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.     

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.     

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.     

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.     

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.     

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.     

Hemangiomas; histologic structure,and treatment

Hemangiomas are considered tumors originating in blood vessels and are classified as ectatic and hyperplastic. Controversy regarding active therapy occurs in the case of strawberry hemangiomas which are hyperplastic capillary hemangiomas. Although they may clear up spontaneously, on rare occasions they may predispose to grave sequelae. Port-wine stain hemangiomas should never be treated with x-ray or radium.     

HEMANGIOMAS—Histologic Structure,and Treatment

Hemangiomas are considered tumors originating in blood vessels and are classified as ectatic and hyperplastic. Controversy regarding active therapy occurs in the case of strawberry hemangiomas which are hyperplastic capillary hemangiomas. Although they may clear up spontaneously, on rare occasions they may predispose to grave sequelae. Port-wine stain hemangiomas should never be treated with x-ray or radium.     

Poliomyelitis; effect of Salk vaccine on severity of paralysis

Nevi are the most common tumors of childhood. Pigmented nevi are classified into blue nevi, intraepidermal nevi, junction nevi, intradermal nevi (or common mole) and combination types. Cutaneous malignant disease in children is rare. Malignant melanoma is rare before puberty. Wholesale removal of benign pigmented nevi in children should be condemned. However, junction nevi located on the palms, soles, genitalia or waistline-that is, in areas subject to frequent trauma-should be excised. Hemangiomas in infants are the most common tumors for which advice is sought. Not all hemangiomas regress spontaneously, and on occasion the persistence or progression of such a lesion may bring about life-long unsightly deformities. Therapy for this type of tumor is simple when given early in life. Hemangiomas involving the ears, nose, lips or eyelids should be treated at once, preferably within a month of the time they appear.     

CUTANEOUS TUMORS OF CHILDREN

Nevi are the most common tumors of childhood. Pigmented nevi are classified into blue nevi, intraepidermal nevi, junction nevi, intradermal nevi (or common mole) and combination types. Cutaneous malignant disease in children is rare. Malignant melanoma is rare before puberty. Wholesale removal of benign pigmented nevi in children should be condemned. However, junction nevi located on the palms, soles, genitalia or waistline—that is, in areas subject to frequent trauma—should be excised.Hemangiomas in infants are the most common tumors for which advice is sought. Not all hemangiomas regress spontaneously, and on occasion the persistence or progression of such a lesion may bring about life-long unsightly deformities. Therapy for this type of tumor is simple when given early in life. Hemangiomas involving the ears, nose, lips or eyelids should be treated at once, preferably within a month of the time they appear.     

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.     

Perspective on hypertension in the elderly.

More than half of elderly men and women have hypertension, leading to a significant risk of increased morbidity and mortality. The cause of hypertension in this age group is unknown. Left ventricular hypertrophy is frequently present, often associated with diastolic dysfunction. Systolic hypertension in the elderly increases the risk of cardiovascular disease, but there are no good data to show that the treatment of isolated systolic hypertension reduces the morbidity or mortality. Good evidence indicates that antihypertensive treatment in this group decreases cardiovascular morbidity and mortality up to age 80, so most elderly hypertensive patients should be treated. An empiric trial of nonpharmacologic therapy can be initiated in those with mild hypertension and no cardiovascular disease, but most patients will require drug therapy. Most elderly hypertensive patients have accompanying illnesses for which they may or may not be taking medications. Some antihypertensive drugs exacerbate coexisting diseases while others augment treatment regimens. Similarly, drugs may interact in a beneficial or adverse way. Finally, drug metabolism is altered by age, leading to problems with toxicity or diminished efficacy. The choice of medication should be based on all such considerations, including the cost and convenience of the drugs available.     

The detection, surveillance and treatment of premalignant gastric lesions related to Helicobacter pylori infection

Gastric cancer is an important worldwide health problem and causes considerable morbidity and mortality. It represents the second leading cause of cancer-related death worldwide. A cascade of recognizable precursor lesions precedes most distal gastric carcinomas. In this multistep model of gastric carcinogenesis, Helicobacter pylori causes chronic active inflammation of the gastric mucosa, which slowly progresses through the premalignant stages of atrophic gastritis, intestinal metaplasia and dysplasia to gastric carcinoma. Detection and treatment of premalignant lesions may thus provide a basis for gastric cancer prevention. However, at present, premalignant changes of the gastric mucosa are frequently disregarded in clinical practice or result in widely varying follow-up frequency or treatment. This review provides an overview of current knowledge on detection, surveillance and treatment of patients with premalignant gastric lesions, and identifies the uncertainties that require further research.     

