “Do not offer endovascular repair (EVAR) to people with an unruptured infrarenal AAA if open surgical repair is suitable. Do not offer EVAR to people with an unruptured infrarenal AAA if open surgical repair is unsuitable because of their anaesthetic and medical condition. Do not offer complex EVAR to people with an unruptured AAA if open surgical repair is

a suitable option, except as part of a randomised controlled trial comparing complex EVAR with open surgical repair.

Do not offer complex EVAR to an unruptured AAA if open surgical repair is unsuitable because of their anaesthetic and medical condition,” they state.

In an effort to explain how NICE comes to these recommendations, the rationale within the document indicates that there is “no evidence that EVAR for people with an unruptured infrarenal AAA provides long-term benefit compared with open surgical repair. While EVAR is associated with fewer perioperative deaths, it has more long-term complications, and these complications mean that people will need further procedures. There is some evidence that EVAR is associated with worse long-term survival than open surgical repair. EVAR also has higher net costs than open surgical repair. The evidence shows that, even if long-term benefits were achievable, they could not plausibly be sufficient to outweigh these costs. Open surgical repair is unsuitable for some people with an unruptured AAA because of their anaesthetic risk and/or medical comorbidities. For these people, the risks of their AAA rupturing, if no repair is attempted, have to be balanced against the perioperative risks and long-term complications associated with EVAR. The evidence shows that the average person receiving EVAR has an uncertain chance of a small net benefit, compared with the large and certain increase in costs. Therefore, the committee agreed that elective EVAR cannot be considered an effective use of NHS resources in this population.”

Endovascular aneurysm repair

The NICE committee found that the evidence for complex EVAR was limited in quantity and quality. However, they note that complex EVAR grafts are much more expensive than standard devices, so the difference in cost between EVAR and open surgical repair is even greater than in infrarenal AAAs. The committee also noted that the instructions for use of the grafts that are currently available do not cover complex AAAs. “Although there is currently no evidence that complex EVAR has better outcomes than open surgical repair, people with complex AAAs have higher perioperative mortality rates. Because of this, a perioperative survival benefit equivalent to that seen with EVAR for infrarenal AAAs could potentially be more influential in complex AAAs. Therefore, the committee agreed that more information would be helpful, so it recommended that the use of complex EVAR should be restricted to randomised trials.”

According to the guideline document, the committee also discussed complex EVAR for patients for whom open surgical repair is not a suitable option because of their anaesthetic risk and/or medical co-morbidities. They agreed that, in this population, people who need complex EVAR could not plausibly have better outcomes than those who need standard infrarenal EVAR. As they had not recommended standard EVAR in this population, the committee agreed that they could not recommend complex EVAR either.

Continued on page 38

38

Sept

Issue

18 71

Advances

Final STABLE I results highlight need for long-term management of type B aortic dissection Five-year follow-up data from STABLE I, a global feasibility study of the Zenith Dissection Endovascular stent (Cook Medical), were presented by Joseph Lombardi (Cooper University Health Care, Camden, USA) at the Society for Vascular Surgery’s Vascular Annual Meeting (VAM; 20–23 June, Boston, USA). In his presentation, Lombardi highlighted the need for “commitment to long-term management of type B aortic dissection” and the risk of aortic growth following thoracic aortic endovascular repair (TEVAR).

T

he study concludes follow-up for the feasibility study, which preceded the STABLE II study. At the 2016 VAM meeting, Lombardi reported initial outcomes of the second trial, saying “These preliminary results from the STABLE II study appear favourable in terms of clinical and anatomical outcomes for the treatment of acute chronic type B aortic dissection.”

STABLE I prospectively enrolled 86 patients at centres in the USA, Europe and Australia in the years 2007– 2012. Of those patients, 89% were followed out to five years with clinical an CT follow-up. The study included patients with type B aortic dissection who required surgical intervention or were not responding well to medical treatment within 90 days of symptom onset. The primary endpoint of 30-day mortality was 4.7% (4/86), with three deaths following acute dissection (5.5%, 3/55) vs. one following non-acute dissection (1/31).

For TEVAR in treatment of complicated type B aortic dissection, Lombardi stated the management goals include prompt diagnosis, alleviation of malperfusion and containment of rupture, maximising false lumen thrombosis and minimising long-term complications.

The Zenith stent used in the STABLE trials is a composite device design, combining a proximal covered stent graft with a bare metal stent.

“Complete false lumen thrombosis in the thoracic aorta increased over time and was observed in 74% of acute and 59% of non-acute patients at five years”, Lombardi et al write in their abstract, published in the Journal of Vascular Surgery. “From before the procedure through five years, there was an overall increase in true lumen diameter and concomitant

Joseph Lombardi

decrease in false lumen diameter in both acute and non-acute patients at the level of the largest diameter in both the thoracic and abdominal aorta. At five years, 66% of acute and 81% of non-acute patients exhibited either a stable or shrinking transaortic diameter in the thoracic aorta; 52% of acute and 24% of non-acute patients experienced growth in trans-aortic diameter in the abdominal aorta.”

Commenting on the outcomes at the VAM in Boston,

Lombardi said aortic remodelling was observed within and beyond the stent-grafted segments in both acute and non-acute dissections. He also stressed that aortic growth after TEVAR for type B aortic dissection is “very real, and may be more prevalent in patients treated in the acute phase”, as well as the importance of longterm commitment to managing type B aortic dissection.

At five years, endpoints included freedom from allcause mortality (80%±6%), freedom from dissection repair-related mortality (84%±6%) and freedom from rupture (92%±4%). “Twenty-five patients underwent secondary intervention through five years,” Lombardi added, 17 of which were acute. Freedom from secondary interventions in both groups was 66%±8% at five years.

“Overall, the acute and nonacute cohorts from the feasibility study appeared to respond similarly to treatment,” Lombardi et al conclude in their abstract, “demonstrating similar clinical outcomes and favourable aortic remodelling in the thoracic and abdominal aorta.”

Reviewing the initial 30-day outcomes for STABLE I acute dissection patients, Lombardi noted at the VAM: “When we compare our data to the pooled SVS dataset by White et al in 2011, and also the pooled results from a meta-analysis on TEVAR by Fattori et al [2013], what strikes you initially is the low mortality rate [of the STABLE I acute cohort] in comparison, and also the low paraplegia rates with the use of this combination system.” The mortality rates of the pooled datasets were 10.6% and 10.2% for White et al and Fattori et al, respectively, as compared to the STABLE I study’s 5.5% mortality at 30 days. The paraplegia rates at 1.8% were indeed also significantly lower in comparison to White et al (9.4%; paralysis or paraparesis) and Fattori et al (4.2%; 30day or in-hospital spinal cord ischaemia) data. The non-acute group similarly showed lower mortality rates in the STABLE I study ( 3.2% vs. 7.1% and 6.6%, respectively), but no significant difference in paraplegia rates (0% vs. 0% and 1.5%, respectively).

NICE draft guideline casts shadow over EVAR for unruptured aneurysms Continued from page 36

Further, the committee did not recommend using complex EVAR in randomised trials in these circumstances, because it would be unethical to randomise people to a treatment with a high risk of perioperative death when there is no prospect of long-term benefits at reasonable cost.

“For each of these recommendations, the committee considered whether there were any specific groups that would benefit from standard or complex EVAR for unruptured AAAs. They explored groups defined by age, sex, AAA diameter and life expectancy, but there were no groups in which the benefits would outweigh the harm and costs,” the guideline states.

The guideline committee acknowledges that the recommendations on EVAR will have a large impact on practice, as EVAR is a widely performed procedure. “EVAR is currently used more frequently than open surgical repair in some areas, so a diverse group of people both within and outside the national screening programme will need

to update their knowledge,” they state. On a more positive outlook, the committee believes that the recommendations will “minimise harm by reducing long-term mortality and the need for reintervention as a result of problems with EVAR. Reductions in EVAR use and subsequent EVAR-related reinterventions will lead to cost savings within the NHS”.

EVAR did not lose out all round, as the NICE draft guideline does allow for the consideration of EVAR for the repair of ruptured aneurysms, at least of the infrarenal kind. They advise that EVAR provides more benefit than open surgical repair for most people, especially for women and for men over the age of 70 years, and open surgical repair is likely to provide a better balance of benefits and harms in men under the age of 70 years.

However, for ruptured complex AAA the guideline instructs that open surgical repair should be considered, but that complex EVAR should not be offered to people with a ruptured AAA if open surgical repair is

suitable, except as part of a randomised controlled trial comparing complex EVAR with open surgical repair.

According to the document’s rationale, the evidence considered by the committee showed that, compared with open surgical repair, a strategy that uses EVAR to repair ruptured infrarenal AAAs provides a balance of benefits and costs. Further, as the average cost-effectiveness results for EVAR were favourable, the committee discussed whether they should recommend EVAR whenever it is possible. They decided not to, for two reasons: “Firstly, there is uncertainty in the evidence for EVAR. People who had EVAR for a ruptured AAA were followed up for at most seven years. People who had EVAR for an unruptured AAA were followed up for 15 years, and the committee noted that these data suggested that EVAR may be worse than open surgical repair in the long run. There are some signs that a similar long-term pattern may develop in trials of ruptured AAA. “Secondly, there was evidence that the

balance of benefits and costs of EVAR varies between different groups of people with ruptured AAA. In particular, women clearly have better short-term survival after EVAR, whereas the evidence favours open surgical repair for younger men. Therefore, the committee recommended that either EVAR or open repair can be considered, and provided detail on the groups for which each approach is likely to be best.

“Complex EVAR is only recommended within the context of a randomised controlled trial because there is currently no evidence to support it as an option for people with ruptured complex AAA.” NICE maintains that they will have little impact on current practice, “as both standard EVAR and open surgery are currently offered to people with ruptured infrarenal AAA. In relation to complex EVAR, the recommendation not to use it outside of randomised trials will limit the use of a technically complex and expensive procedure in people for whom open surgery is a safe and suitable option”.

5

5

5

5

5

CROSSER | ULTRAVERSE 035 | ULTRASCORE | LUTONIX 035 | LIFESTENT 5F ®

5F

™

®

5F

5F

5 F Low Profile 5FFocused Force 5F 5F 5F 5F 5F 5F 5F 5F 5F 5F 5F The ULTRASCORE™ Focused Force PTA Balloon is designed to longitudinally fracture plaque at lower inflation pressures compared to standard PTA. ULTRASCORE™ is part of the 5F ProSeries™ suite of low profile, 5F products.

To learn more, please visit BardProSeries.com

®

5F 5F 5F 5F 5F 5F

®

5F 5F 5F 5F 5F

Please consult product labels and package inserts for indications, contraindications, hazards, warnings, cautions, and information for use.

BD, Forest House, Tilgate Forest Business Park, Brighton Road, Crawley, West Sussex RH11 9BP Illustration by Mike Austin. Copyright © 2018.

All Rights Reserved. © 2018 BD. BD, the BD logo and all other trademarks are property of Becton, Dickinson and Company. Illustrations by Mike Austin. All Rights Reserved.

