Peripheral Blood Mononuclear Cells (PB-MNCs) for the treatment of chronic tissue dystrophy in a complex case of lower limb reconstruction.

BACKGROUND: Recently, the infiltration of a subpopulation of cells represented by mononucleated cells extracted from peripheral blood [Peripheral Blood-Mononuclear Cells (PB-MNCs)] is becoming a useful technique for medical and surgical regenerative procedures. Due to the angiogenetic and regenerative properties of PB-MNCs, the infiltration of these cells is, in our opinion, a new option indicated in the treatment of pathologies characterized by tissue dystrophy, loss of vascularization, and non-healing wounds. CASE PRESENTATION: A 25-year-old active smoker patient was diagnosed with Rhabdomyosarcoma of the anterior tibial muscle of his left leg and treated with neoadjuvant chemo- and radiotherapy (RT). After the tumor excision, the patient developed wound dehiscence with bone exposure and a perilesional radiation-induced chronic dermatitis characterized by skin dyschromia and hair thinning along the treated area. The patient underwent surgical debridement and reconstruction with autologous skin grafts and dermal substitutes, with poor outcomes due to graft failure. The patient was subsequently treated with surgical debridement and coverage with a reverse sural fascia-cutaneous flap. After 13 days, wound dehiscence was observed, and reconstruction of the dehiscent areas was performed with a split-thickness autologous skin graft with no success. After wound debridement, a new split-thickness skin graft was performed, and a concentrate of autologous PB-MNCs was injected in the flap and perilesional skin. After 14 days, graft take was reached, and improvements in perilesional tissue tropism were noted. At 2 months follow-up, the patient appeared completely healed. CONCLUSIONS: In our opinion, the use of PB-MNCs to treat conditions characterized by tissue dystrophy, which require neoangiogenesis and cell regeneration, can be a useful and unconsidered technique that could be utilized to improve tissue tropism. Furthermore, prospective trials are necessary to validate our observations.

Inhibiting DNA methylation as a strategy to enhance adipose-derived stem cells differentiation: Focus on the role of Akt/mTOR and Wnt/ß-catenin pathways on adipogenesis.

Adipose-derived mesenchymal stem cells (ASCs) represent a valid therapeutic option for clinical application in several diseases, due to their ability to repair damaged tissues and to mitigate the inflammatory/immune response. A better understanding of the underlying mechanisms regulating ASC biology might represent the chance to modulate their in vitro characteristics and differentiation potential for regenerative medicine purposes. Herein, we investigated the effects of the demethylating agent 5-azacytidine (5-aza) on proliferation, clonogenicity, migration, adipogenic differentiation and senescence of ASCs, to identify the molecular pathways involved. Through functional assays, we observed a detrimental effect of 5-aza on ASC self-renewal capacity and migration, accompanied by actin cytoskeleton reorganization, with decreased stress fibers. Conversely, 5-aza treatment enhanced ASC adipogenic differentiation, as assessed by lipid accumulation and expression of lineage-specific markers. We analyzed the involvement of the Akt/mTOR, MAPK and Wnt/ß-catenin pathways in these processes. Our results indicated impairment of Akt and ERK phosphorylation, potentially explaining the reduced cell proliferation and migration. We observed a 5-aza-mediated inhibition of the Wnt signaling pathway, this potentially explaining the pro-adipogenic effect of the drug. Finally, 5-aza treatment significantly induced ASC senescence, through upregulation of the p53/p21 axis. Our data may have important translational implications, by helping in clarifying the potential risks and advantages of using epigenetic treatment to improve ASC characteristics for cell-based clinical approaches.

ADM-assisted prepectoral breast reconstruction and skin reduction mastectomy: Expanding the indications for subcutaneous reconstruction.

