Vascular Tumors Of Infancy Research Articles

Efficacy of propranolol and pingyangmycin combination therapy in infantile hemangiomas: Correlation with VEGF Levels

BackgroundInfantile hemangiomas (IH) represent the most prevalent vascular tumors in infants, often necessitating prompt medical intervention due to their potential for rapid growth and complications. This retrospective study aims to evaluate the efficacy of propranolol combined with Pingyangmycin in the treatment of IH and to investigate its correlation with vascular endothelial growth factor (VEGF) levels. MethodsA prospective, observational study was conducted over 12 months, enrolling 120 IH patients. Patients received a combination therapy of propranolol and pingyangmycin for 3 to 6 months. Hemangioma Activity Score (HAS) and serum VEGF levels were assessed at baseline, 30th day, and 90th day post-treatment. ResultsA total of 120 patients diagnosed with IH, including 68 males and 52 females with a mean age of 1.2 years, were enrolled in this study. The HAS at baseline was 8.5 ± 1.7, which significantly decreased to 4.2 ± 1.0 by Day 30 and further reduced to 2.1 ± 0.8 by Day 90 (P < 0.001 for both comparisons). Serum VEGF levels also showed a significant reduction from a baseline of 235.6 ± 42.1 pg/mL to 180.3 ± 34.7 pg/mL at Day 30 and to 122.8 ± 28.9 pg/mL at Day 90 (P = 0.02 and P = 0.01, respectively). The correlation analysis revealed a positive correlation between VEGF levels and HAS scores at all time points, with Pearson correlation coefficients ranging from -0.82 to -0.89 (P < 0.001). Adverse events were mild and transient, occurring in 15% of patients, with the most common being mild hypoglycemia (8%), transient bronchospasm (5%), and gastrointestinal discomfort (2%). All adverse events resolved with symptomatic treatment, and no patient discontinued therapy due to adverse reactions. ConclusionPropranolol treatment for infants with proliferative hemangiomas is significantly effective with minor adverse effects. The mechanism of action may be associated with the downregulation of serum VEGF levels.

Serum apelin as a potential biomarker for infantile hemangiomas.

Infantile hemangiomas (IHs) are common benign vascular tumors in infants. Apelin, an endogenous cytokine, is implicated in the angiogenesis of neoplastic diseases. We aimed to explore the association between apelin and IHs, providing a foundation for clinical applications. We identified differential expression of apelin in proliferative IHs compared to healthy controls (HCs) through bioinformatics analysis of publicly available databases and verified by Immunofluorescence. Enzyme-linked immunosorbent assay was used to quantify the serum levels of apelin and vascular endothelial growth factor (VEGF) in a cohort of 116 cases of proliferative IHs, 65 cases of capillary malformations (CMs), and 70 HCs. Apelin and APJ (APLNR, apelin receptor) were identified as the significantly upregulated differentially expressed genes (DEGs) in proliferative IHs. Immunofluorescence staining indicated high expression of apelin in proliferative IHs, while minimal expression in non-IH lesions. Apelin in IHs was reduced following 6months of propranolol treatment. Serum apelin levels were significantly higher in the IH group compared to both the CM and HC groups. Moreover, apelin exhibited excellent discriminatory ability in distinguishing IHs from HCs, with an area under the curve (AUC) exceeding 0.90. A positive correlation was observed between the levels of apelin and the size of superficial IHs. The expression profiles of VEGF and apelin in IHs were found to be consistent. Apelin shows promise as a potential biomarker for IHs. The association between apelin and IH size, as well as its responsiveness to propranolol treatment, indicates its possible utility as a valuable indicator for the therapeutic evaluation of IHs.

Three-Dimensional Microtumor Formation of Infantile Hemangioma-Derived Endothelial Cells for Mechanistic Exploration and Drug Screening

Infantile hemangioma (IH) is the most prevalent type of vascular tumor in infants. The pathophysiology of IH is unknown. The tissue structure and physiology of two-dimensional cell cultures differ greatly from those in vivo, and spontaneous regression often occurs during tumor formation in nude mice and has severely limited research into the pathogenesis and development of IH. By decellularizing porcine aorta, we attempted to obtain vascular-specific extracellular matrix as the bioink for fabricating micropattern arrays of varying diameters via microcontact printing. We then constructed IH-derived CD31+ hemangioma endothelial cell three-dimensional microtumor models. The vascular-specific and decellularized extracellular matrix was suitable for the growth of infantile hemangioma-derived endothelial cells. The KEGG signaling pathway analysis revealed enrichment primarily in stem cell pluripotency, RAS, and PI3KAkt compared to the two-dimensional cell model according to RNA sequencing. Propranolol, the first-line medication for IH, was also used to test the model's applicability. We also found that metformin had some impact on the condition. The three-dimensional microtumor models of CD31+ hemangioma endothelial cells were more robust and efficient experimental models for IH mechanistic exploration and drug screening.

