IMAGING

Image-Guided Percutaneous Injection Sclerotherapyof Venous Malformations

Subhash Kumar1 & Kranti Bhavana2 & Amit Kumar Sinha3 & Sanjeev Kumar4 & Arun Prasad5& Bhartendu Bharti2 &

Pranav Kumar Santhalia6

Accepted: 13 July 2020# Springer Nature Switzerland AG 2020

AbstractVenous malformations (VM) are the commonest types of vascular malformations, with an appropriate clinico-radiologicaldiagnostic pathway being critical for establishing the correct diagnosis, mapping the extent of disease and involvement ofimportant structures, guiding appropriate therapy, and predicting prognosis.

Ultrasound (US) with color Doppler examination is the first-line radiological investigation with magnetic resonance imagingbeing used for further evaluation, providing the exact lesion extent and involvement of muscles, bones, and neurovascularbundles. Direct puncture phlebography of the lesion confirms the diagnosis and classifies the lesion in four types. Type 1 isan isolated malformation without peripheral drainage, type 2 malformation drains into normal veins, type 3 malformation drainsinto dilated veins, and type 4 malformation represents dysplastic venous ectasia. Treatment is sought for cosmetic reasons, pain,and functional issues.

Sclerotherapy is the first-line treatment and image guidance, either US or phlebographic, is employed for the same. Varioustechniques are described including double or multiple puncture technique, subtraction-guided technique, filling defect technique,or a combination of these. Various sclerosants have been used including dry ethanol, polidocanol, ethanolamine oleate, sodiumtetradecyl sulfate, sodium morrhuate, OKC 432, bleomycin, and doxycycline, either in liquid form or as microfoam preparedusing Tessari’s technique. Typically, multiple sessions are needed and the lesions may recur; however, overall response rate,quality of life improvement, and patient satisfaction are significantly improved.

Local complications like pain, swelling, and ulcerations are common. Major complications of sclerotherapy are infrequent;however, pulmonary embolism, stroke, vision loss, compartment syndrome, tissue necrosis, hemolysis, anaphylaxis, nerve palsy,and pulmonary complications do occur and the patient and treating physicians should be aware of.

Keywords Sclerotherapy . Magnetic resonance imaging . Ultrasound . Venous malformation . Polidocanol . Sodium tetradecylsulfate . Alcohol . Phlebography . Image-guidance

This article is part of the Topical Collection on Imaging

Electronic supplementary material The online version of this article(https://doi.org/10.1007/s42399-020-00412-y) contains supplementarymaterial, which is available to authorized users.

* Subhash Kumardrsubhash.dm@gmail.com

1 Department of Radiodiagnosis, All India Institute of MedicalSciences Patna, Phulwarisharif, Patna, Bihar 801507, India

2 Department of ENT, All India Institute of Medical Sciences Patna,Phulwarisharif, Patna 801507, Bihar, India

3 Department of Pediatric Surgery, All India Institute of MedicalSciences Patna, Phulwarisharif, Patna 801507, Bihar, India

4 Department of CTVS, All India Institute of Medical Sciences Patna,Phulwarisharif, Patna 801507, Bihar, India

5 Department of Pediatrics (T&E), All India Institute of MedicalSciences Patna, Phulwarisharif, Patna 801507, Bihar, India

6 Department of Radiodiagnosis, Nalanda Medical College andHospital, Mahatma Gandhi Nagar, Patna 800026, Bihar, India

https://doi.org/10.1007/s42399-020-00412-y

/ Published online: 5 August 2020

SN Comprehensive Clinical Medicine (2020) 2:1462–1490

Introduction

Venous malformations (VMs) are the commonest type of con-genital vascular malformations (CVMs), present since birth,and growing proportionately with the development of thechild [1]. They have been reported to be constituting from44 to 46% [2], to approximately 70% of all CVMs, i.e., ap-proximately 1% prevalence in the general population [3].

VMs are readily diagnosed based on the clinico-radiologicprofile [4, 5]. A variety of treatment strategies have beenadopted, including conservative management, surgery, abla-tive therapies, and percutaneous injection sclerotherapy (PIS)[6]. Interventional radiology techniques are now at the fore-front of the management of VMs and surgery being opted inselect conditions [7, 8] (Table 1).

Subsequent to the seminal work of Mulliken andGlowacki in 1982, differentiating the vascular anomalies(VAs) into tumors and malformations [12], various otherschemes have been proposed, most notable being thoseof Jackson et al. [13], the Hamburg classification [14],and the ISSVA classification, the latter being widely ac-cepted and currently used [15]. A variety of radiologicalclassification schemes have been described, importantones being shown in Table 2, which serve as a meansto offer suitable treatment, and possibly predict the ther-apeutic response and prognosis.

Clinical features, pathology, genetic abnormalities and ra-diological findings of VMs are summarized in Table 3.

The Sclerosants

PIS refers to the injection of a sclerosant drug into the desiredstructure to cause endothelial destruction and the obliterationof the contained spaces [1, 2, 4–7] (Table 4).

Sclerosants induce a controlled inflammatory response af-ter the endothelial cell death and thrombosis, with the resultantfibroblast proliferation leading to lumen obliteration and ves-sel sclerosis [42].

PIS and embolization are on a continuum, some agents likehypertonic saline being a true sclerosant, and some agents likegelatin foam or polyvinyl alcohol (PVA) being true embolicagents [40–43]. Agents such as Ethibloc, absolute ethanol,ethanol gel (Sclerogel), and N-butyl-2-cyanoacrylate(nBCA) have both sclerosing and embolic characters.

In VMs, PIS will always produce a component of throm-bosis (Fig. 7), via initiation of the intrinsic blood coagulationpathway, due to damage to the endothelium, and [39] exces-sive thrombosis is undesirable as it leads to recanalization aswell as significant inflammation and its resulting sequelae.

Ethanol

Dehydrated ethanol, first used by Sasaki and Yakes for vas-cular indications [42], is the most potent sclerosant, widelyused [42, 44], and acts by a combination of denaturation andextraction of surface proteins, hypertonic dehydration, andthrombosis, ultimately leading to fibrinoid necrosis.

Table 1 Indications andcontraindications of invasivetreatment of venousmalformations

Indications [9] Relative contraindications and risk factors [10, 11]

Disabling pain not responding to conservativemanagement

Functional impairment affecting daily activity orquality of life

Excessive cosmetic implications and/or psychologi-cal disability with poor quality of life

Deformities involving the bony structures

Recurrent infection/sepsis

Recurrent thrombosis

Lesions causing excessively adverse hemodynamiceffects

Hemorrhagic complications: subcutaneous,intramuscular or retroperitoneal hematoma,visceral bleeding, hematuria, bleeding per-rectum,hematemesis, hemoptysis, intracerebral orintraspinal hemorrhage

Lesions within or near important structures

Lesions obstructing inflow and outflow of importantstructures

Lesions in life-threatening areas or in areas with highprobabilities of complications

The proximity of the vascular lesion to major nervetrunks, especially in the presence of preexistingneuropathy

Lesions involving or near the airway or orbit

Extensive cutaneous involvement

VM involving the deep veins of the lower extremities

Severe consumption coagulopathy

Patent foramen ovale

Chronic pulmonary thromboembolism withdecreased reserve

Known allergies to the sclerosants

Acute deep vein thrombosis or pulmonary embolism

Local infection in the area of sclerotherapy or a severegeneralized infection

Prolonged immobility or bed rest

Pregnancy, breast-feeding

Severe peripheral arterial occlusive disease

Poor general health

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Table 2 Radiological classification schemes of venous malformations

Radiologicaltool

Direct puncture phlebography Magnetic resonanceimaging

Ultrasound

Author Puig et al. [16] Goyal et al. [17] Kumar et al. [18]

Classification Type 1: isolated malformation without peripheraldrainage

Type 2: malformation that drains into normal veinsType 3: malformation that drains into dilated veinsType 4: malformation that represents dysplastic venous

ectasia.

