Bleomycin electrosclerotherapy (BEST) for the treatment of vascular malformations. An International Network for Sharing Practices on Electrochemotherapy (InspECT) study group report.

BACKGROUND: Biomedical applications of electroporation are expanding out of the field of oncology into vaccination, treatment of arrhythmias and now in the treatment of vascular malformations. Bleomycin is a widely used sclerosing agent in the treatment of various vascular malformations. The application of electric pulses in addition to bleomycin enhances the effectiveness of the drug, as demonstrated by electrochemotherapy, which utilizes bleomycin in the treatment of tumors. The same principle is used in bleomycin electrosclerotherapy (BEST). The approach seems to be effective in the treatment of low-flow (venous and lymphatic) and, potentially, even high-flow (arteriovenous) malformations. Although there are only a few published reports to date, the surgical community is interested, and an increasing number of centers are applying BEST in the treatment of vascular malformations. Within the International Network for Sharing Practices on Electrochemotherapy (InspECT) consortium, a dedicated working group has been constituted to develop standard operating procedures for BEST and foster clinical trials. CONCLUSIONS: By treatment standardization and successful completion of clinical trials demonstrating the effectiveness and safety of the approach, higher quality data and better clinical outcomes may be achieved.

Dialysis Access Maintenance: Plain Balloon Angioplasty.

Plain balloon angioplasty remains the first-line treatment for dialysis access stenosis. This chapter reviews the outcomes of plain balloon angioplasty from cohort studies and comparative studies. Angioplasty outcomes are more favourable in arteriovenous fistulae (AVF) compared to arteriovenous grafts (AVG) with primary patency at 6 months ranging from 42-63% compared to 27-61%, respectively, and improved for forearm fistulae compared with upper arm fistulae. Higher pressures are required to treat stenoses in AVFs compared to AVGs. Outcomes are worse in more severe stenoses, increased patient age, previous interventions and fistulae that develop early stenoses. Major complication rates following angioplasty in dialysis access are between 3 and 5%. Repeat treatments and the use of adjuncts such as drug-coated balloons and stents can prolong the patency of dialysis access. Level of Evidence No level of evidence (Review paper).

Lymphatic Intervention, the Frontline of Modern Lymphatic Medicine: Part I. History, Anatomy, Physiology, and Diagnostic Imaging of the Lymphatic System.

Recent advances in lymphatic imaging have provided novel insights into the lymphatic system. Interventional radiology has played a significant role in the development of lymphatic imaging techniques and modalities. Radiologists should be familiar with the basic physiology and anatomy of the lymphatic system to understand the imaging features of lymphatic disorders, which reflect their pathophysiology. This study comprehensively reviews the physiological and anatomical aspects of the human lymphatic system as well as the latest lymphatic imaging techniques.

Lymphatic Intervention, the Frontline of Modern Lymphatic Medicine: Part II. Classification and Treatment of the Lymphatic Disorders.

Lymphatic disorders encompass a broad spectrum of diseases involving the lymphatic system, ranging from traumatic lymphatic leaks to lymphatic malformations. Lymphatic disorders can be categorized into traumatic and non-traumatic disorders according to their etiology. These two categories may be further divided into subgroups depending on the anatomical location of the lymphatic pathology and their association with clinical syndromes. Thoracic duct embolization was a milestone in the field of lymphatic intervention that encouraged the application of percutaneous embolization techniques to treat leaks and reflux disorders in the lymphatic system. Additional access routes for embolization, including retrograde thoracic duct and transhepatic lymphatic access, have also been developed. This article comprehensively reviews a variety of options for the treatment of lymphatic disorders, from conservative management to the most recent embolization techniques.

Uterine artery embolisation: fertility, adenomyosis and size - what is the evidence?

