Adipose-derived stem cells in patients with venous ulcers: Systematic review.

OBJECTIVES: Few studies have reported on the safety and durability of adipose-derived stem cells (ADSCs) to support healing in patients with venous leg ulcers (VLU). To establish if there is any evidence to support ADSC use in VLU patients, a systematic review was conducted. METHODS: A systematic review was conducted following the PRISMA guidelines. PubMed and Embase databases were searched for relevant papers. References from retrieved papers were reviewed to identify any extra eligible studies. RESULTS: After duplicate removal, 950 papers were screened for eligibility of which 932 were excluded based on title and abstract. Four papers were included in the final analysis (one randomised study and three non-randomised studies). 66 patients in total received ADSCs for VLU treatment. The only randomised paper reported 6-month healing rates of 75% with ADSCs compared to 50% in controls. 100% healing was achieved in one study. The remaining 2 studies reported 25% and 58% healing; however, they included patients with relatively large VLUs. Pain scores decreased after ADSCs application where reported. No serious procedure related complications were reported. CONCLUSION: ADSCs may enhance ulcer healing in patients with chronic VLU and appears safe based on initial reports. Large, randomised trials are needed to definitively establish the technique's role in VLU patients.

Dermatofibrosarcoma protuberans of the scalp.

Dermatofibrosarcoma protuberans is a rare entity. Due to its high propensity for local recurrence, knowledge of the appropriate management, both surgical and medical, is important for optimal patient outcomes.

GMP-Compliant Production of Autologous Adipose-Derived Stromal Cells in the NANT 001 Closed Automated Bioreactor.

In recent years mesenchymal stromal cells (MSCs) have received a great deal of interest for the treatment of major diseases, but clinical translation and market authorization have been slow. This has been due in part to a lack of standardization in cell manufacturing protocols, as well as a lack of biologically meaningful cell characterization tools and release assays. Cell production strategies to date have involved complex manual processing in an open environment which is costly, inefficient and poses risks of contamination. The NANT 001 bioreactor has been developed for the automated production of small to medium cell batches for autologous use. This is a closed, benchtop system which automatically performs several processes including cell seeding, media change, real-time monitoring of temperature, pH, cell confluence and cell detachment. Here we describe a validation of the bioreactor in an environment compliant with current good manufacturing practice (cGMP) to confirm its utility in replacing standardized manual processing. Stromal vascular fraction (SVF) was isolated from lipoaspirate material obtained from healthy donors. SVF cells were seeded in the bioreactor. Cell processing was performed automatically and cell harvesting was triggered by computerized analysis of images captured by a travelling microscope positioned beneath the cell culture flask. For comparison, the same protocol was performed in parallel using manual methods. Critical quality attributes (CQA) assessed for cells from each process included cell yield, viability, surface immunophenotype, differentiation propensity, microbial sterility and endotoxin contamination. Cell yields from the bioreactor cultures were comparable in the manual and automated cultures and viability was >90% for both. Expression of surface markers were consistent with standards for adipose-derived stromal cell (ASC) phenotype. ASCs expanded in both automated and manual processes were capable of adipogenic and osteogenic differentiation. Supernatants from all cultures tested negative for microbial and endotoxin contamination. Analysis of labor commitment indicated considerable economic advantage in the automated system in terms of operator, quality control, product release and management personnel. These data demonstrate that the NANT 001 bioreactor represents an effective option for small to medium scale, automated, closed expansion of ASCs from SVF and produces cell products with CQA equivalent to manual processes.

A retrospective cohort study of cutaneous squamous cell carcinoma of the scalp: features of disease and influence of sociodemographic factors on outcomes.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) is an increasingly prevalent and potentially fatal disease with considerable implications if not recognized early and treated promptly. Several disease features contribute to a higher risk profile and adverse outcomes in affected patients. AIMS: Given the clinical observation that elderly males from rural communities often present with large SCCs of the scalp, we sought to investigate and describe features of disease and sociodemographic factors from a cohort of patients with scalp SCCs. METHODS: Histology reports of scalp primary SCCs were retrospectively assessed. Disease and demographic features were recorded. Descriptive statistics were generated, and statistical analyses (Fisher's exact, Mann-Whitney U and Spearman's rank test) were utilized to examine relationships between high-risk disease features and sociodemographic features. RESULTS: Ninety-three occurrences of scalp SCC in 61 patients were assessed. The average age at presentation was 78.81 years. Males were predominantly affected at a 14:1 ratio. Half of all tumours were greater than 2 cm (47/93 (50.54%)). The geographical distance from treatment was significantly associated with larger tumours at presentation. (rs = .34 P = 0.002). Recurrence and metastasis rates were determined amongst 188 patients with a primary scalp SCC, and low rates were observed (2.66% and 2.13%, respectively). CONCLUSIONS: Elderly males are inordinately affected by scalp SCC compared to females. Those living further from care exhibited larger tumours at presentation. Data from this study characterize features of SCC of the scalp and provide evidence to suggest that rural isolation may act as a mediator of high-risk presentation and larger tumour size.

Plastic surgery procedure unit: A streamlined care model for minor and intermediate procedures: A cost-benefit analysis.

