Molecular Mechanisms and Physiological Changes behind Benign Tracheal and Subglottic Stenosis in Adults.

Laryngotracheal stenosis (LTS) is a complex and heterogeneous disease whose pathogenesis remains unclear. LTS is considered to be the result of aberrant wound-healing process that leads to fibrotic scarring, originating from different aetiology. Although iatrogenic aetiology is the main cause of subglottic or tracheal stenosis, also autoimmune and infectious diseases may be involved in causing LTS. Furthermore, fibrotic obstruction in the anatomic region under the glottis can also be diagnosed without apparent aetiology after a comprehensive workup; in this case, the pathological process is called idiopathic subglottic stenosis (iSGS). So far, the laryngotracheal scar resulting from airway injury due to different diseases was considered as inert tissue requiring surgical removal to restore airway patency. However, this assumption has recently been revised by regarding the tracheal scarring process as a fibroinflammatory event due to immunological alteration, similar to other fibrotic diseases. Recent acquisitions suggest that different factors, such as growth factors, cytokines, altered fibroblast function and genetic susceptibility, can all interact in a complex way leading to aberrant and fibrotic wound healing after an insult that acts as a trigger. However, also physiological derangement due to LTS could play a role in promoting dysregulated response to laryngo-tracheal mucosal injury, through biomechanical stress and mechanotransduction activation. The aim of this narrative review is to present the state-of-the-art knowledge regarding molecular mechanisms, as well as mechanical and physio-pathological features behind LTS.

Objective Selection Criteria between ALT and Radial Forearm Flap in Oral Soft Tissues Reconstruction.

Different locoregional and free flaps were described for oral soft tissues reconstruction after oncological resections; however, free flaps remain the first choice. Among free flaps, the radial forearm flap (RFF) and the anterolateral thigh perforator flap (ALT) are preferred the most. The lack of standardization of the flap choice leaves the selection to the surgeon's experience. The purpose of our observational study is to provide an algorithm to support the flap choice for the reconstruction of oral soft tissues. Sixty patients with squamous cell carcinoma of oral soft tissues were enrolled in our study. All the patients underwent preoperative magnetic resonance imaging (MRI) to measure the three-dimensional size of the tumor. During the follow-up, the patients were evaluated by using the University of Washington-Quality of Life Questionnaire. The questionnaire score was better for small tumors and worse for large tumors in both functional and relational fields. We observed that most of the overlapping results were obtained for small defects and the choice of RFF, as well as for large defects and the use of ALT. We observed that in the preoperative time, it is possible to select which flap between radial forearm and ALT is more appropriate for oral soft tissues defects reconstruction, according to the size of the tumor evaluated by MRI. We propose a decisional algorithm that suggests the type of flap to use between ALT and RFF.

Lipoaspirate Injection in Relapsing Idiopathic Subglottic Stenosis: Preliminary Results.

OBJECTIVES: The management of idiopathic subglottic stenosis (iSGS) poses a clinical challenge due to high recurrence rates following both endoscopic and open approaches, often leading to tracheostomy. The activation of abnormal T-cells and cytokine pathways has been linked to iSGS pathogenesis. Autologous adipose tissue centrifugation yields lipoaspirate, offering optimal anti-inflammatory effects and biocompatibility widely utilized in various medical settings. This report presents the first 3 cases employing endoscopic dilation (ED) in combination with local lipoaspirate injection to address recurrent iSGS. METHODS: A prospective observational study was conducted, involving multidisciplinary evaluation by the Tracheal Team at the University of Modena. Patients meeting specific criteria were directed to undergo ED + lipoaspirate injection. RESULTS: Three patients fulfilled the inclusion criteria. The mean number of prior endoscopic procedures performed was 8. Endoscopic examination revealed 90% stenosis in patient A, 60% stenosis in patient B, and 60% stenosis in patient C. All patients presented inflammatory tissue or incipient granulations at the stenotic site, with an average time of 6 months between previous procedures. After 15 months, none of the patients required further procedures, and endoscopic examination revealed a significant reduction or disappearance of inflammatory tissue with a stable airway lumen. CONCLUSIONS: The observed results are encouraging in terms of reducing local inflammation and halting stenosis progression, especially in cases of short-term relapsing iSGS.