BACKGROUNDS: Recently a flood of new techniques and studies have been released for prepectoral reconstruction, following strict criteria for selection of patients undergoing skin or nipple sparing mastectomy. Nevertheless a big population of patients that would otherwise benefit from prepectoral techniques has been excluded so far. PATIENTS AND METHODS: Between January 2016 and February 2017, patients undergoing skin reducing mastectomy (SRM) were enrolled at our Institution. We selected patients with large and ptotic (grade II-III) breasts undergoing SRM, followed by a new technique, which involves placement of the implant, wrapped by acellular dermal matrix, in a prepectoral pocket under a dermal flap. Data of all the surgeries were prospectively collected and contracture grade was assessed by Baker scale. Complication rate and cancer recurrence were reported and health related quality of life (HRQOL) measurement was recorded using BREAST-Q questionnaire. At early follow-up, postoperative pain was assessed through VAS scale. RESULTS: 29 patients underwent SRM and 10 patients, meeting inclusions criteria, were enrolled, with a total of 13 operated breasts. Postoperative average pain was assessed as low as 4.1. The median follow-up was 2.6 (range 2.1-3.2) years. Post-operative complications occurred in 1 case of minimal wound dehiscence. No patient reported breast seroma or severe capsular contracture grade. Patient scored high level of satisfaction with breast, psychosocial well-being, sexual well-being, physical impact and overall satisfaction with outcome, at BREAST-Q questionnaire. CONCLUSIONS: In this study we present a modified prepectoral technique for patients undergoing SRM, reporting satisfactory outcomes. These results might support the rationale for expanding the population target of prepectoral reconstruction.

Depression risk among patients with chronic wounds.

OBJECTIVE: A wound is defined as chronic when it requires more than 6 weeks to heal. The link between chronic wounds and depression was first pointed out by House and Hughes in 1996 and later evaluated by other numerous studies. Several studies demonstrate that among chronic skin wounds causing chronical physical disease, the leg ulcers are the most frequently associated with depression. The aim of our study is to evaluate the prevalence of depression in patients with different types of chronic wounds. PATIENTS AND METHODS: We enrolled a total of 33 patients with chronic wounds and 33 healthy controls matched by sex and age. Both patients and controls underwent a BDI II survey. We evaluated 33 patients, with a mean age of 71 years (range 25-87), and 33 controls, with a mean age of 73 years (range 31-88). RESULTS: The average score at the BDI II questionnaire was 14.5 and 8, respectively. CONCLUSIONS: The depression among patients with chronic wounds has a multifactorial origin that should be treated with a multidisciplinary approach. Since the improvement of the psycho-emotional state means better compliance of the patient, we can also expect a better result in terms of efficacy in chronic wound treatment.

A retrospective comparative analysis of risk factors and outcomes in direct-to-implant and two-stages prepectoral breast reconstruction: BMI and radiotherapy as new selection criteria of patients.

Recently prepectoral breast reconstruction (PBR) has showed acceptable outcomes in the short-term. There are few evidence on long-term results and variables which could influence surgical safety. So far, no specific guidelines or indications have been developed for prepectoral technique and heterogeneous inclusion criteria had been used in previous reports. This study revises a series of 397 patients. We conducted a retrospective comparative analysis of risk factors and outcomes between patients undergoing direct to-implant (DTI) and patients undergoing two-stages expander-assisted (TSE) PBR. Univariate binary logistic regression was performed to investigate the association between the incidence of postoperative and aesthetic complications and several variables. 521 breasts were included in the analysis, with an average follow-up of 38 months. 210 patients underwent DTI and 187 TSE PBR. No statistical differences were found between the two populations in term of the characteristics of patients, surgeries and outcomes. Binary logistic regression found no significant association in the TSE group. In the DTI group, a significant association was found between surgical complications and BMI and adjuvant radiotherapy. The association remained significant only for BMI, when investigated with the onset of aesthetic complications. Lower BMI and adjuvant radiotherapy are significantly associated to a higher risk of developing a surgical complication in DTI PBR. Patients at lowest BMI with DTI are prone to develop an aesthetic complication. According to this analysis, we suggest to carefully choose candidates for PBR and propose new selection criteria for subcutaneous techniques.

Comparison between antimicrobial-coated sutures and uncoated sutures for the prevention of surgical site infections in plastic surgery: a double blind control trial.

