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.     

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.     

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.     

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.     

Transiently arterialized hemangiomas: relevant clinical and cardiac issues

Although the majority of hemangiomas of infancy undergo an uncomplicated, predictable course of proliferation followed by involution, a subset of patients sustain a more fastidious course. These include hemangiomas that, at least during part of their life cycle, have a high flow (arterial) component. Hemangiomas with high flow are most frequently located in the liver. These lesions can lead to significant morbidity, with high output cardiac failure. We have identified nonhepatic hemangiomas that have an apparent propensity to develop a high flow element--the parotid, upper arm, scalp, and rarely the upper lip--and present our experience in this report. These lesions appear to behave as transiently "arterialized" hemangiomas.     

STRAWBERRY HEMANGIOMAS—The Natural History of the Untreated Lesion

A review of the literature on the natural history of strawberry hemangiomas revealed over-whelming evidence of the satisfactory spontaneous involution of over 95 per cent of these lesions without the scarring and danger of other sequelae inherent in the various forms of treatment.In a study of 105 strawberry nevi observed for more than one year, 97 per cent of the lesions had either completely disappeared or were regressing satisfactorily.A cross-section study of 1,735 consecutively examined children in routine pediatric practice showed hemangiomas to be present in 10.1 per cent of all infants from birth to one year of age but that this incidence drops to 1.5 per cent in children over five years of age, confirming the fact of spontaneous involution.     

Strawberry hemangiomas; the natural history of the untreated lesion

A review of the literature on the natural history of strawberry hemangiomas revealed over-whelming evidence of the satisfactory spontaneous involution of over 95 per cent of these lesions without the scarring and danger of other sequelae inherent in the various forms of treatment. In a study of 105 strawberry nevi observed for more than one year, 97 per cent of the lesions had either completely disappeared or were regressing satisfactorily.A cross-section study of 1,735 consecutively examined children in routine pediatric practice showed hemangiomas to be present in 10.1 per cent of all infants from birth to one year of age but that this incidence drops to 1.5 per cent in children over five years of age, confirming the fact of spontaneous involution.     

Predicting the course of a congenital hemangioma.

We report a series of 10 congenital hemangiomas which have been followed by serial examinations with the Doppler apparatus, to determine persistence of and increase in A--V fistulae, or a decrease in same. We believe the data on the A--V fistulae correlate inversely with the likelihood of spontaneous regression and involution.     

Role of pigment epithelium-derived factor in the involution of hemangioma: Autocrine growth inhibition of hemangioma-derived endothelial cells

Hemangioma is a benign tumor derived from abnormal blood vessel growth. Unlike other vascular tumor counterparts, a hemangioma is known to proliferate during its early stage but it is followed by a stage of involution where regression of the tumor occurs. The critical onset leading to the involution of hemangioma is currently not well understood. This study focused on the molecular identities of the involution of hemangioma. We demonstrated that a soluble factor released from the involuting phase of hemangioma-derived endothelial cells (HemECs) and identified pigment epithelium-derived factor (PEDF) as an anti-angiogenic factor that was associated with the growth inhibition of the involuting HemECs. The growth inhibition of the involuting HemECs was reversed by suppression of PEDF in the involuting HemECs. Furthermore, we found that PEDF was more up-regulated in the involuting phase of hemangioma tissues than in the proliferating or the involuted. Taken together, we propose that PEDF accelerates the involution of hemangioma by growth inhibition of HemECs in an autocrine manner. The regulatory mechanism of PEDF expression could be a potential therapeutic target to treat hemangiomas.     

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.     

The role of multipotential stem cells in human infantile hemangioma

Hemangioma is the most common benign vascular tumor in infants and children with unknown etiology and pathogenesis. It is characterized by rapid proliferation followed by a slow involution phase. Histological analyses of infantile hemangioma (IH) in the early proliferating phase have generated a number of developmental theories suggesting an embryonic or primitive cell origin. We here hypothesize the IH may originate from multipotential stem cells. Further investigations of these hemangioma-initiating cells may improve our understanding of their function and possibly lead to novel therapeutic modalities for hemangiomas.     

Hemangiomas of the eyelid: visual complications and prophylactic concepts.

We describe a late survey of 51 patients who had hemangiomas of the eyelid in infancy, together with the visual complications found and a program designed for prevention of the latter.     

