Distinguishing soft-tissue hemangiomas from vascular malformations using technetium-labeled red blood cell scintigraphy.

Soft-tissue vascular lesions in children can be classified as either hemangiomas or vascular malformations. The distinction between the two has important prognostic and therapeutic implications. Over the past 8 years, we have evaluated 64 vascular lesions with the technetium-labeled red blood cell (Tc-RBC) scan. Twenty-eight lesions imaged as hemangiomas with intense focal uniform uptake. This diagnosis was confirmed in 27 lesions, or 96 percent. Thirty-six lesions imaged as vascular malformations with abnormal vessels or diffusely increased activity. This diagnosis was confirmed in 35 lesions, or 97 percent. Overall, the Tc-RBC scan was 97 percent accurate in distinguishing hemangiomas from vascular malformations. It is particularly useful when the clinical diagnosis of the lesion may not be evident. Not only can biopsy be avoided, but parents can be reassured at an earlier age and given accurate information regarding prognosis.     

Diagnosis of hepatic hemangiomas with 99mTc-labeled red blood cell scanning: value of SPECT.

99mTc-labeled red blood cell (RBC) scanning is considered a highly specific technique for the study of hepatic hemangiomas. However, planar imaging displays poor sensitivity for the identification of small lesions. The authors consider a survey group of 119 patients, of whom 66 with a presumed diagnosis of hepatic hemangioma, for a total of 77 lesions ranging from 0.8 to 15 cm in diameter. The study was conducted with three-phase planar imaging and single photon emission computed tomography (SPECT). The results, which confirm a high specificity of 99mTc-RBC scanning (100%) in the study of hepatic hemangiomas, show that SPECT significantly improves the detection of these lesions (71%) compared to the delayed static study (52%), with the largest gain for lesions between 2-3.5 cm (83% versus 51%). However, also SPECT has difficulty in detecting lesions of less than 2 cm. With regard to three-phase imaging, the authors point out that the pattern considered characteristic for hepatic hemangiomas (perfusion blood-pool mismatch) is infrequent (13%).     

Sapphire tip technology for YAG laser excisions in plastic surgery

Thirty-two patients with a variety of vascular and nonvascular lesions have been resected over a 3-year period with the neodymium:YAG laser utilizing sapphire peripheral scalpel devices. These innovative peripheral devices concentrate the YAG laser energy to a small area at the end of the scalpel, providing precise incisions with excellent hemostasis. In addition, the tactile sensation of the scalpel contacting tissue is more comfortable and familiar than the "no touch" aspect of other lasers that are held away from the surface and depend on laser light transmission to approach the skin. Total excision with excellent hemostasis was achieved in 17 patients, while 15 patients had subtotal resection. The YAG laser with sapphire scalpels has allowed resection of very difficult and massive hemangiomas previously considered unresectable by standard techniques.     

Hypoxia, hormones, and endothelial progenitor cells in hemangioma

Hemangiomas are the most common tumor of infancy, and although the natural history of these lesions is well described, their etiology remains unknown. One current theory attributes the development of hemangiomas to placentally-derived cells; however, conclusive evidence to support a placental origin is lacking. While placental tissue and hemangiomas do share molecular similarities, it is possible that these parallels are the result of analogous responses of endothelial cells and vascular progenitors to similar environmental cues. Specifically, both tissue types consist of actively proliferating cells that exist within a low oxygen, high estrogen environment. The hypoxic environment leads to an upregulation of hypoxia inducible factor-1alpha (HIF-1alpha) responsive chemokines such as stromal cell derived factor-1alpha (SDF-1alpha) and vascular endothelial growth factor (VEGF), both of which are known to promote the recruitment and proliferation of endothelial progenitor cells. Increased hormone levels in the postpartum period further potentiate the growth of these lesions. In this model, increased stabilization of HIF-1 in concert with increased levels of estrogen create a milieu that promotes new blood vessel development, ultimately contributing to the pathogenesis of infantile hemangiomas.     

