Fungating Malignancies: Management of a Distinct Wound Entity.

GENERAL PURPOSE: To provide information on the surgical management of fungating malignancies as a distinct wound entity. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Identify characteristics of patients in a study examining the treatment of fungating malignancies.2. Select common symptoms experienced by patients with fungating malignancies.3. Explain issues related to the surgical treatment of fungating malignancies.4. Identify a reason why patients with fungating breast masses may avoid medical care.

To address the literature gap on malignant fungating wound treatment by reporting two institutions' experiences with this disease process and proposing practices to improve care. A multi-institutional retrospective review was conducted of 44 patients with 45 malignant fungating wounds over an 11-year period. Patient characteristics, treatment history, and outcomes were analyzed. Of the 44 patients who met the inclusion criteria, 31 (70.5%) were women and 13 (29.5%) were men. The average age at presentation was 63.0 (SD, 16.1) years. The most common malignancy was breast cancer, accounting for more than half of cases (54.5%). The average surface area of the tumors at presentation was 110.3 (SD, 215.0; range, 2.2­1,140) cm 2 , whereas the average surface area at time of discharge/death was 104.6 (SD, 310.7; range, 0­1,800) cm 2 . Neither surface area at presentation ( P = .504) nor surface area at time of final follow-up ( P = .472) were significantly associated with death during the study time frame. In the era of advancing technologies and medical innovation, the benefits of palliative surgery, which helps mitigate an open wound, should not be overlooked. Improving end-of-life care is beneficial to the patient and families alike. As surgeons, we strive for a tangible cure, but providing palliative resection to enable death with dignity might be the most humane service of all.

Cell Enriched Autologous Fat Grafts to Follicular Niche Improves Hair Regrowth in Early Androgenetic Alopecia.

BACKGROUND: Adipose and adipose derived regenerative cells (ADRCs) play an increasing role in androgenetic alopecia. OBJECTIVES: The authors sought to evaluate the safety and feasibility of fat grafts enriched with ADRCs in early androgenetic alopecia. METHODS: Seventy-one patients were treated: 16 with Puregraft fat and 1.0 × 106 ADRCs/cm2 scalp; 22 with Puregraft fat and 0.5 × 106 ADRCs/cm2 scalp, 24 with Puregraft fat alone, and 9 with saline control. Treatments were delivered into the skin and subcutaneous layer of the scalp. A total of 40 cm2 of scalp was treated and macrophotography and global photography were obtained at baseline and at 6, 24, and 52 weeks. RESULTS: A total of 71 patients tolerated the procedures well. No unanticipated associated adverse events were reported. When evaluating all patients at 24 weeks, there were no statistical differences between any of the treatment groups with respect to nonvellus (terminal) hair counts or width. There were increases (mean change from baseline) in terminal hair count for the low-dose ADRC group in the Norwood Hamilton 3 subgroup at week 6 (13.90 ±â€…16.68), week 12 (11.75 ±â€…19.42), week 24 (16.56 ±â€…14.68), and week 52 (2.78 ±â€…16.15). For this subgroup, the difference in hair count between the low-dose ADRC group and no-fat saline control was statistically significant (P = 0.0318) at week 24. CONCLUSIONS: Puregraft fat and ADRCs are safe and well tolerated. In early male hair loss, this therapy demonstrated a statistically significant increase in terminal hair counts relative to the control population at 24 weeks and represents a promising approach for early androgenetic alopecia.

Use of Freshly Isolated Human Adipose Stromal Cells for Clinical Applications.

The clinical use of adipose-derived cells is being explored very actively around the world for various human diseases. Adipose tissue is an abundant tissue source that can be easily harvested using liposuction. Human lipoaspirates contain a significant amount of mesenchymal stromal cells, as well as other progenitors and terminally differentiated cell types. This review covers the isolation of adipose stromal vascular fraction (SVF), the quality control and safety analysis of freshly isolated cell suspensions. The comparison between freshly isolated stromal cells and culture expanded cells from adipose tissue samples is also highlighted. This article provides a brief but comprehensive review about SVF isolation in the clinical setting, cell characterization, and biological potency of freshly obtained adipose stromal cells.

Lateral Intercostal Artery Perforator Flap in Breast Reconstruction: A Simplified Pedicle Permits an Expanded Role.