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.     

Vascular anomalies: hemangiomas

Mulliken and Glowacki categorized vascular anomalies as either hemangiomas or malformations, with the former being the most common tumor of infancy. Despite distinct clinical, radiologic, and histologic findings, the two major types of vascular lesions are often confused. This complicates both patient care and interpretation of the medical literature. A thorough understanding of the presentation, natural history, treatment, and complications of vascular tumors (hemangiomas) and vascular malformations is essential to their proper management. A comprehensive review outlining the diagnosis and treatment of hemangiomas in presented.     

Management of parotid hemangioma in 100 children

Most problematic infantile hemangiomas are successfully treated with pharmacological therapy. However, there are reports that hemangioma of the parotid gland responds poorly to corticosteroid and interferon. To better clarify the management of parotid hemangioma, the authors retrospectively studied the records of 100 consecutive patients, seen between 1975 and 2002. The characteristics of the tumor, including sex ratio, presence at birth, size, side, complications, and involvement of adjacent structures, were recorded. The indications for and response to treatment and the need for surgical procedures were documented and statistically analyzed. The female-to-male ratio was 4.5:1. Forty percent of parotid hemangiomas were on the right side, 36 percent were on the left, and 24 percent were bilateral. Forty-five percent of patients had a premonitory cutaneous lesion at birth. Fifty-nine percent of parotid hemangiomas ulcerated during the early proliferative phase. Eighty-eight percent involved nearby structures (ear, 70 percent; lip, 34 percent; subglottic region, 21 percent; eye, 18 percent; and nose, 3 percent). Seven percent of patients required tracheostomy, and 3 percent had signs of congestive heart failure. Seventy infants received pharmacological treatment. Sixty-seven patients were initially managed with corticosteroids; regression or stabilization was noted in 83 percent of tumors (56 of 67 tumors). Twenty-one patients received interferon: 11 in whom corticosteroid therapy had failed, seven in whom the tumor stabilized with corticosteroid therapy but further regression was needed, and three who had interferon as primary therapy. Ninety-five percent of the lesions that were resistant to corticosteroid subsequently responded to interferon alfa-2a or -2b. The overall response rate to pharmacological therapy was 98 percent. A reconstructive procedure was necessary during the involuting or involuted phase in 66 percent of patients: 92 percent had preauricular excision of redundant skin and/or fibrofatty tissue and 37 percent of patients had auricular revision. In summary, drug therapy was effective in the majority of infants with parotid hemangioma, whether given because the tumor was large, deforming, ulcerated, or involved nearby structures with functional consequences. Infantile hemangioma in the parotid gland responded to pharmacological treatment in a similar manner as hemangioma in other locations.     

Fine needle aspiration biopsy of the liver. A study of 102 consecutive cases

One hundred five CT-guided or ultrasound-guided fine needle aspirations of liver in 102 consecutive patients were reviewed. Adequate histologic confirmation or clinical follow-up of the final diagnosis was available for 86 of the 105 aspirations. A definite diagnosis of malignancy was made in 53 of the 61 aspirations performed on patients with malignant hepatic disease (86.9%). There were no false positives. The most common tumors detected were metastatic adenocarcinomas from an unknown primary or from the colon and rectum. The tumors were typed correctly in nearly all cases. Benign lesions encountered included cysts, abscesses, hemangiomas, cirrhosis and fatty metamorphosis. No serious complications were encountered as a result of aspiration. Guided fine needle aspiration biopsy of focal liver lesions appears to be an accurate, safe and relatively inexpensive method of diagnosis.     

Complications of systemic corticosteroid therapy for problematic hemangioma.

