10.14639/0392-100X-N1310
Objective. Polidocanol sclerotherapy of head and neck venous malformations (VMs) and lymphatic malformations (LMs) has been reported only in limited series. In this manuscript we evaluated the efficacy and safety of polidocanol sclerotherapy in a series of head and neck venous and lymphatic malformations. Methods. This retrospective observational study analysed data on 20 head and neck VMs and LMs that underwent to percutaneous or endoscopic intra-lesional 3% polidocanol microfoam sclerotherapy at our institution. Clinical response was ranked as excellent, moderate and poor based on volume reduction by MRI and resolution of symptoms. Results. The median volume decreased from 19.3 mL to 5.8 mL after sclerotherapy (mean volume reduction: 72.98 ± 16.1%). An excellent-moderate response was observed in 94.4% of cases. We observed a mean volume reduction of 79.5 ± 16.1 in macrocystic LMs, of 76.1 ± 13.0% in VMs, of 60.5 ± 10.9% in mixed lymphatic ones and 42.5% in microcystic lymphatic ones. Conclusions. Polidocanol sclerotherapy appears to be an effective and safe treatment for venous and lymphatic head and neck malformations. We observed the best responses in macrocystic LMs and VMs, whereas mixed lymphatic ones showed a moderate response and microcystic lymphatic ones a poor response.
text/xml
1827-675X
1310
en
Gaetano Paludetti
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
vascular malformations
Sclerotherapy with polidocanol microfoam in head and neck venous and lymphatic malformations
Text.Serial.Journal
https://www.actaitalica.it/
42
Head and neck
2021-07-23
2020-12-15
2022-05-23
2022-05-23
116-125
1
Gaetano Paludetti
2022
10.14639/0392-100X-N1310
116
UOC Otorinolaringoiatria, Area Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
1827-675X
vascular malformations
en
125
Sclerotherapy with polidocanol microfoam in head and neck venous and lymphatic malformations
https://www.actaitalica.it/article/download/1310/648
42
ACTA OTORHINOLARYNGOLOGICA ITALICA 2022;42:116-125; doi: 10.14639/0392-100X-N1310




Head and neck


Sclerotherapy with polidocanol microfoam in head
and neck venous and lymphatic malformations
La scleroterapia con polidocanolo nella gestione delle malformazioni venose
e linfatiche del distretto testa-collo
Eugenio De Corso1, Alessandro Cina2, Giampiero Salonna1, Giovanni Di Cintio1, Simona Gaudino2, Marco Panfili2,
Cesare Colosimo2, Gaetano Paludetti1
1
 UOC Otorinolaringoiatria, Area Testa-Collo, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro
Cuore, Rome, Italy; 2 UOC Radiodiagnostica e Neuroradiologia, Dipartimento di Diagnostica per Immagini, Radioterapia, Oncologia
ed Ematologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy


SUMMARY
Objective. Polidocanol sclerotherapy of head and neck venous malformations (VMs) and
lymphatic malformations (LMs) has been reported only in limited series. In this manuscript
we evaluated the efficacy and safety of polidocanol sclerotherapy in a series of head and
neck venous and lymphatic malformations.
Methods. This retrospective observational study analysed data on 20 head and neck VMs
and LMs that underwent to percutaneous or endoscopic intra-lesional 3% polidocanol mi-
crofoam sclerotherapy at our institution. Clinical response was ranked as excellent, moder-
ate and poor based on volume reduction by MRI and resolution of symptoms.
Results. The median volume decreased from 19.3 mL to 5.8 mL after sclerotherapy (mean
volume reduction: 72.98 ± 16.1%). An excellent-moderate response was observed in 94.4%
of cases. We observed a mean volume reduction of 79.5 ± 16.1 in macrocystic LMs, of
76.1 ± 13.0% in VMs, of 60.5 ± 10.9% in mixed lymphatic ones and 42.5% in microcystic
lymphatic ones.                                                                                   Received: December 14, 2020
Conclusions. Polidocanol sclerotherapy appears to be an effective and safe treatment for          Accepted: February 20, 2021
venous and lymphatic head and neck malformations. We observed the best responses in               Published online: July 23, 2021
macrocystic LMs and VMs, whereas mixed lymphatic ones showed a moderate response
and microcystic lymphatic ones a poor response.                                                   Correspondence
                                                                                                  Giovanni Di Cintio
KEY WORDS: lymphatic malformations, venous malformations, sclerotherapy,                          UOC Otorinolaringoiatria, Area Testa-Collo.
polidocanol, vascular malformations                                                               Fondazione Policlinico Universitario A. Gemelli
                                                                                                  IRCCS, Università Cattolica del Sacro Cuore,
                                                                                                  largo A. Gemelli 8, 00168 Rome, Italy
RIASSUNTO                                                                                         Tel. +39 06 30154439
Obiettivi. La scleroterapia con polidocanolo (POL) nelle malformazioni venose (VM) e              E-mail: dicintiogiovanni@gmail.com
nelle malformazioni linfatiche (LM) della testa e del collo è stata descritta solo in casisiti-
che limitate. In questo lavoro abbiamo valutato l’efficacia e la sicurezza del POL in pazienti      How to cite this article: De Corso E, Cina
affetti da VM e LM della testa e del collo.                                                         A, Salonna G, et al. Sclerotherapy with poli-
Metodi. Sono stati analizzati i dati di 20 pazienti affetti da VM e LM del testa-collo, sot-        docanol microfoam in head and neck venous
toposti a scleroterapia con POL al 3%, iniettato nella lesione per via percutanea o endo-           and lymphatic malformations. Acta Otorhi-
scopica. La risposta è stata classificata come eccellente, moderata o scarsa in base alla           nolaryngol Ital 2022;42:116-125. https://doi.
riduzione del volume valutata mediante risonanza magnetica e alla risoluzione dei sintomi.          org/10.14639/0392-100X-N1310
Risultati. Il volume mediano si è ridotto da 19,3 ml a 5,8 ml dopo il trattamento (ridu-
zione volumetrica media: 72,98 ± 16,1%). Il 94,4% dei casi ha ottenuto una riposta ec-            © Società Italiana di Otorinolaringoiatria
                                                                                                  e Chirurgia Cervico-Facciale
cellente-moderata. In particolare è stata osservata una riduzione volumetrica media del
79,5 ± 16,1% nelle LM macrocistiche, del 76,1 ± 13,0% nelle VM, del 60,5 ± 10,9% LM
                                                                                                                 OPEN ACCESS
miste e del 42,5% nell’unica LM microcistica.
Conclusioni. La scleroterapia con POL sembra essere un trattamento efficace e sicuro: i           This is an open access article distributed in accordance with
                                                                                                  the CC-BY-NC-ND (Creative Commons Attribution-Non-
risultati migliori sono stati ottenuti nelle LM macrocistiche e nelle VM, mentre le LM miste      Commercial-NoDerivatives 4.0 International) license. The
hanno mostrato una moderata risposta e le LM microcistiche una scarsa risposta.                   article can be used by giving appropriate credit and mentio-
                                                                                                  ning the license, but only for non-commercial purposes and
PAROLE CHIAVE: malformazioni linfatiche, malformazioni venose, scleroterapia,                     only in the original version. For further information: https://
polidocanolo, malformazioni vascolari                                                             creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                      Sclerotherapy with polidocanol in head and neck vascular malformations




