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Introduction Oncoplastic breast surgery has evolved the surgical treatment of breast cancer over the past two decades. This practice still lacks validation and poses several dilemmas in terms of safety, local and systemic control, timing of adjuvant treatments and cost-effectiveness. Our case series investigates the effects of a reduced surgical complexity on cosmetic results and quality of life. Methods We treated 76 consecutive patients affected by early stage breast cancer from January 2016 to April 2017. We employed a decision support system to assist the final shared decision making. The communication process before surgery included new specific information on recent evidence about local control of disease and outcomes after multimodality treatment. In order to estimate the oncoplastic complexity, we created a new score based on scars, bilateral procedures and type and timing of reconstructions. We compared the outcomes of this series to that of a previous one from the same institution. Results The medium complexity score (CS) in the current series was significantly lower compared to that of the previous series (medium CS cohort 1 = 3.1 vs medium CS cohort 2 = 1.51; p = 0.001). Complications according to Clavien-Dindo classification did not vary significantly between the two series (p = 0.7). The increased use of primary systemic treatment did not translate into a significantly lower mastectomy rate (cohort 1 = 20% vs cohort 2 = 16%; p = n.s.). There was no significant difference in breast deformities after breast conserving surgery (p = 0.2). The BCCT.Core demonstrated a 67.1% occurrence of “good” results. Quality of life in patients who underwent breast-conserving surgery measured using the Breast-Q demonstrated similar results in the pre-post-op assessment. Conclusions This study hypothesizes that a proper information may impact on patient's decisions and may reduce surgical complexity. This reduction likely has no effects on the main surgical outcomes estimated using standard tools. More investigations should be performed on a larger multi-institutional scale to confirm these conclusions.

The primary study objective is to compare the outcomes of patients taking oral anticoagulant medications in two distinct populations treated according to different management models (comprehensive vs. usual care). (Design: regional prospective cohort study; setting: hospital admission data from two regions). Eligible partecipants were patients taking oral anticoagulant drugs (vitamin K antagonist or direct oral anticoagulants), residents in the Vicenza and Cremona districts from February 1st, 2016 to June 30th, 2017. Patients were identified by accessing the administrative databases of patient drug prescriptions. The primary study outcome was admission to the Emergency Department for stroke, systemic arterial embolism, recurrence of venous thromboembolism or major bleeding. The study evaluated outcomes in 14,226 patients taking oral anticoagulants, of whom 6725 being followed in Cremona with a comprehensive management model. There were 19 and 45 thromboembolic events over 6205 and 6530 patient-years in the Cremona and Vicenza cohort, respectively (IRR 0.44, 95% CI 0.24-0.77). The reduction of events in the Cremona cohort was almost entirely explained by a decrease of events in patients taking VKA (IRR 0.41, 95% CI 0.20-0.78) but not DOACs (IRR 1.08, 95% CI 0.25-5.24). The rate of major bleeding was non-significantly higher in Cremona than in Vicenza (IRI 1.32; 95% CI 0.74-2.40). Across the two cohorts, the risk of bleeding was lower in patients being treated with DOACs rather than warfarin (10/4574 vs. 42/8161 event/person-years, respectively, IRR 0.42 95% CI 0.19-0.86). We conclude that a comprehensive management model providing centralized dose prescription and follow-up may significantly reduce the rate of thromboembolic complications, without substantially increasing the number of bleeding complications. Patients treated with direct oral anticoagulants appear to have a rate of thromboembolic complications comparable to VKA patients under the best management model, with a reduction of major bleeding.

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p &lt, 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p &lt, 0.001), body image (p &lt, 0.001), future perspective (p &lt, 0.001), well-being (p = 0.001), and reductions in fatigue (p &lt, 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p &lt, 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.

