Serum-level changes of vascular endothelial growth factor in children with infantile hemangioma after oral propranolol therapy.

Oral propranolol is the first-line therapy for infantile hemangioma (IH), but its mechanism of action remains unclear. The aim of this study was to evaluate the change in serum vascular endothelial growth factor (VEGF) levels in patients with IH who underwent propranolol treatment. The study included 22 patients with IH receiving propranolol treatment. At three time points-before treatment and 1 and 3 months after treatment-blood samples were examined by enzyme-linked immunosorbent assay for serum VEGF expression. The mean serum VEGF concentration in children with proliferative hemangiomas was 395.0 ± 176.7 pg/mL, approximately twice as high as in patients with venous malformations (mean 170.7 pg/mL) and in healthy controls (204.8 pg/mL, p = 0.006). After 1 month of propranolol treatment, the level had fallen 21.6% (p = 0.003), although the downward trend was less obvious after 3 months of treatment (18.0%, p = 0.63). VEGF expression correlated significantly with the lesion size (correlation coefficient [R] = 0.43, p = 0.046), whereas no correlation was observed with age (R = 0.13, p = 0.56). Serum VEGF levels were higher in patients with IH and fell after 1 month of oral propranolol treatment. Similar results, although less pronounced, were found after 3 months of treatment. Lesion volume and serum level of VEGF were significantly correlated.

Maternal and perinatal risk factors for infantile hemangioma: a case-control study.

Infantile hemangioma (IH) is the most common benign tumor occurring during childhood. We hypothesized that, in addition to already known risk factors, such as female sex, prematurity, and low birthweight (LBW), antenatal vaginal bleeding and progesterone therapy would be highly associated with IH. We randomly selected 650 individuals with IH and matched them with 650 children of the same age and nationality without IH. Trained investigators used a standardized questionnaire to collect data from both groups, including demographic, prenatal, and perinatal characteristics. Prematurity (p < .001, odds ratio [OR] = 2.22, 95% confidence interval [CI] = 1.44-3.41), LBW (p < .001, OR = 3.10, 95% CI = 1.87-5.16) and female sex (p < .001, OR = 2.06, 95% CI = 1.65-2.58) were significantly associated with IH. Maternal vaginal bleeding during the first trimester was shown to be an independent risk factor according to logistic regression analyses (p < .001, OR = 1.6, 95% CI = 1.36-1.91), which was most evident in those receiving progesterone therapy to prevent miscarriage (p < .001, OR = 2.11, 95% CI = 1.77-2.51). Subgroup analyses revealed that the effect was more pronounced in female than in male infants (OR = 2.82, 95% CI = 2.39-3.34). In addition to the known relationships, the present study identified a close relationship between maternal vaginal bleeding and progesterone therapy during early pregnancy and IH. Twins appeared to have a higher incidence of IH than singletons.

[Topical timolol in the treatment of periocular superficial infantile hemangiomas: a prospective study].

OBJECTIVE: To investigate the efficacy and side effect of topical beta-blocker (Timolol Maleate) in the treatment of periocular hemangioma in a prospective study. METHODS: 432 outpatients with infantile hemangioma visited our special clinic service in Shanghai Ninth People's Hospital from July 2010 to December 2011. Among them, 12 superficial periocular lesions were selected in the study. Timolol was used topically on the lesion in every 12 hours. Two independent special doctors evaluated the results according to the pictures before and after four-week application of timolol. RESULTS: Were categorized into four levels: continuous growth (the lesion continues to grow), stable (no visible change), moderate (0-50% of regression) , perfect (more than 50% of improvement). Result of the 12 outpatients, 4 showed perfect result, 2 moderate, 4 stable and 2 continuous growth. No side effect was observed. CONCLUSIONS: Topical timolol is effective and safe in the treatment of superficial periocular infantile hemangioma. It could be considered as the first line treatment of proliferative superficial hemangioma.

Treatment of venous infraorbital dark circles using a long-pulsed 1,064-nm neodymium-doped yttrium aluminum garnet laser.

