Introduction

Occurring in 0.3–0.5% of the population, a vascular anomaly is a consequence of an embryological faux pas that may lead to abnormal angiogenesis or vasculogenesis [1]. With the advent of multi-modal management options, the spectrum of vascular anomalies is now being shared by multiple caregivers including dermatologists, interventional radiologists and pediatric surgeons alike. Anomalies affecting the capillary and venous channels form the bulk of this problem and their management poses a major burden for the pediatric surgeons. In 1982, Mullicken and Glowacki proposed a biological classification to segregate these anomalies into well-defined subgroups [1]. The 20th International workshop held in Melbourne (ISSVA, International Society for the Study of Vascular Anomalies) has come up with the most recent and comprehensive classification system for these anomalies – which are now subdivided into tumors and malformations (Table 1) [2]. As per this system, anomalies affecting the capillary and venous channels are now denoted as hemangiomas and venous malformations respectively. The present article is a descriptive note of the management and outcomes for the aforementioned subgroups.

Table 1 ISSVA classification
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Material and Methods

Retrospective records of children with hemangiomas and venous malformations presenting to the pediatric surgical clinic at a single tertiary care center over past 17 y (January 2000 – December 2016) were reviewed. Sources of data included the operation theater records and a register maintaining their regular follow-up. Demographic profile, site, management and outcomes were recorded and subsequently analyzed. The majority of children were managed as day-care cases, and hence detailed records of the investigations they had undergone could not be traced. However, as a protocol, clinical photographs of the lesion, before the commencement of any therapy and at serial follow-ups were taken for comparison and response assessment. Outcomes were graded into 3 subgroups based on subjective assessment of these images. Group A denoted near total response (>90%), group B denoted 50–90% reduction whereas <50% reduction was included in group C. Data was lacking on those managed expectantly.

Results

A total of 261 patients were included, comprising of 131 males and 130 females. These consisted of 90 cases of hemangioma and 171 cases of venous malformation. The frequency and site distribution of the cases is depicted in Table 2. Both these subgroups are discussed separately in the following sections.

Table 2 Frequency and site distribution of various anomalies
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Hemangiomas

Among the 90 cases of hemangioma, there were 47 females and 43 males (female to male ratio 1.09). The median age at presentation was 11 mo (range 2 mo – 11 y). The majority of these lesions were located in the head and neck region (n = 78; 86.7%) followed by upper limb (n = 5; 5.6%), chest wall (n = 4; 4.4%) and lower limb (n = 3; 3.3%). Systemic steroids in the form of oral prednisolone were administered to 36 children (40%). Prednisolone was administered as a 100-day regime starting with 10 mg/kg/d on alternate days for 20 d and tapered to half of the previous dose every 20 d.

Steroids were supplemented with beta blockade (oral propranolol, 1–3 mg/kg/d in 3 divided doses) since January 2010. Propranolol was continued till 6 mo after complete resolution of the lesion. Eight (8.9%) cases received both steroids and propranolol and 4 cases (4.4%) received only propranolol.

Another subgroup of patients were those who received intralesional sclerotherapy with sodium tetradecyl sulfate (STS) (n = 32; 35.6%). An average of 4.6 sessions (range 1–17) were undertaken per patient with a cumulative injection of 2 ml to as much as 96 ml of drug per patient. Out of 29 children in whom response could be assessed, 16 (55.2%) could be placed in group A and 13 (44.8%) in group B.

Seven patients initially received a course of steroids followed by intralesional injection of STS in the residual lesion. This led to near total resolution in 2 (28.6%) and partial resolution in remaining 5 (71.4%). A small subgroup of patients (n = 3; 3.3%) underwent primary excision of the lesion. There was no intraoperative complications or recurrence in any of the cases. The outcomes with the various modalities are shown in Fig. 1 and outcome in a child with hemangioma managed with combined pharmacotherapy has been shown in Fig. 2.

Fig. 1
figure 1

Outcomes of various treatment modalities in children with hemangioma

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Fig. 2
figure 2

A child with hemangioma of the face managed with oral steroids and beta-blockers (a) At presentation: 3 mo age (b) At 6 mo (c) At 9 mo (d) At 12 mo age

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Venous Malformations

Among the 171 cases of venous malformation, the median age at presentation was 48 mo (range 1 mo – 23 y). The commonest site of involvement was again the head and neck region (49.6%) followed by chest wall (20.1%), lower limb (19.3%) and upper limb (10.6%).