Background Hereditary hemorrhagic telangiectasia (HHT) is a multisystemic inherited vascular disease characterized by a heterogeneous clinical presentation and prognosis. Dietary evaluation is relevant in HHT patients to provide adequate iron and nutrient intake. Additionally, different dietary items have been reported to precipitate epistaxis in this setting. Our primary aim was to investigate the dietary habits of HHT patients through a food-frequency questionnaire (FFQ) to evaluate the presence of precipitants and/or protective factors for epistaxis and the occurrence of possible dietary modifications. The secondary aims were to evaluate the nutritional intake of iron in HHT patients and the self-reported effect of iron treatments on epistaxis. From April 2018 to October 2018, a 138-item FFQ was provided to HHT patients followed up at the HHT Referral Center of Crema Maggiore Hospital. The relationship between food items and epistaxis was ascertained on a separate form. Daily iron intake was calculated to establish the mean iron content of food items reported in the FFQ. Results One hundred forty-nine questionnaires were evaluated [72 females, median age 54 years (12–76). Overall, 26 (18%) patients reported dietary items that improved epistaxis (mostly blueberries and red fruits, green vegetables and legumes), while 38 (26%) reported some dietary items that exacerbated epistaxis (spices, chocolate, alcohol, strawberries and ginger). Dietary modifications were reported in up to 58% of cases. In HHT patients, the mean daily iron intake was 8.46 ± 2.78 mg, and no differences were observed in the iron intake of patients reporting a diet modification and those who did not. Conclusions In the comprehensive management of HHT a healthy and balanced diet, with increased consumption of dietary items with a high iron content, should be encouraged.

Evidence suggests a beneficial role of the Mediterranean Diet (MedDiet) on health-related quality of life (HRQoL) in healthy subjects. HRQoL is relevant in cancer therapy and disease outcomes, therefore we investigated the association between adherence to the MedDiet and HRQoL in breast cancer survivors participating in the multicentre trial DEDiCa. Diet and HRQoL were assessed at baseline in a subgroup of 309 women enrolled within 12 months of breast cancer diagnosis without metastasis (stages I-III, mean age 52±1 yrs, BMI 27±7 kg/m2). The 14-item PREDIMED questionnaire was used to analyse adherence to the MedDiet. HRQoL was assessed with three validated questionnaires measuring physical, mental, emotional and social factors: EQ-5D-3L, EORTC QLQ-C30 and EORTC QLQ-BR23. Analysis of variance (ANOVA) and multivariate analyses were performed to assess the possible role of the MedDiet on HRQoL. Patients with higher adherence to MedDiet (PREDIMED score >7) showed significantly higher scores for physical functioning (p = 0.02) and lower scores on the symptomatic pain scale (p = 0.04) assessed by the EORTC QLQ-C30 questionnaire compared to patients with a lower adherence to MedDiet (PREDIMED score ≤7). Higher scores from the EQ-5D-3L indicating higher well-being were observed mainly in participants with higher MedDiet adherence (p = 0.05). In adjusted multivariate analyses significant positive associations were found between MedDiet, physical functioning (p = 0.001) and EQ 5D-3L score (p = 0.003) while inverse associations were found with pain and insomnia symptoms (p = 0.005 and p = 0.029, respectively). These results suggest that higher adherence to the MedDiet in breast cancer survivors is associated with better aspects of quality of life, specifically higher physical functioning, better sleep, lower pain and generally higher well-being confirming findings in healthy subjects.