OBJECTIVE: Surgical site infection (SSI) produces considerable morbidity and increases health care costs. One of its causes is microbial adherence to the surgical sutures surface. A strategy to avoid microbial colonization is the use of antimicrobial-impregnated sutures. Recently absorbable sutures treated with chlorhexidine (CHX) have been developed. Our study purpose was to compare CHX-coated and uncoated suture in elective plastic surgery. PATIENTS AND METHODS: We conducted a randomized, double-blind, single-centre controlled trial of 18 patients undergoing elective bilateral mammary surgery and 18 patients undergoing skin lesions removals. Patients were divided into 2 groups receiving antibacterial-coated (study group) and uncoated (controlled group) sutures for wound closure. Patients were evaluated for scar results and signs of SSIs were monitored over a period of 30 days (or 1 year in case of prosthetic surgery). Statistical comparison was performed using dependent t-tests for paired samples. RESULTS: For patients undergoing mammary surgery, based on Vancouver Scale, there were no significant differences between the two groups. We noticed that in 8 patients the vertical scars belonging to the control group were larger than the contralateral 8 vertical sutures belonging to the study group. For patients undergoing skin surgery, surgical wounds treated with uncoated sutures were significantly more erythematous than the ones belonging to the study group (Media: 0,8333% vs. 1,5556%, respectively; standard deviation: 9,235 vs. 0,6157; 95%; p=0.0092). CONCLUSIONS: No wounds infection was reported between the two groups. Based on our experience, we conclude that the use of CHX-coated sutures should be considered in case of inflamed lesions removal. Further studies are needed to validate our results.

Effectiveness of antimicrobial-coated sutures for the prevention of surgical site infection: a review of the literature.

OBJECTIVE: Surgical site infections (SSIs) are the third most common hospital-acquired infections and account for 14% to 16% of all such infections, and suture material may play a role in SSI rate. Given this risk of infection, sutures with antimicrobial activity have been developed. Both in vitro and in vivo experiments have shown that triclosan-coated sutures (TCS) are effective in the prevention of SSIs. Our aim is to analyze currently available RCTs, comparing the effect of antimicrobial-coated suture (ACS) with uncoated suture on the occurrence of SSIs following surgical procedures, we highlighted major contributions of most significant studies and evaluate the current "state of the art" on antimicrobial-coated sutures. MATERIALS AND METHODS: We reviewed 15 RCTs comparing antimicrobial-coated sutures with conventional sutures and assessing the clinical effectiveness of antimicrobial sutures to decrease the risk for SSIs. We focused our attention on each variable in all the analyzed study. RESULTS: Our selected RCTs, produced controversial results: 7 RCTs demonstrated a significant benefit, on the contrary, 8 RCTs presented a comparison in which there was no difference. CONCLUSIONS: On the basis of our selected trial results and the heterogeneous findings of our 7 selected meta-analyses, we conclude that even though the question of whether TCSs could reduce the occurrence of SSI remains still open, the antimicrobial suture was effective in decreasing the risk for postoperative SSIs in a broad population of patients undergoing surgery. Alternative substances are becoming clinically relevant, such as Chlorhexidine (CHX) coated sutures and only 6 in vivo scientific studies evaluated them. In vivo studies, large and comparative clinical research trials are necessary to validate the efficacy of CHX-coated sutures thus allowing their use in clinical practice.

Axillary ectopic lobular carcinoma of breast: two rare case reports.

OBJECTIVE: The presence of ectopic or supernumerary breast tissue is a rare event, related to a not complete regression of breast tissue along the milk line. Primary ectopic breast cancer of the axilla can create many difficulties in differential diagnosis with subsequent delayed specific treatments. The incidence of ectopic breast tissue is 0.2-6%, and the axilla is the most common site involved. In this tissue, the same physiologic and pathologic changes as seen in ectopic breast tissue may occur, including carcinoma formation. PATIENTS AND METHODS: Two patients (a 56 years old and 70 years old women) came to our attention for the recent development painless nodular axillary lesions, clinically characterized by an increased thickness, irregular margins and adherence to the floors below. RESULTS: Patients underwent ultrasonography (US) and mammography (MMG) revealing non-specific features of the lesions. Magnetic resonance imaging (MRI), demonstrated margins slightly irregular and a non-specific appearance of each lesion. Both patients underwent wide local excision with axillary lymph node dissection. Histological examination showed infiltrating lobular carcinomas of the breasts. CONCLUSIONS: We describe two unusual cases of ectopic axillary breast carcinoma localization. It is important a correct and fast diagnosis with a local examination, diagnostic instruments, surgical excision and histological examination.

