Impact of Radiation on Implant-Based Breast Reconstruction in Prepectoral Versus Submuscular Planes.

BACKGROUND: Postmastectomy implant-based breast reconstruction (IBR) in the setting of radiation (XRT) comes with a high risk of perioperative complications regardless of reconstruction method. The aim of study was to identify the effects of XRT on IBR using a prepectoral versus submuscular approach. METHODS: A retrospective chart review was performed after institutional review board approval was obtained. Patients at a single institution who had 2-stage IBR from June 2012 to August 2019 were included. Patients were separated into 4 groups: prepectoral with XRT (group 1), prepectoral without XRT (group 2), submuscular with XRT (group 3), and submuscular without XRT (group 4). Patient demographics, comorbidities, and postoperative complications were recorded and analyzed. RESULTS: Three hundred eighty-seven breasts among 213 patients underwent 2-stage IBR. The average age and body mass index were 50.10 years and 29.10 kg/m2, respectively. One hundred nine breasts underwent prepectoral reconstruction (44 in group 1, 65 in group 2), and 278 breasts underwent submuscular reconstruction (141 in group 3, 137 in group 4). Prepectoral tissue expander placement was associated with higher complication rates in the radiated group (38.6% compared with 34.0% submuscular) and lower complication rates in the nonradiated group (26.2% compared with 29.2% submuscular), although significantly less explants were performed in prepectoral group, regardless of XRT status. The 3 most common complications overall were contracture (15.1% radiated, 10.4% nonradiated), infection (18.4% radiated, 11.9% nonradiated), and seroma (15.7% radiated, 10.9% nonradiated). CONCLUSIONS: Two-stage, prepectoral tissue expander placement performs clinically better than submuscular in nonradiated patients compared with radiated patients; however, no statistical significance was identified. Prepectoral had a significantly less incidence of reconstructive failure than submuscular placement regardless of XRT status. Future larger-scale studies are needed to determine statistically significant difference in surgical approach.

The Biointegration of a Porcine Acellular Dermal Matrix in a Novel Radiated Breast Reconstruction Model.

BACKGROUND: Ideal acellular dermal matrices (ADM) for breast reconstruction exhibit native extracellular matrix (ECM) structure to allow rapid biointegration and appropriate mechanical properties for desired clinical outcomes. In a novel in vivo model of irradiated breast reconstruction, we describe the cellular and vascular ingrowth of Artia, a porcine product chemically prepared to mimic the biomechanics of human ADM, with retained natural ECM structure to encourage cellular ingrowth. METHODS: Utilizing the murine dorsal skinfold model, Artia was implanted into 16 C57bl/6 mice. Eight of the mice received a single dose 35 Gy radiation to the skin, followed by 12 weeks to produce radiation fibrosis and 8 mice served as nonradiated controls. Real-time photoacoustic microscopy of vascular integration and oxygen saturation within the ADM were made over 14 days. At 21 days, vascular ingrowth (CD31), fibroblast scar tissue formation (alpha smooth-muscle actin α-SMA, vimentin), and macrophage function (M2/M1 ratio) were evaluated. Scanning electron microscopy images of Artia were produced to help interpret the potential orientation of cellular and vascular ingrowth. RESULTS: Repeated photoacoustic microscopy imaging demonstrated vascular ingrowth increasing over 14 days, with a commensurate increase in oxygen saturation within both radiated and nonradiated ADM-albeit at an insignificantly lower rate in the radiated group. By day 21, robust CD31 staining was seen that was insignificantly greater in the nonradiated group. Of the fibroblast markers, vimentin expression was significantly greater in the radiated group (P < 0.05). Macrophage lineage phenotype was consistent with remodeling physiology in both radiated and nonradiated groups. Scanning electron microscopy demonstrated transversely organized collagen fibrils with natural porous ECM structure to allow cellular ingrowth. CONCLUSIONS: Artia demonstrates appropriate biointegration, with increased oxygen saturation by 14 days, consistent with the performance of other collagen substrates in this model. Radiation fibrosis resulted in higher vimentin expression yet did not impact macrophage phenotype while only modestly decreasing Artia biointegration suggesting that ADM may have a role in reconstructive efforts in a radiated setting. Taken together with its enhanced biomechanics, this porcine ADM product is well poised to be clinically applicable to breast reconstruction.

The Performance of Patient-Worn Actigraphy Devices to Measure Recovery after Breast Reconstruction.

INTRODUCTION: Annually, over 250,000 women are diagnosed with breast cancer with over one-third undergoing mastectomy and contemplating reconstruction. Surgical breast reconstructive options vary in post-operative recovery, yet with a paucity of objective data to inform women of their expected recovery after flap or implant-based reconstruction. As a result, patient decision-making is based primarily on surgeon preference and subjective data regarding perceived invasiveness of surgical options. This study aims to identify recovery outcomes of interest to breast cancer patients and to determine the feasibility of objectively measuring patient recovery after mastectomy and reconstruction using patient-worn actigraphy devices. METHODS: Three survivorship focus groups for patients after mastectomy with and without reconstruction were used to identify recovery outcomes they considered relevant. Cloud storage systems and actigraphy devices were piloted to determine performance. Actigraphy devices were worn by patients peri-operatively to measure post-operative sleep quality and steps taken, normalized to individual patient pre-operative control data. RESULTS: Focus groups identified sleep quality, return to activity (measurable with actigraphy), and driving as variables impacting surgical decision-making. We prospectively measured outcomes for four women undergoing immediate pre-pectoral tissue expander placement and four women undergoing immediate free flap reconstruction. Actigraphy data demonstrated an initial decrease in activity, increase in sleep variability and increased heart rate that approached the patients' pre-operative normalized data as they recovered over time. CONCLUSIONS: These data demonstrate that actigraphy data would be of interest to patients making breast reconstruction decisions and that the data can be successfully collected to inform decision-making.

