Michelle Locke

Human adipose‐derived stem cells: isolation, characterization and applications in surgery

The ideal stem cell for use in functional tissue engineering needs to be abundantly available, harvested with minimal morbidity, differentiated reliably down various pathways and able to be transplanted safely and efficaciously. Adult human adipose tissue contains a population of mesenchymal stem cells, termed ‘adipose‐derived stem cells’ (ASC), which seem to fulfil most, if not all, of these criteria. ASC can be harvested readily, safely, and in relative abundance by modern liposuction techniques. They are capable of differentiating into other mesenchymal tissue types, including adipocytes, chondrocytes, myocytes and osteoblasts. They also show angiogenic properties, with recent evidence of a potential role in healing radiotherapy‐damaged tissue, possibly due to their secretion of vascular endothelial growth factor. Similarly, they may have a role in healing chronic wounds, and as such are being investigated in phase 1 trials for their ability to aid healing of recurrent Crohn’s fistulae. Subsequently they have a wide range of potential clinical uses in all fields of surgery. This article reviews the current and potential clinical applications of ASC in relation to surgery, as well as methods for their isolation, differentiation and molecular characterization.

Concise review: human adipose-derived stem cells: separating promise from clinical need

Human adipose‐derived stem cells (ASCs) have become an increasing interest to both stem cell biologists and clinicians because of their potential to differentiate into adipogenic, osteogenic, chondrogenic, and other mesenchymal lineages, as well as other clinically useful properties attributed to them, such as stimulation of angiogenesis and suppression of inflammation. ASCs have already been used in a number of clinical trials, and some successful outcomes have been reported, especially in tissue reconstruction. However, a critical review of the literature reveals considerable uncertainty about the true clinical potential of human ASC. First, the surgical needs that ASC might answer remain relatively few, given the current difficulties in scaling up ASC‐based tissue engineering to a clinically useful volume. Second, the differentiation of ASC into cell lineages apart from adipocytes has not been conclusively demonstrated in many studies due to the use of rather simplistic approaches to the confirmation of differentiation, such as the use of nonspecific histological dyes, or a small number of molecular markers of uncertain significance. Third, the ASC prepared from human lipoaspirate for different studies differ in purity and molecular phenotype, with many studies using cell preparations that are likely to contain heterogeneous populations of cells, making it uncertain whether ASC themselves are responsible for effects observed. Hence, while one clinical application already looks convincing, the full clinical potential of ASC awaits much deeper investigation of their fundamental biology. STEM CELLS 2011,29:404–411

A 15-year experience with primary breast augmentation

Background: This study evaluated patients who underwent primary breast surgery within a single group practice from 1994 to 2009. Reoperations were divided by reoperation reason into total reoperations and implant-specific reoperations. The authors hypothesized that the implant-specific reoperation rate will provide the most accurate measurement of complications caused by the breast implant device. Methods: A total of 812 patients received the same brand of breast implant for primary breast augmentation or augmentation/mastopexy. Safety and efficacy data were recorded and complication rates were calculated. Statistics were applied using Kaplan-Meier estimated cumulative incidence calculations. Results: This study included 482 patients with saline and 330 patients with silicone implants. The most common complications included capsular contracture, rippling, rupture, infection, and hematoma. A total of 8.2 percent of patients developed Baker grade III/IV capsular contracture by 6 years. The raw incidence of rippling was 7.1 percent, and the rate was significantly increased in underweight patients with subglandular saline implants (p = 0.045). The rate of total reoperation at 1 year was 14.2 percent. While a significantly increased rate of total reoperation was seen for silicone compared with saline implants (p < 0.01), no difference was seen in the rate of implant-specific reoperation for saline compared to silicone implants (p = 0.582). Conclusions: The use of total reoperation rates as an indication of complications of breast implants can lead to both an overestimation of implant-related complications and the inaccurate conclusion that silicone implants result in higher complication rates than saline implants. The implant-specific reoperation rate may provide a more accurate incidence of implant complications than the total reoperation rate, which includes reoperations for factors unrelated to the implant.