One-stage breast reconstruction techniques in elderly patients to preserve quality of life.

OBJECTIVE: The aim of this study was to review one-stage breast reconstruction techniques performed in elderly patients at our institution to identify the criteria of selection of each in terms of outcomes and quality of life. PATIENTS AND METHODS: Patients older than 65 years who underwent one-stage breast reconstruction between January 2004 and July 2014 at our hospital were included. Patients and procedure-related data were collected from the medical records. In particular, patient's age, comorbidities and related ASA physical status, type of one-stage breast reconstruction technique, and criteria of selection were analyzed. Outcomes and results were also evaluated in terms of quality of life using the EORTC QLQ-C30 and -BR23 questionnaires 1 year after surgery. RESULTS: A total of 840 women underwent breast reconstruction, of whom 138 elderly women received one-stage breast reconstruction. There were 118 cases (85.5%) of monolateral reconstructions and 20 cases (14.5%) of bilateral reconstructions, resulting in 138 breast reconstructions. These were performed with permanent inflatable expanders in the sub-muscular position (Group A, n= 50), with acellular dermal matrix and partial sub-muscular anatomic implant (Group B, n= 50), and with Braxon® acellular dermal matrix and anatomic implant with muscle-sparing technique (Group C, n= 38). The EORTC questionnaires showed the best results in Group C regarding the quality of life. CONCLUSIONS: The elderly population is rapidly increasing, and 50% of all breast cancers occur in women older than 65 years; among them, only 2% undergo breast reconstruction. A major aspect of breast cancer treatment and subsequent quality of life is the opportunity for a post-mastectomy reconstructive surgery. As survival rates are improving, a larger proportion of patients live with the long-term consequences of their treatment, and breast reconstruction ensures a better quality of life. To increase the reconstruction rates, surgery should be one-stage, less invasive as possible, allowing rapid recovery, especially in elderly women, in whom comorbidities are often present with a higher anaesthetic risk. Our study highlighted that non-skin sparing mastectomy (SSM) and delayed reconstructions should be addressed with Becker implants; immediate reconstructions after SSM should be followed by acellular dermal matrix (ADM)-assisted implant reconstruction, preferring the wrap technique offers a better quality of life in elderly patients.

Caustic burn caused by intradermal self administration of muriatic acid for suicidal attempt: optimal wound healing and functional recovery with a non surgical treatment.

BACKGROUND: Caustic burns are burns of third and fourth degree caused by strong acids or strong bases. Muriatic acid is often used for suicidal attempt by ingestion. We describe a case of a caustic skin lesion caused by intravenous failed attempt of suicide by injection of Muriatic acid in a woman affected with bipolar-syndrome. Generally, caustic burns are treated by cleansing, escarectomy and coverage with skin grafts. CASE REPORT: We treated the patient with a non invasive technique with collagenase and hyaluronic acid sodium salt cream (Bionect start®), hyaluronic acid-based matrix (Hyalomatrix®) and Vacuum-Assisted Closure (VAC) Therapy®. RESULTS: We obtained complete healing in 6 weeks. CONCLUSIONS: Combined use of non invasive techniques seems to ensure only advantages for both the patients and the Health System. It reduces health care costs and risks for the patients such as nosocomial infections. Patient's compliance is high, as its quality of life. Complete healing of the wound is fast and recovery of function is full.

A new association between hyaluronic acid and collagenase in wound repair: an open study.

BACKGROUND: Most ulcers occur with slough and need debridement treatment. Surgical treatment is usually performed but many patients need an additional chemical therapy to promote healing process. This type of wound bed preparation is slower than surgical one, but it is essential in those patients who are not eligible for surgery because of systemic diseases. A collagenase derived from the bacterium Clostridium hisolyticum is the most used. AIM: To evaluate the safety and the effectiveness of a new collagenase produced by Vibrio algynoliticum. MATERIALS AND METHODS: Forty patients were enrolled and daily treated for five weeks with Bionect Start® ointment. Parameters took into account were fibrin degradation and pain relief. The same team carried out treatment during the study period of five weeks. RESULTS: 32 patients achieved a relevant reduction of the ulcer size, an improvement of the wound bed and a reduction of fibrin and exudates. Among of 32, 14 patients presented with a complete healing. Eight patients had mild or no improvements. The patients referred a remarkable pain reduction, 20 out of 40 patients reported a decrease in pain during treatment, 16 patients referred no pain at all and four patients had no significant changes. CONCLUSIONS: The application of this product on the lesions promotes vascularized granulation tissue and reduces formation of fibrin and exudate. Furthermore, a macroscopical margins proliferation is highlighted after a short time and an improvement of periwound skin is observed during the treatment period. Bionect Start® allowed easy removal of dressing, less pain for patient, reduction of dressing time.