5F 5F 5F 5F 5F 5F

Vascular & Endovascular

Challenges Update 15–18 APRIL 2019 MONDAY–THURSDAY OLYMPIA GRAND • LONDON • UNITED KINGDOM

Aortic Challenges

Peripheral Arterial Challenges

Venous Challenges

Acute Stroke Challenges

Vascular Access Challenges

and introducing

Abstract submissions open WWW.CXSYMPOSIUM.COM/ABSTRACTS

EDUCATION

INNOVATION EVIDENCE

Sept

Issue

18 71

New developments

41

The merits of a 100-year business plan Fred Lampropoulos, chairman and chief executive officer of Merit Medical, spoke to Interventional News about building with lasting value in mind. He attributes the company’s success in developing and acquiring (recent acquisitions include Argon Critical Care, DFINE, Bard’s divestment assets and BioSphere Medical) a product portfolio that spans the breadth of interventional radiology to vision, planning and never putting himself ahead of his employees. ing curve. China is one of our fastest growing areas, and we believe it will continue to grow.

Recently, our market cap hit a record high of US$2.4 billion. Within three to four years, it will be US$5 billion dollars. We started out as a penny stock.

We have R&D going on in numerous locations – in Singapore, China, and India. Another thing that distinguishes us from other small- to medium-sized businesses is the way that we have grown. The US business accounts for almost 50%, but we are also in Central South America, South Africa, North Africa, Iraq, Iran, Syria, Egypt, Lebanon, and Algeria.

What are the main drivers of the healthcare industry at this time of transformation?

Fred Lampropoulos

What makes Merit Medical unique in the healthcare industry?

Planning is an important part of what we do. Our biggest single advantage is that we wrote a 100-year business plan.

That goes back to my military background as a US military officer and combat officer— I fought an enemy that was willing to fight for 100 years. If you look at our products, our programmes, and our global presence, these came about because we thought about them for a long time. We are now 30 years into the 100-year plan. We are not sellers; we are builders, dedicated to building something of lasting value.

And that must be communicated and explained to employees, so that they know that they are safe, there is a future, they are not going to be bought out, and then made redundant. That is a powerful idea. Other key factors are being visionary and disciplined, and understanding the industry.

As a medium-sized company how do you maintain a diverse portfolio in niche areas?

Last year, we introduced 22 new products. We are able to achieve this through a combination of internal research and development as well as strategic and tactical acquisitions.

When we make those acquisitions, we invest in them the same as any other part of the company. We start research projects to enhance the new company, and maintain their facilities and people, thus retaining know-how and tribal knowledge, because that is key to success. People are the key to success.

How do you choose which therapeutic areas you operate in when deciding on acquisition?

We started out in cardiology with a simple polycarbonate control syringe. Then we went on to a digital inflation device. Today, we are the world leader in inflation devices that deploy stents or blow up balloons, even though we do not have a stent. People using the tools want stability, and to be familiar with them. Technology has moved from bare metal

stents, on to self-expanding stents and drug-delivery stents, but the tools that deliver them are constant.

Innovation is also important. Most companies have one inflation device; Merit has six. We always have active research and development projects, and have moved from cardiology into interventional radiology, which candidly is now the largest part of our portfolio.

The equipment for cardiology is also used in interventional radiology, but on a bigger scale, because it works in the heart, feet, legs, liver, kidneys, and lungs, as well as in neural pathways and dialysis and PICC lines. There was a lot of room for improvement and innovation, and because it was so fragmented it meant that we could compete in this arena. Later, we looked at oncology, and bought BioSphere Medical and its EmboSphere microspheres product line in 2010, and we have doubled the size of that company in the last two years with our focus on polyvinyl alcohol (PVA) and gelfoam and a number of embolics that we will bring out in the future.

Where do you see the most interesting growth opportunities in Merit’s product portfolio?

Without revealing any trade secrets and without sharing intelligence, Merit specialises in five areas — endoscopy, critical care, interventional oncology, the peripheral spine, and cardiology. We look for cross capabilities, points of sale that we can be active in and that we have knowledge of. There are common threads that go through all of our specialties.

We also look at areas where other companies had given up, or there was underinvestment, or markets were fragmented.

We tie common threads, where there are opportunities for cross-germination, and the things that we know about into products that we believe can be competitive.

In 30 years, none of our product lines have ever failed – even though, usually, economic cycles eventually decline.

Emerging economies are doing some of the things that were being done in the US 10 to 15 years ago; they use products that are still very good but they are further back in the learn-

It is always innovation, not being afraid of being a global company with a global perspective, understanding the regulatory environment – and not complaining about it.

It is also important to understand emerging trends via an understanding of demographic issues. All of South East Asia is growing rapidly, so we have expanded there.

Another driver is being able to sort through therapies and make decisions about what to invest in. In Europe and Japan, 80 to 85% of procedures are performed through radial artery access, but the USA was slow to adopt it – five years ago it was at 5%, today it is approaching 45%. We have moved a lot of our procedures and training to the USA so as to develop the products and bring about changes in the thought processes in the USA. In politics, the saying is that you should act globally but think locally; doing that is different everywhere.

For instance, people are smaller in Asia; therefore you cannot necessarily sell the same product to someone in Japan that you would in northern Europe. You have to adapt to the local market. This is part of our strategy and the tactics that support it.

What will the future of physician education look like?

Education is essential and it is a long process. Merit has educational and awareness programmes such as ThinkRadial (an educational platform for clinicians and patients focused on the radial approach), ThinkPAE (an educational course for prostrate artery embolization) and ThinkAccess where physicians are trained by physicians. If you provide training for procedures, and supply the products, service those products, and put support structures in place, people stick with what they know, and with companies that support them.

What is Merit’s approach to supporting online education and live events?

We provide a certain amount of online education but we need to do a lot more. We are relatively inexperienced at this point, but we do not intend to remain so, and there will be more investment and academic input into that process in the future.

On a related note, Merit is also involved in developing a bipartisan bill being introduced to the US Congress that will bring more funds into the training of interventional radiologists. We are involved politically and not just interested in selling products, we are interested in building the industry. Interventional radiologists understand patients from head to toe, but they do not control the patient. That is the real challenge—getting more people trained, and then doing a better job of raising awareness, through social media, word of mouth, and advertising, that men and women can choose to have procedures such as a prostate artery embolization or uterine fibroid embolization (UFE). Given that choice, patients will always go for the minimally invasive option.

NOV. 5-8 2018

WYNN LAS VEGAS

8 The Global Education Course for Vascular Medicine and Intervention

NOVEMBER 5-9, 2018

•

WYNN LAS VEGAS

THE ORIGINAL MULTISPECIALTY SYMPOSIUM

For 16 years VIVA has pioneered innovative education by bringing together experts who represent all vascular specialties and has maintained a focus on inclusivity and collaboration.

COMMUNICATION AND COLLABORATION THROUGH TECHNOLOGY

•

In the Global Theater, use tablets with keyboards to connect with faculty and course directors. Find networking opportunities, view job boards, reference presentations, and access other conference tools on the

•

Virtual VIVA app.

In the concurrent sessions, use the mic toss to interact with speakers and attendees.

GLOBAL LIVE CASES Leading experts from Belgium, Germany, New York, Texas, and Tennessee will demonstrate the latest techniques and methods for some of the most challenging cases.

EXPANDED, CREATIVE EDUCATION

• • • •

Wake-up with morning tracks on pharmacotherapy, aortic intervention, venous disease, CLI, and a special track for fellows.

Learn about disruptive technologies and “pipeline” developments.

See 1-on-1 interviews with key thinkers in vascular medicine and intervention at VIVA Unscripted.

Participate in strategic discussion in amphitheater settings.

FELLOWS PROGRAM Physicians in training can take a deep dive into the subjects that matter most to them. And U.S. fellows can present at a world-class conference through our Face-Off and scholarship program.

REGISTER NOW: VIVAPHYSICIANS.ORG/REG Wiro Niessen

NOVEMBER 4-5, 2018 • WYNN LAS VEGAS

VASCULAR NEWS 245 mm x 342 mm.indd 1

Expanded to 2 full days CME Accreditation • Expert Faculty • New VEINS Award 4/3/18 12:00 AM

Sept

Issue

18 71

Meetings

CIO to separate from ISET in 2019 The Symposium on Clinical Interventional Oncology (CIO) will separate from the International Symposium on Endovascular Therapy (ISET), starting from next year. Beginning in 2019, ISET will shift to a four-day format and will take place 27–30 January at The Diplomat Resort (Hollywood, USA), whilst CIO will be held 11–13 October as a standalone conference at the Eden Roc Hotel (Miami Beach, USA).

H

MP, a healthcare event and education charity that runs both CIO and ISET, states in a press release that this is “a move designed to proactively address the growing need for highly specialised, interactive, and practical education for today’s endovascular and vascular specialists.”

Traditionally held concurrently with ISET annually in South Florida, the CIO programme highlights innovative and viable treatments in interventional oncology. HMP claim in a press release that the move to separate the meetings reflects the ever-growing importance of interventional oncology (IO), the commitment to the clinical practice of IO, and the increased demand for IO education.

According to Constantino Peña and Ripal Gandhi (both Miami, USA), longtime ISET course directors: “We are

r

extremely proud to be leading the way in this rapidly evolving field. After 11 successful years, the course directors have found it critical to grow the meeting in order to continue our vision of innovative and practical IO education delivered by best-in-class, multidisciplinary experts in order to improve the lives of millions of patients with cancer using minimally invasive techniques. By creating a dedicated CIO event, we will have the opportunity to expand the focus on clinical content, accommodate new attendees, and continue to train the next generation of physicians in this growing field.”

ISET’s hallmark Live Cases, representing the practical core of the meeting, will be expanded to include an additional 90 minutes of case time. Cases will transmit from several new sites across the USA and around the world. Late-breaking clinical data with a focus on promising new technologies

Barry T Katzen

will also be featured.

In response to the popularity of the “Deep Dive” sessions, the programme will now feature dedicated tracks with interactive sessions woven throughout the course of the meeting. These tracks will be focused on critically relevant topics, including Peripheral Artery Disease, Critical Limb Ischemia, Complex Aortic and Iliac Interventions, Clot Management, Venous Interventions, and Embolotherapy.

Created in 1989 by Barry T Katzen (Miami Cardiac and Vascular Institute, Miami, USA), the founder and chief medical executive of Miami Cardiac & Vascular Institute, ISET is the premier educational forum for physicians and

43

allied health professionals who treat patients with peripheral, cardiac, and neurovascular disease. The annual meeting, which features globally recognised faculty who are experts in their field, draws more than 800 attendees from around the world and delivers practical and hands-on education focused on the latest endovascular approaches, techniques, and technologies.

Katzen comments: “For three decades we have been providing clinicians with premier endovascular education.

Innovative thinking, determination, and dedication to excellence are hallmarks of our great field, and we recognise that clinician education must continually change as the needs of patients and the healthcare landscape change. Together with my fellow course directors, we have enhanced ISET in response to the needs of our participants, and we believe the new investments we have made and the new approaches we are taking will yield the strongest ISET programme yet. We look forward to delivering relevant, real-world endovascular education with a uniquely personal and interactive approach led by globally recognised faculty to a multidisciplinary audience in 2019.”