BACKGROUND: Uterine artery embolisation is well established as a treatment for symptomatic fibroids, however, there remain some uncertainties. We have carried out a focused literature review on three particularly challenging aspects - post-procedure fertility, symptomatic adenomyosis and large volume fibroids and uteri, to enable operators to utilise evidence-based guidance in patient selection, consent, and management. REVIEW: Literature searches were performed of the PubMed/Medline, Google scholar, EMBASE and Cochrane databases. The outcomes of our analysis of studies which recorded fertility rates in women desiring pregnancy following UAE for symptomatic fibroids found an overall mean pregnancy rate of 39.4%, live birth rate of 69.2% and miscarriage rate of 22%. The major confounding factor was patient age with many studies including women over 40 years who already have lower fertility compared to younger cohorts. Miscarriage rates and pregnancy rates in the studies analysed were comparable to the age matched population. Treatment of pure adenomyosis and adenomyosis with co-existing uterine fibroids with UAE has been shown to produce symptomatic improvement with better outcomes in those with combined disease. Although the effectiveness is not as high as it is in pure fibroid disease, UAE provides a viable and safe alternative for patients seeking symptom relief and uterine preservation. Our analysis of studies assessing the outcomes of UAE in patients with large volume uteri and giant fibroids (> 10 cm) demonstrate no significant difference in major complication rates demonstrating that fibroid size should not be a contraindication to UAE. CONCLUSION: Our findings suggest uterine artery embolisation can be offered to women desiring pregnancy with fertility and miscarriage rates comparable to that of the age-matched general population. It is also an effective therapeutic option for symptomatic adenomyosis as well as for the treatment of large fibroids > 10 cm in diameter. Caution is advised in those with uterine volumes greater than 1000cm3. It is however clear that the quality of evidence needs to be improved on with an emphasis on well-designed randomised controlled trials addressing all three areas and the consistent use of validated quality of life questionnaires for outcome assessment to enable effective comparison of outcomes in different studies.

Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts.

BACKGROUND: Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, 'WILD syndrome' (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia), have previously depended on a single case report. METHODS AND RESULTS: We present 21 patients (including the first described case) with similar clinical and immunological phenotypes. All had PL affecting multiple segments, with systemic involvement (intestinal lymphangiectasia/pleural or pericardial effusions) in 70% (n=14/20). Most (n=20, 95%) had a distinctive cutaneous lymphovascular malformation on the upper anterior chest wall. Some (n=10, 48%) also had hyperpigmented lesions resembling epidermal naevi (but probably lymphatic in origin). Warts were common (n=17, 81%) and often refractory. In contrast to the previous case report, anogenital dysplasia was uncommon-only found in two further cases (total n=3, 14%). Low CD4 counts and CD4:CD8 ratios typified the syndrome (17 of 19, 89%), but monocyte counts were universally normal, unlike GATA2 deficiency. CONCLUSION: WILD syndrome is a previously unrecognised, underdiagnosed generalised PL syndrome. Based on this case series, we redefine WILD as 'Warts, Immunodeficiency, andLymphatic Dysplasia' and suggest specific diagnostic criteria. The essential criterion is congenital multisegmental PL in a 'mosaic' distribution. The major diagnostic features are recurrent warts, cutaneous lymphovascular malformations, systemic involvement (lymphatic dysplasia), genital swelling and CD4 lymphopaenia with normal monocyte counts. The absence of family history suggests a sporadic condition, and the random distribution of swelling implicates mosaic postzygotic mutation as the cause.

Image registration and subtraction in dynamic magnetic resonance lymphangiography (MRL) of the legs.

Dynamic contrast-enhanced magnetic resonance lymphangiography (DCE-MRL) is regularly reported as unable to depict lymphatic vessels in healthy limbs. In this study, we aim to improve lymph vessel conspicuity with appropriate registration and subtraction of a reference baseline image. Five unaffected individuals and a single unilateral primary lymphoedema patient were recruited to undergo fat suppressed 3D T 1 weighted spoiled gradient echo imaging of the lower limbs at 3.0 T. Images were quality assessed by two physicians and a medical physicist following registration via one of six registration pipelines, and subtraction of the first post-contrast dynamic image (PC1). Wilcoxon non-parametric testing was performed to compare image quality ranking vs the unregistered images and inter-rater reliability estimated using intraclass correlation coefficient. Signal enhancement curves were also computed in lymphatic vessels for two participants. Subtraction images were considered to improve lymphatic visibility, and three registration pipelines significantly (p < 0.05) outranked those without registration. Those registered to PC1 with an affine and elastic approach were rated best quality (p = 0.006). Moderate inter-rater reliability was observed (intraclass correlation coefficient = 0.71) and signal enhancement behaviour appears affected by registration when motion is evident across the DCE-MRL series. We therefore conclude that lymphatic vessel visibility in DCE-MRL images can be improved with registration and baseline subtraction.

Case Report: Progressive central conducting lymphatic abnormalities in the RASopathies. Two case reports, including successful treatment by MEK inhibition.

