Accepted Manuscript Current concepts in diagnosis and treatment of venous malformations Neuschl Judith, M.D., D.M.D. Ernemann Ulrike, M.D., Ph.D Reinert Siegmar, M.D., D.M.D., Ph.D. Neuschl Matthias, M.D., D.M.D. Hoffmann Jürgen, M.D., D.M.D., Ph.D PII:
S1010-5182(14)00094-8
DOI:
10.1016/j.jcms.2014.03.014
Reference:
YJCMS 1758
To appear in:
Journal of Cranio-Maxillofacial Surgery
Received Date: 10 August 2013 Revised Date:
16 January 2014
Accepted Date: 20 March 2014
Please cite this article as: Judith N, Ulrike E, Siegmar R, Matthias N, Jürgen H, Current concepts in diagnosis and treatment of venous malformations, Journal of Cranio-Maxillofacial Surgery (2014), doi: 10.1016/j.jcms.2014.03.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Current concepts in diagnosis and treatment of venous malformations Neuschl, Judith, M.D., D.M.D. 1, Ernemann, Ulrike, M.D., Ph.D 2, Reinert, Siegmar, M.D., D.M.D., Ph.D. 1 , Neuschl, Matthias, M.D., D.M.D. 1,Hoffmann, Jürgen, M.D., D.M.D., Ph.D 3,
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Department of Oral and Maxillofacial Surgery (Head: Professor Dr. Dr. S. Reinert),
2
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University Hospital Tübingen, Tübingen (Germany)
Department of Diagnostic and Interventional Neuroradiology (Head: Professor Dr. U. Ernemann), University Hospital Tübingen, Tübingen (Germany)
Department of Oral and Maxillofacial Surgery (Head: Professor Dr. Dr. J. Hoffmann),
Authors: Dr. Dr. Judith Neuschl
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University Hospital Heidelberg, Heidelberg (Germany)
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Department of Oral and Maxillofacial Surgery University Hospital Tübingen,
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Osianderstr. 2-8, D-72076 Tübingen, Germany
Professor Dr. Ulrike Ernemann
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Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen,
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Hoppe-Seyler-Straße 3, D-72076 Tübingen, Germany
Professor Dr. Dr. Siegmar Reinert Department of Oral and Maxillofacial Surgery University Hospital Tübingen, Osianderstr. 2-8, D-72076 Tübingen, Germany E-mail: [email protected]
ACCEPTED MANUSCRIPT Dr. Dr. Matthias Neuschl Department of Oral and Maxillofacial Surgery University Hospital Tübingen,
Department of Oral and Maxillofacial Surgery University Hospital Heidelberg Im Neuenheimer Feld 400, D-69120 Heidelberg
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E-mail: [email protected]
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Professor Dr. Dr. Jürgen Hoffmann
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Osianderstr. 2-8, D-72076 Tübingen, Germany
Corresponding Author: Dr. Dr. Judith Neuschl
Department of Oral and Maxillofacial Surgery
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University Hospital Schleswig-Holstein, Campus Kiel, Arnold Hellerstr. 16, D-2410 Kiel, Germany
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E-mail: [email protected]
ACCEPTED MANUSCRIPT Abstract Introduction: Venous malformations are the most common type of vascular malformation, usually detected at birth or during puberty. By occurring during human growth or through localized trauma, pain, functional impairment and aesthetic disfigurement is often observed.
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Ultrasonography, Doppler flow Imaging, and Magnetic Resonance Imaging are the most informative techniques which reveal the extent of tissue involvement and differentiate between high and low flow anomalies.
Therapeutic options for treatment of venous malformations are sclerotherapy with alcohol, ethoxysclerol and
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bleomycin, lasertherapy (Nd:YAG), surgery and combined therapeutic modalities. The aim of percutaneous sclerotherapy is the successive reduction of the volume of the lesion by aseptic inflammation.
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Patients and Methods: This is a review of 51 patients with venous malformation treated by the Interdisciplinary Center for Vascular Anomalies at the University Hospital Tübingen, (Germany), from July, 2002 until January, 2007. The mean age of first consultation in our outpatient department was 26.4 years (median). 12 patients were treated by sclerotherapy with highly concentrated alcohol, 9 by surgery, and 7 by laser therapy. In some cases we combined different treatments. 9 patients had only sclerotherapy, while 3 had a
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combination of preoperative sclerotherapy and surgery. Results: We obtained positive results in patients treated with sclerotherapy and combined sclerotherapy and
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surgery.
Conclusion: Sclerotherapy is safe (under fluoroscopic control), efficient, and can be repeated multiple times.
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Therefore, it should be considered as first line treatment in venous malformations. A combination of a sclerotherapy with surgery is also useful in many cases.
Key words:
Sclerotherapy - aethoxysclerol - venous malformations - vascular malformation – laser therapy Introduction
ACCEPTED MANUSCRIPT Venous malformations are low flow malformations and make up more than 50 % of all vascular malformations (Berenguer et al., 1999). As 80 % of all cases are in the head and neck area, aesthetic disfigurement, facial asymmetry, and functional impairment are often observed (Zheng et al., 2013). Venous malformations develop due to dysplastic venous vessels of the quiescent endothelium (Mulliken and
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Glowacki, 1982). They are congenital and show a proportional growth according to humangrowth (Enjolras and Mulliken, 1993). Occasionally, these malformations can be non-evident until later in life due to very slow flow with gradual venous dilatation (Finn et al., 1983). Typical is commensurate growth or slow progression. The enlargement of a lesion is caused by an increase of blood pressure (Herbetreau et al., 1996). Factors causing
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enlargement are trauma and hormonal changes. Pain occurs because of stasis, microthrombosis and the
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formation of phleboliths.
In clinical examination, venous malformations appear as soft, expressible lesions, which cause asymmetry and functional impairment (Goffinet et al., 2010). A characteristic increase can be detected in a relevant position and during a Valsalva-maneuver. There is no palpable pulsation as found in high-flow arteriovenous malformations, unless they are intraosseous (Arneja and Gosain, 2008; Bagherzadegan et al., 2011; Zer Toros et
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al., 2010, Siniscalchi et al., 2009).
There are various means for diagnosing vascular malformations and several publications favour a defined diagnostic method for treatment planning (Hoffmann et al., 2008; Vesnaver and Dovsak, 2006).