Management and follow-up of a patient with Familial Atypical Multiple Mole-Melanoma (FAMMM) Syndrome.

INTRODUCTION: Familial Atypical Multiple Mole-Melanoma Syndrome (FAMMM) is an autosomal dominant genodermatosis characterized by the presence of a high number of dysplastic nevi and family history of melanoma or pancreatic cancer. Melanomas in FAMMM patients tend to occur at a younger age, although they are clinically similar to sporadic melanomas in terms of overall survival. CASE REPORT: A 45 year-old woman with a family history of melanoma, a type II phototype and numerous (>100) nevi was admitted to our Department of Dermatology and Plastic Surgery. Over the past years, the patient underwent several surgical operations to remove pigmented lesions and two are dysplastic nevi. Since 1995, she underwent surgery to remove four melanomas. She is followed for skin examinations including dermoscopy. CONCLUSION: Identifying high-risk patients for melanoma represents a primary objective for the specialists that are involved in the management of this disease, especially in order to enact all the necessary surveillance and follow-up strategies.

Lipofilling in skin affected by radiodermatitis: clinical and ultrasound aspects. Case report.

In recent years, lipofilling has established itself as one of the most effective and least invasive techniques to treat connective dystrophy subsequent to radiotherapy. We report the case of a patient diagnosed with intraductal carcinoma of the right breast in 1996, at the age of 41. The patient underwent quadrantectomy with ipsilateral axillary lymph node dissection and adjuvant chemotherapy and radiotherapy. Four years later, a recurrence led the patient to undergo a subcutaneous mastectomy and immediate reconstruction, involving the submuscular insertion of a permanent implant. In 2007 the patient suffered both radiodermatitis and capsular contracture around the implant, causing constant pain and significant functional limitation. She first took a leukotriene inhibitor (Zafirlukast, 20 mg daily for 8 months) to reduce the capsular contracture. She then underwent lipofilling (Coleman's technique) of the area affected by radiodermatitis, in which the skin was considerably thinned and visibly ischemic. A second session followed four months later. Clinical, photographic and ultrasound examination revealed clear and lasting thickening of the superficial tissues, increased coverage of the implant, and reduced skin discoloration and tension.

Lip cancer: a 10-year retrospective epidemiological study.

BACKGROUND: Lip cancer is the most frequent tumor of the oral-maxillary region. A high incidence of lip cancer has been reported among the Italian population over the past decade. MATERIALS AND METHODS: This retrospective study analyzes epidemiological data and risk factors for lip cancer among patients who presented to our department between 2000-2010. Statistical analysis for this study was calculated employing Student T and χ-square tests. RESULTS: Of 540 cases, most were found among men (82%), and those aged over 45 years (84.8%). The dominant cancer type was squamous cell carcinoma of the external lower lip (predominantly in men). We recorded high rates of chronic solar exposure, and tobacco and alcohol drinking habits in patients with squamous cell carcinoma. CONCLUSION: Individuals aged over 45 years are at higher risk for lip cancer. The high association of the examined risk factors with the rate of squamous cell carcinoma confirms their role in the development of this type of tumor.

Papillary thyroid cancer in a young woman affected by giant congenital melanocytic nevus, ultrasound diagnosis.

