Infantile hemangiomas, the most common neonatal tumors, are characterized by rapid proliferation which induces various complications. The goal of the study is to develop an algorithm for selection of patients for the treatment of with laser radiation the basis of study characteristics of the infantile hemangiomas with the help non-invasive methods and evaluation of effectiveness carried out by the therapy. Materials and methods. A prospective study of 122 children with infantile hemangiomas aged 1 to 24 months was performed, including assessment of hemangiomas clinical picture, distribution of hemangiomas according to their localization and size, erythemometry and ultrasound scanning. Superficial hemangiomas were detected by Doppler ultrasound in 84 patients (63.6%), combined ones - in 38 patients (28.8%). Findings of hemangioma erythemometry before the course of treatment ranged from 180 to 450 standard units. Results. In 122 children 132 vascular tumors were detected. An algorithm for selection of patients for infantile hemangioma treatment was developed taking into account objective non-invasive methods of ultrasound and skin erythemometry. 2 patients clinical follow-up is recommended, 10 patient is sent for further surgical treatment. The course of treatment is short (1-5 sessions) for 81 patients with superficial hemangiomas. The course of treatment is long (6-10 sessions) for 81 patients with combined hemangiomas Nd:YAP/KTP Q-Sw laser with 3 mm nozzle, radiation wavelength 1079/540 nm was used. Ultrasound examination of all superficially located hemangiomas after the course of laser therapy didn’t show vascular formation and blood flow, the structure of the dermis and hypoderm did not have structural changes in the study. Erythemometry values after treatment to fit the values of the control skin area and 110 - 85 standard units are decreased. Conclusion. An algorithm for selecting patients for Nd: YAP / KTPQ-Sw 1079/540 nm laser treatment was developed including erythemometry, involvement area, depth of involvement, feeding vessel diameter and exclusion of dangerous anatomical localizations.