Introduction                                                       and effective in managing head and neck macrocystic and
                                                                   mixed LMs 12.
Venous and lymphatic malformations are heterogeneous
                                                                   Polidocanol (hydroxy-polyethoxy-dodecane - POL), a syn-
group of pathologies characterised by morpho-structural            thetic long-chain fatty alcohol, is a liquid surfactant with
and/or functional alterations that can affect any type of          endothelial cytolytic properties and has mainly been used
blood and/or lymphatic vessel of any calibre or anatomical         for venous malformations. Polidocanol injection is pain-
district 1. The classification of International Society for the    less, does not induce necrosis if injected intradermally and
Study of Vascular Anomalies (ISSVA) 2 is commonly used             rarely produces allergic or inflammatory reactions 13-17. Re-
and subdivides vascular anomalies into two main groups:            cently, it has also been proposed for lymphatic ones even
vascular tumours and vascular malformations 3. The latter          though it has been investigated in only a limited number of
group encloses high-flow lesions (arteriovenous malforma-          studies based on small samples, including several sites and
tions and arteriovenous fistula) and low-flow ones, includ-        not focused only on head and neck cases 14,17,18.
ing venous and lymphatic malformations.                            Herein, we report our protocol for head and neck lesions
Venous malformations (VMs) account for 44-64% of all vas-          describing our endoscopic and percutaneous approaches
cular malformations, with an incidence in the general popu-        that are performed in close cooperation between an inter-
lation between 0.8%-1% 4. About 40% of VMs affect head             ventional radiologist and ENT surgeon. Specifically, the
and neck region 5. Lymphatic malformations (LMs) result            objective of this study was to analyse the efficacy and safe-
from embryogenetic defects of lymphangiogenesis and 75%            ty of polidocanol sclerotherapy for head and neck vascu-
of cases are localised in the head and neck region and may         lar malformations in term of volume reduction at MRI and
result in functional and aesthetic deficits that may have a        resolution of symptoms at clinical evaluation.
negative psychosocial impact, particularly if untreated 6.
The optimal paradigm for management of venous and lym-
phatic malformations has yet to be established. Management         Materials and methods
strategies include “wait and see” with medical treatment of
exacerbations, sclerotherapy, or surgical resection. From a        Study population and study design
clinical point of view, it is very useful to distinguish between   This is a non-profit retrospective observational study per-
high-flow and low-flow vascular malformations in order to          formed at a single institution. Inclusion criteria were: pa-
determine the most appropriate treatment strategy. In fact,        tients treated by sclerotherapy at our institution because of
percutaneous sclerotherapy, which is not generally indicated       symptoms (dysphagia, dyspnoea, pain), aesthetic concerns
for high-flow lesions, has become a popular alternative to         with a negative psychosocial impact, oncoming risk of air-
surgical treatment for low-flow vascular malformations 7. De       way obstruction, increasing volume at radiological follow-
Maria et al. recently confirmed in a meta-analysis that per-       up. Exclusion criteria were: high flow vascular malforma-
cutaneous sclerotherapy is a very safe and effective modality      tions, previous surgery or previous sclerotherapy for the
for treatment of VMs of the head, neck and face 8.                 lesion to treat. Based on inclusion and exclusion criteria,
To date, several different agents have been proposed for scle-     we analysed data on 23 consecutive patients with head and
rotherapy with variable rates of efficacy. Ethanol, although       neck vascular malformations who were diagnosed, treated
one the first sclerosing agents used for vascular malforma-        and followed at our institution between January 2016 and
tions, is rarely chosen today due to its substantial side ef-      November 2019. Three patients were excluded: one oral
fects, such as skin complications (necrosis, pain and blister-     arteriovenous malformation treated with angiographic em-
ing), peripheral nerve injury, respiratory depression, cardiac     bolisation; two life-threatening mixed giant lymphatic con-
arrhythmia, seizure, rhabdomyolysis and hypoglycaemia 9.           genital malformations requiring surgery (the first treated
In a review in 2016, Horbach et al. reported that the rate of      with surgery and sirolimus; the second with sclerotherapy
complications was higher after ethanol sclerotherapy (18%)         with OK-432–Picibanil, surgery and medical therapy with
compared to other sclerosing agents (0-6%) 7.                      sirolimus).
As an alternative OK-432 (lyophilised mixture of Strep-            LMs were categorised based on cyst dimension as follows:
tococcus pyogenes and benzylpenicillin) has been used to           macrocystic (M > 50% of cysts larger than 2 cm), mixed
treat successfully mainly macrocystic lymphatic malforma-          (mix, < 50% of cysts larger than 2 cm) and microcystic
tions 10. Bleomycin, initially developed as an anti-tumour         (m, all cysts smaller than 2 cm) 19. They were classified
agent, has been used in the treatment of both microcystic          according to the de Serres staging system 20: stage I (uni-
and macrocystic LMs 11. Finally, doxycycline, a broad-             lateral infrahyoid disease), stage II (unilateral suprahyoid
spectrum antibiotic, has been demonstrated to be safe              disease), stage III (unilateral infrahyoid and suprahyoid