Data literatures report numerous association between giant congenital nevus and development alteration; only two cases describe its coexistence with thyroid disorders. However, we report the association of papillary thyroid cancer and giant congenital nevus. Papillary thyroid cancer is the most common differentiated thyroid cancer and has high prevalence in young women. In this paper we report: the case of a 18 years-old woman, affected by giant congenital melanocytic nevus on her back, who came to our observation because of one month of fever and increased volume of latero-cervical lymph nodes. Negative serologic tests allowed us to exclude lymphoma and mononucleosis. Because of the high risk (6%) that giant congenital melanocytic nevi could transform into malignant melanoma, we performed an ultrasound examination (US) of the cervical lymph nodes. The examination extended to the thyroid gland enabled us to visualize the same parenchyma alteration in both thyroid gland and lymph nodes. At last, fine-needle percoutaneus aspiration on thyroid lesion confirmed the presence of papillary carcinoma. In our case, thank to the optimal visualization of the parenchyma structure, US was diriment allowing a diagnosis of primitive thyroid lesion with an involvement of all lymph nodes in the neck. This findings legitimate the role of US as an accurate, noninvasive, radiation free and low-cost imaging technique in detecting differential diagnosis in the cervical lymphadenopathy, as well in preoperative staging thyroid carcinoma.

Cortisone-induced gigantomastia during chemotherapy.

Gigantomastia is a rare, psychologically and physically disabling condition characterized by excessive breast growth. There is no universal consensus on the definition of gigantomastia, but it is most commonly described as breast enlargement that requires removal ranging from 800 to 2000 g, or even a D cup bra size. It typically occurs in the setting of marked hormonal changes such as puberty and pregnancy; however, there have also been a number of reports of gigantomastia in the setting of autoimmune diseases. Rare association of gigantomastia included medicinal aetiologies such as penicillamine, neothetazone, and cyclosporine. The mechanism of action of these pharmacological agents remains unclear. We report the first case of gigantomastia associated with cortisone in the setting of ovary cancer treated with chemotherapy cycles after hysterectomy and bilateral adnexectomy. Moreover, we propose a clinic evidence and a metabolic theory to explain this association.

[Infiltrating ductal breast carcinoma after radiotherapy and chemotherapy for non-Hodgkin's lymphoma in a young woman. Case report]. / Carcinoma duttale infiltrante della mammella dopo radioterapia e chemioterapia per linfoma non Hodgkin in una giovane donna. Case report.

Lymphoma was one of the first cancers curable by radiotherapy and/or chemotherapy. However the increased risk of second malignancies in lymphoma survivors appeared to be the price of success of modern treatment modalities. In particular, breast cancer has been a major concern among women irradiated for lymphoma at a young age. There are several reports of breast cancer after Hodgkin's lymphoma, but few after non-Hodgkin's lymphoma. Owing to the particularity of this condition and the difficulties in its diagnosis and treatment, we wish to report the case of ductal infiltrant carcinoma of the breast in a young woman survived to a non-Hodgkin's lymphoma. Women who are survivors of pediatric lymphoma have a significantly increased risk of subsequent breast cancer compared with the general population and are at a high risk of developing bilateral disease within a short interval. Several studies have shown that the relative risk for secondary breast cancer becomes significantly increased between 5 and 9 years and rises dramatically between 15 and 19 years after lymphoma treatment. Screening programs to detect breast cancer should be initiated early after Hodgkin's and non-Hodgkin's lymphomas. Screening have to include breast self examinations every month, clinical breast examinations every 6 months, and mammography every 2-3 years. The patients should start breast self-examination at puberty. In these high-risk patients, "aggressive" biopsy is appropriate for suspicious lesions.

[The importance of periwound skin in the treatment of "difficult wound"]. / L'importanza della cute perilesionale nel trattamento delle ferite difficili.

A "difficult wound" consists of a loosing of cutaneous substance, with multi factor pathogenesis, that doesn't heal spontaneously. The treatment of this pathology is quite complex and first of all requires the analysis of the aetiopathogenesis of the wound, as it can healed only operating on its causes. Cutaneous wounds are formed by three different parts: bottom, border-edge and periwound skin, that must be analysed before every dressing, without overlooking all their components. Periwound skin is the part of skin that stretches for 10 centimetres beyond the wound edge. Our work aims to describe the importance of periwound skin in wound healing process, analysing clinical variants and specific treatment. Studying periwound skin we can provide many information in order to understand the cause of the lesion, to foresee healing time and to chance and find the most proper dressing, optimizing resources consumption.