Fenestration Improves Acellular Dermal Matrix Biointegration: An Investigation of Revascularization with Photoacoustic Microscopy.

BACKGROUND: Acellular dermal matrices have revolutionized alloplastic breast reconstruction. Furthering our knowledge of their biointegration will allow for improved design of these biomaterials. The ideal acellular dermal matrix for breast reconstruction would provide durable soft-tissue augmentation while undergoing rapid biointegration to promote physiologic elasticity and reduced infectious complications. The inclusion of fenestrations in their design is thought to promote the process of biointegration; however, the mechanisms underlying this theory have not been evaluated. METHODS: Biointegration of standard and fenestrated acellular dermal matrices was assessed with serial photoacoustic microscopic imaging, in a murine dorsal skinfold window chamber model specifically designed to recapitulate the microenvironment of acellular dermal matrix-assisted alloplastic breast reconstruction. Photoacoustic microscopy allows for a serial, real-time, noninvasive assessment of hemoglobin content and oxygen saturation in living tissues, generating high-resolution, three-dimensional maps of the nascent microvasculature within acellular dermal matrices. Confirmatory histologic and immunohistochemical assessments were performed at the terminal time point. RESULTS: Fenestrated acellular dermal matrices demonstrated increased fibroblast and macrophage lineage host cell infiltration, greater mean percentage surface area vascular penetration (21 percent versus 11 percent; p = 0.08), and greater mean oxygen saturation (13.5 percent versus 6.9 percent; p < 0.05) than nonfenestrated matrices by 2 weeks after implantation. By 21 days, host cells had progressed nearly 1 mm within the acellular dermal matrix fenestrations, resulting in significantly more vascularity across the top of the fenestrated matrix (3.8 vessels per high-power field versus 0.07 vessels per high-power field; p < 0.05). CONCLUSIONS: Inclusion of fenestrations in acellular dermal matrices improves the recellularization and revascularization that are crucial to biointegration of these materials. Future studies will investigate the optimal distance between fenestrations.

A Novel Small-Animal Model of Irradiated, Implant-Based Breast Reconstruction.

BACKGROUND: There is currently a need for a clinically relevant small-animal model for irradiated, implant-based breast reconstruction. Present models are inadequate in terms of suboptimal location of expander placement and mode of radiation delivery, correlating poorly with the human clinical scenario. The authors hypothesized that by delivering fractionated radiation and placing an expander under the scalp of the animal, they would achieve soft-tissue changes histologically analogous to those seen in human irradiated, implant-based breast reconstruction. METHODS: This study consisted of 11 immunocompetent, hairless rats divided into three groups as follows: untreated control (n = 3), tissue-expanded scalps (n = 4), and fractionated irradiation plus tissue expansion of the scalp (n = 4). At the completion of the experiment for each group, skin tissue samples were analyzed histologically for vascularity, epidermal and dermal thickness, and collagen fiber alignment or scar formation. RESULTS: Expanded rat epidermis was significantly thicker and dermis was more vascular than nonexpanded skin. The authors observed a greater degree of collagen fiber alignment in the expanded group compared with nonexpanded skin. The combination of irradiation and expansion resulted in significant dermal thinning, vascular depletion, and increased scar formation compared with expanded skin alone. CONCLUSIONS: The authors describe a novel small-animal model for irradiated, implant-based breast reconstruction where histologic analysis shows structural changes in the skin consistent with known effects of radiation therapy and expansion in human skin. This model represents a significant improvement from previous ones and, as such, holds the potential to be used to test new therapeutic agents to improve clinical outcomes.

Incorporation of fluorophore-cholesterol conjugates into liposomal and mycobacterial membranes.

Fluorescently-labeled steroids that emit intense blue light in nonpolar solvent (λem (CH2Cl2)≈440nm, ΦF=0.70) were prepared by treating cholesteryl chloroformate with 4-amino-1,8-naphthalimides. The lipid portion of the conjugates embeds into liposomal membrane bilayers in minutes, leaving the fluorophore exposed to the external aqueous environment. This causes a 40-nm red-shift in λem and significant quenching. DFT optimizations predict the conjugates to be about 30Å long when fully extended, but rotation about the linker group can bring the compounds into an 'L'-shape. Such a conformation would allow the cholesteryl anchor to remain parallel to the acyl chains of a membrane while the fluorescent group resides in the interfacial region, instead of extending beyond it. When incubated with Mycobacterium smegmatis mc2 155, a bacterial species known to use natural cholesterol, the labeled steroids support growth and can be found localized in the membrane fraction of the cells using HPLC. These findings demonstrate stable integration of fluorescent cholesterols into bacterial membranes in vivo, indicating that these compounds may be useful for evaluating cholesterol uptake in prokaryotic organisms.