Botulinum Toxin-A Infiltration to Control Post-Operative Pain after Mastectomy and Expander Reconstruction as Potentially Useful Tool: A Narrative Review.

Botulinum toxin-A (BTX-A), a neurotoxin produced by Clostridium botulinum, was assessed for relieving implant-related pectoralis major muscle's painful spasms. In detail, 100 units of BTX-A can reduce muscle activity and, as a consequence, muscle spasms. The latter is considered the leading cause of post-operative pain after the sub-pectoral tissue expansion, sometimes leading to early expanders' removal. In addition, women choosing post-mastectomy reconstruction surgery seem to suffer worse post-operative pain than those who stop at the mastectomy stage. However, there is no unanimous consensus concerning the potential benefits of BTX-A in reducing pain related to the sub-pectoral placement of tissue expanders in breast reconstruction due to the exiguity of evidence. Therefore, this review aims to describe BTX-A-related evidence in this reconstruction setting. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Training in Vascular Microsurgery: The Ex Vivo Biological Model on Domestic Turkey Leg (Meleagris gallopavo).

There are various models for practicing microsurgical anastomoses, from synthetic to ex vivo and in vivo biological ones. In this study, we present the domestic turkey (Meleagris gallopavo) as an ex vivo biological model in the practice of surgical anastomoses. In our opinion, it represents a model that is very similar to a human one, low cost, and easy to find. In fact, our study shows that the diameters of the arteries and veins used for anastomoses (tibial artery diameter: 2.5 ±â€…0.6 mm; tibial vein diameter: 3.5 ±â€…1.2 mm) are similar to those of human arteries and veins most frequently used in microsurgical free flaps. So, we believe that this animal model is a great model for microsurgical training for doctors who approach this difficult and long to learn discipline.

Highly Concentrated Stabilized Hybrid Complexes of Hyaluronic Acid: Rheological and Biological Assessment of Compatibility with Adipose Tissue and Derived Stromal Cells towards Regenerative Medicine.

Cells and extracts derived from adipose tissue are gaining increasing attention not only in plastic surgery and for aesthetic purposes but also in regenerative medicine. The ability of hyaluronan (HA) to support human adipose stromal cell (hASC) viability and differentiation has been investigated. However, the compatibility of adipose tissue with HA-based formulation in terms of biophysical and rheological properties has not been fully addressed, although it is a key feature for tissue integration and in vivo performance. In this study, the biophysical and biochemical properties of highly concentrated (45 mg/mL) high/low-molecular-weight HA hybrid cooperative complex were assessed with a further focus on the potential application in adipose tissue augmentation/regeneration. Specifically, HA hybrid complex rheological behavior was observed in combination with different adipose tissue ratios, and hyaluronidase-catalyzed degradation was compared to that of a high-molecular-weight HA (HHA). Moreover, the HA hybrid complex's ability to induce in vitro hASCs differentiation towards adipose phenotype was evaluated in comparison to HHA, performing Oil Red O staining and analyzing gene/protein expression of PPAR-γ, adiponectin, and leptin. Both treatments supported hASCs differentiation, with the HA hybrid complex showing better results. These outcomes may open new frontiers in regenerative medicine, supporting the injection of highly concentrated hybrid formulations in fat compartments, eventually enhancing residing staminal cell differentiation and improving cell/growth factor persistence towards tissue regeneration districts.

CGRP Antagonism and Ketogenic Diet in the Treatment of Migraine.

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy.

Comparative Analysis of Nipple Reconstruction Techniques: Five Flap vs. C-V Flap.