Quality of life in vascular anomalies

Hemangiomas and vascular malformations that cause disfigurement or functional limitations may affect the quality life of the affected individual and their families. Negative reaction from strangers, social stigmatization, sadness, stress and low self-esteem are some of the commonly reported effects of having such lesions. Extensive and accurate education about the disease process and advice from support groups may improve quality of life. Psychological intervention may be indicated for some individuals and families.     

The role of submacular surgery in the treatment of choroidal neovascular membranes

The growth of choroidal neovascular membranes (CNVM) beneath the macula can cause significant disturbances of central vision. Conditions such as age-related macular degeneration (AMD) and presumed ocular histoplasmosis syndrome (POHS) are the most common etiologies. The Macular Photocoagulation Study group presented data that clearly showed laser photocoagulation to be beneficial in the treatment of CNVM. Poor visual results and a high rate of recurrence have prompted clinicians to seek out alternative treatments. Experiences with CNVM removal utilizing submacular surgical techniques have shown that central visual function may be restored or preserved in POHS, multifocal choroiditis and idiopathic causes. The Submacular Surgery Trials were designed to investigate whether submacular surgery is more effective in retaining central acuity in patients with subfoveal CNVM, than observation alone. The goal of this paper is to review the role of submacular surgery in the treatment of subfoveal choroidal neovascular membranes.     

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.     

Further phenotypic delineation of subtelomeric (terminal) 4q deletion with emphasis on intracranial and reproductive anatomy

Hypoplastic left heart syndrome(HLHS) refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to 0.036% of all live births. Newborn infants with the condition generally are born at full term and initially appear healthy. As the arterial duct closes, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure. The embryologic cause of the disease, as in the case of most congenital cardiac defects, is not fully known. The most useful diagnostic modality is the echocardiogram. The syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation. Differential diagnosis includes other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow (critical aortic stenosis, coarctation of the aorta, interrupted aortic arch). Children with the syndrome require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major modalities, primary cardiac transplantation or a series of staged functionally univentricular palliations. The treatment chosen is dependent on the preference of the institution, its experience, and also preference. Although survival following initial surgical intervention has improved significantly over the last 20 years, significant mortality and morbidity are present for both surgical strategies. As a result pediatric cardiologists continue to be challenged by discussions with families regarding initial decision relative to treatment, and long-term prognosis as information on long-term survival and quality of life for those born with the syndrome is limited.     

Lumps and bumps: late postsurgical inflammatory and infectious lesions

Late postsurgical infectious or inflammatory complications after facial surgery present a difficult challenge. These complications occur at least 2 weeks after surgical procedures and are often attributable to unique causes, in contrast to complications within the first postoperative week. The most worrisome complications in this period are caused by mycobacterial infections, because these infections can be severe and require a protracted treatment course. A high degree of suspicion is required early in presentation because these lesions can be subtle and similar to other infectious or inflammatory lesions. The authors discuss the clinical manifestations and diagnostic and treatment rationale for late postoperative infectious and inflammatory lesions. The authors also demonstrate and compare the clinical manifestations of mycobacterial infections, bacterial infections, and sterile inflammatory reactions. In addition, the treatment rationale for mycobacterial infections is reviewed. Late postoperative infections caused by mycobacteria are reported with increasing frequency in the cosmetic literature. These cases illustrate diverse challenges in the identification and treatment of late postoperative 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.     

Anidulafungin versus fluconazole in the treatment of Candida albicans chorioretinitis

BackgroundCandida albicans chorioretinitis is the most common cause of endogenous fungal endophthalmitis. Echinocandins are recommended as first-line therapy in the treatment of invasive candidiasis (IC), but in clinically stable patients with IC and endophthalmitis caused by Candida species susceptible to azole compounds these are the first-line treatment due to their better intraocular penetration.Case reportA 42-year-old woman admitted to hospital for duodenal perforation after gastrointestinal surgery and treated with broad-spectrum antibiotics developed C. albicans candidemia. According to protocol, an antifungal treatment with anidulafungin was given. The patient presented no visual symptoms but on routinary ophthalmoscopic examination multiple bilateral chorioretinal lesions were observed. Systemic therapy was changed to fluconazole, with good systemic and ocular results.ConclusionsAzole compounds are the first-line therapy for endophthalmitis associated with candidemia. However, clinical guidelines often propose echinocandins as the first option for IC. In some cases, C. albicans chorioretinitis will require a change in the systemic treatment to assure better intraocular penetration. According to the current evidence and our own experience, routine funduscopy is not necessary in all IC patients. However, we do recommend fundus examination in patients with visual symptoms or those unable to report them (paediatric patients and patients with an altered level of consciousness), and in those who are being treated with echinocandins in monotherapy.