Natural Products for the Prevention, Treatment and Progression of Breast Cancer.

In this review, we summarize the most used natural products as useful adjuvants in BC by clarifying how these products may play a critical role in the prevention, treatment and progression of this disease. BC is the leading cancer, in terms of incidence, that affects women. The epidemiology and pathophysiology of BC were widely reported. Inflammation and cancer are known to influence each other in several tumors. In the case of BC, the inflammatory component precedes the development of the neoplasm through a slowly increasing and prolonged inflammation that also favors its growth. BC therapy involves a multidisciplinary approach comprising surgery, radiotherapy and chemotherapy. There are numerous observations that showed that the effects of some natural substances, which, in integration with the classic protocols, can be used not only for prevention or integration in order to prevent recurrences and induce a state of chemoquiescence but also as chemo- and radiosensitizers during classic therapy.

Surgical treatment of undifferentiated soft tissue sarcoma in a young 17-year-old woman: A case report.

This case report describes the clinical case of a 17-year-old woman with an undifferentiated soft tissue sarcoma in the left supratrocanteric area. The young woman came for observation at our plastic surgery hospital with a large vascular mass visible on her left side which also made walking difficult. Our patient reports the onset of the mass about two months earlier and its growth very quickly. In this case report, we will analyze the demolitive and reconstructive surgical procedures in order to guarantee our patient radical surgery and the possibility of continuing radiotherapy and any specific chemotherapy to avoid the risk of relapse and metastasis over time.

Concerted BAG3 and SIRPα blockade impairs pancreatic tumor growth.

The BAG3- and SIRPα- mediated pathways trigger distinct cellular targets and signaling mechanisms in pancreatic cancer microenvironment. To explore their functional connection, we investigated the effects of their combined blockade on cancer growth in orthotopic allografts of pancreatic cancer mt4-2D cells in immunocompetent mice. The anti-BAG3 + anti-SIRPα mAbs treatment inhibited (p = 0.007) tumor growth by about the 70%; also the number of metastatic lesions was decreased, mostly by the effect of the anti-BAG3 mAb. Fibrosis and the expression of the CAF activation marker α-SMA were reduced by about the 30% in animals treated with anti-BAG3 mAb compared to untreated animals, and appeared unaffected by treatment with the anti-SIRPα mAb alone; however, the addition of anti-SIRPα to anti-BAG3 mAb in the combined treatment resulted in a > 60% (p < 0.0001) reduction of the fibrotic area and a 70% (p < 0.0001) inhibition of CAF α-SMA positivity. Dendritic cells (DCs) and CD8+ lymphocytes, hardly detectable in the tumors of untreated animals, were modestly increased by single treatments, while were much more clearly observable (p < 0.0001) in the tumors of the animals subjected to the combined treatment. The effects of BAG3 and SIRPα blockade do not simply reflect the sum of the effects of the single blockades, indicating that the two pathways are connected by regulatory interactions and suggesting, as a proof of principle, the potential therapeutic efficacy of a combined BAG3 and SIRPα blockade in pancreatic cancer.

BAG3 induces α-SMA expression in human fibroblasts and its over-expression correlates with poorer survival in fibrotic cancer patients.

Hypoxia and angiogenesis in solid tumors are often strictly linked to the development of fibrotic tissues, a detrimental event that compromises the antitumor immunity. As a consequence, tumor aggressiveness and poor patient prognosis relate to higher incidence of tissue fibrosis and stromal stiffness. The molecular pathways through which normal fibroblasts are converted in cancer-associated fibroblasts (CAFs) have a central role in the onset of fibrosis in tumor stroma, thus emerging as a strategic target of novel therapeutic approaches for cancer disease. Several studies addressed the role of BAG3 in sustaining growth and survival of cancer cell and also shed light on the different mechanisms in which the intracellular protein is involved. More recently, new pieces of evidence revealed a pivotal role of extracellular BAG3 in pro-tumor cell signaling in the tumor microenvironment, as well as its involvement in the development of fibrosis in tumor tissues. Here we report further data showing the presence of the BAG3 receptor (Interferon-induced transmembrane protein [IFITM]-2) on the plasma membrane of normal dermal fibroblasts and the activity of BAG3 as a factor able to induce the expression of α-smooth muscle actin and the phosphorylation of AKT and focal adhesion kinase, that sustain CAF functions in tumor microenvironment. Furthermore, in agreement with these findings, bag3 gene expression has been analyzed by high throughput RNA sequencing databases from patients-derived xenografts. A strong correlation between bag3 gene expression and patients' survival was found in several types of fibrotic tumors. The results obtained provide encouraging data that identify BAG3 as a promising therapeutic target to counteract fibrosis in tumors.