The RASopathies are a group of genetic conditions resulting from mutations within the RAS/mitogen-activated protein kinase (RAS-MAPK) pathway. Lymphatic abnormalities are commonly associated with these conditions, however central conducting lymphatic abnormalities (CCLA) have only recently been described. CCLAs may be progressive and can result in devastating systemic sequelae, such as recurrent chylothoraces, chylopericardium and chylous ascites which can cause significant morbidity and even mortality. Improvements in imaging modalities of the central lymphatics have enhanced our understanding of these complex abnormalities. Management is challenging and have mainly consisted of diuretics and invasive mechanical drainages. We describe two adult males with Noonan syndrome with a severe and progressive CCLA. In one patient we report the therapeutic role of targeted molecular therapy with the MEK inhibitor 'Trametinib', which has resulted in dramatic, and sustained, clinical improvement. The successful use of MEK inhibition highlights the importance of understanding the molecular cause of lymphatic abnormalities and utilising targeted therapies to improve quality of life and potentially life expectancy.

Outcome of endovascular treatment of internal iliac artery aneurysms: a single center retrospective review.

PURPOSE: To evaluate the technical feasibility and clinical outcomes of endovascular treatment for internal iliac artery (IIA) aneurysms. MATERIAL AND METHODS: This was a retrospective analysis of 25 patients with 32 IIA aneurysms (mean diameter: 39.1 ± 12.6 mm) who underwent endovascular treatment over a 10-year period, and were available for follow-up. Univariate analysis was used to determine the association between variables (including aortoiliac involvement and technique) and outcome. RESULTS: The IIA inflow was covered with an iliac stent graft (N = 29) or embolized with a plug (N = 3). The IIA outflow was embolized in all but one case in which there was thrombotic occlusion of outflow branches. Outflow embolization using plugs or coils was performed in the distal IIA or anterior/posterior trunks in 9 cases and distal IIA branches in 22 cases. During a mean follow-up period of 39.9 months, 31.2% of aneurysms demonstrated endoleak and 12.5% demonstrated enlargement. Univariate analysis revealed that endoleak was associated with technical failure (p = 0.01) and that endoleak rate was higher in patients who underwent distal IIA branch embolization (p = 0.03). No variable was associated with sac expansion. Major complication occurred in one patient who died from aneurysm rupture. Minor complications were reported in six patients who developed femoral pseudoaneurysm (N = 2, 8%), buttock claudication (N = 3, 12%), and limb graft occlusion (N = 1, 4%). CONCLUSION: Endovascular treatment of IIA aneurysms effectively prevents sac expansion. Endoleak was more frequently observed in cases of technical failure and those in which distal IIA branches were embolized. LEVEL OF EVIDENCE: Level 3b, retrospective cohort study.

Randomised Controlled Trial of Particles Used in Uterine fibRoid Embolisation (PURE): Non-Spherical Polyvinyl Alcohol Versus Calibrated Microspheres.

PURPOSE: The PURE study is a randomised controlled trial (RCT) comparing the clinical and MRI outcomes of patients treated with non-spherical polyvinyl alcohol, ns-PVA (Contour PVA-Boston Scientific-355-500 & 500-700 microns) versus calibrated hydrogel microspheres (Embozene-Varian Inc-700 & 900 microns) for symptomatic uterine fibroids. MATERIALS AND METHODS: Prospective, ethically approved non-sponsored RCT in 84 patients in a single UK tertiary IR unit, ISRCTN registry trial number ISRCTN18191539 in 2013 and 2014. All patients with symptomatic fibroid disease were eligible. UAE followed a standardised protocol with UFS-QOL and contrast-enhanced MRI before and 6 months post UAE. Outcome measures included: (1) Uterine Fibroid Symptom and Quality of Life questionnaire (UFS-QOL). (2) Percentage total and dominant fibroid infarction. (3) Uterine and dominant fibroid volume reduction. (4) Volume of embolics. RESULTS: Sixty-three patients completed the QOL follow-up (33 ns-PVA vs 30 Embozenes), the groups were equivalent at baseline. Patients were followed up for 6 months following UAE. There was no significant difference in symptom scores or HR-QOL between ns-PVA and Embozenes, p = 0.67 and 0.21, respectively. 92.7% of patients treated with ns-PVA achieved > 90% dominant fibroid infarction versus 61.8% treated with Embozenes (p = 0.0016). 66% of patients treated with ns = PVA achieved > 90% total fibroid percentage infarction compared with 35% in the Embozene group (p = 0.011). The mean vials/syringes used were 5.2 with Embozenes versus 4.1 using PVA (p = 0.08). CONCLUSION: The PURE study informs IRs regarding the efficacy of embolic agents in UAE, with superior fibroid infarction on MRI using ns-PVA versus Embozenes however no significant difference in clinical outcomes at 6 months after UAE.

