Targeting the future of axillary staging in breast cancer. A comparative study between axillary surgery and PET/MR Imaging

Introduction: Over time the surgical treatment of axilla in breast cancer has evolved towards a progressive de-escalation. Considering its gradual switch from a therapeutic to a staging procedure, the role of preoperative imaging has strongly increased. To date, an unmet need is to achieve the most accurate assessment of the axilla in order to choose the less invasive surgical treatment. PET/MR is a new imaging tool with promising results on axillary staging. The study hypothesis is that PET/MR might provide a single, one-stage, non-invasive, operatorindependent imaging modality allowing surgeons to select the proper axillary treatment in two different settings of primary surgery for node-negative breast cancer and primary systemic therapy (PST) for node-positive breast tumors. Patients and methods: This study was a prospective comparative study that was carried out at San Raffaele Hospital and planned in two separate groups: • N0 group: patients with node negative early (c/iT<3cm) breast cancer who were candidates to sentinel node biopsy (SNB) and were enrolled to perform an additional PET/MR before surgery. • N+ group: patients with node positive breast cancer undergoing PST who were recruited to perform two PET/MR exams, one before and one after PST. Primary outcome was to compare the staging power between PET/MR vs SNB or axillary dissection in detecting axillary node macro-metastases (>2 mm), evaluating the concordance rate between the two tools. Secondary outcome was to compare PET/MR and Ax-US, evaluating the concordance rate between the two exams. Results: From October 2019 to November 2020 forty-eight patients were recruited and analyzed. • N0 group: 17 patients were analyzed. Mean age was 54.3±11.2 years. All patients had a unifocal luminal cT1-2 breast cancer. After PET/MR twenty new findings were discovered, 20% being false positive. PET/MR concordance rate with SNB was 82.4 %. PET/MR and Ax-US were concordant in 88.2% of cases. • N+ group: 14 patients were analyzed. Mean age was 47.9±14.1 years. Most of them had a cT2- 3(78.6%), triple negative or Her2-ve (64.3%) breast cancer at diagnosis. After initial PET/MR twenty-one new findings were discovered, 9.5 % being false positive. PET/MR concordance rate with SNB was 71.5 %. Preoperative PET/MR and Ax-US were concordant in 92.9% of cases. Conclusions: To date, current evidence are too preliminary to draw meaningful conclusions on the role of PET/MR in breast cancer treatment but results from ongoing prospective trials are awaited in three years and should help decide the potential applications of this cutting-edge imaging tool in breast cancer patients

Feasibility and Safety in Outpatient Clinic

Abstract Throughout the last decade, aesthetic breast surgery has enormously spread in the outpatient clinic setting where plastic surgeons perform the vast majority of procedures under local anesthesia as day-case operations. The "tumescent anesthesia" is defined as the injection of a dilute solution of local anesthetic combined with epinephrine and sodium bicarbonate into subcutaneous tissue until it becomes firm and tense, which is "tumescent." The "cold tumescent anesthesia" (CTA) derives from Klein's solution with the introduction of a new concept, which is the low temperature (4°C) of the injected solution. This novelty adds further anesthetic and hemostatic power to the well-known benefits of tumescent anesthesia. The authors report their experience with CTA in the last 15 years in the setting of aesthetic breast surgery, describing in detail the anesthesia protocol, surgical outcomes, and patient satisfaction. A total of 1541 patients were operated on during the study period and were included in this retrospective analysis. The types of breast procedures were breast augmentation in 762 cases (49.4%), mastopexy with implants in 123 patients (8.0%), mastopexy without implants in 452 cases (29.3%), and breast reduction in 204 cases (13.3%). Patient mean age was 42.8 years (range, 18–67 years). The mean operating time was 37 ± 32 minutes for breast augmentation, 78 ± 24 minutes for mastopexy with implants, 58 ± 18 minutes for mastopexy without implants, and 95 ± 19 minutes for breast reduction. No major complications occurred, and no conversion to general anesthesia was required. The median recovery time was 150 minutes (range, 120–210 minutes), and all patients were discharged within 3 hours after surgery. Wound or implant infections occurred in 33 patients (2.1%), wound dehiscences in 21 (1.4%), and postoperative bleeding requiring return to theater in 2 cases (0.1%). Thirteen patients (0.8%) developed capsular contracture. Fifteen patients (1%) required reintervention due to implant rotation or rupture. The median visual analog scale score was 1.8 (interquartile range, 1–3) after discharge. Patient satisfaction was very high in 91.3% (n = 1407) of the cases. In experienced hands, CTA can shorten operating time with high patient satisfaction and a low complication rate. These preliminary data could be hypothesis generating for future multicenter prospective trials done to confirm the benefits of CTA in other surgical fields