Grade 1: well defined,≤ 5 cm

Grade 2A: welldefined, > 5 cm

Grade 2B: Ill-defined,≤ 5 cm

Grade 3: Ill-defined,> 5 cm

Type 1: well-defined predominantly echogenic orhypoechoic mass, partially or poorlycompressible, without visible connection to ad-jacent veins

Type 2: well-defined mixed echogenicity lesionwith up to 50% anechoic spaces and partiallycompressible without or with few connections toadjacent veins

Type 3: mainly anechoic lesions with tubular orserpentine channels and/or anechoic spaces withor without connections to normal or dilated adja-cent venous system

Type 4: totally diffuse or dysmorphic lesion with orwithout direct connections to adjacent veins.

Table 3 Clinical, pathological, genetic, and radiological characteristics of venous malformations

Relative prevalence Estimated incidence of approximately 1/5000–1/10000 live births; commonest of the CVMs (44–46%, up to 70%),followed by LMs (12%), AVMs (8%), combined malformation syndromes (6%), and CMs (4%) [1, 3, 19, 20].

Morphology Extremely diverse appearance [19] (Fig. 1); extremely variable number and size, mostly soft, partially compressible(Video 1), non-pulsatile, soft tissue masses with normal surface temperature [20]. Shape and size can change withposition or muscle tightening [21]. Smooth rounded phleboliths may be palpable [19, 20]. Some lesions can be firmand tender [19, 20].

Distribution Head and neck (40%), extremities (40%), and trunk (20%); all anatomical site can be involved [19, 20]; most lesions aresporadic and unifocal (93%), multifocal sporadic lesions form about 1% and inherited lesions constitute the rest(cutaneomucosal VM, 1%, and glomuvenous malformations (GVMs), 5%) [22].

Lesion growth Proportionate to patient’s growth; periods of sudden enlargement related to hormonal influences during puberty,pregnancy or oral contraceptive usage; sudden enlargement after trauma, thrombosis or viral infection (more in LMs);decreased size possibly due to ongoing spontaneous thrombosis; however, complete spontaneous resolution almostnever occurs.

Symptoms Related to size and location, mostly presenting with cosmetic concerns, doubt of a neoplastic mass, pain, or deformity.Pathology Thin-walled, variable-sized, dilated, sponge-like channels, with sparse smooth muscle cells (SMCs), adventitial fibrosis,

possessing a flat single layer of endothelium without endothelial hyperplasia [23]; continuous cycle of spontaneousthrombosis and thrombolysis leading to phlebolith formation (Fig. 2) [24]; large lesions associated with local intra-vascular coagulation abnormalities, which can get converted a systemic disseminated intravascular coagulationabnormality (DIC) by a variety of precipitating events, including sclerotherapy, surgery, fracture, prolongedimmobilization, pregnancy or menstruation, with subsequent hemorrhage and multi-organ failure [25].

Genetic abnormalities Mostly sporadic; familial dominant inheritance pattern tied to the chromosome 9p21 (TIE2/TEK gene) [26]; about 50%of sporadic VMs also have the TIE2 somatic mutations [27]; GVMs are autosomal dominant, tied to glomulin(GLMN/FAP68) gene on the chromosome 1p21–22 [28]

Radiography Shows phleboliths, if present, and associated dystrophic calcification and osseous or joint changes, includinghypoplasia, cortical thinning, demineralization, osteolysis, and, rarely, an organized periosteal reaction [29, 30].

Ultrasound (US) and color Doppler(CD) examination

First-line and essential investigation; differentiates various types of VAs and provides flow information [1, 29, 31],assesses the morphological characteristics (Fig. 3), and estimates the extent of anechoic spaces; lesion appearhypoechoic or heterogeneously hypoechoic lesions (80%) [1]; appearance reflecting the varying amount of the fattycomponent, degenerated muscle, connective tissue matrix, thrombus, micro- vs macrovascular spaces and channels[31–33]; anechoic channels seen in less than half of the cases [34]; phleboliths seen in about 20% of cases [1, 32]

CD differentiates VMs from other VAs [1, 32], showing no flow (16%) or monophasic, low-velocity venous flow (84%)cases [20, 32]; occasional arterial vessels can be seen within the lesion (Fig. 4); US guides PIS procedure, in locatingappropriate puncture site and monitoring the spread of foam.

Computed tomography (CT) Lesion appears as hypodense masses and definition is less than US or MRI [1], but can be used in multi-compartmentallesions or when CT angiography is needed (Fig. 5).

MR imaging and MR angiography(MRA)

MRI with MRA is almost always required in evaluation [1, 4, 5, 19, 20, 29, 35], defining the lesion and involvement ofother structures [1, 35, 36], (Video 2) lesions appearing as T2 hyperintense masses, (Fig. 6) with heterogeneous,nodular, peripheral, or progressive centripetal enhancement, as well as predicting outcomes [17].

After sclerotherapy, VMs become heterogenous [1, 35], with increased perilesional T2 hyperintensity which can last upto 3 months [36, 37]; subsequently fibrosis appearing as a hypointense signal along with the progressive shrinkage ofthe VMs.

MRI, however, is not very specific and other vascular malformations and tumors can mimic it, and correlation withclinical findings and US is essential in most cases [38].

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Ethanol’s dose is recommended to be kept below 1 mL/kgper session, and the pediatric dose is usually kept less than0.5 mL/kg per session [45, 46]. Rapid injections produce moreendothelial damage and parenchymal necrosis with lessthrombosis while slower injections produce more thrombosis,but less endothelial damage and necrosis [46].

Increasing the “dwell time” of ethanol, e.g., for 10 to12 min, by adding ethyl cellulose [47, 48], or corn starchZein (Ethibloc) [4, 5], or by using in jellified form (ethanolgel) [49], can increase thrombosis and necrosis; however,prolonged contact can also lead to fistulization and adjacenttissue damage despite lesser deep penetration [45].

Patients receiving up to this maximum limit of ethanol mayreach legal intoxication limits, and have a risk of respiratorydepression, cardiac arrhythmias, seizures, rhabdomyolysis, andhypoglycemia [50], even though mortality is not common, e.g.,

0.6% in a series of AVM embolizations by Yakes et al. [42, 51].Chapot et al. have suggested that ethanol can migrate as a bolus,decreasing the fatal dose below 1 mL/kg, which is a calculationbased upon dilution in total free body water [52]. A dose-dependent acute pulmonary hypertension (PHT) and vasospasminduction can occur [53–56], and so can bronchospasm [55].Bisdorrf et al. have recommended maximum of 0.2 mL/kg eth-anol to be the accepted dose per session [56].