Background: Nipple-areola complex reconstruction represents the final phase in the comprehensive post-mastectomy treatment regimen. Despite the diversity of approaches available, there is currently no universally accepted benchmark technique for this critical aspect of breast reconstruction. In this study, we conducted a comparative assessment of two prominent techniques, the five Flap and C-V Flap. Materials and Methods: Between November 2016 and April 2023, we recruited 100 female patients who had undergone unilateral post-oncological mastectomy and divided them into two groups: Group A comprising 50 patients who underwent the 5-Flap technique, whereas Group B comprising the remaining 50 underwent the C-V Flap technique. Over a 6-month observation period, we assessed nipple projection loss and evaluated overall satisfaction through self-reporting by patients and independent assessments by a medical observer. Results: In our study, none of the reconstructed nipples in Group A (5 Flap) experienced either total or partial necrosis, contrasting with Group B (C-V Flap) which encountered a 10% incidence of partial necrosis and 4% incidence of total necrosis. Furthermore, the average nipple projection loss in Group B was substantial, measuring a 30% reduction from the initial projection at the 1-year mark, whereas Group A demonstrated a significantly lower 13% reduction. Notably, despite these variations in outcomes, both groups reported an equal and high level of satisfaction, with patients and external observers providing an average satisfaction score of 8.0 and 9.0, respectively. Conclusion: The five-flap technique represents a safe and effective approach for patients undergoing nipple reconstruction.

Extremely rare case of unilateral gigantomastia after hormonal stimulation treated with a modified wise pattern technique: A case report.

INTRODUCTION: Gigantomastia, characterized by excessive breast size (usually heavier than 2.5 kg), can result from various causes and significantly affect patients' lives. Surgical intervention is often required, and over time, several techniques have been developed for its treatment. These techniques aim to address the functional and aesthetic concerns associated with gigantomastia, providing relief to patients and improving their quality of life. PRESENTATION OF THE CASE: A 40-year-old primiparous housewife developed unilateral gigantomastia as a consequence of hormone therapy. To address this, a modified reduction mammoplasty procedure was undertaken, incorporating NAC (Nipple-Areola Complex) grafting. The reduction involved removing 3450 g of tissue, resulting in restored breast symmetry and enabling the patient to reintegrate into normal daily life. DISCUSSION: Compared to the traditional technique, the introduction of some modifications in the design allowed for the absence of complications such as dehiscence of the scar at the intersection of the T, the failure of the nipple graft attachment, and the maintenance of a conical shape over time, enabling complete symmetrization of the two breasts. CONCLUSION: The use of a modified version of the Thorek technique allowed for optimal functional and aesthetic restoration even in the case of a significantly disproportionate breast compared to the contralateral one, with no complications.

Squamous Carcinoma of the Oral Cavity in Patient with Fanconi Anemia: A Challenging Reconstruction with Double-barrel Free Fibula Flap Case Report.

Fanconi anemia (FA) is a very rare form of aplastic anemia. Patients with FA have a higher risk of developing solid tumors such as head and neck squamous cell carcinoma, higher risk of local recurrence, and impaired resistance to chemotherapy and radiotherapy treatments than the normal population. In this article, we describe the challenging clinical case of a patient with FA who underwent surgery for the removal of a large squamous cell carcinoma in the oral cavity. Mandibular reconstruction was performed using a biaxial double-barrel fibular flap, with excellent functional aesthetic outcomes.

Multiple Foci of Basal Cell Carcinoma Arising in Rhinophyma: A Case Report and Literature Review.

Background: Rhinophyma is a benign condition caused by the excessive growth of sebaceous glands in the nasal tissue, presenting with symptoms such as nasal hypertrophy, erythema, and papules. Cases of basal cell carcinoma in rhinophyma have been reported in literature, but its etiological role remains unclear. It is uncertain whether rhinophyma is predisposed to neoplasm development or if their coexistence is coincidental. Material and Method: We conducted a literature survey to identify such cases reported over the years. Results: We identified 22 studies reporting a total of 47 cases in the literature, all involving male patients. The most common pattern of occurrence was the rapid growth of a nodular formation within the context of rhinophyma. Discussions and Conclusion: The elucidation of the association between basal cell carcinoma and rhinophyma remains challenging. The presence of multiple foci supports the theory that rhinophyma may play a role in their development, but larger studies are needed to establish a causal relationship.

Telemonitoring Wound Recovery with Smartphone: An Italian Experience during Pandemic Period.