BACKGROUND: Infraorbital dark circles are a common cosmetic problem with multiple causative factors and few studies into the different treatment options. OBJECTIVE: To assess the effectiveness and safety of long-pulsed 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser therapy for infraorbital dark circles caused by visible prominent veins. PARTICIPANTS AND METHODS: Twenty-six patients with venous infraorbital dark circles were treated with a Nd:YAG laser (fluence, 130-140 J/cm(2) ; spot size, 6 mm) in double-pulse mode (pulse width, 6-10 ms; interpulse interval, 20 ms). Patients were examined 12 months after the final treatment. Results were ranked in five categories based on percentage clearance (5 = 100%, 4 = 75-99%, 3 = 50-74%, 2 = 25-49%, 1 ≤ 25% clearance). Patient satisfaction was ranked on a scale of 1 to 3 (1 = minimal improvement; 3 = completely satisfied), and pain was ranked on a scale of 1 to 10 (1 = mild pain; 10 = severe pain). RESULTS: Twenty-six patients completed the study. Objective improvement scores were 5 in all patients, and all patient satisfaction scores were 3. All patients tolerated the moderate pain (mean score 3.6). Transient erythema was observed in all patients. CONCLUSION: Long-pulsed 1,064-nm Nd:YAG-laser treatment appears effective and safe for the treatment of venous infraorbital dark circles and selectively removes visible prominent veins.

[A prospective study of propranolol as first-line treatment for problematic infantile hemangioma in China].

OBJECTIVE: To prospectively assess the efficacy and safety or propranolol as a first-line treatment for problematic infantile haemangioma in China. METHODS: From Mar. 2009 to Feb. 2010, 78 patients with problematic infantile hemangioma were included in the prospective study. The characteristics of the tumor, including sex, age, site, complications, were recorded. The response to treatment at 1 week, at 1 month and at the end of treatment was evaluated. The efficacy of treatment was graded as no response, stabilization, or accelerated regression. The indications for treatment, side effects and relapse after treatment were documented. The mean follow-up period was 16.7 months (range, 12.1-23.6 months). RESULTS: Oral therapy was initiated at mean age of 3.7 months (range, 1.1-9.2 months) as first-line therapy. The mean age at the end of treatment was 11.2 months (range, 5.2-22.3 months). The treatment was lasted for 7.6 months (range, 2. 1-18.3 months). One week after treatment beginning, the hemangioma growth was controlled in all the patients. The accelerated regression was achieved in 88.5% (69/78) of patients after one week of treatment, and 98.7% (77/78) of patients after 1 month of treatment and at the end of treatment. Ulceration was occurred in 14 cases before treatment, which was healed after treatment for 2 months. Minor side effects were happened in 15.4% (12/78) of patients. Rebound growth of lesion was noticed in 35.9% (28/78) of patients. CONCLUSIONS: Propranolol is effective in the treatment of infantile hemangioma with minor side effect. We suggest it should be used as the first-line treatment.

Nodules arising within port-wine stains: a clinicopathologic study of 31 cases.

Nodules are seen in approximately 10%-30% patients within port-wine stains (PWS) and usually regarded as vascular "tumor." However, nodules arising within PWS have not been systematically examined and the precise pathologic characteristics of them are unknown. The aim of this study is to evaluate the clinicopathologic and immunohistochemical features of blood vessels of nodules in 31 cases. A total of 31 biopsy specimens (excision) were obtained from the representative areas of lesion of each patient with nodules. Clinical features of all patients were recorded. Hematoxylin and eosin staining, immunohistochemical staining, and Weigert elastic stain were performed to investigate the histopathologic features of nodules. In a total of 31 subjects, there are 16 patients whose nodules occurred in the area innervated by the second branch of the trigeminal nerve (51.6%), 4 in the first branch (12.9%), 6 in the third branch (19.4%), 2 in both the first, and the second branch (6.5%). Based upon specular microscopic findings, 14 biopsy specimens were designated as pyogenic granuloma (PG) (45.1%), 10 as arteriovenous malformation (AVM) (32.3%), 5 as both (16.1%), and 2 cases as cavernous-like vascular ectasia (6.5%). Moreover, both AVM and PG were prone to occurring in the area innervated by the second branch of the trigeminal nerve. In summary, we believed that both AVM and PG are not rare histologic changes in PWS. Moreover, histologic findings suggest that the major portion of nodules arising within PWS can be categorized into AVM, PG, and AVH associated with PG.