Modulation of BAG3 expression in human normal urothelial cells by Diuron.

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substituted urea herbicide, carcinogenic for the rat urinary bladder. It has been hypothesized that Diuron cytotoxicity, resulting in regenerative proliferation, leads to urothelial hyperplasia and, finally, to bladder tumors, but molecular mechanisms of carcinogenesis have not still fully investigated. Here, we report the results of a study aimed at verifying the involvement of BAG3, an intracellular protein expressed in several tumors, in the Diuron-induced carcinogenesis. For this purpose, we analyzed the effect of Diuron on human primary urothelial cells and on human dermal fibroblasts. We found that while high concentrations of Diuron have a cytotoxic effect in human primary urothelial cells, in the same cells, noncytotoxic concentrations of the herbicide induce BAG3 expression. These findings show that BAG3 is a molecular target of Diuron and unravel the possible involvement of BAG3 protein in bladder carcinogenesis induced by the herbicide. In addition, these results suggest that BAG3 might be a potential early biomarker of damage induced by chronic exposure to Diuron.

Abdominoplasty after bariatric surgery: comparison of three different techniques.

BACKGROUND: Abdominoplasty after massive weight loss is not a cosmetic procedure. The aim of this study was to compare three different techniques for postbariatric abdominoplasty. METHODS: All postbariatric patients that have undergone abdominoplasty from January 2013 to December 2016 were included in the study. Patients were divided into 3 groups: subjects who underwent standard procedure were allocated ingroup A; those cases performed using a synthetic glue were assigned to group B; cases performed with an energy device were inserted in group C. Operative time, length of stay and complications were recorded. RESULTS: Seventy-one abdominoplasties were performed in the selected period. Mean operative time was shorter (P<0.01) in group C (94.3±2.7 minutes) than in group A (112.1±16.8 minutes) and in group B (121±13.2 minutes). Mean length of stay was significantly reduced (P<0.01) in group C (2.4±0.7) when compared to group A (3.5±0.6 days) and group B (3.1±0.5 days). Bleeding occurred in 21 (29.5%) patients (15 in group A, 4 in groupB, 3 in group C; P<0.01). Seroma was detected in 22(30.9%) subjects (14 in group A, 2in group B, 6 in group C; P<0.01). Wound dehiscence and umbilical necrosis were recorded in 7 (9.9%) and 9 (12.6%) patients respectively, without statistical differences. CONCLUSIONS: Both synthetic glue and energy device improve outcomes of postbariatric abdominoplasties. The glue reduces rates of bleeding and seroma. The energy deviceimproves intraoperative hemostasis and shortens operative time.

Management of Complications of First Instance of Hepatic Trauma in a Liver Surgery Unit: Portal Vein Ligation as a Conservative Therapeutic Strategy.

BACKGROUND: According to the National Trauma Data Bank, the liver, after the spleen, is the first most injured organ in closed abdominal trauma. METHODS: From June 2010 to December 2015 we observed in our department of Hepato-biliary Surgery and Liver Transplant Unit of the A.O.R.N. A. Cardarelli of Naples 40 patients affected by hepatic trauma. In our retrospective study, we review our experience and propose portal vein ligation (PVL) as a first - line strategy for damage control surgery (DCS) in liver trauma. RESULTS: 26/40 patients (65%) which received gauze-packing represented our study group. In 10 cases out of 26 patients (38,4%) the abdominal packing was enough to control the damage. In 7 cases (18,4%) we performed a liver resection. In 7 cases, after de-packing, we adopted PVL to achieve DCS. Trans Arterial Embolization was chosen in 6 patients. 2 of them were discharged 14 days later without performing any other procedure.In 3 cases we had to perform a right epatectomy in second instance. Two hepatectomies were due to hemoperitoneum, and the other for coleperitoneum. Two patients were treated in first instance by only doing hemostasis on the bleeding site. We observed 6 patients in first instance. Five of them underwent surgery with hepatic resection and surgical hemostasis of the bleeding site. The other one underwent to conservative management. In summary we performed 15 hepatic resections, 8 of them were right hepatectomies, 1 left hepatectomy, 2 trisegmentectomies V-VI-VII. So in second instance we operated on 10 patients out of 34 (30%). CONCLUSIONS: The improved knowledge of clinical physio-pathology and the improvement of diagnostic and instrumental techniques had a great impact on the prognosis of liver trauma. We think that a rigid diagnostic protocol should be applied as this allows timely pathological finding, and consists of three successive but perfectly integrated steps: 1) patient reception, in close collaboration with the resuscitator; 2) accurate but quick diagnostic framing 3) therapeutic decisional making. Selective portal vein ligation is a well-tolerated and safe manoeuvre, which could be effective, even if not definitive, in treating these subjects. That is why we believe that it can be a choice to keep in mind especially in post-depacking bleeding.