Detergent Sclerosants

Detergent sclerosants (DSs) disrupt cellular membranethrough the mechanism of “protein theft denaturation” by al-tering the surface tension around the surface proteins via in-terference with cell surface lipids (surfactant action) [11, 39,40]. Endothelial damage occurs within the first few seconds of

Fig. 1 Diverse clinical presentations of venous malformations. a Largefacial lesion in a 6-year-old. b Small globular bluish superficial mass atthe edge of tongue. c Multifocal lesion involving a limb and parts of thetrunk. d Barely visible tissue thickening presenting as left cheek

prominence. e Soft, large, boggy swelling of the cheek. f Large bluishswelling involving most of the tongue, note the tracheostomy in situ, toprevent respiratory complications

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the injection of DSs itself [57]. Commonly used DSs includesodium morrhuate (SM), ethanolamine oleate (EO), sodiumtetradecyl sulfate (STS), and polidocanol (POL)(lauromacrogol 400, laureth-9) [40–42].

General details of DSs are detailed in Table 5.DSs are classically used as microfoam, which gives better

results [66], by prolonging the contact time with endotheliumand allowing for dose reduction, first described in 1950 [80],and becoming popular from the mid-1990s [81]. The currentrecommended method was proposed in 2000 by Tessari [82](Video 3).

Antibiotic Agents

OK-432

It is an immunostimulant and antineoplastic drug, usedprimarily in sclerotherapy of LMs, in a dose not exceeding

0.2 mg of OK-432 per single injection [83]. Noperilesional fibrosis is produced; thus, subsequent surgicalresection is not hampered. It is, however, not readily avail-able commercially.

Bleomycin

Bleomycin has three commonly used forms A2, B2, and A5,activating the mTOR pathway to produce a unique G2-phasecell cycle–specific endothelial cytotoxicity [84], with successrate varying from 30 to 95% in reports [85–88], and excellentsize reduction seen in 87% cases in a meta-analysis [89].Response was found about 30% lower than ethanol byZhang et al [90].

The dose is limited to 0.5 U/kg or up to 15 U per session [88,91], with total lifetime dose limited to 5 U/kg body weight or amaximum of 400 U. The most dreaded complication is pulmo-nary fibrosis; however, due to the presumed local concentration

Fig. 2 A 9-year-old girl with venous malformation of the floor of mouth.a clinical photograph. bUS at presentation showing typical appearance ofvenous malformation with about 50% anechoic area. c US-guided foamsclerotherapy image showing the hyperechoic reflections of foam; the

patient was lost to follow up for a year. d US. e Coronal T2W fat-sup-pressed. f Sagittal STIR MR image, showing multiple phleboliths at sub-sequent presentation

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of the drug, it has not been reported with PIS. Acute dose-dependent pulmonary toxicity has been reported rarely [92].Reported complication rates in the literature range from 8.4 to14.7% [88, 93]. As it produces only minimal swelling aftersclerotherapy, it is especially recommended for vulnerable areas

such as the periorbital region, tongue, and parapharyngeal spaces[88, 94]. It can be injected in aqueous form or as foam [94].

Pingyangmycin, which is bleomycin A5, is particularlyused in China, with an overall response of > 95% and a com-plete response varying from 46 to 100%; the prevalence of

Fig. 3 Varying US appearances in venous malformations. a Poorlymarginated lesion with heterogeneous appearance (star). b Well-marginated lesion in tongue examined from submental region, showinga relatively homogenous hypoechoic mass (star). c A relatively margin-ated lesion in handwith irregular central anechoic channels and peripheralsoft tissue. d A deep-seated lesion in thigh showing elongated largespaces (thick arrow) with thrombi (thin arrows). e An isoechoic poorlydefined lesion in the back of a 12-year-old girl, only appreciated becauseof the phlebolith within (arrow). f Forearm lesion showing fine anechoic

channels oriented along the long axis of the limb. g Deep seated thighlesion with slightly large channels oriented along the muscle fibers inter-spersed with echogenic tissue, the overlying tissue being normal (blackarrow) and the underlying surface of the femur clearly seen H) a masse-teric lesion with very fine septae, the lesion being predominantly anecho-ic. i Predominantly anechoic lesion involving a submandibular gland,with irregular spaces. j An anterior chest wall lesion with large venouslake (star)

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Fig. 4 Color Doppler images. aUS image showing lesion withpredominantly anechoic spacesand thin septae. b After probecompression, a collage of red andblue colors is seen. c Axial CT ofright masseteric venousmalformation. d An artery istraversing through the lesion. eGrayscale. f Color image of theleft submandibular–upper cervi-cal lesion with a large branch ofexternal carotid artery traversingthrough the center

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adverse events is reported to be extremely low, approximately2% [60, 95, 96].

Doxycycline

Doxycycline, an antibiotic of the tetracycline group, is mostlyused in the treatment of LMs [97–99], with overall responseranging from 67 to 100% [97], and extremely low to nil com-plications [98]. However, hypoglycemia, metabolic acidosis,and hemolytic anemia can occur, as can yellow teeth discol-oration in children.

Techniques of Injection

1. Blinded/clinical sense [77]: for superficial lesions (as inspider veins), or, limited localized VMs, microfoam canbe injected without any image guidance.

2. US-guided: US offers rapid PIS in office-based or same-day surgery setting, with excellent success rates [18, 63,64, 66]. Subsequent to US-guided puncture and confirma-tion of blood egress, foam is injected under continuousUS monitoring with a 6–15-MHz linear probe. Foam ap-pears as a “white” hyperechoic cluster spreading withinand rapidly replacing the anechoic appearance of the si-nusoids and channels (Fig. 8). The extent and direction ofthe foam movement are monitored by the operator or anassistant (Video 4), within the lesion, in the adjacent nor-mal tissue or reflux into veins (Figs. 9 and 10). In a truePuig type 1 VM, either cavitary or spongiform, thehyperechoic foam will fill up the lesion completely andproduce sharp demarcation from the surrounding tissues.In Puig type 2 lesions, foam egress into the adjacent nor-mal veins can be seen as hyperechoic specks movingwithin the anechoic lumen. As the foam will precludevisualization of deeper structures and subsequent needleinsertions, it is wiser to insert all the needles beforehand

Fig. 5 CT versus US in a case of a neck venous malformation in an 11-year-old boy. a A homogenous appearing large lesion crossing the mid-line and compromising the oropharynx (star). b Inferior section showingirregular contrast pools. cUS image shows spongiform appearance in oneportion (arrow) of the lesion. d US image showing thrombus within a

large lake (dashed arrow) and fine echoes in other areas suggesting stag-nation (thin arrow); note the carotid artery at the top left of the image. eUS image showing reverberation artifacts from foam with acousticshadowing (star); note the prominent internal jugular vein at the top leftof the image; such exquisite anatomy cannot be seen on CT

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(Fig. 11). Nevertheless, by positioning the needle approx-imately in the center of a lesion, it can be assumed that thefoam would spread equally in all directions and in allinterconnected channels and spaces. Gentle repeated pres-sure with the US probe or hand may be done over thelesion, if necessary, to ensure a uniform spread of foamwithin the remaining areas. Mechanical manual compres-sion of surrounding tissues can be used for preventingreflux, or a tourniquet may be applied, and after the pro-cedure, a crepe bandage or pressure dressing may be ap-plied for up to half an hour (Fig. 12).