Hemangiomas of the skin are the most common type of congenital vascular pathology which occurs in 1-3% of the population [1, 2] and are one of the most common causes of patients’ referrals to a dermatologist. Hemangioma (synonym: angiomatous nevus) is a benign tumor arising from the blood vessels. The modern concept of hemangioma genesis suggests that angiogenesis abnormalities result in uncontrolled proliferation of vascular elements [3]. Vascular skin tumors occur in 2-3% of newborns and in 10% of children they appear during the first year of life [4]. Particular attention is paid to the localization of hemangiomas in anatomically dangerous periorbital, perianal, parotid, mucosal areas, as it is likely to indicate a possible adverse and/or complicated prognosis of the disease and the need for active management of these patients [5-7]. In addition to rapid growth, infantile hemangiomas (IHs) can ulcerate, bleed and become infected [8, 9], especially in areas of increased traumatization (back, limbs, lips). Periorbital hemangioma may cause visual impairment: optic nerve obstruction and corneal deformity. Spontaneously regressing hemangiomas often leave atrophic skin changes, telangiectasias and deforming scars [10]. In addition, there is still no consensus among specialists on the strategy of IHs managing [11-14]. Until recently, the main IHs treatment methods were cryodestruction, electrocoagulation, surgical resection, which often left rough skin scars and resulted in poor aesthetic outcomes. The invention of laser systems, such as Nd: YAP / KTP Q-Sw, working on the principle of selective photothermolysis, with selective exposure to blood vessels of hemangioma without skin damaging, resulted in new perspectives of laser utilization in the management of skin vascular neoplasms [16-19]. The high prevalence of skin IHs, the need for thorough selection of children for laser management, the possibility of differentiated choice of management depending on the tumor size, localization, the severity of erythema, and the ultrasound data determine the relevance of this study. The purpose of the study was to develop an algorithm of patients selection for Nd: YAP / KTP Q-Sw laser treatment based on the clinical evaluation and instrumental characteristics of infantile hemangiomas, followed by assessment of the therapy outcomes. The study was carried out in the of laser cosmetology clinic LINLINE and in the of Plastic Surgery and Cosmetology Department of the Federal Budget State educational institution of higher education South Ural state medical university of the Ministry of Health of Russia in 2012-2016. An open, prospective, nonrandomized study of clinical, instrumental features of infantile skin hemangiomas in children aged 1-24 months was performed. Taking into account the inclusion and exclusion criteria 122 children aged 1 to 24 months girls were examined: 22 (18%) boys and 100 (82%). The average age of children was 6.3 ± 0.3 months. The ethical committee of the South Ural state medical university approved the study organization (protocols No 11 of November 9, 2013 and No 10 of December 21, 2017). To achieve the goal and to solve the tasks, clinical, anamnestic, instrumental and statistical research methods were used. MATERIALS AND METHODS The study was carried out in the clinic of laser cosmetology LINLINE and on the basis of the Department of Plastic Surgery and Cosmetology of the State Pediatric University of South Ural State Medical University of the Ministry of Health of Russia in 2012-2016. An open, prospective, nonrandomized study of clinical, instrumental features of infantile hemangiomas in children aged 1-24 months was performed. The average age of children was 6.3 ± 0.3 months, including 22 (18%) boys, and 100 girls (82%) girls, taking into account the inclusion and exclusion criteria for 122 children aged 1-24 months. Informed consent was obtained to participate in the research and processing of personal data from parents and guardians of children in accordance with the Helsinki Declaration of the World Medical Association (WMA Declaration of Helsinki - 2013). The organization of the study was approved by the ethical committee of the Federal State Educational Establishment of Health Care of the Ministry of Health of the Russian Federation (protocols No. 11 of 09.11.2013 and No. 10 of December 21, 2017). To assess the anamnestic features, peri- and intranatal history of children, we developed a diagnostic map and a special protocol for patient examination. According to the data of the questionnaire, the mothers (over 35 years old) of children with IHs (13.1%) were enrolled to the group “late pregnancy”. When assessing heredity hemangiomas in the close relatives were revealed in the same percentage (13.1%). Anemia (5.7%), chronic somatic pathology (4.9%), severe allergy in anamnesis (1.6%) were less frequently recorded in mothers during pregnancy. 