SV-IV Peptide1–16 reduces coagulant power in normal Factor V and Factor V Leiden

Native Factor V is an anticoagulant, but when activated by thrombin, Factor X or platelet proteases, it becomes a procoagulant. Due to these double properties, Factor V plays a crucial role in the regulation of coagulation/anticoagulation balance

Rivaroxaban Monotherapy in Patients with Pulmonary Embolism: Off-Label vs. Labeled Therapy

Oral anticoagulants; Rivaroxaban; Venpus thromboembolismAnticoagulantes orales; Rivaroxaban; Tromboembolismo de venpusAnticoagulants orals; Rivaroxaban; Tromboembolisme de venpusBackground: The use of rivaroxaban in clinical practice often deviates from manufacturer prescribing information. No studies have demonstrated an association between this practice and improved outcomes. Methods: We used the RIETE registry to assess the clinical characteristics of patients with pulmonary embolism (PE) who received off-label rivaroxaban, and to compare their 3-month outcomes with those receiving the labeled therapy. The patients were classified into four subgroups: (1) labeled therapy; (2) delayed start; (3) low doses and (4) both conditions. Results: From May 2013 to May 2022, 2490 patients with PE received rivaroxaban: labeled therapy—1485 (58.6%); delayed start—808 (32.5%); low doses—143 (5.7%); both conditions—54 (2.2%). Patients with a delayed start were more likely to present with syncope, hypotension, raised troponin levels and more severe abnormalities on the echocardiogram than those on labeled therapy. Patients receiving low doses were most likely to have cancer, recent bleeding, anemia, thrombocytopenia or renal insufficiency. During the first 3 months, 3 patients developed PE recurrence, 4 had deep-vein thrombosis, 11 had major bleeding and 16 died. The rates of major bleeding (11 vs. 0; p < 0.001) or death (15 vs. 1; OR: 22.5; 95% CI: 2.97–170.5) were higher in patients receiving off-label rivaroxaban than in those on labeled therapy, with no differences in VTE recurrence (OR: 1.11; 95% CI: 0.25–6.57). Conclusions: In patients with severe PE, the start of rivaroxaban administration was often delayed. In those at increased risk for bleeding, it was often prescribed at low doses. Both subgroups had a worse outcome than those on labeled rivaroxaban

Upper extremity dvt in oncological patients: analysis of risk factors. Data from the RIETE registry