Background One of the most common complications of the use of foreign material, in both reconstructive and cosmetic breast surgery, is capsular contracture. Historically, research on capsular contracture has focused mainly on reducing bacterial contamination through antibiotic solutions. Only secondary studies have focused on pharmacological control of the inflammation process, with particular attention paid to the main inflammation pathway, the arachidonic acid cascade. An important role in the arachidonic acid cascade is played by the omega-3 fatty acids, which are found mainly in oily fish and food supplements. The goal of the present study was to investigate the effects of omega-3 supplements on capsule contraction. Methods Female C57BL/6 mice were implanted with custom-made silicone gel implants and divided into two groups. The treated group received omega-3 oil daily while the control group received water daily by gavage. After mice were euthanized, samples of capsules were collected to evaluate thickness and transforming growth factor (TGF)-β expression. Results The results showed that capsules in the omega-3 group were thinner and more transparent than those found in the control group. In addition, a significant downregulation of the TGF-β2 gene transcript was observed in the omega-3 group. Conclusions Omega-3 supplementation seems to be effective in reducing the occurrence of capsular formation, mainly through inhibition of the TGF-β pathway and impairment of collagen deposit. Omega-3 supplementation is a simple and promising method that could be used to prevent or at least reduce capsular contracture after silicone implant surgery.

In severely obese patients with type 2 diabetes (T2DM), the metabolic benefits after biliopancreatic diversion (BPD) are due to mechanisms independent of weight loss. Therefore, the anti-diabetic effect of BPD in overweight or mildly obese T2DM patients was investigated. Ninety T2DM patients with BMI 25–35 underwent BPD and were evaluated 1 and 5 years after the operation (follow-up rate 100 and 83%, respectively). T2DM control (Hb1Ac

The diagnosis of spindle cell lesions of the breast parenchyma is challenging. Some of these lesions share the expression of CD34, posing differential diagnostic problems, especially in core biopsies. Recently, antibodies against the STAT6 C-terminal, are being used in paraffin-embedded tissues as a surrogate for identifying the NAB2-STA6 fusion gene which is considered a specific molecular marker for solitary fibrous tumor. Accordingly, we investigated the expression of STAT6 in a large series of uncommon spindle cell tumor-like and tumor lesions occurring primarily in the breast parenchyma. We collected 10 classic-type myofibroblastomas, 9 desmoid-type fibromatosis, 6 spindle cell metaplastic carcinoma, 5 benign fibroblastic spindle cell tumors, 3 solitary fibrous tumors, 7 pseudoangiomatous stromal hyperplasias, 2 reactive spindle cell nodules, 1 leiomyoma, 1 spindle cell lipoma, 1 case of inflammatory pseudotumor, 1 nodular fasciitis, 1 myxoma and 1 dermatofibrosarcoma protuberans. A diffuse and strong nuclear STAT6 expression was restricted only to solitary fibrous tumors, while the other lesions were negative or showed only weak cytoplasmic expression. The present study confirms that the demonstration of a diffuse and strong STAT6 nuclear staining is very helpful in distinguishing solitary fibrous tumor from other spindle cell mimics arising in the breast.

Background Mechanisms influencing breast cancer (BC) development and recurrence include hyperglycemia, hyperinsulinemia, high insulin-like growth factor-1, high circulating estrogen, inflammation and impaired cellular differentiation/apoptosis. A lifestyle program that targets all the above mechanisms may be warranted. Low glycemic index (GI) foods produce lower post-prandial glucose and insulin responses and have been associated with lower BC risk. Moderate physical activity post-diagnosis reduces BC recurrence and mortality, partly explained by reduced insulin and estrogen levels. Vitamin D increases cell differentiation/apoptosis and high serum vitamin D levels improve BC survival. Yet no trial has evaluated the combined effect of a low GI diet, moderate physical activity and vitamin D supplementation on BC recurrence in the context of a Mediterranean lifestyle setting. Methods Women (30-74 yr) who had undergone surgery for primary histologically confirmed BC (stages I-III) within the previous 12 months, in cancer centres in Italy, will be randomized to follow, for a maximum of 33 months, either a high intensity treatment (HIT) composed of low GI diet + exercise + vitamin D (60 ng/mL serum concentration) or a lower intensity treatment (LITE) with general advice to follow a healthy diet and exercise pattern + vitamin D to avoid insufficiency. Both interventions are on a background of a Mediterranean diet. Considering a 20% recurrence rate within 3 years for BC cases and a predicted rate of 10% in the HIT group, with power of 80% and two-sided alpha of 0.05, the subject number required will be 506 (n = 253 in each arm). Clinic visits will be scheduled every 3 months. Dietary and exercise counselling and vitamin D supplements will be given at each clinic visit when blood samples, anthropometric measures and 7-day food records will be collected. Discussion DEDiCa study aims to reduce BC recurrence in women with BC using a lifestyle approach with additional vitamin D and to investigate possible cardio-metabolic benefits as well as epigenetic modifications according to lifestyle changes. Given the supporting evidence and safety of the components of our intervention we believe it is feasible and urgent to test it in cancer patients. Trial registration May 11, 2016; NCT02786875. EudraCT Number 2015-005147-14