4.9% of the interviewed mothers had a bad habit such as smoking. Analysis of perinatal risk factors of IH development showed the presence of chronic fetoplacental insufficiency in 4.9% of pregnancies, the low birth weight of the child (less than 2 kg) was noted in 0.8% of cases. More than 20% of children were prematurely born. Low scores on the Apgar scale at birth were determined in 15.6%. Clinical examination of children with IHs included assessment of the vascular neoplasms number, color, boundaries, tumor surface, area, elevation above the healthy skin surface, pulsation on palpation, anatomical localization. Red and bluish color of the vascular tumor was determined. In the majority of cases superficially located tumors are proved to have a classic red color, while those located more deeply in the subcutaneous adipose tissue have a pale blue color. The indistinct boundaries of vascular formation give evidence of the tumor active growth and the tumor is determined as rapidly growing (the proliferative phase), in contrast to vascular formations with distinct boundaries which indicate a stable condition of the vascular tumor. The hemangioma area was divided into 3 categories: less than 1 cm2, from 1 to 10 cm2, more than 10 cm2. The surface of the vascular formation was assessed as smooth or bumpy, the latter is a clinical sign of active growth of a vascular tumor. The pulsation on palpation of a vascular tumor may indicate to an active blood supply to the tumor by a large vessel and an arterial blood flow type. The clinical study yielded more frequent appearance of IH after birth during the first month of life both in boys and girls (in 70.5% of cases). RESULTS In 122 children 132 vascular tumors were registered: 100 girls had 110 vascular neoplasms (83.4%), significantly more than in 22 boys - 22 tumors (16.6%). In the study group 124 (93.9%) red and 8 (6.1%) bluish hemangiomas were registered. Indistinct boundaries indicating to the rapidly growing tumor in the proliferation phase were found in 64 tumors (48.5%). 51.5% of tumors had clear boundaries indicating to a stable state of vascular formation. Of 132 hemangiomas 44.7% had an area less than 1 cm2, 48.5% had from 1 cm2 to 10 cm2, and 6.8% had more than 10 cm2. The height of vascular neoplasms above the surface of healthy skin was 1 mm in 41%, 2 mm - in 50% and 3 mm - in 9%. The presence of pulsation on palpation was recorded in 12 hemangiomas (9.1%). The anatomical localization of IH was analyzed and the most common sites of involvement were revealed on the head and trunk: of 122 people the vascular tumor in the head region was recorded in 51 cases (38.6%), mainly in the scalp and peripheral part of the face. Truncal hemangiomas were found in 41.7% of cases, mostly on the anterior surface (50.9%). The upper and lower extremities were less and equally affected. In boys there were no significant differences in frequency and predominant localization. It is very important to take into account the localization of tumors in anatomically dangerous areas on the mucous membranes, in sites of increased traumatization. Among the examined patients, anatomically dangerous hemangiomas were found in 17 children: 6 (35.2%) in the central part of the face, 2 (11.7%) in the lumbar region, 6 (35, 2%) in the anogenital region, 3 (17.6%) on the hand. The likelihood of a severe or complicated course of hemangioma can be caused by the combination of the following prognostically unfavorable signs: identification of a tumor at birth, rapid growth of hemangioma during the first month of a child’s life, a well-defined pulsation in hemangioma on palpation indicating to the presence of a feeding vessel with a large diameter in the arterial blood flow that contributes to a rapid growth; hemangioma over 2 mm height and the large area of the hemangioma (more than 10 cm). Clinical forms of IHs were verified according to ICD-10 and the classification proposed by Yu.F. Isakov and Yu.A. Tikhonov (1974): simple (superficial), cavernous (deep), and combined. Among all clinical types of hemangioma identified in our study the most common were superficial vascular tumors (n = 84 (63.6%)). Both superficial and combined types of vascular tumors were equally identified in boys (n = 9 (40.9%)). Of 110 vascular tumors in girls superficial (68.1%) and combined (26.4%) types, rarely a deep form (5.5%) were more often identified. Eighty four superficial hemangiomas had red color (100%), a smooth surface (70.2% of cases), well-outlined borders (64.3% of cases), the tumor elevation above the surface of the healthy skin did not exceed 2 mm, the tumor area was no more than 10 cm2 in 96.4% of cases. The growth of superficial hemangiomas during the first month after the appearance was observed in 97.6% of cases. Red color of the tumor (100%), a bumpy surface (92.1% of cases), indistinct borders (76.3% of cases), the tumor height did not exceed 2 mm, the involvement area