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E. De Corso et al.




disease), stage IV (bilateral infrahyoid disease) and stage V    Vascular malformations of upper aero-digestive airways
(bilateral infrahyoid and suprahyoid disease).                   were treated by endoscopic-guided trans-oral direct injec-
The data were directly obtained from our computerised            tion. Previous sedation or general anaesthesia, a 20-gauge
clinical database and medical records. Informed consent          venous catheter (JELCO PLUS; Smiths Medical Japan Ltd,
about privacy and utilisation of clinical data was obtained      Tokyo, Japan) was inserted into the lesion for no more than
from patients at the time of original data collection. The       1 cm (to make sure the right depth has been reached, plastic
data were anonymously analysed. The following data were          cover wrapping the distal portion of 1 cm from the extremi-
taken into consideration: symptoms, site of malformations,       ty of the catheter was removed). The needle was placed into
clinical objective characteristics of the lesions at ENT         the lesion at the point of maximal deformation and then 3%
physical evaluation, videolaryngoscopy, pre-treatment            POL-microfoam was injected after aspiration of part of the
magnetic resonance imaging (MRI) features, treatment             liquid contained within the lesion.
modalities and complications. Finally, we analysed out-          Cervical lesions (without involvement of aero-digestive
comes at 6-months in terms of resolution of symptoms and         airways) were treated by percutaneous procedures under
reduction of radiological volume at MRI.                         local anaesthesia with ultrasound guidance. In these cases,
                                                                 3% POL-microfoam was directly injected under ultrasound
Clinical management                                              guidance with a 20-gauge needle with previous aspiration
In our clinical practice, candidates for sclerotherapy usually   of an adequate amount of liquid contained within the lesion.
undergo pre-operative clinical examination, endoscopy of         We performed all procedures in close collaboration with
the upper airways and MRI. We usually discuss each case          an interventional radiologist in order to share expertise and
with an expert head and neck radiologist to confirm the di-      improve the precision during both ultrasound-guided and
agnosis, characterising the type, site and extension of the      endoscopic-guided injection.
lesion before treatment. All this information is particularly    In case of macrocytic lesions a single injection is per-
important for adequate counselling and treatment planning.       formed, while in other cases additional injections may be
We usually suggest sclerotherapy in case of symptoms (dys-       required. The volume injected depended on the size of the
phagia, dyspnoea, pain), aesthetic concerns with a negative      malformation and on the amount of aspirated content of
psychosocial impact and poor quality of life, oncoming risk      the lesion. However, the maximum dose of injected sclero-
of airway obstruction and increasing volume at radiologi-        sant did not exceed 2 mg/kg of POL independently of the
cal follow-up. Sclerotherapy is generally performed on out-      number of injections. The common pharmaceutical form
patients unless involvement of the upper airways requires        of POL is a 2-mL 3% ampule for injection and contains 60
general anaesthesia and overnight observation. Antibiotics       mg of POL. Hence, the maximum volume of POL liquid
are administered during treatment and paracetamol is given       is 0.067 mL/kg. This means that the maximum volume of
after treatment if required for pain; soft and cold diet plus    foam that can be provided from 3% POL by the Tessari
0.12% chlorhexidine gluconate mouthwash for 5 days are           method using a liquid to air ratio of 1:4 is 0.34 mL/kg.
prescribed in case of upper airway lesions. The first clini-
cal follow-up with ultrasound and endoscopy was usually          Outcomes
performed at 4 weeks after the procedure in all patients. In     Volumetric analysis was carried out by an expert head and
case of moderate volume reduction and/or persistence of          neck radiologist using a workstation (Advanced Worksta-
symptoms, patients are recommended for a second injec-           tion 4.7®, GE Healthcare) with dedicated software (Volume
tion that is usually performed 6-8 weeks after the first one.    Viewer®, GE Healthcare), evaluating pre- and post-proce-
Finally, patients undergo physical and MRI radiological          dural MRI studies. Lesion volume was calculated using
examination at 6 months following the last injection.            semiautomatic segmentation with the summation-of-area
                                                                 technique. The lesion was manually segmented on all axial
Sclerotherapy technique                                          T2-weighted images and the software automatically recon-
The sclerosing solution used in this study was 3% POL mi-        structed and calculated the volume 22,23.
crofoam (Polidocasklerol; Zeria Pharmaceutical Co, Ltd,          The efficacy of the procedure was evaluated in terms of
Tokyo, Japan). The sclerosing foam was provided on-site          resolution of clinical symptoms and volume reduction by
by direct injection using a liquid to air ratio of 1:4. Two      MRI comparing preoperative MRI lesion volume with
syringes were attached by a three-way stopcock, one filled       that at 6 months. An excellent response was assumed if
with POL and the other with air; the foam was obtained           > 90%volume reduction and complete resolution of symp-
by mixing the two syringes with multiple passages as de-         toms was observed; a moderate response was considered in
scribed by Tessari 21.                                           case of 50-90% volume reduction and partial or complete



