Tissue-Material Integration and Biostimulation Study of Collagen Acellular Matrices.

BACKGROUND: Breast reconstruction after mastectomy using silicone implants is a surgical procedure that occasionally leads to capsular contracture formation. This phenomenon constitutes an important and persistent cause of morbidity, and no successful therapies are available to date. Recently, the use of acellular membranes as a protective material for silicone prostheses has been gaining attention due to their ability to prevent this adverse outcome. For this reason, the evaluation of the tissue-material integration and the induced biostimulation by acellular membranes results crucial. Evaluation of in vivo tissue integration and biostimulation induced by three different natural acellular collagen membranes. METHODS: Scanning electron microscopy was performed to analyse the membrane porosity and cells-biomaterial interaction in vitro, both in dry and wet conditions. Adipose-derived stem cells were cultured in the presence of membranes, and the colonisation capacity and differentiation potential of cells were assessed. In vivo tests and ex vivo analyses have been performed to evaluate dermal integration, absorption degree and biostimulation induced by the evaluated membrane. RESULTS: Analysis performed in vitro on the three different acellular dermal matrices evidenced that porosity and the morphological structure of membranes influence the liquid swelling ratio, affecting the cell mobility and the colonisation capacity. Moreover, the evaluated membranes influenced in different manner the adipose derived stem cells differentiation and their survival. In vivo investigation indicated that the absorption degree and the fluid accumulation surrounding the implant were membrane-dependent. Finally, ex vivo analysis confirmed the membrane-dependent behavior revealing different degree of tissue integration and biostimulation, such as adipogenic stimulation. CONCLUSION: The physico-chemical characteristics of the membranes play a key role in the biostimulation of the cellular environment inducing the development of well-organized adipose tissue.

Muscle-Sparing Skin-Reducing Breast Reconstruction with Pre-Pectoral Implants in Breast Cancer Patients: Long-Term Assessment of Patients' Satisfaction and Quality of Life.

INTRODUCTION: Breast cancer is the most frequently diagnosed tumor in women; globally, it accounts 23% of all cancer deaths. Breast reconstruction after oncologic surgery has become crucial to enhance patients' quality of life and alleviate the psychological distress related to the disease. The aim of this study was to assess quality of life and esthetic satisfaction of breast cancer patients undergoing muscle-sparing skin-reducing breast reconstruction (MS-SR) with pre-pectoral implants. METHODS: Sixty-three patients who met definite oncological and reconstructive criteria were enrolled in the study. Specific questionnaires (EORTC QLQ-C30, QLQ-BR23) were administered preoperatively, 1, and 12 months after MS-SR breast reconstruction to evaluate patients' QoL. Satisfaction with procedure and related Quality of Life were assessed through BREAST-Q questionnaire preoperatively and 12 months after surgery. RESULTS: Sixty-three breast cancer patients underwent MS-SR. Seventy-eight procedures were carried out; in 15 patients a bilateral reconstruction was performed. One month after surgery, both EORTC QLQ-C30 and QLQ-BR23 average scores demonstrated a slight drop since preoperative values, but a significant improvement in QoL was documented 12 months after BR (p < 0.05). BREAST-Q test showed significant psychophysical and esthetic satisfaction 12 months postoperatively. CONCLUSIONS: Muscle-sparing skin-reducing breast reconstruction is an established and reliable technique. EORTC QLQ-C30, QLQ-BR23 and BREAST-Q scores showed an improvement of patients' QoL and esthetic satisfaction. Reduction of pain and other surgery-related symptoms are cornerstones of patient well-being. Both physicians and patients should build a thorough awareness of the silver lining of muscle-sparing skin-reducing breast reconstruction based on the high safety profile and highly satisfactory patient-reported results.

The process of EUSOMA certification improves the quality of breast cancer care: the experience of an Italian EUSOMA certificated Breast Unit (BU) according to the results of a cross-sectional study.