Успішний досвід лікування інфантильної гемангіоми зони критичної локалізації місцевими β-блокаторами

Infantile hemangioma (IH) is the most common benign vascular tumor in infants and children under one year of age. 12% of children with IH have a tendency to develop dangerous complications, the development of which depends on the area of tumor localization, its size, growth rate, and the patient's age. Careful history taking and physical examination make it possible to verify IH located in critical localization zones (physiological openings, neck, palms and feet) where complications are most likely to develop and to choose the correct method of treatment in a timely manner. Difficulties may arise for the doctor when choosing between the appointment of local or systemic therapy with β-blockers when the IH is located in the critical localization zone. Purpose - to present possibilities and successful experience of choosing between systemic and local treatment IH with β-blockers in the critical localization zone in a child. Clinical case. 2-month-old boy’s parents came to the clinic with complaints about the appearance of a bright red neoplasm in the area of the upper lip in the child, which appeared 6 days after birth and had a tendency to active increase and infiltration of soft tissue. After examining, a clinical diagnosis was made: infantile hemangioma in the critical localization zone (in the area of the skin of the upper lip) in the proliferation phase. Ultrasound diagnosis of the tumor with a special skin sensor made it possible to establish the depth of infiltration. Taking into account the localization of the tumor next to the vital opening, the rapid growth of the tumor, the risk of breast-feeding disruption due to tumor infiltration of soft tissues and the child's age, a decision was made to refer the child for further examination to rule out contraindications to the appointment of systemic β-blockers. During the follow-up examination, local treatment with the β-blocker propranolol was prescribed. During the next two weeks of using local β-blockers, the growth of the hemangioma stopped, ultrasound recorded the cessation of deep proliferation. According to the obtained results, the doctor made a decision to continue treatment with local β-blockers without switching to systemic treatment. An 8-month course of treatment with local β-blockers made it possible to achieve complete stabilization and further regression of the tumor with an excellent cosmetic effect. Conclusions. Infantile hemangiomas are dangerous tumors in children of the first year of life and require careful observation and timely treatment. The article presents a clinical case of a child with critical localization IH, who was prescribed systemic β-blockers according to treatment protocols. In this case, the treatment with local β-blockers made it possible to obtain an excellent therapeutic and cosmetic effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

