Effectiveness and safety of 1470-nm diode laser fulguration in the management of diffuse venous malformations

Effectiveness and safety of 1470-nm diode laser fulguration in the management of diffuse venous malformations Elena Marín-Manzano, MD,a Covadonga Mendieta-Azcona, MD, PhD,a Luis Riera-del-Moral, MD, PhD,a and Juan Carlos López-Gutiérrez, MD, PhD,b Madrid, Spain

ABSTRACT Background: Venous malformations (VMs) are the most frequent congenital vascular malformations. Pain and deformity are the main symptoms and usually progressive in untreated patients. Current therapeutic options are surgery (frequently partial resections with an uncomfortable postoperative period), sclerotherapy (often limited because of the need for high doses and the potential subsequent toxicity), and percutaneous intralesional laser treatment. The main objective of our study was to analyze efficiency and safety of 1470-nm diode laser treatment in the management of diffuse VMs. Methods: We included patients treated between 2012 and 2018 whose quality of life was severely impaired. Data regarding laser settings, previous and subsequent D-dimer and fibrinogen blood levels, preprocedural and postprocedural assessment of pain by means of a visual analog scale, and reported complications were collected. Results: Twenty-six procedures were performed in 17 patients (76% women); 59% were sporadic VMs, 70% had previously undergone other treatments, and 53% needed continuous analgesic treatment. The median pain reduction after the intervention, measured on the visual analog scale, was 5 points (P < .001). A significant decrease in the postoperative Ddimer values (P ¼ .003) was observed in all patients. There were five postoperative complications in four patients, and none was life-threatening. Conclusions: The diode laser appears to be effective for treatment of diffuse VMs. It allows a reduction of the volume and symptoms of the malformation and is well tolerated by the patients. There is no currently described limitation in terms of dosage or number of procedures, making this a good alternative therapeutic option for these malformations. (J Vasc Surg: Venous and Lym Dis 2019;-:1-12.) Keywords: 1470-nm diode laser; Diffuse venous malformations; Effectiveness

Congenital vascular malformations are always present at birth, although sometimes they are not visible up to weeks, months, or years later. They have an estimated incidence of 1.5%,1 and approximately two-thirds are predominantly venous. Incidence shows no sex or racial preferences. Venous malformations (VMs) normally became symptomatic with pain, edema, functional alteration, or deformity. They frequently grow proportionally with the patient and expand in response to hormonal changes, an incomplete surgical resection, or trauma and never spontaneously involute.2 Their clinical course cannot be predicted. They are usually progressive and incurable in diffuse cases.3 This chronic process severely impairs the

From the Department of Angiology and Vascular Surgery,a and Department of Pediatric Plastic Surgery,b University Hospital La Paz. Author conflict of interest: none. Correspondence: Elena Marín-Manzano, MD, Department of Angiology and Vascular Surgery, Hospital Universitario La Paz, Paseo de la Castellana, 261, 28046 Madrid, Spain (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the Journal policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 2213-333X Copyright Ó 2019 by the Society for Vascular Surgery. Published by Elsevier Inc. https://doi.org/10.1016/j.jvsv.2019.09.013

patients’ quality of life. In addition, these malformations often affect cosmetically important areas, with an important psychosocial impact. When VMs are diffuse, there are few available therapeutic options: pressure garments4; anticoagulant agents,2 such as low-molecular-weight heparin, fondaparinux, or direct oral anticoagulants5; and mammalian target of rapamycin inhibitors, such as sirolimus.6 Surgery in these patients aims to reduce volume of the malformation and to relieve associated symptoms, especially in zones with thrombosis or phleboliths. Removal of extensively malformed areas may trigger complications like hemorrhage, coagulopathies (including disseminated intravascular coagulation), hematoma, wound dehiscence, abnormal scarring, and neurovascular bundle injuries.7 Another option is endovascular treatment. This offers the possibility of sclerotherapy or embolization with different physical agents.3 Embolization is performed with coils, plugs (occasionally used in truncular VMs), Onyx (ev3, Covidien, Plymouth, Minn), and glue; sclerotherapy is performed with liquids (alcohol) or foams (polidocanol and sodium tetradecyl sulfate [STS]).8 These techniques may have limitations for patients with diffuse VMs that mainly derive from the adverse effects of sclerosing substances and the large volumes needed to treat 1