INTRODUCTION: The adherence to recognized guidelines and the constant monitoring of performance throughout quality indicators (QIs) are strategic tools to improve the quality of care. The study is aimed to assess the effect of the EUSOMA (European Society of Breast Cancer Specialists) certification process on the quality of breast cancer care of an EUSOMA certified Breast Unit (BU) of Northern Italy. MATERIALS AND METHODS: Seventeen mandatory and recommended EUSOMA QIs, based on 594, were analysed for the years 2015-2018. Univariate logistic regression models were performed to compare QIs performance in the years before and after obtaining the EUSOMA certification (2015-6 vs. 2017-8). RESULTS: Compared to the years 2015-6, the second period of BU activity showed a higher number of QIs achieving both the minimum standard (15 vs. 11) and the 100% of completeness (6 vs. 1). There was a significant improvement of the two QIs evaluating the proportion of Ductal Carcinoma in situ receiving just an operation (from 76% to 95.2%; p=0.033) and the completeness of the prognostic characterisation of invasive cancers (from 94.6% to 99.5%; p=0.022). Conversely, the QI related to the endocrine-sensitive invasive carcinoma receiving adjuvant hormonal therapy dropped from 92.1% to 85.9% (p=0.042) and was significantly lower for patients over 74 compared to those aged ≤54 (73.8% vs. 94.7%; p<0.0001 Fisher's exact test). CONCLUSIONS: The EUSOMA certification process enhanced the clinical practice, promoting a tailored-patient primary systemic or adjuvant therapy and avoiding unnecessary invasive surgical and local-regional treatments.

Comparative study of patient outcomes between direct to implant and two-stage implant-based breast reconstruction after mastectomy.

BACKGROUND: Breast reconstruction plays a central role in the outcome management of patients with breast cancer, particularly in terms of quality of life (QoL), which must be weighed carefully when considering the available surgical options. In the context of implant-based breast reconstruction, immediate replacement with prosthesis (direct-to-implant (DTI)) and acellular dermal matrix (ADM) is gaining popularity, at the expense of the traditional two-stage implant-based breast reconstruction with tissue expander (TE), and the literature suggests that patients tend to prefer interventions with "immediate" therapeutic efficacy and aesthetic satisfaction that obviate the need for further invasive surgery. We investigated this hypothesis by administering the BREAST-Q™ questionnaire to two groups of patients who had undergone the respective procedures. METHODS: We performed a cross-sectional observational study of 192 consecutive mastectomy patients who received implant-based reconstruction, comparing health-related quality of life (HR-QoL), patient-related outcomes (PROs) and satisfaction in patients who had undergone immediate dual plane DTI with ADM (96) versus the two-stage submuscular approach (96). We also counted the number of surgeries required in each group to achieve a definitive outcome. FINDINGS: Our study revealed no major differences in terms of QoL scores, with the two approaches being largely comparable. However, single-stage reconstruction seems to offer the additional advantages of better satisfaction with the care received, sparing the patient temporary body image dissatisfaction and reducing the number of surgeries required, thereby lessening the burden on the patient, the healthcare system and society as a whole.

Italian recommendations on enzymatic debridement in burn surgery.

INTRODUCTION: Nexobrid®, a bromelain-based type of enzymatic debridement, has become more prevalent in recent years. We present the recommendations on enzymatic debridement (Nexobrid®)'s role based on the practice knowledge of expert Italian users. METHODS: The Italian recommendations, endorsed by SIUST (Italian Society of Burn Surgery), on using enzymatic debridement to remove eschars for burn treatment were defined. The definition followed a process to evaluate the level of agreement (a measure of consensus) among selected experts, representing Italian burn centers, concerning defined clinical aspects of enzymatic debridement. The consensus involved a multi-phase process based on the Delphi method. RESULTS: The consensus panel included experts from Italy with a combined experience of 1068 burn patients treated with enzymatic debridement. At the end of round 3 of the Delphi method, the panel reached 100% consensus on 26 out of 27 statements. The panel achieved full, strong consensus (all respondents strongly agreed on the statement) on 24 out of 27 statements. DISCUSSION: The statements provided by the Italian consensus panel represent a "ready to use" set of recommendations for enzymatic debridement in burn surgery that both draw from and complete the existing scientific literature on the topic. These recommendations are specific to the Italian experience and are neither static nor definitive. As such, they will be updated periodically as further quality evidence becomes available.