CLINICAL ASPECTS OF DIFFERENT PHARMACEUTICAL FORMULATIONS OF PROPRANOLOL IN THE TREATMENT OF INFANTILE HEMANGIOMA

Infantile hemangiomas are one of the most common benign vascular tumors in infants and children.Because hemangiomas can resolve spontaneously, they usually do not require specific treatment unless theproliferation interferes with normal function or causes interference with the function of essential vital organs. Thereare several types of therapy, but in recent decades the use of propranolol has become more common due to itsexcellent effectiveness.The purpose of this paper is to analyze different pharmaceutical formulations of propranolol in the treatment ofinfantile hemangioma, including technological differences of the oral and topical pharmaceutical dosage forms ofpropranolol. The European Medicines Agency (EMA) has approved the commercially available oral propranololtherapy in the countries of the European Union, but this is not yet happened in our country. Recommendations tofollow and use the protocols for the oral application of propranolol in the treatment of this disease are difficult dueto the fact that this drug formulation is not registered in our country and patients are forced to obtain it fromcountries where it is registered.The use of syrup as an oral form of therapy has been clinically proven and has a high percentage of efficiency ininfantile hemangioma, but side effects such as sleep disturbance, bronchospasm, hypoglycemia, hypotension.The goal of this publication is to propose the most appropriate topical formulation of propranolol for external use ininfantile hemangioma through a review of relevant published data on the use of various pharmaceutical formulationsof propranolol in clinical studies and documents from the European Medicines Agency,In this paper, we used compilation and comparison methods, as most useful for a high-quality critical evaluation ofthe literature regarding problematic topics, in our case the pharmaceutical formulation of propranolol, the effect ofclinical treatment and the required legislation, and which have the potential to promote clearer, sharedunderstandings and accelerate advances in the research.Our results were focused on obtained and published data related to pharmaceutical-technological aspects ofproduction of topical formulations and the effect of clinical application, especially when it is necessary to defineexactly the amount of the released active compound from the topical form (cream, ointment or gel) and itsabsorption through the skin.Topical form of propranolol avoids the side effects of oral administrated propranolol, can help maintain a high levelof active ingredient in a local or focal region, and has an easy way of administration.The obtained research data showed that the topical application and penetration of propranolol through the skin isgood and has a lower and controlled systemic absorption. To achieve this, the choice of the formulation and theexcipients used are particularly important. Lipophilic formulations have limited release and penetration ofpropranolol. The best results are achieved by using a hydrophilic cream.After the research done, we can conclude that the production of topical formulations containing specific activecomponents with a strong systemic effect, such as propranolol, can be carried out in galenic laboratories or hospitalpharmacies. For this, already existing validated equipment and excipients that are readily available can be used.We believe that the use of topical pharmaceutical forms for local application, even in children such as the case ofpropranolol in infantile hemangioma, is justified, especially to the fact that so far no side effects have beenregistered even after long-term therapy.

Evaluating the efficacy of different treatment modalities in cases of infantile hemangioma

ObjectiveThis study aimed to evaluate different treatment modalities of infantile hemangiomas with their benefits and side effects within 3 months of treatment.BackgroundThe most common vascular tumors in infants are infantile hemangiomas, usually present as a premonitory mark with rapid postnatal growth, followed by slow involution. For those requiring systemic medications, early treatment is critical.Patients and methodsA randomized-controlled trial was conducted on 120 patients with hemangioma distributed into four treatment groups. The first group was treated by placebo, the second group was treated by topical timolol only, the third group was treated by topical timolol + oral propranolol and the fourth group was treated by topical timolo + intralesional steroid.ResultsSignificant response was found in 90.9% of the patients in the topical timolol + oral propranolol group, 78.1% of the patients in the topical timolol-only group and 72.7% of the patients in the topical timolol + intralesional steroid group. In terms of the side effects, the topical timolol + intralesional steroid had the most side effects (54.5%), followed by the topical timolol + propranolol group (45.5%) and the topical timolol-only group (18.8%). There was a statistically significant difference in lesion size, the visual analog scale, side effects, and response.ConclusionThe combination of topical timolol with oral propranolol is a very rapid, effective, simple, and safe treatment for compound hemangiomas, achieving more remarkable clinical results and fewer side effects than other methods of treatment. Therefore, we can use this combination as the first line of treatment.

Role of Propranolol in Management of Infantile Haemangioma: Our Experience

Background: Infantile hemangiomas are the most common vascular tumors in infants and the most common benign soft-tissuetumors in infants and children with a prevalence of 4-10%. Most of the haemangiomas are self-resolving by the age of 7 years butfew present as a challenge for management. Up to 30% require treatment like systemic corticosteroids, laser therapy, interferon-á,cryotherapy, embolization, radiotherapy, and intralesional sclerotherapy, all showing variable results. Since 2008 propranolol iseffective in the management of challenging cases. At present, although many international and national studies have been done toevaluate different treatment modalities of infantile hemangioma, none is done in our local setups. Moreover, there is no specificagreed dose or guidelines. for the use of propranolol in the management of infantile hemangioma for which our results can help.Objectives: This study aimed to evaluate the therapeutic effect of propranolol in the management of infantile hemangioma in ourpopulation to help in developing a proper dose regime with minimum adverse effects.Materials And Methods: This prospective interventional study was conducted in the department of Pediatric surgery Bacha KhanMedical Complex, Swabi, Pakistan. The duration of the study was 26 months. After detailed history and investigation, the patientswere started on a lower dose (1mg/kg/day in three divided doses) of propranolol and observed for six hours in the ward. After oneweek the dose was increased (2 mg/kg/day in three divided doses). The outcome was presented in terms of the percentage ofregression of the mass as effective or non-effective.Results: A total of 18 patients were treated with propranolol with a male to female ratio of 1:4. All patients tolerated the dose and hadminimal side effects. All patients responded to the treatment with some early responders (n=16, 88.8%) while others respondinglate.Conclusion: Our study showed that propranolol starting at a low dose after six months of age with gradually increasing it can havea good outcome with minimal side effects. Hence looking at its safety, we can say that propranolol can be given for small and nonproblematic hemangiomas as well.Keywords: Infantile Hemangioma, therapeutic effect, propranolol

