Standardized Pre-clinical Surgical Animal Model Protocol to Investigate the Cellular and Molecular Mechanisms of Ischemic Flap Healing.

BACKGROUND: Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. Our goal was to provide a step-by-step methodological protocol for creating an alternative standardized, more economical, and transferable pre-clinical animal research model of excisional full-thickness wound healing following a simulated autologous tissue transfer which includes the primary ischemia, reperfusion, and secondary ischemia events with the latter mimicking flap salvage procedure. RESULTS: Unlike in the most frequently used classical unilateral McFarlane's caudally based dorsal random pattern skin flap model, in the herein described bilateral epigastric fasciocutaneous advancement flap (BEFAF) model, one flap heals under normal and a contralateral flap-under perturbed conditions or both flaps heal under conditions that vary by one within-subjects factor. We discuss the advantages and limitations of the proposed experimental approach and, as a part of model validation, provide the examples of its use in laboratory rat (Rattus norvegicus) axial pattern flap healing studies. CONCLUSIONS: This technically challenging but feasible reconstructive surgery model eliminates inter-subject variability, while concomitantly minimizing the number of animals needed to achieve adequate statistical power. BEFAFs may be used to investigate the spatiotemporal cellular and molecular responses to complex tissue injury, interventions simulating clinically relevant flap complications (e.g., vascular thrombosis) as well as prophylactic, therapeutic or surgical treatment (e.g., flap delay) strategies in the presence or absence of confounding risk factors (e.g., substance abuse, irradiation, diabetes) or favorable wound-healing promoting activities (e.g., exercise). Detailed visual instructions in BEFAF protocol may serve as an aid for teaching medical or academic researchers basic vascular microsurgery techniques that focus on precision, tremor management and magnification.

Complications in Prolonged Intraoperative Ischemia Time in Free Flap Breast Reconstruction: A Systematic Review and Meta-Analysis.

BACKGROUND: Autologous tissue transfer is an effective option for breast reconstruction post-mastectomy, with microsurgical techniques continually evolving. However, a comprehensive analysis of the relationship between prolonged ischemia time during free flap-based breast reconstruction and increased postoperative complications is still lacking. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. Methodological quality was evaluated using the MINORS criteria. Studies meeting inclusion criteria were analyzed for total complications, complete and partial flap loss, and secondary outcomes. Data heterogeneity and risk ratios were assessed. RESULTS: Seventeen studies encompassing 5636 patients and 6884 free flaps were included. The mean age of patients was 49.43 years (95% CI: 48.27-50.60), with a mean BMI of 26.09 (95% CI: 21.97-30.21), and an average post-harvesting free flap ischemia time of 70.35 min (95% CI: 56.71-83.98). These analyses revealed a heightened risk of total complications (RR: 1.99, 95% CI: 1.61-2.46), complete flap loss (RR: 3.15, 95% CI: 1.32-7.52), partial flap loss (RR: 1.91, 95% CI: 0.92-4.00), hematoma (RR: 1.79, 95% CI: 0.96-3.32), and infection (RR: 2.12, 95% CI: 1.32-3.42) in cases with ischemia time exceeding 60 min. Venous complications predominated in free flap failure cases. CONCLUSIONS: Effectively managing ischemia time could be crucial in free flap breast reconstruction to potentially reduce postoperative complications. Although there is a correlation between managing ischemia time and reducing postoperative complications, further research is needed to investigate the possible causation behind this relationship. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Microfat Grafting in Nasal Surgery.

BACKGROUND: Injectable fillers are sometimes necessary to correct slight skin irregularities. However, there have been reports of necrosis after injection of alloplastic materials and heterogeneous transplants. On the other hand, the advantages of autogenous tissue grafts over those fillers are well established. Volumetric reshaping of the face with autologous tissue injection is a popular and reliable method with good long-term results. However, procedures performed on the fragile skin of the nose are prone to complications. OBJECTIVES: The author conducted a study of injectable autologous microfat grafting to the nose in patients with secondary nasal deformities. METHODS: During a 5-year period, 313 patients who had secondary nasal deformities with slight skin irregularities or severe nasal skin damage were treated with microfat grafting. At each patient's first injection session, excess harvested fat was cryopreserved for subsequent injection. To correct minor irregularities, 0.3 to 0.8 mL of microfat was injected during each session; for major irregularities or defects, 1 to 6 mL was required for each session. RESULTS: One to 3 injections of microfat provided satisfactory results in all patients who had minor irregularities. For patients with multiple and severe irregularities, 3 to 6 injections were necessary and resulted in high patient satisfaction. In another group of patients, with severe traumatic skin damage, 6 to 16 injections were necessary for reconstruction. After repeated injections, each patient's skin damage was repaired. CONCLUSIONS: Autologous microfat injection appears to be safe and effective for correcting slight irregularities of the nose. LEVEL OF EVIDENCE: 4.