was up to 10 cm (50% of cases) were more often observed in cases with combined as well as superficial hemangiomas. The growth of combined hemangiomas during the first month after the appearance was observed in 94.7% of cases. Deep hemangiomas had a bluish color (80%), a bumpy surface (80%), indistinct borders (90%), 4-6 mm above the skin surface height, more than 10 cm2 area. The growth of hemangioma within the first month after the appearance occurred in more than 90% of patients. The study of children phototype in case of IHs showed the prevalence of the second type of photosensitivity (T. Fitzpatrick), the most common in the European population. During the second stage of the study an instrumental evaluation of neoplasms was carried out, which included erythemometry and ultrasound scanning of the vascular tumor. To give an objective assessment of hemangiomas, erythemometry of both hemangioma and a vascular tumor-free area of healthy skin in the symmetrical portion was carried out. The mean values of erythemometry didn’t differ significantly in various parts of the body, the highest index was registered in the anogenital region (335.2 ± 12.3 conventional units), slightly lower in the central region of the face (331.1 ± 15.5 c.u.), on the trunk (322.4 ± ± 16.3 c.u.), the minimum - in the lumbar region (302.8 ± 15.8 c.u.). The maximum erythemometry values in case of a deep hemangioma are identified on the peripheral part of the face, the minimum values are on the extremities and trunk. A number of significant differences in the values of erythemometry due to the type of blood supply to the vascular tumor were identified. The maximum values were obtained in patients with arterial blood flow type which had significant differences with all compared groups. Venous and arterial-venous types showed almost identical values, the absence of differences between these groups indicates the predominance of the venous blood flow over the arterial one. In cases without a feeding vessel, minimal erythemometry values were revealed, which had significant differences with all compared groups. A B Fig. 1. (А) 1 - month-old boy with combined hemangioma of him right scapular area S = 0,5 см2, 385 conventional units of erythemoometry. (B) By means of ultrasound (5-20 MGz) deepness of tumor 0,36 сm; feeding vessel of venous bloodflow type, diameter of vessel 0,05 сm Of 132 IHs the diagnosis of proliferative phase was made in 127 (96.2%) cases; the phase of stabilization in 5 (3.8%) cases characterized by cessation of tumor area and volume growth, the appearance of areas with pale vascular pattern, absence of hemangiomas in involution phase. The proliferative phase is marked by the highest value of erythema due to the activation of angiogenesis processes. These values are significantly different from those in stabilization phase. Of 84 superficial hemangiomas diagnosis of proliferative phase was made in 80 (95.2%) of cases; the phase of stabilization in 4 (4.8%). The highest erythema value 333.7 ± 6.18 c.u. was determined in the progressing phase, the lower indices were - 217.7 ± 8.3 c.u. in the phase of stabilization. Combined hemangiomas were identified only in the proliferative phase, the erythema value was 324.3 ± ± 9.6 c.u. In deep tumors the erythema index in the proliferative phase has a maximum value of 312.5 ± ± 8.9, and value of 125.1 ± 3.2 is lower in the stabilization phase indicating the significant value differences. Ultrasound scanning of infantile skin hemangiomas was carried out in B-mode to determine the depth, volume, characteristics of the tumor structure, the relationship with the surrounding tissues. In the CDI mode bloodflow within the neoplasm, its direction and character, the projection and diameter of the feeding vessels were evaluated. In 132 examined tumors ultrasound confirmed the presence of a feeding vessel in 85 (64.4%) hemangiomas, its absence in 47 (35.6%) cases. A feeding vessel up to 0.05 cm in diameter was revealed in 16 vascular tumors (18.9% of cases), the vessel diameter ranged from 0.05 cm to 0.15 cm - in 66 (77.6%), the feeding vessel more than 0,15 cm - in 3 neoplasms (3.5%). The feeding vessel with arterial type of blood flow was revealed in 18 (21,2%) vascular tumors, venous type of blood flow - in 49 (57.6%), arteriovenous - in 18 (21.2%) vascular neoplasms. Vascular tumors with a feeding vessel of arterial type had the highest peak systolic velocity in contrast to hemangiomas with arteriovenous and venous blood flow. The index of peripheral resistance (RI) reflecting the state of resistance to the blood flow was the highest in hemangiomas with arterial blood flow, indicating the significant differences from the indices of venous and arteriovenous blood flow types. High indices of systolic and diastolic blood flow velocity in superficial hemangiomas were registered in the arterial and arteriovenous type of blood flow (Fig. 1). According to the