3. Fluoroscopy/DSA guided (Figs. 13 and 14): The works ofStefan Puig and colleagues [16, 100, 101], and Dubois[91, 102], using the direct puncture phlebography (DPP)techniques, have changed the way VMs are treated.Commonly, a 22-gauge [100], and occasionally 21–27-G [103, 104], butterfly needle (scalp vein) is used forpuncturing an appropriate site, with longer metal needlesor angiocaths used for deeper sites, spinal or Chiba needlefor very deep sites, and bent needles at certain sites likesuperficial lesions, the oral cavity, or the tongue [11](Fig. 15). Image guidance allows precise positioning(Video 5). In the absence of spontaneous blood return,

the needle connected to the syringe through a length ofextension tubing is progressively withdrawn along withgentle suction, which will return blood [1]. Then, a smallamount of low-osmolarity iodinated contrast material,typically iohexol 350 mg/ml, is injected to obtain aphlebogram [105]. Slow injections with image acquisitionat 1–2 frames/s are typically used.

DPP will demonstrate the endoluminal portion of themalformation, and further sclerotherapy technique, needleplacement, and the drug dose are planned. Connections toadjacent and deep veins are best seen with DPP, and thelesion classified as per Puig et al. [16], and spongiform,cavitary, or diffuse/dysmorphic types [1]. However, inpractice, a variety of appearances will be seen, as withUS or MRI, and each VM poses unique therapeutic andtechnical challenges (Fig. 16).

Puig et al. described the “double puncture technique”of PIS [100], in which a needle is placed in the lesioncenter or one edge and another one at the periphery.Foam, or liquid sclerosant, when injected, displaces theblood or previously injected contrast, which comes outthrough the peripheral needle—the “vent needle”—thusreleasing pressure and allowing complete filing of the

Fig. 6 MRI of a case of VMinvolving the tongue. a AxialT2W and b Sagittal STIR imageshowing an infiltrating lesioninvolving most the right side oftongue compromising theoropharynx. cAxial and d sagittal,fat-suppressed T2W images, aftertwo sessions of bleomycinsclerotherapy, showing completeresolution of the lesion

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lesion with the drug. Multiple needles can be used if re-quired. The procedure is terminated when an adequatepre-targeted area or volume is treated, maximal allowedsclerosant dose per session is used up, or a high level oflocal resistance is noted during the injection. Someworkers inject contrast after the procedure as a control.

The current technique in vogue utilizes DSA [105,106]. However, fluoroscopy can also be used. Afterinjection of contrast, foam is injected under DSA. Thebackground contrast gets subtracted and a smallamount of contrast in the tubing comes out, which isfollowed by the foam (appears white). This is called the“filling-defect” technique [59].

A similar technique for liquid sclerosants was de-scribed by Spence et al. and Agid et al., who performedslow DSA image acquisition while injecting the non-contrast-mixed drug into the pre-opacified lesion whileviewing with simultaneous fluoroscopic subtraction;and called it the ‘negative subtraction’ technique [88,107]. A combination of techniques is commonly used[105].

The volume of drug injected and the total number ofsessions vary widely in the literature. Blaise et al. usedUS-guided sclerotherapy and injected a volume of POLfoam which was necessary to induce venous spam butnever more than 10 mL of POL per session [64].Yamaki et al. used 1 mL/kg of POL and 0.4 mL/kg ofEO [66]. Li et al. used a maximum of 6 mL of 5% SM[59]. While these are the total dose per session, theactual injection per needle puncture varies accordingto the method. Typically, in the filling-defect tech-nique, the foam injection is stopped when the entirecontrast volume previously injected has been pushedto the periphery, or the foam appeared in the drainingvein [59]. In this technique, the quantity of sclerosantapproximately equals the volume of contrast agentinjected beforehand [4, 5]. For larger lesions, lesioncan be divided into multiple segments arbitrarily andthen treated from the center to the periphery, or fromone side to another. Ahmad et al. used an average of0.5 mL of STS for each 2 mL volume of the lesion[103]. Alakailly et al. used a similar strategy [77].Stuart et al., in their series of 204 patients treated with3% STS under fluoroscopic guidance, preferably thedouble puncture needle, injected the sclerosant till re-sistance was felt or sooner if the operator believed aneffective dose had been delivered [79]. Cabrera et al.aspirated back through the injection needle, and ifblood returned, then the drug was injected further,while aspirate of white or pink material indicated ade-quate injection [63]. Sclerosant volume vis-à-vis lesionvolume, however, has no effect on treatment outcomes[108].Ta

ble4

Com

monly

used

agentsin

VM

sclero(embolo)therapy

[4–6,11,29,39–41]

Alcohol

Detergents

Antibiotics

Liquidem

bolic

Dehydratin

gagent

Irritants/miscellaneous

Dry

ethanol

Sodium

tetradecyl

Sulfate(STS):−

1%and3%

OK432

(Picibanil)

N-Butyl-2-cyanoacrylate

(nBCA)

Hypertonicsalin

eChrom

ated

glycerin(Sclerem

o)with

25%

glucose

Polid

ocanol

*Polidocanol:−

1%and3%

(0.25to4%

)Bleom

ycin

EVOH(O

NYX/PHIL)

Boilin

gcontrast

Polyiodinatediodine

Ethanolgel(Ethanolingelform

boundto

agentslik

eethylcellulose)

Sodium

morrhuate

Doxycyclin

eLipiodol

HypertonicSodium

chloride

with

dextrose

Sterile

talcum

powder

Alcoholicsolutio

nof

zein

(Ethibloc)

Ethanolam

ineoleate(Etham

oline5%

)Fibrin

glue

72%

glycerine

Steroids

Invertsugar

Phenol

Sodium

Salicylate

*Polidocanol

isaweakalcohol

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Technical Challenges in VM Sclerotherapy

1. Contrast extravasation (Fig. 17): Findings onphlebography include initial globular contrast pool whichlater spreads into linear or curvilinear margins, visualiza-tion of linear striations to suggest intramuscular injection,lack of visualization of any draining veins, and failure ofcontrast medium to clear after a few seconds. In suchconditions, the needle should be reinserted/repositionedpreferably under US guidance.

2. Foam extravasation/tissue injection (Fig. 10): On US, itpresents has a continuous thin layer of echogenicity withsubjacent artifacts. On phlebography, it appears as arounded white shadow not matching the shape of the pre-viously injected contrast shape, as well as displacement ofthe contrast to one side, and relatively increased resistance

to injection. The extraluminal injection can result in se-vere tissue necrosis, ulceration, neuropathy, and musclecontracture hence sclerosant should not be injected in sus-picious extravasation.

3. Compartment syndrome [109]: Post-procedural swell-ing is due to a combination of inflammatory edema andintra-lesional thrombosis and is a marker for bothprolonged recovery as well as therapeutic efficacy[110]. In some locations, e.g., forearm and calf, thechance of nerve compression and compartment syn-drome are higher. The following measures can be ap-plied for prevention:

& The double/multiple puncture technique to remove excessblood and sclerosant.

& Aspiration of sclerosant a few minutes after injection.

Fig. 7 Thrombus formation in a nasal tip venous malformation aftersclerotherapy. a CECT image showing a hypodense mass. b Clinicalphotograph prior to sclerotherapy. c US image showing the lesion to be

made of small anechoic spaces. d needle inserted in the lesion forsclerotherapy (arrow). e US image after a week shows isoechoicthrombus in most of the lesion (star) and a small residue (arrow)

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Table 5 Common detergent sclerosants

Sodiummorrhuate

Polidocanol Ethanolamine oleate Sodium tetradecyl sulfate

General In use foralmost acentury invenousdiseases[58].