BACKGROUND: The lateral intercostal artery perforator (LICAP) flap is a versatile second-tier option in breast reconstruction. The flap is rotated from redundant lateral chest fold on an easily dissected skin bridge pedicle without microsurgery in an outpatient setting. This series illustrates safety and effectiveness of the LICAP flap for prosthesis coverage when a muscle flap is not available or desired. In some cases, it even provides adequate soft tissue to reconstruct the breast mound without an implant. METHODS: Lateral intercostal artery perforator flaps performed for breast reconstruction at an ambulatory surgery center were reviewed. RESULTS: A total of 39 flaps were performed on an outpatient basis for a variety of breast reconstruction indications. One immediate reconstruction with bilateral LICAP flaps was performed after mastectomy. All remaining flaps were for delayed breast reconstruction. Mean operative time for each flap was 65 minutes, and concomitant procedures were performed in 25 of 27 patients. Follow-up was 5 to 96 months. There was 1 major complication (2.5%) and 5 minor (12.8%) complications. CONCLUSIONS: This series demonstrates unique advantages of the LICAP flap for a variety of breast reconstruction problems, including outpatient setting, no muscle sacrifice, flap reliability, and low donor site morbidity. These results confirm previous reports in post bariatric augmentation that the LICAP flap reliably supplies a large skin/adipose flap from the redundant tissue of the lateral chest fold with minimal morbidity even after radiation. The LICAP flap warrants closer consideration in breast reconstruction.

Adipose Stromal Vascular Fraction Isolation: A Head-to-Head Comparison of 4 Cell Separation Systems #2.

INTRODUCTION: With stromal vascular fraction (SVF) cell and adipose-derived stem cell-based technologies translating into the clinical setting, numerous isolation systems have been developed for the point of care isolation of SVF cells from adipose tissue. A relative lack of performance data on these systems can make objective assessment difficult for prospective clinicians. This study compared the performance of 4 SVF cell isolation systems. METHODS: Four isolation systems were compared: the MultiStation by PNC International, the LipoKit by MediKhan, the GID SVF-2 platform by GID Europe Ltd, and the StemSource 900/MB system by Cytori Therapeutics, Inc. Identical lipoaspirate samples for 5 separate donors were used. Stromal vascular fraction output was compared in terms of nucleated cell yield, viability, residual collagenase activity, sterility of the output, colony-forming unit-fibroblast frequency, frequency of CD31-/CD34+/CD45- cells, and operating statistics. RESULTS: Mean process time ranged from 65.4 to 120.8 minutes. Mean nucleated cell yield per milliliter of tissue processed ranged from 1.01 × 10 cells/mL to 6.24 × 10 cells/mL. Mean cellular viability ranged from 50.3% to 84.02%. Residual collagenase activity was negligible across all systems. Observed colony-forming unit-fibroblast frequency ranged from 0.495% to 1.704%. No significant difference was observed in frequency of CD31-/CD34+/CD45- cells. Results of the anaerobic/aerobic cultures were mixed. CONCLUSIONS: There was considerable variability between the outputs of each system. The system used by a clinician should be tailored to the individual needs of the practice. There is a range of cost options available. This study may help clinicians make more educated decisions when choosing an isolation system to meet their clinical needs.

Clinical Safety of Stromal Vascular Fraction Separation at the Point of Care.

INTRODUCTION: Pluripotential cells in adipose tissue may be important in long-term volume retention and regenerative effects of fat grafting. Unfortunately, graft harvest with lipoaspiration significantly depletes the population of stromal vascular cells, which includes adipose stem cells. Stromal vascular fraction (SVF) cells may be isolated from excess lipoaspirate at the point of care and used to replenish fat grafts, a technique termed cell-assisted lipotransfer (CAL). Preclinical and clinical evidence supports the rationale of CAL but clinical adoption of the strategy requires evidence of clinical safety. This prospective, level 1 study reports clinical safety of SVF-enhanced fat grafting using a manual, collagenase-based separation process to isolate autogenous progenitor cells from lipoaspirate at the point of care. METHODS: One hundred sixty-four subjects underwent 174 SVF-enhanced autologous fat grafting procedures at the university stem cell center between August 2009 and November 2014 for a variety of cosmetic and reconstructive indications. RESULTS: Cell-assisted lipotransfer was performed for a variety of cosmetic and reconstructive indications. The mean time of the SVF isolation process was 91 minutes. Because of the frequent concomitant procedures, the average operating room time increased by only 11 minutes. Mean follow-up was 19.9 months. There were no major complications and 6 minor complications. No collagenase or neutral protease related complications were observed. CONCLUSIONS: This series of 174 CAL cases demonstrates that SVF cell isolation using a standardized, manual, collagenase-based process at the POC is equivalent in safety compared to nonenhanced fat grafting. These results support expanded use of CAL in the clinical research setting.

Skin-sparing mastectomy: a survey based approach to defining standard of care.