[Clinical application of imiquimod for the treatment of infantile hemangiomas].

OBJECTIVE: To explore the clinical application of imiquimod for the treatment of infantile hemangiomas (IH). METHODS: 320 children with IH, including 250 superficial cases, 20 deep cases, and 50 mixed cases, were treated with 5% imiquimod cream every other day for 16 weeks. The clinical efficacy and side effects were evaluated at one year of age. RESULTS: The total effective rates of the superficial, deep, and mixed IH were 61.2% (153/250), 10.0% (2/20) and 60.0% (30/50) respectively, showing no statistical difference between superficial and deep type (P = 0.874), but significant difference between superficial and mixed (P < 0.01), deep and mixed type (P < 0.01). 56.0% (28/50) of mixed IH showed proliferation of its deep lesions. Slight skin erythema and crusting were the most common side effects. CONCLUSIONS: 5% imiquimod cream is effective and safe in superficial IH and superficial lesions of mixed IH with minimal skin reactions. The dysplasia of local tissue and systemic growth retardation are not found. It should be avoided to apply the cream to IH located around the cavities and skin fold. Imiquimod cream is a simple and convenient home-nursing medication. It can reduce care burden of family. Thus topical use of imiquimod can be considered as a good clinical indication for the treatment of superficial lesions of IH.

[The pathological characteristics and clinical significances of maturational change of port-wine stain].

OBJECTIVE: In this study histologic observations were presented to elucidate the possible mechanism of maturational change of port-wine stain(PWS). METHODS: Normal PWS(3 cases) , thicken PWS (11 cases) and nodular PWS (9 cases) were included to present histologic observations. RESULTS: Normal PWS, only shows mild dilated, thin-walled vessels within superficial dermis. Thicken PWS, shows further dilated vessels and sebaceous gland throughout dermis and superficial subcutaneous fat. Nodular PWS can be divided into three groups. I Similar to thicken PWS, shows further dilated vessels and sebaceous gland throughout dermis and superficial subcutaneous fat. II Shows Large number of dilated vessels, honeycombing and less vascular mesenchymal. III Tenacious texture shows mild dilated vessels, diffused collagen, mesenchymal rarefaction, lymphocyte infiltration and lymphedema change. CONCLUSIONS: Histologic examination revealed not only the expected vascular abnormalities, but also a number of widely distributed hamartomatous changes in thicken and nodular PWS. The complex hamartomatous changes suggest a genetically determined, multilineage developmental field defect in the pathogenesis of PWS.

[Non-involuting congenital hemangioma: a study for diagnosis and treatment].

OBJECTIVE: To study the history, clinical symptoms, imaging and histology of a rare distinct infantile hemangioma. METHODS: 12 patients (5 female, 7 male; aged 18 months - 26 years) diagnosed as non-involuting congenital hemangioma were retrospectively analyzed. The history, imaging, histologic examination and the treatment were collected. RESULTS: Most of the patients had only one lesion which was round or ovoid, flat or plaque-like. The average size was about 5 cm x 6 cm. The overlying skin was usually had coarse telangiectasia with central or peripheral pallor. The skin has a high skin temperature. Magnetic resonance imaging, computed tomography angiography and digital subtraction angiography findings were similar to those of common infantile hemangioma. Histologic examination revealed lobular collections of small, thin-walled vessels with a large, often stellate, central vessel. "Hobnailed" endothelial cells lined along the intralobular vessels. Small arteries were observed "shunting" directly into lobular vessels or into abnormal extralobular veins. All lesions were easily excised without recurrence. CONCLUSIONS: Non-involuting congenital hemangioma is a distinct infantile vascular tumor. It should be diagnose early and treated appropriately.