Weak alcohol, widely used, safe andcheap, nonionic, weak anestheticdrug [61–65]

The pro-inflammatory ‘oleic acid’and the anti-clotting ‘ethanol-amine’ components create a pur-ported hemostatic balance [68]

Anionic surfactant originallydescribed by Reiner in 1946 [75]

Special use Nearly painless injection [4], thusavoiding general anesthesia [18]

It rarely causes cutaneous ulceration,even if superficially injected [39]

EO has been used by various workers[69–74]; considered relatively safeto use in situations where vascularstructures are in nerves’ proximity

Increasingly used in the treatment ofvascular malformations [76–79].

Concentrationand dose

5%; 6 mL[59]

0.25–4%; 6–10 mL [18, 63–66] 1.25%, 2.5%, and 5%; 0.3 to 16 mL[68–74]; maximum 20 mL, or0.4 mL/kg

3%; up to 16 mL

Complications Pain andswelling[60]

29.3% minorcomplica-tions inseries of Liet al. [59]

0–16%; Skin necrosis, pigmentation,superficial thrombosis, hypotension,and bradycardia [63, 64], significantpost-procedure swelling [65]; toxici-ty has been evaluated extensively[67]

3% [41]; pleural effusions, edema,infiltration, and pneumonitis.

Renal insufficiency, hepatotoxicity,and intravascular hemolysis athigher doses may requireprophylactic haptoglobin [70].

3.1–12.5%. Excessive swelling, skinnecrosis, excessive pain, nerveinjury, urticaria, anaphylaxis,hemolysis, and hematuria

Clinicalsuccess

61–65.2%excellent tototalresolution[59, 60]

Sclerosing efficacy could be less thanSTS, EO, or ethanol [65], eventhough the clinical results have beensatisfying in the literature (60–92%)[18, 41, 63, 64].

More likely expected outcomebetween 60 and 80% [71]; up to90% [72, 73]

33% complete response, 83% overallresponse [41]; potential lessereffectiveness of STS outweighsthe higher risks associated withethanol

Fig. 8 US-guided sclerotherapy examples. a Complex-shaped lesion(white star). b Foam appearing as white speck fills the lesion and thecontour of the lesion is reproduced (thin dashed arrows). c Gingivo-buccal lesion (black star). d Foam fills the lesion completely (thick dashed

arrow). eAwell-marginated lesion. f The foam fills the lesion completelytill the lesion edge (short arrows). gA buccal lesion (hollow star). h Foamfills some of the spaces (star) and other areas are devoid of thehyperechoic signal (long arrows)

1473SN Compr. Clin. Med. (2020) 2:1462–1490

& Using sclerosants producing minimal swelling, e.g.,bleomycin

& Dilute nBCA followed by foam sclerosant injection [111].& Corticosteroids and icepack.& Avoidance of tight circumferential dressings.& Tracheostomy before treatment of large lesions around the

airway.& Partial lesion treatment in each sclerotherapy session.

4. Deep vein thrombosis (DVT) [10]: VMs with rapid,uncontained drainage to critical venous channels have ahigher risk of DVT, as well as systemic complications likehemoglobinuria. In such situations:

& Close the venous outflow by using endovenous laser ther-apy, coils, or nBCA. [111, 112]

& Treat patients with prophylactic LMWH for 2 weeks afterthe procedure.

& Consider a temporary inferior vena cava filter.& Use low dose of sclerosants and ambulate early to prevent

stasis. [10]

5. The risk of skin necrosis in superficial lesions:

& Observe skin color and hardening of the lesion whileinjecting the sclerosant.

& Place cannula in the deepest part of the malformation withadequate healthy tissue between the skin entrance and thelesion.

& Consider using laser or dilute sclerosant.& Apply cold saline to the skin during sclerotherapy.& Use mucosal surface for lesion access instead of skin

where possible.& Use POL where possible.

Fig. 9 aDeep-seated thigh venousmalformation treatedwith polidocanolfoam sclerotherapy (white star). b Foam egress into a muscular vein (thinblack arrow). c Foam egress into another large intramuscular vein (dashed

white arrow). d Large deep-seated thigh venous malformation (blackstar). e Foam refluxing into the great saphenous vein (thick short arrow)

1474 SN Compr. Clin. Med. (2020) 2:1462–1490

6. Rapid egress of contrast/sclerosants (Video 6):Increasing the “dwell time” is desirable here [4, 5,111], by using foam [11, 42], mixing the drug withlipiodol [112, 113], and using ethibloc [102],ethylcellulose [48], or ethanol-gel [49]. Tourniquet,pneumatic cuff, US probe pressure, or manual compres-sion can be used to compress the veins, however, withthe risk of overdistension of the VM and extravasationand/or sudden release of sclerosant bolus or thrombusinto circulation after the release of the tourniquet [112].New tools like nBCA, EVOH, pushable or detachablecoils, Amplatzer plugs, and intravenous balloon

occlusion can all be used alone or in combination [4,5, 29, 93, 111, 112]. nBCA is a highly versatile tool;however, multiple punctures and delivery catheters maybe needed.

In VMs, nBCA may be used to block the connectingveins and the dysplastic channels, and to cause an intra-lesional partial embolic occlusion of the venous chan-nels which are subsequently filled with ethanol or foam[111] (Fig. 18). Recently, it has been used to embolizethe VM preoperatively with a significant reduction inblood loss and excellent resection outcomes [114].

EVOH can also be used instead of nBCA [112]; ad-vantages include prolonged injection times and filling ofinterconnecting vascular channels due to its lava-likeflowing property, thus avoiding multiple vascular ac-cesses, and lesser inflammatory and cytotoxic effect.

7. Large lesions and the lure of injecting higher doses ofsclerosant: Foam injections have to be given relativelyrapidly, and the action of the drug at a site farther awayfrom injection site is likely to be less [11], which can bean issue in large VMs. These are obviated to some extentby using liquid sclerosants like ethanol that flow alongthe path of least resistance [100], and potentially coverlarger volumes, however, with possible higher compli-cation rates. With large lesions, especially Puig types 1and 2, the procedure can go relatively smoothly, and theoperator must be careful not to exceed safe doses. Asimple workaround is to insert multiple needles at somedistance, e.g., at 3-cm intervals [18], and inject the foamrapidly in sequence to fill the desired area with the max-imum permissible quantity, before the drug washes outto other parts of the VMand gets diluted or flows into theconnecting veins (Fig. 11). Another issue with large le-sions is the patchy nature of sclerosis with intervening

Fig. 11 Rapid sclerotherapy technique. a Three needles have been inserted in a large thigh venous malformation. b Foam injection started from themiddle needle. c Rapid successive injection via all three needles

Fig. 10 A thin venous malformation in an extremity (star) with a sub-fascial spread of foam (arrows) due to intra-procedure needle malposition

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non-sclerosed disease. This can be controlled to someextent by dividing the lesion arbitrarily in sections, alsoUS examination at each follow-up and before sclerother-apy. For large Puig types 3 and 4 lesions, there is a riskof injecting large quantities because the lesion may notbe cured fast enough. Also, relatively small quantities inthese lesions still run off into the systemic circulationrapidly and the actual safe dose may be much lower thanrecommended.