The Overwhelming Postsplenectomy Sepsis: Role of Plastic Surgeon.

The overwhelming post-splenectomy infection (OPSI) is a feared late complication of splenectomy, with high morbidity and a mortality rate of up to 50%. Although the management of this syndrome is the duty of clinical physicians, the interest of plastic surgeons in OPSI is related to the injury that can occur in tissues with an end circulation, such as the limb extremities, nasal tip, and lips. In the management of OPSI, surgical techniques are not highlighted. The role of the plastic surgeon can be fundamental for the prevention of further extension of the necrotic tissue, improving as much as possible the vascularization around it. Moreover, a critical role in the management of OPSI is avoiding superinfection of the necrotic areas by combining different techniques and methods, such as surgical debridements, negative pressure wound therapy, and conservative treatment. Last but not least, functional and aesthetic restoration of the injured parts is of paramount importance for the final outcome. In this article, we describe the management of two unvaccinated patients with necrosis of the extremities after OPSI.

Radial forearm flap versus antero-lateral thigh flap in oral soft tissue reconstruction: update and statistical analysis on our 77 consecutive cases for an objective selection criteria.

BACKGROUND AND AIM: The radial forearm free flap (RFFf) and the antero-lateral thigh flap (ALTf) are considered the "key flaps" for oral cavity reconstruction. Nowadays, the literature lacks of an objective and standardized decision-making algorithm for the flap choice. The aim of this study is to describe a decision-making algorithm concerning the more appropriate flap, RFFf or ALTf, in the reconstruction of intra-oral soft tissues based on the volumetric analysis of the defect with a pre-operative Magnetic Resonance Imaging (MRI), updating our previous surgical experience. METHODS: We conducted a retrospective observational study including 77 patients who underwent microsurgical reconstruction with RFFf or ALTf after tumor resection of the soft tissues in the oral cavity. During follow-up, patients were evaluated using the UW-QOL questionnaire. RESULTS: Analyzing the scores of the UW-QOL questionnaire based on the size of the tumor on preoperative MRI we found that for tumor volume <50cc and between 50-70cc, the patients reconstructed with RFFfobtained statistically significant better scores compared to the ALTf group, while for tumor volume >70cc, the patients reconstructed with ALTf reported statistically significant better scores. CONCLUSIONS: Pre-operative RMI-guided volumetric assessment of oral cancer plays a key role in the planning of adequate soft tissue reconstruction and can objectively help surgeons in the correct choice of the flap (RFFf vs. ALTf) for each case based on preoperative tumor size, suggesting for defects <50cc and between 50 and 70 cc a reconstruction with RFFf, while for defects >70cc a reconstruction with ALTf.

Gynecomastia: an uncommon, destabilizing condition of the male adolescent. our therapeutic choice.

Gynecomastia is the benign enlargement of breast's the glandular tissue in male population. Gynecomastia can involve fatty and/or glandular tissue. At the basis of pediatric gynecomastia there is a multifactorial imbalance in the ratio of estrogen to androgens tissue levels. In more than 95% of the cases gynecomastia development is idiopathic. Secondary causes of gynecomastia in adolescents are relatively rare (less than 5%) and may arise from uncommon pathological conditions. Gynecomastia is self-limited and regresses in 1-3 years in 84%, 47% and 20% of adolescents with mild, moderate and severe gynecomastia. The correct first line of therapy is observation and reassurance in the treatment of mild cases. In order to manage adolescent gynecomastia is advised to adopt a tailored therapy. Despite gynecomastia is a common condition only few adolescents need cosmetic or antalgic treatment. Medical therapy should be considered in patient with emotional distress or psychological limitation on normal activities. Finally, if gynecomastia does not go in remission after two years surgical procedures should be performed. The aim of this article is to be an updated discussion of pubertal gynecomastia in every way and report our surgical experience with a retrospective study. In conclusion surgical treatment of this condition is a quiet rare procedure but, in according to global literature we demonstrated that it is a safe surgery with low rate of complications.

Case report: Endoscopic closure with double stenting and autologous fascia lata graft of large tracheo-esophageal fistula.