Quality of Life and Early Functional Evaluation in Direct-to-Implant Breast Reconstruction After Mastectomy: A Comparative Study Between Prepectoral Versus Dual-Plane Reconstruction.

BACKGROUND: In conservative mastectomies, in which the native skin envelope is preserved, positioning an implant in the submuscular plane commonly leads to functional consequences like upper limb movement impairment and animation phenomena. In recent years, however, a new conservative prepectoral breast reconstruction technique has been proposed, with demonstrated surgical safety and aesthetic effectiveness. The aim of our study was to explore and compare the functional and aesthetic outcomes of the prepectoral/acellular dermal matrix (ADM)-wrapped implant procedure versus subpectoral/ADM-assisted reconstruction. PATIENTS AND METHODS: A retrospective nonrandomized comparative study of 94 patients (121 breasts) undergoing direct-to-implant breast reconstruction after skin-/nipple-sparing and skin reduction was conducted from February 2013 to October 2017. Fifty-five patients (group A) received subpectoral ADM-assisted reconstruction with dual-plane implant positioning, and 39 patients (group B) received prepectoral partially or totally ADM-wrapped implant reconstruction. Patients were allocated to either group A or B depending on the mastectomy flap thickness and vitality, as assessed clinically during the operation. Details of rehabilitation program, postoperative pain at 72 hours, postoperative analgesic therapies, demographic data, and complications were recorded. Upper limb function was assessed before and 1 month after surgery by a physiatrist according to a precise protocol. Patients were asked to fill in the BREAST-Q reconstruction questionnaire after surgery to evaluate outcomes. RESULTS: Differences in upper limb function between groups, namely flexion (P = .03), abduction (P = .003), internal rotation (P = .02), and external rotation (P = .05), were statistically significant. Although most patients required postoperative rehabilitation, the individual rehabilitation intervention frequency was greater in the subpectoral group (91% in group A vs 74% in group B). There was also a significant difference in postoperative pain (within 72 hours), with less pain perceived in the prepectoral group (P = .01). Furthermore, prepectoral patients reported slightly better postoperative quality of life than subpectoral patients, particularly in the domains of sexual well-being (P = .005) and satisfaction with breast (P = .002). CONCLUSION: In our case series, prepectoral implant positioning with partial or total ADM coverage led to less impairment of upper limb function in terms of flexion, abduction, and internal and external rotation, and also reduce the need for rehabilitation. Furthermore, as a result of the less invasive procedure, prepectoral patients had less immediate postoperative pain and were more satisfied with breast appearance.

Eschar removal by bromelain based enzymatic debridement (Nexobrid®) in burns: European consensus guidelines update.