Reconstruction options following nipple-sparing mastectomy (NSM) are diverse and not yet investigated with level IA evidence. The analysis of surgical and oncological outcomes of NSM from the Italian National Registry shows its safety and wide acceptance both for prophylactic and therapeutic cases. A further in-depth analysis of the reconstructive approaches with their trend over time and their failures is the aim of this study. Data extraction from the National Database was performed restricting cases to the 2009–2014 period. Different reconstruction procedures were analyzed in terms of their distribution over time and with respect to specific indications. A 1-year minimum follow-up was conducted to assess reconstructive unsuccessful events. Univariate and multivariate analyses were performed to investigate the causes of both prosthetic and autologous failures. 913 patients, for a total of 1006 procedures, are included in the analysis. A prosthetic only reconstruction is accomplished in 92.2 % of cases, while pure autologous tissues are employed in 4.2 % and a hybrid (prosthetic plus autologous) in 3.6 %. Direct-to-implant (DTI) reaches 48.7 % of all reconstructions in the year 2014. Prophylactic NSMs have a DTI reconstruction in 35.6 % of cases and an autologous tissue flap in 12.9 % of cases. Failures are 2.7 % overall: 0 % in pure autologous flaps and 9.1 % in hybrid cases. Significant risk factors for failures are diabetes and the previous radiation therapy on the operated breast. Reconstruction following NSM is mostly prosthetic in Italy, with DTI gaining large acceptance over time. Failures are low and occurring in diabetic and irradiated patients at the multivariate analysis.

Background The increased complexity of the decisional process in breast cancer surgery is well documented. With this study we aimed to create a software tool able to assist patients and surgeons in taking proper decisions. Methodology We hypothesized that the endpoints of breast cancer surgery could be addressed combining a set of decisional drivers. We created a decision support system software tool (DSS) and an interactive decision tree. A formal analysis estimated the information gain derived from each feature in the process. We tested the DSS on 52 patients and we analyzed the concordance of decisions obtained by different users and between the DSS suggestions and the actual surgery. We also tested the ability of the system to prevent post breast conservation deformities. Results The information gain revealed that patients preferences are the root of our decision tree. An observed concordance respectively of 0.98 and 0.88 was reported when the DSS was used twice by an expert operator or by a newly trained operator vs. an expert one. The observed concordance between the DSS suggestion and the actual decision was 0.69. A significantly higher incidence of post breast conservation defects was reported among patients who did not follow the DSS decision (Type III of Fitoussi, N = 4; 33.3%, p = 0.004). Conclusion The DSS decisions can be reproduced by operators with different experience. The concordance between suggestions and actual decision is quite low, however the DSS is able to prevent post- breast conservation deformities.

