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The Aesthetic Surgery Education and Research Foundation

Award Winners and Funded Projects
Pathogenesis of BIA-ALCL Print

The ASERF Scientific Research Committee and Board of Directors are pleased to announce the following grant award:

Researcher: Marshall Kadin, MD

Grant Award: ASERF Interim Grant

Amount Awarded: $ 193,110

Project Name: Pathogenesis  of BIA-ALCL

Project Summary: Hypothesis: Anaplastic cells in BIA-ALCL produce cytokines that shape the tumor microenvironment (Figure 1). Our preliminary results indicate that anaplastic cells in culture produce IL-13 which induces immunoglobulin heavy chain class switch of plasma cells to produce IgE. We found IgE bound to the surface of mast cells and antigen presenting cells (APC) within involved tissues. Mast cells produce prostaglandin D2 (PGD2) which recruits Th2 cells and eosinophils prominent in BIA-ALCL lesions. A possible source of IgE is plasma cells in tumors and regional lymph nodes. Neither IL-13, IgE nor PGD2 has been quantified in malignant seromas before nor after treatment or compared to benign seromas. Whether IgE binds to bacteria or tumor associated antigens also has not been explored. IL-13 can be produced by effector T cells and innate lymphoid cells (ILCs) which will be addressed in this proposal. We hypothesize there will be different clinical presentations according to the cellular origin and functional polarization of anaplastic cells, specifically the Th1/ILC1 phenotype may associated with clinically indolent behavior and the Th3/ILC3 phenotype with invasive tumors.

To address our hypothesis our specific aims are:

Aim 1- Determine the significance of cytokine, prostaglandin D2 and IgE levels in benign and malignant seroma fluids and blood at clinical presentation and after treatment.

Aim 2- Determine if anaplastic cells are derived from effector T cells or innate lymphoid cells.

   Subaim 1- Determine which subset anaplastic cells belong to- Th1/1LC1, Th2/ILC2, or Th3/ILC3.

   Subaim 2- Is there a difference in subsets between in situ and invasive disease?

   Subaim 3- Can Th3/ILC3 anaplastic cells be repolarized to Th1/ILC1?

Aim 3- Identify precursors of BIA-ALCL with a similar phenotype in capsules, seroma fluids and regional lymph nodes.

AIM 4- Determine if IgE binds to bacterial and/or tumor associated antigens

 
Fibroblast Subpopulations in Radiation-induced Capsular Contracture Print

The ASERF Scientific Research Committee and Board of Directors are pleased to announce the following grant award:

Researcher: Michael Longaker, MD

Grant Award: ASERF Interim Grant

Amount Awarded: $39,000

Project Name: Fibroblast Subpopulations in Radiation-induced Capsular Contracture

Project Summary: "Breast implants, whether for augmentation or reconstruction, are associated with several well-known risks and complications, the most common of which is capsular contracture. Despite continued improvements in breast implant design over the past five decades, capsular contracture still remains a significant problem, with reported rates between 15% and 45% (Headon, Kasem et al. 2015). Furthermore, the incidence of contracture, as well as severity of contracture, is worsened by adjuvant radiation therapy for breast cancer (McCarthy, Pusic et al. 2005). Although thought to be also influenced by a variety of other exogenous factors including surgical technique, implant location, hematoma formation, and infection or biofilm formation, a common underlying etiology and pathogenesis remains poorly defined.

Capsular contracture begins as an inflammatory foreign body response after implantation, and while the ensuing fibrotic reaction can help to maintain position of the implant, an excessive response can result in pain and deformity of the breast. Histologic studies have shown an accumulation of macrophages, lymphocytes, and fibroblasts, the latter of which lay down multi-directional collagen fibers during initial capsule formation. Continued accumulation and activity of fibroblasts along with differentiation into myofibroblasts, however, results in thickened, dense bands of highly aligned fibers. Several studies have also correlated fibroblast density and cellular alignment with capsular contracture, and more recent reports have shown a functional difference in fibroblasts, with dysregulation of several inflammatory and fibrotic genes noted when comparing fibroblasts derived from non-contracted and contracted breast implant capsules (Kyle and Bayat 2015). Emerging data has now shown specific fibroblast subpopulations to exist, and in particular, CD26+ fibroblasts have been implicated in disordered dermal collagen deposition following radiotherapy (Rinkevich, Walmsley et al. 2015).