Introduction: Radiotherapy and esophageal stenting are usually employed to manage esophageal localization of distant cancer. However, they are also related to the occurrence of an increased risk of tracheoesophageal fistula. Tracheoesophageal fistula management in these patients involves dealing with poor general conditions and short-term prognosis. This paper presents the first case in literature of bronchoscopic fistula closure through an autologous fascia lata graft placement between two stents. Case report and aim: A 67-years-old male patient was diagnosed with pulmonary squamous cell carcinoma in the inferior lobe of the left lung with mediastinal lymph node metastasis. After a multidisciplinary discussion, bronchoscopic repair of tracheoesophageal fistula with autologous fascia lata was decided without the removal of the esophageal stent due to the high risk on the esophagus possibly related to such a procedure. Oral feeding was progressively introduced without the development of aspiration symptoms. Videofluoroscopy and esophagogastroduodenoscopy were performed at 7 months showing no signs of tracheoesophageal fistula patency. Conclusion: This technique might represent a low risks viable option for patients unsuitable for open surgical approaches.

Autologous Marrow Mesenchymal Stem Cell Driving Bone Regeneration in a Rabbit Model of Femoral Head Osteonecrosis.

Osteonecrosis of the femoral head (ONFH) is a progressive degenerative disease that ultimately requires a total hip replacement. Mesenchymal stromal/stem cells (MSCs), particularly the ones isolated from bone marrow (BM), could be promising tools to restore bone tissue in ONFH. Here, we established a rabbit model to mimic the pathogenic features of human ONFH and to challenge an autologous MSC-based treatment. ON has been originally induced by the synergic combination of surgery and steroid administration. Autologous BM-MSCs were then implanted in the FH, aiming to restore the damaged tissue. Histological analyses confirmed bone formation in the BM-MSC treated rabbit femurs but not in the controls. In addition, the model also allowed investigations on BM-MSCs isolated before (ON-BM-MSCs) and after (ON+BM-MSCs) ON induction to dissect the impact of ON damage on MSC behavior in an affected microenvironment, accounting for those clinical approaches foreseeing MSCs generally isolated from affected patients. BM-MSCs, isolated before and after ON induction, revealed similar growth rates, immunophenotypic profiles, and differentiation abilities regardless of the ON. Our data support the use of ON+BM-MSCs as a promising autologous therapeutic tool to treat ON, paving the way for a more consolidated use into the clinical settings.

Extended and unusual indications in jaw reconstruction with the fibula flap: An overview based on our 30-year experience.

Since the introduction of fibula flap as a reconstructive technique, an evolution of indications has been observed. Our first report of a traumatic mandibular reconstruction using fibula flap was in 1992. The vast majority of indications for surgery, are: malignant tumors, benign neoplasms, osteoradionecrosis and traumas. Nevertheless, extended indications have been described such as the treatment of dentoalveolar defect without bone discontinuity or reconstruction of maxilla defect up to type III (A and B), according to Cordeiro's classification. Unusual indications include cleft palate malformations with bone discontinuity less than 6 cm. Moreover, a particular attention should be focus on fibula flap harvest with more innovative technologies than traditional use of monopolar or bipolar and their advantages in pre and postoperative management.

Lipofilling after Laser-Assisted Treatment for Facial Filler Complication: Volumetric and Regenerative Effect.

BACKGROUND: Nonresorbable substances are still injected to enhance soft-tissue volumes and fill subcutaneous defects. The minimally invasive intralesional laser treatment can remove foreign substances and the inflammatory reaction, eventually leaving depression and scar tissue in the treated area. Fat grafting can restore volume loss and improve scar tissue. METHODS: From March of 2010 to February of 2017, 33 patients were studied. All of them had suffered from inflammatory reactions to permanent facial fillers and had been treated with the 808-nm diode laser at the authors' institution. The evacuation of material had left facial asymmetry and visible depression. To restore facial aesthetic units, fat grafting was performed. The minimum follow-up was 6 months. RESULTS: Volume restoration was recognized (according to the Global Aesthetic Improvement Scale) as significantly improved in 22 patients, moderately improved in eight patients, and slightly improved in three patients. Improvement in atrophic and scarred tissues (with an apparent thickening of the skin or even elimination of scars) was also assessed with the following results: 25 patients were very much improved and eight were moderately improved. CONCLUSIONS: This is the first study on filler-induced complications of the face treated by intralesional laser treatment followed by lipofilling. A systematic approach to volume restoration is proposed to patients who had filler removal of the face. There was a high degree of patient satisfaction with this technique. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Standardization and Selection of High-risk Patients for Surgical Wound Infections in Plastic Surgery.

