Gloria Semprini

Impact of intraoperative radiotherapy on cosmetic outcome and complications after oncoplastic breast surgery.

Breast cancer is one of the most common tumors in the population worldwide. Conservative breast surgery (CBS) is one of the preferred surgical options, because both the oncologic and esthetic needs of the patient can be addressed. CBS surgical outcomes tend to be more effective with reduced chances of disease recurrence when radiotherapy (RT) treatment is considered as an adjunct treatment, either applied during surgery (IORT) and/or after (EBRT). The purpose of our study was to compare surgical outcomes between IORT and EBRT after CBS. In the past 5 years, we performed CBS in 489 patients in our clinic. Of these patients, 83 underwent adjunct treatment with IORT and 109 were treated with EBRT in accordance with our university approved clinical protocol. Surgical outcomes, early complication rates, and esthetic results were compared between these two groups of CBS patients, with a mean follow‐up time of 17 months. IORT allowed breast irradiation treatment to be performed without effecting overlying skin, thus cosmetic outcomes tended to be favorable. Esthetic postoperative results assessed with the Breast Cancer Conservation Treatment (BCCTcore) software showed that the differences between IORT and EBRT were not statistically significant (including those patients that underwent further oncoplastic techniques after EBRT). The disease recurrence rates between the two groups were not significantly different. IORT is a safe, fast, and feasible technique that provides effective and comparable CBS outcomes for patients with breast cancer.

The breast cancer: a comparison among different diagnostic and therapeutic protocols