Surgical Versus Sequential Hybrid Treatment of Carotid Body Tumors.

Carotid body tumor (CBT) are slow-growing tumors that develop in the cervical region at the carotid bifurcation. . In a randomized study, 33 patients were treated for CBT excision: 10 patients performed preoperative embolization (PE) and 23 were treated only by isolated traditional surgery (N-PE). The first group includes patients undergoing preoperative embolization. The second group of patients (N-PE) included 11 males and 12 females. Intraoperative complications were lower in patients treated with a hybrid procedure (PE): sections of the cranial nerves were recorded in 7% of cases compared to 12% of the surgical procedure (P-value = 0.72); while the reversible nerve lesions (P value = 0.21) and the permanent ones (P value = 0.46), were instead similar in both procedures. The comparative blood loss during the operative procedure shows a P-value of 0.02. Operating times, reversible damage of the cranial nerves , incidence of stroke (0% vs1%, P value> 0.99) and post-operative hospital stay (4.1 vs. 4.2 days, P value = 0.91) did not show differences in the two groups of patients. The analysis of the results detects pre-operative embolization of CBT in reducing intraoperative blood loss and resection of the cranial nerves..

Management of Zygomatic Fractures in Young Patients: Technical Modifications for Aesthetic and Functional Results.

INTRODUCTION: The zygomaticomaxillary complex is very vulnerable to injury because of its intrinsically prominent convexity. There are 2 different surgical approaches for the therapy of these fractures: closed reduction and open reduction. In the open reduction 2 or 3 fixation points with related incisions are usually necessary in dislocated fractures: osteosynthesis must be performed starting from zygomaticofrontal suture when dislocated at this site, followed by zygomatic body fixation on the anterior sinus wall, anterior orbital floor margin fixation, and finally orbital floor reconstruction in case of eye globe dislocation with diplopia. AIM: This study evaluated the combination of the transconjunctival (TC) approach without canthotomy in association with the transoral maxillary approach and lateral rim skin incision (SI) without canthotomy for frontozygomatic dislocated fractures to achieve proper reduction and stabilization without any aesthetic decay in young patients. A less invasive and more aesthetic technique is shown for treating dislocated zygomaticomaxillary complex fractures with 2 or 3 fixation points and platelet-rich fibrin (PRF) use to promote tissue healing. MATERIALS AND METHODS: Ten patients (mean age: 32) were referred for dislocated zygomaticomaxillary complex fracture. Five patients were treated by TC approach without canthotomy in association with the transoral maxillary approach and, when needed, eyebrow SI without canthotomy for frontozygomatic dislocated fractures (group 1). Five more patients were treated by traditional subciliar incision at lower eyelid and vertical lateral incision at lateral margin of the orbit (group 2). Autologous PRF for orbital floor reconstruction was used. The follow-up period was 6 months long. Follow-up radiographs (TC) and photos were routinely used to evaluate the adequacy of reduction and lower eyelid right position or retraction. RESULTS: All cases were successful; there were no problems at surgery and postoperative time. During the 6-month follow-up, all 5 patients of group 1 showed satisfactory facial symmetry, no noticeable scarring, no ectropion or lower eyelid significant droop, and no functional impairment. Mean difference for lower eyelid droop between the 2 groups of patients was 1.4 mm at T1 and 1.2 mm at T2. DISCUSSION: Aesthetic result is a priority in the treatment planning of orbitozygomatic fractures because of the fundamental role of the eye and lid area in the aesthetic of the face. In our experience best aesthetic results were achieved through a latero cantal horizontal SI combined to a vertical periosteal incision at the frontozygomatic rim without canthotomy, thus performing a different double-layer incision. In the patients with large orbital floor dislocation, reconstructive titanium mesh was covered by autologous PRF membranes, which can improve the vascularization of the surgical site, by promoting neoangiogenesis. CONCLUSIONS: In young patients these techniques are indicated because of the need of better aesthetic results that can be achieved by preventing postoperative functional impairment with lower eyelid droop and unnatural aesthetic asymmetry of the 2 lower lids. This more conservative technique resulted in better aesthetic results, avoiding most common complications.

