Local treatment with electrochemotherapy of superficial angiosarcomas: Efficacy and safety results from a multi-institutional retrospective study.

BACKGROUND: Angiosarcoma is an aggressive vascular neoplasm with a high propensity for local recurrence. Electrochemotherapy is an emerging skin-directed therapy, exerting prominent cytotoxic activity, and antivascular effects. Its efficacy in angiosarcoma has not been investigated. METHODS: This multicenter retrospective analysis reviewed patients who underwent electrochemotherapy from 2007 to 2014 for superficial advanced angiosarcomas. Bleomycin was administered intravenously and delivered within tumors by means of percutaneously applied electric pulses, according to the European Standard Operating Procedures for Electrochemotherapy. Tumor assessment was performed using RECIST (version 1.1). Toxicity (CTCAE, v4.0) and local progression-free survival (LPFS) were also evaluated. RESULTS: Nineteen patients (13 with locally advanced and 6 with metastatic angiosarcomas) were treated. Tumor sites were: scalp (n = 5), breast (n = 8), other skin sites (n = 3), and soft tissue (n = 3). Target lesions (n = 54) ranged in size from 1.5 to 2.5 cm (median, 2 cm). Treatment was well tolerated. After 2 months, an objective response was observed in 12/19 (63%) patients, complete in 8 (42%). One-year LPFS within treatment field was 68%. Local symptom improvement included palliation of bleeding (5/19 patients) and pain relief (6/19 patients). CONCLUSIONS: Electrochemotherapy may represent a new locoregional treatment for selected patients with superficial angiosarcomas. J. Surg. Oncol. 2016;114:246-253. © 2016 Wiley Periodicals, Inc.

Electrochemotherapy of a Multirecurrent Dermatofibrosarcoma Protuberans of the Orbital Margin: A Case Report.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous sarcoma with high recurrence rate. Radical surgery is the treatment of choice, although in cosmetically-sensitive areas such as the head and neck, this option is often not pursued. Electrochemotherapy (ECT) is a minimal invasive anti-tumor modality which is increasingly being used to treat skin metastases from different malignancies. A 31-year-old woman presented with subcutaneous local multirecurring DFSP located at the proximal end of the left eyebrow. ECT was offered as a palliative treatment to avoid radical disfiguring surgery. Two days following ECT, the patient was discharged in good general health. Partial tumor regression was appreciable at two months' follow-up by ultrasound and magnetic resonance imaging. At six months, residual fibrotic tissue was observed; at three years, no evidence of the tumour was detected. In our case, ECT achieved good local tumor control with excellent cosmetic results, preserving the patient's quality of life.

CBX7 gene expression plays a negative role in adipocyte cell growth and differentiation.

We have recently generated knockout mice for the Cbx7 gene, coding for a polycomb group protein that is downregulated in human malignant neoplasias. These mice develop liver and lung adenomas and carcinomas, which confirms a tumour suppressor role for CBX7. The CBX7 ability to downregulate CCNE1 expression likely accounts for the phenotype of the Cbx7-null mice. Unexpectedly, Cbx7-knockout mice had a higher fat tissue mass than wild-type, suggesting a role of CBX7 in adipogenesis. Consistently, we demonstrate that Cbx7-null mouse embryonic fibroblasts go towards adipocyte differentiation more efficiently than their wild-type counterparts, and this effect is Cbx7 dose-dependent. Similar results were obtained when Cbx7-null embryonic stem cells were induced to differentiate into adipocytes. Conversely, mouse embryonic fibroblasts and human adipose-derived stem cells overexpressing CBX7 show an opposite behaviour. These findings support a negative role of CBX7 in the control of adipocyte cell growth and differentiation.

Fat and epidermal cell suspension grafting: a new advanced one-step skin regeneration surgical technique.

BACKGROUND: Dystrophic skin scarring commonly occurs following skin cancer resections. In particular, the cosmetic outcome of skin graft reconstructions, following epidermoidal carcinoma removal, is generally poor due to wide marginal tumour excision, loss of subcutaneous tissues, and subsequent pigmented atrophic scarring of the graft coverage. Skin grafting sequelae need a three dimensional correction to restore either the epidermal layer or the dermal/subdermal volume and vascularization. METHODS: The surgeons combined CO2 laser ablation, subdermal lipofilling according to the Coleman's technique and epidermal cell suspension autografting to correct wide depressed and dyschromic facial scar. The Authors applied this new technique on three nasal skin cancer resected patients: two of them actually need a longer follow-up, the third patient, a 48 yr old caucasian male, presented a skin grafting scar due to sclerodermiform basal cell carcinoma removal. This case is reported discussing pre-intra and post-operative records up to a complete twelve months follow-up. RESULTS: Records at six and twelve months follow-up after surgery demonstrate a fully integrated skin graft and a good restoration of the treated area, presenting the same texture and pigmentation of the adjacent untreated skin. Optimal, stable three-dimensional skin cosmetic restoration was obtained in a single stage surgical procedure. CONCLUSION: Autologous non-cultured epidermal cell suspension transplantation on an epidermal laser ablated skin area, in combination with lipofilling subdermal reconstruction, appears to be an effective, simple and time-saving method to correct skin graft sequelae, in skin cancer patients. This new technique allows to restore a three-dimensional morphological structure of the treated area and to recover a natural appearance of the skin at the same time. The Authors believe that this technique can be safely used to treat any kind of dystrophic scarring.

Treatment of irradiated expanders: protective lipofilling allows immediate prosthetic breast reconstruction in the setting of postoperative radiotherapy.