Clinical experience with a shape memory polymer peripheral vascular embolisation plug: a case series.

BACKGROUND: Shape memory polymers are materials that are manufactured in a certain shape, can be stored in a temporary deformed shape, and then return to - or remember - their original shape upon exposure to external stimuli such as temperature and moisture. This property lends itself to application in endovascular medical devices. Peripheral vasculature embolisation devices incorporating this novel technology have become commercially available and this case series, where the data were collected as part of a post market registry, outlines initial clinical experience with these novel devices. RESULTS: Eight cases are described in this series. The disease state/conditions for which embolisation was indicated were right common iliac artery aneurysms (n = 3), a type II endoleak into the thoracic aorta following thoracic endovascular aneurysm repair (n = 1), a left inferior gluteal artery aneurysm (n = 1), left internal iliac artery aneurysms (n = 2), and a case of splenomegaly, where splenectomy was planned after the embolisation procedure (n = 1). Target arteries were 5-10 mm in diameter. In each case, at least one IMPEDE Embolization Plug (IMP-Device) of an appropriate diameter was used. All procedures were technically successful and target vessel thrombosis was achieved in all cases. Follow-up imaging available during the 45-90-day data collection timeframe showed sustained vessel occlusion. This case series includes examples of situations commonly encountered when embolising the peripheral vasculature, namely, the use of one or multiple devices in a single vessel and in combination with the use of other embolic devices (e.g., microcoils, gelatin sponge, and PVA particles) in the same case. There were no adverse events related to the specific use of the device. CONCLUSIONS: This small series illustrates the safety and efficacy of this novel sponge-based embolic device for the embolisation of small and medium sized arteries and further experience will demonstrate the utility of the shape memory polymer devices.

Role of interventional radiology in placenta accreta spectrum (PAS) disorders.

Placenta accreta spectrum (PAS) disorders are rare but potentially life-threatening obstetric conditions, which can result in severe post-partum haemorrhage (PPH). Traditional management necessitates peripartum hysterectomy, but this carries high rates of morbidity and mortality. More recently, interventional radiology techniques have been developed in order to reduce morbidity and preserve fertility. This article summarises and compares the various reported interventional radiology techniques. Arterial embolisation performed to treat PPH is the therapeutic option which is supported by the highest degree of evidence. The role of preventative procedures, such as temporary balloon occlusion of the internal iliac arteries or distal aorta, continues to be debated due to conflicting outcome data and concerns regarding associated morbidity. The choice of which, if any, interventional radiological technique is utilised is determined by local expertise, available resources and the planned obstetric approach. The most complex patients are likely to benefit from multidisciplinary management in high-volume centres.

Predicting the Fibroid-Migratory Impact of UAE: Role of Pre-embolization MRI Characteristics.

AIM: To investigate potential factors on MR imaging that could be used to predict migration of uterine fibroids post-UAE. METHODS AND MATERIALS: We retrospectively reviewed patients referred for UAE having pre-procedural and 6 months post-procedural MRI, at a tertiary centre, over a 1-year period. Pre- and post-UAE images were reviewed in 64 women by two radiologists to identify the sub-type, dimensions, and infarction rate of each dominant fibroid. The shortest distance between the fibroid and the endometrial wall was measured to determine intramural fibroid movement. Paired sample T tests and two-sample T tests were used to compare between pre- and post-embolization variations and between migrated and non-migrated intramural fibroids, respectively. After preliminary results suggested potential predictors of intramural fibroids migration, we tested our findings against the non-dominant intramural fibroids in the same patients. RESULTS: Review of images revealed 35 dominant intramural fibroids, of which eight migrated to become submucosal fibroids, while five were either partially or completely expelled. These 13 migrated fibroids had a shorter pre-procedural minimum endometrial distance (range 1-2.4 mm) and greater maximum fibroid diameter (range 5.1-18.1 cm), when compared to non-migrating fibroids. On image reassessment, the migrated non-dominant intramural fibroids had a minimum endometrial distance and maximum fibroid diameter within the same range. CONCLUSION: Intramural fibroids with a minimum endometrial distance less than 2.4 mm and a maximum fibroid diameter greater than 5.1 cm have a high likelihood of migrating towards the endometrial cavity after UAE.