N factor erythroid 2-related factor 2 (Nrf2)is a transcription factor that regulate expression of a battery of cytoprotective genes.Over expression of Nrf2 was found in many types of cancers, and created an environment advantageous for cancer cell survival.At physiological concentrations, quercetin as a flavonoid compound can inhibit Nrf2 and sensitized cancer cells to chemotherapeutic agents. We reported quercetin loaded in phytosomeas advanced nanoparticlescarrierkilled cancer cells by more specific when combined with doxorubicin. In this study, we prepared nanophytosoms of quercetin to enhance the bioavailability of quercetin and improve passive targeting in breast cancer cells. Our results showed that co-treatment of the cells with nano particles containing quercetin and doxorubicin has the highest percentage of cell death in MDA-MB 231cells (p<0.05).Furthermore, quercetin-loaded nanoparticles reduced Nrf2 gene expression at mRNA level in the cells higher than quercetin alone (p<0.05). Similarly, expression of downstream genes forNrf2 including NQO1 and MRP1 were reduced significantly (p<0.05).Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhances permeability cancer cells to chemical treatment and may thus be considered as a potential delivery system to increase the therapeutic protocols in cancer patients.R Human cytomegalovirus (HCMV) infection has been found in breast cancer. Our research group has recently detected HCMV in most neoplastic cells in sentinel lymph nodes and brain metastases (BMs) of breast metastases of breast cancer. The exact mechanism by which BMs develop is unknown. Several risk factors are associated with BMs. These include human epidermal growth factor receptor 2–positive breast cancer, triple-negative breast cancer and COX-2 expression, as well as enhanced expression of integrin αvβ3, CXCR4/SDF-1 and CD44. COX-2 expression is thought to mediate impaired bloodbrain barrier functions, while CXCR4/SDF-1, CD44, and integrin αvβ3 are thought to mediate increased metastatic potential to the brain and promote angiogenesis, which may contribute to the development of BM. HCMV infection induces CD40 on the surface of the infected cells that interact with CD40L and results in VEGF production. Moreover, increased expression of integrin αvβ3, CXCR4/SDF-1, and CD44 may promote angiogenesis and initiate metastasis formation. High expression of HCMV-US27, another putative chemokine receptor, has been associated with enhanced expression of CXCR4 and induces cellular migration. In addition, HCMV infection increase expression of CD44, which increases cell–cell interactions, cell adhesion, and migration of infected cells. The prevalence of HCMV proteins and nucleic acids is very high in primary and metastatic tumors and may drive the development of metastasis; therefore, this virus may represent a potential therapeutic target in metastatic cancer. The long term goal of my study is to further understand the oncomodulatory role of HCMV in breast cancer and metastasization.B metastases occur in ~15 % of patients with advanced breast cancer. Their incidence is particularly high in triple negative and HER2-positive disease (30-50%). Therapeutic options for brain metastases are limited and patients with central nervous system involvement have very poor prognosis. In order to better understand the biology of brain metastases, we studied tumour microenvironment in the brain using pre-clinical models of breast cancer brain metastases. In addition to characterizing the inflammatory tumour microenvironment, we developed a pre-clinical strategy for an improved delivery of therapeutic agents into the brain using bone marrow-derived macrophages.T (also known as ANO1 or DOG1) was identified as a pore-forming subunit of the Ca2+-activated Clchannel, and plays an important role in driving the amplification of 11q13 in many types of human cancer.TMEM16A is responsible for facilitating cell growth and metastasis of TMEM16A-expressing,HER2-positive breast cancer cells. Recently, we found a significant decrease in TMEM16A expression and its functional activity induced by vorinostat, a pan-histone deacetylase inhibitor (HDACi) in HER2-positive breast cancer cell line YMB-1. Both pharmacological blockade and siRNA-induced inhibition of HDAC3 elicited a large decrease in TMEM16A expression and its functional activity in YMB-1. Additionally, we recently found that genetic and pharmacological inhibition of TMEM16A is responsible for the regulation of HER2 expression. Taken together, TMEM16A is epigenetically regulated by HDAC inhibition and in malignancies with a frequent gene amplification of TMEM16A, HDAC3 inhibition exerts the suppressive effects on cancer cell viability via a downregulation of TMEM16A.B cancer is one of the most commonly occurring malignant neoplasms among women. Survival from breast cancer has improved steadily over time in many developed countries. Ethnic differences in survival of breast cancer were reported in the USA. Limited evidence suggests that people from culturally and linguistically diverse (CALD) background have lower than average rates of population in cancer screening in Australia. The aim of this research is to understand breast cancer knowledge and screening practices among Muslim migrant women (MMW) living in Sydney metropolitan area. Participants of the study are Muslim migrant women (N=101), over the age of 35 living in metropolitan Sydney; were recruited using convenient and snowball techniques. Survey instrument was used to gather data. Results show that the mean age of the participants’ was 44.9 years, 54% had tertiary education, 57% were unemployed and mostly married (84%). Bivariate results show that education, employment and religious priority are significantly associated with breast cancer knowledge (P<0.05). Breast screening participation was significantly associated with age, residency, English ability, refusal to see male practitioners and breast cancer knowledge (P<0.05). Notable barriers of screening include pain, unnecessary radiation, lack of GP recommendation and something negative may be discovered, suggesting policy implications.T cost of healthcare in the United States is higher than all other developed countries. Despite these expenditures, outcomes lag behind others especially the United Kingdom, when looking at variables such as quality, access, efficiency, equity and healthy lives. The National Comprehensive Cancer Network, The American Society of Clinical Oncology, The United States Preventive Services Task Force, The National Cancer Institute, along with other organizations are increasing their focus on valuebased, evidence-based cancer care as the United States transitions to the era of the Affordable Care Act (ACA). The ACA in some ways mimics the successful program now in place for many years in the United Kingdom which ranks number 1 in three of the five categories noted above. The full discussion of this abstract will review the latest cancer facts and figures in the United States and contrast those to other developed countries such as the United Kingdom. Appropriate risk reduction and prevention strategies, cancer screening controversies, diagnostic testing, treatment options, surveillance and survivorship data will be tabulated, reviewed, and discussed with an economic focus.T negative breast cancers (TNBC) are among the most aggressive and therapy resistant breast tumors and currently possess almost no molecular targets for therapeutic option in this horizon. In the present study we discerned the molecular mechanisms of potential interaction between ER stress response and the MEK/ERK pathway in inducing apoptosis in TNBC cells. Here we observed that induction of ER stress alone was not sufficient to trigger significant apoptosis but simultaneous inhibition of the MEK/ERK pathway enhanced ER stress induced apoptosis via a caspase dependent mechanism. Our study also demonstrated nifetepimine, a dihydropyrimidone derivative as a potent anti-cancer agent in TNBC cells. Nifetepimine downregulated MEK/ERK pathway in MDAMB-231 and MDAMB-468 cells and resulted in blockage of ER stress mediated GRP78 upregulation. Detailed mechanistic studies also revealed that nifetepimine by down-regulating pERK expression also declined the promoter binding activity of TFII-I to the GRP78 promoter and in turn regulated GRP78 transcription. Studies further extended to in vivo Swiss albino and SCID mice models also revalidated the anti-carcinogenic property of nifetepimine. Thus our findings cumulatively suggest that nifetepimine couples two distinct signalling pathways to induce the apoptotic death cascade in TNBC cells and raises the possibility for the use of nifetepimine as a potent anti-cancer agent with strong immune-restoring properties for therapeutic intervention for this group of cancer bearers.Methods: We conducted a single centre, retrospective study in patients who started adjuvant AIs for invasive breast cancer. As per World Health Organization criteria, normal BMD, osteopenia and osteoporosis were defined as T scores of >-1, -1 to >-2.5, and ≤-2.5 respectively. In addition, we measured the frequency of therapeutic intervention at T score cut-off of <-2 as recommended by most guidelines. Subsequently, 4 awareness sessions were conducted to encourage physicians to request a base line DEXA scan for new patients starting adjuvant AIs. The practice was re-audited 5 months later.