Compound haemangioma of lower lip: an interesting and rare case report

Haemangiomas are common benign vascular tumours of infancy and childhood. Haemangiomas occur in 10-12% of children of 1 year of age and most of them are self-resolving within 9 years of age. Most common sites are head and neck (around 90%) and lip is one of the preferred sites. Sometimes persistence of haemangiomas may require surgical intervention. Capillary haemangiomas generally located superficially and cavernous haemangiomas located deep. Mixed capillary-cavernous haemangiomas or compound haemangiomas are one of the rarer types and location at lip rarest. Here we report a 14-years-old boy presented to paediatric surgery outdoor with swelling in lower lip for last 3 years. The excisional biopsy done with a clinical diagnosis of granuloma and sent for histopathological study. On microscopy of tissue sections given from lesion showed stratified squamous epithelium with sub epithelium revealing two distinct areas of capillary haemangioma component and cavernous haemangioma component within the lesion. So, final diagnosis of capillary-cavernous haemangioma (compound haemangioma) was made without any granuloma or malignant component. Patient followed up for six months and he was completely asymptomatic without any residual disease and recurrence.

Multifocal kaposiform haemangioendothelioma: Another sirolimus success story

Kaposiform haemangioendothelioma (KHE) is a rare, infiltrative, vascular tumour of infancy and early childhood that is often complicated by the Kasabach-Merritt phenomenon (KMP), a consumptive coagulopathy. We describe the case of a 7-year-old boy who presented with a left shoulder mass, splenic hypodensities, bony lesions, and a coagulopathy. The histopathological findings were consistent with KHE. Emergent treatment of KHE involves correction of the coagulopathy with blood products, while pharmacotherapy is aimed at reducing the tumour size. Emerging data suggest a role for mammalian target of rapamycin (mTOR)-inhibitors, e.g. sirolimus, in the treatment of progressive KHE, to which our patient had an excellent clinical response. Our recommendation is that KHE should be considered in the differential diagnoses of an ill-defined, infiltrating, soft-tissue mass. Pharmacotherapy including an mTOR-inhibitor should be instituted in patients with symptomatic KHE. Long-term follow-up of residual KHE lesions is essential as they follow an unpredictable course.

Study on the Mechanism of Targeted Poly(lactic-coglycolic acid) Nano-Delivery Carriers in the Treatment of Hemangiomas.

Hemangiomas, also called infantile hemangiomas (IH), are the most common congenital benign vascular tumors in infants and young children. At present, there are many treatment methods for proliferative hemangiomas, which have different effects and lack predictability. Propranolol has gradually replaced glucocorticoids as the first-line treatment for infants and young children with hemangiomas. However, premature discontinuation is prone to relapse, and the efficacy and safety of medication need to be further studied and determined. The exact pathogenesis of hemangiomas is still unclear. Therefore, in this study, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used as drug delivery carriers, propranolol was encapsulated, and PLGA-propranolol (PLGA-PP) nanodelivery preparations were prepared and targeted. Anisotropy and pharmacokinetics were preliminary studied. At the same time, after the treatment of HemECs cells with PLGA-PP in gradient concentration in vitro, CCK-8 method was used to detect the cell proliferation, and Anyixin-V/PI double staining method was used to detect the apoptosis rate of cells. The effect of PLGA-PP nano-delivery vector on hemangioma was studied by western blot method to detect the expression level of Id-1 protein in HemECs. The results showed that after PLGA-PP treated HemECs for 24 h, PLGA-PP significantly inhibited HeECs proliferation and promoted their apoptosis, and the intracellular Id-1 protein expression was also reduced. Therefore, this study believes that the mechanism of PLGA-PP nano-targeted delivery preparations in the treatment of hemangiomas is achieved by down-regulating the Id-1 gene, thereby inhibiting the colonization of HemECs and promoting its apoptosis effect.

