Alessandra Marchi

Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells.

Background: There is evidence that stem cells contribute to the restoration of tissue vascularization and organ function. The objective of this study was to assess the presence of adipose-derived adult stem cells left in their natural scaffold in the purified lipoaspirate and to assess the clinical effectiveness of lipoaspirate transplantation in the treatment of radiation side effects. Methods: This study was designed beginning with surgical procedures in 2002 and envisaging a continuous patient follow-up to 31 months. Twenty consecutive patients undergoing therapy for side effects of radiation treatment with severe symptoms or irreversible function damage (LENT-SOMA scale grade 3 and 4) were enrolled. Purified autologous lipoaspirates (60 to 120 cc) taken from a healthy donor site were administered by repeated low-invasive computer-assisted injection. Therapy outcomes were assessed by symptoms classification according to the LENT-SOMA scale, cytofluorimetric characterization, and ultrastructural evaluation of targeted tissue. Results: In the isolated stromal vascular fraction of 2 cc of human lipoaspirate, cells with mesenchymal stem cell physical properties and immunophenotype were in average 1.07 ± 0.5 percent (n = 4), with a clonogenic fraction of 0.139 percent. At least 1.02 × 103 colony-forming units–fibroblast were present in each lipoaspirate. Ultrastructure of target tissue systematically exhibited progressive regeneration, including neovessel formation and improved hydration. Clinical outcomes led to a systematic improvement or remission of symptoms in all evaluated patients, including otherwise untreatable patients exhibiting initial irreversible functional damage. Conclusions: This surgical procedure is a low-invasive therapeutic approach for resolving the late side effects of radiotherapy. According to the proposed hypothesis of the ischemic nature of radiolesions, treatment with lipoaspirate transplantation is potentially extended to other forms of microangiopathies.

Adipose-Derived Mesenchymal Stem Cells: Past, Present, and Future

It is likely that in the future, the past decade in the historyof plastic surgery will be remembered for the introductionof reconstructive therapies based on the use of stem cells.Of the variety of different approaches that have been pro-posed, those that have been most widely used in recentyears, and which therefore seem most promising for thefuture, are those using adipose-derived mesenchymal stemcells [1]. The current use and the immense promise of stemcells from adipose tissue are due largely to three aspectsthat make the procedure simple:1. The possibility of minimally invasive autologoustransplants. Adipose-derived mesenchymal stem cellsare obtained by lipoaspiration followed by centrifuga-tion. They can be directly injected into areas to betreated immediately after extraction, there in theoperating theatre.2. Cell expansion is not necessary. As said, the cells canbe injected immediately after extraction, along withthe lipoaspirate that surrounds them. They do not needto be pre-expanded in vitro. To complete the concept,the addition of the lipoaspirate means that what areinjected are ‘‘stem cell niches’’ in which the cells aresurrounded by a glycoproteic scaffold, including tissuefactors that would be eliminated with digestion of thematrix if treated with collagenase—an indispensablestep if expansion in vitro were necessary.3. Age is no barrier. The procedure can be carried out atany time in a patient’s life since adipose stem cells areabundant even in the elderly and show the ability torepair lesionated tissues highly efficiently.The efficacy of the technique has been confirmedrepeatedly and under a variety of different conditions. Howdid this use of adipose-derived mesenchymal stem cellsoriginate and develop? And above all, what are the futuretherapeutic possibilities of this technique?The Past: Fat as a FillerAt times, medical research originates from old ideas thatwere not sufficiently investigated or interpreted in the past.What we are discussing is a good example: The idea ofautologous transplants of fatty tissue is not new in plasticsurgery. There are publications about the use of fat as afiller that date back to the end of 19th century. The tech-nique of ‘‘lipofilling’’ developed out of these experiencesand has been used to treat thousands of patients with a widerange of indications. However, despite its undoubtedadvantages, the simple injection of fat was not withoutproblems, the most significant being the poor reproduc-ibility of results and the risk of generating ‘‘nodules,’’which can lead to oil cysts or, less frequently, to granulo-mas. Credit is due to Coleman for directing attention tothese limitations, which were linked to the techniques usedto extract and inject fat, and for laying the foundations for amore effective use of adipose tissue [2]. His main insightwas to understand the importance of a uniform distributionof the lipoaspirate injected into the tissue to be treated,

Tissue-engineered breast reconstruction with Brava-assisted fat grafting: a 7-year, 488-patient, multicenter experience.