The Breast Cancer: a Comparison among Different Diagnostic and Therapeutic Protocols

To the Editor: Experience gained in years of breast cancer research has given rise to the definition of complex and articulated treatment plans. It is safe to say that nowadays, no modern breast surgery unit can fail to involve more than one specialist in its activities [1]. On the other hand, there is still no single protocol, nor even any consensus among the scientific community on the most appropriate timing of the treatments needed to deal with breast cancer [2]. Every different patient care strategy has its pros and cons. In times when economic resources need to be managed more rationally, there is not just an ethical requirement to fulfill, but also a second important one: the chosen protocol must be as cost-effective as possible. The breast surgery protocol adopted at the Udine Surgery Department is the result of an effort to extend this same concept, offering patients a treatment plan that limits the number of treatments they receive to a minimum. All breast cancer patients registered at the clinic are studied by performing breast ultrasound, bilateral mammography, and needle biopsy, followed by magnetic resonance imaging (MRI) of the breast. These tests, including the MRI, are conducted for all patients (not just for dubious cases) to enable an accurate diagnosis of the disease and obtain a precise picture of the lesion’s extent, so that the most suitable, definitive surgery can be planned (aiming for oncological radicality), thus avoiding any need for any further resurgery. When sentinel lymph node biopsy (SLNB) during surgery is required, we have recently adopted the one-step nucleic acid amplification (OSNA) method. Finding a positive lymph node leads to a full axillary lymphadenectomy, completed during the same surgical procedure. Here again, this avoids any need to reoperate after obtaining a definitive histology report [3]. OSNA has drastically reduced the time the pathologist needs to examine the sample, indirectly reducing our operating times too [4]. The breast surgery protocol adopted at our Surgery Department differs in two aspects from what is the standard model, because all patients routinely undergo breast MRI, and any SLNB entails an intraoperative histologic examination. The treatment protocol for breast cancer adopted at our clinic closely resembles the approach taken by such an internationally acknowledged organization as the European Institute of Oncology (IEO) in Milan. The only difference between the IEO’s protocol and the one adopted in Udine lies in that the IEO also does not conduct an MRI routinely in all cases. The aim of this study was to compare the three above-described breast surgery protocols from the economic standpoint, calculating their costs when applied to the case series of surgical procedures performed at our Surgery Department in Udine over a 5-year period. The study considered 767 consecutive patients at the Udine Surgery Department from November 2005 to December 2010. For each patient, we analyzed the available first-level test results and established whether the MRI findings had prompted any changes in the treatment strategy. We considered the type of surgery performed, and particularly any recourse to SLNB. Lymph node positivity would require an axillary lymphadenectomy during the same surgical procedure and we recorded all the cases in which axillary lymphadenectomy was performed. For the data set thus obtained, each parameter of the breast cancer pathway was associated with the corresponding cost to the health care organization. The various costs were combined for each patient, based on the type of surgery performed and the protocol applied. For each patient, we thus obtained three different costs, i.e., the actual cost and those that would have been incurred for the same patient with the same disease had they been treated according to Address correspondence and reprint requests to: Federico Cattin, General Surgery Department, University of Udine, P.le Santa Maria della Misericordia 3, Udine 33100, Italy, or e-mail: doctorfef@gmail.com