Systemic corticosteroid therapy has been used to treat hemangiomas for 30 years; yet, there are no studies of possible complications. We reviewed the database of the Vascular Anomalies Center at the Boston Children's Hospital and gathered information on short- and long-term side effects in children who were given systemic corticosteroids for problematic hemangiomas. In addition, a questionnaire regarding early and late consequences was sent to the families of children who were treated with corticosteroids from 1983 to 1997. Of 300 patients with hemangiomas, 80 children were identified as having received a full course of systemic corticosteroids for problematic tumors. Complete data were collected on 62 of these children. The response rate to the questionnaire was 78 percent (n = 62 of 80). The initial dose of corticosteroid varied from 2 to 3 mg/kg/ day. Duration of therapy ranged from 2 to 21 months (mean, 7.9 months; median, 6.5 months). The follow-up interval from the cessation of therapy ranged from 6 months to 15 years (mean, 4 years; median, 3 years). Short-term complications included cushingoid facies (n = 44; 71 percent), personality changes (n = 18; 29 percent), gastric irritation (n = 13; 21 percent), fungal (oral or perineal) infection (n = 4; 6 percent), and diminished gain of height (n = 22; 35 percent) and weight (n = 26; 42 percent). A total of 91 percent of children who had diminished gain of height (n = 20) returned to their pretreatment growth curve for height by 24 months of age. One child, who was treated at another institution with a dose of 20 mg/kg/day for 6.5 months that was slowly tapered over 18 months, was petite 6 years after ending therapy. Another child treated with an initial dose of 2 mg/kg/day for 5 months was smaller than predicted at the age of 6 years, but she was born prematurely and was on ventilatory support for respiratory distress. Three children treated with the standard dose and duration were at a low percentile for weight 4, 5, and 10 years after the cessation of therapy. Statistical analysis showed a correlation between diminished gain of height with duration of therapy and age at initiation of treatment. One child had corticosteroid myopathy that resolved with cessation of therapy. We found no evidence for immunologic suppression, i.e., there was no increase in the number of bacterial infections during corticosteroid administration. In conclusion, systemic corticosteroids can be safely given to treat endangering hemangiomas in infants at doses of 2 to 3 mg/kg/day, which are slowly tapered and stopped before the age of 1 year. Short-term side effects were minor and transient, and no serious long-term complications occurred.     

Biodegradable estradiol microspheres do not affect uterine involution or characteristics of postpartum estrus in mares

Quarterhorse mares were used to investigate effects of estradiol-17beta on uterine involution, duration of estrus, interval to ovulation, and fertility achieved by breeding on the first postpartum estrus. On the day of foaling, mares were injected with biodegradable poly (DL-lactide) microspheres containing either 100 mg estradiol-17beta (25 mares) or no drug (27 mares). The treatment period was considered to last for 12 to 15 d. Estrus was determined by teasing mares (n=16) with a stallion. Ovulation was detected by transrectal ultrasonographic examination of ovaries (n=48). On Days 6, 11 and 16 post partum, transrectal ultrasonography was used to measure cross-sectional diameters of the uterine body, uterine horns, and fluid within the uterine lumen (n=28). Uteri were swabbed for bacteriologic culture, and uterine biopsies were obtained from the previously gravid uterine horn on Days 11 and 16 post partum, for assessment of endometritis and morphometric analysis of endometrial histioarchitecture (n=19). Twenty-two mares were bred on foal-heat, and pregnancy was determined by transrectal ultrasonography on 14 to 16 and 30 to 35 d after breeding. With only one exception (diameter of previously gravid uterine horn on Day 11), mean values for all measures of uterine involution did not differ between treatment groups (P > 0.05). No differences were detected between treatment group means for length of estrus or interval to ovulation (P > 0.05). No differences were detected between treatment group liklihoods for recovery of potential bacterial pathogens, presence of endometritis, or presence of intrauterine fluid at 11 or 16 d post partum (P > 0.05). Pregnancy rate of mares treated with estradiol (5 11 ; 45%) was not different from that of control mares (9 11 ; 82%; P > 0.05). Estradiol treatment did not hasten uterine involution, increase duration of estrus, delay ovulation, or increase fertility in these postpartum mares.     

Intralesional corticosteroid therapy for infantile hemangiomas

Intralesional corticosteroid injections were performed in 31 hemangiomas in 30 infants aged 1 to 10 months at first injection. One to five injections were given, spaced 6 weeks apart. Lesions were located throughout the head and neck region, except one that was on the buttock. A mixture of betamethasone acetate and triamcinolone acetonide was used. Four lesions (13 percent) virtually disappeared, ten (32 percent) showed greater than 50 percent reduction in volume, ten (32 percent) showed definite but less than 50 percent reduction in volume, and seven (23 percent) showed little or no decrease in size. None showed further growth. All injections were performed without anesthesia, and there were not significant complications. We conclude that intralesional corticosteroid injections are safe and effective in properly selected infants with hemangiomas.