Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial.

Importance: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent. Objective: To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography. Design, Setting, and Participants: The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023. Intervention: Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group). Main Outcomes and Measures: The primary end point of the study was distant disease-free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations. Results: Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor-positive ERBB2 (formerly HER2 or HER2/neu), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group. Conclusions and Relevance: In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan. Trial Registration: ClinicalTrials.gov Identifier: NCT02167490.

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.

Micrometastases in the sentinel node after neoadjuvant therapy. Is axillary dissection still required?

The present review intends to discuss the controversies and strengths in clinically node-positive patients with axillary nodal status ypN i+ / mi after neoadjuvant chemotherapy. Over the past 20 years, a de-escalation approach toward axillary surgery has been observed in patients with breast cancer. The worldwide use of sentinel node biopsy in the upfront setting and after primary systemic therapy substantially reduced surgical complications or late sequelae and eventually improving quality of life of patients. However, the role of axillary dissection is still unclear in patients with low residual disease post-chemotherapy, namely those with micrometastases in the sentinel node, and its prognostic role is still not very clear. The aim of the present narrative review is to report the available evidence on this topic, discussing the pros and cons of performing axillary lymph node dissection in the infrequent finding of micrometastases in the sentinel node after neoadjuvant chemotherapy. We will also describe the ongoing prospective studies which are expected to shed light and guide future decisions.

Uncertainties and controversies in axillary management of patients with breast cancer.

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.

Localization Techniques for Non-Palpable Breast Lesions: Current Status, Knowledge Gaps, and Rationale for the MELODY Study (EUBREAST-4/iBRA-NET, NCT 05559411).

BACKGROUND: Surgical excision of a non-palpable breast lesion requires a localization step. Among available techniques, wire-guided localization (WGL) is most commonly used. Other techniques (radioactive, magnetic, radar or radiofrequency-based, and intraoperative ultrasound) have been developed in the last two decades with the aim of improving outcomes and logistics. METHODS: We performed a systematic review on localization techniques for non-palpable breast cancer. RESULTS: For most techniques, oncological outcomes such as lesion identification and clear margin rate seem either comparable with or better than for WGL, but evidence is limited to small cohort studies for some of the devices. Intraoperative ultrasound is associated with significantly higher negative margin rates in meta-analyses of randomized clinical trials (RCTs). Radioactive techniques were studied in several RCTs and are non-inferior to WGL. Smaller studies show higher patient preference towards wire-free localization, but little is known about surgeons' and radiologists' attitudes towards these techniques. CONCLUSIONS: Large studies with an additional focus on patient, surgeon, and radiologist preference are necessary. This review aims to present the rationale for the MELODY (NCT05559411) study and to enable standardization of outcome measures for future studies.

Axillary surgery after neoadjuvant therapy in initially node-positive breast cancer: international EUBREAST survey.

BACKGROUND: There is no consensus on axillary management after neoadjuvant therapy (NAT) in patients with clinically node-positive (cN+) breast cancer. To investigate current clinical practice, an international survey was conducted among breast surgeons and radiation oncologists. The aim of the first part of the survey was to provide a snapshot of international discrepancies regarding axillary surgery in this context. METHODS: The European Breast Cancer Research Association of Surgical Trialists (EUBREAST) developed a web-based survey containing 39 questions describing clinical scenarios in the setting of axillary management in patients with cN1 disease converting to ycN0 after NAT. The survey was then distributed to breast surgeons and radiation oncologists via 14 breast cancer societies between April and October 2021. RESULTS: Responses from 349 physicians in 45 countries were recorded. The most common post-NAT axillary surgery in patients with cN1 disease converting to ycN0 was targeted axillary dissection (54.2 per cent), followed by sentinel lymph node biopsy (SLNB) alone (20.9 per cent), level 1-2 axillary lymph node dissection (ALND) (18.4 per cent), level 1-3 ALND (4 per cent), and targeted lymph node biopsy (2.5 per cent). For SLNB alone, dual tracers were most commonly used (62.3 per cent). Management varied widely in patients with ambiguous axillary status before initiation of treatment or a residual metastatic burden in the axilla after NAT. In patients with ycN+ tumours, ALND was the preferred surgical approach for 66.8 per cent of respondents. CONCLUSION: These results highlight the wide heterogeneity in surgical approaches to the axilla after NAT. To standardize the guidelines, further data from clinical research are urgently needed, which underlines the importance of the ongoing AXSANA (EUBREAST-3) study.

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.

PET/MRI for Staging the Axilla in Breast Cancer: Current Evidence and the Rationale for SNB vs. PET/MRI Trials.

