الفهرس 
VASCULOGENESIS AND ANGIOGENESISOnly 14 pages are availabe for public view
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Abstract
H
emangioma is the most common benign vascular lesion in infancy and childhood., with an incidence ranging from 1-12% depending on age and population studied (Zhang et al., 2005). Cutaneous hemangiomas usually develop soon after birth. They represent a biologically unique process characterized histologically by a high endothelial cell turnover (Smolinski and Yan, 2005).
In contrast, vascular malformations are congenital vascular defects resulting from errors in vascular development that appear at birth. They are composed of a mixture of dilated sinusoidal lymphatic, venous, or arterial vessels and never undergo spontaneous involution (Enjolras et al., 2007).
The pathogenesis of hemangioma formation is likely to involve increased angiogenesis. The degree of angiogenesis in a hemangioma depends on a net balance of the effects of angiogenic and antiangiogenic factors (Chang et al., 1999; Bielenberg, 1999 and Tan et al., 2000).
Vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) appear to be essential for vasculogenesis and angiogenesis (Greene and Fishman, 2005; Gupta and Zhang, 2005).
This study is a cross-sectional case-control study which was carried out to detect the utility of serum levels of angiogenic growth factors (VEGF & bFGF) for clinical assessment of cutaneous vascular anomalies in infants and children: objectively distinguish hemangioma and vascular malformations, stage the hemangioma, monitor its clinical course and estimate the efficacy of therapeutic interventions.
The study was carried out over the period from August 1st, 2010 to July 31, 2011. It was conducted at the Vascular Anomaly Clinic of the Pediatric Surgery Department, Pediatrics Hospital, Ain Shams University.
The study comprised 60 infants and children (1 month-13 years of age) with vascular cutaneous anomalies whose diagnosis was definite and typical based on history and physical examination supported by imaging studies using Doppler ultrasonography). They were all attending the Vascular Anomaly Clinic of the hospital for clinical evaluation, follow up and/or treatment of their cutaneous vascular lesions.
Cases were identified in the following 3 groups
1. Infantile cutaneous hemangiomas in the proliferating phase, during 1st year of life, where the tumor is growing (n=25). Their ages ranged from 1-11months
2. Infantile cutaneous hemangiomas in the involuting phase, after the 1st year of age where the tumor is either regressing gradually or stable (n=23). Their ages ranged from >1up to 13years.
3. Cutaneous vascular malformation included venous malformations and capillary malformations; were mostly present at birth and grew in proportion to child growth with no history of rapid progression or slow regression (n=12). Their ages ranged from 3-5 years.
4. In addition, 20 healthy infants and children with age range from 8months-13 years were included as a negative control group.
Exclusion criteria: Infants and children with associated other deep vascular abnormalities, based on imaging studies, were excluded.
Patients included were subjected to the following:
Complete history taking and clinical examination done with special emphasis on lesion location, size, type, color, consistency, compressibility and local temperature and complications, if present
Investigations
- Doppler ultrasonographic evaluation of the cutaneous lesion, if not previously evaluated.
- Abdominal Ultrasonography: to diagnose any associated visceral affection.
- Assessment of serum levels of VEGF and bFGF) by ELISA.
The results of study revealed
It was obvious from our clinical observation that most of hemangioma cases collected over the study period were females (45 out of 48 cases).
Marked variability in the sizes of the vascular lesion were also encountered in our studied cases with cutaneous vascular anomalies. The lesions measured were mostly covering a skin area varying from 1 up to 130 cm2 with a mean size of 39 cm2. Only 5 out of 60 cases of the study encountered complications: ulceration, bleeding or infection.
Different treatment modalities were applied for 62% of hemangioma cases before the time of enrollment. Beta blockers alone or in combination with steroids were the most frequently applied therapeutic interventions.
The statistical results of the present study showed that there was highly significant increases in serum VEGF & bFGF levels in all patient subgroup as compared with control (p<0.001, respectively).
Serum vascular endothelial growth factor (VEGF) concentrations were significantly elevated, median (IQR): 1500(950-2206) pg/ml in proliferating phase hemangiomas, 2000(1500-2875) pg/ml in involuting phase hemangiomas and 800(750-850) pg/ml in vascular malformations, as compared with negative control group: 150(120-200) pg/ml (p<0.01, respectively).
Moreover, serum VEGF levels were significantly higher in both proliferating & involuting phases of hemangioma than in vascular malformations (p<0.001, respectively). This observation may provide an objective basis for distinguishing hemangiomas from vascular malformations. The differences among proliferating and involuting hemangiomas, however, were non-significant (p>0.05).
It is worth mentioning that in our cases, when considering the clinical course of progression/regression as obtained from history, we found a significant reduction in VEGF levels in cases whose lesions had regressed in size spontaneously as compared with apparently stable or progressive lesions (p<0.05).
The results of our study also demonstrated that Basic fibroblastic growth factor (bFGF) serum levels were high in patients with hemangiomas (whether progressive or involuting) and with vascular malformations as compared with control without vascular lesions. Similar levels found in all groups of patients, including vascular malformations (p>0.05). No significant statistical differences were found between children with proliferative hemangiomas and children with involuting ones and vascular malformations (p>0.05).
Our results on bFGF serum levels does not seem to show the expected differential results for differentiating hemangiomas from vascular malformation or predicting the phase of the tumor.
In addition, there was no significance difference between treated and non- treated cases in levels of both angiogenic markers (bFGF, VEGF) (p>0.05, respectively).
Correlation study revealed that neither bFGF nor VEGF serum levels were significantly corrrelated to the age or the size of the vascular lesion.
Moreover, serum levels of both markers were not significantly correlated to each other (p>0.05, respectively).