[Regeneration and rehabilitation. Plastic surgery practice in a rehabilitation centre.] / Rigenerazione e Riabilitazione. Esperienza di chirurgia plastica in un centro di riabilitazione.

OBJECTIVES: Regenerative Surgery aims at the restoration of the loss of structures and functions of the body using four innovative approaches: physical energies, biomaterials, cell products and stem cells. METHODS: The Authors provide an overview of their experience with Regenerative Surgery procedures at the Plastic Surgery Unit of the University of Pavia, Istituti Clinici Scientifici Salvatore Maugeri, in a 10 years period, from 2007 to 2017, for the treatment of extensive acute soft tissue loss, chronic ulcers, disabling scars and degenerative pathologies with different aethiology. RESULTS: Regenerative Surgery is a well-established and effective practice in a modern Plastic Surgery Unit. CONCLUSIONS: Regenerative methods are effectively used both as exclusive options in case of absolute contraindication to traditional surgery and as alternative to the latter in order to provide the same outcome with less invasiveness or in combination with minor traditional surgical procedures to reduce the overall surgical burden.

Versatile use of dermal substitutes: A retrospective survey of 127 consecutive cases.

BACKGROUND: Dermal substitutes are currently largely used for the treatment of huge skin loss in patients in critical general health conditions, for the treatment of severe burns and to promote the healing process in chronic wounds. AIMS: The authors performed a retrospective assessment of their experience with bioengineered skin to possibly identify the most appropriate clinical indication and management for each substitute. MATERIALS AND METHODS: The study involved 109 patients with 127 skin defects repaired with dermal substitutes over a 9 years period, from 2007 to 2016. Hyalomatrix® was used in 63 defects, whereas Integra® and Nevelia® were used in 56 and 8 defects, respectively. RESULTS: The statistical analysis failed to reveal a correlation between the choice of a specific dermal substitute and any possible clinical variable except in the soft-tissue defects of the scalp where Hyalomatrix® was electively used. CONCLUSIONS: In the authors' experience, the scalp defects followed a radical excision of skin tumours that included the periosteum. Here, the preliminary cover with a hyaluronan three-dimensional scaffold constantly allowed for the regeneration of a derma-like layer with a rich vascular network fit for supporting a split-thickness skin graft. Nevertheless, the authors still prefer Integra® when the goal is a better cosmetic outcome and Hyalomatrix® when a faster wound healing is required, especially in the management of deep wounds where the priority is a fast obliteration with a newly formed tissue with a rich blood supply. However, these clinical indications still are anecdotally based.

Prefabricated Composite Graft for Eyelid Reconstruction.

The authors propose a prefabricated chondromucosal composite graft to reconstruct full-thickness defects of the lower eyelid. The technique was used in a patient suffering from a locally invasive basal cell carcinoma of the lower eyelid, who had previously undergone an extensive submucosal nasal septum resection. One week prior to the eyelid resection, the anterior skin surface of the auricular concha was replaced with a full-thickness oral mucosa graft. One week later, a full-thickness excision of the right lower eyelid was performed and the prefabricated chondromucosal auricular graft was used to restore the posterior lamella. The anterior lamella was reconstructed with a bipedicled myocutaneous flap from the upper eyelid. Because of the patient's scheduling needs, the medial pedicle of the flap was divided 28 days later and the lateral one after further 37 days. All the procedures were performed under local anesthesia. This technique adds a simple key detail to other time-honored reliable techniques, thus outlining an extremely convenient sequence for full-thickness eyelid reconstruction. The easily prepared prefabricated chondromucosal graft might be associated with any of the previously described flaps, thus providing a versatile and reliable method of posterior lamella reconstruction.

Hyaluronan-induced cosmetic reconstruction of the nostril.