Current practice in autologous fat transplantation: suggested clinical guidelines based on a review of recent literature.

After more than a century of use, fat grafting is firmly entrenched in the skill set of plastic surgeons. While macrofat grafting is relatively predictable and reliable, microfat grafting by injection is still in the stages of technical evolution. Review of the current literature suggests that revascularization may take up to 21 days to reach the center of a microfat graft. We recommend harvesting by excision (or gentle aspiration), processing by short and gentle centrifuge to separate the layers, and reinjection of the lower layer via a fine cannula (for example, 17 gauge for the face) and a 1-mL syringe with multiple passes, injecting only a tiny amount with each pass as the needle is withdrawn, to obtain the most reliable clinical outcome.

Breast Implant-Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk.

Background: The association between breast implants and breast implant–associated anaplastic large cell lymphoma (ALCL) has been confirmed. Implant-related risk has been difficult to estimate to date due to incomplete datasets. Methods: All cases in Australia and New Zealand were identified and analyzed. Textured implants reported in this group were subjected to surface area analysis. Sales data from three leading breast implant manufacturers (i.e., Mentor, Allergan, and Silimed) dating back to 1999 were secured to estimate implant-specific risk. Results: Fifty-five cases of breast implant–associated ALCL were diagnosed in Australia and New Zealand between 2007 and 2016. The mean age of patients was 47.1 years and the mean time of implant exposure was 7.46 years. There were four deaths in the series related to mass and/or metastatic presentation. All patients were exposed to textured implants. Surface area analysis confirmed that higher surface area was associated with 64 of the 75 implants used (85.3 percent). Biocell salt loss textured (Allergan, Inamed, and McGhan) implants accounted for 58.7 percent of the implants used in this series. Comparative analysis showed the risk of developing breast implant–associated ALCL to be 14.11 times higher with Biocell textured implants and 10.84 higher with polyurethane (Silimed) textured implants compared with Siltex textured implants. Conclusions: This study has calculated implant-specific risk of breast implant–associated ALCL. Higher-surface-area textured implants have been shown to significantly increase the risk of breast implant–associated ALCL in Australia and New Zealand. The authors present a unifying hypothesis to explain these observations.

Tug 'O' war: challenges of transverse upper gracilis (TUG) myocutaneous free flap breast reconstruction.

Autologous tissue microsurgical breast reconstruction is increasingly requested by women following mastectomy. While the abdomen is the most frequently used donor site, not all women have enough abdominal tissue excess for a unilateral or bilateral breast reconstruction. A secondary choice in such women may be the transverse upper gracilis (TUG) myocutaneous flap. This study reviews our experience with TUG flap breast reconstruction looking specifically at reconstructive success rate and the requirement for secondary surgery. A total of 16 free TUG flaps were performed to reconstruct 15 breasts in eight patients over a period of five years. Data were collected retrospectively by chart review. Follow up ranged from 14 to 41 months. During the follow up period, there was one (6.3%) complete flap loss in an immediate breast reconstruction patient. Four further flaps (25%) failed in their primary aim of breast reconstruction, as they required additional significant reconstruction with either deep inferior epigastric perforator (DIEP) flaps (two flaps (12.5%), one patient) or augmentation with silicone breast implants (two flaps (12.5%), one patient), giving a successful breast reconstruction rate with the TUG flap of only 66.7%. In all of the remaining reconstructed breasts, deficient flap volume or breast contour was seen. Eight flaps were augmented by lipofilling. A total of 62.5% of the donor sites had complications, namely sensory disturbance of the medial thigh (25%) and poor scar (37.5%) requiring revision. This series demonstrates a high rate of reconstructive failure and unsatisfactory outcomes from TUG flap breast reconstruction. We feel this reinforces the necessity of adequate pre-operative patient assessment and counselling, including discussion regarding the likelihood of subsequent revisional surgery, before embarking on this form of autologous breast reconstruction.