Facial rejuvenation with staged injections of cryopreserved fat and tissue cocktail: clinical outcomes in the past 10 years.

BACKGROUND: Facial rejuvenation by autologous fat transfer is common in aesthetic plastic surgery. The main drawback is progressive resorption, requiring repeated harvesting and microfat grafting. OBJECTIVE: The authors present a method for cryopreservation of excess harvested fat and tissue to enable subsequent use of previously harvested excess material. METHODS: Fat grafts were harvested using a 50-mL syringe and a 3- or 4-mm cannula. A tissue "cocktail" composed of dermis, fascia, and fat was prepared from excised scar tissue, tissue from abdominoplasty, or tissue from reduction mammaplasty. Cocktail specimens were placed in sterile tubes, immersed in a liquid nitrogen tank (-196°C), and stored at -80°C. At 3- to 6-month intervals, repeated cryopreserved fat graft injections were performed. Patients were evaluated by comparing preoperative and postoperative photographs. RESULTS: Between 2000 and 2010, a total of 5199 cryopreserved fat or tissue injections were performed in 2439 consecutive patients (age range, 19-80 years). Nasolabial folds and lips were the most common injection sites. Clinical outcomes were satisfactory, and improved contour was achieved in most patients after repeated injections. CONCLUSIONS: Cryopreservation of excess tissue for future injection is promising since repetitive injections are often required after resorption of microfat grafts. In our study, the survival of cryopreserved tissue cocktail or fat was comparable to that of fresh fat grafts and is therefore an effective adjuvant method for facial rejuvenation.

Meshed Split-Thickness Autograft With a Viable Cryopreserved Placental Membrane Overlay for Lower-Extremity Recipient Sites With Increased Risk of Graft Failure.

Introduction: Meshed split-thickness skin grafting represents a rapid and effective technique for surgical wound closure. Factors such as ongoing inflammation, microbial colonization, and a poorly vascularized wound bed increase the rate of skin autograft failure up to 33%. Because of the inherent angiogenic, anti-inflammatory, antimicrobial, and antifibrotic properties of human placental membranes, the complementary use of human placental membranes may promote graft survival and improve success rate for complete ulcer resolution. Methods: In this case series, a viable cryopreserved placental membrane was used as a meshed split-thickness skin grafting overlay in 6 high-risk patients with various comorbidities and recalcitrant nonhealing lower-extremity wounds. Results: The mean size of grafted wounds was 130.3 cm2. The average graft take-rate by postoperative days 10 to 14 was 92.5%, with complete epithelialization of all skin graft interstices observed between days 10 and 21. Transplanted autograft tissues did not lyse or dissolve, and sites remained free of infection and maceration throughout postoperative follow-up. Complete wound closures remained intact at the 12-month follow-up visit. Discussion: Thus far, our clinical experience has warranted the complementary use of viable cryopreserved placental membrane and meshed split-thickness skin grafting to reduce the need for repeat surgical interventions or prolonged local wound care due to graft loss or failure in high-risk patients.

Recent advances in microvascular autologous breast reconstruction after ablative tumor surgery.

Breast cancer is a ubiquitous disease and one of the leading causes of death in women in western societies. With overall increasing survival rates, the number of patients who need post-mastectomy reconstruction is on the rise. Especially since its psychological benefits have been broadly recognized, breast reconstruction has become a key component of breast cancer treatment. Evolving from the early beginnings of breast reconstruction with synthetic implants in the 1960s, microsurgical tissue transfer is on the way to become the gold standard for post oncology restoration of the breast. Particularly since the advent of perforator based free flap surgery, free tissue transfer has become as safe option for breast reconstruction with low morbidity. The lower abdominal skin and subcutaneous fat tissue typically offer enough volume to create an aesthetically satisfying breast mound. Nowadays, the most commonly used flap from this donor site is the deep inferior epigastric artery perforator flap. If the lower abdomen is not available as a donor site, the gluteal area and thigh provide a number of flaps suitable for breast reconstruction. If the required breast volume is small, and there is enough tissue available on the upper medial thigh, then a transverse upper gracilis flap may be a practicable method to reconstruct the breast. In case of a higher amount of required volume, a gluteal artery perforator flap is the best choice. However, what is crucial in addition to selecting the best flap option for the individual patient is the timing of the operation. In patients with confirmed post-mastectomy radiation therapy, it is advisable to perform microvascular breast reconstruction only in a delayed fashion.