8. Small and/or superficial lesions and unstable needle[Fig. 19]: US-guided injection or a blind injection af-ter proper lesion puncture is a good technique here,and the authors use a long horizontal course of theneedle or the needle tip bent at 45 to 90 degrees insome situations.

9. Doubtful needle position midway of injection(Fig. 20): the needle must be inserted to its maximallength possible, in a straight or oblique path throughnormal subcutaneous tissue and muscle, to achievestability. Even then, there is a chance of needlemalpositioning during injection. Suspicion arises dueto a mismatch between the shape of the preinjectedcontrast and foam or suddenly increased resistance.Stopping foam injection and injecting a small amountof contrast helps in this situation, which will confirmthe extravasation, and so is viewing the nativeunsubtracted mode instead of DSA mode, which willshow the contrast within the lesion displaced to oneside by the air within the foam. Further injections aregiven after needle repositioning.

Fig. 12 Compression of draining vein. a A large infiltrating cervicalvenous malformation (star); note the carotid artery (arrow). b internaljugular vein is compressed manually, arrow points to the fine low-level

echoes due to the intravenous blood stagnation. c foam sclerotherapy ofthe lesion with near-total filling

Fig. 13 A typical case of DSA guided sclerotherapy. a needle placed inthe center of a small forearm Puig type 1 lesion and phlebographyperformed. b Foam injected under slow frame rate, at the start of theinjection, the contrast in the tubing is injected and the foam

subsequently follows. c Image at near completion of sclerotherapy; thefoam has near completely filled the lesion and the contrast has beendisplaced in the periphery

1476 SN Compr. Clin. Med. (2020) 2:1462–1490

10. Puncture of a large venous channel (Fig. 21):VMsmay have large channels or may connect to large veinslike the internal jugular or superficial femoral. Mosttimes US-guided puncture safely avoid puncturingthem; however, phlebography should be employed insuch lesions to check for large vein puncture or rapidefflux.

11. US versus fluoroscopy: US is a very enticing anduseful tool, especially in the pediatric age group

patients, and recommended to be used in most casesof foam sclerotherapy, especially because of the “re-al-time” needle visualization allowing precise posi-tioning, manipulation, and repositioning (Fig. 22).However, phlebography is needed in complex casesand with liquid sclerosants. In the authors’ practice,approximately 90% of cases are treated by US guid-ance alone.

Fig. 14 DSA guided foam sclerotherapy of a deltoid venousmalformation in a 13-year-old girl. a Coronal STIR image showing thelarge infiltrating intramuscular lesion. b A needle has been inserted deepinto the lesion. c Subtraction phlebography showing a cavitary form ofthe lesion without any reflux into normal or abnormal vein. d Anotherneedle attempted to be inserted into the lower part of the lesion resulted in

intramuscular insertion (black arrow). e Another needle inserted in themiddle part shows spontaneous egress of blood mixed contrast comingout of the needle hub (oval outline). f After injecting foam in this part,another puncture was done and the vent needle still shows contrastegressing out (white oval outline)

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12. Intra-arterial injection: Sclerosants affect arteries dif-ferently, and intimal damage is not generally ob-served due to the rapid flow; however, occasionalthrombosis does occur, and cases of limb gangrenewith resultant limb amputation have also been re-ported. In the varicose vein literature, intra-arterialfoam injection reportedly has about 50% complica-tions, and steroids and pulse dye laser have beenreported to be useful in treating such cases [115,116]. Phlebography, preferably under subtraction,should be employed for uncertain needle positionsin relation to large arteries.

13. The need for follow-up MRI: while US is recommendedat each visit, MRI is not, unless there is a perceivedchange in the disease character, which is against thenormal course of events. However, MRI provides objec-tive measurements and is also needed in late recurrences.MRI with contrast may be done after completion of ther-apy; however, a minimum of 6-month delay (1-month to

1-year variation in literature) is recommended for theinflammation to subside completely [1, 20].

14. Multi-disciplinary planning: A multidisciplinary treat-ment of VMs is imperative for safe and successful vas-cular anomaly treatment programs [117].

15. Anesthesia requirement: Same-day surgery settingis routinely used now for PIS [18, 63, 64].Apprehensive adult patients may be prescribed an-xiolytics like alprazolam 0.25 mg the night beforethe procedure, and for the actual procedure, a localanesthetic cream like lidocaine 2.5%–prilocaine2.5% may be applied locally [18]. PIS with POLusing US guidance rarely needs any anesthesia. Forchildren, intravenous sedation and analgesia withpropofol and fentanyl are usually sufficient.Ethanol almost always requires general anesthesia[100, 118–122], even though there have been re-ports of outpatient basis treatment with low dosesof ethanol under local anesthesia. [123].

Fig. 15 Needles used in sclerotherapy. a A needle attached to a shortconnecting tube has been inserted in a floor of mouth lesion. b Twobutterfly needles are inserted in an upper cervical malformation, anothervent needle has been inserted slightly inferiorly. c A needle bent in itsanterior part and attached to a short connecting tube has been inserted in alarge tongue malformation. dAn obliquely inserted needle in a superficialright cervical lesion. e A deep-seated thigh lesion (solid arrow) was

accessed using a spinal needle; the dashed arrow is pointing to the femur.f A posteriorly located tongue lesion has been accessed using a needlepassing through the muscle layer. g A forearm venous malformationtreated by multiple punctures. In all cases, the needles have been insertedas deep as possible to keep them firmly in place ensuring that a minimumlength of the needle is outside the surface

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16. Choice of sclerosants: While ethanol, STS, POL, andbleomycin are four distinct favorites at present, a varietyof other drugs are also used, and newer drugs will keepcoming in the market.

Side Effects

Complication reporting in the literature varies greatly depend-ing upon the patient group, sclerosant type and technique,complication definition, follow up techniques, and durations(Table 6).

All sclerosants and all techniques have side effects and canbe fatal, local pain and swelling being ubiquitous [18, 66],sometimes even with bleomycin (Fig. 23), and expected re-sponses of the therapy. These can be treated with

acetaminophen (paracetamol) [21], or steroids in select cases.Minor side effects like nausea, vomiting, and dizziness arecommon. Skin or mucosal blistering, discoloration, necrosis,and ulceration are also relatively common especially with eth-anol and in superficial lesions. Blanched or discolored skin,which is relatively well marginated, is a predictor of futureulceration and necrosis. No compression should be appliedin such cases. An icepack may be used for 3 days and antibi-otics prescribed. The ulcerations rarely need debridement orskin grafting. Mucosal ulcerations usually heal without scar-ring. Occasionally skin scarring may occur, or a sinus/fistulaformation may take place which may be particularly difficultto treat.

Nerve palsy is less common and alarming but less harmfulif identified andmanaged properly. Peripheral and facial nervepalsymust be checked before discharging the patient. Areas ofdecreased sensation usually resolve spontaneously in a fewweeks to months and are often not reported by patients.