Contrast-Enhanced Ultrasound of Congenital and Infantile Hemangiomas: Preliminary Results From a Case Series.

OBJECTIVE. The contrast-enhanced ultrasound (CEUS) imaging features of hepatic vascular tumors in infants, including infantile hemangioma (IH) and congenital hemangioma (CH), are not well reported. Frequent inaccurate use of lesion terminology in the literature has created diagnostic confusion. The purpose of this study is to describe the CEUS features of IH and CH. MATERIALS AND METHODS. Ten patients, ranging in age from 8 days to 16 months, with hepatic vascular tumors were included for retrospective analysis. Gray-scale ultrasound, color Doppler ultrasound, and CEUS features were reviewed, and interobserver kappa coefficients were calculated. Final diagnoses were clinically determined by a pediatrician with expertise in vascular anomalies except in one patient who underwent surgical excision. RESULTS. Of the 10 patients, five had CHs and five had IHs. All 10 lesions were hyperenhancing in the early arterial phase. In the portal venous phase, four of five (80%) CHs showed hyperenhancement relative to normal liver parenchyma, whereas four of five (80%) IHs showed isoenhancement. In the late phase, washout of contrast material was seen in three of five (60%) IHs, whereas one IH remained isoenhancing and one IH was hyperenhancing. None of the CHs showed late washout. Interobserver kappa coefficients for CEUS features ranged from 0.60 to 1.00. CONCLUSION. Except for the CEUS feature portal venous phase enhancement (κ = 0.60), good to excellent (κ = 0.74-1.00) agreement about CEUS features of IHs and CHs was observed. A significant proportion of IHs (60%) showed washout at delayed phase imaging, which has also been reported with malignancies. Recognition of the overlap in imaging appearance of these two entities is vital to preventing misdiagnosis of malignancy.

LASER SURGERY FOR SKIN VASCULAR TUMORS IN INFANTS

In young children, benign vascular tumors (VT) are most often manifested as congenital hemangioma and infantile hemangioma. There are considered clinical variants, pathogenesis, evaluation of severity and approaches to assessing the effectiveness of laser surgical treatment for VT in infants. For the first time, there are presented numerical criteria for selecting the optimal laser system to provide the relevant photo-obstruction of the pathological vascular bed, reducing the risk for the development of side effects in the early and remote period after the laser radiation exposure. Comparison of the values of the coefficients of complete absorption of oxyhemoglobin and hemoglobin at different stages of vascular tumor development shows the optimal laser treatment of vascular tumors can be realized by the laser radiation with a wavelength of 578 nm, since it is absorbed to the maximum extent by the main vascular photothermophores - oxyhemoglobin and hemoglobin. Taking into account the features of the angioarchitecture of the pathological vascular bed of the papillary dermis, to prevent the occurrence of petechial hemorrhages (purpura) immediately after the procedure, laser irradiation should be carried out in a pulsed mode with a pulse duration of 15-20 ns. To prevent thermal damage to the reticular layer of the dermis, it is advisable to use a laser pen with a diameter of 0.6-1 mm. The choice of optimal conditions for radiation exposure ensures high efficiency of the laser treatment of vascular tumors, which have been becoming one of the most promising directions in modern hospital-replacing technologies in pediatric laser surgery.

Is Propranolol as Safe as Reported in Managing All Pediatric Hemangiomas

Introduction: Hemangiomas are the most common benign vascular tumors of infancy. Infantile (IHs) and congenital (CHs) hemangiomas are similar in appearance, but differ in their presentation and behavior. Definitive diagnosis of IHs reflects presence of the GLUT1 marker; CHs have different markers. Despite the hypoglycemia seen in beta-blocker overdose, propranolol has a long-standing record of safety in various pediatric indications. With this history, and its effectiveness in IHs, it has become the drug of choice in IHs, and initial therapy in CHs. Case Report: A 4-year-old previously healthy African-American girl …

Risk of infantile hemangiomas in the offspring of women with autoimmune disease and the pathogenic implications of these lesions.