[Superselective ethanol endovascular therapy under digital subtraction angiography for craniofacial arteriovenous malformations].

OBJECTIVE: To introduce superselective endovascular therapy under digital subtraction angiography for craniofacial arteriovenous malformations using absolute ethanol, and to assess the efficacy and complications of the method. METHODS: A retrospective review of patient medical and imaging records was performed. 8 patients (7 male, 1 female, 11-50 years) with craniofacial arteriovenous malformations underwent staged selective ethanol endovascular therapy (1-4 times, median 2 times). Clinical follow-up (8-24 months, mean 12.1 months) was performed in all patients, and results from imaging follow-up (2-6 months, mean 4.3 months) were available in 4 patients. Therapeutic outcomes were established by evaluating the clinical outcome of symptoms, as well as the degree of devascularization at follow-up angiography. RESULTS: 16 sessions of selective ethanol endovascular therapy were performed in 8 patients. 5 of 8 patients were cured, 2 had improvement, 1 had no change. Selective ethanol endovascular therapy was considered effective in 7 patients (87.5%). 4 patients will need further treatment sessions for residual arteriovenous malformations. Blistering, superficial skin necrosis and transient hemolysis occurred in 4 of 8 patients. All the complications were healed with observation. No major complications occurred. CONCLUSION: Superselective ethanol endovascular therapy under digital subtraction angiography has the potential for cure of craniofacial arteriovenous malformations and is able to obtain excellent cosmetic results, and with acceptable risk of complications.

[Isolation, culture and characterization of endothelial cells in infantile hemangioma].

OBJECTIVE: To establish a method for the reliable isolation and culture of infantile hemangioma endothelial cells (HemECs) in vitro. METHODS: Proliferative hemangioma specimens were digested by collagenase to form a single cell suspension. The HemECs were isolated using anti-CD31 coated dynabeads. The CD31+ cells were grown in fibronectin coated dishes. HemECs were identified by morphological characteristics and immunocytochemistry. The cells were also examined for their ability to intake LDL. RESULTS: The method enabled the rapid isolation of HemECs that demonstrated typical endothelial cobblestone morphology in culture. The cells were positively stained for CD31, vWF. They also were labeled with DiI-Ac-LDL. CONCLUSIONS: This technique can effectively isolate endothelial cells from the proliferative hemangiomas. These cells could be further used to research the mechanism of proliferation and degeneration of infantile hemangioma.

[Noninvasive laser therapy for skin superficial venous malformations with long pulsed Nd:YAG laser].

OBJECTIVE: Conventional therapies for skin superficial venous malformations have demonstrated poor efficacy and many side effects. This prospective study assessed the effectiveness and safety of noninvasive long pulsed 1064 nm Nd: YAG laser therapy for superficial venous malformations. METHODS: Twenty-two patients, aged 9 months to 67 years, skin types III, with skin superficial venous malformations were treated with the Nd:YAG laser at fluences of 140 - 150 J/cm2, with 6 mm spot size and double pulse model(pulse width 7 - 8ms, interpulse interval 20 ms). Contact cooling was used to protect epiderm. Patients were examined 1 month and 6 months after the last treatment. Results Were graded as percent clearance in five groups: 0%, 1% - 25%, 26% - 50%, 51% - 75%, 76% - 100%. RESULTS: Twenty-two patients completed the study with maximal 5 treatment sessions. At 6 months after the final session, 76% - 100% clearance was observed in 96.3% of the treated sites, 100% improvement was observed in 37% of the treated sites. Pain during treatment was variably perceived by patients. Transient erythema were seen in 8 (38.1%) patients, but could resolve in 1 day to 1 month. None of patients have purpura, permanent pigmentation change and scarring. CONCLUSIONS: Noninvasive long pulsed 1064 nm Nd: YAG laser is effective and safe enough for the treatment of skin superficial venous malformations and selectively remove superficial vessels. The side effects are minimal while ideal cosmetic results can be achieved.