Fig. 16 Direct puncture phlebography appearances. a Well-defined le-sion in the foot with small connected spaces. b Poorly defined deep-seated lesion with irregular small and large channels and spaces withdrainage into a normal vein. c slightly more dysmorphic lesion with

drainage into normal-sized veins. d Cavitary lesion with large venousspaces. e spongiform lesion with very fine reticulations. f Dysplasticvenous channels making up the lesion with drainage into normal-sizedveins. g Hugely ectatic lesion draining into large leg veins

1479SN Compr. Clin. Med. (2020) 2:1462–1490

Fig. 17 Sclerotherapy of a lesioninvolving the floor of the mouth.a Phlebography showingspongiform Puig type 2 lesionwith communication to normal-appearing vein. b During theprocedure, another punctureshows the typical intramuscularcontrast injection appearing aslinear striations. c Phlebographyafter needle repositioning. dFoam injection after needlerepositioning

Fig. 18 Embolization of large draining vein prior to sclerotherapy. a Coronal STIR image showing a large infiltrating venous malformation in the distalleg with a large draining vein. b US image of the large-caliber vein. c Post nBCA plug, foam sclerotherapy was done

1480 SN Compr. Clin. Med. (2020) 2:1462–1490

However, if a future nerve palsy due to swelling is suspected,then steroids should be prescribed. Fasciotomy may be rarelyneeded. For motor nerve palsy, rehabilitation should be startedafter the initial edema and swelling phase has passed.

Mostly with ethanol, and with all sclerosants, exists a smallrisk of hemoglobinuria, which is somewhat dose-dependent,hence found with complex and large VMs, and seen in up toone-third of the cases, and are mostly transient. Hydrationwith crystalloids is both preventive and therapeutic.Alkalization with sodium bicarbonate, furosemide, and hapto-globin may be used.

Anaphylactic reactions and reversible cardiovascular com-plications like bradyarrhythmia, hypotension, and cardiac ar-rest also are known with most sclerosants.

More infrequent and occasionally severe complicationsinclude permanent nerve palsy, muscle fibrosis and con-tracture, compartment syndrome, superficial thrombophle-bitis, deep vein thrombosis (DVT), pulmonary embolism,transient pulmonary hypertension, bronchospasm, abdomi-nal, retroperitoneal or cerebral hemorrhage, renal insuffi-ciency, severe intravascular hemolysis, hepatotoxicity,and cardiovascular collapse. Deaths with PIS of VMs arenow extremely rare.

Other agents

Osmotic solutions like hypertonic saline and chemical irritantslike 4% polyiodinated iodine as well as boiling contrast have

been used for sclerotherapy [39, 40, 42, 128]; however, thereports are few and not used by many workers for VMsclerotherapy.

Expected Outcomes of Sclerotherapy

Counseling and goal-setting is of utmost importance. About70% of patients have improvement, and smaller lesions canresolve completely, but diffuse lesions need lifelong surveil-lance probably, and the probability of recanalization and re-growth exists even after apparent cure.

Most follow-ups are clinical and on US, and “patient satis-faction” has been traditionally considered a good indicator ofthe therapeutic outcome, apart from the anatomical and clini-cal corrections [18, 118, 120, 124] (Fig. 24).

Other Therapies

Real-time MR-guided sclerotherapy is an evolving technique,with possible utility in challenging lesions. A combination ofsequences, mostly including SSFP, trueFISp, FLASH, andVIBE, are used for needle placement, and injection and mon-itoring of gadolinium contrast and sclerosants [74, 129].

Surgery can be opted for in truncular lesions, debulkinglarge lesions, lesions not responding to PIS, urgent treatment,and cosmetic corrections.

Fig. 19 Sclerotherapy ofsuperficial venous malformation.a Needle tracked horizontallythrough the lesion for a distanceto achieve a stable position(arrow). b Polidocanol foamsclerotherapy of the lesion, withcomplete filling

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Percutaneous ablative therapies can be used, and includelaser for superficial and mucosal lesions, radiofrequency fordeep and large lesions, and cryoablation for nonresponsivecases, and especially in the recently described entity offibroadipose venous anomaly (FAVA) [130–132].

Summary

ISSVA classification has given clarity to the nomenclatureof vascular anomalies, and radiologists, both diagnostic and

interventionists, play a critical role in managing such caseswithin a multidisciplinary environment. Clinical evaluationguides towards a probable diagnosis of VM, and subse-quently, US with CD, and in most cases, MRI is used tocharacterize the lesions, determine the size and extent of theanechoic spaces, and define the extent and infiltration intoadjacent tissues. DPP is useful in confirming the diagnosis;however, it is used mostly along with the therapeutic PISprocedure. Cavitary, spongy, dysmorphic lesions can beseen and Puig’s classification is widely used. The identifi-cation of the connecting draining veins is critical to

Fig. 20 Sclerotherapy of a spongiform venous malformation in a 6-year-old boy. a initial subtraction phlebography. b Start of foam injection. cMidway of foam injection, at this point, there was some resistance felt. dSmall amount of contrast injected to check position shows proper positionwith spongiform appearance, note the different layers—the innermost isthe freshly injected contrast, the middle is the foam and the outermost isthe earlier injected displaced contrast; subsequent to further foam

injection, there would be another central core of white foam. e The samepatient; the needle was malpositioned; note the globular lobulated con-trast pool. f After repositioning of the needle, proper spongiform appear-ance is noted. g Form sclerotherapy is performed. h Fluoroscopic spotimage, unsubtracted view, showing the radiolucency of the foam and aperipheral layer of displaced contrast, the extravasated contrast pool liesat the bottom

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treatment. A variety of sclerosants are used, of which an-hydrous ethanol is the most studied, most potent, and argu-ably most complication-prone drug, which has to be usedunder GA with proper monitoring. DSs in microfoam formmade using original or modified Tessari’s technique haveevolved as effective and safe alternatives, and STS, POL,EO, SM are most widely used. POL has especiallyestablished itself as a very safe drug with the ability to offertherapy under US guidance on an outpatient basis. Allagents cause pain and swelling, which however is lesserwith bleomycin; hence, it is used in critical locations likethe orbit, oropharynx, etc. Fluoroscopic guidance is consid-ered essential for ethanol injection with the prevention of arunoff into the systemic circulation being a major aim.Double/multiple punctures, negative subtraction, filling de-fect, and combination of techniques are used in fluoroscop-ic or subtraction mode for both liquid and foam sclerosants.All agents can cause complications varying from nausea,bronchospasm, skin ulcerations, nerve palsy, hemoglobin-uria, muscle fibrosis, and cardiovascular events including

Fig. 21 Inadvertent puncture oflarge vein in a complex leftcervical venous malformation. aAnterior portion of the lesionappears like Puig type 2. b Foaminjection performed with ease. cAnother needle insertedposteriorly results in resistance toinjection and a “pool” of contrast.d Slight repositioning results inpuncture of a large vein with thefilling of the internal jugular vein,further sclerotherapy wasabandoned and the patient calledfor another session after 4 weeks

Fig. 22 A case of lower lip venous malformation with intra-procedureneedle repositioning under US guidance. On the left is a portion of themalformation filled with foam (black arrow); the same needle (arrow) wasthen repositioned across the ‘septum’ into the poorly filling portion (whitestar) and sclerotherapy continued

1483SN Compr. Clin. Med. (2020) 2:1462–1490

Table6

Com

plications

ofcommonly

used

sclerosants

Author,year

[ref]

Patients

Age

Sclerosant

Com

plications

Tan

etal.,2007

[78]

7231.7

years(14–62

years)

STS

Nomajor,7

minor

(3.1%

persession,9.7%

perp

atient)—

skin

necrosis/ulcer,paresthesia,allergicreaction

Alakaillyetal.,2015

[77]