118
                                                                   Sclerotherapy with polidocanol in head and neck vascular malformations




resolution of symptoms; poor response was noted in case         Table I. Cases series: demographics, vascular malformations and anatomic
of < 50% volume reduction and partial or no resolution of       distribution.
symptoms. In our experience, the polidocanol was com-            Case series                                             N = 20
pletely resorbed at the post treatment MRI at 6 months.         Demographics
Our experience with polidocanol sclerotherapy began in            Age                                               26.85 ± 14.4 DS
2016, and thus the maximum length of follow-up is 4 years,                                                            (range 7-60)
with a mean long-term follow-up of 34 months. We usually          Female                                               8/20 (40%)
perform clinical ENT evaluation and ultrasound monitor-           Male                                                12/20 (60%)
ing every year.                                                 Vascular malformations
We also evaluated the safety, side effects, average length of     Venous malformations                                 7/20 (35%)
stay and need for supportive medical treatment.                   Lymphatic malformations (LMs)                       13/20 (65%)
                                                                    Macrocystic LMs                                   7/13 (53.8%)
Statistical analysis                                                Mixed LMs (Macrocystic and Microcystic)           5/13 (38.5%)
Clinical and demographic characteristics were described             Microcystic LMs                                   1/13 (7.7%)
with descriptive statistics. In particular, the quantitative    Anatomic distribution
variables were represented by minimum, maximum, medi-             Lateral neck region                                  4/20 (20%)
an, range, average and standard deviation (SD), and quali-        Oropharynx                                           3/20 (15%)
tative ones by absolute and percentage frequencies.               Oral cavity                                          4/20 (20%)
SPSS program version 25.0 (SPSS Inc; IL, USA) was used            Parotid - parapharyngeal space                       2/20 (10%)
for statistical analysis. Continuous values such as volume        Parotid - masticatory space                          3/20 (15%)
of the lesions, were expressed as median and range. Volume        Submandibular-floor of the mouth                     3/20 (15%)
reduction was express as mean ± SD. Baseline and post-            Eyelid                                                1/20 (5%)
treatment values were compared using Student’s test for
paired samples in normally distributed values and Mann-
Whitney U-test for non-normally distributed data. Results
                                                                17.5 mm; CC, AP, LL, respectively) (p < 0.05). The median
were considered significant for p < 0.05.
                                                                pre-treatment volume evaluated by dedicated software was
                                                                20.58 mL (range 0.3 mL-436.8 mL) and decreased to 6.1
Results                                                         mL post-sclerotherapy (range 0.05 mL-176 mL) (p < 0.05).
Twenty patients were included in the analysis [8 females        Finally, a mean volume reduction of 73.38% was observed
(40%); mean age 26.3 ± 14.4 years (range 7-60)] who un-         considering all cases.
derwent direct intra-lesional sclerotherapy with 3% POL mi-     A subanalysis based on the type of lesion was performed.
crofoam; 7/20 (35%) were paediatric patients ≤ 18 years and     Preoperative median volume for VMs was 3.5 mL (range
13/20 (65%) were adults. None had previously received sur-      0. 3mL-436.8 mL) and reduced post-operatively to 0.3 mL
gical treatment or sclerotherapy with sclerosant agents. The    (range 0.05 mL-176 mL), with a mean volume reduction
lesions were classified based on the ISSVA classification as    of 76.1% (p < 0.05). The median preoperative volume of
follow: 13/20 (65%) LMs and 7/20 (35%) VMs. LMs were            LMs was 21.5 mL (range 0.96 mL-117 mL) and decreased
macrocystic in 7/13 (53.8%), mixed in 5/13 (38.5%) and mi-      post-treatment to 6.5 mL (range 0.08 mL-16.9 mL), with a
crocystic in 1/13 (7.7%). According to the de Serres staging    mean volume reduction of 71.8% (p < 0.05). Considering
system, 3/13 (23.1%) were stage I, 6/13 (46.1%) stage II,       the type of LM, we observed that the median volume re-
3/13 (23.1%) stage III and 1/13 (7.7%) stage V.                 duction decreased from 19.6 mL (range 0.9 mL-117 mL) to
Baseline characteristics of patients and anatomic localisa-     5.1 mL (range 0.08 mL-11.3 mL) (p < 0.05) in macrocystic
tion of the head and neck lesions are reported in Table I.      LMs; from 21.5 mL (range 10.1 mL-21.5 mL) to 6.5 mL
Clinical characteristics for each patient are summarised in     (range 3.5 mL-10.5 mL) (p < 0.05) in mixed LMs; from
Table II. We treated 12 patients by a percutaneous proce-       29.3 mL to 16.9 mL in microcystic one. The volume reduc-
dure under ultrasound guidance and 8 patients by direct         tion was 79.5% in macrocystic LMs, 67.1% in mixed LMs
endoscopic injection as reported in Table III.                  and 42.5% in the microcystic one.
We observed a significant difference between pre-treatment      In our series, the average amount of POL injected was 3.58
mean MRI diameters [46.8 x 32.8 x 28.8 mm; cranio-              cc (3-10 cc) and general anaesthesia was required in 6/20
caudal (CC), antero-posterior (AP), laterolateral (LL),         (30%) patients. The mean duration of hospitalisation was
respectively] versus post-treatment ones (31.3 x 21.5 x         1.15 days. Table III shows the effectiveness, safety and tech-