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the VM, including the risk of pulmonary fibrosis from bleomycin,9 pulmonary embolism from alcohol,10 visual alterations or scotomas, pulmonary hypertension or cardiac failure from the absorption of polidocanol foams,11 and necrosis of treated or adjacent areas from alcohol and STS.9,12 Many centers now consider the endovenous laser to be a first line of treatment in varicose veins because it has better medium- and long-term results than conventional surgery13 or sclerotherapy.14 A few years ago, the intralesional laser was introduced as a therapeutic alternative in some patients with VMs. Series of patients showing its effectiveness and safety in limited or extensive orofacial lesions have been published,15,16 all using an 810-nm diode laser. Although the most appropriate wavelength to treat this pathologic process is still a topic of debate, the 1470-nm diode laser has been shown to be the most suitable for treating varicose veins and can also be used with clinically acceptable results in the case of a diffuse VM.17,18 To clarify these questions, a study was carried out with the main objective of analyzing the efficiency and safety of a 1470-nm diode laser for treating diffuse VMs by La Paz Hospital’s vascular anomalies center. Secondary objectives were to evaluate patients’ tolerance of and compliance with the laser treatment as well as the possibility of its combination with the other available techniques, surgery and sclerotherapy.

METHODS A retrospective observational study of all patients with a diffuse VM treated in our unit from January 2012 to June 2018 was carried out. All patients signed an informed consent form, and the protocol was approved by the ethical committee of the University Hospital La Paz (code HULP: PI-3200). Criteria for inclusion were the following: Subcutaneous or intramuscular venous or glomuvenous (low-flow) malformations, visible or detectable by ultrasound. Diffuse extension, depth, and involvement of different anatomic regions or muscle compartments within the same anatomic zone. Diffuse VM was defined as a malformation that affects more than one anatomic region (head and neck, trunk, or extremity) or two tissue planes.19 Symptomatic patients with significant reduction in their quality of life due to pain, edema, deformity, or functional impairment. Criteria for exclusion were the following: General contraindication to the required anesthesia. Deep lesions not easily visible in the surgical field or with ultrasound and lesions close to critical structures in which the procedure could not be safely performed (ie, intra-abdominal or intrathoracic VM) or that presented a high risk of neurovascular damage.

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ARTICLE HIGHLIGHTS d

d

d

Type of Research: Single-center retrospective cohort study Key Findings: Of 17 patients with diffuse venous malformations (VMs) who underwent 26 procedures with the 1470-nm diode laser, 16 (94%) had a reduction in pain as measured with a visual analog scale. Mean pain reduction was 5 points (45%; range, 2-9 points [25%-100%]; P ¼ .001). All patients showed a decrease in the postoperative D-dimer level with a mean reduction of 45% (range, 3%-95%; P ¼ .001). None of the five postoperative complications in four patients were life-threatening. Take Home Message: The intralesional laser technique is efficient and safe for treatment of diffuse VMs. It is minimally invasive, is well tolerated by patients, and has few complications. Intralesional laser intervention should be kept in mind as a first-line treatment in patients with diffuse VMs.

Variables analyzed. The following patient-related variables were evaluated: demographic data (age, sex, race), personal or familial background (obstetric records of the patients and any other medical, surgical, or congenital familial anomalies), clinical data (type of lesion, extension and anatomic location, need for previous medication, and previous interventions on the lesion), and analytic data (preoperative and postoperative D-dimer and fibrinogen levels). Variables regarding the surgical procedure, such as type of anesthesia, wavelength of the fiber, power (expressed in watts) and energy (expressed in joules) applied, and days of hospitalization, were also collected. The following variables were analyzed in relation to postoperative results: presence of complications, visual analog scale (VAS) score for pain, new hemorrhagic episode, consumption of medication (lower dose or lower step in the World Health Organization [WHO] analgesic ladder20), 3- and 6-month postoperative D-dimer and fibrinogen levels, visits to the hospital, and patient self-reported clinical improvement (improvement of functional limitation or subjective reduction of malformation volume with associated cosmetic improvement). Intralesional laser technique. Ultrasound was used preoperatively to assess the area to be treated and intraoperatively to verify the correct position of the laser fiber within the lumen of the VM before applying the energy. The laser fiber was directly introduced through different percutaneous accesses. In all cases, a spherical bare-tip fiber of 600 mm and 1470-nm wavelength (Technoparc Alemania Inc, Madrid, Spain) was used. Total energy liberated and power (higher than conventional venous treatments) were noted. The skin was continuously irrigated with cold saline solution to avoid skin burns.