Ulcerated anogenital hemangioma of infancy

Ten female infants were referred for symptomatic hemangiomas in the anogenital area. (One had had steroid treatment prior to consultation.) The natural history of these lesions is well known. Virtually all will spontaneously involute over a period of years. However, the lesions reported were particularly troublesome because of repeated ulcerations and subsequent pain. Prior treatment had been local wound care with antibiotic ointment and Telfa-type dressings. After referral from a family practitioner or pediatrician, argon laser treatment was performed in an outpatient setting. Eight of the 10 patients were treated with local anesthesia, and 2 had general anesthesia. All lesions healed in 1 to 5 weeks. No patients referred during this period were excluded from this series. All who received treatment were included. All the lesions involuted following treatment. In our estimation, the final result is identical to what may be expected after spontaneous involution of an ulcerated or infected hemangioma. The major difference is that involution occurred in a few weeks in laser-treated patients rather than a period of months or years. Ulcerated hemangiomas of the anogenital area have significant morbidity that can be efficiently avoided with the use of argon laser therapy. Lesions of the anogenital area have a strong predilection for females.     

Leishmania chagasi: in vitro differentiation of promastigotes monitored by flow cytometry

A sequential development from a less infective to an infective stage of Leishmania promastigotes growing in culture has been previously reported. The aim of this work was to investigate whether freeze-fracture electron microscopy and flow cytometry would be able to provide some reliable morphological markers of in vitro differentiation of Leishmania chagasi promastigotes. The flow cytometry technique discriminates between the L. chagasi promastigotes from the different stages of their in vitro differentiation. The "forward scatter" intensity of the parasite, very high 15 hr after seeding when the parasites were very condensed and with a high DNA content per particle, strongly decreased during the culture course. Parallel experiments have shown a striking correlation between forward scatter intensity, growth curves, and infectivity of promastigote populations. By contrast, freeze-fracture techniques showed that in either less infective or infective promastigote plasma membranes, the intramembrane particles density in protoplasmic fracture faces (about 2800/micron 2) and in exoplasmic fracture faces (about 1000/micron 2) was independent of the time of cultivation. The amount of filipin lesions, which reflects the cholesterol content within the plasma membrane, was also constant throughout the culture course. Both data suggest that the architecture of the plasma membrane is an intrinsic characteristic of the promastigote stage. This study shows that whereas freeze-fracture electron microscopy does not provide markers for the differentiation of Leishmania promastigotes, flow cytometry may on the other hand be of value as a screening test for promastigote populations allowing the characterization of their developmental stages in in vitro cultures.     

Karyotypic changes detected by comparative genomic hybridization in a stillborn infant with chorioangioma and liver hemangioma

BACKGROUND: Placental hemangioma (chorioangioma) and congenital hemangioma are relatively common tumors, which on rare occasions may occur together. Very little is known about the pathogenetic mechanisms underlying these lesions. CASE: Herein we describe a rare case of a stillborn infant with chorioangioma, placental mesenchymal dysplasia, and liver cavernous hemangioma. In addition, we present the findings of the karyotype analysis of these lesions, which was done with the bacterial artificial chromosome arrays using the comparative genomic hybridization method. The chromosomal abnormalities that we found were deletions at 2q13 and 7p21.1 and were common to both placental and liver lesions. CONCLUSIONS: None of the identified chromosomal aberrations have been previously associated with chorioangiomas or hemangiomas. Important genes that lie in these DNA regions may be implicated in the pathogenesis of congenital hemangiomas and mesenchymal dysplasia.     

Hemangiomas - current therapeutic strategies

Hemangiomas are benign neoplasms of the vasculature frequently encountered in children. Several studies have shown that these tumors are characterized by excessive angiogenesis. Although benign, the lesions can present with complications, and may thus require treatment. There are multiple therapeutic options available for patients with problematic or life threatening hemangiomas, some of which have serious side effects. Randomized clinical trials and evidence-based studies on the efficacy of these treatments is still lacking. The recognition that excessive angiogenesis underlies hemangiogenesis offers an opportunity for the development of safer therapeutic strategies that are based on the inhibition of angiogenesis. We review medical therapies currently employed in the management of hemangiomas and the role of angiogenesis inhibition in hemangioma therapy.     