The majority of venous malformations were managed with intralesional sclerotherapy with STS (n = 165; 96.5%). Sclerotherapy was given under general anesthesia to the majority of the patients. Subjective clinical assessment of the extent of cystic spaces in the lesion was used as a guide for deciding the amount to be injected (15 mg STS/ml). A 26G hypodermic needle was inserted from a point outside of the periphery of the lesion to reach the intralesional cystic space, which was aspirated for confirmation. Such sessions were repeated at 3-weekly intervals till all the cystic spaces were obliterated. One hundred sixty-five children with venous malformation underwent 762 sessions of sclerotherapy (range 1–34 sessions) during which they received an average of 40.4 ml of STS per case (range 2–434 ml). Response could be assessed based on subjective assessment of clinical photographs in 145 children. The median size (maximum dimension) of the lesions at presentation was 5 cm (range 1–30 cm). Of these, 6 had already been operated earlier with residue or recurrence of the lesion, which was managed with sclerotherapy. Residue was excised in 1 child post-sclerotherapy. In 2 children (1.2%), the lesion was well localized and, thus, excised primarily. Three children (1.8%) with a venous malformation of the cheek received oral steroids with complete resolution in all 3. One child (0.6%) received propranolol with no response. The outcomes with the various modalities are depicted in Fig. 3. It was noted that outcome was better in children with smaller sized lesions and those requiring lesser amount of STS volume (Fig. 4). Group B response, i.e., approximately 70% reduction in size of a lower lip venous malformation post-sclerotherapy has been shown in Fig. 5.

Fig. 3
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Outcomes of various treatment modalities in children with venous malformations

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Fig. 4
figure 4

Relation between outcome and (a) amount of STS injected and (b) size of lesion

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Fig. 5
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A child with venous malformation involving the lower lip, managed with intralesional sclerotherapy with STS: (a) At presentation (b) Post treatment

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Discussion

Hemangiomas

Vascular tumors comprise mainly of benign hemangiomas with only a small percentage occupied by the malignant tumors. The natural course of an infantile hemangioma includes inconspicuity at birth, rapidly progressive growth for first few months (80% of ultimate size by 3 mo) followed by spontaneous regression over several years (by 4 y in the majority) leaving a fibrofatty residuum [3]. The pathogenic endothelial cell proliferation is promoted by Vascular endothelial growth factor (VEGF) and estradiol, thereby explaining the high female to male ratio of 3:1 to up to 9:1 [4]. In the present study, there were no malignant tumors encountered. However, the sex ratio was almost equal (1.09) in contrast to that reported in the literature.

A strategy of “active non-intervention” has been described for these lesions owing to their spontaneous involution with time. However, medical management may be required in about 20% of cases – those with large lesions or causing cosmetic or functional compromise. In the present retrospective review, owing to lack of data on children managed expectantly, these cases have not been included. Propranolol is the drug of choice for systemic treatment. It is a beta-adrenergic receptor blocker that acts by inducing vasoconstriction, influencing signal transduction pathways of angiogenic factors [Basic fibroblast growth factor, Vascular endothelial growth factor (VEGF)] and inducing apoptosis of endothelial cells [5]. It is most effective in the proliferative phase, however, it should not be administered during the 1st wk of life when the risk of symptomatic hypoglycemia is maximal [6]. It should be given till at least 6 mo after resolution of the lesion to avoid chances of relapse. Propranolol is effective in nearly 90% of the cases while the remaining are non-respondents. Relapse during weaning has been seen in about 9% [7]. Price et al., in their series of 59 patients who received propranolol, reported resolution (defined as >75% clearance) in 81% [8]. Talaat et al. reported resolution in 75% and >50% clearance in 94% of their 80 cases over a mean 6.5 mo [9]. Lou et al. performed a meta-analysis comparing propranolol effect vs. other treatments in infantile hemangiomas (n = 324) and found it to be significantly better than other treatment modalities including steroids [10]. Corticosteroids are also very effective and were the previous gold standard drugs for hemangiomas. The mechanism is based on inhibition of VEGF and consequent inhibition of endothelial cell proliferation [1]. They may be administered topically or systemically, and outcomes have been reported with a third having improvement, another third having no response and the remaining third having stabilization of lesion size [11]. The overall response rate of use of oral prednisolone (2.9 mg/kg/d over 1.8 mo) was reported to be 84% (range 60–100%) and the mean rebound rate was 36% (range 0–65%) in a meta-analysis (n = 184) [12]. Propranolol and prednisolone may be combined to have a synergistic effect. In a randomized trial comparing the effect of propranolol (Group A) vs. prednisolone (Group B) vs. both combined (Group C), mean initial response time (days) was significantly lower in groups A (4.1 ± 3.3) and C (4.7 ± 3.4) as compared to B (9.8 ± 7.8) [13]. Also, on visual analogue scale, color fading, flattening and size reduction were significant and earlier in groups A and C as compared to group B. Also, group C was comparable but no better than group A. The present study also showed satisfactory effectiveness of these drugs given both as isolated and combined therapy with complete resolution in 75% of children who received only beta blockade (n = 4), 61.1% of children who received only steroids (n = 36) and 62.5% of children who received both (n = 8).

