Topical timolol in the treatment of periocular superficial infantile hemangiomas: a prospective study / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and side effect of topical beta-blocker (Timolol Maleate) in the treatment of periocular hemangioma in a prospective study.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

A prospective study of propranolol as first-line treatment for problematic infantile hemangioma in China / 中华整形外科杂志

<p><b>OBJECTIVE</b>To prospectively assess the efficacy and safety or propranolol as a first-line treatment for problematic infantile haemangioma in China.</p><p><b>METHODS</b>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).</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>Propranolol is effective in the treatment of infantile hemangioma with minor side effect. We suggest it should be used as the first-line treatment.</p>

Clinical application of imiquimod for the treatment of infantile hemangiomas / 中华整形外科杂志

<p><b>OBJECTIVE</b>To explore the clinical application of imiquimod for the treatment of infantile hemangiomas (IH).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

The pathological characteristics and clinical significances of maturational change of port-wine stain / 中华整形外科杂志

<p><b>OBJECTIVE</b>In this study histologic observations were presented to elucidate the possible mechanism of maturational change of port-wine stain(PWS).</p><p><b>METHODS</b>Normal PWS(3 cases) , thicken PWS (11 cases) and nodular PWS (9 cases) were included to present histologic observations.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Pathological characteristics and clinical significance of macrochilia secondary to venular malformation / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To analyze the histologic characteristics of macrochilia secondary to port-wine stain and to elucidate the possible mechanism.</p><p><b>METHODS</b>Twenty-one cases of macrochilia secondary to venular malformation were included and the histology of the lesions was observed by light microscope.</p><p><b>RESULTS</b>Histological examination revealed vascular abnormalities and a number of widely distributed hamartomatous changes in macrochilia secondary to venular malformation. The average vessel diameter is (39.8 +/- 15.7) microm. The degree of hamartomatous change: mild (1 case), moderate (7 cases) and severe (13 cases).</p><p><b>CONCLUSIONS</b>The complex hamartomatous changes suggest a genetically determined, multilineage developmental field defect in the pathogenesis of venular malformation.</p>

Non-involuting congenital hemangioma: a study for diagnosis and treatment / 中华整形外科杂志

<p><b>OBJECTIVE</b>To study the history, clinical symptoms, imaging and histology of a rare distinct infantile hemangioma.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>Non-involuting congenital hemangioma is a distinct infantile vascular tumor. It should be diagnose early and treated appropriately.</p>

Superselective ethanol endovascular therapy under digital subtraction angiography for craniofacial arteriovenous malformations / 中华整形外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Isolation, culture and characterization of endothelial cells in infantile hemangioma / 中华整形外科杂志

<p><b>OBJECTIVE</b>To establish a method for the reliable isolation and culture of infantile hemangioma endothelial cells (HemECs) in vitro.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Noninvasive laser therapy for skin superficial venous malformations with long pulsed Nd:YAG laser / 中华整形外科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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%.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Role of urinary basic fibroblast growth factor in differentiating hemangiomas from vascular malformation / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate a novel method to differentiate hemangioma from vascular malformation, to stage hemangiomas and to monitor the efficacy of management for hemangioma.</p><p><b>METHODS</b>The urinary basic fibroblast growth factor (bFGF) concentration of 144 cases (including 69 cases of proliferating hemangiomas, 41 cases of involuting hemangiomas, 23 cases of vascular malformations and 11 negative controls) was examined using enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The differences of urinary bFGF concentration among proliferating hemangiomas, involuting hemangiomas, vascular malformations and negative control were all significant, while the differences between the latter three groups were not significant.</p><p><b>CONCLUSIONS</b>Our findings suggest that examination of urinary bFGF concentration using ELISA technique is helpful in differentiating hemangioma from vascular malformation, staging hemangiomas and dynamically monitoring the efficacy of treatment for hemangiomas. Our results probably shed new light on the potential pathogenesis of hemangiomas and vascular malformation.</p>

The relationship between the expression of HIF-1alpha and the angiogenesis in infancy hemangioma / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the expression of HIF-1alpha and its roles on the vascular endothelial cell growth factor (VEGF) and microvessel density (MVD ) in hemangioma.</p><p><b>METHODS</b>Immunohistochemical streptavidin/peroxidase(SP) stain was applied to examine the expression of HIF-1alpha, VEGF and CD34. The amount of microvessel was counted, which the endothelial cell expressed CD34.</p><p><b>RESULTS</b>The nuclei and cytoplasm of the endothelial cell showed positive staining for HIF-1alpha in hemangioma. In 28 cases, positive rate for HIF-1alpha was 64%, for VEGF was 71.4%. In the proliferating phase, positive rate for HIF-1alpha was 87.5%, for VEGF was 93.7%. However, the positive rate for HIF-1alpha, in the involuting phase, was 33.3%, and for VEGF was 41.7%. There was a very significantly different between two phases (P < 0.01). In the proliferating phase, MVD was 73.4 +/- 14.63 . In the involuting phase, MVD was 30.2 +/- 9.1 (P < 0.01). The correlation between the HIF-1alpha and VEGF was positive (P < 0.01). There was a positive correlation between the HIF-1alpha and MVD (P < 0.01).</p><p><b>CONCLUSIONS</b>There might be a special hypoxia microenvironment in endothelial cell of the hemangioma in proliferating phase , which could up-regulate the expression of the HIF-1alpha protein. The HIF-1alpha protein could also up-regulate the VEGF protein and then result in the angiogenesis.</p>