CD26, also known as dipeptidyl peptidase IV (DPP-4), is a homodimeric type II transmembrane glycoprotein closely related to fibroblast activation protein-? and functions as a serine exopeptidase for peptide hormones and for extracellular matrix remodeling (Thielitz, Vetter et al. 2008). CD26 also serves as a binding protein for fibronectin and collagen. Inhibitors of CD26 have potent anti-inflammatory effects, and their use to enhance incretin activity has already been approved by the FDA for treatment of type II diabetes (Drucker 2003). CD26 inhibitors have also been found to decrease proliferation, TGF-?1 expression, and collagen and fibronectin production by normal and keloid-derived fibroblasts (Thielitz, Vetter et al. 2008). As development of thicker and more aligned collagen fibers have been found to be a key feature of capsular contracture, CD26 inhibitors have the potential to alter severity of this fibrotic response.

Among women undergoing bilateral mastectomies with expander placement prior to adjuvant radiation therapy, studies have demonstrated an over four-fold increase in capsular contracture on the irradiated side (Chen, Momeni et al. 2016). These patients therefore offer the ability to investigate the role CD26+ fibroblasts play in the development of radiation-induced capsular contracture, with the contralateral non-irradiated, less contracted breast providing a point of comparison. Our central hypothesis is that the frequency of CD26+ fibroblasts is increased in irradiated, contracted breast capsules, and their enhanced fibrotic capacity can be reduced by CD26 inhibitors to decrease capsular contracture severity. Three Specific Aims have been proposed to evaluate this.

Specific Aim #1: To define the frequency of CD26+ fibroblasts in irradiated and non-irradiated breast implant capsules. In our preliminary data, we have observed increased numbers of CD26-staining fibroblasts within irradiated, contracted capsules relative to contralateral non-irradiated capsules. In this Aim, we will expand on this finding, using live fibroblast harvest and flow cytometry in addition to immunofluorescent staining for CD26, vimentin, and ?-smooth muscle actin (SMA) to quantify this difference.

Specific Aim #2: To determine differences in gene expression among CD26+ and CD26- fibroblasts from irradiated and non-irradiated breast capsules. Given the role of CD26+ fibroblasts in radiation-induced dermal fibrosis, we will evaluate expression of genes known to regulate inflammation (TNF-?), tissue remodeling (MMP-12), extracellular matrix deposition (TGF-?1 and COL1A1), and contracture (?-SMA) in capsule-derived fibroblasts. Live fibroblast harvest and flow cytometry will be performed to isolate CD26+, CD26-, and unsorted fibroblasts from both radiated and non-radiated capsules for transcript analysis.

Specific Aim #3: To evaluate the effects of CD26 inhibition on fibroblast function. CD26 inhibitors have been shown to reduce the fibrotic function of dermal fibroblasts. In this Aim, we will evaluate procollagen I and fibronectin production by CD26+, CD26-, and unsorted fibroblasts from radiated and non-radiated capsules in response to treatment with a CD26 inhibitor."

 
Body Contouring Following Bariatric Surgery: Effects on Obesity-Related Functional and Psychosocial Impairment Print

The ASERF Scientific Research Committee and Board of Directors are pleased to announce the following grant award:

Researcher: Valentina Ivejaz, MD

Grant Award: ASERF Interim Grant

Amount Awarded: $13,046

Project Name: Body Contouring Following Bariatric Surgery: Effects on Obesity-Related Functional and Psychosocial Impairment

Project Summary: Bariatric surgery, or weight loss surgery (WLS), is the most effective treatment for morbid obesity, often resulting in massive weight loss and improved medical and psychosocial functioning. Burgeoning research suggests that the majority of WLS patients desire body contouring surgery (BCS) to remove loose skin following WLS. Many patients, however, are unable to obtain BCS due to financial and insurance barriers. There is a dearth of literature prospectively examining WLS and BCS outcomes. Specifically, little is known about changes that occur pre- and post-BCS among WLS patients and whether BCS helps improve obesity-related and psychosocial functioning in this patient group, who often exhibit greater medical and psychological comorbidities relative to the general population.

Thus, the purpose of the present study is two-fold: 1) to prospectively examine obesity-related (e.g., weight, disability) and psychosocial (e.g., mood, body image) outcomes in individuals who undergo body contouring surgery (BCS) following WLS, and 2) to compare WLS patients who obtain BCS (BCS group) versus those who seek, but do not obtain, BCS (WLS group). Such studies may help determine which patients derive the most benefit from BCS following bariatric surgery.