INTRODUCTION: Bromelain-based Enzymatic Debridement has been introduced as an additional concept to the burn surgeon's armamentarium and is best indicated for mid-to deep dermal burns with mixed patterns. Increasing evidence has been published focusing on special regions and settings as well as on limitations of Enzymatic Debridement to improve patient care. To better guide Enzymatic Debridement in view of the increasing experience, there is a need to update the formerly published consensus guidelines with user-orientated recommendations, which were last produced in 2017. METHODS: A multi-professional expert panel of plastic surgeons and burn care specialists from twelve European centers was convened, to assist in developing current recommendations for best practices with use of Enzymatic Debridement. Consensus statements were based on peer-reviewed publications and clinical relevance, and topics for re-evaluation and refinement were derived from the formerly published European guidelines. For consensus agreement, the methodology employed was an agreement algorithm based on a modification of the Willy and Stellar method. For this study on Enzymatic Debridement, consensus was considered when there was at least 80 % agreement to each statement. RESULTS: The updated consensus guidelines from 2019 refer to the clinical experience and practice patterns of 1232 summarized patient cases treated by the panelists with ED in Europe (2017: 500 cases), reflecting the impact of the published recommendations. Forty-three statements were formulated, addressing the following topics: indications, pain management and anesthesia, large surface treatment, timing of application for various indications, preparation and application, post-interventional wound management, skin grafting, outcome, scar and revision management, cost-effectiveness, patient´s perspective, logistic aspects and training strategies. The degree of consensus was remarkably high, with consensus in 42 out of 43 statements (97.7%). A classification with regard to timing of application for Enzymatic Debridement was introduced, discriminating immediate/very early (≤12 h), early (12-72 h) or delayed (>72 h) treatment. All further recommendations are addressed in the publication. CONCLUSIONS: The updated guidelines in this publication represent further refinement of the recommended indication, application and post-interventional management for the use of ED. The published statements contain detailed, user-orientated recommendations aiming to align current and future users and prevent pitfalls, e.g. for the successful implementation of ED in further countries like the USA. The significance of this work is reflected by the magnitude of patient experience behind it, larger than the total number of patients treated in all published ED clinical trials.

A Novel Inexpensive Technique to Seal Negative Pressure Wound Therapy on External Fixation Devices.

Negative pressure wound therapy, a tool widely applied to treat lower limb traumas, is useful in reconstructive procedures. However, obtaining an airtight vacuum seal when using a negative pressure dressing around an external fixation device can be complicated and time-consuming. The plastic drape seldom adheres to screws, pins, or wires and, as such, the vacuum seal is jeopardized. In surgical departments, colostomy paste is widely used, readily available, and applied where pins and wires make contact with the plastic drape. It is a fast, practical, and inexpensive method of preventing air leakage. In conclusion, to obtain an airtight seal between the skin and an external fixation device, colostomy paste may be used to ensure an optimal tight seal, even for complex and extended wounds, for 3-5 days without complications or the requirement for additional dressing changes. Furthermore, it is inexpensive, readily available, simple to use, and quick to apply.

Radiological anatomy of the perforators of the gluteal region: The "radiosome" based anatomy.

BACKGROUND: The superior (SGA) and the inferior gluteal artery (IGA) perforator flaps are widely used in pressure-sore repair and in breast reconstruction. The aim was to exhaustively depict the topographical anatomy of the whole system of perforators in the buttock. METHODS: Eighty lower-extremity computed tomographic angiography (CTA) of patients (20 males/20 females, mean age 61-years old, range 38-81) were considered. The source artery, location, type, and caliber of gluteal perforators were analyzed. The location of perforators was reproduced using a standardized two-dimensional grid on the coronal plane, centered onto defined bone landmarks. We defined "radiosome" the cutaneous vascular territory of a source artery inferred through the representation of its whole perforator system at the exit point through the deep fascia. RESULTS: A mean number of 25.6 ± 5.7 perforators in the gluteal region was observed, distributed as follows: 11.6 ± 4.8(45.2%) from SGA; 7.9 ± 4.5(30.8%) from IGA; 1.5 ± 0.8(5.8%) from fifth lumbar artery; 1.2 ± 0.8(4.7%) from internal pudendal artery; 1.2 ± 1(4.8%) from lateral circumflex femoral artery; 0.3 ± 0.7(1.2%) from circumflex iliac superficial artery. At least one large (internal diameter > 1 mm) SGA septocutaneous perforator was present in 77.5% of patients. CONCLUSIONS: The gluteal region is vascularized by perforators of multiple source arteries. Septocutaneous perforators of SGA and IGA were planned along a curve drawn from the posterior-superior border of the iliac crest to the greater trochanter. The lumbar artery perforators are clustered over the apex of the iliac crest; the internal pudendal artery perforators are clustered medially to the ischiatic tuberosity. Contributions can also come from the sacral and superficial circumflex iliac arteries.

Evaluation of the effectiveness of the prepectoral breast reconstruction with Braxon dermal matrix: First multicenter European report on 100 cases.