INTRODUCTION: The advent of wide-awake local anaesthesia has led to a reduced need for main theatre for trauma and elective plastic procedures. This results in significant cost-benefits for the institution. This study aims to show how a dedicated 7 days/ week plastic surgery procedural (PSP) unit, performing both elective and trauma surgeries, can lead to significant cost-benefits for the institution. METHODS: Retrospective review of all cases performed in the PSP unit between 1 September and 31 August 2018. We utilised hospital directory admissions data and the hospital's intranet operating theatre system to calculate hospital days saved. Cost analysis was performed using Saolta financial data. RESULTS: A total of 3058 operations were performed. Of these operations, 2388 cases were elective and 670 were trauma cases. The average waiting time for trauma cases for main operating theatre was 1.4 days, saving a total of 487 hospital days. The total savings associated with hospital bed days were €347,861. The estimated resource savings from performing a procedure in PSP compared with main theatre with regional anaesthesia were €529.00 and €391.00 without regional anaesthesia. The cost saved due to resources was therefore €337,226. The total cost-benefit associated with performing surgeries in PSP including hospital days and resources saved was calculated as €685,087. CONCLUSION: This study shows the benefit of performing elective and trauma operations in minor procedure units such as PSP. PSP results in a more efficient service, reducing waiting times for surgery, shorter hospital stay, reduced operating cost and an overall significant cost saving.

An assessment of histological margins and recurrence of melanoma in situ.

BACKGROUND: Melanoma in situ (MIS) accounts for up to 27% of all melanomas. MIS has no metastatic potential and the aim should be to excise the lesion completely with a clear histological margin, although margin clearance remains undefined. We aimed to assess the relation of histological excision margins of MIS to recurrence and progression to invasive disease. METHODS: We analyzed all patients with MIS excised by wide local excision or staged excision in our institution over a 5-year period from December 2008 to January 2014 using a prospectively maintained database. Clinicopathologic details included patient demographics, anatomical site of lesion, melanoma subtype, histological excision margin, and recurrence. RESULTS: A total of 410 patients had MIS excised during this time, the majority of which were lentigo maligna subtype (79%). The average histological excision margin was 3.7 mm. The rate of recurrence was 2.2% (9/410), with a median follow-up of 23 months. Lentigo maligna had a similar rate of recurrence to non-lentigo MIS (2.3% vs 1.2%) (P = 0.69). The mean excision margin of those that recurred was 1.9 mm compared with an average of 3.8 mm in those that did not. The rate of recurrence of MIS with histological excision margin ≤3.00 mm was 3.8% compared with 0.5% in those with a histological margin >3.00 mm (P = 0.03). One case of MIS recurred as invasive disease. CONCLUSION: At institutions using wide local excision or staged excision for MIS, a histological margin of >3.0 mm is required to achieve a low recurrence rate.

The pinking shears: a novel tool for improving skin graft cosmesis.

SUMMARY: A significant aesthetic disadvantage to split skin grafts is the obvious transition between the graft and the normal skin. We report on a novel method to interrupt this transition point by using pinking shears, which are dressmaking scissors with saw-toothed blades that create a chevron pattern instead of a straight edge. We describe a case where the pinking shears were utilized on a split skin graft and Integra for reconstruction of the skin on a volar forearm. This technique allows for breaking-up of the transition point between the skin graft and normal skin and gives rise to an improved aesthetic outcome as the boundary is significantly less well-defined. This novel method shows promise and further study is certainly warranted.

Plastic surgical delivery systems for targeted gene therapy.

The expansion of gene therapy applications from inherited disorders to acquired conditions has been mirrored by an exponential rise in both experimental work and clinical trials. This review highlights current plastic surgical delivery systems and clinical applications for targeted gene therapy. We revisit some of the vectors used both experimentally and in clinical gene therapy trials, with an emphasis on developments in plastic surgical delivery systems resulting in improved targeting of therapeutic genes. In addition, we discuss a novel technique for the delivery of gene therapy using the ex vivo transduction of free flaps, developed in our laboratory. This delivery system achieves targeted high-level transgene expression with minimal demonstrable systemic toxicity. Advances in delivery systems are essential for translating basic research into clinical therapeutics.

Ex vivo transduction of microvascular free flaps for localized peptide delivery.

Gene therapy is a promising modality for the treatment of soft tissue malignancies. Our laboratory has developed a novel technique of gene transfer using microvascular free flaps that addresses many of the current barriers preventing gene therapy from achieving widespread clinical use. Our previous work has demonstrated our ability to transduce free flaps with an adenovirus encoding the reporter gene lacZ. In this current study, we show that microvascular free flaps can be transduced with an adenovirus encoding the angiogenesis inhibitor endostatin with high levels of local flap expression. These transduced free flaps were able to serve as "biologic pumps" and were able to secrete endostatin into the serum as demonstrated by enzyme-linked immunosorbent assay. This form of "biologic brachytherapy" could provide a novel approach for the continuous delivery of therapeutic genes to a localized area while avoiding many of the practical obstacles currently limiting gene therapy.