The use of chromophore gel-assisted blue light phototherapy (Lumiheal) for the treatment of surgical site infections in breast surgery

Dear Editor, We would like to share our experience using the same device in the management of surgical site infections in breast surgery. A 39 years old patient came to our attention, affected by a left breast cancer which came out in a situation of gigantomasty. The patient underwent, prior to surgery, a neoadjuvant chemotherapy for tumor mass reduction, therefore in the operatory theater we performed a left lumpectomy with complete axillary dissection (due to lymph nodes involvement), in connection with a right reduction mammoplasty for symmetrization purposes. In the 10th postoperative day, an ample infection of both the surgical wounds came out, with an abundant secretion. An immediate treatment with Amoxicillin/Clavulanate per os (1 g three times per day) was set up together with a wound site biopsy for bacterial detection. Nine days later the biopsy response was a MRSA infection, which led to a Trimethoprim/Sulfamethoxazole per os therapy (160 + 800 mg two times per day). The patient began a series of wound medications based on Hydrofibers (Aquacell Ag, Convatec Ltd, Greensboro, NC, USA) as a first, then on Polyurethane foam (Mepliex Ag, Mölnlycke Health care, Goteborg, Sweden) and in the end on negative pressure (PICO, Smith & Nephew, London, UK). 18 medication sessions were performed in 2 months without any perceivable results and with a progressively increasing pain in the affected site. At the end of this period a new surgical site biopsy was done, showing the persistence of the MRSA infection. The whole cost of the disposable medications was about

A simple way to improve the safety of the surgical field

1000. Considering the unsatisfactory results of traditional medications, we began a therapy with Lumiheal (Klox Ltd, Laval, Quebec, Canada), with a 5 minutes blue light exposure twice in every session, two times a week. Eleven Lumiheal applications were performed, with a complete wound healing and a satisfactory aesthetic result. The Lumiheal therapy resulted well tolerated with no complications and, beginning from the second session, helped to progressively reduce local pain as well. Thanks to this medication, the patient was able to undergo a programmed postoperative radiotherapy 3 months after surgery, this means into the range of its maximum efficacy. The patient underwent also adjuvant chemotherapy, with no particular effects over scars or signs of infection relapse. At the present time the patient shows a complete healing with no signs of cancer relapse. Considering the particular efficacy of chromophore phototherapy in controlling wound infections and stimulate neoangiogenesis, we consider Lumiheal as a useful tool in surgical site infection management, and we use it as a second‐line therapy in any kind of lesions resisting to the standard one. Further clinical randomized trials are needed to better evaluate this clinical approach, but our preliminary results using Lumiheal seem very promising in treating surgical infections.

Oncoplastic surgery and cancer relapses: cosmetic and oncological results in 489 patients.

Electrocoagulation produces fumes that contain tiny particles, which can travel considerable distances from the place where the fumes are generated, becoming deposited in the pulmonary alveoli. breasts in 15% and the respiratory system in 10% of cases. Only 1–3% of all reported cases are malignant.[3] Even though the true recurrence rate following resection is unknown, wide resection of the tumour when it occurs in a digital nerve is recommended by Slutsky[1] based on its propensity for local recurrence. The use of radiotherapy and chemotherapy is advisable only in treating the malignant forms of such tumours.[2]