Intralesional corticosteroid injections for infantile hemangioma

Infantile hemangiomas(IHs) are the most common benign soft-tissue tumors in infancy;about 10%–15% of them may result in various complications that require active management. The current first-line treatment for IH is oral propranolol;however, some studies recommend intralesional corticosteroid injections for small, limited, deep, or prominent tumors because of concern regarding serious systemic complications related to propranolol. This review summarizes and analyzes the current clinical studies on corticosteroid injections in IHs, discusses treatment norms, and explores future research directions.

Clinical Evaluation of Color Doppler Ultrasound in Selecting the Optimal Treatment Modality for Infantile Hemangioma

Objective We investigated the efficacy and safety of 1064 nm Nd： YAG laser, intense pulsed light （IPL）, and lauromacrogol injection in the treatment of hemangioma, in order to evaluate the value of color Doppler ultrasound guidance in choosing the optimal treatment modality. Methods Infantile patients who were clinical diagnosed as hemangiomas were randomly divided into group A, who had color Doppler ultrasound examinations before the treatment, and group B who had the treatment without ultrasound evaluation. Patients in the group A were assigned into subgroups according to the depth of lesion by sonography： group A-1 for those who had a lesion depth 〈1.2 mm, and took intense pulsed light therapy; group A-2 for those who had a lesion depth ≥1.2mm and 〈 3 mm, and took long pulse 1064 nm Nd：YAG laser therapy; group A-3 for those who had a lesion depth ≥3mm and 〈5 mm, and were treated by IPL combined with long pulse 1064 nm Nd：YAG laser treatment; Group A-4 for those who had a lesion depth ≥5 mm, and took lauromacrogol injection therapy. Patients in the group B took long pulse 1064 nm Nd：YAG laser treatment without preoperative ultrasound evaluation. The efficacy and adverse reactions of the treatments between the groups were evaluated and compared statistically. Results Totally 113 patients with 128 skin lesions were enrolled in this study, 85 in the group A （mean age 6.8±7.9 months） and 28 in the group B （mean age 6.9±9.9 months）. The mean depth of hemangioma was 3.3±1.1 mm in the group A, ranging from 0.5-7.8 mm, with 0.8±0.4 mm, 2.2±0.4 mm, 4.2±0.6 mm and 6.2±0.7 mm in group A1, A2, A3 and A4, respectively. The cure rates and effective rates in the group A were significantly higher than those in the group B （cure rates： 64.5% vs 56.3%, U=3.378, P=0.045; effective rates： 89.5% vs 78.1%, U=4.163, P=0.041）. The adverse effect rates of the group A （vesicle 20.0%, pigmentation 46.9%, scarring 17.7%） were lower than those of the group B （vesicle 21.9%, pigmentation 60.4%, scarring 25.0%）. Incidences of pigmentation and scarring were statistically significantly different （U=3.884, P=0.034, and U=4.016, P=0.032 respectively） between the two groups. Conclusion With the guidance of color Doppler ultrasound, the efficacy and safety of long pulse 1064 nmNd：YAG laser, intense pulsed light, and lauromacrogol injection in the treatment of infantile hemangioma have better outcomes compared to laser treatment alone without preoperative ultrasound examination.

Topical Propranolol Hydrochloride Gel for Superficial Infantile Hemangiomas

The clinical efficacy and safety of topical propranolol hydrochloride gel in the treatment of superficial infantile hemangiomas (IHs) were assessed. Fifty-one cases of IHs from Oct. 2010 to Sept. 2011 were subjected to the topical propranolol hydrochloride gel intervention in Fuzhou General Hospital of Nanjing Military Commands, China. Changes in size, texture, color, peak systolic velocity of the hemangiomas, resistance index and adverse effects were observed. The results were evaluated by using Achauer system, and responses of IHs to pranpronolol were considered scaleⅠ(poor) in 4 patients (17.24%), scaleⅡ(moderate) in 18 patients (24.14%), scale Ⅲ (good) in 22 patients (44.83%) and scale Ⅳ (excellent) in 7 patients (13.79%). The response of superficial hemangiomas was significantly better than other hemangiomas (P<0.05), and no differences in response were found among different primary sites (P>0.05). Our study indicates that topical application of 3% propranolol hydrochloride gel is effective and safe in treating IHs.

