Background:Traditionally, tissue expanders (TEs) for breast reconstruction have been placed beneath the pectoralis major muscle with or without acellular dermal matrix. More recently, full acellular dermal matrix coverage has been described for prepectoral TE placement. Our study aims to explore differences in clinical and quality-of-life (QOL) outcomes for prepectoral versus subpectoral TE breast reconstruction.Methods:We identified patients who underwent postmastectomy breast reconstruction with prepectoral or subpectoral TE placement between 2011 and 2015 and completed QOL surveys. Primary outcomes were postoperative pain and QOL scores. Secondary outcomes were clinical outcomes. We used Wilcoxon rank-sum test, chi-square test, and linear regression to compare outcomes. Postoperative follow-up for each patient was at least 60 days, except that of pain scores, which were at least 30 days. Mean age was 49 ± 10 years.Results:Twenty-six prepectoral TE patients and 109 subpectoral TE patients met inclusion criteria. Pain scores were significantly lower at 12 hours, 1 day, 7 days, and 30 days postoperatively for the prepectoral group, compared with the subpectoral group, even after adjusting for confounding variables [PO12H: Sub-Pectoral (SP) median (interquartile range), 7 (5–8), Pre-Pectoral (PP), 5 (2.5–7.5), P value = 0.004; PO1D: SP, 5 (4–6), PP 3 (2–4), P value = < 0.001; PO7D: SP, 2 (0–4), PP, 0 (0–2), P value = 0.004; PO30D: SP, 0 (0–2), PP, 0 (0–0), P value = 0.039)]. Breast-Q scores were not significantly different between study groups. RAND-36 Physical Health scores were lower among prepectoral TE patients.Conclusions:Prepectoral TE breast reconstruction presents an opportunity to improve upon current reconstructive methods and does result in significantly lower pain scores. The associated risks have yet to be fully described and are important considerations, as these prepectoral patients had lower physical health outcome scores.

Therapeutic, II.

Medical devices and implants made of synthetic materials can induce an immune-mediated process when implanted in the body called the foreign body response, which results in formation of a fibrous capsule around the implant. To explore the immune and stromal connections underpinning the foreign body response, we analyzed fibrotic capsules surrounding surgically excised human breast implants from 12 individuals. We found increased numbers of interleukin 17 (IL17)–producing γδ+ T cells and CD4+ T helper 17 (TH17) cells as well as senescent stromal cells in the fibrotic capsules. Further analysis in a murine model demonstrated an early innate IL17 response to implanted synthetic material (polycaprolactone) particles that was mediated by innate lymphoid cells and γδ+ T cells. This was followed by a chronic adaptive CD4+ TH17 cell response that was antigen dependent. Synthetic materials with varying chemical and physical properties implanted either in injured muscle or subcutaneously induced similar IL17 responses in mice. Mice deficient in IL17 signaling established that IL17 was required for the fibrotic response to implanted synthetic materials and the development of p16INK4a senescent cells. IL6 produced by senescent cells was sufficient for the induction of IL17 expression in T cells. Treatment with a senolytic agent (navitoclax) that killed senescent cells reduced IL17 expression and fibrosis in the mouse implant model. Discovery of a feed-forward loop between the TH17 immune response and the senescence response to implanted synthetic materials introduces new targets for therapeutic intervention in the foreign body response.

SUMMARY Early full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women, and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44+ progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44+p27+ cells in parous women, and showed using explant cultures that parity-related signaling pathways play a role in regulating the number of p27+ cells and their proliferation. Our results suggest that pathways controlling p27+ mammary epithelial cells and the numbers of these cells relate to breast cancer risk, and can be explored for cancer risk assessment and prevention.

Background Soft tissue repair is currently limited by the availability of autologous tissue sources and the absence of an ideal soft tissue replacement comparable to native adipose tissue. Extracellular matrix (ECM)-based biomaterials have demonstrated great potential as instructive scaffolds for regenerative medicine, mechanically and biochemically defined by the tissue of origin. As such, the distinctive high lipid content of adipose tissue requires unique processing conditions to generate a biocompatible scaffold for soft tissue repair. Methods Human adipose tissue was decellularized to obtain a matrix devoid of lipids and cells, while preserving ECM architecture and bioactivity. To control degradation and volume persistence, the scaffold was crosslinked using hexamethylene diisocyanate and 1-Ethyl-3-(-3-dimethylaminopropyl) carbodiimide. In vitro studies with human adipose-derived stem cells were used to assess cell viability and adipogenic differentiation on the biomaterial. In vivo biocompatibility and volume persistence were evaluated by subcutaneous implantation over 12 weeks in a small animal model. Results The scaffold provided a biocompatible matrix supporting the growth and differentiation of adipose-derived stem cells in vitro. Crosslinking the matrix increased its resistance to enzymatic degradation. Subcutaneous implantation of the acellular adipose matrix in Sprague-Dawley rats showed minimal inflammatory reaction. Adipose tissue development and vascularization was observed in the implant, with host cells migrating into the matrix indicating the instructive potential of the matrix for guiding tissue remodeling and regeneration. Conclusions With its unique biological and mechanical properties, decellularized adipose ECM is a promising biomaterial scaffold that can potentially be used allogenically for the correction of soft tissue defects.

Therapeutic, III.

Without irradiation, skin overlying implants is associated with better sensation recovery than DIEP flap skin. However, with irradiation, DIEP flap skin had better sensation recovery than did skin over implants. Neurotization trended toward improvement in sensation in DIEP flaps.

Using careful patient selection and careful pathological evaluation of the subareolar breast tissue at surgery, NSM can be an oncologically safe procedure in patients where this is important to their quality of life. A prospective study based on focused selection criteria and long-term follow-up is currently in progress.