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Assessment of the effectiveness and safety of the procedure. Clinical variables of pain improvement and functionality were noted, as were reductions in analgesic medication requirements according to the WHO analgesic ladder,20 improvement in pain perception through the VAS, and decreased coagulopathy by D-dimer and fibrinogen levels. Safety was assessed by registering complications of the procedure. The ClavienDindo classification (Table I), which divides complications after the procedure into five degrees based on the need for further treatment, was used to grade the complications.21,22 All patients were examined at outpatient clinics at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery and then annually. In all the cases, postoperative pain assessment was performed using VAS after the intervention. As reported elsewhere,23 a panel study was also conducted to evaluate therapeutic outcome. Three physicians (two vascular surgeons and one pediatric surgeon) who were not involved in the patients’ treatment rated two pretreatment and two post-treatment color photographs of the VM. The results were graded on a 5-point scale: 1, no change or worse; 2, minor improvement; 3, marked improvement but malformation still obvious; 4, nearly normal appearance; and 5, apparently cured.23 Magnetic resonance imaging after the intervention was also available in some patients to evaluate volume reduction, but it was not included in the protocol. Routine ultrasound examination was carried out in every outpatient visit. Data on continuous variables are presented as medians and range; crude analyses were performed using the Mann-Whitney U test because data distribution departed from normality. Categorical variables were analyzed with the c2 test. The Wilcoxon statistical test was used to compare quantitative measurements before and after the intervention. P values <.05 were considered statistically significant. All statistical analysis computations were performed using SPSS Statistics version 21 (IBM Corp, Armonk, NY).

RESULTS From January 1, 2012, to June 30, 2018, a total of 26 procedures with the 1470-nm diode laser were performed on 17 patients with a diffuse VM; 1 patient underwent 7 subsequent procedures, and 1 patient underwent 2 more procedures. Three (17%) patients were men and 14 (82%) were women. Sixteen (94%) were of European origin and one (6%) was of Asian origin. The mean age was 32 years (range, 8-58 years). The remaining demographic and clinical characteristics of the patients are summarized in Table II. None of our patients had a family history of congenital vascular anomalies. In 13 (76%) patients, the indication for surgery was the VM itself, and in 3 (17%), surgery was

Table I. Clavien-Dindo complications

classification

of

surgical

Grade

Definition

Grade I

Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions Allowed therapeutic regimens are: drugs as antiemetic, antipyretics, analgetics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the beside.

Grade II

Requiring pharmacological treatment with drugs other than such allowed for grade I complications Blood transfusions and total parenteral nutrition are also included

Grade III

Requiring surgical, endoscopic, or radiological intervention

Grade IIIa

Intervention not under general anesthesia

Grade IIIb

Intervention under general anesthesia

Grade IV

Life-threatening complication (including central nervous system: brain hemorrhage, ischemic stroke, subarachnoidal bleeding, but excluding transient ischemic attacks) requiring intermediate care/intensive care unit management

Grade IVa

Single organ dysfunction (including dialysis)

Grade IVb

Multiorgan dysfunction

Grade V

Death of a patient

Suffix “d”

If the patient suffers from a complication at the time of discharge, the suffix “d” (for “disability”) is added to the respective grade of complication. This label indicates the need for a follow-up to fully evaluate the complication.

From Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240:205-13. Reproduced with permission of Wolters Kluwer Health, Inc.

recommended to enable associated (musculoskeletal) treatment. In two of these three cases, the aim was to perform a knee arthroplasty in the face of huge arthritic degeneration in patients who had been rejected in other centers. The third case was a patient with a large malformation of the left lower limb and left hemipelvis with severe left hip arthritis also rejected for hip replacement in another center. In those three patients, the open surgical approach (mandatory for the joint replacement) provided direct vision of the malformation despite its being a deep malformation. As the lesions were visible, none was excluded. All the patients had elevated D-dimer levels before surgery, with a median of 2483 ng/mL (range, 88036,000 ng/mL). None of the patients had a fibrinogen level

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Table II. Demographic and clinical characteristics of the patients Patient No.

Type of vascular malformation

Location

Previous treatment of the malformation

Associated comorbidities

1

Glomuvenous

RUL þ RHT

SGI þ SCL þ LS

Consumption coagulopathy

2

Capillary venous

LUL þ LHT

SGI (palm grove and third finger) þ SCL

No

3

VM

RHT þ right breast

No

No

4

VM

Neck and left side of face

No

No

5

VM

Left foot

No

No

6

VM

RUL þ RHT þ right breast

LS þ SGI þ SCL

No

7

VM

LLL (left hip and thigh)

2 EMB þ SGI

No

8

Capillary venous

LLL

No

9

Glomuvenous

RLL (right knee)

SCL

No

10

Glomuvenous

RHT

SGI þ SCL þ LS

No

11

VM

RLL

SGI þ SCL þ LS

No

12

VM

RLL (right knee)

SGI þ SCL

No

13

Capillary lymphatic venous

Left hemibody

SGI þ LS

CLOVES

14

Lymphatic venous

Left thigh and scrotum

SGI þ SCL

No

15

VM

LHT þ LUL

SGI þ SCL þ LS

No

PIK3CA mutation

16

VM

LUL

EMB þ LS

No

17

Capillary venous

RHT

No

Factor XI and XII deficit and breast cancer

CLOVES, Congenital lipomatosus overgrowth, vascular malformations, epidermal nevus, and skeletal deformities syndrome; EMB, embolization; LHT, left hemithorax; LLL, left lower limb; LS, laser; LUL, left upper limb; PIK3CA, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha; RHT, right hemithorax; RLL, right lower limb; RUL, right upper limb, SCL, sclerotherapy; SGI, surgical intervention; VM, venous malformation. a According to the World Health Organization (WHO) analgesic ladder.20

below 150 ng/dL; the median was 287 ng/dL (range, 150771 ng/dL). The median platelet count was 211  103/mL (range, 99-530  103/mL). Regarding the procedure, 16 of 17 patients underwent general anesthesia (because the extension of the VM was extremely large), and 1 patient underwent a popliteal block. In 3 of 17 (17%) patients, simultaneous partial surgery to extract painful phleboliths was also carried out; in another 3 patients (17%), a simultaneous joint arthroplasty was performed; and in 2 patients (12%), concomitant sclerotherapy was conducted. Intraoperative parameters regarding laser use and the duration of hospital stay are shown in Tables III and IV, respectively. The results of the follow-up variables are presented in Table IV. The mean time until hospital discharge was

24 hours (range, 20-168 hours). There were five postoperative complications in four patients, giving an overall rate of 19%, and in none of them was the complication lifethreatening. According to the Clavien-Dindo classification,22 three (11%) of them corresponded to grade I (two skin burns and one self-limited pneumothorax), another one (4%) corresponded to grade II (neuropathy of the sciatic nerve), and the last one (4%) corresponded to grade IIIa (femoral pseudoaneurysm and arteriovenous fistula requiring repair by regional anesthesia). The last patient was the only one requiring reintervention in our series. These complications were successfully managed, and their final effect on the patients was not significant. In 16 of 17 patients (94%), there was a reduction in pain associated with the VM after intervention as measured

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Table II. Continued. Antiaggregant or Phleboliths anticoagulant agent

Analgesic treatmenta

Symptoms

Yes

Yes

Step 3 (paracetamol 500 mg as needed, tapentadol 50 mg bid, pregabalin 75 mg bid, amitriptyline 50 mg at bedtime)

Pain and functional limitation

Yes

Yes

Step 1 (ibuprofen 600 mg bid)

Pain

Yes

Yes

No

Pain and hemorrhage

No

Yes

No

Pain

Yes

Yes

Step 1 (paracetamol 500 mg bid, ibuprofen 600 mg bid)