PRIMARY AIMS and HYPOTHESES:

Aim #1: To examine the outcomes of BCS on obesity-related and psychosocial functioning among weight loss surgery patients at 1 month and 3 months following BCS.

Hypothesis #1: Individuals undergoing BCS following weight loss surgery will report significant improvements in obesity-related and psychosocial functioning following BCS.

Aim #2: To test for group differences in outcomes between the WLS and BCS groups.

Hypothesis #2: The BCS group will report significantly greater improvements in obesity-related and psychosocial functioning than the WLS group.

SECONDARY AIM AND HYPOTHESIS

Aim #3: To explore baseline characteristics as predictors of outcome.

Hypothesis #3: In this exploratory analysis, demographic variables (sex, age, and ethnicity/race) and clinical variables (body image dissatisfaction, body mass index, depression levels) will be tested as predictors of change in the primary body contouring surgery outcomes.

 
The Effect of Amniotic Membrane and Fat Grafts on Capsular Contracture Print

The ASERF Scientific Research Committee and Board of Directors are pleased to announce the following grant award:

Researcher: Hooman Soltanian

Grant Award: ASERF Interim Grant

Amount Awarded: $24,000

Project Name: The Effect of Amniotic Membrane and Fat Grafts on Capsular Contracture 

Project Summary: Capsular contracture is a common problem in both breast augmentation and implant-based breast reconstruction cases, which are among the most frequently performed plastic surgery procedures today. Capsular contracture can lead to cosmetic deformity, pain, emotional hardship and can result in additional, unplanned procedures and post-operative recovery time. In spite of the prevalence and morbidity of this problem, few studies have offered solutions for altering the underlying pathophysiology (1), and there are currently no clinical means for managing this problem other than performing revisionary surgical procedures.

Two tissues that have shown interesting properties in surgical fields are human amniotic membrane (HAM) and autologous fat. HAM has been shown to have anti-inflammatory, anti-scarring and antimicrobial effects (2). Similarly, fat grafting has been used to treat the sequelae of radiation-induced skin changes, a phenomenon which has been explained by the effect of Adipose Derived Stem Cells (ADSCs) on fibrotic tissues (3,4). Given the anti-inflammatory and anti-fibrotic properties of these tissues, we believe that HAM and autologous fat grafts could be used to prevent and/or treat capsular contracture. The current study will examine the effect of HAM and fat grafts on radiation induced fibrosis; a first step in possible human application.

 
The Validation of the Efficacy of a "Breast Implant Teaching Model" to improve patient, resident, and staff education in breast augmentation Print

The ASERF Scientific Research Committee and Board of Directors are pleased to announce the following grant award:

Researcher: Caroline Glicksman, MD

Grant Award: ASERF Interim Grant

Amount Awarded: $4,150

Project Name: The Validation of the Efficacy of a "Breast Implant Teaching Model" to improve patient, resident, and staff education in breast augmentation 

Project Summary: Substantial effort has been placed on rede?ning breast augmentation as more than just a surgical procedure. Peer reviewed publications document that complication rates and revision rates can be reduced when a greater emphasis is placed on preoperative patient education. Today, comprehensive patient education requires the physician become a more effective communicator. It is also important that any additional staff members such as patient educators and surgical coordinators, who often play an integral role in implant selection and the informed consent process, be trained in a similar fashion. Decisions made by the patient pre-operatively may have more of an impact on the quality of their result and its longevity than the surgical procedure itself, and it is during the educational portion of the breast implant consultation that surgeons have the best opportunity to introduce informed consent documents that will hold patients accountable for their decisions.

Most plastic surgeons and their staff develop their communication skills over many years. Of?ces are increasingly turning towards tools and technology to enhance their patient’s educational experience. Methods that include the senses; visual, touch, listening, 3-D images, and models, all improve the informed consent process. The breast implant teaching model was developed to provide patients with the opportunity to better comprehend their own anatomy, understand how their breast implants will be sized, where the breast implants may be placed, and most importantly, how we can best avoid producing the most common breast implant complications. The Breast Implant Teaching Model is an anatomically correct, life-sized mannequin. It will be inexpensive to fabricate, it is portable, and it is designed to bridge the common cultural and intellectual barriers that typically exist in patient education and the informed consent process.

 
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