The effective regulation of T cell responses is dependent on opposing signals transmitted through two related cell-surface receptors, CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Dimerization of CTLA-4 is required for the formation of high-avidity complexes with B7 ligands and for transmission of signals that attenuate T cell activation. We determined the crystal structure of the extracellular portion of CTLA-4 to 2.0 angstrom resolution. CTLA-4 belongs to the immunoglobulin superfamily and displays a strand topology similar to Valpha domains, with an unusual mode of dimerization that places the B7 binding sites distal to the dimerization interface. This organization allows each CTLA-4 dimer to bind two bivalent B7 molecules and suggests that a periodic arrangement of these components within the immunological synapse may contribute to the regulation of T cell responsiveness.

Background: Mastectomy and implant-based reconstruction is typically performed in a hospital setting (HS) with overnight admission. The aim of this study was to evaluate postoperative complications and outcomes with same-day discharge from an ambulatory surgery center (ASC) compared with the same surgery performed in the HS. Methods: Patients who underwent mastectomy and immediate prepectoral tissue expander reconstruction were included in this retrospective study. Surgery was performed in an ASC with same-day discharge or the HS with overnight observation or same-day discharge. Patient demographics, operative details, outcomes, complications, and patient satisfaction were compared. Results: One hundred six women (183 breasts) underwent surgery in the HS, and 103 women (177 breasts) had their surgery in an ASC between August 2014 and September 2019. Demographics, comorbidities, and operative details were similar. Although there was no difference in the rates of most major complications, infectious complications requiring operative intervention were less frequent in the ASC [2.3% (n = 4) versus 11.5% (n = 21); P = 0.001]. Patient satisfaction, evaluated with a 5-point Likert scale, was higher in the ASC. Conclusions: Mastectomy and prepectoral reconstruction in an ASC is a safe alternative to the standard approach of performing this procedure in the HS. Although the rates of most surgical complications are similar between the HS and ASC, we have found a significantly reduced rate of major infectious complications requiring surgical intervention in the ASC which reduces overall cost and patient morbidity. Finally, patient satisfaction was higher in the ASC compared with the HS.

Post-mastectomy reconstruction is performed using implant-based or autologous techniques. Many women refuse or are poor candidates for implant-based reconstruction. We previously described a single-stage autologous technique that was most applicable in obese women with significant ptosis that made use of the mastectomy skin flap and subcutaneous tissue to reconstruct a breast mound. Here, we extend this technique to smaller breasted women by incorporating a second stage of skin tailoring and fat grafting. This technique does not require donor site surgery nor extended operative and recovery times. It extends the indications for autologous reconstruction to nonideal candidates and to developing countries where cost limits access.

Background:Reconstructive surgeons are encountering an increasing number of obese women requiring postmastectomy reconstruction. These patients are poor candidates for autologous and prosthetic-based reconstructions as they have a high rate of reconstructive failure, surgical complications, and poor aesthetic outcomes. We demonstrate here the utility of the previously described Goldilocks mastectomy with free nipple grafts as a safe bridge to second stage implant-based breast reconstruction.Methods:Ten consecutive morbidly (BMI > 40) or super obese (BMI>50) women underwent bilateral Goldilocks mastectomy with free nipple grafts followed by second stage subpectoral implant placement at least three months postoperatively. Patients were assessed for implant-related complications including malposition, capsular contracture, dehiscence, and extrusion.Results:Ten postmastectomy reconstructions in patients with BMIs ranging from 37 to 50 with a mean BMI of 45 underwent bilateral Goldilocks mastectomy with free nipple grafts. Two patients had wound healing complications after Goldilocks mastectomy but were completely healed within 8 weeks. There were no instances of delayed wound healing or reconstructive failure after prosthetic placement. With at least 9 months of follow-up on all patients, no patient has had a capsular contracture, significant malposition, or other complication requiring reoperation.Conclusion:The obese patient poses a significant reconstructive challenge for which no reproducible approach has been described. Here, we present a 2-stage strategy: the previously described Goldilocks mastectomy with free nipple grafts followed by second stage subpectoral definitive implant placement. This is the first proposed description of a reliable strategy for postmastectomy reconstruction in the morbidly and super obese.