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E. De Corso et al.




Table II. Clinical characteristics of patients.
 Case          Sex, age                         Site                                     Symptoms                            Type of                            de Serres 20
                                                                                                                            vascular                          staging system
                                                                                                                           malformation                           for LMs
 1                 F, 19                     Lateral neck region                         Swelling                          Macrocystic LM                               I
 2                 M, 18              Parotid – Parapharyngeal space                     Bleeding                          Macrocystic LM                              II
 3                 F, 15            Submandibular – Floor of the mouth                   Swelling                            Mixed LM                                  II
 4                 M, 28                     Lateral neck region                         Swelling                          Macrocystic LM                               I
 5                 M, 38            Submandibular – Floor of the mouth                   Swelling                          Macrocystic LM                             III
 6                 F, 30                     Lateral neck region                         Swelling                            Mixed LM                                 III
 7                 M, 24                Oropharynx – Hypopharynx                        Swallowing                         Microcystic LM                              V
 8                 M, 25                          Pharynx                               Swallowing                              VM                                    NA
 9                 M, 22               Tongue – Floor of the mouth                      Swallowing                         Macrocystic LM                              II
 10                M, 26                         Oropharynx                               Globus                           Macrocystic LM                             III
 11                M, 18                        Oral Vestibule                           Bleeding                               VM                                    NA
 12                M, 35                Parotid – Masticatory space                 Pain at mastication                      Mixed LM                                  II
 13                M, 8                 Parotid – Masticatory space                 Pain at mastication                         VM                                    NA
 14                F, 60             Tongue – Lips – Temporal region               Impaired mastication                         VM                                    NA
 15                M, 17                     Lateral neck region                    Infection, Swelling                    Macrocystic LM                              I
 16                 F, 7                Parotid – Pharyngeal space                   Swallowing, Pain                           VM                                    NA
 17                F, 26                            Eyelid                                 Ptosis                               VM                                    NA
 18                F, 58                           Tongue                          Impaired mastication                         VM                                    NA
 19                F, 15                Parotid – Masticatory space                      Swelling                            Mixed LM                                  II
 20                M, 48            Submandibular – Floor of the mouth                   Swelling                            Mixed LM                                  II
LM: lymphatic malformation; VM: venous malformation; NA: not-applicable.



Table III. Technical details, safety and outcomes of the procedures.
 Case        MRI pre             MRI post      % volume        Symptom                   Anaesthesia        Guidance          No.            Complications            Outcome
            dimension           dimension      reduction       resolution                                                   sessions
            dCCxLLxAP          dCCxLLxAP
 1            64x33x23              41x22x11            -79.6%          Complete                L               US               2                 No                 Moderate
 2            53x43x15              41x30x11            -60.4%          Complete                L               US               2               Swelling             Moderate
 3            15x34x38              11x24x26            -64.6%           Partial                L               US               2                Pain                Moderate
 4            45x31x20              22x11x10            -91.3%          Complete                L               US               1                 No                 Excellent
 5            50x33x36              26x14x16            -90.2%          Complete                L               US               1                 No                 Excellent
 6            43x37x26              36x28x20            -51.3%           Partial                L               US               2                 No                 Moderate
 7            47x40x30              39x32x26            -42.5%            None                  G           Endoscopy            2                 No                   Poor
 8           100x32x27              84x23x21             -53%            Partial                G           Endoscopy            2               Swelling             Moderate
 9            12x11x14                8x5x4             -91.3%          Complete                L           Endoscopy            1                 No                 Excellent
 10           42x30x30              32x24x23            -53.3%           Partial                G           Endoscopy            2                Pain                Moderate
 11           11x24x20               5x11x9             -90.6%          Complete                L          Transoral/US          1                 No                 Excellent
 12           35x31x43              26x24x26            -65.2%           Partial                L               US               1                 No                 Moderate
 13           37x33x30              29x24x18            -65.8%           Partial                G               US               1               Swelling             Moderate
 14           30x16x12               12x7x6             -91.3%          Complete                G          Transoral/US          1                 No                 Excellent
 15           76X40X74              34x20x32            -90.3%          Complete                L               US               1                 No                 Excellent
 16          140x100x60             94x75x48            -59.7%           Partial                G          Transoral/US          2                Pain                Moderate
 17            16x7x5                12x4x2             -82.9%          Complete                L               US               1                 No                 Moderate
 18           28x16x15               12x9x6             -90.4%          Complete                L          Transoral/US          1                 No                 Excellent
 19           51x47x80              39x26x37            -80.5%          Complete                L               US               1                 No                 Moderate
 20           41x32x33              31x22x17            -73.2%          Complete                L               US               1                 No                 Moderate
L: local anaesthesia; G: general anaesthesia; dCC: cranio-caudal diameter; LL (latero-lateral); AP (antero-posterior) dCCxLLxAP are expressed in millimetres; US: ultrasound.