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Ultrasonography, Doppler flow Imaging, and Magnetic Resonance Imaging are the most informative techniques which reveal the extent of tissue involvement and differentiate between high and low flow anomalies. MRI
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results show high signal cavities in T2- weighted images and phleboliths can easily be detected as round lowsignal formations (Berenguer et al., 1999). As it is about dysplastic venous vessels they do not opacify with arteriography (Burrows et al., 1983). Diagnosis using CT angiography is mainly reserved to high flow malformations such as arteriovenous lesions (Bagherzadegan et al., 2011; Ermer et al., 2013, Tao et al., 2010). Percutaneously applied sclerotherapy, by use of highly concentrated ethanol, has been reported to be an efficient treatment of venous malformations (Berenguer et al., 1999; Gelbert et al., 2000; Johnson et al., 2002; Pappas and Persky, 1988; Yakes et al., 1990). The ambition of percutaneous sclerotherapy is the successive reduction of the volume of the lesion by aseptic inflammation. Other options for treatment of venous malformations are laser therapy, surgery and combined therapeutic modalities.
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Patients and Methods This study included 51 patients with venous malformations who were treated at the interdisciplinary centre for vascular anomalies at the University Hospital of Tübingen, Germany, between July, 2002 and January, 2007.
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Average age of first consultation was 26.4 years (median). The oldest consultation was 76.9 and the youngest 0.4 years of age. The sex ratio (male:female) was 1: 1.4. 48 % of patients had been treated previously in
another place. 34.6 % of the patients showed an increase in the size of the malformation and 21 % had a
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functional lesion due to the vascular malformation. In 86.1 % lesions were located in the head and neck region, 2.8% on the trunk, and in 11.1 % on the extremities. The lesions located in the head and neck region (86.1 %)
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were distributed in the face (21.44%), cheek (17.86%), tongue (14.29%), intraoral (10.71%), forehead (7.14%), chin (3.57%), infraorbital (3.57%), nasal (3.57%) and parotid region (3.57%).
For diagnostics, we arranged an MRI in 37 % of patients In 29 % we relied on clinical examination without any imaging.
The aim of this review and appraisal of the treatment outcomes was to establish guidelines for different
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strategies of therapy. We undertook an analysis of sclerotherapy for venous malformations to determine the results of using 96 % ethanol and 3 % ethoxysclerol as a sclerosing agent, laser therapy (LITT Nd:Yag) and surgery, the complication rate, and whether age, sex, size of location, tissue involved or number of treatment
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sessions are correlated with outcome.
A precondition for sclerotherapy was a diagnostic MRI using contrast medium absorption (Figure 2). The
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malformation was punctured and the sclerosing agent was injected into the cavities of the lesion under contrast medium enhanced radiographic control (Figure 3). We used 96 % ethanol and 3 % ethoxysclerol as a sclerosing agent. The sclerosing agent caused denudation of the endothelium, inflammation, thrombosis, swelling and finally fibrosis of the malformation. Desired results were observed about 6- 8 weeks after therapy (Figure 4). Transcutaneous Nd:YAG Laser treatment was useful in cutaneous and subcutaneous venous malformations. By continuous ice cooling and compression of the malformation a depth of 0.8- 1,5 cm could be reached. Local cooling reduced the risks of side effects in the deeper skin layers. The ice was applied on the integument and
ACCEPTED MANUSCRIPT the laser beam was adjusted at right angles to the skin. Treatments were repeated after 6- 8 weeks. The effects of laser therapy were observed after a couple of sessions. We used special Hoshiaki-ice, which is clear of inclusions and does not absorb or reflect light. Interstitial application of the Nd:YAG laser was indicated in deep and extensive venous malformations. A bare fibre was
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placed intra-lesional trough a cannula. The fibre protruded out of the cannula by about 5 mm. It’s position was controlled by a red helium-neon control lamp. By pushing the fibre back and forward, a thermal damage of the endothelium was obtained.
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We used the Nd:YAG laser with a wavelength of 1064 nm, 50 W power, for 5- 10 seconds with a speed of 0,10,5 mm/ sec. Surface temperature was monitored digitally to avoid burning. A wavelength of 1064 nm was
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used, power of 5- 20 W, for 1- 5 seconds and speed of 0,2- 1mm/ sec.
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Results
The MRI-morphology of the venous malformations was well circumscribed in 50 % of the cases and diffuse or infiltrating in 50 %. 55.6 % of circumscribed malformations were macrocystic, 22.1 % microcystic and 23.9 %
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mixed. In 42.9 % of cases, the lesion was under 20 cm² and in 28.6 % the lesion was over 60 cm². Phleboliths were detected in 44.5 %.
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In the treatment of Venous Malformations, we used sclerotherapy in 40 % of cases, surgery or sclerotherapy and surgery in combination in 30 %, and laser therapy in 30 %. Two weeks after sclerotherapy 61 % of cases experienced pain, 77 % swelling and 38 % discoloration. Six weeks after sclerotherapy there was a decrease in the size of the lesion in 66 % of the cases, aesthetic improvement in 50 % and an improvement of the discoloration in 27 %. No patient complained of pain or swelling. In three patients, there was no reduction of the malformation and one patient had scars. 86 % of patients, felt there had been an overall improvement following sclerotherapy and 16 % felt there had been no change. Clinical examination six weeks after sclerotherapy revealed a reduction of the lesion in 79 % of cases and no change in 26 %. There was no progression of the lesion on any patient. 84 % of patients told us therapy was worthwhile
ACCEPTED MANUSCRIPT and 37 % of patients were satisfied by an improved aesthetic result. 31 % of patients were disappointed following their sclerotherapy. We saw a morphological reduction of the malformation on MRI after sclerotherapy in 30 % of cases and in all cases there was a decrease of signal in T2-weighted MRI due to the fibrosis induced in the malformation.
surgery in 69 % of cases and as a pre-operative treatment in 31 %.
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Sclerotherapy was used as a pre-operative treatment and as a single therapy. We used sclerotherapy without
Patients, who were treated by laser therapy had Nd:YAG-therapy in 77,8 % and IPL-therapy in 22.2 % . Laser-
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and light therapy sessions were repeated 2- 8 times.
Complications were hypo- and hyperpigmentation, which occurred in 11,1 % of cases. There was no significant
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reduction in the size of the lesion after laser- and light therapy, but we found an improved aesthetic result of discoloration in 22.2 %.
Discussion
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60 % of all malformations are not detected at birth but later in life. This occurs because of a very slow flow and steady venous pooling with gradual venous dilatation (Arnejan and Gosain, 2006). There is no sexual preference in vascular malformations, with an equal male to female ratio (Arnejan and Gosain, 2006; Brock et
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al., 1987; Cohen, 2006; Jacobs and Walton, 1976). In our studies, venous malformations were located in the region of the head and neck in 86 % of cases, on the trunk in 3 %, on the extremities in 11 % (Kohout et al.,
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1998).