Tissue loss of the nostrils presents a considerable surgical challenge due to the greatly reduced availability of local tissue within such a peculiar anatomical region. The traditional reconstructive methods, such as direct suture, secondary healing, skin grafts, and local skin flaps, have shown poor provision of desirable cosmetic outcomes in this area. The authors propose an innovative and alternative method of cosmetic reconstruction of small skin defects of the nostril based on a hyaluronan-induced skin regeneration. Such a procedure allowed the healing of relatively large areas of skin loss with the formation of a truly regenerated tissue whose clinical features closely resemble those of the local normal skin. Nevertheless, the proposed procedure is lengthy and time-consuming and requires high levels of cooperation from patients. In our practice, the hyaluronan-induced skin regeneration is now considered the first choice for cosmetic reconstruction of small defects of the nostril in needy patients.

[Safety of use assessment in a radio-frequency medical device]. / Valutazione della sicurezza d'impiego di un'apparecchiatura elettromedicale ad emissione di radiofrequenza.

The authors assessed the operating safety physical parameters of a bipolar radiofrequency device for aesthetic purposes. According to both Italian and EU guidelines, the authors considered: magnetic field environmental emission levels, electricity induced in the opertator's limbs, operator's exposure and radiofrequency specific absorbance rate (SAR) in treated tissues. Measurements were carried out with isotropic sensors and an inductive current indicator. Results pointed out excellent safety levels regarding environment, operators and patients as well, although such radiofrequency equipment cannot be used on patients with pacemakers, neurostimulators and other vital function controlling devices.

Long term assessment of intralipotherapy in Madelung's disease.

Madelung's disease is characterised by multiple symmetric abnormal fat masses in the head, neck and upper limbs. Surgical excision or liposuction is the only realistic available option, although palliative in nature. The serial intralipotherapy with phosphatidylcholine/deoxycholate has been proposed as a non-invasive treatment of Madelung's disease. The authors used serial intralipotherapy with phosphatidylcholine/deoxycholate in two patients affected by Madelung's disease. Three injections per lesion per patient were performed with 1 month's interval. Pre- and 6 months' post-treatment dimensions were assessed with ultrasound scan and patients were observed along a 5 years' clinical follow-up. A 42.5% average size reduction was reported in all treated lesions. About 33% recurrence rate was observed in the 5 years' follow-up. We confirm the efficacy of intralipotherapy in the non-invasive palliative treatment of Madelung's disease, as a valid option to reduce the volume and limit the growth of the pathological adipose masses.

Depletion of the nasal reserve after a mole excision.

The authors present an original case report to warn of a possible severe functional complication that might follow a simple facial skin procedure. A 55-year-old woman underwent excision of a mole along the alar-facial groove, which seemingly healed without immediate complications. Ultimately the patient reported an ipsilateral nasal obstruction 2 months postoperatively. Intranasal inspection and a computed tomography scan revealed a severe septum deviation that had been previously clinically unapparent. The authors argue that the skin-scarring process progressively counterbalanced the action of the levator labii superioris alaeque nasi muscle fascicle to the nostril. Such an action had been compensating for a subtotally compromised nasal air flow from a preexisting severe septal deviation. In this context, skin scarring was enough to impair a minimal residual nasal respiratory reserve. The authors therefore advise performing an internal nasal inspection at all times prior to any sort of skin surgery around the alar-facial groove. This will allow detection of any subclinical functionally compensated preexisting septal deviation or any other intranasal obstruction that could manifest at a later stage.

Hyaluronic acid three-dimensional scaffold for surgical revision of retracting scars: a human experimental study.

An observational study was carried out at the Plastic and Reconstructive Surgery Unit of the University of Pavia - Salvatore Maugeri Research and Care Institute, Pavia, Italy, to assess the clinical and histological long-term outcomes of autologous skin grafting of fresh surgical wounds following previous repair with a hyaluronic acid three-dimensional scaffold (Hyalomatrix®). Eleven fresh wounds from surgical release of retracted scars were enrolled in this study. A stable skin-like tissue cover was observed in all of the treated wounds in an average 1 month's time; at the end of this study, after an average of 12 months' time, all of the reconstructed areas were pliable and stable, although an average retraction rate of 51·62% was showed. Histological observation and immunohistochemical analysis displayed integration of the graft within the surrounding tissues. A regenerated dermis with an extracellular matrix rich in type I collagen and elastic fibres and with reduced type III collagen rate was observed. The epidermis and dermoepidermal junction featured a normal appearance with well-structured dermal papillae, too. Although the histological features would suggest regeneration of a skin-like tissue, with a good dermis and no signs of scarring, the clinical problem of secondary contracture is still unsolved.