BACKGROUND: Immediate two-stage prosthetic breast reconstruction in the setting of postmastectomy radiotherapy (PMRT) currently is hardly achieved with the fast-track expander exchange proposed by Cordeiro and colleagues or the delayed-immediate breast reconstruction proposed by Kronowitz and Robb. Each of these techniques has important drawbacks and complications. To overcome these problems, the authors in 2011 described lipofilling on irradiated expanders in patients undergoing unplanned PMRT (Cagliari University Hospital [CUH] protocol) for early breast cancers with specific risk factors. The authors report their experience after expanding the use of such a protocol for any immediate expander/implant reconstruction in a patient undergoing PMRT. METHODS: The timing for advanced breast cancer involves immediate reconstruction with a tissue expander, complete tissue expansion, radiotherapy (RT) after neoadjuvant chemotherapy starting 2-3 months after mastectomy, one or two fresh fat-grafting sessions at least 6 weeks after RT, and an expander-implant exchange with anterior capsulectomy at least 3 months after the completion of fat grafting. The timing for early breast cancers with specific risk factors involves immediate reconstruction with a tissue expander, complete tissue expansion during postoperative chemotherapy, RT 6 months after mastectomy, one or two fat-grafting sessions 6 weeks after RT, and an expander-implant exchange with anterior capsulectomy at least 3 months after the completion of fat grafting. From 2008 to 2012, 16 patients undergoing total mastectomy and immediate expander-implant breast reconstruction with subsequent PMRT were treated according to the CUH protocol. RESULTS: The results have been extremely encouraging, with rates of ulceration and implant exposure in the radiotreated area dropping to 0 %. These results were retrospectively compared with those for a control group of 16 patients who underwent immediate implantation of an expander. In this latter group, the extrusion rate of the implant in the end was 31.25 %, and this was statistically significant (p < 0.03). The shape and symmetry also were significantly better in the lipofilled patients. CONCLUSION: Protective lipofilling on irradiated expanders appears to be a valid technique for avoiding ulceration and implant exposure after PMRT while allowing a complete expansion. LEVEL OF EVIDENCE IV: 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 .

SLN melanoma micrometastasis predictivity of nodal status: a long term retrospective study.

BACKGROUND: Completion lymph node dissection (CLND) is the gold standard treatment for patients with a positive sentinel lymph node (SLN) biopsy. Considering the morbidity associated with CLND it is important to identify histological features of the primary tumor and/or of SLN metastasis that could help to spare from CLND a subset of patients who have a very low risk of non-SLN metastasis. The objective of this study is to identify patients with a very low risk to develop non-SLNs recurrences and to limit unnecessary CLND. METHODS: A retrospective long-term study of 80 melanoma patients with positive SLN, undergone CLND, was assessed to define the risk of additional metastasis in the regional nodal basin, on the basis of intranodal distribution of metastatic cells, using the micro-morphometric analysis (Starz classification). RESULTS: This study demonstrates that among the demographic and pathologic features of primary melanoma and of SLN only the Starz classification shows prognostic significance for non-SLN status (p<0.0001). This parameter was also significantly associated with disease-free survival rate (p<0.0013). CONCLUSION: The Starz classification can help to identify, among SLN positive patients, those who can have a real benefit from CLND. From the clinical point of view this easy and reliable method could lead to a significant reduction of unnecessary CLND in association with a substantial decrease in morbidity. The study results indicate that most of S1 subgroup patients might be safely spared from completion lymphatic node dissection. Furthermore, our experience demonstrated that Starz classification of SLN is a safe predictive index for patient stratification and treatment planning.

Merkel cell polyomavirus in Merkel cell carcinoma of Italian patients.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive human malignancy of elderly or immunosuppressed patients. Clonal integration of a new human polyomavirus, the Merkel cell polyomavirus (MCPyV), has been reported in MCC patients. The main objective of the study was the detection of MCPyV and viral expression in clinical samples of Italian patients who were diagnosed MCC. FINDINGS: DNA and RNA were extracted from nine MCCs to detect the presence of MCPyV. Viral large T gene (LT1 and LT3), and viral capsid gene (VP1) were detected by polymerase chain reaction (PCR) based methods, and the amplified PCR products were subjected to direct sequencing. The presence of viral T antigen and/or viral capsid DNA sequences was demonstrated in eight of the nine MCC lesions, whereas RNA transcripts were detected in three MCCs. CONCLUSIONS: These findings indicate a potential role of MCPyV in the pathogenesis of at least a subset of MCCs.

Purification and characterization of adipose-derived stem cells from patients with lipoaspirate transplant.

Techniques for medical tissue regeneration require an abundant source of human adult stem cells. There is increasing evidence that adipose stem cells contribute to restoration of tissue vascularization and organ function. The object of our study was to isolate and characterize adult adipose-derived stem cells from patients undergoing on lipoaspirate transplant with the aim to improve tissue regeneration. Adipose-derived stem cells were isolated and purified from the lipoaspirate of 15 patients and characterized for CD markers and the ability to differentiate toward the adipogenic lineage. We found that purified adipose stem cells express high level of CD49d, CD44, CD90, CD105, CD13, and CD71 and these markers of staminality were maintained at high level for at least 3 months and seven passages of in vitro culture. As expected, these cells resulted negative for the endothelial and hematopoietic-specific markers CD31, CD106, CD34, and CD45. Differentiation towards adipogenic lineage demonstrated that purified adipose-derived stem cells are still able to become adipocytes at least 3 months after in vitro culture. The analysis of Akt and MAPK phosphorylation confirmed a modulation of their activity during differentiation. Interestingly, we established for the first time that, among the p53 family members, a strong upregulation of p63 expression occurs in adipocytic differentiation, indicating a role for this transcription factor in adipocytic differentiation. Taken together, these data indicate that purified lipoaspirate-derived stem cells maintain their characteristic of staminality for a long period of in vitro culture, suggesting that they could be applied for cell-based therapy to improve autologous lipoaspirate transplant.