Interferon and vincristine have also been used for hemangiomas although they have not gained wide popularity amongst physicians owing to their associated adverse effects. These agents have not been used in authors’ clinical practice also.

Venous Malformations

Venous malformations are slow-flow vascular lesions characterized by enlarged endothelial cell venous channels surrounded by sparsely distributed vascular smooth muscle [14]. They are present at birth as bluish compressible masses distributed in the head and neck region (40%), extremities (40%) or trunk (20%). In the present review, this distribution was slightly different with 50% of vascular malformations occurring in the head and neck region, 30% in extremities and 20% over the trunk.

Various treatment options are available for management of children with venous malformations of varying severity, but none offers a cure. The aims of management include halting the progress of the disease, alleviating symptoms such as pain and decrease the disfigurement caused by huge lesions rather than eradication of the lesion per se. Intralesional injection sclerotherapy is the most commonly employed treatment option. A sclerosant causes endothelial irritation resulting in inflammation and subsequent fibrosis. Commonly used drugs for this purpose include sodium tetradecyl sulfate (STS), polidocanol, sodium morrhuate, ethanolamine and bleomycin [15]. Phlebography may be combined with sclerotherapy to assess the extent of the lesion and venous outflow before injection. Better results have been seen when the sclerosant is administered under general anesthesia whereby large quantities of the drug can be injected under controlled conditions into the cystic spaces.

In a meta-analysis published in 2013, amongst the various sclerosants evaluated, there were 5 studies that used STS for sclerotherapy (n = 143) [16]. Based on objective analysis (volume reduction of the lesion), a cure rate (>90% reduction) of 12%, improvement (25–90% reduction) of 57% and failure (<25% reduction) of 31% was noted. The subjective symptomatic cure was noted in 16.2%, improvement in 58.6% and little or no change in 25% of cases. In the present study also, most of the sclerotherapy sessions were carried out under general anesthesia using STS. Success rates ranging from a near total resolution in 20% to partial response in more than 50% patients were noted.

Surgical excision may be done in well-localized small lesions only. For larger lesions or those not amenable to sclerotherapy, debulking may be done but is fraught with a lot of complications including bleeding and recurrence. Occasionally, pre-excision sclerotherapy may be given to decrease the size and blood loss. In the present study, 6 children had already been operated at presentation with residual lesions. These were managed with sclerotherapy with good outcome in all. One child with venous malformation in the back received multiple sessions of sclerotherapy followed by excision of the residual lesion.

Conclusions

Therapeutic options include pharmacotherapy, sclerotherapy and surgical excision for the majority of these lesions. The decision regarding the choice and timing of each modality should be individualized based on location, size, type of the lesion and complications. Beta-blockers and corticosteroids have proved to be highly effective drugs for the eradication of vascular tumors or hemangiomas. On the other hand, huge venous malformations, by virtue of their etiopathogenesis, may not benefit from surgical excision or debulking alone. They may require a multimodal approach for their management. All in all, the goal of management in these lesions should be to improve the functional and esthetical problems, or rather, the quality of life in these patients, and not aim at the elimination of the lesion per se.