Effects of Comano Spring Water-derived Bacterial Lysates on Skin Regeneration: An Ex-vivo Study.

BACKGROUND/AIM: A native non-pathogenic bacterial microflora was identified in Comano (TN, Italy) spring water. The aim of this study was to investigate the regenerative effects of some of the bacterial lysates extracted from this water in a human ex-vivo skin experimental wound model. MATERIALS AND METHODS: Bacterial lysates were extracted from four new isolates: lysate 1 (L1) - closest relative Rudaea cellulosilytica, phylum Proteobacteria; lysate 2 (L2) - closest relative Mesorhizobium erdmanii, phylum Proteobacteria; lysate 3 (L3) - closest relative Herbiconiux ginseng, phylum Actinobacteria; lysate 4 (L4) - closest relative Fictibacillus phosphorivorans, phylum Firmicutes. Their regenerative effects were investigated in a human ex-vivo skin experimental wound healing model at 3 (T1), 5 (T2), and 10 days (T3). RESULTS: The samples cultured with the L2 lysate displayed both an earlier and complete restoration of all the skin layers and their features were the closest to the normal skin. The regenerated epidermis demonstrated a complete maturation as the normal epidermis. The papillary dermis appeared mature, and the reticular dermis displayed both collagen and elastic fibres regularly parallel to the skin surface. An anti-inflammatory effect was displayed by the L1 lysate, but this action did not constitute a regenerative effect, suggesting that pathways for inflammation and regeneration might be different. CONCLUSION: The therapeutic power of spring waters is not exclusively related to their mineral composition, but it may also be attributable to their native non-pathogenic bacterial microflora.

Immediate Postoperative Treatment of Keloids with Intraoperative Radiation Therapy Technology: A Pilot Study.

BACKGROUND: The combination of surgery and postoperative radiotherapy allows for the most effective results with keloids. In this trial, surgery and intraoperative radiation therapy (IORT) technology were used-the hypothesis being that the earlier the application of postoperative radiotherapy, the better the wound healing evolution. METHODS: The study included 16 patients with 21 keloids. The keloids were radically excised and repaired with direct suture or local skin flaps. Collimated electron radiotherapy was applied within 45 minutes of surgery. The outcomes were assessed according to the modified Patient and Observer Scar Assessment Scale; the modified Vancouver Scar Scale; and the modified Common Terminology Criteria for Adverse Events v. 4.0 for skin and subcutaneous tissue disorders. RESULTS: Recurrences were observed in one out of 16 patients, and in two out of 21 keloids (9.5%). The modified Patient and Observer Scar Assessment Scale demonstrated a statistically significant improvement in pain, itching, color, stiffness, thickness, and irregularity after the treatment. The modified Patient and Observer Scar Assessment Scale displayed a statistically significant improvement in the scar vascularity, pigmentation, thickness, and pliability after the treatment. The modified Vancouver Scar Scale demonstrated a statistically significant improvement in 90.48% of the scars after the treatment. The modified Common Terminology Criteria for Adverse Events v. 4.0 for skin and subcutaneous tissue disorders demonstrated an improvement in erythema multiforme and skin pain across the whole sample, with a temporary hyperpigmentation in 19% of the scars after the treatment. CONCLUSION: The combination of surgery and collimated electron radiotherapy with IORT technology demonstrated favorable results in 90.5% of the cases.

Pathological nerve patterns in human basal cell carcinoma.

