Aesthetic results following breast cancer surgery: A prospective study on 6515 cases from ten Italian Senonetwork breast centers.

Breast cancer treatment has deeply changed in the last decades, since clinical and oncological cure cannot be achieved without patient's satisfaction in term of aesthetic outcomes. Several methods have been proposed to objectively assess these results. However, Italian breast centers have not yet agreed on measurable, reproducible and validated aesthetic outcome indicators to monitor their performance. METHODS: The study was designed and conducted by Senonetwork, a not-for-profit association of Italian breast centers. Ten breast centers were selected based on specific eligibility criteria. This multicentre observational prospective study recruited 6515 patients with diagnosis of in situ or invasive breast cancer who underwent breast surgery in the years 2013-2016. Thirteen indicators of aesthetic results and of related quality of care were analyzed. Data collection and analysis were conducted using a common study database. RESULTS: On average, seven out of ten centers were able to collect data on the proposed indicators with a proportion of missing values < 25%. By expert consensus based on study results, some seven indicators have been defined as "mandatory" while the remaining six have been defined as "recommended" because they require further refinement before they can be proposed for monitoring aesthetic outcomes or because there are doubts on the feasibility of data collection. The minimum standard is reached for 5 of 13 indicators. This finding and the wide range between centers reveal that there is ample room for improvement. CONCLUSIONS: From the present study useful measurable aesthetic parameters have emerged, leading to the definition of target objectives that breast centers can use for benchmarking and improvement of quality of care.

Secondary breast angiosarcoma: A multicentre retrospective survey by the national Italian association of Breast Surgeons (ANISC).

BACKGROUND: Breast angiosarcoma is a malignant mesenchymal neoplasm, which accounts for approximately 2% of all soft tissue sarcomas. Secondary breast angiosarcoma (SBA) may be related to chronic lymphedema after a mastectomy with lymph node dissection (Stewart Treves syndrome) and previous radiotherapy for complications from breast radiation treatment. It is a very rare condition; therefore, diagnosis and management are still a challenge. METHODS: The ANISC collected SBA data by means of a survey sent to all Italian breast centres in the ANISC. The clinicopathological characteristics and the management of this disease were analysed. RESULTS: Twenty-four centres participated in this survey in which 112 cases of SBA were analysed. The median age of the women with SBA was 68.9 years and it appeared approximately 90 months after the first irradiation for breast cancer. In 92% of cases, a mastectomy was performed without axillary dissection for those patients having a high grade of SBA (74.2%). The prognosis was worse in the high-grade cases (overall survival-OS: 36 months) as compared with the low-grade cases (OS: 48 months). After a follow-up of 5 years, 50.5% of the patients were still alive. Disease-free survival (DFS) was 35 months, and there were no differences between the groups of patients with either high- or low-grade histology. CONCLUSIONS: Secondary breast angiosarcoma is a very aggressive disease associated with a short survival outcome. The surgical approach still remains an important step in the course of treatment; furthermore, an accurate histological examination is helpful in establishing the prognosis of the patient. A mastectomy is mandatory. A longer OS was observed in patients with low-grade angiosarcoma as compared to high-grade angiosarcoma (C.I. 40-57 vs. 31-41 months).

Neoadjuvant systemic treatment for breast cancer in Italy: The Italian Society of Surgical Oncology (SICO) Breast Oncoteam survey.

The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a survey to explore the state of the art of neoadjuvant treatment for breast cancer in Italy, specifically focusing on cases treated during the two-year period 2014-2015. A questionnaire was sent to Italian Breast Units with a minimum of 150 new breast cancer cases treated/year according to the Senonetwork directory and to the SICO Breast Oncoteam Breast Unit network. A total of 23/107 Breast Units submitted the survey, reporting a total amount of 20156 cases of breast carcinoma (17241 invasive, 2915 in situ) treated in the biennium, corresponding approximately to 20% of newly diagnosed breast cancers in Italy. In the United States, medical treatment before surgery for breast cancer is indicated in about 22.7% of newly diagnosed cases according to the National Cancer Database, while a German study reported approximately 20% of cases treated with neoadjuvant therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres, showing heterogeneity in neoadjuvant treatment indications, even in multidisciplinary breast units. Better resources should be engaged to achieve a standardised quality indicator for neoadjuvant treatment, and this indicator could be included among the European Society of Breast Cancer Specialists (EUSOMA) quality indicators. In the near future, we plan to develop a second survey to better test improvements in the employment of neoadjuvant therapy after the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen Conference recommendations.

Breast-conservative surgery with and without radiotherapy in patients aged 55-75 years with early-stage breast cancer: a prospective, randomized, multicenter trial analysis after 108 months of median follow-up.

