Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including δ-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.
Although the O'Brien modification allows approximately 50 percent further advancement than the Z-plasty modification compared with the standard Moberg flaps, the increase correlates to a large area of exposed neurovascular bundles at the volar base of the thumb, which requires secondary coverage. However, all Z-plasty donor-sites could be closed primarily. Primary closure of all donor sites will decrease healing time, wound complications, digital nerve sensitivity, and cosmetic appearance. This study is the first to show a significant increase in Moberg flap advancement using Z-plasty lengthening at the thumb base while avoiding any increased morbidity.
Infantile hemangioma (IH) is the most common tumor of the pediatric age group, affecting up to 4% of newborns ranging from inconsequential blemishes, to highly aggressive tumors. Following well defined growth phases (proliferative, plateau involutional) IH usually regress into a fibro-fatty residuum. Despite the high prevalence of IH, little is known regarding the pathogenesis of disease. A reported six fold decrease in IGF2 expression (correlating with transformation of proliferative to involuted lesions) prompted us to study the IGF-2 axis further. We demonstrate that IGF2 expression in IH is strongly related to the expression of a cancer testes and suspected oncogene BORIS (paralog of CTCF), placing IH in the unique category of being the first known benign BORIS positive tumor. IGF2 expression was strongly and positively related to BORIS transcript expression. Furthermore, a stronger association was made when comparing BORIS levels against the expression of CTCF via either a percentage or difference between the two. A common C/T polymorphism at CTCF BS6 appeared to modify the correlation between CTCF/BORIS and IGF2 expression in a parent of origin specific manner. Moreover, these effects may have phenotypic consequences as tumor growth also correlates with the genotype at CTCF BS6. This may provide a framework for explaining the clinical variability seen in IH and suggests new insights regarding CTCF and BORIS related functionality in both normal and malignant states.
Although innovation and entrepreneurship are complementary in the process of creating new products, plastic surgeons are frequently discouraged by the challenges associated with the regulatory and administrative environments in patent filing. The following primer provides a step-by-step guide for understanding patents and outlines the steps and costs involved in patent filing. To improve opportunities for successful patent filing, we elaborate on some of the common pitfalls in the process, including the timing of public disclosure, conducting a private art search, selecting a patent attorney or agent, determining the level of inventor involvement, and navigating academic and employment contracts. The innovative drive in plastic surgery provides a strong impetus for strengthening knowledge about patents and patent filing in order to support efforts for providing high-value patient care.
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