New Techniques in Relation to New Concepts of the Aesthetic of the Face: Technical Considerations and Aesthetic Evaluation.

Aesthetic of the face is greatly changed in relation to common standards of the past. Modern concepts of beauty from popular models of beautiful faces to actors show a biprotrusive asset with high tension for soft tissues. Facial symmetry has been proposed as a marker of developmental stability that may be important in human mate choice. Any deviation from perfect symmetry can be considered a reflection of imperfect development. The goal of maxillofacial surgery should be to give the best results for both aesthetic and functional aspects. Following these new concepts of aesthetic of the face, new surgical procedure by osteodistraction techniques will lead to a very natural final result by harmonizing the face. The aim of this study was to detect aesthetic results on 10 patients operated for skeletal discrepancies by maxillary distraction and jaw repositioning compared with other 10 patients operated by conventional techniques on a 5-point scale by Likert.

Severe Type 2 Diabetes Induces Reversible Modifications of Endothelial Progenitor Cells Which are Ameliorate by Glycemic Control.

BACKGROUND: Circulating endothelial progenitors cells (EPCs) play a critical role in neovascularization and endothelial repair. There is a growing evidence that hyperglycemia related to Diabetes Mellitus (DM) decreases EPC number and function so promoting vascular complications. AIM OF THE STUDY: This study investigated whether an intensive glycemic control regimen in Type 2 DM can increase the number of EPCs and restores their function. METHODS: Sixty-two patients with Type 2 DM were studied. Patients were tested at baseline and after 3 months of an intensive regimen of glycemic control. The Type 2 DM group was compared to control group of subjects without diabetes. Patients with Type 2 DM (mean age 58.2±5.4 years, 25.6% women, disease duration of 15.4±6.3 years) had a baseline HgA1c of 8.7±0.5% and lower EPC levels (CD34+/KDR+) in comparison to healthy controls (p<0.01). RESULTS: The intensive glycemic control regimen (HgA1c decreased to 6.2±0.3%) was coupled with a significant increase of EPC levels (mean of 18%, p<0.04 vs. baseline) and number of EPCs CFUs (p<0.05 vs. baseline). CONCLUSION: This study confirms that number and bioactivity of EPCs are reduced in patients with Type 2 DM and, most importantly, that the intensive glycemic control in Type 2 DM promotes EPC improvement both in their number and in bioactivity.

Reconstruction of traumatic defect of the lower third of the leg using a combined therapy: negative pressure wound therapy, acellular dermal matrix, and skin graft.

The reconstruction of lower third of the leg is one of the most challenging problems for plastic and reconstructive surgeons and current approaches are still disappointing. We show an easy option to obtain a coverage of traumatic pretibial defects with good aesthetic and functional results: the association of negative pressure wound therapy, acellular dermal matrix, and skin graft. The choice of this combined therapy avoids other surgical procedures such as local perforator flaps and free flaps that require more operating time, special equipment, and adequate training.

Infections in breast implants: a review with a focus on developing countries.

The risk of surgical site infection is always present in surgery; the use of prosthetic materials is linked to an increased possibility of infection. Breast augmentation and breast reconstruction with implants are gaining popularity in developing countries. Implant infection is the main complication related to breast aesthetic and reconstructive surgery. In the present paper, we reviewed the current microbiological knowledge about implant infections, with particular attention to risk factors, diagnosis, clinical management, and antibiotic prophylaxis, focusing on reports from developing countries. After breast aesthetic surgery, up to 2.9% of patients develop a surgical site infection, with an incidence of 1.7% for acute infections and 0.8% for late infections. The rate of surgical site infection after post-mastectomy breast reconstruction is usually higher, ranging from 1% to 53%. The clinical features are not constant, and bacterial culture with antibiogram is the gold standard for diagnosis and for identification of antibiotic resistance. While waiting for culture results, empiric therapy with vancomycin and extended-spectrum penicillins or cephalosporins is recommended. Some patients require removal of the infected prosthesis. The main methods to bring down the risk of infection are strict asepsis protocol, preoperative antibiotic prophylaxis, and irrigation of the surgical pocket and implant with an antibiotic solution.

Coverage of the neurovascular unit of the fingertip using a reverse homodigital dorsal flap.

The exposure of bone, tendons, vessels, and nerves in a digital defect is one of the most frequent and severe problems to solve in hand surgery and current approaches are still disappointing. We show the use of an homodigital adipofascial flap taken from the same finger for covering the pulpar defect in a one-step surgical technique able to preserve the digital artery.