Specialists deliver embolization Masterclass at GEST 2018 US Masterclasses at the Global Embolization Cancer Symposium (GEST) US 2018 again delivered an authoritative display on the practicalities of embolization tools and techniques. The special sessions, where experts show delegates how to use particular embolic agents and different embolization techniques, joined by a panel of opinion leaders, continue to be a popular element of the annual symposium.

M

n,

12:00 AM

arc Sapoval (Paris, France) and Jafar Golzarian (Minnesota, USA), co-founders and directors of the meeting, told Interventional News: “The Masterclass is really a part of our brand. From a remote room, device experts manipulate different devices, so that attendees can ask questions and interact. This year, the Masterclass demonstrated almost everything we use, including all of the embolization devices from coils to plugs, all of the ablation devices, all the particles, and all the liquid embolics.”

Gary Siskin (New York, USA) joined Sapoval for the first Masterclass on coils and plugs, with the former promising a session that would be relevant: “We want to relate this Masterclass to the clinical situation.”

Using models, they showed how different plugs can be deployed within vessels, and looked at screw detachment mechanisms. Panel members offered tips on effective detachment, including the advice to “bring the microcatheter right up to where the screw is, and use the catheter as a little bit of resistance to prevent it spinning”. A plug for larger vessels was also demonstrated.

The session then moved on to coils, both pushable and detachable, with Siskine emphasising the continuing need for pushable coils: “In today’s world, our fellows get so much experience with detachables, but pushable coils really are an important part of the agents that we use for embolization.” A lively discussion then followed between the panel and the demonstrators about the best way to load pushable coils, and helpful hints on how to avoid problems were put forward.

Four examples of detachable coils were illustrated, focusing on release mechanisms, and fibred and non-fibred types. The demonstrators also took a detailed look at a hydrogel system. Once hydrated, the coil occupies greater volume, explained Siskin: “The thought is that you can use fewer of these coils based on the filling the hydrogel offers you.”

A key theme that emerged, and that was to recur in the second masterclass, was the importance of correct catheter sizing. Sapoval emphasised the “need to focus on the appropriate microcatheter when you want to achieve coil delivery”. Siskin agreed: “We spend a lot of time on embolics and other parts of the procedure, but it is important to make sure you have the right catheter in place for the embolic agent you want to use.”

In the second Masterclass on liquid agents and microcatheters, Sapoval was joined by Daniel Sze (Stanford, USA) and Yasuaki Arai (Tokyo, Japan). Together, they examined microcatheters from all the major companies.

The panel and the demonstrators highlighted the importance of pre-planning when undertaking procedures, and once again pointed to the key role played by choosing the most appropriate microcatheter for the intended procedure.

Delegates were also treated to a detailed description of the various materials required for successful glue embolization, and a demonstration of the ‘sandwich technique’ by Sze. Sapoval underlined the importance of viscosity rather than concentration when using ethylene vinyl oxide copolymer (EVOH-based) liquid agents.

In keeping with GEST’s objective of remaining cutting edge, Sapoval rounded off the Masterclass by showcasing an “interesting and breaking innovation”. Using a 3D-printed anatomical model of a hepatic artery from a real patient scan, he demonstrated a new microcatheter (SeQure; Guerbet) that has side-holes to prevent bead reflux. “This raises a whole new approach for us in terms of microparticular embolization and takes into account the potential damage by the reflux of particles. This is a new opportunity, with obviously a need for clinical testing,” he said.

GEST Masterclass featuring (L to R) Marc Sapoval, Daniel Sze and Yasuaki Arai

BSIR 2018 ANNUAL MEETING

14TH-16TH NOVEMBER 2018 B O U R N E M O U T H I N T E R N AT I O N A L C E N T R E U K BSIR 2018 ANNUAL MEETING HIGHLIGHTS • • • • • •

IR in Trauma GI Bleeding Prostate Embolisation NHS Future Operating Role Complex Cases Changing face of Oesophageal & Colonic Stenting

• Interventional Oncology 4th Pillar of Cancer Care • Peripheral Angioplasty • IVC Filters • Fistula Intervention • Malformations • AAA

Graham Plant Professorship Lecture: Dr Alex Barnacle Wattie Fletcher Lecture: Dr Nigel Hacking Distinguished International & National Expert Faculty BSIR Workshops & Master Classes MDTs & Debates: Scientific Sessions and Research Updates Society of IR Nurses & Radiographers (SIRNR) Programme BSIR/BSIRT Trainee Day: Friday 16th November 2018 Dedicated programme for Trainees Medical Students & Foundatiobn Doctors with an interest in IR

For all Information about the 2018 Annual Meeting, Scholarships, Educational Grants, Membership, Exhibition and Sponsorship please go to www.bsir.org (meeting section)

VISIT THE BSIR BOOT H @ CIRSE

BSIR Secretariat: British Society of Interventional Radiology (BSIR), 63 Lincoln’s Inn Fields, London WC2A 3JW Tel: +44 (0)20 7406 5998 • Email: office@bsir.org • Web: www.bsir.org

H

Sept

Issue

18 71

New frontiers in IR: Global outreach Fabian Laage Gaupp and Andrew Kesselman discuss the global imbalance of interventional radiologists (IRs), and highlight the need for countries with more established IR services to share their knowledge and expertise.

FABIAN LAAGE GAUPP ANDREW KESSELMAN COMMENT & ANALYSIS

I

nterventional radiology (IR) has come a long way in the USA since it was pioneered over half a century ago, now offering diagnostic and therapeutic procedures for a wide range of indications, ranging from biopsies and aspirations to radioembolization of tumours. However, despite the growing importance of IR in the industrialised world, the majority of the world’s population today still has no access to IR services. In Tanzania, for example, a population of 60 million people is not served by even a single interventional radiologist. Few interventional radiologists work in Ghana, Nigeria, and Kenya, but there has been no wide-scale, concentrated effort to introduce IR training in subSaharan Africa outside of South Africa.

Given the importance IR now holds in Western healthcare systems, it may be an opportune time to establish goals and opportunities for IR on a global scale.

Many surgical specialties have a long tradition in global health. Operation Smile, one of the most well-known global surgery organisations, has facilitated over 270,000 cleft lip and palate repairs around the world since its founding in 1982. In 2017 alone, almost 4,000 medical professionals donated over 400,000 hours of their time to Operation Smile, treating over 20,000 patients. The global effort to grow developing countries’ expertise in IR, by contrast, has been minimal, with

no systematic IR outreach organisation or structured training programmes to date. It is time for IR to catch up to other specialties in equalising access to important health care options in underserved regions.

To this end, the global radiology aid organisation RAD-AID International is initiating training programmes at partner sites in low- and middle-income countries, with the goal to increase access to IR around the world. Introduction of services will be tailored to the needs and resources of each country based on an initial assessment. For instance, in Tanzania, CT [computed tomography] is available, so it is possible to train radiologists in a different set of procedures than in a place where CT is not already present.

Through this customised approach, we plan to introduce the procedures that are most urgently needed, within the realm of feasibility given local resources.

Last year, we performed an objective infrastructure assessment in Tanzania, evaluating availability of imaging facilities, equipment, nursing services, and technologists. This evaluation demonstrated that while ultrasound, fluoroscopy and CT are available, IR knowledge and training programmes are completely missing. Basic image-guided procedures such as core needle biopsy, abscess drainage, and nephrostomy are not routinely performed, limiting available

diagnostic and therapeutic options for many indications.

Consider this example: a 20 year-old female presents to the emergency room with a pelvic abscess in the setting of ruptured appendicitis. Currently her only treatment option in Tanzania is surgical exploration and washout, which carries surgical risks and may require long-term hospitalisation. If IR was available, ultrasound or CT guided abscess drainage in combination with antibiotics could help avoid emergent surgery in the acute setting. This and many other examples highlight the definite and acute need for IR in Tanzania.

Establishing an IR training programme requires a combination of hands on practical training and access to educational resources, including lectures, textbooks, and training videos. Instead of focusing on bringing trainees to the USA for fellowship, RAD-AID aims to facilitate the creation of training centres in the countries that need them. The central component of this approach is organising teaching trips to partner programmes in resource-limited settings, allowing for training of residents in their own practice environment. This ensures that the training applies to local disease patterns and resources.

Each visiting team will consist of an IR attending, a nurse, and a technologist.

This group will spend two to four weeks at a training site, focusing on handson training of residents, nurses, and technologists. Given the wide range of IR procedures that will need to be taught, multiple deployments to each site over the course of several years will be necessary, until local expertise is sufficient to provide sustainable teaching capacity for future trainees.

To accompany the practical training and provide access to IR teaching resources, RAD-AID and the Resident Fellow Student Council of the SIR [Society of Interventional Radiology] are working on a variety of projects, including live-

Radiation

45

streaming of IR lectures from US teaching institutions, an IR curriculum for the resource-limited setting, IR training videos, and virtual reality options for training and mentorship. In addition, academic institutions in the USA can provide opportunities for trainees from partner programmes to do IR observerships and research projects to expose them to the academic IR setting.

In combination, these training methods may provide a way of establishing IR programmes at sites around the world that would otherwise not have access to IR. Training platforms will be adapted and evolve over time based on areas of specific need and continued assessment.

There is tremendous potential in the expansion of IR services to regions of the world that currently have no access to these lifesaving therapies. As IR has changed and continues to change practice patterns in the USA, it will in turn impact healthcare systems and patients’ lives all around the world. As interventional radiologists, as well as participants in a larger medical community, we can aim to provide the support needed to implement sustainable projects in resource-limited settings to generate a lasting global impact.

Go here to learn more about the IR programme of RAD-AID: www.rad-aid. org/programs/interventional-radiology/ To learn more about the Tanzania outreach programme in particular, go here: globalhealth.radiology.yale.edu Fabian Laage Gaupp is an interventional radiology resident at Yale University School of Medicine, New Haven, USA. Andrew Kesselman is an interventional radiologist at Weill Cornell Medicine, New York, USA, specialising in minimally invasive image guided procedures and comprehensive management of vascular and oncologic disease. The authors cite no relevant disclosures. Kesselman is the IR programme director for the non-profit RAD-AID.

One in five UK doctors say under staffing has affected patient safety The annual census of UK consultants and higher speciality trainees indicates that more than half of all consultants and two thirds of trainees reported frequent gaps in trainees’ rotas, with one in five respondents saying these are causing significant problems for patient safety in hospitals.

T

he report, which has been jointly published by the Royal College of Physicians and Surgeons of Glasgow, the Royal College of Physicians of Edinburgh, and the Royal College of Physicians of London, also shows: n Almost half of advertised consultant posts remain unfilled because of a lack of suitable applicants n Consultants and trainees are working around 10% more than their contracted hours. This equates to trainees working an extra six weeks and consultants an extra month unpaid a year n 33% of the current consultant workforce are predicted to reach their intended retirement age

in the next decade. Medical student places need doubling now to fill this and the gap left generally by doctors leaving the profession n Satisfaction among consultants and trainees with working in general internal medicine remains significantly lower than with specialty-working.