Aim: The aim of the study is to up date informations on the clinical characteristics and outcome of patients with upper-extremity deep vein thrombosis (DVT) from the Informatised Registry on Venous Thromboembolism (RIETE). Methods: RIETE is an ongoing registry of consecutive patients with symptomatic, objectively confirmed, acute venous thromboembolism. In this analysis the clinical characteristics and 3-month outcome of all cancer patients with upper-extremity DVT were evaluated. Results: Up to February 2006, a total of 14,391 patients with symptomatic, objectively confirmed acute venous thromboembolism had been enrolled in RIETE. Of the 2,945 patients with active cancer 196 (6.7%) had arm DVT: 104 had catheter-associated DVT. Most cancer patients with arm DVT were males, younger than 65, and had a low incidence of additional risk factors or underlying diseases. Twenty of them (10%) had symptomatic pulmonary embolism (PE). Most patients were treated with low-molecular-weigh heparin, both initially (94%) and after discharge (75%). During the 3-month follow-up period 12 patients (6.1%) developed VTE recurrences (PE 6, DVT 6), 8 (4.1%) had major bleeding (fatal in 3), 43 (22%) died. Conclusions: Our data from the RIETE registry show that upper limb DVT is a serious complication in patients with cancer, with a high incidence of recurrences and bleeding complications.Цель: обновить базу данных по клиническим характеристикам и течению заболевания у больных с тромбозом глубоких вен верхних конечностей (ТГВ) с использованием системы регистра венозного тромбоэмболизма (СРВТ). Методы: СРВТ является непрерывной системой регистрации больных с симптомами объективно подтвержденной острой венозной тромбоэмболии. Проанализированы клинические характеристики и течение болезни на протяжении месяцев у больных онкологического профиля с ТГВ. Результаты: в период декабря 2006 г. были обследованы 14 391 больных с симптоматической объективно подтвержденной острой венозной тромбоэмболией при помощи системы СРВТ. Из 2945 больных с прогрессирую­щим течением заболевания у196 (6,7%) человек выявили ТГВ верхних конечностей: у 104 — ассоциированный с катетером ТГВ. Большинство больных с ТГВ верхних конечностей — лица мужского пола в возрасте моложе 65 лет и с низкой частотой дополнительных факторов риска или первичного заболевания. У 20 из них (10%) отмечали симптомы эмболии легочной артерии (ЭЛА). Больные получали низкомолекулярный гепарин и в начале исследования (94%), и по его окончании (75%). В течение последующих трех месяцев у12 больных (6,1%) развился рецидив венозной тромбоэмболии (ВТЭ) (ЭЛА – у 6 больных, ТГВ – у 6 больных), у 8 (4,1%) отмечали кровотечение (3 случая с летальным исходом), 43 (22%) пациента умерли. Выводы: данные СРВТ системы показали, что ТГВ верхних конечностей является серьезным осложнением у больных, онкологического профиля, сочетающимся с высокой степенью развития рецидива и осложнений, сопровождающихся кровотечениями

Ovarian reserve of women with and without BRCA pathogenic variants: A systematic review and meta-analysis.

INTRODUCTION Preliminary clinical evidence suggests a detrimental effect of pathogenic variants of BRCA1 and 2 genes on fertility outcome. This meta-analysis evaluates whether women carrying BRCA mutations (BRCAm) have decreased ovarian reserve, in terms of Anti-Muellerian Hormone (AMH), compared to women without BRCAm (wild-type). MATERIAL AND METHODS Systematic searches of PubMed, Medline, Scopus, Embase, Science Direct and the Cochrane Library from inception until July 2020 were conducted. All studies comparing AMH level in fertile age women, with and without BRCA pathogenic variants were considered. Sub-analyses were performed according to age, presence of breast cancer, and type of mutation. RESULTS Among 64 studies, 10 series were included. For the entire cohort, a trend of reduced AMH level were found between BRCAm carriers and women without pathogenic variants. BRCAm carriers aged 41-years or younger had lower AMH levels compared to 41-years or younger wild type women (OR: 0.73 [95%CI-1.12;-0.35]; p = 0.0002). This finding was confirmed for BRCA1m carriers (OR: 1 [95%CI-1.96;-0.05]; p = 0.004) whereas no difference was observed between BRCA2m carriers and wild type women. The same analysis on breast cancer patients with and without BRCAm achieved the same results. CONCLUSION Young BRCA1m carriers seem to have lower AMH level compared with wild type women and therefore a potential decreased ovarian reserve

The impact of the COVID-19 pandemic on surgical management of breast cancer:global trends and future perspectives