Complications of sclerotherapy are ulceration, swelling and peripheral facial paralysis (Berenguer et al., 1999). After puncture, a contrast agent is injected to show the extent and drainage of the malformation. Macrocystic malformations have a better response to sclerotherapy than microcystic malformations. We saw a significant reduction of the malformation after sclerotherapy. We used 3 % ethoxyslerol and 96 % ethanol as sclerosing agents. 96 % ethanol was more effective than ethoxysclerol and had a good success rate, but complications were seen more frequently. Therefore, ethoxysclerol is indicated in cutaneous malformations to avoid necrosis (Shireman et al., 1997).
ACCEPTED MANUSCRIPT Several studies using bleomycin as an alternative sclerosing agent in the treatment of venous malformation and haemangiomas have reported treatment efficacy and low complication rates (Muir et al., 2004; Zhao et al., 2004; Jin et al., 2008; Luo et Zhao 2011). Spence et al. published good subjective and objective results after bleomycin percutaneous sclerotherapy in the treatment of venous malformations in the facial region. They
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recommended this agent in the treatment of venous malformation in the periorbital area and regions related to the airway (Spence et al., 2010). Therefore bleomycin may be an alternative sclerosant agent for facial regions.
Surgical excision was useful for localized lesions, as they are often present after several treatments of
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sclerotherapy (Berenguer et al., 1999). In diffuse venous malformations, which are located near to major
anatomic structures, a total surgical excision is not possible. In these cases laservtherapy is used (Poetke et al.,
possible to apply the sclerosing agent.
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1997; Poetke, 2003). Sclerotherapy is limited in small vessels without caverns or emissary veins, where it is not
Nd:YAG- laser therapy is used in cases of small vessels without caverns or in deeply located malformations. Laser treatment can minimize swelling and flow, as well as cause thrombosis in the malformation. The Nd:YAG
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laser is most effective for venous malformations because of its potential penetration and its degree of thermal injury (Greve and Raulin, 2006; Poetke et al., 1997). A Neodymium: Yttrium-Aluminium-Garnet-Laser has a wavelength of 1064 nm. It can be used ascontinuous wave or pulsed and can reach a middle power of 1000
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Watt (Böhm et al., 1989). Pulsed Nd:YAG-Lasers have a pulse length of up to 100 ms (Hohenleutner, 1997). Using a wavelength of 1064 nm a dermal depth of 8 mm can be reached. The non-visible infrared light is
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absorbed by the blood, therefore, the endothelium is damaged, nearby tissue is preserved and the laser effect is under the surface. The Nd:YAG laser treatment is published as an useful therapeutic option in vascular malformation especially in venous malformations (Vesnaver and Dovsak, 2006; Vesanver and Dovsak, 2009)
Conclusion Sclerosants constitute the first-line therapy for the management of Venous Malformations, which can be performed several times. Well-localized lesions amenable to excision should be removed surgically. Surgical excision can be performed in single or multiple stages with or without preoperative sclerotherapy
ACCEPTED MANUSCRIPT Conflict of Interest The authors do not have any financial or personal relationship with any other person or organisation that could
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inappropriately influence (bias) this work.
Captions to Illustrations (Legends)
ACCEPTED MANUSCRIPT Figure 1: Clinical appearance of a venous malformation of the cheek before percutaneous sclerotherapy. Figure 2: MRI diagnostics with coronal and axial T2w sign.
showing the extent and drainage of the venous malformation.
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Figure 3: Radiographic control using a contrast agent before percutaneous sclerotherapy
Figure 4: Clinical appearance of a venous malformation of the cheek after percutaneous
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sclerotherapy.
References
ACCEPTED MANUSCRIPT Arnejan, J. S., Gosain, A. K.: An Approach to the Management of Common Vascular Malformations of the Trunk. J Craniofac Surg 17: 761- 766, 2006
Arneja, J. S., Gosain, A. K. : Vascular Malformations. Plast Reconstr Surg 121: 195- 206,
RI PT
2008
Bagherzadegan, N., Hohlweg-Majert, B., Mücke, T., Haerle, S., Deppe, H., Wolff, K.-D.,
SC
Hölzle, F.: Microvascular bone grafting: A new long-term solution for intraosseous
M AN U
arteriovenous malformation of the mandible in children. J Craniofac Surg 39: 431- 434, 2011
Berenguer, B., Burrows, P., Zurakowski, D., Mulliken, J. B.: Sclerotherapy of craniofacial venous malformations: complications and results. Plast Reconstr Surg 1: 1- 11, 1999
TE D
Böhm, M., Grothues-Spork, M, Berlien, H.-P.: Anwendungsfelder des Lasers, 1- 6 in: Angewandte Lasermedizin, Lehr- und Handbuch für Praxis und Klinik. Hrsg. Berlien, H.-P.,
EP
Müller, G. Ecomed Verlagsgesellschaft Landsberg, München, Zürich, 1989
Brock, M. E., Smith, R. J. H., Parey, S. E., Mobley, D. L.: Lymphangioma. An otolaryngologic
AC C
perspective. Int J Pediatr Otorhinolaryngol 14: 133- 140, 1987
Burrows, P.E., Mulliken, J.B., Fellows, K.E., Strand, R.D.: Childhood hemangiomas and vascular malformations: Arteriographic differentiation. Am J Roentgenol 141: 483- 488, 1983
Cohen, M. M. Jr.: Research Review. Vascular Update: Morphogenesis, Tumors, Malformations, and Molecular Dimensions. Am J Med Genet A 140: 2013- 2038, 2006
ACCEPTED MANUSCRIPT Enjolras, O., Mulliken, J. B.:The current management of vascular birthmarks. Pediatric Dermatol 10: 311- 313, 1993
Ermer, M., Gutwald, R., Schumacher, M., Schmelzeisen, R., Taschner,C.: Use oft he radial
RI PT
forearm artery for secondary embolization of an extensive life-threatening arteriovenous malformation oft he mid-face and anterior skull base – A case report. J Craniomaxilllofac
SC
Surg 41: 258- 264, 2013
Finn, M. C., Glowacki, J., Mulliken, J. B.: Congenital vascular lesions: Clinical application of a
M AN U
new classification. J Pediatr Surg 18: 894- 900, 1983
Gelbert, F., Enjolras, O., Deffrenne, Amymard, A., Mounayer, C., Merland, J. J.: Percutanous sclerotherapy for venous malformationsof the lips: a retrospective study of 23 patients.