1318.2

years(8

months–534years)

STS

Pain

andedem

ain

all,superficialu

lcerationin

2(11.76%),

ecchym

osisin

1patient

(5.88%

)Lietal.,

2009

[59]

2321

years(5

months–39

years)

SMNomajor;m

ildpain

in17

sessions

(29.3%

,skinblisterin

2sessions

(3.4%)

Yun

etal.,2009

[118]

158

14.3

years(1–58years)

Ethanol

Skin

necrosis(8%),nervepalsy(13%

),haem

oglobinuria

(8%),othersystem

ic(4%)-total3

3%Goyaletal.,2002

[17]

5911.4

years(1–22years)

Ethanol

9%;self-lim

iting;skinnecrosis(n

=1)

andblistering

(n=3)

Aronniemietal.,2016

[119]

127

21.5

years(3.4–76.0years)

Mostly

STSandPO

L,som

ecasesof

ethanol,

bleomycin,doxycycline,laser,andnB

CAoccasionally

Total12.5%—mostly

minor;4

severe

hemorrhage

Nakam

uraetal.,2014

[120]

4828.2

years(11–69

years)

Mostly

POL;ethanol

orEOifPO

Lineffective

2major

complications

(ARF,

nervepalsy);p

ainandsw

ellin

gin

mostcases

Blaiseetal.,2011

[64]

2433.6

years(7–78years)

POL

2minor

Cabrera

etal.,2003

[63]

5050;2

6.5(8–62years)

POL

4skin

pigm

entatio

n,3skin

necrosis,2

intra-arterialinjection

Yam

akietal.,2008

[66]

8914.5

years

POL

Painandsw

ellin

guniversal;no

major

complications;m

inor—

skin

necrosis,hem

oglobinuria,renalfailure

Gorman

etal.,2018

[108]

3415.5

years(2.8–66.1years)

Ethanol,S

TS,

orcombinatio

n8major

(chronicpain,com

partmentsyndrom

e,decreased

mobility,prolonged

nervepalsy);1

9minor

Veräjänkorvaetal.,2016

[121]

6336

years(3–88years)

Polid

ocanol,O

K-432,ethanol,and

glue

16%

(pain13%,fever,hem

atom

a,necrosis2%

each)

Kum

aretal.,2018

[18]

5318.1

years(range

4–45

years)

POL

Localsitepain

30/52patients;chestp

ain2/53

patients

Hoque

etal.,2011

[73]

8315.1

years(3

months–21

years)

EO

Painandsw

ellin

gallpatients,4hadskinsloughing,no

major

Stieneretal.,2016

[122]

5429

years(9–61years)

Ethanol

Minor

complications

in16.7%

(paresthesia,facialp

alsy,

blistering,ulceration);m

ajor

in5.6%

(necrosis,Horner’s

syndrome,jointstiffness)

Orlando

etal.,2010

[123]

3924

years(11–59

years)

Ethanol

(under

localanesthesia)

7.7%

localp

araesthesia,51%

superficialthrom

bophlebitis,

2.6%

skin

ulcer,2.6%

hyperpigmentation

Khaito

vich

etal.,2019

[124]

153

21y(6

weeks–67years)

Ethanol

Class

3and4complications

3%and2%

respectively

Lee

etal.,2001

[44]

30–

Ethanol

26.7%—ischem

icbullae,tissuefibrosis,D

VT,pulmonary

embolism,nerve

palsy,temporary

pulm

onaryhypertension

Karim

ietal.,2018

[125]

345

13.5

years(4–42years)

STS

6.6%

(anaphylaxis,ulcer,nerve

palsy,auriclenecrosis,airway

edem

a)Inbarajetal.,2018

[126]

4424y(m

edianage)

STS

9%(venousbleeding,arterialinjurytolin

gualartery,swellin

gof

tongue,haematuria)

Rautio

etal.,2004

[127]

202months–58

years9months

Ethanol

1case

hadnervepalsy

Spence

etal.,2010

[88]

3734.4

years(18–62

years)

Bleom

ycin

12.5%

minor

transientcom

plications

(infection,nausea,

vomiting,tem

porary

skin

discoloration)

1484 SN Compr. Clin. Med. (2020) 2:1462–1490

arrhythmias and cardiopulmonary collapse. Dose limitationof sclerosants within safety limits is critical, and adequatepre-, intra- and post-procedure management is imperative.Approximately 70% of good clinical response is expectedoverall with very low major complications. Newer thera-pies including the liquid embolics such as nBCA andEVOH, ablative therapies like cryoablation, and RFA areevolving and older therapies like boiling contrast are beingoutdated.

Author Contribution Dr. Subhash Kumar: conception and de-sign acquisition of data, analysis and interpretation of data,drafting the article or revising it critically for important intel-lectual content, final approval of the version to be published,agrees to be accountable for all aspects of the work if ques-tions arise related to its accuracy or integrity

Dr. Kranti Bhavana: acquisition of data, analysis and inter-pretation of data, drafting the article or revising it critically forimportant intellectual content, final approval of the version tobe published, agrees to be accountable for all aspects of thework if questions arise related to its accuracy or integrity

Dr. Amit Kumar Sinha: acquisition of data, drafting thearticle or revising it critically for important intellectual con-tent, agrees to be accountable for all aspects of the work ifquestions arise related to its accuracy or integrity

Dr. Sanjeev Kumar: acquisition of data, final approval ofthe version to be published, agrees to be accountable for allaspects of the work if questions arise related to its accuracy orintegrity

Dr. Arun Prasad: acquisition of data, drafting the article orrevising it critically for important intellectual content, agrees

Fig. 24 ‘Good response’ after sclerotherapy. a Large thigh venousmalformation with large anechoic spaces (black star). b US-guidedpolidocanol foam sclerotherapy, screen-grab image. c Follow-up USimage after six sclerotherapy sessions showing echogenic lesion with

significantly decreased volume; however, the lesion has not “completelysubsided,” the patient has had complete relief of pain and ‘clinical swell-ing’ and has been followed - up till 3 years

Fig. 23 Excessive hard swelling after sclerotherapy with 30 U ofbleomycin in a left cheek lesion. The swelling took 10 weeks to subsideand the patient refused further treatment, although there was more than50% lesion resolution after the first therapy

1485SN Compr. Clin. Med. (2020) 2:1462–1490

to be accountable for all aspects of the work if questions ariserelated to its accuracy or integrity

Dr. Bhartendu Bharti: acquisition of data, agrees to be ac-countable for all aspects of the work if questions arise relatedto its accuracy or integrity

Dr. Pranav Kumar Santhalia: conception and design, acqui-sition of data, final approval of the version to be published,agrees to be accountable for all aspects of the work if ques-tions arise related to its accuracy or integrity

Compliance with Ethical Standards

Conflict of Interest The authors declare that they have no conflict ofinterest.

Ethical Standard All procedures performed in the study were in accor-dance with the ethical standards of the institutional research and ethicscommittees and with the 1964 Helsinki declaration and its later amend-ments or comparable ethical standards. The requirement of review hadbeen waived off by the institute ethics committee.

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2. Mulligan PR, Prajapati HJS, Martin LG, Patel TH. Vascularanomalies: classification, imaging characteristics and implicationsfor interventional radiology treatment approaches. Br J Radiol.2014;87:20130392. https://doi.org/10.1259/bjr.20130392.

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