Keratoacanthoma arising after site injection infection of cosmetic collagen filler.

INTRODUCTION: Over one million treatments in more than 40 countries have been administered Zyplast implants. Infections at collagen implant sites have occurred in fewer than one per thousand treated patients. PRESENTATION OF CASE: We present a case report of a 27-year-old man; he developed a severe granulomatous reaction in the site of resolvable collagen filler injection Zyplast, and one month later developed a cutaneous nodular lesion. Histological examination of the lesion revealed Keratoacanthoma (KA) with surgical margins free of tumor. We performed two surgical corrections within a period of six months on multiple hypertrophic skin scars of the face. Two years after the last excision, the patient continued to be free of any recurrence. DISCUSSION: Keratoacanthoma (KA) is a benign skin tumor with a quick growth pattern but may regress spontaneously. Though the exact etiology of KA is uncertain, it is found to be more frequent in elderly people, on photo-exposed skin areas and cutaneous infection site. Bovine collagen intradermal injections, though catabolized over the time in the patient, can raise several complications already described in technical literature, but we want underline that cutaneous infection near filler injection site can develope KA as described in our case report. CONCLUSION: KA must be considered as a new local unforeseeable complication of bovine collagen injection to fill facial soft tissue when occurred a face cutaneous infection. We believe that radical excision is the golden standard.

Clinical and histologic effects from CO2 laser treatment of keloids.

Keloids and hypertrophic scars are abnormal responses to wound healing. In general, keloids exhibit a proliferative growth beyond the margins of the scar and remain persistent; while hypertrophic scars are contained to the original wound and may regress over time. In particular, keloid formation is one of the most challenging clinical problems, with increasing frequency in surgical practice. Many treatments are available such as intralesional corticosteroids, topical applications, cryotherapy, surgical excision, radiation therapy, silicone gel sheeting, pressure therapy, and laser therapy. There are no set guidelines for the treatment of keloids and the most common treatments are individualized and depended on the distribution, size, thickness, and consistency of lesions. The authors have evaluated carbon dioxide laser successfully in the treatment of keloids and the aim of this study was to determine the immediate and long-term histologic and clinical effects of keloids after carbon dioxide laser. Fifty consecutive patients (40 females, 10 males, ages 18-60 years, mean age 40 years) with moderate to severe keloids were evaluated. All the patients received regional treatments (deltoid, elbow, chin, and ear) in an outpatient setting with a high-energy pulsed CO2 laser. Significant immediate and prolonged clinical improvement in skin tone, texture, and appearance of carbon dioxide laser was examined in all patients. Dermal remodeling was observed also on histologic examination of biopsied tissue after treatment. Carbon dioxide laser appears to be effective and well tolerated for the treatment of keloids, avoiding the adverse effects and lengthy recovery time.

Negative-pressure pulmonary edema presented with concomitant spontaneous pneumomediastinum: Moore meets Macklin.

Negative-pressure pulmonary edema is an unusual complication mainly associated with general anesthesia. It is caused by excessive negative intrathoracic pressure following a deep inspiration against an acute airway obstruction. The resultant decreased intrathoracic pressure amplifies venous return to the right heart and increases pulmonary capillary wedge pressure that can be further amplified by massive sympathetic discharge due to hypoxia. The combination of increased venous return and pulmonary capillary wedge pressure favours the shift of fluid into the pulmonary interstitium with resultant pulmonary edema. Conversely, spontaneous pneumomediastinum (SP) results from alveolar rupture following an excessive positive intrathoracic pressure. The air leaks out of the alveoli and along the perivascular space toward the mediastinum. We experienced a case of negative pulmonary edema which presented in association with SP. Pneumomediastinum is probably caused by an excessive positive intrathoracic pressure for a subsequent expiration against a closed airway. In the present case, both complications resolved with conservative management.

[Atypical clinical presentation of pigmented purpuric dermatosis]. / Atypische klinische Manifestation einer Pigmentpurpura.

The term pigmented purpuric dermatosis (PPD) is used for a group of mainly asymptomatic, sometimes pruritic dermatoses that are clinically characterized by an eruption of pinpoint purpuric lesions along with yellow, orange, red and/or brown, often patchy pigmented areas. Traditionally five subtypes have been distinguished, but atypical clinical patterns may also occur. Because of the variable clinical spectrum and the similar histopathologic findings, a strict nosological classification is sometimes difficult or even impossible to achieve. We report a case of PPD with atypical clinical features in a young woman, underlining the difficulties in the clinical classification of this spectrum of diseases.