Identifying potential regulators of infantile hemangioma progression through large-scale expression analysis: a possible role for the immune system and indoleamine 2,3 dioxygenase (IDO) during involution

Hemangiomas are benign endothelial tumors. Often referred to as hemangiomas of infancy (HOI), these tumors are the most common tumor of infancy. Most of these lesions proliferate rapidly in the first months of life, and subsequently slowly involute during early childhood without significant complications. However, they often develop on the head or neck, and may pose a significant cosmetic concern for families. In addition, a fraction of these tumors can grow explosively and ulcerate, bleed, or obstruct vision or airway structures. Current treatments for these tumors are associated with significant side effects, and our knowledge of the biology of hemangiomas is limited. The natural evolution of these lesions creates a unique opportunity to study the changes in gene expression that occur as the endothelium of these tumors proliferates and then subsequently regresses. Such information may also increase our understanding of the basic principals of angiogenesis in normal and abnormal tissue. We have performed large-scale genomic analysis of hemangioma gene expression using DNA microarrays. We recently identified insulin-like growth factor 2 as a potentially important regulator of hemangioma growth using this approach. However, little is known about the mechanisms involved in hemangioma involution. Here we explore the idea that hemangioma involution might be an immune-mediated process and present data to support this concept. We also demonstrate that proliferating hemangiomas express indoleamine 2,3 dioxygenase (IDO) and discuss a possible mechanism that accounts for the often slow regression of these lesions.     

Polyoma virus middle-T-transformed PECAM-1 deficient mouse brain endothelial cells proliferate rapidly in culture and form hemangiomas in mice

Wild-type mouse brain endothelial (bEND) cells transformed with the polyoma virus middle-T proliferate rapidly in culture and form hemangiomas in mice. These cells express high levels of platelet/endothelial cell adhesion molecule-1 (PECAM-1), a molecule shown to be important during hemangioma formation. In this study, we have examined the ability of polyoma virus middle-T-transformed mouse bEND cells prepared from PECAM-1-/- mice to proliferate in culture and form hemangiomas in mice. We show that these cells express a number of endothelial cell markers and share a similar morphology with PECAM-1+/+ bEND cells. PECAM-1-/- bEND cells exhibit a limited ability to form tubes in Matrigel and rapidly form hemangioma when injected into nude mice, very similar to PECAM-1+/+ bEND cells. These cells, however, have increased proliferation, slower migration, altered endothelial cell adhesion molecule expression, and are less adherent when compared to PECAM-1+/+ bEND cells. Therefore, lack of PECAM-1 expression impacts polyoma middle-T-transformed endothelial cell proliferative, adhesive, and migratory properties without impacting their ability to rapidly form hemangiomas in mice or poorly organize to capillary-like structures in Matrigel.     

Skeletal changes associated with vascular malformations

Five hundred and eighty birthmarks were reviewed; 356 were hemangiomas and 224 were malformations. Bony alterations occurred in association with only 1 percent of hemangiomas, in contrast with 34 percent of patients with vascular malformations. These alterations in bone development were classified according to size, shape, and density changes. Hypertrophy and distortion were typical of lymphatic malformations. Hypoplasia and demineralization were characteristic findings in the extremity venous malformations. Destructive and intraosseous changes were more commonly noted in the arterial or high-flow lesions. Possible mechanisms of altered skeletal growth include mechanical, physiological, and developmental processes.     