Commenting on the findings of the census, David Galloway, president of the Royal College of Physicians and Surgeons of Glasgow, says: “I am glad that the three Royal Colleges have once again joined together to produce this important piece of work. It is vital that everyone involved in the NHS now reflects on these findings and takes all the action necessary to

replicate best practice and address the challenges that this document has highlighted. What is of particular concern is the finding that almost one in five consultants across the UK reported that rota gaps cause significant problems for patient safety in their hospital. This is an unsustainable situation which must be addressed as a matter of urgency.”

46

Sept

Issue

18 71

New beginnings

Ghana’s first interventional radiologist defies sceptics to establish an IR programme Benjamin Sarkodie was the first interventional radiologist in Ghana, and is currently at the Korle Bu Teaching hospital, Accra, Ghana. Additionally, Sarkodie is a full time lecturer at the University of Ghana medical school, also in Accra. Passionate about expanding access to life-saving interventional radiology procedures, he talks to Interventional News about the progress of the Ghana Society of Interventional Radiology (GSIR) and the challenges it is facing.

You founded the GSIR in November 2015.

What were your ambitions and how have they been realised?

In the past three years, the GSIR has achieved a lot of successes. We have encouraged the promotion and adoption of interventional radiology among Ghanaian physicians and surgeons, as well as the general population through education and awareness creation. As interventional radiology is a relatively new specialty, and especially so in Ghana, we have organised workshops, conferences and seminars to help promote it.

We have also reached out to the public through radio, television, print and social media. We continue to see a rise in demand for minimally invasive therapy in Ghana.

What was your initial reception like when you decided to found this society?

world, we continue to get closer and closer to our goals in making interventional radiology a dominant treatment alternative in this country.

What is currently the main priority for the GSIR?

Priority number one is education, priority number two is education and priority number three is education—for both physician/ surgeons and the general public. Through collaborations with the Singapore General Hospital, we hope to continue to add more interventional radiologists, while also training some radiologists in Ghana to help increase capacity.

Do you remain the only interventional radiologist in the country?

Thank God we now have a second one and another person is in training!

We were confident that we would reach out to colleagues and the public to promote and encourage the adoption of interventional radiology in Ghana. The sceptics noted I was the only interventional radiologist in Ghana and questioned the society’s relevance and abilities. However, through collaborations with other societies and interventional radiologists around the

What is the most difficult aspect of working in Ghanaian hospitals?

Affordability of care. Often some patients do not get to access our services because they cannot afford it.

The most exciting things are putting smiles on the faces of my patients through the combination of medicine and technology.

Benjamin Sarkodie and colleagues in the operating room

Could you describe a particularly memorable case you have performed in Africa?

We have done a lot of memorable cases. One such case was a lower gastrointestinal bleeding in a 70-year-old man whose Haemoglobin remained 4g/dl, and who was hemodynamically unstable in the face of multiple transfusions.

We were called in and, after an initial angiogram, we embolized a bleeding aberrant vessel supplying part of his colon. The patient has since stopped bleeding and is doing well.

What changes would you like to see in healthcare in resource-poor countries?

Healthcare is a function of any economy and so I would like to see good transformations in the economies of developing countries. By so doing, a lot more people could afford good and alternative healthcare.

I also hope to see a strengthening of the national health insurance schemes, so that many interventional radiology procedures can be covered. The future looks promising, with great opportunities.

Leipzig Interventional Course | 22.1.–25.1.2019 Save the date!

22.1.–25.1.2019

Abstract submission for LINC 2019 is NOW open!

Deadline for submission will be October 21, 2018

Submit your abstract for the following categories: Call for original research/scientific work Call for challenging cases/complications

Online registration is NOW open!

Call for clinical trials Call for innovation

Submit now!

Live case transmission · Symposia · Complication session · Poster session For more information: www.leipzig-interventional-course.com · Course Organisation: www.cong-o.com LI19 ad_225x153_cirse daily.indd 1

11.07.18 15:18

Sept

Issue

18 71

Stroke

Researchers find major inequalities in acute stroke treatment across Europe Every year, up to 1.3 million people in Europe suffer a first stroke. Acute stroke treatment strategies such as acute treatment of patients in a stroke unit, intravenous thrombolysis and endovascular treatment significantly improve the outcome for patients with ischaemic stroke and thus reduce its socioeconomic burden. However, reliable data on access to and delivery of acute stroke treatment strategies throughout Europe are lacking.

T

he European Stroke Organisation (ESO), the European Society of Minimally Invasive Neurological Therapy (ESMINT), the European Academy of Neurology (EAN) and the patient organisation Stroke Alliance for Europe (SAFE) have therefore surveyed stroke experts from 44 of 51 European countries on the best available information regarding national access to and delivery rates of acute stroke unit care, intravenous thrombolysis, and endovascular treatment.

The results of this survey identify major inequalities in acute stroke treatment, with many countries reporting

rates that were far below highest country rates. This article shows in which countries patients still have no or obviously inadequate access to appropriate acute stroke treatment.

According to Urs Fischer, Professor for Acute Neurology and Stroke at the University Hospital Bern, up to 226,662 additional patients could be treated with intravenous thrombolysis and an additional 67,347 with endovascular treatment each year. “Many stroke victims in Europe still have no access to acute stroke treatment,” he said.

“If stroke unit care, intravenous

Penumbra launches JET 7 and Penumbra JET D in USA Penumbra has announced US commercial availability of the Penumbra JET 7 and Penumbra JET D reperfusion catheters powered by the Penumbra Engine aspiration source. The Penumbra JET 7 and JET D reperfusion catheters deliver deep vacuum aspiration power of the Penumbra Engine to enable physicians to extract thrombus effectively and safely in acute ischaemic stroke patients.

T

he Penumbra JET 7 is the Penumbra System’s seventh generation reperfusion catheter for proximal large vessel occlusions, and JET D Reperfusion Catheter is designed specifically for distal occlusions. JET 7 Reperfusion Catheter has a large 0.072” lumen for deep vacuum aspiration and is designed for trackability and navigation, featuring 20 transitions from the proximal shaft to distal tip, a progressive distal coil wind for superior flexibility and Quad-Wire technology in the proximal shaft for enhanced pushability. JET D brings deep vacuum aspiration power to distal occlusions with a smaller profile.

“The JET 7 Reperfusion Catheter with its advanced tracking technology and large 0.072” aspiration lumen is the most advanced device for stroke. In my clinical experience, I was able to easily and quickly navigate the JET 7 through tortuous anatomy to the face of the clot and achieve full revascularisation after a single pass,” said Alejandro M Spiotta, Medical University of South Carolina, Charleston, USA. “We know from our own published experience that increases in aspiration lumen size have led to faster recanalisation times and higher likelihood of success at first pass without compromising safety.”

Penumbra announces acquisition of controlling interest in MVI health Penumbra has announced it has closed on the acquisition of a controlling interest in its joint venture, MVI Health. After closing the transaction, Penumbra increased its ownership to 90% of the equity of MVI Health for US$20 million in upfront cash consideration.

MVI Health, originally formed in May 2017, is a joint venture between Penumbra and Sixense Enterprises, a leader in virtual reality software and tracking solutions for enterprise. Since its founding, MVI Health has been developing virtual reality technology for healthcare applications.

MVI Health, headquartered in Alameda, USA, is supported by investments from Penumbra and licensed intellectual property and other resource contributions from Sixense Enterprises.

thrombolysis and endovascular therapy would be routine practice throughout Europe, many more victims could survive their stroke without a major handicap”. According to Fischer, these inequalities not only have a major impact on the patients, but also on their families and the socioeconomic burden. “Recent studies have shown, that acute stroke treatment is highly cost effective—if you treat your patients right, you will not only improve the quality of life of the patient and his family, you will also save money for your society”, he said. Therefore, efforts have to be

47

done to increase the number of stroke units, intravenous thrombolysis and endovascular stroke therapy. “We have to talk to governments, politicians, health care specialists and stroke physicians in order to set up and improve the system in regions, where acute stroke treatment is lacking!”

In May 2018, ESO and SAFE presented the Stroke Action Plan for Europe to set achievement goals for stroke care by 2030. This survey already provided important insights for the Stroke Action Plan authors. The findings from this survey are relevant for future health-care planning in Europe and beyond.

Standardised stroke protocol can ensure stroke patients are treated within 60 minutes

A

new study shows that developing a standardised stroke protocol of having neurointerventional teams meet suspected emergent large vessel occlusion (ELVO) stroke patients upon their arrival at the hospital achieves a median doorto-recanalisation time of less than 60 minutes. The study was presented at the Society of NeuroInterventional Surgery’s (SNIS) 15th Annual Meeting.

Door to Revascularisation in Less than 60 Minutes: A Cost and Benefit Analysis mentions that while standardised protocols for imaging and transport to the angiography suite, as well as a standardisation of the thrombectomy procedure, help save time, the most important time savings comes from having a neurointerventional team meet the patient when they arrive in the emergency room. The five-person team includes one registered nurse (RN), two technologists, one anaesthesiologist, and one neurointerventionalist.

“Level 1 trauma centres require trauma surgeons and anaesthesiologists to be in-house 24/7. By requiring Level 1 stroke centres to do the same, we could potentially help more ELVO patients make full recoveries,” said Donald Frei, lead author of the study and a neurointerventionalist based in Colorado, USA. Rapid endovascular thrombectomy helps patients with ELVO achieve the best outcomes, but standardising stroke protocols to ensure timely and safe care does come at a cost.

The study considered 1,162 ELVO alerts met by the neurointerventional team. Of these, 314 patients (27%) received a thrombectomy. In cases in which a thrombectomy was not performed, the RN and technologists are paid two hours each of overtime pay, averaging to a total cost of more than US$200,000 in overtime pay annually for the salaried staff. This does not include physician time spent.

“This study shows that stroke systems of care can and should be streamlined to ensure the best possible outcomes for patients,” said Frei. “The associated costs also suggest that in-house neurointerventional teams at hospitals may be the most effective option for rapid and safe care. The additional annual cost in overtime pay for the team is far outweighed by the huge benefit in decreasing the costs of lifelong disability because many more patients can return to independence.”

Innovative thinking, determination, and dedication to excellence are hallmarks of our great field, and we recognize that clinician education must continually change as the needs of patients and the healthcare landscape change. Together with my fellow Course Directors, we’ve enhanced ISET in response to the needs of our participants, and we believe the new investments we’ve made and the new approaches we’re taking will yield the strongest ISET program yet.

”

BARRY KATZEN, MD, FACC, FACR, FSIR ISET Course Director

SEE WHAT’S NEW FOR YOU AT ISET.ORG 

Legendary Live Cases Expanded



New Course Directors Added





Dedicated Tracks for Customized Learning

27–30 January, 2019 The Diplomat Hollywood, Florida USA

More Hot Topic Sessions

I N T E R N A T I O N A L

2018-ISET_IN_ad_Sept.indd 1

S Y M P O S I U M

O N

E N D O V A S C U L A R

T H E R A P Y

8/17/18 10:08 AM

10:08 AM

Sept

Issue

18 71

New developments

FDA updates advisory letter on devicerelated type III endoleak risks An update to last year’s FDA letter, expressing concern over risk of type III endoleaks in relation to endovascular graft systems, now states that the increased risk is specific to one device which was discontinued in 2014.