We report the outcomes of the European prospective study on prepectoral breast reconstruction using preshaped acellular dermal matrix for complete breast implant coverage. Seventy-nine patients were enrolled between April 2014 and August 2015 all over Europe using a single protocol for patient selection and surgical procedure, according to the Association of Breast Surgery and British Association of Plastic Reconstructive and Aesthetic Surgeons joint guidelines for the use of acellular dermal matrix in breast surgery. The preshaped matrix completely wraps the breast implant, which is placed above the pectoralis major, without detaching the muscle. A total of 100 prepectoral breast reconstructions with complete implant coverage were performed. This series, with mean follow-up of 17.9 months, had two cases of implant loss (2.0%) including one necrosis of the nipple and one wound breakdown (1.0% respectively). No implant rotations were observed. Good cosmetic outcomes were obtained with natural movement of the breasts and softness to the touch; none of the patients reported experiencing pain or reduction in the movements of the pectoralis major muscle postoperatively. The use of preshaped acellular dermal matrix for a complete breast implant coverage in selected patients is safe and gives satisfactory results, both from the aesthetic view point and the low postoperative complication rates. Further studies reporting long-term outcomes are planned.

Skin-Reduction Breast Reconstructions with Prepectoral Implant.

UNLABELLED: Skin-reduction mastectomy with prepectoral implant reconstruction is a novel technique for immediate breast reconstruction, with subcutaneous implant placement in patients eligible for skin-reducing mastectomy. Implants were placed above the pectoralis muscles in a compound pocket made by a dermal flap and acellular dermal matrix. The procedure was performed on 33 breasts in 27 selected patients. In three cases, there was skin ischemia; in one case, it healed spontaneously; and in two patients, a surgical necrosectomy and primary closure were needed. No implant loss occurred. This new technique proved to be a useful alternative, with good cosmetic results, in selected patients requiring mastectomy. These preliminary results need to be confirmed by long-term and comparative studies. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Association of CDK4 germline and BRAF somatic mutations in a patient with multiple primary melanomas and BRAF inhibitor resistance.

Many genetic alterations, including predisposing or somatic mutations, may contribute toward the development of melanoma. Although CDKN2A and CDK4 are high-penetrance genes for melanoma, MC1R is a low-penetrance gene that has been associated most consistently with the disease. Moreover, BRAF is the most frequently somatically altered oncogene and is a validated therapeutic target in melanoma. This paper reports a case of multiple primary melanoma with germline CDK4 mutation, MC1R variant, and somatic BRAF mutation in nine out of 10 melanomas, indicating that a common pathogenesis, because of a predisposing genetic background, may be shared among distinct subsequent melanomas of probable clonal origin. After 3 months of targeted therapy with BRAF inhibitor, our patient developed resistance with rapid progression of the disease leading to death. This is the first case in which early resistance to BRAF inhibitor has been reported in a patient with CDK4 germline mutation.

Daily serum collection after acellular dermal matrix-assisted breast reconstruction.

BACKGROUND: The acellular dermal matrix (ADM)-assisted breast reconstruction technique is widely known, but discouraging results due to early postoperative complications have been reported. As the literature identifies seroma as the most common issue after breast surgery without identifying its pathogenesis, we aimed to report the trend of postoperative daily serum collection after ADM-assisted breast reconstruction and compare it with data in the literature in order to discover more about this little-known topic. METHODS: A retrospective study on 28 consecutive patients who received ADM-assisted breast reconstruction between February 2013 and February 2014 was performed. In order to reduce the number of variables that could affect serum production, only one brand of ADM was used and all tissues were handled gently and precisely. The daily drainage volume was recorded per patient during the first four days of hospitalization. Likewise, postoperative complications were noted during routine follow-up. RESULTS: In total, five (17.9%) bilateral and 23 (82.1%) unilateral ADM-assisted breast reconstructions (33 implants) were performed. The mean age, body mass index, and length of hospital stay were 53.6 years, 21.3 kg/m(2), and 4.5 days, respectively. One major complication led to implant loss (3.0%), and nine minor complications were successfully treated with ambulatory surgery (27.3%). Serum collection linearly decreased after 24 hours postoperatively. CONCLUSIONS: Daily drainage decreased following the theoretical decline of acute inflammation. In concordance with the literature, daily serum production may not be related to the use of ADM.