Skin-sparing mastectomy (SSM) followed by immediate reconstruction has been advocated as an effective treatment option for patients with early-stage breast carcinoma. It markedly improves the quality of breast reconstruction through preservation of the natural skin envelope and a smaller incision. The purpose of this study was to investigate general surgeons' attitudes towards SSM. A postal questionnaire survey of California general surgeons was conducted regarding SSM. Of 370 respondents who stated they performed breast cancer surgery, 331 perform mastectomy for cancer with planned immediate reconstruction. Ninety per cent of respondents did not feel that SSM resulted in higher rates of local recurrence. In addition, 70 per cent felt that the cosmetic results of immediate breast reconstruction after SSM were better than those after a standard mastectomy. Despite this, only 61 per cent perform SSM in most cases when immediate breast reconstruction is planned. The majority of general surgeons perform SSM and therefore it should be considered standard of care. Despite a growing body of literature demonstrating high rates of patient satisfaction and long-term oncologic safety with SSM, there remains significant variation in practice patterns among general surgeons. Additional effort in general surgery education regarding the feasibility and safety of SSM is needed.

Goldilocks Mastectomy with Bilateral In Situ Nipple Preservation Via Dermal Pedicle.

Patients who don't want or can't have formal breast reconstruction after mastectomy surgery can be considered for a Goldilocks mastectomy, where the breast fullness is recreated from what is left behind after the gland tissue is removed from underneath the skin in a breast reduction pattern. A Goldilocks mastectomy does not require the use of implants or tissue transfer from other parts of the body and may be completed in a single surgery. This is best suited for larger breasted women who are willing to have much smaller breasts as a result. Previously, it was a challenge to be able to preserve the nipples when this operation was performed; however, this article describes a patient who had a bilateral Goldilocks mastectomy for right breast cancer who was able to save her nipples by keeping the blood flow in place from the surrounding skin. Conventional breast reconstruction after mastectomy is a challenge for larger breasted women. The Goldilocks mastectomy technique was designed to make best use of the redundant lower pole skin and subcutaneous fat to recreate a breast mound without a prosthetic implant or autologous tissue transfer. In its original description, the Goldilocks mastectomy did not include a means for nipple preservation. In this report, we describe the further refinement of the Goldilocks procedure that preserves the nipple areolar complex using a dermal pedicle. A patient with large pendulous breasts and right breast carcinoma underwent a bilateral Goldilocks nipple-sparing mastectomy and immediate reconstruction without an implant or flap.

A Method for Isolation of Stromal Vascular Fraction Cells in a Clinically Relevant Time Frame.

There is increasing interest in the clinical applications of adipose-derived stem cells (ASCs) and the stromal vascular fraction (SVF) based on promising preclinical data. As adipose-derived therapeutics begin to translate into the clinical setting, it is important to maintain patient safety as well as uniformity in technique. Here, we describe a method for isolation of stromal vascular fraction cells in a clinically relevant time frame. Analytical laboratory techniques are mentioned, but respective protocols are not provided here.

Review: Proposed Methods to Improve the Survival of Adipose Tissue in Autologous Fat Grafting.

In 2009, the American Society of Plastic Surgeons Task Force on Autologous Fat Grafting (AFG) determined that autologous fat grafting was a safe procedure with a relatively low rate of complications. This consensus opinion unleashed a wave of popularity as plastic surgeons discovered the procedures' efficacy in a wide variety of cosmetic and reconstructive indications. Frequently reported cosmetic applications include soft-tissue augmentation of breast, buttocks, hips, face, and hands, whereas reconstructive applications include adjunct for breast reconstruction contour problems, plantar fat pad improvement, and correction of various posttraumatic and surgical contour deformities. Recognition of other regenerative effects of fat grafting expanded the use AFG for improvement of hypertrophic scar tissue, postradiation sequelae, lipodystrophy, hyperpigmentation, senile skin changes, and actinic damage. The popularity of AFG is supported by a remarkably low risk of complications, minimal scars, and readily available donor sites. Despite recognition of the advantages of AFG, there still is no consensus regarding optimal techniques of harvest, graft preparation, and injection. Further, the yield of permanent volume falls within a very wide range. In this article, we review the basic science of fat grafting, proposed methods offered to improve engraftment, and reported outcomes of AFG procedures.

Mechanical versus enzymatic isolation of stromal vascular fraction cells from adipose tissue.

Clinical use of adipose-derived stem cells (ASCs) for a variety of indications is rapidly expanding in medicine. Most commonly, ASCs are isolated at the point of care from lipoaspirate tissue as the stromal vascular fraction (SVF). The cells are immediately administered to the patient as an injection or used to enrich fat grafts. Isolation of ASCs from adipose tissue is a relatively simple process performed routinely in cell biology laboratories, but isolation at the point of care for immediate clinical administration requires special methodology to prevent contamination, ensure integrity of clinical research and comply with regulatory requirements. A lack of practical laboratory experience, regulatory uncertainty and a relative paucity of objective published data can make selection of the optimum separation method for specific indications a difficult task for the clinician and can discourage clinical adoption. In this paper, we discuss the processes which can be used to separate SVF cells from fat tissue. We compare the various mechanical and enzymatic methods. We discuss the practical considerations involved in selecting an appropriate method from a clinical perspective. Studies consistently show that breakdown of the extracellular matrix achieved with proteolytic enzymes affords significantly greater efficiency to the separation process. SVF isolated through mechanical methods is equally safe, less costly and less time consuming but the product contains a higher frequency of blood mononuclear cells and fewer progenitor cells. Mechanical methods can provide a low cost, rapid and simple alternative to enzymatic isolation methods, and are attractive when smaller quantities of ASCs are sufficient.