E

ndologix’ AFX Strata, an endovascular graft system indicated for endovascular aneurysm repair (EVAR), ceased to be manufactured by the company in 2014. In December 2016, Endologix issued a recall of the “small remaining quantity” of AFX Strata devices remaining in hospital inventories. However, the FDA highlight, the device is still in use in patients who had it implanted prior to discontinuation or recall.

The FDA’s original 2017 letter described an increase in type III endoleaks reported by several sources including the Administration’s own Medical Device Reporting (MDR) system and manufacturers’ Annual Clinical Updates to Physicians. The increased risks were associated with EVAR and endovascular graft systems, but the FDA were not specific as to which systems could be affected, instead recommending reports of adverse events from physicians and manufacturer compliance with MDR regulations and reporting requirements.

Since the 2017 letter, the FDA now write, the increased risks were narrowed down to the AFX Strata based on new information, observing “greater risk for a type III endoleak compared to other endovascular abdominal aortic aneurysm (AAA) graft systems.

Type IIIa endoleaks were, as estimated by

Endologix, 0.9% at two years and 5% at five years, while type IIIb endoleak rates were 0.66% at two years and 2.4% at five years. “Because these estimates are calculated using voluntary reporting and units sold, the rate estimates may be low compared to the true endoleak event rates”, the FDA write.

Matt Thompson, chief medical officer for Endologix, says, “The FDA update does not disclose risks beyond those already communicated to health care practitioners in safety notice issued

by Endologix in December 2016, which requested that all remaining AFX Strata devices be returned from the field and emphasised the fact that Endologix has not manufactured AFX Strata grafts since 2014.”

“Endologix is committed to working collaboratively with the FDA,” comments John Onopchenko, the company’s chief executive officer. “Our current commercially available versions of the AFX system, the AFX Duraply and AFX2 products, are manufactured using a different ePTFE processing methodology and include additional product improvements.

“These AFX Duraply and AFX2 products are not the subject of today’s FDA-issued awareness notification. Through our comprehensive system of post-market surveillance, anonymised registry

The IR residency necessity WAEL SAAD MINHAJ KHAJA COMMENT & ANALYSIS With the graduation of the first ever interventional radiology residents from a US university, Wael Saad and Minhaj Khaja discuss the importance of having a dedicated IR residency programme.

T

he evolution of the interventional radiology (IR) residency hit a milestone this year with the graduation of the first two IR Residents in the USA, both from the University of Michigan. Nishant Patel and Michael Cline completed their IR residency training in June 2018.

The creation of an integrated primary residency in IR has long been in the works. However, a handful of programmes (at the University of Virginia, the University of Rochester, the University of Pennsylvania, and the University of Michigan, all USA) did have focused IR training programmes prior to the establishment of the IR residency at the University of Michigan.

Perhaps the most consistent legacy programme of these is the University of

Virginia (UVA) programme, established

by Alan Matsumoto and John Fritz Angle (both of the Department of Radiology and Medical Imaging, UVA, Charlottesville, USA).

Since the approval of the IR residency in 2014 by the Accreditation Council for Graduate Medical Education, the educational paradigm in vascular and interventional radiology has been evolving at a rapid pace. Under the leadership and direction of Reed Dunnick (chair), Janet Bailey (diagnostic radiology programme director), Wael Saad (IR division director), Bill Majdalany (IR fellowship programme director) and Minhaj Khaja (clinical pathway programme director and graduate), the collaborative team strategically established the Vascular and

49

data, and the only randomised trial to compare EVAR systems (the LEOPARD trial), we have a strong, growing evidence base that supports the use of the AFX Duraply and AFX2 systems for patients with AAA. We are proud of, and committed to, advancing our collaborative work with the FDA on behalf of our patients, customers, and the broader clinical community.”

At this time, the FDA advise health care providers monitor affected patients and ensure annual follow-up to monitor for type III endoleaks.

“The FDA continues to work collaboratively with Endologix,” they write, “to assess the treatment options for patients with the AFX with Strata device and type III endoleaks, and to provide further instructions in the labelling on this concern.”

This most recent FDA letter ends: “Device manufacturers and user facilities must comply with applicable MDR regulations. Health care personnel employed by facilities that are subject to FDA’s user facility reporting requirements should follow the reporting procedures established by their facilities. Prompt reporting of adverse events can help the FDA identify and better understand the risks associated with medical devices.

“The FDA will keep the public informed as any new information or recommendations become available.”

Interventional Radiology (VIR) Clinical Pathway at Michigan in 2013, with the plan to transition to the IR residency. The VIR Clinical Pathway was established in such a way that the trainees could easily transfer into the IR residency programme of the future, and were therefore poised to be pioneers. It was modelled after the UVA-programme which we, having attended that university, were very familiar with. It should be noted that the key to this success was the collaborative relationship between IR training (Minhaj Khaja), the diagnostic radiology training (Janet Bailey), and the surgery internship training. This collaboration not only enabled the Michigan programme to be one of the first in the nation, but was noted by the Radiology Review Committee (RRC) site visit.

The first IR residency programmes were approved by the Accreditation Council for Graduate Medical Education in spring of 2015, with the first match that same year. There were only eight resident positions and a handful of programmes involved in the first year. Today, there are over 75 programmes and 130 positions each year. Having been among the first programmes approved for the IR residency and having a pre-established

VIR Clinical Pathway, Michigan’s residents were able to easily transfer into the IR residency and the training paradigm of the future. The Michigan IR residency integrated programme, now with a tailored, linked surgical preliminary year, has two graduates and 16 trainees in the programme, spanning all six years of the curriculum. The latest recruited years have three integrated IRresidents per class.

Cline has remained on staff at the Ann Arbor Veterans Administration Hospital, and is a faculty member at the University of Medicine and Health Sciences, Basseterre, St. Kitts & Nevis. Patel has moved out west to Denver to begin his career at Radiology Imaging Associates, USA. I am sure the entire IR community can join us in congratulating them in representing our future as pioneers and torch-bearers. We thank all of those who were vital to making this a reality at our institution, as well as nationally.

Wael Saad is a professor of Radiology, Vascular and Interventional Radiology at Michigan Medicine, the University of Michigan, Ann Arbor, USA. Minhaj Khaja is an assistant professor of Radiology at Michigan Medicine, the University of Michigan, Ann Arbor, USA.

I am sure the entire IR community can join us in congratulating them in representing our future as pioneers and torchbearers.

25

th

SUBMIT YOUR ABSTRACT!

myESR.org/abstract-submission

Sept

Issue

18 71

Industry news

Industry News Boston Scientific announces agreement to acquire Veniti

Boston Scientific has signed an agreement to acquire Veniti, a privately-held company which developed and commercialised the Vici venous stent system for treating venous obstructive disease. Boston Scientific has been an investor in Veniti since 2016 and currently owns 25% of the company. The transaction price for the remaining stake consists of US$108 million upfront cash, as well as up to US$52 million in payments contingent upon US Food and Drug Administration (FDA) approval of the Vici stent system.

The self-expanding, nitinol Vici stent system was developed specifically for use in the venous anatomy, which presents different challenges than placing stents in the arterial vascular system.

“This stent system was designed with the distinctive demands of the venous system in mind, and built to provide physicians with a high-quality lumen across a variety of venous anatomies and disease states,” said Jeff Elkins, president and CEO of Veniti.

The Vici stent system received CE Mark in 2013 and Veniti submitted a pre-market approval (PMA) application to the US FDA in June, leveraging results from the recently completed VIRTUS pivotal study.

Currently in the USA, there are no stent technologies specifically indicated for use in the peripheral venous system.

“With the unique benefits of this differentiated technology and the strong experience of Boston Scientific in the overall venous market, we believe the Vici stent will become an important choice for physicians who choose stents to treat patients suffering from venous disease,” said Jeff Mirviss, senior vice president and president, Peripheral Interventions, Boston Scientific. “Along with our leading AngioJet thrombectomy platform and venous product pipeline, we look forward to meeting the needs of physicians treating both chronic and acute venous disease.”

The completion of this transaction is imminent, subject to customary closing conditions.

BD acquires TVA Medical, makers of everlinQendoAVF System

BD (Becton, Dickinson and Company) announced it has completed the acquisition of TVA Medical, a company that develops minimally invasive vascular access solutions for patients with chronic kidney disease requiring haemodialysis including the everlinQ endoAVF System.

The addition of TVA Medical enables BD to offer the everlinQ endoAVF System, a new endovascular arteriovenous (AV) fistula creation technology that adds to the company’s end-stage renal disease portfolio of dialysis catheters, drug-coated balloons, standard angioplasty balloons and endovascular stent graft products. This technology will further improve BD’s ability to serve physicians and their patients by providing a minimally invasive option for creating critical AV fistulas for hemodialysis procedures.

Q50 Plus

EverlinQ endoAVF System to become WavelinQ EndoAVF System On 22 June, the US FDA announced De Novo marketing authorisation for the everlinQ endoAVF System. The system uses two, thin,

flexible, magnetic catheters that are inserted into the ulnar artery and the ulnar vein in the arm through a small puncture. When placed close to each other, the magnets in each catheter attract, pulling the vessels together. After confirming alignment, an electrode from the venous catheter delivers radiofrequency energy to create the connection between the artery and vein. Embolization of the brachial vein is then recommended. The fistula is confirmed with an angiogram (X-ray image of the vascular system) to show that arterial blood is flowing to the lowpressure venous system. The procedure minimises the amount of vessel and skin trauma compared to traditional fistula creation using open surgery.

The everlinQ endoAVF System enables an additional AV fistula location for patients than what is typically done surgically. The device is already commercially available in Europe and Canada. The product name will be transitioned to WavelinQ EndoAVF System during integration.

This transaction is not expected to have a material impact on BD results for fiscal 2018 or 2019.

Future results for TVA Medical will be reported under the Peripheral Intervention business within the Interventional Segment at BD. Terms of the transaction were not disclosed.

Guerbet announces commercial partnership with Imalogix

Guerbet has announced a commercial partnership with Imalogix, a company focusing on artificial intelligence process and workflow solutions.

The commercial partnership combines Guerbet’s diagnostic and interventional imaging with the cloud-based human and machine-intelligence capabilities of Imalogix to proactively identify areas that impact care delivery to reduce variability and improve the quality, safety and efficiency of care around radiation dose management.

According to a press release, the Imalogix Platform gives healthcare organisations the tools to understand and manage the process, quality and safety related to diagnostic imaging and interventional procedures, and meet evolving regulatory standards surrounding radiation dose management.

“Guerbet is thrilled to deliver an AI-powered solution that brings together data in a meaningful way to evolve the standard of care to patients for managing radiation dose,” says Massimo Carrara, Guerbet vice president for North America.