Introduction: The rapid spread of COVID-19 across the globe is forcing surgical oncologists to change their daily practice. We sought to evaluate how breast surgeons are adapting their surgical activity to limit viral spread and spare hospital resources. Methods: A panel of 12 breast surgeons from the most affected regions of the world convened a virtual meeting on April 7, 2020, to discuss the changes in their local surgical practice during the COVID-19 pandemic. Similarly, a Web-based poll based was created to evaluate changes in surgical practice among breast surgeons from several countries. Results: The virtual meeting showed that distinct countries and regions were experiencing different phases of the pandemic. Surgical priority was given to patients with aggressive disease not candidate for primary systemic therapy, those with progressive disease under neoadjuvant systemic therapy, and patients who have finished neoadjuvant therapy. One hundred breast surgeons filled out the poll. The trend showed reductions in operating room schedules, indications for surgery, and consultations, with an increasingly restrictive approach to elective surgery with worsening of the pandemic. Conclusion: The COVID-19 emergency should not compromise treatment of a potentially lethal disease such as breast cancer. Our results reveal that physicians are instinctively reluctant to abandon conventional standards of care when possible. However, as the situation deteriorates, alternative strategies of de-escalation are being adopted. Implications for Practice: This study aimed to characterize how the COVID-19 pandemic is affecting breast cancer surgery and which strategies are being adopted to cope with the situation. © 2020 AlphaMed Pres

Effects of the dose of erythropoiesis stimulating agents on cardiovascular events, quality of life, and health-related costs in hemodialysis patients: the clinical evaluation of the dose of erythropoietins (C.E. DOSE) trial protocol

<p>Abstract</p> <p>Background</p> <p>Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin levels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of randomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular outcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted hemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for the management of anemia in patients with end stage kidney disease.</p> <p>Methods/Design</p> <p>This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204 hemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous epoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall outside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non fatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.</p> <p>Discussion</p> <p>The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of hemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and harms of different fixed ESA doses.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00827021</p

Clinical correlates of "pure" essential tremor: the TITAN study

BackgroundTo date, there are no large studies delineating the clinical correlates of "pure" essential tremor (ET) according to its new definition.MethodsFrom the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of "pure" ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum.ResultsOut of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) "pure" ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options.DiscussionThe findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of "pure" ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of "pure" ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies

Evaluating the ability of an artificial-intelligence cloud-based platform designed to provide information prior to locoregional therapy for breast cancer in improving patient's satisfaction with therapy: the CINDERELLA trial

Background: Breast cancer therapy improved significantly, allowing for different surgical approaches for the same disease stage, therefore offering patients different aesthetic outcomes with similar locoregional control. The purpose of the CINDERELLA trial is to evaluate an artificial-intelligence (AI) cloud-based platform (CINDERELLA platform) vs the standard approach for patient education prior to therapy. Methods: A prospective randomized international multicentre trial comparing two methods for patient education prior to therapy. After institutional ethics approval and a written informed consent, patients planned for locoregional treatment will be randomized to the intervention (CINDERELLA platform) or controls. The patients in the intervention arm will use the newly designed web-application (CINDERELLA platform, CINDERELLA APProach) to access the information related to surgery and/or radiotherapy. Using an AI system, the platform will provide the patient with a picture of her own aesthetic outcome resulting from the surgical procedure she chooses, and an objective evaluation of this aesthetic outcome (e.g., good/fair). The control group will have access to the standard approach. The primary objectives of the trial will be i) to examine the differences between the treatment arms with regards to patients' pre-treatment expectations and the final aesthetic outcomes and ii) in the experimental arm only, the agreement of the pre-treatment AI-evaluation (output) and patient's post-therapy self-evaluation. Discussion: The project aims to develop an easy-to-use cost-effective AI-powered tool that improves shared decision-making processes. We assume that the CINDERELLA APProach will lead to higher satisfaction, better psychosocial status, and wellbeing of breast cancer patients, and reduce the need for additional surgeries to improve aesthetic outcome