Pain

No

Yes

Step 1 (ibuprofen 500 mg tid, pregabalin 75 mg bid, amitriptyline 50 mg at bedtime)

No

No

Step 2 (tramadol 50 mg tid, pregabalin 75 mg bid, etoricoxib 60 mg once daily)

Yes

No

No

Yes

No

Step 1 (paracetamol 1000 mg bid, ibuprofen 600 mg bid)

Pain

Pain and functional limitation (degenerative osteoarthritis of hip) Pain Pain and functional limitation (degenerative osteoarthritis of knee)

Yes

No

No

Pain

No

No

No

Pain

Yes

No

Yes

No

Step 1 (paracetamol 500 mg bid, ibuprofen 400 mg bid)

Pain and hemorrhage

No

No

No

Pain and hemorrhage

Yes

No

Step 1 (paracetamol 500 mg tid, ibuprofen 400 mg bid)

Pain

No

Yes

No

Pain

No

No

Step 1 (paracetamol 600 mg as needed)

Pain

Step 2 (tramadol 50 mg tid, etoricoxib 60 mg once daily, pregabalin 75 mg bid)

with the VAS; the mean pain reduction after intervention was 5 points (45%; range, 2-9 points [25%-100%]; P ¼ .001). In one (6%) patient, there was an increase (þ2) in the VAS score after surgery as the result of neuropathic pain. Regarding analgesic drug consumption, three patients decreased one step on the WHO analgesic ladder (patients 2, 9, and 17); seven remained on the same step, but medication was reduced in all of them. None of the patients suffered new hemorrhagic episodes or needed additional visits to the hospital. All the patients selfreported functional and cosmetic improvement, including patient 7, who presented with neuropathic pain. The mean time of follow-up was 19 months (range, 3-48 months). In 11 of 17 patients (65%), improvement of clinical evolution continued 6 and 12 months after

Pain and functional limitation (degenerative osteoarthritis of knee)

surgery. Most of the complications (four of five) were solved within a maximum of 3 to 6 weeks. The only patient with a clinically persistent complication continued to suffer neuropathic pain in the foot at 12 months after the intervention. Postoperative D-dimer and fibrinogen levels were calculated in 19 of 26 (73%) procedures at a mean time of 3 months after surgery (range, 2-6 months). All patients showed a decrease in the postoperative D-dimer level with a mean reduction of 949.5 ng/dL (45%; range, 9013.127 ng/dL [3%-95%]; P ¼ .001). None of the patients had a postoperative fibrinogen level below 150 ng/dL; the median was 212 ng/dL (range, 108-698 ng/dL). Evaluation of the therapeutic outcomes assessed by physicians not involved in the treatment of the patients

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Table III. Variables related to the intralesional laser procedure Patient No. 1

Procedure No.

Power, W

Energy, J

1

13

NK

2

13

21,366

3

13-15

NK

4

13-15

12,000 25,000

5

15

6

13-15

11,356

7

15-20

26,995

8

15-30

36,000

2

9

9

4824

3

10

15

28,600

11

13-15

22,000

12

15

28,100

4

13

13-15

24,363

5

14

15

1200

6

15

15

2400

7

16

15

37,000

8

17

6.5-7.5

1274

9

18

15

NK

10

19

15

21,164

11

20

23-29

34,679

12

21

15

NK

13

22

9-11

NK

14

23

9-11

NK

15

24

9-11

NK

16

25

9-11

NK

17

26

15-16

NK

NK, Not known.

using a 5-point scale23 resulted in a mean value of 3 (marked improvement but malformation still obvious; range, 2-4; Figs. 1-6). Routine ultrasound examinationsdalways performed by the same physiciandshowed sclerosis of the treated areas in 13 (76%) of the 17 patients.