The Imalogix self-learning neural network enables organisations to understand and benchmark in real-time best practices from the mass learnings across a network of providers to drive continuous improvement. Deep learning recommendations highlight where and how changes can be made to enable organisations to proactively change behaviour down to the scanner, protocol and operator level. Insights into procedure length, utilisation, and workflow help organisations understand how to become more efficient and optimise patient flow.

PERT Consortium and BTG form strategic partnership

BTG has announced a strategic partnership with the PERT Consortium to advance the science of pulmonary embolism treatment and promote the

51

implementation of PERT programmes across the USA. The partnership was announced at the annual PERT Consortium Meeting (22–23 June, Nashville, USA).

In the USA, pulmonary embolism afflicts 500,000– 600,000 patients annually and is either a primary or secondary cause of death in 150,000–200,000 of these individuals. In their new partnership, BTG and the PERT Consortium are uniting to address this disease via expanding options for professional education, expanding clinical research, establishing quality benchmarks for care of pulmonary embolism, and developing new mobile technologies to convene PERT teams and improve decision-making.

Paradise System

Otsuka Holdings, Otsuka Medical Devices and ReCor Medical to merge

Otsuka Holdings, Otsuka Medical Devices, and ReCor Medical have signed a merger agreement pursuant to which Otsuka Holdings will acquire the remaining shares in ReCor from its current holders. The transaction is subject to approval by ReCor’s shareholders.

Otsuka Holdings’ acquisition follows the announcement by ReCor that the US FDA has given its approval to initiate a pivotal clinical study, RADIANCE II, for the evaluation of the Paradise renal denervation system for the safe and effective reduction of blood pressure in patients with hypertension. Previously, data from RADIANCE-HTN SOLO demonstrated a statistically significant reduction in blood pressure with the Paradise System in hypertensive patients.

Following the acquisition, according to a press release, ReCor plans to continue to develop and evaluate the Paradise System in patients with hypertension in preparation for worldwide commercialisation, as well as explore its use in additional clinical applications such as heart failure, kidney disease and metabolic disorders, while also building the Otsuka Medical Devices’ incubation and clinical development hub in the USA and Europe.

Merit Medical named exclusive distributor of Q50 Plus

Merit Medical Systems has been named the exclusive global distributor of the Q50 Plus Stent Graft Balloon Catheter (QXMédical). The Q50 Plus is used in abdominal and thoracic endovascular aneurysm repair (EVAR) procedures to repair abdominal aortic aneurysms and thoracic aortic aneurysms. It is also suitable for temporary occlusion of large vessels.

The Q50 Plus features a broad balloon diameter range of 10mm to 50mm and is compatible with 12 French introducer sheaths. Constructed from a proprietary polyurethane technology, the balloon catheter is strong yet compliant and also offers exceptional balloon inflation and deflation rates, MeritMedical indicates in a press release.

The Q50 Plus is available with either a 65cm length catheter or a 100cm length catheter and is designed with a unique tapered flexible tip to facilitate device passage.

52

Sept

Issue

18 71

Section Name

SIR

20 19

The Annual Scientific Meeting is where we’ll shape the future of IR. In a post-SIR 2018 attendee survey, more than 75% of respondents called the meeting the “best place to get IR education.”

Austin is the capital of Texas and a dynamic and multicultural city. A natural choice to showcase the innovation of IR, its profile as a health care hub is expanding as is its surge in the technology sector.

Registration opens Oct. 1, 2018 Abstract submission is open until Sept. 27, 2018

SIRMEETING.ORG

SIR2019_Inl– News-STD_fpg-ad.indd 1

7/30/18 2:08 PM

Sept

Issue

18 71

Clinical news

Clinical News Gore announces successful patient implant of endovascular stent graft of the ascending aorta

Gore have announced the first implant in conjunction with the Gore ARISE study of the Gore Ascending Stent Graft, an investigational device and the only endovascular stent graft specifically designed to treat type A dissections of the ascending aorta. The successful procedure took place on August 14, 2018 at Memorial Hermann Medical Center in Houston (USA), by Anthony Estrera, and Bruce Tjaden, as part of the Gore ARISE study.

ARISE is the first multicentre, early feasibility study approved by the US Food and Drug Administration (FDA) to investigate the use of a minimally invasive device to treat type A dissection. The national principal investigator is Michael Reardon, from Houston Methodist Hospital, (Houston, USA). The study initially investigated the use of the Gore Tag Thoracic Branch Endoprosthesis (aortic extender) in type A dissection, which is also being evaluated in its own pivotal study to assess safety and effectiveness in treating lesions of the aortic arch and descending thoracic aorta. The new purpose-built Gore Ascending Stent Graft will be used for the remainder of the study to allow investigators to gain a better understanding of how new technology can advance treatment options for this condition.

The Gore Ascending Stent Graft features a precise delivery system that is designed to allow for accurate, controlled deployment in complex anatomies. The delivery system features unique angulation control that gives physicians the option to angulate the device to achieve orthogonal placement to the ascending aorta.

Type A aortic dissection is a tear in the lining of the ascending aorta, above the heart, that creates a second channel of blood flow. It is an emergent condition that requires immediate surgery upon diagnosis. The current standard of care for these patients is open surgery involving a sternotomy—cracking the chest and spreading the two halves of the rib cage apart to gain access to the heart and ascending aorta. This is a very invasive and involved surgery that includes temporarily stopping the heart to prevent blood flow during the surgical repair.

“There is a great need for a less-invasive treatment option for type A dissections, which are fatal for nearly half of all sufferers within 48 hours of onset,” Estrera said. “I’m excited that Gore is breaking ground in this area with the development of the first endovascular device specifically designed to meet the anatomical, curvature, and deployment precision requirements unique to the ascending aorta. This device, upon approval, could provide a treatment option for type A dissection patients who are not suitable for open surgery and a less-invasive treatment for all patients with this condition.”

Not all patients with type A aortic dissection are suitable for open surgery. The average sufferer of ascending aortic dissention is male and in his early 60’s, although it can also affect females and a wide age range and age groups. Risk factors that may complicate open surgery include previous thoracic surgical repair, visceral malperfusion, neurologic deficit, presentation with a concurrent myocardial infarction, cardiac tamponade, obesity, advanced aged, and poor renal, cardiac, or pulmonary function. The Gore study will investigate how an endovascular stent graft, delivered via catheter, may be used to line the dissected portion of the ascending aorta as a less-invasive alternative to open surgical repair. Similar endovascular therapies have proven to reduce the risk of complications and recovery times.

Laminate Medical Technologies announces first forearm fistula cases in Germany

Laminate Medical Technologies (Laminate), a privately-

2:08 PM

held start-up developing the VasQ implanted blood vessel external support device for patients requiring arteriovenous (AV) fistula as vascular access for haemodialysis, have announced the first forearm fistula cases in Germany.

“As one of the worldwide first users of the VasQ external scaffold for AV anastomosis for forearm fistula creation, I am very excited about the device and the possible short, middle and long-term benefits it may provide to patients. Its application is very easy and its handling adds very little time to the fistula procedure. Since it is well established that the geometrical configuration of the AV-anastomosis is crucial for reducing the future risk of perianastomotic stenosis, in my personal opinion it would be particularly advantageous to apply the VasQ device in patients with significant distance between the radial artery and forearm cephalic vein, and therefore avoid the related unnecessary and sometimes inevitable kinking of the perianastomotic vein and associated stenosis. With excitement I am awaiting the first results of the forearm VasQ device“, says Robert Shaverdyan, head of the Vascular Access Centre, Asklepios Clinic Barmbek in Hamburg, Germany.

“For me as a Vascular Access surgeon, keeping things simple is the key. Using the VasQ Forearm device is as simple as the upper arm procedure, with the same smooth and familiar handling.

VasQ Therefore, I am excited to see the great results of the upper arm confirmed in forearm access patients”, adds Christos Petridis, head of the Division of Vascular Surgery at Marienkrankenhaus Hamburg, Germany.

Developed by Laminate, VasQ is intended for patients with kidney failure in need of dialysis requiring vascular access through an AV fistula.

VasQ is an external scaffold placed over the fistula, creating an optimal geometric configuration with the artery and reducing the tension in the vein. This allows proper blood flow during dialysis while reducing vein blockage created by thickening of the vein wall. VasQ is a CE marked device already in use in hospitals in Europe and in Israel.

LUCY one-year results presented at VAM

One-year results from the LUCY (Evaluation of females who are underrepresented candidates for abdominal aortic aneurysm repair) registry were reported at the Society for Vascular Surgery Vascular Annual Meeting (VAM; 20–23 June, Boston, USA). The LUCY study is the first to prospectively evaluate endovascular aneurysm repair (EVAR) outcomes in women who have more complex aortic anatomy and, subsequently, have worse reported outcomes than men undergoing EVAR. The LUCY one-year data expand on the 30-day results presented last year, showing that at least 28% more women are eligible for minimally-invasive EVAR when using the Ovation Abdominal Stent Graft System (Endologix) than when using other EVAR systems.

The LUCY study is a prospective, consecutively enrolling, non-randomised, multicentre, post-market registry evaluating the Ovation System for the endovascular treatment of abdominal aortic aneurysms (AAA) in women. The

Ovation graft and delivery system

53

study enrolled a total of 225 patients, including 76 females in the treatment group and 149 males in the control group, at 39 sites in the USA. The primary endpoint of the study was the 30-day major adverse event rate and secondary endpoints included serious and non-serious adverse events through one year.

The one-year LUCY data showed that, despite having more complex anatomy at the time of the index procedure than men, women had similar outcomes to men following treatment with the ultralow profile (14F) Ovation device: Freedom from AAA-related morality: 100% in women vs. 98.6% in men Freedom from reintervention for Type 1a endoleak: 98.6% in women vs. 97.9% in men Freedom from rupture: 100% in both women and men Freedom from conversion: 100% in both women and men Freedom from all device-related reintervention: 97.2% in both women and men

DETOUR I 12-month data show promising durability of bypass system

Results from the DETOUR I trial evaluating the DETOUR System (PQ Bypass) for percutaneous bypassshowed promising 12-month durability for patients with extremely long blockages in the superficial femoral artery.

The data were presented at the Society for Vascular Surgery Vascular Annual Meeting (VAM; 20–23 June, Boston, USA).

The trial enrolled lesions longer and more complex than those typically studied in superficial femoral artery clinical trials, with an average lesion length of 37cm, 100% TASC II C/D, 96% chronic total occlusions (CTO), and 81% with moderate-to-severe calcification.

The DETOUR I trial, a prospective, single-arm, multicentre, core lab-adjudicated study, enrolled and treated 77 patients and 81 lesions. Primary and primary-assisted patency at 12 months in all lesions of the DETOUR I trial was 73% and 80%, respectively.

Secondary patency was achieved in 94% of patients.

Additional safety and effectiveness outcomes include 100% freedom from amputation, 99% freedom from acute limb ischaemia, and Rutherford improvement of ≥2 classes in 90% of patients.

“The lesions treated in DETOUR I were more than just long, they were extremely long, completely blocked, and severely calcified,” said Dainis Krieviņš, vascular surgeon and director of the Institute of Research at Pauls Stradins Clinical University Hospital.