The apoptosis in various stages of infantile hemangioma

Objective: To detect the apoptosis in various stages of infantile hemangioma. Methods:Total 52 samples of infantile hemangioma (including 8 fresh samples) were included in this study. Agarose gel electrophoresis, transmission electron microscopy(TEM) and in situ TdT mediated dUTP-biotin nick end labeling(TUNEL) staining were used to observe the apoptosis. H-E staining was used to analyze the number of cells,the number and area of microvessels in hemangiomas. Results: The typical “ladder” occurred in the DNA electrophoresis of the hemangioma tissue in the late proferating stage. Many apoptotic cells were found in infantile hemangiomas with TEM. TUNEL staining identified that there were apoptotic cells througout the pathologic evolution of infantile hemangioma and the AI(%) was the highest in the late proferating stage. There existed close relationship between the AI(%) and the total number of cells in hemangioma. Conclusion: The decrease of cells resulted from the apoptosis may be the major cause of the spontaneous involution of infantile hemangioma.

Clinical observations on the treatment of infantile hemangiomas with topical imiquimod 5% cream

Objective： To observe the efficacy and safety of topical imiquimod 5% cream in the treatment of uncomplicated infantile hemangiomas （IHs）. Methods： A total of 68 IHs were treated with topical imiquimod 5% cream. Among them, 36 were superficial, 22 were mixed, and 10 were deep. The size of IHs ranged from 1.0 cm × 1.5 cm to an area of a whole forearm. All the hemangiomas were in a proliferative stage. Imiquimod was applied 3 times weekly in 44 patients and 5 times weekly in 24 patients for up to 36 weeks. Results： All superficial IHs improved, and 18 achieved complete clinical resolution, 10 had excellent improvement, 5 showed moderate improvements, and 3 patients displayed minimal improvement. Two mixed IHs showed excellent improvement, 3 showed moderate improvement and 5 manifested minimal improvements. The remaining 12 mixed IHs and all deep IHs did not respond to the therapy. The total incidence of local adverse events was 58.82%（40/68）, which included erythema or edema, local itching, incrustation or peeling, erosion or ulceration, although most of these were mild to moderate reactions and did not affect the treatment. Scarring occurred in 2 mixed IHs. No systemic side effects developed. Conclusion： Imiquimod 5% cream may be a safe and effective alternative for the treatment of superficial IHs and some mixed IHs in which the superficial component predominates. An appropriate treatment duration for proliferative IHs treated with this therapy may be 24 weeks. Some local adverse events, such as crusting and erosion with possible scarfing potential may occur and should be addressed by prompt, but temporary, discontinuation of the imiquimod. Topical imiquimod 5% cream can be prudently used in the treatment of IHs larger than 5.0 cm × 5.0 cm in newborns and infants less than 6 months of age. To our knowledge, this is the largest IH group treated with imiquimod that has been reported in the literature to date.

Stem cells in infantile hemangioma

Background:Infantile hemangioma(IH)is the most common tumor of infancy and the pathogenesis is still unclear.Recent new evidences have been shown that IH arises from stem cells.Data sources:Based on recent original publications from Pub Med,Elsevier and Google Scholar,a large number of articles about pathogenesis and treatment of IH were selected by their titles and abstracts.Results:The hemangioma-derived stem cells expressed stem cell-specific marker CD133 and mesenchymal markers CD29,CD44,and comprised between 0.1%and 1%of the cells in proliferating-phase IH.During the proliferative phase,stem cells differentiated into large amounts of endothelial cells and pericytes;while during the involuting phase,stem cells became less and predominantly differentiated toward adipocytes.Signaling pathways like VEGF/VEGFR,Notch signaling,were found to be related to these processes.Corticosteroids,Rapamycin and propranolol had a significant effect on stem cells by inhibiting the cell growth or differentiation,or participating in maintaining the cell stability.Conclusions:Stem cells derived from hemangioma play an important role in the pathogenesis of IH,and may be important targets of therapy.