兴修水利枢纽后汉江产漂流性卵鱼类的繁殖生态

汉江产漂流性卵的鱼类至少有25种,其中经济鱼类有草鱼、青鱼、鲢、鳙、鯮、鳤、鳡、长春鳊、赤眼鳟、铜鱼、吻鮈、鳜以及三种红鲌属鱼类。       

Local serum levels of vascular endothelial growth factor in infantile hemangioma: Intriguing mechanism of endothelial growth

The pathogenesis of hemangiomas still remains poorly understood. Dysregulation of angiogenesis has been proposed to play a central role in hemangioma pathogenesis. The aim of our study was to determine the peripheral and local serum levels of VEGF in patients with hemangiomas and vascular malformations. Material and methods: The study group consisted of 52 children with infantile hemangioma (33 with proliferative lesions, 19 with involuting lesions), 14 children with vascular malformations and 36 healthy children. VEGF serum levels were analyzed by an ELISA assay and the values between the groups were compared. Results: The serum peripheral VEGF concentrations in children with proliferative hemangiomas were significantly higher than in patients with involuting hemangiomas, vascular malformations and controls. There was no correlation between the measured cytokine level, hemangioma size, and the age of the patients. The local serum VEGF levels in 29 children with hemangiomas were distinctly lower than in the peripheral blood, both in 20 proliferating hemangiomas (p < 0.0001) and 9 involuting ones (p = 0.007); and the difference between females and males was non-significant (NS p = 0.06). Conclusions: (1) VEGF serum levels vary in the different phases of hemangioma growth and may help to distinguish hemangiomas from vascular malformations; (2) obtained local results may support the intrinsic theory of endothelial cell proliferation in hemangiomas.     

Extended use of sodium tetradecyl sulfate in treatment of hemangiomas and other related conditions

Sodium tetradecyl sulfate, a sclerosing agent, has been used in 18 patients in the treatment of difficult hemangiomas not amenable to surgery alone, with or without adjunctive operation, in eyelid and lip lesions, in saccular and large posterior and hypopharyngeal hemangiomas, in Klippel-Trenaunay syndrome, in variceal bleeding around a Koch ileal pouch, and as an adjunct to selective embolization in a patient with a facial A-V malformation. Sodium tetradecyl sulfate was injected intralesionally in aliquots of 0.05 to 0.1 cc at multiple sites in total doses not exceeding 2.0 to 4.0 cc. Two patients showed questionable or no improvement. The remaining 16 patients experienced modest to striking improvement with only very minimal complications in the form of superficial desquamation of skin. The conclusion is, therefore, that sodium tetradecyl sulfate, used appropriately, is a safe and frequently effective agent in the treatment of hemangiomas and a number of similar or related problems. Clinical results will be presented.     

Risk stratification in hemangiomas of infancy

Hemangiomas of infancy are very common tumors, but they are heterogeneous in their behavior. A small, but significant, subset causes medical complications or permanent disfigurement, but due to their heterogeneity, there is no appropriate "one size fits all" approach to management. In addition, the rapid evolution of this tumor over the first weeks-to-months of infancy renders even more difficult the task of predicting which infants will have medical complications or permanent disfigurement. This article outlines the clinical characteristics that help to stratify hemangiomas into those which are high risk, and likely to require either active treatment or closer scrutiny, and those which are low risk, and likely to behave in an innocuous manner. Five major factors are emphasized: the age of the child, the location of the hemangioma(s), the total number of hemangiomas present, the hemangioma subtype, and the presence and nature of dermal involvement.     

Primary thyroid angiosarcoma: an unusual localization

ABSTRACT: The finding of thyroid nodules is a very common occurrence in routine clinical practice. Approximately 5% to 7% of the entire population have thyroid nodules. Vascular lesions are one of the most controversial issues in thyroid pathology. These include benign lesions such as hemangiomas and, rarely, malignant tumors such as angiosarcomas or undifferentiated angiosarcomatoid carcinomas. In particular, angiosarcoma of the thyroid gland is a rare, highly aggressive malignant vascular tumor and in Italy the greatest geographical incidence of this lesion is witnessed near the Alps. Here, a case of thyroid angiosarcoma in a 71-year-old man with a history of goiter for about 20 years is described. The unusual localization of this lesion, the difficulties in reaching a definitive diagnosis for this particular histological type of primary tumor and a history of long-standing multinodular goiter in thyroid of an older man from outside the Alpine region prompted us to report this case of thyroid angiosarcoma mainly to discuss surgical, histopathological and immunohistochemical features.     