TE D
Neuroradiology 42: 692- 696, 2000
Goffinet, L., Laure, B., Tayeb, T., Amado, D., Herbreteau, D., Arbeille, P., Goga, D.: An
EP
arteriovenous fistula of the maxillary artery as a complication of Le Fort I osteotomy. J Craniomaxillofac Surg 38: 251- 254, 2010
AC C
Greve, B., Raulin, C.: Laser- und Lichttherapie von vaskulären Hauterkrankungen. Hautarzt 57: 537- 550, 2006
Herbetreau, D., Enjolras, O., Gelbert, F., Borsik, M., Riche, M.C., Lemarchand Venencie, F., Reizine, D., Merland, J.J.: The current management of cervico-cephalicvenous malformations. Pediatr Surg Int 11: 304- 307, 1996
ACCEPTED MANUSCRIPT Hoffmann, J., Schmid, J., Breuning, H., Rebmann, H., Besch, D., Ernemann, U., Reinert, S.: Differential diagnosis and treatment of vascular anomalies. J Craniomaxillofac Surg 36: 148- 149, 2008
Hohenleutner, U., Abd El-Raheem, T., Bäumler, W., Wlotzke, U., Landthaler, M.: Naevi
RI PT
flammei im Kindes und Jugendalter. Behandlung mit dem Blitzlampen-gepumpten Farbstofflaser. Hautarzt 46: 87- 93, 1995
SC
Hohenleutner, U.: Möglichkeiten und Grenzen der Lasertherapie, 91- 98 in: Benigne
Gefäßfehl- und Neubildungen der Haut. Interdisziplinäre Diagnostik und Therapie. Blackwell
M AN U
Verlag Berlin, 1997
Jacobs, A. H., Walton, R. G.: The incidence of birthmarks in the neonate. Pediatrics 58: 218-
TE D
222, 1976
Jin, Y., Lin, X., Li, W., Hu, X., Ma, G:, Wang, W.: Sclerotherapy after embolization of draining vein: a safe
EP
treatment for venous malformations, J Vasc Surg 47: 1292- 1299, 2008
Johnson, P. L., Eckard, D. A., Brecheisen, M. A., Girod, D. A., Tsue, T. T.: Percutaneous
AC C
Ethanol Sclerotherapy of Venous Malformations of the Tongue. Am J Neuroradiol 23: 779- 782, 2002
Kohout, M. P., Hansen, M., Pribaz, J. J., Mulliken, J. B.: Arteriovenous malformations of head and neck: Natural history and management. Plast Reconstr Surg 102: 643- 654, 1998
Luo, Q., Zhao, F.: How to use bleomycin A5 for infantile maxillofacial haemangiomas: Clinical evaluation of 82 consecutive cases. J Craniomaxilllofac Surg 39: 482- 486, 2011
ACCEPTED MANUSCRIPT
Muir, T., Kirsten, M., Fourie, P., Dippenaar, N., Ionescu, G. O.: Intralesional bleomycin injection (IBI) treatment for haemangiomas and congenital vascular malformations. Pediatr Surg Int 19: 766- 773, 2004
RI PT
Mulliken, J. B., Glowacki, J.: Hemangiomas and vascular malformations in infants and
422, 1982
SC
children: A classification bases on endothelial characteristics. Plast Reconstr Surg 69: 412-
Pappas, D. C., Persky, M. S.: Evaluation and treatment of head and neck venous vascular
M AN U
malformations. Ear Nose Throat J 77: 914- 916, 1988
Poetke, M., Philipp, C., Berlien, H.-P.: Ten years of laser treatment of hemangiomas and vascular malformations: techniques and results, 82- 91 in: Laser Surgery in Children. Berlien,
TE D
H.-P., Schmittenbecher, P.P. (ed.), Springer Verlag Berlin, 1997
Poetke, M.: Laser treatment in haemangiomas and vascular malformations, III-6.1, 444- 482
EP
in: Applied Laser Medicine, Berlien, H.-P., Müller, G.J. Springer Verlag, Berlin, 2003
AC C
Shireman, P. K., Mc Carthy, W. J., Yao, J. S. T.: treatment of venous malformations by direct injection with ethanol. J Vasc Surg 26: 838- 844, 1997
Siniscalchi, E. N., Minutoli, F., Catalfamo, L., Romano, F., Longo, M., De Ponte, F. S.: Intraosseous mandibola arterio-venous malforamations: Case report. J Craniomaxilllofac Surg 37: 106- 109, 2009
ACCEPTED MANUSCRIPT Spence, J. Krings, T., terBrugge, K. G., Da Costa, L. B., Agid, R.: Percutaneous sclerotherapy for facial venous malformations: subjective clinical and objective MR Imaging follow-up results. Am J Neuroradiol 31: 950- 960, 2010
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Tao, Q., Lu, B., Bhatia, K. S. S., Qiao, B., Zheng, Q.-Q., Chen, Z.-F.: Three-dimensional CT angiography for the diagnosis and assessment of arteriovenous malformations in the oral and maxillofacial region. J
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Craniomaxillofac Surg 38: 32- 37, 2010
Vesnaver, A., Dovsak, D. A.: Treatment of vascular lesions in the head and neck using Nd: YAG laser. J
M AN U
Craniomaxillofac Surg 37: 17- 24, 2006
Vesnaver, A., Dovsak, D. A.: Treatment of large vascular lesions in the orofacial region with the Nd:YAG laser. J Craniomaxillofac Surg 37: 191- 195, 2009
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Yakes, W. F., Haas, D. K., Parker, S. H.: Symptomatic vascular malformations: ethanol embolotherapy. Radiology 170: 1059- 1066, 1989
EP
Yakes, W. F., Luethke, J. M., Parker, S. H.: Ethanol embolisation of vascular malformations.