The purpose of this study was to analyze the risk of maternal autoimmune disease or associated treatments on infantile hemangiomas (IHs), a common benign vascular tumor in infants, and to better understand how maternal chronic inflammation may play a factor in the pathogenesis of these lesions. Eligible women from the United States and Canada who enrolled before 19 weeks' gestation and delivered at least one live born infant were recruited as part of the Organization of Teratology Information Specialists (OTIS) Autoimmune Disease in Pregnancy Project from 2004-2013. A total of 51/969 (5.3%) and 8/240 (3.3%) infants with IH were born to mothers with and without autoimmune disease, respectively (OR 1.61; 95%CI, 0.75-.44). The presence of ulcerative colitis (UC) in the mother was significantly associated with IH in the child (OR 3.46; 95%CI, 1.29-9.26). The five largest IH occurred within the autoimmune disease cohort and to women taking a biologic medication. These results imply that UC may be a risk factor for IH development, and that chronic inflammation may influence the development of these lesions. This potential link between IH and autoimmune disease warrants further investigation.

Propranolol Versus corticosteroids for Infantile Hemangiomas: A Randomized Control Trial in a Tertiary care Hospital

Infantile hemangiomas are the most common vascular tumor of infancy and childhood. Sometimes these lesions interfere with normal function &amp; produce serious disfigurement that is unlikely to resolve on its own and then treatment is required. While evidence most supports the use of corticosteroids, there is no well- studied or Federal Drug Administration (FDA) approved systemic therapy for haemangiomas of Infancy. Dramatic improvement of complicated haemangioma by propranolol has recently been reported, but to date, details for initiating therapy, monitoring and potential risks in relation to Corticosteroids were not compared in a large scale. This research was designed to observe the effectiveness of oral propranolol compared to oral corticosteroid aimed at treatment of clinically important groups of infantile hemangiomas that require aggressive treatment. We conducted a randomized control study among the diagnosed case of infantile hemangiomas, age of &lt;10 years. The total sample size was 60 (30 for propranolol group i.e. in group A, and 30 for corticosteroid group i.e. in group B) &amp; grouping was done with the simple random technique. A clinical &amp; photograph based VAS (Visual Analogue Scale) scale with a defined monitoring schedule was used for evaluation of treatment response. Our study result showed, (3.33%) patients of group A, response to color change (red-purple-grey) within 1st month of treatment whereas none of the patient (0.00%) of group B had any response to color by this time. Patients response to propranolol therapy was also continued even up to 5th month (3.33%) but it was absent (0.00%) in corticosteroid therapy even after 4th month &amp; p= 0.025, that was statistically significant. Regarding the mean size (diameter) of the tumor, most of the tumor size reduced and near to stabilize at 4th month in group A, but in group B, the rate was slower and needed longer time (5-6 month), the p value was 0.030. Again 60% of tumor became non-palpable at 3rd week of treatment in group A patients, but in group B, 70% of tumor was still remain palpable on that time &amp; p=0.001, that was statistically significant. Again, in Propranolol therapy group, the rate of complications was (24%) whereas in Corticosteroid therapy group, it was (76%).The p value was 0.020 that was also statistically significant. Hence, the present study results denote that, oral propranolol can be considered as an emerging and effective treatment over oral corticosteroid therapy for infantile hemangiomas.

589 N-myc downstream regulated gene 1(NDRG1) promotes proliferation and differentiation of infantile hemangioma cells

Infantile hemangioma (IH), the most common vascular tumor in infants, is characterized by during the first weeks to months of a child’s life, followed by a spontaneous involution over 10 years. However, its cellular origin and biological signals for uncontrolled growth are poorly understood, and specific pharmacological treatment is unavailable. Recently, we evaluated differences of mRNA expression and protein levels of FOXO1, NDRG1 and RICTOR between proliferating and involuting IH endothelial cells. We found that FOXO1 was decreased and NDRG1 was increased in IH endothelial cells during proliferation phase. Here, we investigated the effects of NDRG1 and FOXO1 expression in IH endothelial cells. Downregulation of NDRG1 expression in IH endothelial cells by siRNA transfection decreased differentiation of endothelial cells. Increased FOXO1 expression correlated with decreased expression of differentiation markers. Thus, our findings indicate that NDRG1 and FOXO1 are potential targets for regulating IH proliferation.