BACKGROUND: The aim of the present study was to show that the Infection Risk Index (IRI), based on only 3 factors (wound classification, American Society of Anesthesiologists score, and duration of surgery), can be used to standardize selection of infection high-risk patients undergoing different surgical procedures in Plastic Surgery. METHODS: In our Division of Plastic Surgery at Modena University Hospital, we studied 3 groups of patients: Group A (122 post-bariatric abdominoplasties), Group B (223 bilateral reduction mammoplasties), and Group C (201 tissue losses with first intention healing). For each group, we compared surgical site infection (SSI) rate and ratio between patients with 0 or 1 risk factors (IRI score 0 or 1) and patients with 2 or 3 risk factors (IRI score 2 or 3). RESULTS: In group A, patients with IRI score 0-1 showed an SSI Ratio of 2.97%, whereas patients with IRI score 2-3 developed an SSI ratio of 27.27%. In group B, patients with IRI score 0-1 showed an SSI ratio of 2.99%, whereas patients with IRI score 2-3 developed an SSI ratio of 18.18%. In group C, patients with IRI score 0-1 showed an SSI ratio of 7.62%, whereas patients with IRI score 2-3 developed an SSI ratio of 30.77%. CONCLUSIONS: Existing infection risk calculators are procedure-specific and time-consuming. IRI score is simple, fast, and unspecific but is able to identify patients at high or low risk of postoperative infections. Our results suggest the utility of IRI score in refining the infection risk stratification profile in Plastic Surgery.

Autologous fat grafting in the treatment of a scleroderma stump-skin ulcer: a case report.

Here we describe the case of a 60-year-old-woman with systemic sclerosis sent to our Scleroderma Unit to treat digital stumps. The stumps were successfully treated with autologous fat grafting (crown-shape infiltration). Our technique of autologous lipotransfer improved wound healing in a scleroderma patient with stump-digital ulcers where all other options failed.

Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression.

INTRODUCTION: Adipose tissue (AT) has become a source of mesenchymal stromal/stem cells (MSC) for regenerative medicine applications, in particular skeletal disorders. Several enzymatic or mechanical procedures have been proposed to process AT with the aim to isolate cells that can be locally implanted. How AT is processed may impact its properties. Thus, we compared AT processed by centrifugation (C-AT) to microfragmentation (MF-AT). Focusing on MF-AT, we subsequently assessed the impact of synovial fluid (SF) alone on both MF-AT and isolated AT-MSC to better understand their cartilage repair mechanisms. MATERIALS AND METHODS: MF-AT and C-AT from the same donors were compared by histology and qRT-PCR immediately after isolation or as ex vivo cultures using a micro-tissue pellet system. The in vitro impact of SF on MF-AT and AT-MSC was assessed by histological staining and molecular analysis. RESULTS: The main AT histological features (i.e., increased extracellular matrix and cellularity) of the freshly isolated or ex vivo-cultured MF-AT persisted compared to C-AT, which rapidly deteriorated during culture. Based on our previous studies of HOX genes in MSC, we investigated the involvement of Homeobox Protein HOX-B7 (HOXB7) and its target basic Fibroblast Growth Factor (bFGF) in the molecular mechanism underlying the improved performance of MF-AT. Indeed, both these biomarkers were more prominent in freshly isolated MF-AT compared to C-AT. SF alone preserved the AT histological features of MF-AT, together with HOXB7 and bFGF expression. Increased cell performance was also observed in isolated AT-MSC after SF treatment concomitant with enhanced HOXB7 expression, although there was no apparent association with bFGF. CONCLUSIONS: Our findings show that MF has a positive effect on the maintenance of AT histology and may trigger the expression of trophic factors that improve tissue repair by processed AT.

Diagnosis and treatment of upper eyelid lipoma: A case report.