Oncoplastic surgery is redefining breast cancer surgery today. Despite the lack of randomised clinical trials, current evidence suggests at least equivalent oncological outcomes, reduced re-excision rates and superior aesthetic results. This review outlines the arguments for the superiority of this new approach over the current standard of care and discusses some of the difficulties with regards to training and mentoring the next generation of surgeons.

Background:Oncoplastic breast-conserving surgery describes a set of techniques that allow for generous oncological resection with immediate tumor-specific reconstruction. These techniques are classically divided into either volume displacement (local breast flaps and or reduction mammaplasty/mastopexy strategies) versus volume replacement strategies (transfer of autologous nonbreast tissue from a local or distant site and, less commonly, implant placement). There have been few descriptions of merging these 2 classical approaches to facilitate breast-conserving surgery. The purpose of this report was to evaluate the efficacy of combining the most common oncoplastic volume displacement strategy (Wise pattern mammaplasty) with simultaneous autologous volume replacement from the lateral intercostal artery perforator (LICAP) flap to reconstruct the extensive partial mastectomy defect in patients with ptosis.Methods:A retrospective analysis of 25 consecutive patients with multifocal or multicentric breast cancers who underwent simultaneous volume replacement from the LICAP flap and volume displacement (Wise pattern mammaplasty) to achieve breast conservation was performed between January 2016 and January 2018. Clinical outcomes and postoperative complications were examined.Results:Twenty-five consecutive patients with a mean age of 56 years (range, 37–74 years) and mean body mass index of 28 kg/m2 (range, 22–37 kg/m2) all successfully underwent breast conservation by simultaneously employing the LICAP flap and Wise pattern mammaplasty to reconstruct the partial mastectomy defect. The average resection specimen weight was 220 g (range, 130–310 g) and average size of the malignancy resected was 6.5 cm (range, 3.7–9.2 cm). Three patients (12%) required re-excision for close or positive margins but were ultimately cleared. There were no complications related to the donor site. There were 4 patients (16%) with delayed wound healing related to the Wise pattern closure but no instances of LICAP necrosis or failure.Conclusions:The merger of Wise pattern volume displacement and autologous volume replacement techniques represents a novel strategy that is useful in the most challenging breast conservation patients with some degree of ptosis.

Summary: Centers of excellence strive for high rates of breast conservation surgery. Given the increased patient satisfaction, evidence for improved survival, decreased rates of complications, reduced costs, and fewer surgical procedures compared to mastectomy and reconstruction, this makes sense. As such, surgeons have devised approaches to offer breast conservation to patients with more extensive disease that would have been classically recommended to undergo mastectomy. These ambitious attempts at breast conservation are supported by recent studies that have established their oncological safety. “Extreme oncoplasty” refers to Wise-pattern volume displacement surgery where the breast is immediately reconstructed after a multifocal or multicentric breast cancer is excised. The authors that described this concept also described a Wise-pattern “split reduction” to allow for excision of the skin directly over the cancer, insuring a clear anterior margin. Although extreme oncoplasty has been broadly discussed and published on by many groups, there are few reports that provide insight into the surgical details necessary to successfully perform this surgery. Here, we combine three different oncoplastic techniques: the Wise-pattern split reduction, immediate nipple reconstruction, and autologous volume replacement to demonstrate our approach to extreme oncoplastic breast conservation in a challenging patient.

Summary:Nipple-sparing mastectomy (NSM) and reconstruction is challenging in ptotic patients with additional risk factors. Here, these problems are addressed with a staged strategy that extends NSM and reconstruction to patients with grade 3 ptosis and additional risk factors of diabetes, obesity, and macromastia. Three stages are used to perform a mastectomy, reposition the nipple, and reduce the skin envelope using the Wise pattern. This is followed by definitive implant placement in a final fourth stage. All patients successfully completed their reconstructions without a single instance of implant loss. Using a staged approach, NSM and reconstruction in high-risk ptotic patients is feasible. This is facilitated by using multiple surgical delays and insuring a well-healed skin envelope and optimal nipple position before any prosthetic device is placed.