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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.

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 (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 ear is a high-risk location for skin cancer due to frequent sun exposure. The ear’s anatomical features, such as thin skin overlying cartilage, minimal subcutaneous tissue, and close proximity to subcutaneous lymphatic channels, confer increased risk of invasion and metastasis. Cutaneous neoplasms of the ear are common, and the auricle is the third most common site for basal cell carcinomas (BCCs). Squamous cell carcinomas (SCCs) also commonly develop on the ear, and they may be more prevalent than BCCs.1 They tend to behave aggressively with high rates of recurrence and metastasis.2,3 Due to the occult location of crevices of the external ear and the potential for a lesion to develop on the posterior aspect, late diagnosis is common. The purpose of this study was to review skin malignancies of the ear in our institution over a 5-year period looking at tumor characteristics, demographics, excision margins, recurrence, and metastatic spread.

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.

Intro: Pathophysiology of hypertrophic scar formation remains unclear, potentially involving mechanical strain, burns, or infection. We sought to specifically examine the role of mechanical strain in hypertrophic scars. To do so, we developed and characterized a novel murine model which uses mechanical strain to produce hypertrophic scars in mice. Methods: Paired incisions were created on C57BL6 mice (n = 20). After closure, mechanical strain was applied across one wound using a novel device; the other wound was a control. Starting at day 3, mechanical strain was increased every other day over 4 wks. Wounds were harvested each week, and examined histologically using Sirius red, DAPI, BrdU for proliferation, and caspase 3 for apoptosis. Results: Strained wounds showed features of hypertrophic scars: raised borders, loss of rete pegs and adnexal structures in the epidermis overlying scars, blood vessels that were perpendicular and fibrillary collagen that was parallel to skin surface. Features persisted beyond 6 months. Wound collagen deposition in strained wounds increased 6-fold at 1 wk and over 12-fold at 2–4 wks, in parallel to an increase in number of stromal cells within scar (28-fold). This resulted in an increase in number of cells per unit area of collagen (over 42%). In all wounds, there was no significant difference in proliferation. There was a significant reduction in blood vessel (4-fold) and fibroblast (3-fold) apoptosis at 1–4 wks in strained wounds. Conc: Mechanical strain alone is sufficient to produce hypertrophic scars in this model that are indistinguishable from human scars. Notably, hypertrophic scars appear to result from a marked reduction in apoptosis, rather than from a significant proliferation and upregulation of cellular collagen deposition, validating previous in vitro studies.