An important problem of plastic surgeons is monitoring wound healing, loss of substance, and postsurgical scar in different pathologies of the skin. Face to face monitoring is expensive and cannot be performed in periods of social crisis such as the recent COVID-19 pandemic. The use of telemedicine techniques is rising in this field of healthcare, promising the same results as the standard follow-up with more flexibility and savings. The purpose of this case study was to evaluate the effectiveness of remote monitoring and treatment through remote follow-up using digital applications. We followed up 25 patients with postoperative or diabetic ulcers for a period of 6 months (ranging from 2 to 6 months). We have performed clinical assessments using the Scar Cosmesis Assessment and Rating scale, and we have measured patient satisfaction using questionnaires. We chose to use the application for smartphone, describing the types of ulcers, number and average consultations, and the type of recovery, whether partial or complete. Monitoring wound recovery was very easy, and the patients found the experience very satisfactory. The total number of consultations was 255 with a significant reduction in outpatient visits during the pandemic period. Telemedicine is a useful tool in wound management and can be used to provide an optimal health care service with no inferior results to standard care.

Correction of Rippling in Implant-based Breast Reconstruction with Serratus Fascia Flap.

Implant-based breast reconstruction represents the most popular procedure for the treatment of women undergoing skin-sparing mastectomy. In selected patients, it allows for obtaining an excellent appearance of the reconstructed breast with great satisfaction to the patient. However, aesthetic and functional results can be affected by complications requiring reoperation. Among them, rippling is an undesired occurrence associated with implant-based reconstruction. It consists of a cutaneous manifestation, visible and/or palpable, of the implant wrinkles and edge which appear mostly when the patient leans forward. To treat this contour deformity, several techniques have been described such as acellular dermal matrices and autologous tissues. In this study, we intend to add the serratus anterior fascial flap within the autologous options in the treatment of implant rippling, reporting our experience.

Mondor's disease as a complication in breast surgery in a male patient. The first ever reported case in literature.

Mondor's disease (MD) is an uncommon clinical condition characterized by thrombophlebitis of the superficial veins of the anterolateral thoracoabdominal wall. In this paper we present the first ever reported case of Mondor's disease in male patient after surgical correction of gynecomastia with liposuction assisted skin sparing adenectomy.

Polydatin Incorporated in Polycaprolactone Nanofibers Improves Osteogenic Differentiation.

Polycaprolactone nanofibers are used as scaffolds in the field of tissue engineering for tissue regeneration or drug delivery. Polycaprolactone (PCL) is a biodegradable hydrophobic polyester used to obtain implantable nanostructures, which are clinically applicable due to their biological safety. Polydatin (PD), a glycosidic precursor of resveratrol, is known for its antioxidant, antitumor, antiosteoporotic, and bone regeneration activities. We aimed to use the osteogenic capacity of polydatin to create a biomimetic innovative and patented scaffold consisting of PCL-PD for bone tissue engineering. Both osteosarcoma cells (Saos-2) and mesenchymal stem cells (MSCs) were used to test the in vitro cytocompatibility of the PD-PCL scaffold. Reverse-phase (RP) HPLC was used to evaluate the timing release of PD from the PCL-PD nanofibers and the MTT assay, scanning electron microscopy, and alkaline phosphatase (ALP) activity were used to evaluate the proliferation, adhesion, and cellular differentiation in both osteosarcoma and human mesenchymal stem cells (MSCs) seeded on PD-PCL nanofibers. The proliferation of osteosarcoma cells (Saos-2) on the PD-PCL scaffold decreased when compared to cells grown on PLC nanofibers, whereas the proliferation of MSCs was comparable in both PCL and PD-PCL nanofibers. Noteworthy, after 14 days, the ALP activity was higher in both Saos-2 cells and MSCs cultivated on PD-PCL than on empty scaffolds. Moreover, the same cells showed a spindle-shaped morphology after 14 days when grown on PD-PCL as shown by SEM. In conclusion, we provide evidence that nanofibers appropriately coated with PD support the adhesion and promote the osteogenic differentiation of both human osteosarcoma cells and MSCs.

Hyaluronan-Based Gel Promotes Human Dental Pulp Stem Cells Bone Differentiation by Activating YAP/TAZ Pathway.