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                                                                                      Sclerotherapy with polidocanol in head and neck vascular malformations




nical details of the procedures. In terms of effectiveness,                       ing 13/20 (65%) patients, a second treatment was proposed,
we observed an excellent response in 9/20 (45%) patients,                         even if 5/13 (38.4%) patients refused because of clinical
a moderate response in 10/20 (50%) and poor response in                           symptomatic improvement. Finally, 8/13 (61.6%) patients
only 1 patient (5%). Figures 1, 2 and 3 show, respectively,                       underwent a second injection and 7/13 (53.8%) obtained a
a case of excellent response of a macrocystic LM of the                           moderate response and 1/13 (7.7%) patients had a poor one
floor of the mouth/submandibular region, a case of moder-                         at 6-month follow-up.
ate response of rhino-oropharyngeal VM and a case of poor                         At long-term follow-up, we did not observe relapse or re-
response of oro-hypopharyngeal microcystic LM.                                    growth of treated lesions confirming that our results were
According to the type of malformation, we observed the                            stable over time. Regarding the safety of polidocanol scle-
following responses: in macrocystic LMs an excellent re-                          rotherapy, no complications were noted during any treat-
sponse in 4/7 (57.1%) and a moderate one in 3/7 (42.9%);                          ment session. One patient developed a significant pharyn-
in mixed LMs, a moderate response in all cases (5/5); in the                      geal swelling after the first injection that resolved in 2-3
single treated microcystic LM, a poor response; in VMs, an                        days with oral steroids, two patients complained of a sig-
excellent response in 3/7 (42.9%) and a moderate one in                           nificant swelling of the parotid region after intra-lesional
4/7 (57.1%). Figures 4 and 5 show two cases of excellent                          injection that resolved in 2-3 days with oral steroids and
response of the oral vestibule VM and tongue VM, respec-                          two patients referred moderate-severe pain after the proce-
tively.                                                                           dure that resolved in one day with paracetamol. All other
All patients who obtained an excellent response (7/20)                            patients experienced only mild pain or mild oedema im-
achieved the result after a single session. In the remain-                        mediately after the procedure. No other complications such




 A                                                     B                                                    C




 D                                                     E                                                    F

Figure 1. Case 5 (Tabs. II-III): patient with macrocystic-LM of the floor of the mouth and submandibular region which achieved excellent response after one ses-
sion of 3% POL sclerotherapy. (A, B): pre-treatment images; (D, E): post-treatment images; (C, F): pre-treatment and 6-months follow up MRI respectively. The
LM volume decreased from 30.8 mL to 3.0 mL.



                                                                                                                                                          121
E. De Corso et al.




 A                                       B                                      C                                       D




 E                                       F                                      G                                       H

Figure 2. Case 8 (Tabs. II-III): patient with VM of the pharynx which achieved moderate response after two sessions of 3% POL sclerotherapy. Upper row: pre-
treatment MRI study and endoscopic view; Lower row: post-treatment MRI study (at 6 months follow up) and endoscopic view. (A, E): axial T2 fat saturated images
through the oropharynx; (B, F): axial T2 fat saturated images through the lower portion of nasopharynx; (C, G): coronal T2 fat saturated images (red dotted line: the
level of the axial images through the oropharynx, yellow dotted line: the level of the axial images through the nasopharynx); (D, H): pre and post-treatment endo-
scopic views, respectively. The VM volume decreased from 44.9 mL to 21.1 mL.