objectives of the study, the next step was to create an algorithm for selecting patients for Nd: YAP / KTP Q-Sw 1079/540 laser therapy. According to E.A. Shakhno (2012) Nd: YAP / KTP Q-Sw 1079/540 nm laser penetration A B C Fig. 2. (А) 6 - month-old girl with combined hemangioma on her left hand before laser therapy. (B) After 10 sessions laser therapy. (C) After 12 months a course of therapy into blood-containing tissue reaches depth up to 0.8 cm, thus it became the criterion for strict selection of patients. According to the clinical instrumental study of IHs, a patient selection algorithm forNd: YAP / KTP Q-Sw laser treatment with wavelengths of 1079/540 nm was developed based on 5 criteria: 1) exclusion of periorbital localization of hemangioma; 2) erythemometry values from 180 up to 450 c.u.; 3) the area of the involvement is 1-10 cm2; 4) depth of localization less than 1.0 cm; 5) the feeding vessel diameter less than 0.15 cm. The study group enrolled 122 patients with 132 hemangiomas for Nd: YAP/KTP Q-switched 1079/540 laser treatment. According to the selection criteria, a patient with periorbital hemangioma (the first criterion) was excluded; 8 (6.1%) patients with visually evident blue color of the tumor and erythemometry values ranged from 125 to 179 c.u. (the second criterion) were also excluded. Some patients didn’t meet the third criterion. Clinical evaluation revealed the area of infantile hemangioma to be larger than 10 cm2 in one patient, who was excluded; two neoplasms (1.5%) also dropped out of the study, because their size was less than 1 cm2 and required dynamic observation. Two patients with the localization of the tumor in subcutaneous fat tissue were excluded from the study (the fourth criterion) after ultrasound scanning of the tumor and measurement of its depth (tumor localization deeper than 1 cm). Thirteen patients with 13 hemangiomas (10.66%), 10 deep and 3 superficial, were excluded from the study group. Thus, according to the selection criteria for laser therapy, 109 children with a total of 119 hemangiomas were selected. Thirty eight tumors were of a combined type because the depth of the involvement was more than 0.5 cm. A long course of 6-10 laser sessions was recommended to such patients. Eighty one superficial hemangiomas were exposed to a short course of laser therapy. Nd:YAP/KTP Q-Sw laser with 3 mm nozzle, radiation wavelength 1079/540 nm was used to treat 119 vascular tumors. Parameters of laser with 3 mm nozzle are the following: energy density 7,07-63,7 J/cm2 with a pulse frequency of 1-3 Hz, treatment in a scanning mode without overlapping of light spots till the appearance of a darker color of the tumor. The first procedure was both a treatment and a test, since the treatment was performed by a laser with the minimum energy density (7.07 J/cm2). Our experience has shown that such level of energy density is sufficient for hemangioma treatment in the region of the vermilion border, external genital organs, the skin on the palms and soles. Exposure to the skin of the scalp required higher energy density (34.0 J/cm2). To treat superficial hemangiomas patients underwent a short course of laser exposure with the energy density of 7.07-14.1 J/cm2, a pulse frequency of 1-2 Hz (1-5 sessions), for combined hemangiomas they underwent a long course with laser energy density of 14.1-21.2 J/cm2, a pulse frequency of 2-3 Hz, 6-10 sessions (Fig. 2). Selection of laser energy density was carried out individually. Treatment was repeated at intervals from 2 to 8 weeks. In proliferation phase of the vascular tumor the interval between sessions was 2 weeks to minimize a tumor recurrence. If the tumor was in the stabilization phase an interval between sessions was longer, from 4 to 6 weeks. DISCUSSION To complete the course of therapy the following clinical criteria were manifested: a tumor flattening and erythemometry values to less than 110 c.u., which corresponded to the normal skin value in the control area fixed symmetrically during the primary examination. According to after treatment ultrasound data the vascular involvement and feeding vessels were not visualized, the dermis and hypodermis structure was without structural changes. After treatment changes such as normal skin color and complete alignment of the tumor surface with surrounding tissues were noted in all children (81 patients) with superficial hemangiomas. After laser treatment of 38 combined hemangiomas an intensive skin color faded to a normal in 92.1% of cases, and hemangiomas turned pale in 7.9% of cases. At the same time complete alignment of the tumor surface with surrounding tissues was also noted in 92.1% of cases, and partial flattening in 7.9% of cases after laser treatment. Comparative erythemometry before and after the sessions and comparison with the control area of healthy skin were instrumental criteria for evaluating the effectiveness of laser treatment. The