Background: The ability of autologous fat transfer to reconstruct an entire breast is not established. The authors harnessed the regenerative capabilities of external expansion and autologous fat transfer to completely reconstruct breasts. Methods: The authors performed 1877 Brava plus autologous fat transfer procedures on 616 breasts in 488 women to reconstruct 99 lumpectomies, 87 immediate breast reconstructions, and 430 delayed total breast reconstructions. After 2 to 4 weeks of Brava expansion, which increased volume by 100 to 300 percent, the authors diffusely grafted the breasts with 100 to 400 ml (225 ml average) of 15 g–sedimented, manually harvested lipoaspirate. The procedure was repeated every 8 to 14 weeks until completion. The authors compared costs of this reconstruction with established deep inferior epigastric artery perforator/transverse rectus abdominis musculocutaneous flaps and implant procedures. Results: Follow-up ranged from 6 months to 7 years (mean, 2.5 years), with 0.5 percent locoregional recurrence. Four hundred twenty-seven women completed the reconstruction, whereas 12.5 percent dropped out (2.5 percent medical, 10 percent personal reasons). Completion required 2.7 procedures for nonirradiated and 4.8 procedures for irradiated mastectomies. Patients recovered soft, natural appearing breasts with nearly normal sensation. Complications included five pneumothoraces and 20 ulcerative infections. Radiographically recognized benign palpable masses were observed in 12 percent of nonirradiated and 37 percent of irradiated breasts. The cost of Brava plus autologous fat transfer is 47 percent and 66 percent that of current reconstruction alternatives. Conclusion: Brava plus autologous fat transfer is a minimally invasive, incisionless, safe, economic, and effective alternative for breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Autologous fat grafting in breast cancer patients

In the frame of the debate on the oncological safety of autologous fat grafting in breast reconstruction, we comment on the Personal View article recently appeared on The Breast by Lohsiriwat and colleagues (Breast 2011; 20:351–357), which reports a literature analysis, questioning the safety of fat grafting in patients with breast cancer. When mentioning the work by Rigotti et al. (Aesth Plast Surg 2010; 34:475), Authors claim that the methodology “should be criticized, because the risk of LRR (Late Relapse Rate) decreases with time and cannot be considered as equivalent in the pre and post lipofilling period”. This bias exists and was discussed for the dependent-group analysis reported in that paper; conversely, Authors lack mentioning that comparable relapse-free survival probabilities were found (log-rank test 1⁄4 1.69; p 1⁄4 0.19) in the frame of an independent–group analysis, designed to compare LRR in the period from surgery to first fat grafting session (Period I) in a group of patients, with LRR in the period starting from first fat grafting session, in average 20 months after surgery, of a second independent patient cohort. This result was confirmed (log-rank test 1⁄4 1.27; p 1⁄4 0.26) also when taking out from Period I the first 20 months after surgery, in order to avoid any possible bias on LR risk equivalence. In addition, Authors criticize the exclusion from the study of 104 breast conservative treatment patients, proving to have overlooked the reported patient inclusion criteria, according to which only 13 breast conservative treatment patients could have been

Computer assisted planning of autologous fat grafting in breast

Autologous fat grafting is an emerging and promising surgical technique in regenerative medicine, and its application is quickly spreading in plastic and reconstructive surgery of the breast. However, despite the advantages of the technique, surgical complications may occur, such as implanted tissue necrosis and resorption and onset of microcalcifications. In view of the hypothesis that the uniformity of the lipoaspirate transplantation is related to graft survival and a lower probability of complications, we developed an interactive lipomodeling planning software application based on a genetic algorithm that allows automatic optimization of the uniformity of fat tissue distribution. The input dataset consists of a 3D model of the patients thorax, created from MRI scans, on which relevant structures are segmented. The developed software was tested starting from either an automatically generated plan or an initial guess of the optimal surgical plan, and in both cases the application yielded a consistent improvement in the planned fat tissue distribution by optimizing the position of the insertion points and the direction of the insertion pathways. On the basis of the simulations performed, the use of genetic algorithms for optimization of the geometry of autologous fat transfer in the breast proved to be effective. These results will foster further activities focused on the comparison of predicted optimized geometries and those obtained in real surgical cases as a means of obtaining a deeper knowledge of the potential influence of a uniform fat tissue distribution on the quality of the surgical outcome. The presented application is also put forward as representing a noteworthy step towards the clinical application of computer assisted planning tools in breast surgery.

Refinements in microvascular repair of extended oromaxillofacial defects with radial forearm free flap.

The radial forearm free flap (RFFF) is one of the most widely used and versatile fasciocutaneous free flaps in head and neck reconstruction because of its qualities--the consistent vascular anatomy; the thin and pliable nature; the minimal hair presence; and the possibility of harvesting and transferring it as a composite tissue flap, with bone, tendon, and nerve. The RFFF provides a method of single-stage reconstruction of wide residual defects after excision of advanced cancer (T3-T4) in the head and neck region. We present our ten-year experience with RFFF and the good results obtained with some refinements, which allowed us to verify the efficacy of the oral competence using the palmaris gracilis tendon as a sling. We also present the possibility of harvesting long segments of radius (up to 18 cm), and the discovery that use of antithrombotic or anticoagulant therapy is not necessary for the flap survival. This treatment does not guarantee a complete recovery, but it can improve the quality of the patients life.