The peculiar combined, or binary involvement of epithelium and stroma makes basal cell carcinoma (BCC) a unique tumour. Nerve fibres have been shown to play an active role in different cancers. A prospective observational study was carried out on punch biopsies harvested within BCC surgical excision specimens. A total of 10 samples of histologically diagnosed BCC, derived from 10 different patients (five females, five males), was included in the study. Within the BCCs, seven different histological sub-types were identified: morphea-like, basosquamous, micronodular, mixed nodular-micronodular, adenoid, nodular and superficial multifocal. Nerve fibres were stained for indirect immunofluorescence targeting protein gene product 9.5. Three different morphological patterns of nerve fibre distribution within the BCCs were identified. Pattern 1 displayed a normal skin nerve pattern, in which the fibres were dislodged by the growing tumour masses. Pattern 2 featured a ball of curved, tangled nerve fibres close to the tumour masses, slightly resembling piloneural collar nerve fibres, wrapped around hair follicles in the normal anatomical setting. Pattern 3 showed nerve fibres crowding in the sub-epidermal layer with focal epidermal hyperinnervation. Such a pattern is reminiscent of the typical anatomical neuro-epithelial interaction in mechanosensory organs. Our study may disclose a hidden third player, of nerves. Thus, tissue involvement of BCCs may be better represented by the triad of epithelium, stroma and nerves, each component retaining some features associated with its developmental setting.

Allogenic platelet gel in the treatment of pressure sores: a pilot study.

Although platelet gel is considered one of the most popular tools in the treatment of chronic ulcers, current consensus on its use is not unanimous. A prospective randomised trial was carried out at the Plastic Surgery Unit of the 'Salvatore Maugeri' Foundation Hospital of Pavia (Italy). The study involved 13 patients affected by spinal cord injury with 16 pressure sores over a period of 20 months. The ulcer was considered the experimental unit of the study irrespective of the number of ulcers per patient. Each consecutive ulcer was randomised to be treated either with allogenic platelet gel or with current best practice approach to chronic wounds dressing protocol. At the end of the treatment 15 ulcers out of 16 improved clinically. No statistically significant difference was demonstrated in volume reduction between the two groups, although a statistically significant difference could be demonstrated in the onset time of granulation tissue proliferation as in the wounds treated with platelet gel the healing process was triggered earlier. Our study suggests that platelet gel is mostly effective within the first 2 weeks of treatment while a prolonged treatment does not provide any significant advantage versus the current best practice approach to chronic wounds protocols.

Nonmelanoma Skin Cancers: Embryologically Relevant Sites and UV Exposure.

BACKGROUND: Traditionally, nonmelanoma skin cancers (NMSCs) are considered mainly UV-related malignancies. Nevertheless, a strong correlation between the embryologically relevant sites (ERS) of the head and neck and the preferential sites of onset of basal cell carcinomas (BCCs) has long been supposed and demonstrated. The aim of this research was the investigation of the potential correlation between the ERS of the head and neck and the sites of tumor onset in all of the NMSCs. METHODS: The distribution of 1165 NMSC was correlated with the ERS of the head and neck using the universally accepted anatomical diagrams featuring the congenital head and neck clefts and an original anatomical diagram showing the most credited sites of the embryonic fusion planes of the auricle. RESULTS: In our sample, both BCC and SSC display an increased likelihood of onset in the ERS of the head and neck. A proportion of 93.10% BCCs was distributed within ERS, while 6.90% derived from non-embryologically relevant sites (P < 0.001). A proportion of 69.70% SCCs was distributed within ERS, while 30.30% derived from non-embryologically relevant sites (P < 0.001). The probability of tumors within ERS was significantly higher for BCC versus SCC (P < 0.001), with BCCs having a 5-fold increase in the probability of occurring in ERS compared to SCCs (P < 0.001). CONCLUSIONS: The ERS might host areas of cellular instability yielding to the development of an NMSC. The environmental UV exposure plays a relatively main role versus dysontogenic factors in the pathogenesis of SCC.