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Radiographics 10: 787- 796, 1990
Zer Toros, S., Zorlu, A., Deveci, I., Deveci, H. S., Naiboglu, B., Gökceer, T.: Traumatic arteriovenous fistula of the upper lip: a case report. J Craniomaxillofac Surg 38: 485- 487, 2010
Zhao, J. H., Zhang, W. F:, Zhao, Y. F.: Sclerotherapy of oral and facial venous malformationms with use of pingyangmycin and/ or sodium morrhuate. Int J Orla Maxillofac Surg 33: 463- 466, 2004
ACCEPTED MANUSCRIPT Zheng, J. W., Mai, H. M., Zhang, L., Wang, Y.A., Fan, X. D., Su, L.X., Qin, Z. P., Yang, Y. W., Jiang, Y. H., Zhao, Y. F., Suen, J. Y.: Guidelines for the treatment of head and neck venous malformations. Int J Clin Exp Med 22: 377-
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S1010-5182(14)00094-8
DOI:
10.1016/j.jcms.2014.03.014
Reference:
YJCMS 1758
To appear in:
Journal of Cranio-Maxillofacial Surgery
Received Date: 10 August 2013 Revised Date:
16 January 2014
Accepted Date: 20 March 2014
Please cite this article as: Judith N, Ulrike E, Siegmar R, Matthias N, Jürgen H, Current concepts in diagnosis and treatment of venous malformations, Journal of Cranio-Maxillofacial Surgery (2014), doi: 10.1016/j.jcms.2014.03.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Current concepts in diagnosis and treatment of venous malformations Neuschl, Judith, M.D., D.M.D. 1, Ernemann, Ulrike, M.D., Ph.D 2, Reinert, Siegmar, M.D., D.M.D., Ph.D. 1 , Neuschl, Matthias, M.D., D.M.D. 1,Hoffmann, Jürgen, M.D., D.M.D., Ph.D 3,
1
Department of Oral and Maxillofacial Surgery (Head: Professor Dr. Dr. S. Reinert),
2
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University Hospital Tübingen, Tübingen (Germany)
Department of Diagnostic and Interventional Neuroradiology (Head: Professor Dr. U. Ernemann), University Hospital Tübingen, Tübingen (Germany)
Department of Oral and Maxillofacial Surgery (Head: Professor Dr. Dr. J. Hoffmann),
Authors: Dr. Dr. Judith Neuschl
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University Hospital Heidelberg, Heidelberg (Germany)
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Department of Oral and Maxillofacial Surgery University Hospital Tübingen,
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Osianderstr. 2-8, D-72076 Tübingen, Germany
Professor Dr. Ulrike Ernemann
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Department of Diagnostic and Interventional Neuroradiology, University Hospital Tübingen,
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Hoppe-Seyler-Straße 3, D-72076 Tübingen, Germany
Professor Dr. Dr. Siegmar Reinert Department of Oral and Maxillofacial Surgery University Hospital Tübingen, Osianderstr. 2-8, D-72076 Tübingen, Germany E-mail: [email protected]
ACCEPTED MANUSCRIPT Dr. Dr. Matthias Neuschl Department of Oral and Maxillofacial Surgery University Hospital Tübingen,
Department of Oral and Maxillofacial Surgery University Hospital Heidelberg Im Neuenheimer Feld 400, D-69120 Heidelberg
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E-mail: [email protected]
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Professor Dr. Dr. Jürgen Hoffmann
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Osianderstr. 2-8, D-72076 Tübingen, Germany
Corresponding Author: Dr. Dr. Judith Neuschl
Department of Oral and Maxillofacial Surgery
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University Hospital Schleswig-Holstein, Campus Kiel, Arnold Hellerstr. 16, D-2410 Kiel, Germany
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E-mail: [email protected]
ACCEPTED MANUSCRIPT Abstract Introduction: Venous malformations are the most common type of vascular malformation, usually detected at birth or during puberty. By occurring during human growth or through localized trauma, pain, functional impairment and aesthetic disfigurement is often observed.
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Ultrasonography, Doppler flow Imaging, and Magnetic Resonance Imaging are the most informative techniques which reveal the extent of tissue involvement and differentiate between high and low flow anomalies.
Therapeutic options for treatment of venous malformations are sclerotherapy with alcohol, ethoxysclerol and
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bleomycin, lasertherapy (Nd:YAG), surgery and combined therapeutic modalities. The aim of percutaneous sclerotherapy is the successive reduction of the volume of the lesion by aseptic inflammation.
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Patients and Methods: This is a review of 51 patients with venous malformation treated by the Interdisciplinary Center for Vascular Anomalies at the University Hospital Tübingen, (Germany), from July, 2002 until January, 2007. The mean age of first consultation in our outpatient department was 26.4 years (median). 12 patients were treated by sclerotherapy with highly concentrated alcohol, 9 by surgery, and 7 by laser therapy. In some cases we combined different treatments. 9 patients had only sclerotherapy, while 3 had a
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combination of preoperative sclerotherapy and surgery. Results: We obtained positive results in patients treated with sclerotherapy and combined sclerotherapy and
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surgery.
Conclusion: Sclerotherapy is safe (under fluoroscopic control), efficient, and can be repeated multiple times.
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Therefore, it should be considered as first line treatment in venous malformations. A combination of a sclerotherapy with surgery is also useful in many cases.
Key words:
Sclerotherapy - aethoxysclerol - venous malformations - vascular malformation – laser therapy Introduction
ACCEPTED MANUSCRIPT Venous malformations are low flow malformations and make up more than 50 % of all vascular malformations (Berenguer et al., 1999). As 80 % of all cases are in the head and neck area, aesthetic disfigurement, facial asymmetry, and functional impairment are often observed (Zheng et al., 2013). Venous malformations develop due to dysplastic venous vessels of the quiescent endothelium (Mulliken and
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Glowacki, 1982). They are congenital and show a proportional growth according to humangrowth (Enjolras and Mulliken, 1993). Occasionally, these malformations can be non-evident until later in life due to very slow flow with gradual venous dilatation (Finn et al., 1983). Typical is commensurate growth or slow progression. The enlargement of a lesion is caused by an increase of blood pressure (Herbetreau et al., 1996). Factors causing
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enlargement are trauma and hormonal changes. Pain occurs because of stasis, microthrombosis and the
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formation of phleboliths.
In clinical examination, venous malformations appear as soft, expressible lesions, which cause asymmetry and functional impairment (Goffinet et al., 2010). A characteristic increase can be detected in a relevant position and during a Valsalva-maneuver. There is no palpable pulsation as found in high-flow arteriovenous malformations, unless they are intraosseous (Arneja and Gosain, 2008; Bagherzadegan et al., 2011; Zer Toros et
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al., 2010, Siniscalchi et al., 2009).
There are various means for diagnosing vascular malformations and several publications favour a defined diagnostic method for treatment planning (Hoffmann et al., 2008; Vesnaver and Dovsak, 2006).