“Endovascular devices currently approved for use on these incredibly challenging lesions have surprisingly low durability in lesions that are half the size of the average DETOUR lesion and fail approximately 40% of the time by the 12-month milestone. This truly highlights the need for the minimally invasive DETOUR procedure for long, complex SFA lesions.”

Percutaneous femoropopliteal bypass (the DETOUR procedure) is an entirely new procedure enabled by the DETOUR System.

The DETOUR procedure creates a pathway with PQ Bypass’s proprietary stent grafts, originating in the SFA, travelling through the femoral vein, and ending in the popliteal artery, bypassing the diseased part of the artery. The stent grafts re-direct oxygen-rich blood around the blockage, restoring blood flow to the lower leg and foot of the patient.

VasQ

54

Sept

Issue

18 71

Section Name

ECIO 2019 European Conference on Interventional Oncology April 8-11 Amsterdam, Netherlands www.ecio.org

LEADERS IN ONCOLOGIC INTERVENTIONS Submit y abstractsour October 2 by 9!

C RSE

Cardiovascular and Interventional Radiological Society of Europe

Sept

Issue

18 71

Product news

Product News Gore moulding and occlusion balloon for endovascular aortic repair receives approval in the USA, Japan, and Europe

Gore has announced FDA 510(k) clearance, approval from the Japanese Ministry of Health, Labour, and Welfare, and receipt of CE mark for the innovative Gore moulding and occlusion balloon, a compliant polyurethane balloon catheter designed in close collaboration with clinicians to assist in the expansion of self-expanding stent grafts or to temporarily occlude large-diameter vessels. The new device meets all endovascular aortic repair (EVAR) procedural requirements—a single balloon that replaces the need for multiple moulding and occlusion balloons.

The device’s proven radial expansion force across the range of EVAR device sizes enables physicians to consistently seat and seal grafts with confidence.

This more efficient graft seal may reduce procedural time and the risk of type I endoleaks. The device is also engineered with the lowest profile to reduce the potential of access-related complications, and its excellent pushability and trackability offers enhanced control with uncompromised inflation and deflation time.

“We have worked closely with clinicians to engineer a single balloon that truly changes both the physician and the patient experience,” said Eric Zacharias, Gore vascular business leader. “This milestone is one of several in our ongoing dedication to treating the entire aorta, and to helping physicians offer the best patient experience possible.”

The new device is supplied in a single catheter length of 90cm to enable use with current Gore Excluder devices as well as future Gore devices while still being compatible with a 180cm length guidewire.

Besides adding value through consistently reliable technical success and patient experience, the use of a single balloon allows for efficiency and inventory optimisation. “We know our physicians are concerned with both technical performance and with economic value to their practices,” Zacharias said. “Use of a single moulding and occlusion balloon during an EVAR case reduces intraoperative waste, minimising overall instrument cost per procedure. The potential to reduce operating room and catheter lab time may contribute to faster room turnover and more on-time procedural starts.”

IN.PACT Admiral DCB launched in Japan

Medtronic has announced the full commercial launch of the IN.PACT Admiral drug-coated balloon (DCB) in Japan. The launch follows the completion of a postmarket clinical trial, which enrolled 300 patients.

IN.PACT Admiral received approval last year from the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of peripheral arterial disease (PAD) in the superficial femoral arteries (SFA) and popliteal arteries. The MHLW also granted reimbursement approval for the IN.PACT Admiral in December of 2017.

“In Japan, there is a significant need for new technologies to safely and effectively treat PAD,” says Tony Semedo, president, Medtronic Japan. “Earlier this year, we presented both one- and two-year results from the IN.PACT SFA Japan study, representing consistency in clinical data shared on IN.PACT Admiral to-date. Now with the completion of our post-market study, we will become the first company to bring DCB IN.PACT

technology to Japanese physicians and their patients.”

Approval for IN.PACT Admiral in Japan was based on data from MDT-2113 (IN.PACT SFA Japan), which enrolled 100 patients across 11 sites and randomised treatment to either DCB (n=68) or standard percutaneous transluminal angioplasty (PTA) (n=32).

The results were consistent with one-year findings from the pivotal IN.PACT SFA Trial, showing a low clinically-driven target lesion revascularisation (CDTLR) rate and high patency rate.

IN.PACT SFA Japan demonstrated 93.9% primary patency in the DCB group as compared to 46.9% in the PTA group at one year based on Kaplan-Meier Estimate (p<0.001). Additionally, one-year results showed a CD-TLR rate of 2.9% for the DCB group compared to 18.8% in the PTA group (p=0.012). In IN.PACT SFA Japan, major adverse events were also lower for the DCB at one year (4.4% compared to 18.8% in the PTA group; p=0.028), with no major target limb amputations or all-cause death in both treatment groups.

Most recently, two-year data from IN.PACT SFA Japan were presented at the Leipzig Interventional Course (LINC; 30 January–2 February, Leipzig, Germany). Results were also consistent with two-year findings from the IN.PACT SFA Trial.

The IN.PACT Admiral drug-coated balloon has been approved in Japan to treat de novo and non-stented restenotic lesions with length <=200mm in superficial femoral and popliteal arteries with reference vessel diameters of >=4mm and <=7mm. The DCB’s primary mode of action is physical dilatation of the vessel lumen

by PTA, and the proven paclitaxel drug is intended to reduce restenosis.

First-ever CE mark of a bioresorbable scaffold for below-the-knee PAD

Motiv bioresorbable scaffold

Reva Medical, a company developing bioresorbable polymer technologies for vascular applications, has announced that its Motiv bioresorbable scaffold is the first drug-eluting bioresorbable scaffold to receive CE mark approval for treatment of below-the-knee peripheral artery disease.

Late last year, Reva announced its plans to expand use of its technology in peripheral artery disease. The approval of MOTIV delivers that milestone and for the first time brings bioresorbable technology to this patient population.

Motiv is made from Tyrocore, Reva’s proprietary polymer designed specifically for vascular scaffolds.

Tyrocore is inherently radiopaque, making Motiv visible under X-ray to ensure accurate placement in the artery.

The company will identify over the next few months select centres to assess the product’s performance, inform future product development activities and determine its complete commercial strategy in peripheral vascular applications. Reva expects Motiv’s first use in patients to be in late 2018 or early next year.

“Reva did not just achieve its own milestone with CE mark of Motiv, we achieved a therapeutic milestone for patients with critical limb ischaemia (CLI),” said Reggie Groves,

55

Reva’s CEO. “Tyrocore and our polymer technology have a broad range of therapeutic applications. This is our first step beyond the coronary arteries, and we look forward to bringing a new treatment option to peripheral artery disease patients and their physicians.”

The most common indication for patients receiving below-the-knee (BTK) revascularisation is CLI. If left untreated, CLI can progress to severe infection and amputation.

Research has shown that early-stage intervention is cost-effective and efficacious compared to late stage treatments like amputation. These interventions are intended to restore blood flow to the blocked artery in order to reduce pain and save the limb. Drugeluting bioresorbable scaffolds such as Motiv present a significant opportunity to improve the treatment of patients suffering from CLI because of the potential to extend drug delivery and to enable retreatment without the risks associated with metal stents.

FDA approves RADIANCE-II study of Paradise ultrasound denervation system

Paradise ultrasound

The RADIANCE-II study of the Paradise Ultrasound Denervation System (ReCor Medical) for the treatment of hypertension has been approved by the US Food and Drug Administration (FDA).

Building upon the recent positive results of the RADIANCE-HTN SOLO study, RADIANCE-II will be a randomised, sham-controlled, blinded study in patients with moderate hypertension, powered to demonstrate the safety and efficacy of the Paradise System’s ability to lower blood pressure. ReCor expects to initiate enrolment in RADIANCE-II in October of 2018.

“We have had a very constructive dialogue with the FDA during the past nine months to craft what we believe is a strong study to develop a robust set of clinical data to support the future FDA review for PMA approval,” comments Leslie Coleman, vice president of Regulatory & Medical Affairs. “At the time of PMA submission we plan to have four independentlypowered, blinded, sham-controlled, randomised studies of the Paradise System in patients with different stages of hypertension—our SOLO, TRIO, REQUIRE, and RADIANCE-II studies—approaching a total of nearly 500 patients, with outcomes as long as three years.”

“Our Steering Committee and medical advisors have been instrumental in the design of the Global RADIANCE Clinical Program—including the RADIANCE-II pivotal study—for the USA, Europe, Japan and Korea,” adds Helen Reeve-Stoffer, vice president of Clinical Affairs. “Given the recent positive SOLO results, and subsequently the numerous review articles in medical journals, we recognise the potential impact the Paradise System may have in the treatment of hypertension for millions of patients world-wide.

Accordingly, ReCor is committed to conduct rigorous, randomised, controlled studies to demonstrate the safety and efficacy of the Paradise System to lower blood pressure, thus helping physicians to evaluate how, in whom, and when to use Paradise for the treatment of hypertension.”

Paradise is an ultrasound-based system for endovascular denervation of the renal nerves. Renal denervation is a potential therapeutic option for treatment of hypertension, one of the most prevalent medical conditions. The Paradise System bears a CE mark but is not approved for sale in the USA. ReCor Medical is conducting the RADIANCE-HTN clinical trial under an IDE from the US FDA in the USA and Europe.

56

Section Name

Sept

Issue

18 71

Sept

Issue

18 71

Product News FDA approves Ellipsys Vascular Access System for non-surgical dialysis fistula creation

Ellipsys Vascular Access System (Avenu Medical) has been granted De Novo marketing authorisation from the Food and Drug Administration (FDA). Ellipsys is a minimallyinvasive catheter-based system designed for end-stage renal disease (ESRD) patients requiring haemodialysis.

“Good vascular access makes a tremendous difference in patient outcomes,” says long time kidney patient advocate Terry Litchfield. “This revolutionary nonImpede embolization plug gets US surgical fistula creation can reduce the pain and suffering FDAclearance associated with traditional fistula surgery, lessen failed Shape Memory Medical announced it has received 510(k) surgeries and reduce catheter time for patients.” clearance from the US Food and Drug Administration Since 1966, the AV fistula has been surgically created (FDA) for the Impede embolization plug. The device is in an operating room by sewing a vein and an artery indicated to obstruct or reduce the rate of blood flow in together, usually in the arm. When this is done, blood the peripheral vasculature. It is available in three sizes, to from the artery will pass through the vein increasing its treat vessels up to 10mm in diameter. flow rate and diameter. This makes the vein suitable for The Impede embolization plug received CE marking in the insertion of the needles required for haemodialysis August 2017 and has been used to treat patients in New treatment. An AV fistula is the preferred method for Zealand and in several countries in the European Union. vascular access as there is evidence of longer term Speaking about the device, Jafar Golzarian, patency, improved flow rates and fewer complications interventional radiologist with University of than other methods of vascular access.