PURPOSE: Presentation of a rare lesion: a case of upper eyelid lipoma. OBSERVATIONS: A 76-year-old otherwise healthy woman presented with a right upper eyelid swelling. Her medical history was recorded. On ophthalmologic examination a soft, non-ulcerated and not well-circumscribed mass was evident. An ultrasonography examination was carried out showing a hyperechoic non capsulated mass situated between the superior orbital margin and the orbicularis oculi muscle. CONCLUSIONS AND IMPORTANCE: Eyelid lipomas must be differentiated from herniated orbital fat, cystic lesions, tumours, and the lacrimal gland.A pre-operative differential diagnosis of eyelid lipoma can be done through medical history, ophthalmologic, and ultrasonography examinations. Nevertheless, in case of doubt a magnetic resonance imaging (MRI) should be performed to assess a possible orbital involvement and to plan for the right surgical procedure to be performed.

Factors related to delayed treatment: A case report of a huge cutaneous horn and review of the literature.

We present a case of a man with a giant cutaneous horn over his frontal region. This case has been presented for the size of the lesion, due to delayed treatment, and to illustrate the reasons why the growth of this lesion has been possible in a western country, in the 21st century. It was a solitary, not painful lesion which caused significant aesthetic problems. The diagnosis was based on an ultrasonographic study and the treatment of choice was a surgical excision. This case is an opportunity to review the literature about the cutaneous horns, to talk about the main causes of delayed diagnosis and treatment of cutaneous lesions and, to define the role of the specialist in the assessment of emotions and patient support.

Tattooing of the nipple-areola complex: What not to do. A case series.

INTRODUCTION: Reconstruction of the nipple areola complex (NAC) is the final and easier step of breast reconstruction. However, surgeons, especially if trainees, typically have not developed tattoo skills during their training. The aim of this report is to share advice developed in our clinical practice that would minimize patient complaints and complications while performing NAC tattoos. METHODS: From January 2016 to May 2018, reconstruction of NAC was performed in 48 consecutive patients. Nipple reconstruction was performed initially using skin flaps and this was followed three to eight months later by NAC tattooing. We analyzed medical reports at 12 months follow-up where we usually record patient satisfaction (very satisfied, satisfied, dissatisfied) and every patient's complaint or complication. RESULTS: Thirty-two patients (67%) were very satisfied of NAC tattooing, twelve patients (25%) satisfied, while four patients (8%) dissatisfied. Patients complained for not having involved in choosing color, areas without sufficient pigment, extreme darkness of the tattooed NAC and artificial look. CONCLUSION: Tattooing is a simple and safe procedure, with a high satisfaction rate. Based on our experience, despite some technical aspects have to be considered, it is a procedure that can be safely performed by plastic surgical trainees.

Tip of the Tongue Reconstruction with Prelaminated Fasciomucosal Radial Forearm Free Flap.

Tongue cancer is the most common malignant neoplasm of the oral cavity. Occurrence in the tip of the tongue (TOT) is rare. We describe a case report of a TOT tumor excision and reconstruction with a prelaminated fasciomucosal radial forearm free flap. A 41-year-old white man was referred to our department for a squamous cell carcinoma of the tip of the tongue. The patient worked as an air traffic control official; therefore, conservation of speech intelligibility, both in Italian and English language, was of paramount importance. A transoral excision of TOT, bilateral selective neck dissection, and reconstruction with prelaminated fasciomucosal radial forearm free flap were performed. Adjuvant radiotherapy was necessary. The patient was completely re-established as an air traffic control officer. Successful tongue reconstruction of smaller defects depends on thinness, pliability of flap, and conservation of tongue mobility. Surgical options for TOT reconstruction are facial artery muscolomucosa flap, Zhao flap, radial forearm free flap, or primary suture. In the authors' opinion, a fasciomucosal prelaminated RFFF offers a series of advantages for TOT reconstruction. The absence of subcutaneous tissue makes the PFRFFF much thinner than fascio-cutaneous flaps. Compared with mucosal loco-regional flaps, prelaminated flaps allow the preservation of oral mucosa lining while providing adequate bulk and reduced scar formation for optimal func- tional recovery. In our case report, the fasciomucosal flap allowed an adequate reconstruction of TOT volume with good functional and aesthetic outcomes. The flap's added bulk and its minimal scar retraction granted free tongue movement and optimal speech intelligibility.