BACKGROUND: Hyaluronans exist in different forms, accordingly with molecular weight and degree of crosslinking. Here, we tested the capability to induce osteogenic differentiation in hDPSCs (human dental pulp stem cells) of three hyaluronans forms: linear pharmaceutical-grade hyaluronans at high and (HHA) low molecular weight (LHA) and hybrid cooperative complexes (HCC), containing both sizes. METHODS: hDPSCs were treated with HHA, LHA, HCC for 7, 14 and 21 days. The effects of hyaluronans on osteogenic differentiation were evaluated by qRT-PCR and WB of osteogenic markers and by Alizarin Red S staining. To identify the involved pathway, CD44 was analyzed by immunofluorescence, and YAP/TAZ expression was measured by qRT-PCR. Moreover, YAP/TAZ inhibitor-1 was used, and the loss of function of YAP/TAZ was evaluated by qRT-PCR, WB and immunofluorescence. RESULTS: We showed that all hyaluronans improves osteogenesis. Among these, HCC is the main inducer of osteogenesis, along with overexpression of bone related markers and upregulating CD44. We also found that this biological process is subordinate to the activation of YAP/TAZ pathway. CONCLUSIONS: We found that HA's molecular weight can have a relevant impact on HA performance for bone regeneration, and we unveil a new molecular mechanism by which HA acts on stem cells.

The "Five-flap" Technique for Nipple-Areola Complex Reconstruction.

Nipple-areola complex reconstruction aims to be the last step in the postmastectomy treatment procedure. Different techniques have been developed with the purpose of achieving optimal symmetry in position, size, shape, pigmentation, and permanent projection of the reconstructed nipple, but to date, there is no gold standard technique. The five-flap technique provides an easy, simple nipple-areola complex reconstruction method, effectively maintaining longer nipple projection, with a negligible rate of complications. METHODS: From November 2018 to April 2021, a total of 21 female patients with an absent unilateral nipple-areolar complex due to postoncological mastectomy were subjected to our technique consisting of a combination of local flaps and a full-thickness skin graft. Patients were observed for 6 months to estimate the percentage of the nipple projection loss. Overall satisfaction was evaluated by the patients themselves and by an external medical observer at the end of the follow-up period. RESULTS: None of the reconstructed nipples experienced either total or partial necrosis. Two minor complications were observed. Nipple projection loss was negligible with an average reduction of 12% from the initial projection. The nipple-areolar complex shape remained excellent in all cases, with minimal alteration of the immediate postoperative results. The total average satisfaction score was 8.0 for patients and 9.0 for external observers. CONCLUSION: The five-flap technique represents a simple, safe, and efficacious procedure in patients with implant-based reconstruction requiring moderate to very projected nipples.

Anti-Inflammatory Drugs as Anticancer Agents.

Inflammation is strictly associated with cancer and plays a key role in tumor development and progression. Several epidemiological studies have demonstrated that inflammation can predispose to tumors, therefore targeting inflammation and the molecules involved in the inflammatory process could represent a good strategy for cancer prevention and therapy. In the past, several clinical studies have demonstrated that many anti-inflammatory agents, including non-steroidal anti-inflammatory drugs (NSAIDs), are able to interfere with the tumor microenvironment by reducing cell migration and increasing apoptosis and chemo-sensitivity. This review focuses on the link between inflammation and cancer by describing the anti-inflammatory agents used in cancer therapy, and their mechanisms of action, emphasizing the use of novel anti-inflammatory agents with significant anticancer activity.

The Role of Oxidative Stress and Hormones in Controlling Obesity.

The accumulation of adipose tissue in the body occurs because the energy introduced with food and drink exceeds that expense, but to understand why this imbalance is established and why it is maintained over time, it is important to consider the main causes and risk factors of excess weight. In this review, we will refer to the main factors linked to obesity, starting from oxidative stress to hormonal factors including the role of obesity in breast cancer. Among the many hypotheses formulated on the etiopathology of obesity, a key role can be attributed to the relationship between stress oxidative and intestinal microbiota. Multiple evidences tend to show that genetic, epigenetic, and lifestyle factors contribute to determine in the obese an imbalance of the redox balance correlated with the alteration of the intestinal microbial flora. Obesity acts negatively on the wound healing, in fact several studies indicate morbid obesity significantly increased the risk of a post-operative wound complication and infection. Currently, in the treatment of obesity, medical interventions are aimed not only at modifying caloric intake, but also to modulate and improve the composition of diet with the aim of rebalancing the microbiota-redox state axis.