Staging and management of extracranial arteriovenous malformations / 中华整形外科杂志

<p><b>OBJECTIVE</b>Congenital arteriovenous malformations(AVM) are considered to be the most difficult and challenging problems in the treatment of hemangiomas and vascular lesions. This study focused on the natural history, the clinical classification, the choice and effectiveness of various treatments.</p><p><b>METHODS</b>This retrospective review included 83 patients with extracranial arteriovenous malformations, who were referred to our department over the past 6 years. The anatomic patterns, clinical staging, respective treatments, influential factors of endovascular treatment, causes of recurrence were analyzed.</p><p><b>RESULTS</b>According to clinical manifestations, arteriovenous malformations were categorized as three clinical stages: the quiescence, the expansion and the decompensation stages. Most AVMS in the quiescence stage only require endovascular treatment while those in the decompensation stage require surgical resection. Angiography was performed not only for diagnosis of AVM but also as an initial therapeutic step in the form of embolization, which might be the only means to some AVM without surgical possibility or necessity.</p><p><b>CONCLUSION</b>The new concept of staging and management is expected to be helpful for diagnosis and treatments of AVM.</p>

The regulating effect of antisense-S-Oligo on TYR gene expression and melanin production of melanocytes / 中华整形外科杂志

<p><b>OBJECTIVE</b>Despite the causes for melanin increase, the increased gene expression of TYR is a common pathological process. Based on this viewpoint, antisense-S-Oligo of TYR was designed and synthesized to regulate synthesis of melanin in order to explore the treatment for skin pigmentation.</p><p><b>METHODS</b>The cultured melanocytes were divided into 3 groups. The group 1 was treated with endothelin, group 2 treated with ultraviolet ray and group 3 was used as the control. In each group, the 5' antisense-S-Oligo, the 3' antisense-S-Oligo, the mixed antisense-S-Oligo of TYR or Dotap only was added. The melanin content and TYR gene expressions were examined.</p><p><b>RESULTS</b>The 5' antisense-S-Oligo, the 3' antisense-S-Oligo and the mixed antisense-S-Oligo significantly inhibited the increase of melanin content and TYR gene expression, which were caused by endothelin or ultraviolet ray treatment. Of the three treatments, the 3' antisense-S-Oligo showed the strongest effect.</p><p><b>CONCLUSION</b>Antisense-S-Oligo has significant regulating effects on TYR gene expression and melanin content. The 3' antisense-S-Oligo is more effective than the 5' antisense-S-Oligo.</p>

The expression of activin A and transforming growth factor-beta 1 during rabbit mandibual distraction osteogenesis / 中华整形外科杂志

<p><b>OBJECTIVE</b>To examine the expression of activin A (ACT A) and transforming growth factor-beta 1 (TGF-beta 1) during mandibular lengthening and elucidate the difference between the role of ACT A and TGF-beta 1 during mandibular distraction osteogenesis.</p><p><b>METHOD</b>Skeletally mature white new zealand rabbits were established right mandibular distraction osteogenesis model. The regenerating tissue of animals' lengthened mandibes were harvested at different time points to have immunohistochemistric research of ACT A, TGF-beta 1 protein and analysis ACT A, TGF-beta 1 mRNA by using RT-PCR semiquantitative mean.</p><p><b>RESULTS</b>AT the end of latency period day, positive stain of ACT A were found in the osteoblasts while positive stain of TGF-beta 1 was found in mesenchymal cells. At the end of distraction phase, fibrosis tissue had no stain of ACT A, but had strong stain of TGF-beta 1. At the period of fixation days of 20 days, both cytoplasm of osteoblasts and extracellular matrix in primary mineralization front were strongly stained of ACT A. The osteoblasts, osteoid and osteocytes in peripheral new bone zone were moderately stained of ACT A. TGF-beta 1 had strongly positive stained in fibrosis zone and weekly positive stained in primary mineralization front and peripheral new bone zone. There were also broad activin A stains in cytoplasm of osteoblasts, osteoid and cytoplasm of ACT A, TGF-beta 1 in osteocytes after distraction for 30 days. Activin A mRNA began to express at the end of latency period. Expression for activin A mRNA increased gradually along with the beginning of distraction and at the peak in distraction of 10 days and 20 days, while TGF beta 1 mRNA increased at the peak at the end of latency period.</p><p><b>CONCLUSION</b>ACT A and TGF beta 1 have different role during rabbit mandibular distraction osteogenesis.</p>

Indentification of differentially expressed genes in proliferating and involuting hemangiomas by cDAN microarray analysis of gene-expression profiles / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the differentially expressed genes of proliferating and involuting hemangiomas by cDNA microarray analysis of gene-expression profiles in an effort to identify the key disease-related genes.</p><p><b>METHODS</b>Samples were processed from total RNA and purified to mRNA, which was reverse-transcripted and hybridized onto Biodoor Genechip expression microarrays. Analyses were performed to determine the consensus pattern of gene expression in the proliferating and involuting stages of the same hemangioma and the changes in the expression level.</p><p><b>RESULTS</b>In proliferating hemangioma, 79 genes were overexpressed, and 115 genes were underexpressed in comparison with the involuting hemangioma. Some cytokines and growth factors such as neurotensin, Nov, CYR6, keratinocyte growth factor, interleukin-10 were overexpressed in proliferative hemangioma. In involuting hemangioma, apoptotic factors such as bcl-2 binding component, cytochrome C were overexpressed. The overexpression of Nov, CYR6, c-myc implied that angiogenesis and oncogenes might participate in the pathogenesis of hemangiomas. Mitochondria activated apoptotic passage (cytokines, bcl-2, cytochrome C) and Wnt/beta-catenin passage(Frizzled, beta-catenin, c-myc) were involved.</p><p><b>CONCLUSION</b>The development of hemangiomas may be the results of imbalance of cell proliferation and apoptosis.</p>