OBJECTIVES: Breast-conserving therapy (BCT), including postoperative whole breast irradiation (WBI), is generally accepted as the treatment of choice for most patients with early-stage breast cancer. The question whether WBI is mandatory in all patients remains one of the most controversial issues in BCT. To answer this question, a randomized, prospective, multicentre study was launched in January 2001. Primary endpoints of the study were to assess the cumulative incidence of in-breast-recurrences (IBR) and overall survival (OAS) after conservative surgery (BCS) with or without WBI. METHODS: From January 2001 until December 2005, 749 patients with unifocal infiltrating breast cancer up to 25 mm, 0-3 positive axillary lymph nodes, no extensive intraductal component or lymphvascular invasion from 11 centres in Italy, were randomly assigned to BCS+WBI (arm 1:373 patients) or BCS alone (arm 2:376 patients). Treatment arms were well balanced in terms of baseline characteristics. Systemic adjuvant therapy was administered according to the institutional policies. Kaplan-Meier method was used for survival analysis and log-rank test to evaluate the difference between the two arms. RESULTS (Last analysis 31.12.2012): After median follow-up of 108 months, 12 (3.4%) IBR were observed in arm 1 and 16 (4.4%) in arm 2. OAS was 81.4% in arm 1 and 83.7% in arm 2. There was no statistically significant difference regarding IBR and death in the two treatment groups. CONCLUSIONS: These data are promising and suggest that WBI after BCS can be omitted in selected patients with early stage breast cancer without exposing them to an increased risk of local recurrence and death. Longer follow-up is needed to further consolidate these results.

Impact of capsaicin on mast cell inflammation.

Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FcERI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism (such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4), histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders.

Role of vitamins D, E and C in immunity and inflammation.

Inflammatory responses are operationally characterized by pain, redness, heat and swelling at the site of infection and trauma. Mast cells reside near small blood vessels and, when activated, release potent mediators involved in allergy and inflammation. Vitamin D modulates contraction, inflammation and remodeling tissue. Vitamin D deficiency has been linked to multiple diseases and several data have demonstrated a strong relationship between serum vitamin D levels and tissue function. Therapy targeting vitamin D3 signaling may provide new approaches for infectious and inflammatory skin diseases by affecting both innate and adaptive immune functions. Mast cells are activated by oxidized lipoproteins, resulting in increased expression of inflammatory cytokines and suggesting that the reduction of oxidation of low density lipoprotein by vitamin E may also reduce mast cell activation. Vitamin C is also an anti-oxidant well-known as an anti-scurvy agent in humans. Vitamin C inhibits peroxidation of membrane phospholipids and acts as a scavenger of free radicals and is also required for the synthesis of several hormones and neurotransmitters. In humans, vitamin C reduces the duration of common cold symptoms, even if its effect is not clear. Supplementation of vitamin C improves the function of the human immune system, such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis and delayed-type hypersensitivity. Vitamin C depletion has been correlated with histaminemia which has been shown to damage endothelial-dependent vasodilation. However, the impact of these vitamins on allergy and inflammation is still not well understood.

Vascular endothelial growth factor (VEGF), mast cells and inflammation.

Vascular endothelial growth factor (VEGF) is one of the most important inducers of angiogenesis, therefore blocking angiogenesis has led to great promise in the treatment of various cancers and inflammatory diseases. VEGF, expressed in response to soluble mediators such as cytokines and growth factors, is important in the physiological development of blood vessels as well as development of vessels in tumors. In cancer patients VEGF levels are increased, and the expression of VEGF is associated with poor prognosis in diseases. VEGF is a mediator of angiogenesis and inflammation which are closely integrated processes in a number of physiological and pathological conditions including obesity, psoriasis, autoimmune diseases and tumor. Mast cells can be activated by anti-IgE to release potent mediators of inflammation and can also respond to bacterial or viral antigens, cytokines, growth factors and hormones, leading to differential release of distinct mediators without degranulation. Substance P strongly induces VEGF in mast cells, and IL-33 contributes to the stimulation and release of VEGF in human mast cells in a dose-dependent manner and acts synergistically in combination with Substance P. Here we report a strong link between VEGF and mast cells and we depict their role in inflammation and immunity.

IL-36 receptor antagonist with special emphasis on IL-38.

IL-36 is another family member of IL-1 and induces the production of proinflammatory cytokines and activates MAPK and NFkB pathways. IL-36 is a common mediator of innate and adaptive immune response and is inhibited by IL-36 receptor antagonist (RA). IL-36RA acts on IL-36 receptor ligand which exerts proinflammatory effect in vivo and in vitro. IL-38 binds to IL-36 receptor as does IL-36RA and has similar biological effects on immune cells. IL-38 is also a member of IL-1 cytokine and shares some characteristics of IL-1RA, binding the same IL-1 receptor type I. IL-38 plays a role in the pathogenesis of inflammatory diseases, exerting protective effect in some autoimmune diseases. Both IL-38 and IL-36RA have an anti-inflammatory biological effect, however in some cases have contrary effects.