Management of acute and chronic iliofemoral venous outflow obstruction: a multidisciplinary team consensus.

The aim of this manuscript was to establish a consensus for the management of acute and chronic venous obstruction among specialists in the UK. Specialist physicians representing vascular surgery, interventional radiology and hematology were invited to 3 meetings to discuss management of acute and chronic iliofemoral obstruction. The meetings outlined controversial areas, included a topic-by-topic review; and on completion reached a consensus when greater than 80% agreement was reached on each topic. Physicians from 19 UK hospitals agreed on treatment protocols and highlighted areas that need development. Potential standard treatment algorithms were created. It was decided to establish a national registry of venous patients led by representatives from the treating multidisciplinary teams. Technical improvements have facilitated invasive treatment of patients with acute and chronic venous obstruction; however, the evidence guiding treatment is weak. Treatment should be conducted in centers with multi-disciplinary input; robust, coordinated data collection; and regular outcome analysis to ensure safe and effective treatment and a basis for future evolvement.

Are complication rates lower with 4-Fr versus 6-Fr transfemoral arterial access - prospective audit at a single interventional radiology centre.

BACKGROUND: Femoral arterial access constitutes the first step in a significant proportion of interventional endovascular procedures. Whilst existing reports describe sheath size as an independent risk factor for bleeding complications in radial arterial access for coronary intervention, the influence of sheath size on overall complication rates and morbidity following femoral arterial access is not well described. This prospective single centre study reports our experience of vascular sheath size, patient and procedural factors in influencing complication rates following femoral arterial access. From April 2010 to May 2013, data was collected prospectively for all femoral arterial access procedures performed in the Interventional Radiology department of a tertiary hospital. For vascular sheath size <6-Fr, haemostasis was achieved by manual compression. For 6-Fr sheath size, a closure device was used in the absence of any contraindication. RESULTS: Of the 320 femoral access cases with eligible inclusion criteria, 52.5% had 4-Fr whilst 47.5% had 6-Fr vascular sheaths inserted. Overall post procedure complications rates were significantly higher following 6-Fr sheath (17/152 (11.2%)) versus 4-Fr systems (3/168 (1.8%)) (p=0.0007) mostly comprising self-limiting hematoma. There was no significant difference in major complications that required escalation of treatment. CONCLUSION: No significant difference has been demonstrated between the use of either sheath systems for major complications. The practical limitations of a smaller system, combined with existing body of evidence, may not justify the routine use of 4-Fr sheath systems as the primary sheath size for all endovascular procedures.

Embolization of the internal iliac artery before EVAR: is it effective? Is it safe? Which technique should be used?

PURPOSE: To assess the clinical outcomes of internal iliac artery (IIA) embolization before endovascular aneurysm repair (EVAR). METHODS: Between 2002 and 2011, 88 patients underwent IIA embolization prior to EVAR. Sixty-five patients underwent unilateral and 23 underwent bilateral IIA embolization. A total of 111 IIAs were embolized: 56 were embolized with coils, 41 with Amplatzer plugs, and 14 with a combination of embolic agents. The outcomes were assessed retrospectively by reviewing medical records and follow-up imaging. RESULTS: IIA embolization was technically successful in 95.7% of cases. Type 2 endoleak from previously embolized IIAs was seen in 4 cases, and in 1 case this was significant necessitating re-intervention. Buttock claudication was reported in 38% of cases, whereas new onset erectile dysfunction occurred in 10% of cases. No severe ischemic complications, such as spinal cord ischaemia or buttock necrosis, were reported. Analysis comparing unilateral versus bilateral embolization, simultaneous versus sequential embolization, and the type of embolic material used showed no statistical significance. CONCLUSION: IIA embolization is technically successful and effective in preventing significant type 2 endoleak in the majority of cases. It is a relatively safe procedure without major complications, but the incidence of buttock claudication and erectile dysfunction remain relatively high, and patients should be consented appropriately. There is no significant benefit for adopting a particular embolization technique, but there is a tendency towards reduced pelvic ischaemia with proximal embolization. Four cases of type II endoleak occurring after technically successful IIA embolization supports the school of thought that IIA should be embolized prior to coverage and extension of the distal landing zone.