 A                                 B                                   C                           D                                 E




 F                                 G                                   H                           I                                 L

Figure 3. Case 7 (Tabs. II-III): patient with microcystic-LM of the oro-hypopharynx which achieved poor response after two sessions of 3% POL sclerotherapy.
Upper row: pre-treatment MRI study and endoscopic view. Lower row: post-treatment MRI study (at 6 months follow up) and endoscopic view. (A, F): axial T2 fat
saturated images through the oropharynx; (B, G): axial T2 fat saturated images through the hypopharynx; (C, H): coronal T2 fat saturated images (red dotted line:
the level of the axial images through the oropharynx; yellow dotted line: the level of the axial images through the hypopharynx); (D, I): pre-treatment and post-
treatment endoscopic views of oropharynx, respectively; (E, J): pre-treatment and post-treatment endoscopic view of hypopharynx, respectively. The LM volume
decreased from 29.3 mL to 16.8 mL



122
                                                                                       Sclerotherapy with polidocanol in head and neck vascular malformations




                                                                                    POL sclerotherapy has been reported to be safe and effec-
                                                                                    tive for treatment of VMs 15. In a recent manuscript, Hou
                                                                                    et al. 16 described their experience of POL sclerotherapy in
                                                                                    47 patients with VMs and reported a poor outcome for only
                                                                                    2/47 patients. POL sclerotherapy of LMs has been reported
                                                                                    in only a few series and rarely in head neck lesions 14,17,24.
                                                                                    Yamaki et al. 17 described a series of 32 LMs treated with
                                                                                    polidocanol sclerotherapy. In that series, only 47% of cases
                                                                                    had a head and neck localisation. The authors observed
 A                                        B                                         excellent and moderate responses in 88% of patients and
                                                                                    concluded that polidocanol sclerotherapy should be con-
                                                                                    sidered in the treatment of LMs, particularly those that are
                                                                                    exclusively macrocystic.
                                                                                    Jain et al. 13 reported a heterogenous series of vascular mal-
                                                                                    formations treated with 1% polidocanol and observed an
                                                                                    80% or greater decrease in the volume of the lesion in the
                                                                                    majority of patients; however, they did not further classify
                                                                                    lymphangiomas based on dimension of the cysts. Blaise et
 C                                        D
                                                                                    al. 18 described a series of 24 cases of low-flow vascular
                                                                                    malformations treated with polidocanol (only 9 were locat-
Figure 4. Case 11 (Tabs. II-III): patient with with VM of the oral vestible which   ed in the head and neck region), reporting > 50% reduction
achieved excellent response after one sessions of 3% POL sclerotherapy. (A,         in 37.5% of cases and < 50% reduction in 58.3% of cases.
B): pre-treatment sagittal and axial T2 fat saturated images; (C): pre-treatment    All studies have confirmed the excellent safety of POL scle-
VM of the oral vestibule; (D): 6-month post treatment follow-up. The VM vol-
ume decreased from 2.7 mL to 0.2 mL.                                                rotherapy even if there is some disagreement in terms of ef-
                                                                                    fectiveness. This discrepancy is justified by the rarity and sig-
                                                                                    nificant heterogeneity of vascular malformation in terms of
as intra-lesional bleeding, fever, secondary infections, or                         the location, type and dimension. In this series, we describe a
neurological deficits were observed.                                                series of exclusively head and neck vascular malformations,
Moreover, we never observed obstruction of upper aero-                              including upper airway lesions, demonstrating that POL scle-
digestive airways after sclerotherapy.                                              rotherapy is an effective and safe procedure both for VMs and
                                                                                    LMs. In fact, at 6 months follow-up we observed a mean MRI
                                                                                    volume reduction of 73.38% in the entire series. We observed
Discussion                                                                          an excellent response in one single injection in 35% of pa-
At present, there are no guidelines for the treatment of head                       tients, and a moderate response in 60% of patients with one
and neck vascular malformations. Surgery remains the gold                           or two injections. Overall, an excellent-moderate response
standard in most cases, although it is burdened by poor aes-                        was observed in 95% of cases. The number of treatment ses-
thetic and functional results. Nowadays, sclerotherapy has                          sions required using POL in our series is comparable to that
become a first-choice treatment, especially in low-flow vas-                        of other agents 7. Regarding morbidity of the procedure, we
cular malformations (venous and lymphatic ones), because                            observed only mild side effects that were easy to manage in
it is moderately invasive, well tolerated and effective.                            the early post-operative period. Finally, at long-term follow-
Numerous sclerosing agents have been proposed over the                              up, we observed that our results were stable over time. We
years. Recently, microfoam injection has become increas-                            believe that one factor contributing to the high success rate
ingly popular thanks to its unique properties and ease of                           is our radiologist-ENT multidisciplinary approach that is
management. In particular, POL is a non-ionic surfactant                            extremely beneficial in the management of these patients in
sclerosing agent that can reduce the volume of malforma-                            both the pre-treatment setting to characterise the lesion and
tion by directly damaging the vascular endothelial cells                            during the procedure to maximise outcomes. Cooperation is
thanks to activation of cellular calcium signalling and nitric                      particularly important in the pre-treatment setting in order to
oxide pathways. The POL foam displaces blood instead of                             identify the best candidate for sclerotherapy, and the optimal
diluting in it, allowing strict control of the concentration                        time to proceed. Decision to treat in fact is based not only on
of the agent in the vessel and leading to homogeneous dis-                          functional and aesthetic concerns, but also on radiologically
tribution within the lumen. Ultrasound-guided microfoam                             documented increases in dimensional lesion.



                                                                                                                                                       123
E. De Corso et al.




  A                                                   B                                                   C




  D                                                   E                                                   F

Figure 5. Case 18 (Tabs. III-IV): patient with VM of the tongue which achieved excellent response after one sessions of 3%POL sclerotherapy. Upper row: pre-
treatment images; Lower row: post-treatment images. The VM lesion decreased from 2.9 mL to 0.2 mL. In the same patient we also treated a little VM of the
inferior lip with good result.