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Ultrasonography, Doppler flow Imaging, and Magnetic Resonance Imaging are the most informative techniques which reveal the extent of tissue involvement and differentiate between high and low flow anomalies. MRI
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results show high signal cavities in T2- weighted images and phleboliths can easily be detected as round lowsignal formations (Berenguer et al., 1999). As it is about dysplastic venous vessels they do not opacify with arteriography (Burrows et al., 1983). Diagnosis using CT angiography is mainly reserved to high flow malformations such as arteriovenous lesions (Bagherzadegan et al., 2011; Ermer et al., 2013, Tao et al., 2010). Percutaneously applied sclerotherapy, by use of highly concentrated ethanol, has been reported to be an efficient treatment of venous malformations (Berenguer et al., 1999; Gelbert et al., 2000; Johnson et al., 2002; Pappas and Persky, 1988; Yakes et al., 1990). The ambition of percutaneous sclerotherapy is the successive reduction of the volume of the lesion by aseptic inflammation. Other options for treatment of venous malformations are laser therapy, surgery and combined therapeutic modalities.
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Patients and Methods This study included 51 patients with venous malformations who were treated at the interdisciplinary centre for vascular anomalies at the University Hospital of Tübingen, Germany, between July, 2002 and January, 2007.
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Average age of first consultation was 26.4 years (median). The oldest consultation was 76.9 and the youngest 0.4 years of age. The sex ratio (male:female) was 1: 1.4. 48 % of patients had been treated previously in
another place. 34.6 % of the patients showed an increase in the size of the malformation and 21 % had a
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functional lesion due to the vascular malformation. In 86.1 % lesions were located in the head and neck region, 2.8% on the trunk, and in 11.1 % on the extremities. The lesions located in the head and neck region (86.1 %)
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were distributed in the face (21.44%), cheek (17.86%), tongue (14.29%), intraoral (10.71%), forehead (7.14%), chin (3.57%), infraorbital (3.57%), nasal (3.57%) and parotid region (3.57%).
For diagnostics, we arranged an MRI in 37 % of patients In 29 % we relied on clinical examination without any imaging.
The aim of this review and appraisal of the treatment outcomes was to establish guidelines for different
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strategies of therapy. We undertook an analysis of sclerotherapy for venous malformations to determine the results of using 96 % ethanol and 3 % ethoxysclerol as a sclerosing agent, laser therapy (LITT Nd:Yag) and surgery, the complication rate, and whether age, sex, size of location, tissue involved or number of treatment
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sessions are correlated with outcome.
A precondition for sclerotherapy was a diagnostic MRI using contrast medium absorption (Figure 2). The
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malformation was punctured and the sclerosing agent was injected into the cavities of the lesion under contrast medium enhanced radiographic control (Figure 3). We used 96 % ethanol and 3 % ethoxysclerol as a sclerosing agent. The sclerosing agent caused denudation of the endothelium, inflammation, thrombosis, swelling and finally fibrosis of the malformation. Desired results were observed about 6- 8 weeks after therapy (Figure 4). Transcutaneous Nd:YAG Laser treatment was useful in cutaneous and subcutaneous venous malformations. By continuous ice cooling and compression of the malformation a depth of 0.8- 1,5 cm could be reached. Local cooling reduced the risks of side effects in the deeper skin layers. The ice was applied on the integument and
ACCEPTED MANUSCRIPT the laser beam was adjusted at right angles to the skin. Treatments were repeated after 6- 8 weeks. The effects of laser therapy were observed after a couple of sessions. We used special Hoshiaki-ice, which is clear of inclusions and does not absorb or reflect light. Interstitial application of the Nd:YAG laser was indicated in deep and extensive venous malformations. A bare fibre was
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placed intra-lesional trough a cannula. The fibre protruded out of the cannula by about 5 mm. It’s position was controlled by a red helium-neon control lamp. By pushing the fibre back and forward, a thermal damage of the endothelium was obtained.
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We used the Nd:YAG laser with a wavelength of 1064 nm, 50 W power, for 5- 10 seconds with a speed of 0,10,5 mm/ sec. Surface temperature was monitored digitally to avoid burning. A wavelength of 1064 nm was
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used, power of 5- 20 W, for 1- 5 seconds and speed of 0,2- 1mm/ sec.
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Results
The MRI-morphology of the venous malformations was well circumscribed in 50 % of the cases and diffuse or infiltrating in 50 %. 55.6 % of circumscribed malformations were macrocystic, 22.1 % microcystic and 23.9 %
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mixed. In 42.9 % of cases, the lesion was under 20 cm² and in 28.6 % the lesion was over 60 cm². Phleboliths were detected in 44.5 %.
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In the treatment of Venous Malformations, we used sclerotherapy in 40 % of cases, surgery or sclerotherapy and surgery in combination in 30 %, and laser therapy in 30 %. Two weeks after sclerotherapy 61 % of cases experienced pain, 77 % swelling and 38 % discoloration. Six weeks after sclerotherapy there was a decrease in the size of the lesion in 66 % of the cases, aesthetic improvement in 50 % and an improvement of the discoloration in 27 %. No patient complained of pain or swelling. In three patients, there was no reduction of the malformation and one patient had scars. 86 % of patients, felt there had been an overall improvement following sclerotherapy and 16 % felt there had been no change. Clinical examination six weeks after sclerotherapy revealed a reduction of the lesion in 79 % of cases and no change in 26 %. There was no progression of the lesion on any patient. 84 % of patients told us therapy was worthwhile
ACCEPTED MANUSCRIPT and 37 % of patients were satisfied by an improved aesthetic result. 31 % of patients were disappointed following their sclerotherapy. We saw a morphological reduction of the malformation on MRI after sclerotherapy in 30 % of cases and in all cases there was a decrease of signal in T2-weighted MRI due to the fibrosis induced in the malformation.
surgery in 69 % of cases and as a pre-operative treatment in 31 %.
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Sclerotherapy was used as a pre-operative treatment and as a single therapy. We used sclerotherapy without
Patients, who were treated by laser therapy had Nd:YAG-therapy in 77,8 % and IPL-therapy in 22.2 % . Laser-
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and light therapy sessions were repeated 2- 8 times.
Complications were hypo- and hyperpigmentation, which occurred in 11,1 % of cases. There was no significant
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reduction in the size of the lesion after laser- and light therapy, but we found an improved aesthetic result of discoloration in 22.2 %.
Discussion
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60 % of all malformations are not detected at birth but later in life. This occurs because of a very slow flow and steady venous pooling with gradual venous dilatation (Arnejan and Gosain, 2006). There is no sexual preference in vascular malformations, with an equal male to female ratio (Arnejan and Gosain, 2006; Brock et
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al., 1987; Cohen, 2006; Jacobs and Walton, 1976). In our studies, venous malformations were located in the region of the head and neck in 86 % of cases, on the trunk in 3 %, on the extremities in 11 % (Kohout et al.,
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1998).