Infantile Haemangioma: Treatment in a Preterm Infant

Infantile Haemangioma (IH) is the most frequent benign vascular tumor of infancy, with an incidence of 23% in preterm infants, 2-3% in neonates and 10% after 1 year. Active treatment is indicated when large size or specific areas are involved, to prevent complications like ulceration, bleeding, infection and to diminish the potential scar. Ulceration is the most common complication and occurs in 16% or IH. There are very few reports concerning treatment of IH in preterm infants, although it’s higher incidence at this age. Topical timolol has recently been reported to be an effective and safe treatment for superficial infantile haemangioma.

Infantile Hemangiomas: An Updated Review on Risk Factors, Pathogenesis, and Treatment.

Infantile hemangiomas (IHs) are the most common vascular tumors in infants, appearing in early infancy and ultimately regressing with time. Clinical presentation may vary, with a minority of lesions causing impairment of vital function (e.g., respiratory or visual obstruction), permanent scarring, and/or disfigurement. The pathogenesis of IH is complex and poorly understood. Risk factors implicated in their development include preterm birth and placental anomalies. IH presents a myriad of clinical challenges, including correct diagnosis and whether or not to pursue treatment. This article is a review of the current literature regarding pathogenesis, clinical presentation, treatment, and prognosis of IH. Birth Defects Research 109:809-815, 2017. © 2017 Wiley Periodicals, Inc.

Regulation of endothelial cell proliferation of infantile hemangioma through mTORC2 and NDRG1 signaling pathways

Infantile hemangioma (IH), the most common vascular tumor in infants, is characterized by during the first weeks to months of a child's life, followed by a spontaneous involution over 10 years. Although benign, some IHs cause deformation and destruction of features or endanger life. Propranolol, a nonselective β-adrenergic receptor (βAR) has proved efficacious for problematic IH and can lower cAMP levels and activate the MAPK pathway downstream of βARs. Recent in vitro and in vivo studies show that rapamycin, an mTOR (mammalian target of rapamycin) inhibitor, reduces the self-renewal capacity of the hemangioma stem cells, diminishes differentiation potential, and inhibits the vasculogenic activity of these cells. mTOR functions in two distinct complexes, mTORC1 and mTORC2, and little is known regarding the relative contribution of mTORC1 versus mTORC2 in vascular endothelial cells. The aim of this study was to assess the role of rapamycin-insensitive companion of mTOR (Rictor) in control of infantile hemangioma proliferation and cell signaling mechanism in human umbilical vein endothelial cells. We found that Rictor ablation inhibited VEGF-induced endothelial cell proliferation in vitro. The loss of Rictor reduced the phosphorylation of PKCα and NDRG1 without affecting the mTORC1 pathway. Our results showed that loss of Rictor down-regulated phosphorylation of S6 by which IH cell growth and proliferation were greatly suppressed. The role and mechanism of Rictor in IH were assessed by western blotting and real time PCR. Taken together, these data indicate that mTORC2 is significant for VEGF-mediated IH cell proliferation through the regulation of PKCα and NDRG1.

Morphological characterization of infantile hemangiomas: An Indian study

Context: Vascular tumors of infancy and childhood consist of a number of clinicopathologically distinct entities. Infantile hemangiomas (IH) constitute the bulk of these tumors. As they are seldom biopsied, we do not encounter an opportunity to study them, and this is evident from the paucity of reported cases in pathology literature from India. Clinicians and pathologists alike have traditionally tended to lump these tumors, under overly generic terms like capillary hemangioma which do little to guide proper clinical management. Aims: To delineate the morphological features that characterize IHs and outline the morphological changes seen in different phases of evolution of this tumor. Subjects and Methods: We characterized 21 cases of IHs over a period of 60-months. Mast cells were counted in 10 fi elds of high density, and mast cell density per square millimeter area was calculated. Results: Female to male ratio was 1:1.6. Head and neck were the most common region involved (71.4%). Morphological features were described. Mast cell density/square millimeter area ranged from 126.9 to 285.7. Spearman correlation coeffi cient was 0.681 (P = 0.676). Statistical Analysis: Spearman correlation coefficient was used to analyze the relationship between mast cell numbers and the age of the lesion. Conclusions: Morphological features seen on routine microscopy can easily help distinguish a lobular capillary hemangioma from an IH or a congenital hemangioma even in the absence of relevant clinical details, pointing to a need for looking beyond using a generic term of capillary hemangioma.