Adipose stromal vascular fraction isolation: a head-to-head comparison of four commercial cell separation systems.

BACKGROUND: Supplementation of fat grafts with stromal vascular fraction cells is an emerging technique used to improve graft reliability. A variety of systems for isolating stromal vascular fraction cells are commercially available. The lack of performance data obtained operating the systems in a standardized environment prevents objective assessment of performance. This prospective, blinded study compared performance of four commercially available stromal vascular fraction isolation systems when operated in a clinical outpatient surgery environment. METHODS: Four different systems were compared: (1) PNC's Multi Station, (2) CHA Biotech Cha-Station, (3) Cytori Celution 800/CRS System, and (4) Medi-Khan's Lipokit with MaxStem. Identical lipoaspirate samples from five separate volunteer donors were used to evaluate system process time, viable cell yield, composition, residual enzyme, and operating costs. RESULTS: The mean processing time ranged from 88 to 115 minutes. The highest mean number of viable nucleated cells was obtained using the Celution System (2.41 × 10 cells/g) followed by the Multi Station (1.07 × 10 cells/g). Lipokit and Cha-Station systems yielded nearly a log fewer nucleated cells (0.35 × 10 cells/g and 0.05 × 10 cells/g, respectively). The Celution System also yielded significantly more endothelial cells, CD34/CD31 cells, and adipose-derived stem cells (colony-forming unit-fibroblast). Residual enzyme levels observed with the Multi Station, Cha-Station, and Lipokit, respectively, averaged 5.1-, 13.0-, and 57-fold higher than that observed with the Celution System. CONCLUSIONS: Although all systems generated measurable amounts of stromal vascular fraction, significant variability exists in the number, identity, and safety profiles of recovered viable cells. Side-by-side clinical trials will be required to establish the relevance of these differences.

Novel pathway of adipogenesis through cross-talk between adipose tissue macrophages, adipose stem cells and adipocytes: evidence of cell plasticity.

INTRODUCTION: Previous studies highlight a complex relationship between lineage and phenotype for adipose tissue macrophages (ATMs), adipose stem cells (ASCs), and adipocytes, suggesting a high degree of plasticity of these cells. In the present study, using a novel co-culture system, we further characterized the interaction between ATMs, ASCs and adipocytes. RESEARCH DESIGN AND METHODS: Human adipocytes and the stromal vascular fraction containing ATMs and ASCs were isolated from human adipose tissue and co-cultured for 24 hours. FACS was used to characterize ATMs and ASCs before and after co-culture. Preadipocytes generated after co-culture were characterized by immunostaining for DLK (preadipocytes), CD14 and CD68 (ATMs), CD34 (ASCs), and Nile Red staining for lipid drops. qRT-PCR was used to quantify adipogenic markers such as C/EBPα and PPARγ. A novel fluorescent nanobead lineage tracing method was utilized before co-culture where fluorescent nanobeads were internalized by CD68 (+) ATMs. RESULTS: Co-culture of adipocytes with ATMs and ASCs increased the formation of new preadipocytes, thereby increasing lipid accumulation and C/EBPα and PPARγ gene expression. Preadipocytes originating after co-culture were positive for markers of preadipocytes, ATMs and ASCs. Moreover, fluorescent nanobeads were internalized by ATMs before co-culture and the new preadipocytes formed after co-culture also contained fluorescent nanobeads, suggesting that new preadipocytes originated in part from ATMs. The formation of CD34(+)/CD68(+)/DLK (+) cell spheres supported the interaction of ATMs, ASCs and preadipocytes. CONCLUSIONS: Cross-talk between adipocytes, ATMs and ASCs promotes preadipocyte formation. The regulation of this novel adipogenic pathway involves differentiation of ATMs to preadipocytes. The presence of CD34(+)/CD68(+)/DLK(+) cells grouped in spheres suggest that paracrine interactions between these cell types plays an important role in the generation and proliferation of new preadipocytes. This phenomenon may reflect the in vivo plasticity of adipose tissue in which ATMs play an additional role during inflammation and other disease states. Understanding this novel pathway could influence adipogenesis, leading to new treatments for obesity, inflammation, and type 2 diabetes.