Breast sculpturing: overcoming the limits of traditional approaches in breast reduction.

BACKGROUND: A technique based on original refinements of the vertical breast reduction was developed in our department. The aim of the technique was the safe and aggressive sculpture of an attractive breast mound with minimal scarring and long-lasting results that is easy to perform and suitable for teaching purposes in a surgical training unit. METHODS: Fifty consecutive patients who were to undergo bilateral breast reduction were prospectively enrolled in the study. Accurate standard anthropometric measurements and photographs were taken preoperatively and postoperatively at 2, 6, 12, 24, and 36 months. A selective breast liposuction plus a superior pedicle breast reduction with a vertical scar skin pattern was performed in all cases. RESULTS: Nipple lifting ranged from 5 to 14 cm; reduction of the distance between the inframammary fold and the nipple ranged from 0.5 to 7 cm; breast base width reduction ranged from 0 to 7 cm. CONCLUSION: This technique further contributes to vertical mammaplasty refinements, enhancing the key role of selective liposuction prior to surgical dissection of the breast. The basic principle is to convert a large breast into a middle-sized one, making vertical scar breast reduction the most appropriate technique for all cases. A thorough and selective liposuction of the breast mound reduces the breast cone base width safely and with virtually no limitations, thus breaking a taboo of traditional breast reduction techniques.

The Role of Autologous Dermal Micrografts in Regenerative Surgery: A Clinical Experimental Study.

The aim of the study was the objective assessment of the effectiveness of a microfragmented dermal extract obtained with Rigenera™ technology in promoting the wound healing process in an in vivo homogeneous experimental human acute surgical wound model. The study included 20 patients with 24 acute postsurgical soft tissue loss and a planned sequential two-stage repair with a dermal substitute and an autologous split-thickness skin graft. Each acute postsurgical soft tissue loss was randomized to be treated either with an Integra® dermal substitute enriched with the autologous dermal micrografts obtained with Rigenera™ technology (group A-Rigenera™ protocol) or with an Integra® dermal substitute only (group B-control). The reepithelialization rate in the wounds was assessed in both groups at 4 weeks through digital photography with the software "ImageJ." The dermal cell suspension enrichment with the Rigenera™ technology was considered effective if the reepithelialized area was higher than 25% of the total wound surface as this threshold was considered far beyond the expected spontaneous reepithelialization rate. In the Rigenera™ protocol group, the statistical analysis failed to demonstrate any significant difference vs. the controls. The old age of the patients likely influenced the outcome as the stem cell regenerative potential is reduced in the elderly. A further explanation for the unsatisfying results of our trial might be the inadequate amount of dermal stem cells used to enrich the dermal substitutes. In our study, we used a 1 : 200 donor/recipient site ratio to minimize donor site morbidity. The gross dimensional disparity between the donor and recipient sites and the low concentration of dermal mesenchymal stromal stem cells might explain the poor epithelial proliferative boost observed in our study. A potential option in the future might be preconditioning of the dermal stem cell harvest with senolytic active principles that would fully enhance their regenerative potential. This trial is registered with trial protocol number NCT03912675.

Platelet Rich Plasma Enhancement of Skin Regeneration in an ex-vivo Human Experimental Model.

This study reports on the development of an original, ex-vivo wounded skin culture protocol using autologous Platelet Rich Plasma (PRP) and enriched Dulbecco's Modified Eagle's Medium (DMEM). Human skin samples obtained from specimens harvested during reduction mammoplasty procedures, were injured in their central portion-to create a standard wound-and cultured under three different conditions: - enriched DMEM with saline solution in the central wound (control)- enriched DMEM with the same medium in the central wound- enriched DMEM plus 2.5% autologous PRP, with the same PRP added medium in the central wound. Morphological analysis was carried out at 0 h (T0) and on days 1, 3, 5 and 10 (T1-T3-T5-T10) using Hematoxylin and Eosin; Masson's trichrome staining; Weigert staining and Ki-67 staining to identify the skin histological features in the different experimental conditions. The combination of DMEM and PRP allowed a favorable modulation of the epithelial cells and fibroblasts proliferation, and a relevant anti-inflammatory action. PRP also demonstrated an inhibitory effect on both the collagen and elastic fibers' de-structuration and a favorable modulation of the re-organization of these fibers. The step by step histological and immune-histo-chemical regenerative effects of PRP on human skin wound repair and regeneration process was observed over a period of 10 days.