Background Nipple sparing mastectomy is deemed surgically and oncologically safe based on a long lasting literature data from reviews of single institution series. This study aims at evaluating surgical and oncological outcomes of NSM on a large multi-institutional scale, by means of the Italian National registry. Methods In July 2011 a panel of Italian specialists agreed upon and designed a National database of NSM. Centers with at least 150 cancers per year and following the National follow-up schedule guidelines could participate inserting any NSM case performed, retrospectively and prospectively from that moment on. In March 2015 analysis of data was accomplished. Dataset for this study consists of cases performed in the period between January 1st 2009 and December 31st 2014. Results 913 Women were included in the analysis, for a total of 1006 procedures. Prophylactic mastectomies were 124 (12.3%). MRI utilization increased over time. NSM failure rate, with NAC removal for any reason was 11.5%. NAC necrosis rate was 4.8%. Larger skin-flap necrosis rate was 2.3%. Major surgical complications rate was 4.4%. Oncological outcomes were calculated among primitive EBC cases only: locoregional recurrences rate was 2.9%, NAC recurrence 0.7%. Systemic recurrence rate was 1.0%. Five deaths (0.7%) were registered. Conclusions More than 10% of NSM procedures are prophylactic mastectomies. MRI is gaining more importance over time. Surgical and oncological results show that NSM is effective. This National multicentric analysis enables a comparison of results with no geographical differences and a "safe" state of the art of NSM in Italy.

Breast cancer during pregnancy is a dramatic event that interrupts one the most joyful aspects of the life of a woman. The diagnostic/therapeutic setting is deeply affected by the presence of a second individual (the fetus) during its intrauterine development. For this reason, the most common decisional pathways need to be modified to minimize collateral effects. Termination of pregnancy is a possible issue that has to be discussed, although currently no evidence is available regarding any benefit in terms of improved survival.

Breast cancer is the worldwide leading cause of cancer incidence among women. Night shift work exposure has been recently considered one of the significant breast cancer risk factors in industrialized countries. The mechanisms by which this work exposure may be responsible for cancer development is still discussed. In the last 15 years, many authors have paid attention to the relationship between night shift work and breast cancer risk. In the current study, eight case-control studies and four prospective epidemiological studies describing such relationship are discussed. A positive correlation between night shift work and breast cancer risk was described in 8 out of 12 studies. However, different reasons suggest that some of these studies have an Achilles heel according to the International Agency of Cancer (IARC) indications. Both the circadian system alteration and the melatonin output reduction, related to the exposure to light-at-night during night shift work, remain the most valid hypotheses on the causal relation of shift work and breast cancer. Overall, the results of the present study suggest that there is an association between night shift work and breast cancer development in western countries. However, further studies are needed to confirm such association and to understand which biomolecular mechanisms may be involved in the pathogenesis of cancer diagnosed in patients with night shift work exposure.

Background Breast cancer is the most commonly diagnosed cancer among U.S. women .The 5-year survival rate for this tumour is nowadays 85%, and the 61% of these women are still alive at 15 years. When depression symptoms are present as a consequence of breast cancer treatments, they may interfere negatively with patients’ quality of life. The aim of this study was to examine the effects of breast cancer treatment on the quality of life and the impact of depression on the health-related life. Methods We enrolled 173 women aged 65-75 years with early stage breast cancer diagnosed over the last 10 years, initially recruited to participate in a study examining heath-related quality of life in the first 5 years after breast cancer diagnosis. Participants were divided into four groups: 1) 46 breast cancer survivors (aged 65-70); 2) 62 women diagnosed with breast cancer (aged 65-69); 3) 32 women with recurrent breast cancer after 10 years (aged 66-75); 4) 30 women in good health status (aged 60-70). The Geriatric Depression Scale was used as a routine part of a comprehensive geriatric assessment. Collection of data for the application of instruments, such as sociodemographic variables (age, educational level, social state) and clinical date (stage and time of the disease and treatment), was carried out by trained researcher assistants. Results Our results demonstrated the correlation between depression and previous cancer experiences. In fact, in patients with cancer experience, the grade of depression was significantly higher compared to healthy subjects. Furthermore, we demonstrated that the patients with recurrent breast cancer were severely depressed compared to other groups. Conclusions A high percentage of participants were identified as having emotional and/or well being problems. Further investigations on the cause of depression problems cancer-related are needed.