From bench to bedside: use of human adipose-derived stem cells.

Since the discovery of adipose-derived stem cells (ASC) in human adipose tissue nearly 15 years ago, significant advances have been made in progressing this promising cell therapy tool from the laboratory bench to bedside usage. Standardization of nomenclature around the different cell types used is finally being adopted, which facilitates comparison of results between research groups. In vitro studies have assessed the ability of ASC to undergo mesenchymal differentiation as well as differentiation along alternate lineages (transdifferentiation). Recently, focus has shifted to the immune modulatory and paracrine effects of transplanted ASC, with growing interest in the ASC secretome as a source of clinical effect. Bedside use of ASC is advancing alongside basic research. An increasing number of safety-focused Phase I and Phase IIb trials have been published without identifying any significant risks or adverse events in the short term. Phase III trials to assess efficacy are currently underway. In many countries, regulatory frameworks are being developed to monitor their use and assure their safety. As many trials rely on ASC injected at a distant site from the area of clinical need, strategies to improve the homing and efficacy of transplanted cells are also being explored. This review highlights each of these aspects of the bench-to-bedside use of ASC and summarizes their clinical utility across a variety of medical specialties.

Aesthetic and technical refinements in latissimus dorsi implant breast reconstruction: A 15-year experience

BACKGROUND The latissimus dorsi myocutaneous flap and implant breast reconstruction procedure has undergone many refinements over its lifetime. In fact, the authors have made many aesthetic and technical refinements to their own approach to breast reconstruction. OBJECTIVES The authors review the historical progression of latissimus flap and breast reconstruction techniques and compare these to their own 15-year experience. METHODS A retrospective chart review was conducted for all latissimus and implant breast reconstructions performed by the senior author (MAC) from July 1994 to June 2009, for a total of 52 procedures in 31 patients. Surgical and oncological data, complications, and outcomes data were recorded. RESULTS The mean age of the patients at time of surgery was 47.6 years. Average mastectomy weight was 283 grams and average final implant volume was 364 cc. Average follow-up was three years, four months. Of the 52 total procedures, 34.6% were immediate breast reconstructions utilizing skin-sparing mastectomy (SSM); 13.5% of the reconstructed breasts also had preservation of the areola (areolar-sparing mastectomy [ASM]). The most common complication was donor site seroma (40.4%). Aesthetic and surgical refinements identified over the time period included the adoption of SSM and ASM techniques, immediate nipple reconstruction, the placement of an adjustable saline implant to allow for postoperative size adjustment, and implant placement in the prepectoral position. The overall latissimus dorsi implant reconstruction success rate was 94.2% (49/52). CONCLUSIONS The data demonstrated a successful outcome for latissimus dorsi and implant breast reconstruction for patients with a low or normal body mass index and a small (A to C cup) breast size. The aesthetic outcome of latissimus dorsi breast reconstruction has been improved over the past 15 years by the adoption of SSM and ASM techniques. Immediate nipple reconstruction and the placement of an adjustable saline implant potentially render this procedure a true single-stage reconstruction. Prepectoral implant position provides good aesthetics while preserving the subpectoral space for future management of capsular contracture if required.

Variable presentation of anaplastic large‐cell lymphoma in patients with breast implants

Anaplastic large‐cell lymphoma (ALCL) has recently been reported in women with breast implants. The incidence of breast implant‐related ALCL is extremely rare and most surgeons would not expect to see this disease in their career. However, the senior author has had three women present to his practice with ALCL over a 2‐year period.

Our experiences managing a rare cranio-orbital cleft.

A unilateral upper lateral orbital cleft, fitting the description of the extremely rare Tessier cleft number 9 is reported. The management and surgery of this patient are discussed, and the relevant literature is reviewed. The usefulness of three-dimensional computed tomography reconstructions and plastic models in planning the surgery is discussed.