Alfonso Luca Pendolino

Toll-Like Receptor 4 Expression in Human Breast Implant Capsules: Localization and Correlation with Estrogen Receptors.

Background: Capsular contracture is the most common complication following breast augmentation and reconstruction. Myofibroblasts, which are specialized fibroblasts with contractile activity, are involved in its pathogenesis. Toll-like receptor 4 stimulation in fibroblasts induces transcription of genes involved in extracellular matrix remodeling and tissue repair; furthermore, it enhances sensitivity to transforming growth factor-&bgr;1 and promotes transition to myofibroblasts. 17&bgr;-Estradiol, by binding to its main receptors, &agr; and/or &bgr;, increases the expression of toll-like receptor 4 and the production of proinflammatory mediators by macrophages; moreover, it promotes extracellular matrix production and myofibroblasts contraction and differentiation. The aim of the study was to investigate the expression of toll-like receptor 4 in breast implant capsules and its relationship with estrogen receptors. Methods: The study enrolled 30 women who underwent expander removal following breast reconstruction. Specimens were stained with hematoxylin and eosin, Masson trichrome, immunohistochemistry, and immunofluorescence for toll-like receptor 4, &agr;-smooth muscle actin (a marker of myofibroblasts), estrogen receptor-&agr;, and estrogen receptor-&bgr;. Results: Toll-like receptor 4 was expressed by fibroblasts and myofibroblasts of capsular tissue. Its expression positively correlated with estrogen receptor-&bgr; expression (p = 0.012). A positive correlation was found between estrogen receptor-&bgr; and &agr;-smooth muscle actin expression (p = 0.037). Conclusions: This study demonstrates the expression of toll-like receptor 4 in myofibroblasts of capsular tissue and its correlation with estrogen receptor-&bgr; positivity. Activation of toll-like receptor 4 and estrogen receptor-&bgr;, and their interplay, may be involved in myofibroblast differentiation and in the profibrotic pathogenic process underlying capsular contracture.

The Effects of Negative Pressure on Blood Supply and the Adipogenic Role of Edema

Sir:We read with great interest the recent article by Heit et al. entitled “External Volume Expansion Increases Subcutaneous Thickness, Cell Proliferation, and Vascular Remodeling in a Murine Model,”1 in which the authors accurately described the effect of vacuum-assisted closure in mice. Neverthele

The role of angiogenesis, inflammation and estrogen receptors in breast implant capsules development and remodeling

BACKGROUND Capsular contracture is the most common complication following breast implant placement. The multiple factors unbalancing the physiological response to the foreign body have not been fully elucidated. The aim of this study was to investigate the role of neo-angiogenesis, inflammation and estrogen receptors in peri-prosthetic tissue development and remodeling. METHODS The study enrolled 31 women who underwent expander substitution with definitive implant. Specimens were stained with hematoxylin/eosin, Masson trichrome, immunohistochemistry and immunofluorescence for alpha-smooth muscle actin, estrogen receptor-α (ER-α), estrogen receptor-β (ER-β), Collagen type I and III, CD31 (as a marker of neo-angiogenesis) and vascular endothelial growth factor (VEGF). Inflammatory infiltration was quantified and analyzed. Transmission electron microscopy was performed for ultrastructural evaluation. RESULTS Myofibroblasts, mainly localized in the middle layer of capsular tissue, expressed VEGF, ER-α and ER-β. ER-β expression positively correlated with Collagen type I deposition (p= 0.025). Neo-angiogenesis was predominant in the middle layer. CD31 expression positively correlated with Collagen type I expression (p=0.009) and inflammatory infiltration grade (p= 0.004). The degree of inflammatory infiltration negatively correlated with the time from implantation (p = 0.022). DISCUSSION The middle layer is key in the development and remodeling of capsular tissue. Myofibroblasts produce VEGF, that induces neo-angiogenesis. New vessels formation is also correlated to the inflammatory response. Collagen deposition is associated with ER-β expression and neo-angiogenesis. These findings may prelude to targeted pharmacologic therapies able to control such interactions, thus hampering the self-sustaining loop promoting the progression of physiologic fibrosis toward pathologic contracture.

Tattoo preservation during surgical procedures

License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php Open Access Surgery 2013:7 19–27 Open Access Surgery Dovepress

Desmoid tumor occurrence in female siblings not associated with familial adenomatous polyposis: genetic or sporadic form?

Sir, Desmoid tumors (DTs) are rare tumors which belong to heterogenous group of soft tissue tumors. Affected patients usually fall within the age range of 10–40 years, with a higher prevalence among women during their fertile period [1]. Desmoids may occur either sporadically or as an extra-colonic manifestation of familial adenomatous polyposis (FAP). This association was first discovered by Nichols in 1923 [2] and confirmed by McAdam and Goligher in 1970 [3]. Genetic factors involved in DTs are not completely known, although mutations of APC or β-catenin genes are probably to be the main factors for tumor development, especially in FAP-associated forms [4]. Nonetheless, causes of DTs are still uncertain. Besides specific mutations in the APC gene, risk factors for the development of DTs include even previous surgical procedures, pregnancy, and female sex. Trauma in the tumor site may elicit DTs. It seems that the increased risk after surgery may be due to the activation of fibroblasts, normally involved in repairing tissue damage [5]. Sporadic DTs are more common in female than in male patients. This can be explained by the regulatory role which estrogens play. Indeed, fibroblasts have been demonstrated to exhibit a proliferative response to estrogens; on the other hand, there are evidences of regression of tumors by estrogens blockade and their occasional disappearance after menopause [6]. About 50 % of DTs recur in anterior abdominal wall and arise from musculoaponeurotic structures, especially the rectus and internal oblique muscles and their fascial coverings, and occasionally from the external oblique muscle and the transversalis muscle or fascia [7]. We describe the case of two female siblings who developed abdominal wall desmoids within 5 months apart from each other. They had no family history of FAP and colorectal diseases, but both had previous surgery. A 34-year-old woman was admitted to our hospital for the presence of a palpable, painless lesion in the sovrapubic area, fixed to the abdominal wall. The M. Langella :A. L. Pendolino (*) : P. F. Delle Femmine : P. Persichetti Plastic and Reconstructive Surgery Unit, Università Campus Bio-Medico di Roma, 00128 Rome, Italy e-mail: lucapendolino@msn.com