Impact of IL -9 and IL-33 in mast cells.

Cytokines serve as chemical communicators from one cell to another and most of them have pro-inflammatory activity. Mast cells have been recognised as important mediators of the pathogenesis of allergy and inflammation, suggesting a role for IL-33-mediated mast cell activation. IL-33 was recently identified as a ligand for the orphan IL-1 family receptor T1/ST2 and is mainly expressed by mast cells, fibroblasts, epithelial cells, and endothelial cells, particularly in high endothelial venules. IL-33 is a potent inducer of pro-inflammatory cytokines such as IL-1, IL-6, IL-13 and TNF, and chemokines (MCP-1), by mast cells. Substance P is capable to induce VEGF from mast cells, and IL-33, the newest pro-inflammatory member of the IL-1 cytokine family, augments the effect of SP in VEGF transcription and translation protein. IL-9 is a pleiotropic and is expressed by multiple T helper (TH) cell subsets. IL-9 promotes the expression of mast cell pro-inflammatory cytokines in vitro and is involved in Th2 responses. This article focuses on recent developments of mast cells, IL-9 and IL-33, and recent literature and investigations were reviewed.

Interleukin-9 and mast cells.

Mast cells are granulated hematopoietic cells derived from stem cells that reside in nearly all tissues and are involved in protection of a host from bacterial infection with a protective and pathogenic activity. Mast cells are important for both innate and adaptive immunity in tissues which are in close contact with the environment. These cells express proinflammatory cytokines such as IL-1, IL-6, IL-8 and tumor necrosis factor which are necessary for innate immunity. Mast cells also produce interleukin-9 and enhance mast cell expression of several cytokines including IL-1beta, IL-5, IL-6, IL-9 and IL-13. In addition, IL-9 can induce mast cell production of TGF-beta which can have proinflammatory downstream effects. IL-9 can function as either a positive or a negative regulator of immune responses and can have a detrimental role in allergy and autoimmunity. Furthermore, IL-9 contributes to disease by promoting mast cell expansion and production of IL-13 which in turn contributes to airway hyperresponsiveness. Here, in this editorial we review the interrelationship between IL-9 and mast cells.

Nutrition and cancer prevention.

Cancer cells invade surrounding tissues and metastasize to distant sites. Diet high in fat is a strong link to, and perhaps causes, a high incidence of tumours. Trans-fatty acid might impair the function and it could be involved in the development of cancer. Cholesterol is also strongly suspected to be involved in the development of tumours, therefore it is important for everyone to eat well, especially for people with cancer to prevent the body tissues from breaking down and helping to rebuild the normal tissue that may have been affected by the treatments. Factors secreted by adipocytes and macrophages such as TNF-alpha and other inflammatory proteins are involved in inflammation in cancer. In addition, MCSF which up-regulates adipocyte tissue is also important for the stimulation of fat cell proliferation and is expressed by human adipocytes. Many cytokines, such as IL-1, IL-6, IL-8, IL-32, IL-33 and MCP-1, are biomarkers for cancer and chronic diseases along with transcription factors NFκB and AP-1; these last two factors are important bioactive substances on the molecular mechanism of the control of genes which in turn affect cellular metabolism. In this paper we revisit the interrelationship between cancer and metabolism.

Role of mast cells in innate and adaptive immunity.

Mast cells play a central role in inflammatory and immediate allergic reactions and are necessary for allergic reactions. Mast cells play a role in the pathophysiology of autoimmune diseases and appear to be especially important in inflamed tissues, because they infiltrate tissues and produce a variety of cytokines. Mast cells are important for both innate and adaptive immunity in tissues that are in close contact with the environment, i.e. the skin, the airways and the lung, and the lining of the intestine. However, there are still many unsolved issues of mast cell functions, including their regulatory mechanism on cell differentiation in bone marrow; for example, the cytokines and transcription factors necessary for their differentiation and expansion, as well as the molecular mechanism underlying basophil migration from the bloodstream to peripheral tissues such as lymph nodes still need to be clarified.

Endothelial cells, cholesterol, cytokines, and aging.

It has been reported that high levels of cholesterol and triglycerides are associated with increased risk of developing atherosclerosis and shorter life. In fact, vascular endothelial dysfunction occurs during the human aging process. Accumulation of lipids in vascular endothelium activates leukocytes to produce cytokines and chemokines which recruit macrophages. On the other hand, macrophages augment inflammatory response and secrete vascular endothelial growth factor, a key cytokine that mediates angiogenesis and inflammatory response. In addition, hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Here, we review the interrelationship between endothelial cells, high level of cholesterol, and aging.