Distribution and pheotype changes of macrophage in infantile hemangioma

Objective To observe distribution and phenotypc changes of macrophage in infantile hemangioma. Methods Forty - three infantile hemangioma samples were harvested from resection operation,Distribution and phenolype changes of macrophages labelled with CD68,

Infantile hemangiomas screening modalities for primary care physicians

Infantile hemangiomas are the most common benign vascular tumors in children.They present a characteristic natural history of spontaneous involution after a phase of initial proliferation.A small but significant minority demonstrates incomplete regression or complications and requires prompt intervention.Prediction of the evolution of infantile hemangiomas is challenging because of their morphological and behavioral heterogeneity.The decision between referral for treatment and observation is sometimes difficult,especially among non-expert physicians,with the risk of missing the period for optimizing outcomes in case of delayed intervention.The aim of this review is to update our knowledge,especially of the primary care providers,regarding the ongoing difficulties of the early clinical evaluation of infantile hemangiomas,and to outline the importance of current practical scoring tools for the identification of the lesions which require expert consultation and referral.

Risk factors for infantile hemangioma:a meta-analysis

Background Infantile hemangioma(IH)is one of the most common tumors in infants.Its pathogenesis is complex and poorly understood.The risk factors of IH have been extensively studied from clinical and epidemiological perspectives in recent years,but the conclusions in the literature reports are inconsistent.To provide a reference for the prevention of hemangioma,we conducted a meta-analysis of the published studies of potential risk factors for IH.Methods The Cochrane Library,Ovid,PubMed,and Web of Science databases were searched systematically.Log odds ratios(log ORs),logistic regression standard errors and 95%confidence intervals(CIs)were used to compare the correlation between IH and potential risk factors.Review Manager 5.3.3 was used for the statistical analysis.Results Six studies were included and 17 potential risk factors were eventually evaluated.P values<0.05 were found for female gender(P<0.01,OR 2.04,95%CI 1.65–2.51),low birth weight(P<0.01,OR 4.39,95%CI 3.05–6.31),multiple gestation(P=0.01,OR 2.39,95%CI 1.21–4.71),preterm birth(P=0.03,OR 2.37,95%CI 1.07–5.23),progesterone therapy(P<0.01,OR 2.73,95%CI 2.12–3.51),and family history(P=0.01,OR 1.98,95%CI 1.16–3.38).Conclusions This meta-analysis revealed that risk factors,including female gender,low birth weight,multiple gestation,preterm birth,progesterone therapy,and family history may affect the occurrence of IH.

Intracranial Abnormalities of Infantile Hemangiomas in the Head and Neck Regions: A Retrospective MRI Study

Objective:Few reports have described intracranial hemangiomas and structural brain and/or arterial anomalies in patients with infantile hemangiomas.This study was performed to examine the magnetic resonance imaging findings of intracranial abnormalities in a group of infants with hemangiomas in the head and neck regions.Methods:We reviewed our hemangioma treatment center database from January 2010 to July 2018 to assess the prevalence of intracranial abnormalities in infants with hemangiomas in the head and neck regions.Clinical and electronic magnetic resonance imaging data were also retrieved from the patients’medical charts.Results:Of 436 patients with infantile hemangiomas in the head and neck regions,23(5%)had intracranial abnormalities,including 20(23%)with segmental hemangiomas and 3(1%)with focal hemangiomas.In total,14 patients had intracranial hemangiomas located within the ventricle and cisterns or ipsilateral lesions involving the extradural space.Eight patients had intracranial structural abnormalities,such as cerebellar dysplasia,Dandy-Walker malformation,and hydrocephalus.Five patients had intracranial arterial anomalies,and three patients had arteriovenous malformations.Conclusions:These findings support the hypothesis that intracranial hemangiomas are commonly associated with segmental infantile hemangiomas in the head and neck regions.

Pediatric vascular tumors of the liver:Review from the pathologist’s point of view

Differential diagnosis of pediatric vascular liver tumors can be challenging due to inconsistent nomenclature,histologic overlap and the rarity of some entities.Here we give an up-to-date overview of the most important entities.We discuss the clinic,histology and pathophysiology of hepatic congenital and infantile heman-gioma,hepatic epithelioid hemangioendothelioma and hepatic angio-sarcoma.