Therapeutic coagulation induced in cavernous hemangioma by use of percutaneous copper needles.

Fifty-two patients with cavernous hemangiomas were therapeutically coagulated by use of percutaneous copper needles. Of the 52 patients, 32 had cavernous hemangiomas of the face and neck and 20 had cavernous hemangiomas of the trunk and extremities. All have gained effective treatment. Through in vitro tests, animal experiments, and clinical studies, I have confirmed that copper needles produce coagulation and destruction of cavernous hemangiomas. The mechanism, indications, technique, prevention and treatment of complications, and an analysis of copper concentrations in the patients' blood are discussed. My conclusion is that this is a simple, safe, and effective treatment for cavernous hemangiomas.     

Status of the "dead point" of blood flow in anastomoses of superficial cerebral arteries as affected by an acute increase of blood pressure

Changes in pial arteries diameter and the condition of blood flow "dead point" in arterial anastomoses were established using the brain window during an acute increase of mean arterial pressure (MAP) induced by intravenous injection of norepinephrine (NE) with microcineangiography and the analysis of films and frames on a montage table and TAS ("Leitz"). During an acute increase of MAP the movement of blood flow "dead point" in anastomoses and the expansion of plasma segments occurred much more frequently than in normotension. The stabilization of blood flow "dead point" was observed at high constant MAP. Pronounced dilation of both pial arteries and veins first occurred in anastomoses, then spread to arterial branches. It is assumed that high vulnerability of the brain vessels of the borderline zones is due to breakthrough in autoregulation of cerebral blood flow on its upper limit and depends on the repeatedly changing directions of the blood flow and its moving "dead point", as the peripheral resistance of arterial anastomoses-forming branches under these circumstances changes in an irregular manner.     

Surgical management of parotid hemangioma

Hemangiomas represent one of the most common childhood neoplasms. They are often managed conservatively, requiring numerous years for spontaneous involution. No effective medical treatment has been reported for children with large, deforming hemangiomas of the parotid gland and overlying cheek. The authors retrospectively studied 17 children who underwent surgical resection of parotid hemangiomas at Childrens Hospital Los Angeles from 1997 to 2003. All 17 patients had improvements in facial asymmetry and deformity. There were no major complications. Minor complications included hematoma (11.8 percent), transient facial nerve palsy (11.8 percent), and blood transfusion (5.9 percent). All operations were performed on an outpatient basis. Surgical resection of parotid hemangiomas provides an aesthetic benefit to young children with low associated morbidity. Early resection by an experienced surgeon should be considered as a treatment option for these disfiguring lesions.     

An anatomical basis for prognosis of malignant melanoma.

Clinical observations during surgery have led us to speculate that an anatomic basis may in fact exist for the poor prognosis associated with malignant melanoma arising in certain recognized "high-risk" areas. In our study we have treated and followed 45 patients with primary malignant melanoma for over 5 years. During the course of treatment, we identified variations in anatomic characteristics at the tumor sites. Criteria were established for high- and low-risk locations by the neurovascular structure encountered. We speculate that these sites that have neurovascular windows provide a readily accessible vascular pathway for the dissemination of malignant cells to deeper visceral structures and may account for the poor prognosis associated with primary lesions in these locations. Thirty patients were classified as being at high risk for developing metastasis, whereas 13 were classified as being at low risk; 2 patients were in a special-risk category. To date, 12 of the 30 patients with "high-risk" melanoma have gone on to develop metastatic disease, which represents 40 percent of that group, whereas none of the patients classified as "low risk" have developed metastases during the same period.