DISCUSSION Preliminary studies by Apfelberg et al24 suggested that the intralesional laser might provide a modality for treatment of vascular anomalies. These authors began using argon lasers to treat different vascular lesions, such as port-wine stains, hemangiomas, and telangiectasias. During the 1990s, the use of different modes and types of laser proliferated in the treatment of different types of vascular anomalies. Initially, the neodymium:yttriumaluminium-garnet (Nd:YAG) laser was employed to treat hemangiomas, used in continuous mode and for intralesional photocoagulation.25 Until a decade ago, Nd:YAG and pulsed dye lasers were the most used lasers for treatment of vascular lesions in percutaneous mode.26-28 Subsequently, the diode laser began to be used in the

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endolesional treatment of vascular lesions as an analogy to its use in the treatment of lower limb varices. Treatment with the intralesional laser is preferable to superficial treatment for several reasons, mainly the lower incidence of skin injury and the better result in deeper lesions.29,30 Since the first publication of use of the intralesional laser on vascular lesions in 1999, there have been many publications about its use, mainly in the fields of dermatology, ophthalmology, and surgery of the orofacial territory.15,16,27-32 The first series that included patients with VMs outside the craniofacial area was reported in 2014,33 although it is heterogeneous in terms of the nature of the malformation (66% were venous) and the type of laser used (Nd:YAG in 90%). A large series of patients with extratruncular VMs treated with an 810-nmwavelength laser diode was reported in 2011 and extended in 201434,35 (164 patients with an average follow-up of 22 months). Forty-three patients (26%) presented with minor complications; one (0.6%) had a clinically relevant and persistent complication, a peroneal nerve injury producing a loss of sensation and an equine foot for about 6 months. High rates (90%-95%) of saphenous vein occlusion have been widely reported, with the 810-nm and 1320-nm diode lasers being the treatment of choice for varicose veins.17,36,37 An occlusion rate of 100% has been achieved using the radial fiber with a 1470-nm wavelength, which has also decreased the amount of energy required and resulted in less pain and discomfort in the postoperative period17,37,38; thus, this technique is the most commonly used for treating saphenous vein insufficiency. Absorption with the 1470-nm wavelength is selective through water and tertiary hemoglobin or deoxyhemoglobin, making this modality especially suitable for the treatment of pure VMs. Its penetration power is low because of its high affinity for water, which constitutes 80% of all tissue. To date, there have been no publications on the use of this intralesional laser wavelength on VMs. Our group of patients presented with diffuse, infiltrative, and extensive VMs, which limited the therapeutic options. In addition, 12 patients (70%) had undergone previous interventions (surgery in 10 of 12) and did not describe it as a satisfying experience. Extensive resections imply high rates of perioperative complications: diffuse injuries, frequently associated coagulopathy due to the extended malformation of the endothelial surface in touch with the blood with the subsequent risk of hemorrhage and need for transfusions, hematoma, dehiscence, and further reinterventions. The patients who had previously undergone surgery (n ¼ 10) had all had a long hospital stay (between 1 and 3 weeks) with a slow and tedious recovery with associated complications of transfusion (three patients), hematoma (three patients), and dehiscence (two patients). The postoperative period after laser treatment was favorable in 16 of 17 patients (94%),

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Table IV. Variables related to the follow-up and description of the parameters analyzed before and after the procedure VAS score Patient No. 1

Procedure No. 1

Decrease, Before After No. (%)

D-dimer level, ng/mL Before 3022

After

9

5

4 (44)

2

8

4

4 (50)

3

8

5

3 (38)

NA

4

8

3

5 (62)

22,621 20,628

5

7

3

4 (43)

4063

1035

Decrease, No. (%)

Complicationsa (grade)

Evaluation of outcomesb

Duration of hospital admission, hours

3

48

1344

1678 (56)

None

944

91 (9)

None

NA

36

None

36

1993 (9)

None

24

3823

240 (6)

None

24

6

9

5

4 (56)

12,149

6246

5903 (49)

None

24

7

8

4

4 (50)

16,163

6724

9439 (58)

None

24

8

9

4

5 (56)

6968

2369

4599 (66)

None

2

9

8

3

5 (63)

3482

3392

90 (3)

None

3

3

10

8

1

7 (88)

5171

4598

573 (11)

None

3

11

8

1

7 (88)

15,495

2368

13,127 (85)

None

20 20

12

8

1

7 (88)

2368

4

13

9

0

9 (100)

880

224

656 (75)

5

14

9

6

3 (33)

1145

631

514 (45)