Axillary surgery in breast cancer (BC) is no longer a therapeutic procedure but has become a purely staging procedure. The progressive improvement in imaging techniques has paved the way to the hypothesis that prognostic information on nodal status deriving from surgery could be obtained with an accurate diagnostic exam. Positron emission tomography/magnetic resonance imaging (PET/MRI) is a relatively new imaging tool and its role in breast cancer patients is still under investigation. We reviewed the available literature on PET/MRI in BC patients. This overview showed that PET/MRI yields a high diagnostic performance for the primary tumor and distant lesions of liver, brain and bone. In particular, the results of PET/MRI in staging the axilla are promising. This provided the rationale for two prospective comparative trials between axillary surgery and PET/MRI that could lead to a further de-escalation of surgical treatment of BC. • SNB vs. PET/MRI 1 trial compares PET/MRI and axillary surgery in staging the axilla of BC patients undergoing primary systemic therapy (PST). • SNB vs. PET/MRI 2 trial compares PET/MRI and sentinel node biopsy (SNB) in staging the axilla of early BC patients who are candidates for upfront surgery. Finally, these ongoing studies will help clarify the role of PET/MRI in BC and establish whether it represents a useful diagnostic tool that could guide, or ideally replace, axillary surgery in the future.

Axillary evaluation in ductal cancer in situ of the breast: challenging the diagnostic accuracy of clinical practice guidelines.

BACKGROUND: Staging of the axilla is not routine in ductal cancer in situ (DCIS) although invasive cancer is observed in 20-25 per cent of patients at final pathology. Upfront sentinel lymph node dissection (SLND) is advocated in clinical practice guidelines in certain situations. These include expected challenges in subsequent SLN detection and when the risk for invasion is high. Clinical practice guidelines are, however, inconsistent and lead to considerable practice variability. METHODS: Clinical practice guidelines for upfront SLND in DCIS were identified and applied to patients included in the prospective SentiNot study. These patients were evaluated by six independent, blinded raters. Agreement statistics were performed to assess agreement and concordance. Receiver operating characteristic curves were constructed, to assess guideline accuracy in identifying patients with underlying invasion. RESULTS: Eight guidelines with relevant recommendations were identified. Interobserver agreement varied greatly (kappa: 0.23-0.9) and the interpretation as to whether SLND should be performed ranged from 40-90 per cent and with varying concordance (32-88 per cent). The diagnostic accuracy was low with area under the curve ranging from 0.45 to 0.55. Fifty to 90 per cent of patients with pure DCIS would undergo unnecessary SLNB, whereas 10-50 per cent of patients with invasion were not identified as 'high risk'. Agreement across guidelines was low (kappa = 0.24), meaning that different patients had a similar risk of being treated inaccurately. CONCLUSION: Available guidelines are inaccurate in identifying patients with DCIS who would benefit from upfront SLNB. Guideline refinement with detailed preoperative work-up and novel techniques for SLND identification could address this challenge and avoid overtreatment. LAY SUMMARY: The decision whether to operate on the axilla in women with a diagnosis of ductal cancer in situ (DCIS) is based on the risk of an undiagnosed underlying invasive cancer and on the concern that resection of the breast will not allow for accurate axillary mapping afterwards. Guidelines stem from older knowledge and are heterogeneous. In this study, different breast cancer guidelines were tested in a patient cohort from the SentiNot prospective trial for uniformity of interpretation and diagnostic accuracy. Results show that guidelines did not allow for easy and uniform interpretation and had the predictive ability of the toss of a coin. This suggests that guidelines regarding the need of axillary evaluation in patients operated for DCIS need to be revised and that techniques that will address the conundrum should be developed.

The decision whether to operate on the axilla in women with a diagnosis of ductal cancer in situ (DCIS) is based on the risk of an undiagnosed underlying invasive cancer and on the concern that resection of the breast will not allow for accurate axillary mapping afterwards. Guidelines stem from older knowledge and are heterogeneous. In this study, different breast cancer guidelines were tested in a patient cohort from the SentiNot prospective trial for uniformity of interpretation and diagnostic accuracy. Results show that guidelines did not allow for easy and uniform interpretation and had the predictive ability of the toss of a coin. This suggests that guidelines regarding the need of axillary evaluation in patients operated for DCIS need to be revised and that techniques that will address the conundrum should be developed.

Surgical Management of the Axilla in Clinically Node-Positive Breast Cancer Patients Converting to Clinical Node Negativity through Neoadjuvant Chemotherapy: Current Status, Knowledge Gaps, and Rationale for the EUBREAST-03 AXSANA Study.

In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).

Fibrin Sealants and Axillary Lymphatic Morbidity: A Systematic Review and Meta-Analysis of 23 Clinical Randomized Trials.

BACKGROUND: use of fibrin sealants following pelvic, paraaortic, and inguinal lymphadenectomy may reduce lymphatic morbidity. The aim of this meta-analysis is to evaluate if this finding applies to the axillary lymphadenectomy. METHODS: randomized trials evaluating the efficacy of fibrin sealants in reducing axillary lymphatic complications were included. Lymphocele, drainage output, surgical-site complications, and hospital stay were considered as outcomes. RESULTS: twenty-three randomized studies, including patients undergoing axillary lymphadenectomy for breast cancer, melanoma, and Hodgkin's disease, were included. Fibrin sealants did not affect axillary lymphocele incidence nor the surgical site complications. Drainage output, days with drainage, and hospital stay were reduced when fibrin sealants were applied (p < 0.0001, p < 0.005, p = 0.008). CONCLUSION: fibrin sealants after axillary dissection reduce the total axillary drainage output, the duration of drainage, and the hospital stay. No effects on the incidence of postoperative lymphocele and surgical site complications rate are found.

Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations.

INTRODUCTION: The potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. METHODS: A panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. RESULTS: According to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). DISCUSSION: This review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients' values. Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.

What we learned in axillary management of breast cancer patients at the American society of clinical oncology (ASCO) 2020 virtual meeting? The EUBREAST point of view.

In 2020, the American Society of Clinical Oncology (ASCO) annual meeting was held as a virtual conference. Overall, 461 abstracts focused on breast cancer management. As European Breast Cancer Association of Surgical Trialists (EUBREAST) we summarize and comment the results of these abstracts dealing with axillary management in breast cancer patients and offer an interpretation on how these findings may be incorporated into clinical practice and further research.

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.

Axillary observation alone versus sentinel node biopsy: past, present and future perspectives.

The evolution of axillary surgery in breast cancer has led from complete axillary dissection (AD) to sentinel node biopsy (SNB). It has not stopped yet but continues with a progressive de-escalation of surgical procedures aiming at axillary conservation. In parallel, the meaning of axillary surgery has changed as well. Over time, the dual role of both a therapeutic and a staging procedure has decreased leaving room to other modalities to treat and stage breast cancer. Although, the gold standard for axillary staging in early breast cancer remains SNB, the idea that axillary surgery could be even omitted has been proposed. The concept of abandoning axillary surgery is revolutionary but not new. Historical literature provides interesting data on patients who did not receive any axillary treatment at all with no impact on their survival. Starting from this, several ongoing trials are working to demonstrate that in selected breast cancer cohorts the information deriving from axillary surgery is superfluous and "axillary observation" alone is as effective as SNB. Whilst surgery has been de-escalated to less invasive procedures, systemic treatment, radiotherapy, multigene assays and advanced imaging modalities have gained ground in the management of breast cancer. New research is expected to help select the subgroups of patients for whom axillary surgery is not necessary anymore. This is a qualitative review reporting the most relevant literature data from historical trials on the omission of axillary surgery to the most recent and ongoing ones.

Axillary management after neoadjuvant treatment.

Since its introduction nearly 30 years ago, sentinel lymph node biopsy (SLNB) has become the standard technique to stage the axilla for the great majority of patients with early breast cancer. While the accuracy of SLNB in clinically node-negative patients who undergo neoadjuvant chemotherapy (NAC) is similar to the upfront surgery setting, modifications of the technique to improve the false negative rate are necessary in node-positive patients at presentation. Currently, patients who present with matted nodes, cN1 patients who fail to downstage to cN0 with NAC and those with pathological residual disease have an indication to undergo axillary lymph node dissection. Ongoing trials will confirm if extensive nodal irradiation can replace surgery in patients with residual nodal disease after NAC and if nodal radiotherapy can be omitted in patients who achieve nodal pathological complete response. The aim of this review was to focus on the open questions on the management of the axilla after NAC.

Personalized Risk-Benefit Ratio Adaptation of Breast Cancer Care at the Epicenter of COVID-19 Outbreak.

Northern Italy has been one of the European regions reporting the highest number of COVID-19 cases and deaths. The pandemic spread has challenged the National Health System, requiring reallocation of most of the available health care resources to treat COVID-19-positive patients, generating a competition with other health care needs, including cancer. Patients with cancer are at higher risk of developing critical illness after COVID-19 infection. Thus, mitigation strategies should be adopted to reduce the likelihood of infection in all patients with cancer. At the same time, suboptimal care and treatments may result in worse cancer-related outcome. In this article, we attempt to estimate the individual risk-benefit balance to define personalized strategies for optimal breast cancer management, avoiding as much as possible a general untailored approach. We discuss and report the strategies our Breast Unit adopted from the beginning of the COVID-19 outbreak to ensure the continuum of the best possible cancer care for our patients while mitigating the risk of infection, despite limited health care resources. IMPLICATIONS FOR PRACTICE: Managing patients with breast cancer during the COVID-19 outbreak is challenging. The present work highlights the need to estimate the individual patient risk of infection, which depends on both epidemiological considerations and individual clinical characteristics. The management of patients with breast cancer should be adapted and personalized according to the balance between COVID-19-related risk and the expected benefit of treatments. This work also provides useful suggestions on the modality of patient triage, the conduct of clinical trials, the management of an oncologic team, and the approach to patients' and health workers' psychological distress.

Aesthetic Breast Surgery Under Cold Tumescent Anesthesia: Feasibility and Safety in Outpatient Clinic.

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.