Complications of sclerotherapy are ulceration, swelling and peripheral facial paralysis (Berenguer et al., 1999). After puncture, a contrast agent is injected to show the extent and drainage of the malformation. Macrocystic malformations have a better response to sclerotherapy than microcystic malformations. We saw a significant reduction of the malformation after sclerotherapy. We used 3 % ethoxyslerol and 96 % ethanol as sclerosing agents. 96 % ethanol was more effective than ethoxysclerol and had a good success rate, but complications were seen more frequently. Therefore, ethoxysclerol is indicated in cutaneous malformations to avoid necrosis (Shireman et al., 1997).
ACCEPTED MANUSCRIPT Several studies using bleomycin as an alternative sclerosing agent in the treatment of venous malformation and haemangiomas have reported treatment efficacy and low complication rates (Muir et al., 2004; Zhao et al., 2004; Jin et al., 2008; Luo et Zhao 2011). Spence et al. published good subjective and objective results after bleomycin percutaneous sclerotherapy in the treatment of venous malformations in the facial region. They
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recommended this agent in the treatment of venous malformation in the periorbital area and regions related to the airway (Spence et al., 2010). Therefore bleomycin may be an alternative sclerosant agent for facial regions.
Surgical excision was useful for localized lesions, as they are often present after several treatments of
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sclerotherapy (Berenguer et al., 1999). In diffuse venous malformations, which are located near to major
anatomic structures, a total surgical excision is not possible. In these cases laservtherapy is used (Poetke et al.,
possible to apply the sclerosing agent.
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1997; Poetke, 2003). Sclerotherapy is limited in small vessels without caverns or emissary veins, where it is not
Nd:YAG- laser therapy is used in cases of small vessels without caverns or in deeply located malformations. Laser treatment can minimize swelling and flow, as well as cause thrombosis in the malformation. The Nd:YAG
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laser is most effective for venous malformations because of its potential penetration and its degree of thermal injury (Greve and Raulin, 2006; Poetke et al., 1997). A Neodymium: Yttrium-Aluminium-Garnet-Laser has a wavelength of 1064 nm. It can be used ascontinuous wave or pulsed and can reach a middle power of 1000
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Watt (Böhm et al., 1989). Pulsed Nd:YAG-Lasers have a pulse length of up to 100 ms (Hohenleutner, 1997). Using a wavelength of 1064 nm a dermal depth of 8 mm can be reached. The non-visible infrared light is
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absorbed by the blood, therefore, the endothelium is damaged, nearby tissue is preserved and the laser effect is under the surface. The Nd:YAG laser treatment is published as an useful therapeutic option in vascular malformation especially in venous malformations (Vesnaver and Dovsak, 2006; Vesanver and Dovsak, 2009)
Conclusion Sclerosants constitute the first-line therapy for the management of Venous Malformations, which can be performed several times. Well-localized lesions amenable to excision should be removed surgically. Surgical excision can be performed in single or multiple stages with or without preoperative sclerotherapy
ACCEPTED MANUSCRIPT Conflict of Interest The authors do not have any financial or personal relationship with any other person or organisation that could
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inappropriately influence (bias) this work.
Captions to Illustrations (Legends)
ACCEPTED MANUSCRIPT Figure 1: Clinical appearance of a venous malformation of the cheek before percutaneous sclerotherapy. Figure 2: MRI diagnostics with coronal and axial T2w sign.
showing the extent and drainage of the venous malformation.
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Figure 3: Radiographic control using a contrast agent before percutaneous sclerotherapy
Figure 4: Clinical appearance of a venous malformation of the cheek after percutaneous
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sclerotherapy.
References
ACCEPTED MANUSCRIPT Arnejan, J. S., Gosain, A. K.: An Approach to the Management of Common Vascular Malformations of the Trunk. J Craniofac Surg 17: 761- 766, 2006
Arneja, J. S., Gosain, A. K. : Vascular Malformations. Plast Reconstr Surg 121: 195- 206,
RI PT
2008
Bagherzadegan, N., Hohlweg-Majert, B., Mücke, T., Haerle, S., Deppe, H., Wolff, K.-D.,
SC
Hölzle, F.: Microvascular bone grafting: A new long-term solution for intraosseous
M AN U
arteriovenous malformation of the mandible in children. J Craniofac Surg 39: 431- 434, 2011
Berenguer, B., Burrows, P., Zurakowski, D., Mulliken, J. B.: Sclerotherapy of craniofacial venous malformations: complications and results. Plast Reconstr Surg 1: 1- 11, 1999
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Böhm, M., Grothues-Spork, M, Berlien, H.-P.: Anwendungsfelder des Lasers, 1- 6 in: Angewandte Lasermedizin, Lehr- und Handbuch für Praxis und Klinik. Hrsg. Berlien, H.-P.,
EP
Müller, G. Ecomed Verlagsgesellschaft Landsberg, München, Zürich, 1989
Brock, M. E., Smith, R. J. H., Parey, S. E., Mobley, D. L.: Lymphangioma. An otolaryngologic
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perspective. Int J Pediatr Otorhinolaryngol 14: 133- 140, 1987
Burrows, P.E., Mulliken, J.B., Fellows, K.E., Strand, R.D.: Childhood hemangiomas and vascular malformations: Arteriographic differentiation. Am J Roentgenol 141: 483- 488, 1983
Cohen, M. M. Jr.: Research Review. Vascular Update: Morphogenesis, Tumors, Malformations, and Molecular Dimensions. Am J Med Genet A 140: 2013- 2038, 2006
ACCEPTED MANUSCRIPT Enjolras, O., Mulliken, J. B.:The current management of vascular birthmarks. Pediatric Dermatol 10: 311- 313, 1993
Ermer, M., Gutwald, R., Schumacher, M., Schmelzeisen, R., Taschner,C.: Use oft he radial
RI PT
forearm artery for secondary embolization of an extensive life-threatening arteriovenous malformation oft he mid-face and anterior skull base – A case report. J Craniomaxilllofac
SC
Surg 41: 258- 264, 2013
Finn, M. C., Glowacki, J., Mulliken, J. B.: Congenital vascular lesions: Clinical application of a
M AN U
new classification. J Pediatr Surg 18: 894- 900, 1983
Gelbert, F., Enjolras, O., Deffrenne, Amymard, A., Mounayer, C., Merland, J. J.: Percutanous sclerotherapy for venous malformationsof the lips: a retrospective study of 23 patients.