None

NE

24

6

15

9

3

6 (67)

29,249 16,440 12,809 (44)

None

3

24

7

16

7

9

2 (NE)

NE

168

8

17

8

5

3 (38)

NA

NA

None

NE

24

9

18

9

3

6 (67)

NA

NA

None

3

72

10

19

8

NA

Pneumothorax (I)

3

24

11

20

7

0

7 (100)

Skin burns and infection (I)

3

24

6 (75)

2483

1767 6036

12

21

8

2

13

22

8

NA

14

23

8

NA

NA

15

24

8

NA

34,346

NA

24 20

1608

None

875 (35)

NA 5012

1024 (17)

Skin burns, skin necrosis (I)

Neuropathy sciatic (II) Femoral pseudoaneurysm and arteriovenous fistulas (III)

20 4

20

NA

NA

None

NE

72

NA

3260

None

2

24

638

None

2

24

None

2

24

None

2

24

None

4

24

16

25

9

3

6 (67)

>36,000

17

26

8

6

2 (25)

884

NA 6733 34,000 (95) 478

406 (46)

NA, Not available; NE, not evaluable; VAS, visual analog scale. a According to Clavien-Dindo classification.22 b Three physicians not involved in the treatment of the patients rated two pretreatment and two post-treatment color photographs only for patients with a complaint of disfiguring venous malformations and graded them on a 5-point scale: 1, no change or worse; 2, minor improvement; 3, marked improvement but malformation still obvious; 4, nearly normal appearance; and 5, apparently cured.23

showing prompt recovery, rapid return to daily activities (reduced duration of hospital stay), and significant reduction in VAS score and D-dimer values. Two patients underwent several laser procedures (one patient had three procedures and another one had eight procedures). The previous surgical resection in the patient with eight laser procedures had followed a torpid postoperative period with the need for transfusion and slow recovery. After the intralesional laser intervention, none of our patients wanted to undergo a surgical resection for its perioperative risks and the painful recovery. This

indicates that at least in our series, the rates of adherence to and satisfaction with laser were much higher than with surgical resection. Of the 12 patients (70%) with previous interventions, 10 (83%) had undergone preceding sclerotherapy or embolization. In many cases, sclerotherapy is the treatment of choice for sporadic small VMs, above all if the lesion is not septated. In a diffuse VM, there are some disadvantages related to the dose and its associated toxicity. At present, there is no consensus as to what is the best sclerosant agent; two systematic reviews concluded that alcohol,

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Fig 1. Patient 1. A1, Magnetic resonance images before procedure. A2, Clinical pictures before procedure. B, Clinical pictures after procedure.

polidocanol, and STS are the most effective.39,40 Alcohol has traditionally been the main sclerosant agent used on VMs because of its effectiveness and low recurrence rate. However, it produces such intense pain in the injection site that general anesthesia is necessary, and afterward, there is severe tissue inflammation. Therefore, its use may be extremely dangerous, given its associated toxicity and morbidity.23 Minor transitory complications, such as pain, dysesthesias, neuropathic pain, and cutaneous necrosis, have been found in up to 30% of the reported cases.41,42 Major complications from sclerotherapy with alcohol (which constitutes 16% of the procedures) are transitory pulmonary hypertension, pulmonary embolism,10 deep venous thrombosis, nerve or deep tissue damage, compartment syndrome, and nervous collapse due to acute pulmonary hypertension.39,43,44 Another sclerosing agent used in the treatment of VMs is STS in foam, although it has been suggested to be less effective than alcohol or polidocanol, especially in diffuse VMs.45 Since Cabrera et al46 and Pascarella et al47 reported using polidocanol foam, many others have demonstrated

its usefulness and effectiveness in localized VMs.8 Nevertheless, the results are not as good in diffuse VMs, in which sclerosing materials are less effective, the rate of recanalization is higher and faster, and associated consumption coagulopathy is frequent.3,8,23,45,48 Therefore, as all the cases in our series were patients with diffuse VM, sclerotherapy would not have been recommended as the first-line treatment. Bleomycin has been reported to have a lower complication rate than other sclerosants; it does not cause skin and mucosal necrosis, and it is considered a first-choice sclerosant in the treatment of localized VMs.49 The complication rate after sclerotherapy in VMs is highly variable and may range from 9.7% to 65%.45,50 This variability is due to the different materials used, the heterogeneity of the patients, and especially the high variability in the definition of complication. Different classifications have been proposed, including the Clavien-Dindo classification.21,22 Aronniemi et al21 used it to evaluate the results of sclerotherapy in peripheral VMs in a series of 127 patients with a global complication