Primary malignant vascular tumors of the liver in children:Angiosarcoma and epithelioid hemangioendothelioma

Primary malignant vascular neoplasms of the liver,angiosarcoma and epithelioid hemangioendothelioma,are extremely rare entities in the pediatric population.International Society for the Study of Vascular Anomalies classification system is recommended for the pathologic diagnosis of hepatic vascular lesions in this age group.In this article,we highlight the clinicopathologic characteristics of hepatic angiosarcoma and epithelioid hemangioendothelioma in the pediatric population.Hepatic angiosarcoma in children shows a slight female predominance with an average age of 40 mo at diagnosis.The distinct histologic features include whorls of atypical spindled cells and eosinophilic globules,in addition to the general findings of angiosarcoma.Histologic diagnosis of pediatric hepatic angiosarcoma is not always straightforward,and the diagnostic challenges are discussed in the article.Hepatic epithelioid hemangioendothelioma also demonstrates a female predominance,but is more commonly identified in adolescents(median age at diagnosis:12 years).Histologically,the lesion is characterized by epithelioid cells and occasional intracytoplasmic lumina with a background of fibromyxoid stroma.While WWTR1-CAMTA1 and YAP1-TFE3 fusions have been associated with epithelioid hemangioendothelioma,there are currently no known signature genetic alterations seen in pediatric hepatic angiosarcoma.Advancement in molecular pathology,particularly for pediatric hepatic angiosarcoma,is necessary for a better understanding of the disease biology,diagnosis,and development of targeted therapies.

Infantile hepatic hemangiomas:looking backwards and forwards

Infantile hepatic hemangiomas(IHHs)are common benign tumors seen in the liver of infants.IHHs are true infantile hemangiomas(IHs)and have phases of proliferation and involution parallel to those of cutaneous IHs.The definition and classification of IHH are still confusing in the literature.The mechanisms during the pathogenesis of IHH have yet to be discovered.The clinical manifestations of IHH are heterogeneous.Although most IHH lesions are asymptomatic,some lesions can lead to severe complications,such as hypothyroidism,consumptive coagulopathy,and high-output congestive cardiac failure.Consequently,some patients can possibly encounter a fatal clinical condition.The heterogeneity of the lesions and the occurrence of disease-related comorbidities can make the treatment of IHH challenging.Oral propranolol is emerging as an effective systemic approach to IHH with obvious responses in tumor remission and symptom regression.However,the precise clinical characteristics and treatment strategies for patients with severe IHH have not yet beenwell established.Here,we summarize the epidemiology,pathogenicmechanism,clinical manifestations,diagnosis,and treatment of IHH.Recent updates and future perspectives for IHH will also be elaborated.

Imaging findings of multiple infantile hepatic hemangioma associated with cardiac insufficiency

Background:Infantile hepatic hemangioma(IHH)as a benign liver tumor in infancy and childhood is commonly associated with high output cardiac failure.The present study aims to describe the imaging findings in a patient who was diagnosed as having multiple IHH with congestive cardiac insuffi ciency.Methods:The imaging findings and clinical manifestations of the patient with multiple IHH associated with cardiac insuffi ciency were retrospectively reviewed.Results:Ultrasonography showed multiple intrahepatic lesions with mixed echoes and markedly expanded hepatic veins and the inferior vena cava of the patient.Echocardiography revealed right heart insufficiency and pulmonary hypertension.Contrast-enhanced MRI showed early mild enhancement of lesions and more obvious delayed enhancement.The patient died after combined therapy of surgery and hormone.Conclusions:The imaging findings of multiple IHH associated with cardiac insufficiency are typical and diagnostic.Early imaging assessment may facilitate the diagnosis and treatment of the disease.

Topical imiquimod treatment of cutaneous vascular disorders in pediatric patients:clinical evaluation on the efficacy and safety

Objective:To evaluate the clinical effect of topical imiquimod treatment on cutaneous vascular disorders in pediatric patients.Methods:A retrospective investigation was conducted in 25 pediatric patients with cutaneous vascular disorders,including 19 infantile hemangiomas(IHs)(12 superficial/7 mixed type),5 nevus flammeus(NF),and 1 pyogenic granuloma(PG).Imiquimod 5% cream was applied every other day for 4 to 16 weeks(average 9.6 weeks).Results:Of the 19 IHs treated,an overall efficacy of 52.6% was achieved,with a clinical resolution rate of 15.8%,excellent rate of 26.3%,and moderate rate of 10.5%.The superficial type responded the best at 66.7%,while the mixed type showed only 28.6% effectiveness,which was predominantly from their superficial parts.No obvious response was noted in the 5 patients with NF.Side effects were observed in 78.9% of the patients,mostly mild to moderate local irritations and occasionally severe reactions such as thick crusting and ulceration.Systemic side events were observed in 4 IH patients including fever and digestive tract reactions.No recurrence was observed during the follow-up examination.Conclusions:Topical imiquimod could be an alternative option for the treatment of uncomplicated superficial IHs with satisfactory tolerability.