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Neuroradiology 42: 692- 696, 2000
Goffinet, L., Laure, B., Tayeb, T., Amado, D., Herbreteau, D., Arbeille, P., Goga, D.: An
EP
arteriovenous fistula of the maxillary artery as a complication of Le Fort I osteotomy. J Craniomaxillofac Surg 38: 251- 254, 2010
AC C
Greve, B., Raulin, C.: Laser- und Lichttherapie von vaskulären Hauterkrankungen. Hautarzt 57: 537- 550, 2006
Herbetreau, D., Enjolras, O., Gelbert, F., Borsik, M., Riche, M.C., Lemarchand Venencie, F., Reizine, D., Merland, J.J.: The current management of cervico-cephalicvenous malformations. Pediatr Surg Int 11: 304- 307, 1996
ACCEPTED MANUSCRIPT Hoffmann, J., Schmid, J., Breuning, H., Rebmann, H., Besch, D., Ernemann, U., Reinert, S.: Differential diagnosis and treatment of vascular anomalies. J Craniomaxillofac Surg 36: 148- 149, 2008
Hohenleutner, U., Abd El-Raheem, T., Bäumler, W., Wlotzke, U., Landthaler, M.: Naevi
RI PT
flammei im Kindes und Jugendalter. Behandlung mit dem Blitzlampen-gepumpten Farbstofflaser. Hautarzt 46: 87- 93, 1995
SC
Hohenleutner, U.: Möglichkeiten und Grenzen der Lasertherapie, 91- 98 in: Benigne
Gefäßfehl- und Neubildungen der Haut. Interdisziplinäre Diagnostik und Therapie. Blackwell
M AN U
Verlag Berlin, 1997
Jacobs, A. H., Walton, R. G.: The incidence of birthmarks in the neonate. Pediatrics 58: 218-
TE D
222, 1976
Jin, Y., Lin, X., Li, W., Hu, X., Ma, G:, Wang, W.: Sclerotherapy after embolization of draining vein: a safe
EP
treatment for venous malformations, J Vasc Surg 47: 1292- 1299, 2008
Johnson, P. L., Eckard, D. A., Brecheisen, M. A., Girod, D. A., Tsue, T. T.: Percutaneous
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Ethanol Sclerotherapy of Venous Malformations of the Tongue. Am J Neuroradiol 23: 779- 782, 2002
Kohout, M. P., Hansen, M., Pribaz, J. J., Mulliken, J. B.: Arteriovenous malformations of head and neck: Natural history and management. Plast Reconstr Surg 102: 643- 654, 1998
Luo, Q., Zhao, F.: How to use bleomycin A5 for infantile maxillofacial haemangiomas: Clinical evaluation of 82 consecutive cases. J Craniomaxilllofac Surg 39: 482- 486, 2011
ACCEPTED MANUSCRIPT
Muir, T., Kirsten, M., Fourie, P., Dippenaar, N., Ionescu, G. O.: Intralesional bleomycin injection (IBI) treatment for haemangiomas and congenital vascular malformations. Pediatr Surg Int 19: 766- 773, 2004
RI PT
Mulliken, J. B., Glowacki, J.: Hemangiomas and vascular malformations in infants and
422, 1982
SC
children: A classification bases on endothelial characteristics. Plast Reconstr Surg 69: 412-
Pappas, D. C., Persky, M. S.: Evaluation and treatment of head and neck venous vascular
M AN U
malformations. Ear Nose Throat J 77: 914- 916, 1988
Poetke, M., Philipp, C., Berlien, H.-P.: Ten years of laser treatment of hemangiomas and vascular malformations: techniques and results, 82- 91 in: Laser Surgery in Children. Berlien,
TE D
H.-P., Schmittenbecher, P.P. (ed.), Springer Verlag Berlin, 1997
Poetke, M.: Laser treatment in haemangiomas and vascular malformations, III-6.1, 444- 482
EP
in: Applied Laser Medicine, Berlien, H.-P., Müller, G.J. Springer Verlag, Berlin, 2003
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Shireman, P. K., Mc Carthy, W. J., Yao, J. S. T.: treatment of venous malformations by direct injection with ethanol. J Vasc Surg 26: 838- 844, 1997
Siniscalchi, E. N., Minutoli, F., Catalfamo, L., Romano, F., Longo, M., De Ponte, F. S.: Intraosseous mandibola arterio-venous malforamations: Case report. J Craniomaxilllofac Surg 37: 106- 109, 2009
ACCEPTED MANUSCRIPT Spence, J. Krings, T., terBrugge, K. G., Da Costa, L. B., Agid, R.: Percutaneous sclerotherapy for facial venous malformations: subjective clinical and objective MR Imaging follow-up results. Am J Neuroradiol 31: 950- 960, 2010
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Tao, Q., Lu, B., Bhatia, K. S. S., Qiao, B., Zheng, Q.-Q., Chen, Z.-F.: Three-dimensional CT angiography for the diagnosis and assessment of arteriovenous malformations in the oral and maxillofacial region. J
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Craniomaxillofac Surg 38: 32- 37, 2010
Vesnaver, A., Dovsak, D. A.: Treatment of vascular lesions in the head and neck using Nd: YAG laser. J
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Craniomaxillofac Surg 37: 17- 24, 2006
Vesnaver, A., Dovsak, D. A.: Treatment of large vascular lesions in the orofacial region with the Nd:YAG laser. J Craniomaxillofac Surg 37: 191- 195, 2009
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Yakes, W. F., Haas, D. K., Parker, S. H.: Symptomatic vascular malformations: ethanol embolotherapy. Radiology 170: 1059- 1066, 1989
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Yakes, W. F., Luethke, J. M., Parker, S. H.: Ethanol embolisation of vascular malformations.
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Radiographics 10: 787- 796, 1990
Zer Toros, S., Zorlu, A., Deveci, I., Deveci, H. S., Naiboglu, B., Gökceer, T.: Traumatic arteriovenous fistula of the upper lip: a case report. J Craniomaxillofac Surg 38: 485- 487, 2010
Zhao, J. H., Zhang, W. F:, Zhao, Y. F.: Sclerotherapy of oral and facial venous malformationms with use of pingyangmycin and/ or sodium morrhuate. Int J Orla Maxillofac Surg 33: 463- 466, 2004
ACCEPTED MANUSCRIPT Zheng, J. W., Mai, H. M., Zhang, L., Wang, Y.A., Fan, X. D., Su, L.X., Qin, Z. P., Yang, Y. W., Jiang, Y. H., Zhao, Y. F., Suen, J. Y.: Guidelines for the treatment of head and neck venous malformations. Int J Clin Exp Med 22: 377-
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