IL-37 (IL-1F7) the newest anti-inflammatory cytokine which suppresses immune responses and inflammation.

Cytokines such as interleukins, chemokines and interferons are immunomodulating and inflammatory agents, characterized by considerable redundancy, in that many cytokines appear to share similar functions. Virtually all nucleated cells, but especially epithelial cells and macrophages, are potent producers of cytokines. The objective of this study is to review the detailed mechanism of action and the biological profiles of IL-37, the newest anti-inflammatory cytokine. This review focuses on IL-37, a key cytokine in regulating inflammatory responses, mainly by inhibiting the expression, production and function of proinflammatory cytokines: IL-1 family pro-inflammatory effects are markedly suppressed by IL-37.

IL-36 a new member of the IL-1 family cytokines.

Interleukin-36 (IL-36) is a pro-inflammatory cytokine which plays an important role in innate and adaptive immunity. IL-36 activates MAPK and NF-kB pathways and is produced by many different cells. This cytokine is a family member of interleukin-1 (IL-1) and plays an important role in the pathophysiology of several diseases. Here we summarise and review the new aspects of this important pro-inflammatory cytokine.

Relationship between cancer and psychology: an updated history.

The mechanism and formation of cancer have always been topics of interest for scientists, even for doctors in ancient times. Nowadays a great role for cancer is played by psychological stress which promotes relevant changes in neuronal activity and gene regulations across the different brain areas. It has been reported by many authors that stress can have an important role in the immune system and may be relevant in the formation of cancer. Our observations, in accordance with other research studies, confirm the importance of the influence of depression, linked to neuroendocrine stress, on the enhancement of cancer pathogenesis by inhibiting anti-tumor immune responses. In this article we review the past and present history of the relationship between cancer and psychology.

Cholesterol and vitamins: revisited study.

The link between low density lipoprotein and coronary heart disease has been widely studied. Oxidized LDL damages the artery wall, and a diet rich in vitamins and low in saturated fat and cholesterol may reduce this risk. Not only hypercholesterolemia but also low levels of high density lipoprotein cholesterol are critical risk factors for atherosclerosis and related diseases. It has been reported that high doses of B complex vitamin may be useful in lowering blood cholesterol and triglyceride levels in the body, however the use of this compound has been limited by an annoying flush and concern for toxicity. Niacin is a B-complex vitamin with anti-atherosclerotic properties and is an effective medication for raising high density lipoprotein. The combination of niacin with other lipid-lowering drugs, such as statins, reduces the dynamic of atherosclerosis disease. In addition, vitamin E is one of the most important lipid soluble anti-oxidants in humans, and reduces atherosclerosis plaque, coronary artery diseases and myocardial infarction. Vitamin E protects the integrity of membranes by inhibiting lipid peroxidation. In this study we revisited the interrelationship between cholesterol, low density lipoproteins and vitamins.

Atherosclerosis: a classic inflammatory disease.

Atherosclerosis is an inflammatory disease due to a diet high in saturated fat, hypercholesterolemia, obesity, hypoglycemia, etc. mainly mediated by the infiltration of macrophage and T cells into the vascular wall. Once the endothelial is damaged monocytes penetrate the tissue and are transformed in scavenger cells. Upon stimulation of Th1 cells, a group of cytokines is released and contributes to the inflammatory response of atherosclerotic tissue. When macrophages proliferate they amplify inflammatory response through the secretion of growth factors and cytokines such as TNF and IL-1. In addition, chemokines such as RANTES and other C-C chemokines are generated, and matrix metalloprotinease 9 (MMP-9) are produced by activated monocytes. However, the immune system in atherosclerosis still remains unclear. Here, in this study we revisited the inter-relationship between atherosclerosis and inflammation.

Conservative surgery with and without radiotherapy in elderly patients with early-stage breast cancer: a prospective randomised multicentre trial.

Breast conserving therapy (BCT) including postoperative irradiation of the remaining breast tissue is generally accepted as the best treatment for the majority of patients with early-stage breast cancer. The question is whether there is a necessity for irradiating all patients. Between 2001 and 2005, 749 women aged 55-75 years with infiltrating breast carcinoma were randomly assigned to breast conservative surgery, with or without radiotherapy (RT), to evaluate the incidence of in-breast recurrence (IBR). After 5 years of median follow-up, the cumulative incidence of IBR was 2.5% in the surgery-only arm and 0.7% in the surgery plus RT arm. There are no differences in terms of overall survival and distant disease-free survival. The preliminary evaluation suggests that breast irradiation after conservative surgery can be avoided without exposing these patients to an increased risk of distant-disease recurrence. Prolonged follow-up will further clarify the possible risks and late sequelae potentially induced by breast RT.