What's new on primary Hodgkin's lymphoma of the breast? A case report and review of the literature.

INTRODUCTION: According to literature, primary Hodgkin's lymphomas of the breast represent one of the rarer entity in the primary breast lymphoma (PBL) scenario. This is the reason why these tumors are insidious in mammary oncology. PRESENTATION OF THE CASE: We report a case of HL primitive breast in an elderly patient in whom radiology suspected an advanced breast cancer with ipsilateral axillary involvement and in which the fine-needle aspiration came back not significant. DISCUSSION: Eighteen cases of primary Hodgkin's lymphoma of the breast has been described in Literature in a very large period of time: from 1928 to 2016. The nodular sclerosis type is the most frequent histological variant. CONCLUSION: Their rarity together with the fact that radiological investigations are not significant for the purpose of an exact diagnosis, make these lesions extremely difficult to identify.

Effects of Fat Grafting Containing Stem Cells in Microstomia and Microcheilia Derived from Systemic Sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease with multisystem involvement, dominated by a general fibrosis. The early stage of the disease is associated with progressive damage to microcirculation, particularly in the respiratory tract, the gastrointestinal tract and skin. The face assumes a typical appearance characterized by microstomia (reduction of mouth opening) and microcheilia (thinning of the lips). These conditions cause a considerable reduction in performance status of patients. We treated them by fat grafting, rich in adipose stem cells, and we evaluated through time clinical, functional and aesthetic evaluation of oral pathology associated with SSc. MATERIALS AND METHOD: From September 2014 to May 2016, we enrolled and treated seven patients in the plastic, reconstructive and aesthetic surgery clinic. Through time, we evaluated the following parameters: evaluation of mouth opening (maximum opening in superior-inferior and lateral directions) and lip thicknesses, both measured by doctors of the aforementioned operating unit; variation in the quality of life as perceived by patients according to the MHISS scale (Mouth Handicap Systemic Sclerosis); variation in severity of labial fibrosis assessed by microscopic analysis of pre- and post-fat transfer samples in the pathology clinic; safety of the protocol, according to the management of side effects resulting from the procedure; aesthetic evaluation, made by external observers and non-experts in the field, on pre- and post-operative photographs. RESULTS AND CONCLUSIONS: We reported satisfying results, both functionally and aesthetically, for all parameters except one, for which the sample size might have proven critical. These data should be a starting point for further experimental research and clinical trials. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Human adipose stem cell differentiation is highly affected by cancer cells both in vitro and in vivo: implication for autologous fat grafting.

Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour progression, raising some concerns regarding their use in regenerative medicine. In this context, we co-cultured either SAOS2 osteosarcoma or MCF7 breast cancer cells with human adipose stem cells (hASCs), in order to evaluate potential effects of cancer cells on hASCs differentiation, in vitro and in vivo. In this study we observed that both SAOS2 and MCF7 cell lines induced an increase in hASCs proliferation, compared to hASCs alone, but, surprisingly, neither changes in the expression of CD90, CD29, CD324 and vimentin, nor variations in the Twist and Slug mRNAs were detectable. Noteworthy, SAOS2 and MCF7 cells induced in hASCs an upregulation of CD34 expression and stemness genes, including OCT3/4, Nanog, Sox2 and leptin, and a decrease in angiogenic factors, including CD31, PDGFα, PDGFRα, PDGFRß and VEGF. SMAD and pSMAD2/3 increased only in hASCs alone. After 21 days of co-culture, hASCs differentiated both in adipocytes and endothelial cells. Moreover, co-injection of MCF7 cells with hASCs led to the formation of a highly vascularized tumour. Taken together our findings suggest that mesenchymal stem cells, under tumour cell induction, do not differentiate in vitro or facilitate the angiogenesis of the tumour in vivo, thus opening interesting new scenarios in the relationship between cancer and stem cells. These findings may also lead to greater caution, when managing autologous fat grafts in cancer patients.