Correlation Between the Sites of Onset of Basal Cell Carcinoma and the Embryonic Fusion Planes in the Auricle.

OBJECTIVES: This study aims at the identification of the distribution of basal cell carcinomas (BCCs) in the auricle in correlation with the currently most credited sites of the embryonic fusion planes of the auricle. METHODS: An overall number of 69 patients with 72 BCCs of the auricle were enrolled in the study over a period of 14 years, from June 2003 to October 2017. All the cases underwent medical preoperative digital photography and the specific location of each BCC was coded on an original full-size anatomical diagram of the auricle derived from the reports by Streeter, Wood-Jones, Park, Porter, and Minoux showing the currently most credited sites of the embryonic fusion planes arbitrarily featured as two 5-mm-wide ribbon-like areas: (1) the hyoid-mandibular fusion plane (HM-FP) running from the upper margin of the tragus toward the concha and then deflecting toward the lower margin of the tragus and (2) the free ear fold-hyoid fusion plane (FEFH-FP) running from the cranial-most portion of the helix to the mid-portion of the ascending helix. The latter fusion planes were comprehensively termed embryological fusion planes (EFP) while all of the remaining surface of the auricle was comprehensively termed non-fusion area (NFA). The surfaces of all of the latter areas were calculated using the ImageJ software. RESULTS: According to our data, the greatest number of BCCs was observed within the currently most credited sites of the embryonic fusion planes of the auricle. The latter sites displayed a 12-fold increased tumor incidence in comparison with the remaining surface of the ear. CONCLUSIONS: A correspondence between the sites of onset of BCCs and the sites of merging and/or fusion of embryonal processes was demonstrated in the auricle. Therefore, the latter sites might be considered as high-risk areas for the development of a BCC. Such an evidence provides further support to the hypothesis of an embryological pathogenesis of BCC.

Unrecognized Cell Torpidity as a Risk Factor in Elective Plastic Surgery.

Supplemental Digital Content is available in the text.

Generation of human epidermal constructs on a collagen layer alone.

Because engineered tissues are designed for clinical applications in humans, a major problem is the contamination of cocultures and tissues by allogenic molecules used to grow stem cells in vitro. The protocols that are commonly applied to generate epidermal equivalents in vitro require the use of irradiated murine fibroblasts as a feeder layer for keratinocytes. In this study, we report a simple procedure for growing human keratinocytes, isolated from adult skin, to generate an epidermal construct on a collagen layer alone. In this model, no human or murine feeder layers were used to amplify cell growth, and isolated keratinocytes were seeded directly at high cell density on the collagen-coated flasks or coverslips in an epithelial growth medium containing low calcium concentration. Morphological, immunochemical, and cytokinetic features of epithelial colonies grown on the collagen layer were typical of keratinocytes and were comparable with those reported for keratinocytes grown on a feeder layer. The stratification of keratinocytes generated 3-dimensional synthetic constructs displaying a tissue architecture comparable with that of natural epidermis. Epithelial cells expressed specific markers of keratinocyte terminal differentiation, including involucrin and filaggrin. Nevertheless, the number of cell layers was lower than in natural skin, and electron microscopical analysis revealed that the overall organization of these layers was poor compared with natural epidermis, including the formation of junctional complexes, basement membrane, and keratinization. The lack of epithelial-mesenchymal interactions that occur during skin histogenesis may account for such an incomplete maturation of epidermal constructs.