Minnesota Health, Minnesota, USA, stated, “It is A new innovation for dialysis patients and clinicians, exciting to see the approval of new developments in Ellipsys is a less-invasive alternative to the traditional embolizationtechnology, offering physicians a new creation of AV fistulas and is designed to be used by a alternative to embolization coils.” physician under local or regional anaesthesia in all sites Commenting on this regulatory milestone and of service including hospital outpatient departments, ongoing clinical usage, Shape Memory Medical’s ambulatory surgical centres and physician offices. president and CEO, Ted Ruppel, said, “The Impede According to Avenu, ultrasound is used to guide embolization plug is an exciting development in the Ellipsys catheter through the skin to the preembolization technology, expanding the options open to determined vascular target. The catheter delivers a physicians treating conditions requiring occlusion of the small amount of thermal energy that fuses a sutureless peripheral vasculature.” and permanent anastomosis, or connection, between The devices feature proprietary Shape Memory the vein and artery allowing the creation of an AVF. Polymer (SMP) technology developed at Texas Unlike surgery, the Ellipsys System uses a minimally A&M University and Lawrence Livermore National invasive, endovascular approach that leaves the skin Laboratory. Shape Memory Medical was founded without a scar, and the vascular bed undisturbed and to commercialise stable, predictable embolization intact without leaving any foreign material implanted solutions for a variety of clinical applications. The SMP (including suture). After the procedure, the patient technology includes porous polymeric materials capable leaves with just a band aid. of changing from a catheter-deliverable shape to a Clearance was granted after the FDA reviewed “memorised” larger conformable shape when delivered data from a non-randomised, US multicentre study of into a blood vessel. The company continues to develop 103 patients. The study was designed to demonstrate SMP technology for an expanded range of clinical uses, the safety and efficacy of the Ellipsys System for the including neurovascular applications. percutaneous creation of an AV fistula.

With both internally developed and licensed “This approval marks a seismic shift for the patients technologies, Shape Memory has 26 issued US patents and physicians within the ESRD community. We can and multiple patents under review on a worldwide basis. now offer a faster, more efficient and less-invasive This intellectual property includes the use of SMP for a option for patients requiring vascular access here in the variety of clinical applications, a press release from the USA and worldwide,” says Mark Ritchart, president company states. of Avenu Medical. “For too long there has been a shortage of dedicated vascular surgeons who can create Terumo gets CE mark for Kanshas AV fistulas leading to delays in performing the surgery drug-coated balloon catheter for lower and requiring expensive, temporary catheter access. extremities Our Ellipsys System has the potential to significantly Terumo has announced receiving the CE mark for increase the number of clinicians performing vascular its Kanshas drug-coated balloon catheter used in the access procedures, thereby reducing these delays. treatment of lower extremity This, in turn, will result in reduced morbidity and the peripheral arterial disease. cost associated with temporary catheter access. In With a September launch short, it represents a quality of life improvement planned in Europe, Terumo opportunity for this patient community.” is expected to be the first “Using the Ellipsys Vascular Access System Japanese company to launch is very similar to common procedures such drug-coated balloon sales as obtaining venous and arterial access in Europe, and the European with ultrasound,” says Jeffrey E Hull, launch will be followed with director of the Richmond Vascular launches in Latin America and Center in Richmond, USA. “Most Asia, as well. physicians involved in vascular A drug-coated balloon catheter is a access have the endovascular skills Kanashas medical device coated with a drug that required and will learn to use the drug-coated suppresses cell proliferation on the balloon Ellipsys System quickly.” balloon catheter surface. When the balloon is expanded,

Market watch

57

it comes into contact with the blood vessel walls, transferring the drug to the vascular tissues, which is expected to suppress restenosis.

Early data on head-to-head comparisons of drugcoated balloons are beginning to emerge.

Kanshas can be expected to have an enhanced therapeutic effect due to Terumo’s proprietary uniform micro-crystal coating named Unicoat, which has been designed so that the coated drug is less likely to migrate before it reaches the lesion and then transfers swiftly to vascular tissue when the balloon is expanded. Product line-up of long balloon with a range up to 200mm can be treated for long lesions, which are common in the lower extremities.

Terumo is aiming to expand its peripheral vascular intervention business globally and is building up its product portfolio, a company release states. The launch of Kanshas is part of this strategy. Going forward, Terumo is determined to enhance its contribution to medical treatment in the endovascular field, the release adds.

Archimedes biodegradable biliary and pancreatic stent gets CE mark

Amg International, a wholly owned subsidiary of Q3 Medical Devices, announced that it has received CE mark approval for their novel biodegradable biliary and pancreatic stent technology, allowing the company to begin selling the product in Europe and other markets.

Archimedes is the only fully biodegradable biliary and pancreatic stent approved for placement in obstructed biliary or pancreatic ducts. While biliary and pancreatic duct stents are typically made of plastic or metal, the Archimedes stent is made of a combination of dissolving materials permitting different rates of degradation depending on the clinical indication.

The Archimedes stent is designed to completely degrade via hydrolysis in approximately 12 days, 20 days or 11 weeks, depending on its composition.

The stent is designed to maintain duct patency, without occlusion as it degrades, due to its patented design. It is intended as an option to avoid repeat procedures to remove traditional non-biodegradable plastic stents, avoiding adding additional cost of care and risk for patients.

“This CE mark approval is a major advancement in the treatment of obstructive biliary and pancreatic disorders and provides physicians such as myself, a truly innovative and advanced treatment option for my patients,” said Sundeep Lakhtakia of the Asian Institute of Gastroenterology in Hyderabad, India. “This is great news, as a fully biodegradable stent has the potential to reduce complication rates and procedural costs typically associated with biliary Archimedes and pancreatic biogradable biliary stenting,” and pancreatic stent noted Paul Yeaton, chief of Gastroenterology at the Carilion Clinic in Roanoke, USA. Eric K Mangiardi, CEO of Q3 said, “The Archimedes biodegradable stent represents a major breakthrough in the treatment of obstructive biliary and pancreatic disorders, and also in the field of biodegradable and bioresorbable materials and their application in medical devices moving forward.”

He added, “This technology has numerous benefits for patients, doctors, and healthcare providers as it has the potential to reduce complication rates typically associated with plastic stents and removal procedures.”

In a recent safety and efficacy clinical study, including 53 patients, conducted in India and Malaysia, the Archimedes stent showed zero stentrelated complications during the study period.

58

Sept

Issue

18 71

Events

Product News Sirtex prefers US$1.4 billion CDHCGP bid to Varian’s acquisition offer

Sirtex has announced entering into a binding scheme implementation deed with CDH Genetech (CDH) and China Grand Pharmaceuticals and Healthcare Holdings Limited (CGP). It has also announced the termination the Varian Scheme in relation to the proposed Sirtex acquisition.

Sirtex shareholders will be entitled to A$33.60 in cash for each Sirtex share held if the CDHCGPScheme is implemented. The Scheme Consideration represents a 20% premium to the Varian offerprice of A$28 per Sirtex share, an announcement from Sirtex states.

Background to the CDHCGP Sirtex acquisition bid On 30 January 2018, Sirtex announced it had entered into a binding Scheme Implementation Deed with Varian Medical Systems under which it was proposed that Varian acquire 100% of the shares

in Sirtexby way of a Scheme of Arrangement for A$28.00 per share.

Subsequently, on 4 May 2018, prior to the Varian Scheme Meeting to approve the Varian Scheme, Sirtexreceived an unsolicited nonbinding, indicative and conditional proposal from CDH Investments to acquire 100% of Sirtex for a cash price of A$33.60 per share. On 5 May 2018, Sirtex announced the adjournment of the Varian Scheme Meeting.

On 22 May 2018, Sirtex announced it had received an offer capable of acceptance from CDH for the acquisition of all of the shares in Sirtex by way of scheme of arrangement, including a draft scheme implementation deed.

On 14 June 2018, Sirtex announced the termination of the Varian Scheme and that it was entering into a binding scheme implementation deed with CDH and CGP. CDH Genetech is an entity wholly-owned by funds advised by CDH Investments.

The interim chairman of Sirtex, John Eady, said: “The Board has undertaken a comprehensive investigation of the merits and risks of the CDHCGP proposal, including seeking specialist advice in relation to specific regulatory, legal, funding and other risks. Based on the materially higher offer price and our evaluation of the associated risks, the Board of Sirtex has formed the unanimous view that the CDH-CGP proposal is a superior proposal and is in the best interests of shareholders.”

The CDH-CGP Scheme is subject to independent expert review on behalf of shareholders, shareholder approval, and regulatory and legal approvals.

An announcement from Sirtex notes that the Sirtex board unanimously recommended that Sirtexshareholders vote in favour of the CDHCGP scheme and intend to vote shares in their control in favour of the proposed CDH-CGP scheme, subject to Sirtex not receiving a superior proposal and the independent expert concluding that the CDH-CGP scheme is in the best interests of Sirtexshareholders.

On completion of the CDHCGP Scheme, Sirtex will be ultimately owned 51% by funds advised by CDH, and 49% by CGP, the announcement from Sirtex adds.

Calendar of events 14–16 September

ILCA 2018: The International Liver Cancer Association’s 12th Annual Conference London, UK

W www.ilca2028.org

22–25 September

CIRSE 2018: Cardiovascular and Interventional Radiological Society of Europe Lisbon, Portugal E info@cirse.org

W www.cirse.org

27–29 September

ACTiVE (Advanced Therapies in Venous Interventions) Chicago, USA www.sirweb.org

5−6 October

25−28 October

14−16 November

W http://imri2018.org

Canberra, Australia

Bournemouth, UK

24−27 October

W www.ranzcr2018.com

Interventional MRI (iMRI) Symposium 2018 Boston, USA

Southeastern Angiographic Society (SEAS) 2018 Abingdon, USA

W www.seas-web.org

25−26 October

RANZCR: Royal Australian and New Zealand College of Radiologists E ranzcr@encanta.com.au

1–4 November

Spectrum Miami, USA

W thespectrumconference.org

ESIR (European School of Interventional Radiology) course: Mastering Liquid Embolics

5–9 November

VIVA 2018: Vascular and Interventional Advances

BSIR 2018: British Society of Interventional Radiology Annual Meeting W www.bsir.org

8 December

EuroStream Comprehensive Prostatic Artery Embolization (PAE) Course Barcelona, Spain

W www.EuroSTREAMpae.com

2019

Las Vegas, USA

22–25 January

Zaragoza, Spain

W vivaphysicians.org

W www.cirse.org/esir2018

13–17 November

Leipzig, Germany

E office@esir.org

VEITHsymposium

LINC: Leipzig Interventional Course

26–30 January

ISET: International Symposium on Endovascular Therapy Hollywood, Florida, USA W www.iset.org

28–29 January

MIOLive 2019 (Mediterranean Interventional Oncology Live) Rome, Italy

W www.miolive.eu

21–24 February

APSCVIR: Asian Pacific Society of Cardiovascular and Interventional Radiology Bali, Indonesia

W www.apscvir2019.com

W www.linc2019.com

New York, USA

W www.veithsymposium.org

Interventional News is a trusted, independent source of news and opinion in the interventional world.

Sign up for a free print subscription* and e-newsletter subscription**

www.interventionalnews.com *Available for US and EU readers only ** Available worldwide