mean erythemometry indices irrespective of the clinical type of the tumor after treatment did not differ significantly from each other, nor in comparison with the control area of the skin and indicate a good cosmetic effect of the therapy in general. The absence of significant differences in erythemometry values of superficial and combined hemangiomas after treatment in comparison with the values of the control skin area confirms the adequate selection of therapy modes and a good cosmetic effect regardless of the tumor localization. Ultrasound examination of all superficially located hemangiomas after the course of laser therapy didn’t show vascular formation and blood flow, the structure of the dermis and hypoderm did not have structural changes in the study of 81 hemangiomas, i.e. in 100% of cases. Ultrasound scanning of 38 combined hemangiomas revealed echo signs of involution phase: 2-fold reduction of the tumor depth, a significant reduction of the blood flow in 3 (7.9%) formations, the remaining 35 (92.1%) combined hemangiomas were not visualized, the blood flow was not determined , the structural changes in the dermis and hypodermis were absent. Parents stated that the aesthetic criterion of effectiveness was important and included both the medical professional’s opinion and parent satisfaction with treatment. To evaluate the aesthetic outcome objectively the Social Support Questionnaire (SSQ) questionnaire was used, which reflects patient satisfaction with the results of therapy. All respondents (parents) noted that therapy results justified their expectations: after the course of laser treatment 97.2% of parents evaluated the therapeutic effect as “Very Much Improved” and 2.8% - as “Much Improved”. No negative evaluation marks of the treatment results as “Improved partially” or “No change” were given by respondents. The assessment of treatment outcomes showed the scores 2.9. on the Global Aesthetic Scale (GAIS) (Fig. 3). The assessment of aesthetic outcome of the treatment showed fully coincident opinions of parents and medical specialists. Fig. 3. The assessment of results by doctor on the Global Aesthetic Scale (GAIS) after a course of the laser treatment CONCLUSIONS Infantile hemangiomas, regardless of gender, are often single, superficial, appear within the first month after birth (70.5%), with a predominant involvement of the head and trunk; superficial hemangiomas are of red color (100%), with an smooth surface (70.2%), clear boundaries (64.3%), an area of involvement of not more than 10 cm2 (96.4%); combined IHs are of red color (100%), with a bumpy surface (92.1%), unclear boundaries (76.3%); deep IHs - blue (80%), bumpy surface (80%), unclear boundaries (90%); the growth of any form of hemangioma during the first year of life was observed in more than 90% of cases; more than 95% of tumors are diagnosed in the proliferation phase. Erythemometry values in children with superficial and combined IHs did not differ significantly with any form and localization of the vascular tumor. The maximum erythema index was obtained in the arterial type of blood flow; with a mixed type of blood flow the venous component predominated. Ultrasound more often revealed superficial tumors with a feeding vessel in 64% of cases, with predominance of venous blood flow (57.6%) and diameter not exceeding 0.15 cm (77.6%); combined and deep hemangiomas had significantly low peak systolic velocity and an index of peripheral resistance. An algorithm for selecting patients for Nd: YAP / KTPQ-Sw 1079/540 nm laser treatment was developed including erythemometry, involvement area, depth of involvement, feeding vessel diameter and exclusion of dangerous anatomical localizations. A short course (1-5 sessions) of laser treatment was used for superficial hemangiomas, and a long course (6-10 sessions) for combined ones. Clinical and aesthetic efficacy of laser therapy was confirmed by manifestation of normal skin coloring, the alignment of tissues in 100% of superficial hemangiomas, and in more than 92% of combined tumors. Parents (97.2%) evaluated the therapeutic effect as “Very Much Improved”, the average GAIS score was 2.98. After treatment values of erythemometry, regardless of the tumor location and the clinical form did not differ from the control area of healthy skin. Ultrasound showed no blood flow, unchanged dermis and hypodermis structure in 100% of cases of superficial hemangiomas and in 92.1% in combined forms.

T V Trapeznikova

Southern Ural State Medical University

Author for correspondence.
Email: tayana_tr@mail.ru

Assistant of the Department of Plastic Surgery South Ural State Medical University of Southern Ural State Medical University

T P Pisklakova

Southern Ural State University, National research university

Email: tayana_tr@mail.ru

V O Gubina

Southern Ural State Medical University

Email: tayana_tr@mail.ru

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