This study should be interpreted in the context of its strengths                this study are related to its retrospective design and the lack of
and limitations. The strength of our study lies in the homoge-                  standardised method for evaluation of symptoms.
neity of treatment strategy: in fact, it is a single-centre study,
thus ensuring homogeneity in technique and patient care. All                    Conclusions
patients received the same procedure, and all patients were
required to undergo MRI before treatment and at 6 months af-                    Our data suggest that polidocanol sclerotherapy, performed
ter the last injection. None of the lesions had been previously                 in cooperation with a radiologist and otolaryngologist, is an
treated and all lesions were localised in the head and neck                     effective and safe procedure in cases of head and neck ve-
region. To best of our knowledge, this is one of the larger case                nous malformations and macrocystic lymphatic ones, and
series of low flow vascular malformations of head and neck                      provided very good results in mixed lymphatic malforma-
treated with POL foam sclerotherapy. We also performed a                        tions as well. These promising results should be confirmed
subanalysis for type of malformation, observing better re-                      by further and larger prospective studies in order to estab-
sponses in head and neck macrocystic LMs and VMs. Fur-                          lish the best indications for this agent.
thermore, in agreement with literature data, we observed a
moderate response in all mixed LMs and a poor response in                       Conflict of interest statement
microcystic LMs. Finally, we confirmed the safety and ef-                       The authors declare no conflict of interest.
fectiveness of the endoscopic-guided intralesional injection
of sclerosing agent for treatment of upper airway malforma-                     Funding
tions, firstly described in a small case series 25. The limits of               This research did not receive any specific grant from fund-



124
                                                                                     Sclerotherapy with polidocanol in head and neck vascular malformations




ing agencies in the public, commercial, or not-for-profit                       10
                                                                                     Greinwald JH, Burke DK, Sato Y, et al. Treatment of lymphangiomas
sectors.                                                                             in children: an update of Picibanil (OK-432) sclerotherapy. Otolar-
                                                                                     yngol Head Neck Surg 1999;121:381-387. https://doi.org/10.1016/
                                                                                     S0194-5998(99)70225-1
Authors’ contributions                                                          11
                                                                                     Parashar G, Shankar G, Sahadev R, et al. Intralesional sclerotherapy
Conceptualization: EDC; methodology: GS and GDC; val-                                with bleomycin in lymphatic malformation of tongue an institutional
idation: EDC; formal analysis: AC, SG and MP; investiga-                             experience and outcomes. J Indian Assoc Pediatr Surg 2020;25:80-84.
                                                                                     https://doi.org/10.4103/jiaps.JIAPS_2_19
tion: SG, MP, AC, GS and GDC; data curation: EDC and
                                                                                12
                                                                                     Cheng J. Doxycycline sclerotherapy in children with head and neck
GDC; writing – original draft preparation: EDC and GDC;                              lymphatic malformations. J Pediatr Surg 2015;50:2143-2146. https://
writing –review and editing: EDC and GDC; supervision:                               doi.org/10.1016/j.jpedsurg.2015.08.051
CC and GP; project administration: EDC and GDC. All au-                         13
                                                                                     Jain R, Bandhu S, Sawhney S, et al. Sonographically guided percu-
thors have read and agreed to the published version of the                           taneous sclerosis using 1% polidocanol in the treatment of vascu-
manuscript.                                                                          lar malformations. J Clin Ultrasound 2002;30:416-423. https://doi.
                                                                                     org/10.1002/jcu.10091
                                                                                14
                                                                                     Wang L, Liu F, Huang S. Percutaneous lauromacrogol foam sclero-
Ethical consideration                                                                therapy for the treatment of acute airway compression caused by lym-
This study was approved by the Institutional Ethics Com-                             phatic malformations in infants. Biomed Res Int 2018;2018:3878960.
mittee (Fondazione Policlinico Universitario Agostino                                https://doi.org/10.1155/2018/3878960
Gemelli IRCCS) [Approval Number/Protocol Number                                 15
                                                                                     Grieb D, Meila D, Greling B, et al. Craniofacial venous malforma-
11142/20 (ID3035)].                                                                  tions treated by percutaneous sclerotherapy using polidocanol: a
                                                                                     single-center experience. Acta Radiol Stockh Swed 2019;60:593-601.
The research was conducted ethically, with all study pro-                            https://doi.org/10.1177/0284185118795326
cedures being performed in accordance with the require-                         16
                                                                                     Hou F, Chen J, Xia M, et al. Percutaneous sclerotherapy with po-
ments of the World Medical Association’s Declaration of                              lidocanol under the guidance of ultrasound for venous malforma-
Helsinki.                                                                            tions in children - A retrospective cohort study from a single tertiary
Written informed consent was obtained from each partici-                             medical center. Medicine (Baltimore) 2020;99:e18839. https://doi.
                                                                                     org/10.1097/MD.0000000000018839
pant/patient for study participation and data publication.                      17
                                                                                     Yamaki T, Sasaki Y, Hasegawa Y, et al. Percutaneous ultrasound-
                                                                                     guided sclerotherapy with polidocanol microfoam for lymphatic
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