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Fig 2. Patient 2. Clinical pictures before (A) and after (B) procedure.

rate of 24%. When they analyzed the results according to the degree of the complications, they noticed that all the severe complications (grade IV and grade V) belonged to patients with diffuse VMs. This indicates that in patients

with diffuse VMs, sclerotherapy is less effective and has higher complication rates, with complications that may be severe or even fatal.21 In our series, three of the five complications corresponded to grade I, one to grade II,

Fig 3. Patient 3. A1, Magnetic resonance images before procedure. A2, Clinical pictures before procedure. B, Clinical pictures after procedure.

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Fig 4. Patient 4. A1, Magnetic resonance image before procedure. A2, Clinical picture before procedure. B, Clinical picture after procedure.

and one to grade IIIa. This shows that in our patients with diffuse VMs, the 1470-nm diode laser treatment was a safe technique with a low complication rate, and the only complications that did occur were not severe. Based on our initial experience, treatment with the intralesional laser may make it possible to minimize the surgical procedure, reducing the size of incisions, duration of the intervention, hemorrhage, and need for transfusion, all of which simplifies the postoperative period. In our series, three patients underwent simultaneous laser treatment and surgery for phlebolith extraction, another three had laser treatment and a joint replacement, and three had sclerotherapy and laser treatment. Although the improvement in pain cannot be solely attributed to the intralesional laser, our results demonstrate that the intralesional laser may be easily used as a complementary tool to other available alternative treatments or in cases in which surgery would not be

possible. One patient underwent eight intralesional laser procedures and another patient underwent three, and there were no complications or limitations associated with the number of procedures performed in the same patient. We also had no complication or limitation caused by the dose or energy applied. So far, there are no known limitations in this regard, but this is the first series of diffuse VMs to be treated with this particular type of laser. Diffuse VMs are rare and difficult to manage, without curative treatment in most cases. The available therapeutic options are based on three pillars: surgery, sclerotherapy, and laser. It is not uncommon to use a combination of the three treatments in different evolutionary times or

Fig 5. Patient 11. Clinical pictures before (A) and after (B) procedure.

Fig 6. Patient 6. Clinical pictures before (A) and after (B) procedure.

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during the same procedure. Laser is a nonaggressive and well-tolerated procedure and can be used with a low complication rate in these patients. In light of these results, intralesional laser intervention should be kept in mind as a first-line treatment of patients with diffuse VMs.

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CONCLUSIONS According to the results of our series, the 1470-nm diode laser appears to be more effective than its predecessors.17,18 The advantages of using this procedure in diffuse VMs are the following: d d d

d

d

d

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It is an efficient and safe technique. It has a low number of complications. It is minimally invasive and well tolerated by patients, as proven by a decrease in the VAS score. It reduces the size of the lesions and thus their symptoms. By decreasing the pathologic endothelial surface, it is associated with a reduction of consumption coagulopathy, as demonstrated by the decrease in D-dimer levels. It is complementary to other existing techniques as it can be combined with surgery or sclerotherapy. There is no reported dose limitation, restriction on session number, or toxicity.

Despite that the intralesional laser is a promising tool in the management of diffuse VMs, current experience is limited. Larger series of patients are needed to confirm our results, to optimize selection of candidates, and to further minimize complications.

AUTHOR CONTRIBUTIONS Conception and design: EMM, LRM, JLG Analysis and interpretation: EMM, CMA, LRM, JLG Data collection: EMM, CMA Writing the article: EMM, JLG Critical revision of the article: EMM, CMA, LRM, JLG Final approval of the article: EMM, CMA, LRM, JLG Statistical analysis: EMM Obtained funding: Not applicable Overall responsibility: EMM

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Submitted May 16, 2019; accepted Sep 4, 2019.