Arming Mesenchymal Stromal/Stem Cells Against Cancer: Has the Time Come?

Since mesenchymal stromal/stem cells (MSCs) were discovered, researchers have been drawn to study their peculiar biological features, including their immune privileged status and their capacity to selectively migrate into inflammatory areas, including tumors. These properties make MSCs promising cellular vehicles for the delivery of therapeutic molecules in the clinical setting. In recent decades, the engineering of MSCs into biological vehicles carrying anticancer compounds has been achieved in different ways, including the loading of MSCs with chemotherapeutics or drug functionalized nanoparticles (NPs), genetic modifications to force the production of anticancer proteins, and the use of oncolytic viruses. Recently, it has been demonstrated that wild-type and engineered MSCs can release extracellular vesicles (EVs) that contain therapeutic agents. Despite the enthusiasm for MSCs as cyto-pharmaceutical agents, many challenges, including controlling the fate of MSCs after administration, must still be considered. Preclinical results demonstrated that MSCs accumulate in lung, liver, and spleen, which could prevent their engraftment into tumor sites. For this reason, physical, physiological, and biological methods have been implemented to increase MSC concentration in the target tumors. Currently, there are more than 900 registered clinical trials using MSCs. Only a small fraction of these are investigating MSC-based therapies for cancer, but the number of these clinical trials is expected to increase as technology and our understanding of MSCs improve. This review will summarize MSC-based antitumor therapies to generate an increasing awareness of their potential and limits to accelerate their clinical translation.

Overall survival in patients with lung adenocarcinoma harboring "niche" mutations: an observational study.

Objective: In addition to the most common somatic lung cancer mutations (i. e., KRAS and EGFR mutations), other genes may harbor mutations that could be relevant for lung cancer. We defined BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET mutations as "niche" mutations and analyzed. The aim of this retrospective cohort study was to assess the differences in the overall survival (OS) of patients with lung adenocarcinoma harboring niche somatic mutations. Results: Data were gathered for 252 patients. Mutations were observed in all genes studied, except c-MET, DDR2, MAP2K1, and RET. The multivariable analysis showed that 1) niche mutations had a higher mortality than EGFR mutations (HR = 2.3; 95% CI = 1.2-4.4; p = 0.009); 2) KRAS mutations had a higher mortality than EGFR mutations (HR = 2.5; 95% CI = 1.4-4.5; p = 0.003); 3) niche mutations presented a similar mortality to KRAS mutations (HR = 0.9; 95% CI = 0.6-1.5; p = 0.797). Methods: Three cohorts of mutations were selected from patients with lung adenocarcinoma and their OS was compared. Mutations that were searched for, were 1) BRAF, c-MET, DDR2, HER2, MAP2K1, NRAS, PIK3CA, and RET; 2) K-RAS; and 3) EGFR. Differences in OS between these three cohorts were assessed by means of a multivariable Cox model that adjusted for age, sex, smoking habits, clinical stages, and treatments. Conclusions: Niche mutations exhibited an increased risk of death when compared with EGFR mutations and a similar risk of death when compared with KRAS mutations.

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine.

Mesenchymal stem/stromal cells (MSCs) have been widely studied in the field of regenerative medicine for applications in the treatment of several disease settings. The therapeutic potential of MSCs has been evaluated in studies in vitro and in vivo, especially based on their anti-inflammatory and pro-regenerative action, through the secretion of soluble mediators. In many cases, however, insufficient engraftment and limited beneficial effects of MSCs indicate the need of approaches to enhance their survival, migration and therapeutic potential. Genetic engineering emerges as a means to induce the expression of different proteins and soluble factors with a wide range of applications, such as growth factors, cytokines, chemokines, transcription factors, enzymes and microRNAs. Distinct strategies have been applied to induce genetic modifications with the goal to enhance the potential of MCSs. This review aims to contribute to the update of the different genetically engineered tools employed for MSCs modification, as well as the factors investigated in different fields in which genetically engineered MSCs have been tested.