The use of banked skin in the Burns Centre of Verona.

BACKGROUND: The use of glycerol and subsequent research enabling the conservation of tissues over time have led to the establishment and development of tissue banks, first in the USA and then in Europe. The Verona Tissue Bank was instituted in 2003 as the Regional Centre for the storage of skin and bone, adding to the already existing Italian banks at Turin, Milan, Cesena and Siena. This retrospective study analyses the use of banked skin (autologous and allogeneic grafts) from April 2003 (date of starting activity) to December 2007, in 171 patients with burns and four with necrotising fasciitis at the Burns Centre of Verona. MATERIALS AND METHODS: Homologous skin was used for superficial and deep skin burns to protect the residual structures, thus facilitating healing by spontaneous re-epithelialisation, and for deep burns after eschar removal to clean and prepare the base of the lesion for the definitive autologous graft. The placement of a homologous graft alone led to spontaneous healing of lesions in 65 patients (36 aged >15 years and 29 aged <15 years) with superficial skin burns, while the remaining 106 patients (84 aged >15 years and 22 aged <15 years) with deeper burns underwent surgery. CONCLUSIONS: The results obtained confirm the essential role of banked skin in covering superficial burns in order to protect important underlying structures and in deep burns by guaranteeing a good preparation of the base of the lesion for the subsequent definitive autologous graft.

[Spontaneous rupture of the femoral artery after radiotherapy: a case report]. / Rottura spontanea dell'arteria femorale dopo radioterapia: presentazione di un caso clinico.

Radiation-induced arteriopathy is a well-known disease whose incidence is not known and which usually arises chronically many years after radiation therapy. When it arises acutely, spontaneous rupture or, more rarely, thrombosis of the involved vessel may occur. Spontaneous rupture can occur within 4 to 32 weeks of radiotherapy, and usually affects the carotid artery involved in radiotherapy of the neck and head. Spontaneous rupture of the femoral artery is a very rare event and only a few cases have been reported in the literature. In this paper we report a case of spontaneous rupture of the left femoral superficial artery after adjuvant radiotherapy following surgery for a liposarcoma of the spermatic cord with multiple local recurrences, successfully treated with an extra-anatomic bypass through the obturator canal and rectal muscle flap.

Propeller flaps for leg reconstruction.

Leg soft tissue defects with bone or tendon exposure need to be covered with a flap. Various local and free flaps with more or less consistent donor site defects have been described in the past. After the introduction of the perforator-based flap concept, new flaps have also been described for the leg. An evolution and simplification of the perforator flap concept, together with the 'free style' flap harvesting method, are the propeller flaps, i.e. local flaps, based on a perforator vessel, which becomes the pivot point for the skin island that can, therefore, be rotated up to 180 degrees . In this prospective study, six consecutive patients, having post-traumatic soft tissue defects of the leg or knee prosthesis infection, with bone or tendon exposure, were treated with propeller flaps. Complete and stable coverage of the soft tissue losses was obtained in all cases with an inconspicuous, only cosmetic, donor site defect. No flap necrosis was observed, with the exception of a small superficial necrosis of the tip of one flap, due to the inclusion in the design of scarred tissue. In two cases, transient venous congestion was observed and resolved spontaneously. Mean operative time was 2 h (ranging from 60 min to 6 h when an orthopaedic procedure was also needed) and mean hospital stay after surgery was 10 days. Propeller flaps allow the coverage of wide defects, can be raised with a relatively simple surgical technique, have a high success rate and good cosmetic results without functional impairment. In the light of this they can be considered among the first surgical choices to resurface complex soft tissue defects of the leg.