Neoadjuvant Chemotherapy in Breast Cancer: Evaluation of the Impact on Surgical Outcomes and Prognosis.

The correlation between TNM staging and histology variations in a sample of patients who underwent neoadjuvant chemotherapy demonstrates a positive impact on both increasing conservative surgery and achieving pCR, resulting in better outcomes in terms of disease-free survival (DFS) and the risk of relapse. Benefits have also been highlighted in terms of cosmetic outcomes, postoperative complications, and psychological benefits. However, the overall outcomes must be evaluated according to the subtype and individual characteristics of the patients.

Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC).

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. MATERIAL AND METHODS: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. RESULTS: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. CONCLUSIONS: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials.

Low neutrophil-to-lymphocyte ratio and pan-immune-inflammation-value predict nodal pathologic complete response in 1274 breast cancer patients treated with neoadjuvant chemotherapy: a multicenter analysis.

Background: Systemic inflammatory markers draw great interest as potential blood-based prognostic factors in several oncological settings. Objectives: The aim of this study is to evaluate whether neutrophil-to-lymphocyte ratio (NLR) and pan-immune-inflammation value (PIV) predict nodal pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in node-positive (cN+) breast cancer (BC) patients. Design: Clinically, cN+ BC patients undergoing NAC followed by breast and axillary surgery were enrolled in a multicentric study from 11 Breast Units. Methods: Pretreatment blood counts were collected for the analysis and used to calculate NLR and PIV. Logistic regression analyses were performed to evaluate independent predictors of nodal pCR. Results: A total of 1274 cN+ BC patients were included. Nodal pCR was achieved in 586 (46%) patients. At multivariate analysis, low NLR [odds ratio (OR) = 0.71; 95% CI, 0.51-0.98; p = 0.04] and low PIV (OR = 0.63; 95% CI, 0.44-0.90; p = 0.01) were independently predictive of increased likelihood of nodal pCR. A sub-analysis on cN1 patients (n = 1075) confirmed the statistical significance of these variables. PIV was significantly associated with axillary pCR in estrogen receptor (ER)-/human epidermal growth factor receptor 2 (HER2)+ (OR = 0.31; 95% CI, 0.12-0.83; p = 0.02) and ER-/HER2- (OR = 0.41; 95% CI, 0.17-0.97; p = 0.04) BC patients. Conclusion: This study found that low NLR and PIV levels predict axillary pCR in patients with BC undergoing NAC. Registration: Eudract number NCT05798806.

Case Report: Male Lobular Breast Cancer in Hereditary Cancer Syndromes.

Background: Lobular breast carcinoma (LBC) is considered an exceptionally rare disease in men, including only 1% of all male breast malignancies. The majority of LBCs have negative immunohistochemical staining for E-cadherin (CDH1) expression, and the loss of CDH1 function was traditionally implicated in the tumorigenesis of diffuse gastric cancer as well as LBC. It is well recognized that LBC in women could be involved in both hereditary breast and ovarian cancer (HBOC) and hereditary diffuse gastric cancer (HDGC) syndromes; however, there are no data present in literature about the involvement of male LBC in these inherited conditions. Methods: BRCA1, BRCA2, and CDH1 genes were performed on DNA from peripheral blood using next-generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification analyses. BRCA2 and CDH1 somatic gene analyses were performed on breast tumoral DNA using the NGS sequencing approach. Results and conclusions: Here, we describe two men affected by LBC, the carriers of a pathogenic variant of BRCA2 and CDH1 genes, respectively. Our data, including somatic and germline results, demonstrate a strong relationship between male LBC and HBOC/HDGC syndromes, excluding a sporadic origin of LBC in these two patients. Male LBC could represent a sentinel cancer for inherited syndrome identification, and early identification of cancer susceptibility could improve cancer prevention both for men and women in these families. The history of the LBC patient carrier of the CDH1 variant suggests to include male LBC genetic testing criteria and male breast surveillance in HDGC guidelines.

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients.

BACKGROUND: Type of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized. PATIENTS AND METHODS: 1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR). RESULTS: Independent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75-0.80). After external validation the accuracy of the nomogram was confirmed. CONCLUSION: The accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.

Pure Ductal Carcinoma In Situ of the Breast: Analysis of 270 Consecutive Patients Treated in a 9-Year Period.

INTRODUCTION: Ductal carcinoma in situ (DCIS) is an intraductal neoplastic proliferation of epithelial cells that are confined within the basement membrane of the breast ductal system. This retrospective observational analysis aims at reviewing the issues of this histological type of cancer. MATERIALS AND METHODS: Patients treated for DCIS between 1 January 2009 and 31 December 2018 were identified from a retrospective database. The patients were divided into two groups of 5 years each, the first group including patients treated from 2009 to 2013, and the second group including patients treated from 2014 to 2018. Once the database was completed, we performed a statistical analysis to see if there were significant differences among the 2 periods. Statistical analyses were performed using GraphPad Prism software for Windows, and the level of significance was set at p < 0.05. RESULTS: 3586 female patients were treated for breast cancer over the 9-year study period (1469 patients from 2009 to 2013 and 2117 from 2014 to 2018), of which 270 (7.53%) had pure DCIS in the final pathology. The median age of diagnosis was 59-year-old (range 36-86). In the first period, 81 (5.5%) women out of 1469 had DCIS in the final pathology, in the second, 189 (8.9%) out of 2117 had DCIS in the final pathology with a statistically significant increase (p = 0.0001). From 2009 to 2013, only 38 (46.9%) were in stage 0 (correct DCIS diagnosis) while in the second period, 125 (66.1%) were included in this stage. The number of patients included in clinical stage 0 increased significantly (p = 0.004). In the first period, 48 (59.3%) specimen margins were at a greater or equal distance than 2 mm (negative margins), between 2014 and 2018; 137 (72.5%) had negative margins. Between 2014 and 2018 the number of DCIS patients with positive margins decreased significantly (p = 0.02) compared to the first period examined. The mastectomies number increased significantly (p = 0.008) between the 2 periods, while the sentinel lymph node biopsy (SLNB) numbers had no differences (p = 0.29). For both periods analysed all the 253 patients who underwent the follow up are currently living and free of disease. We have conventionally excluded the 17 patients whose data were lost. Conclusion: The choice of the newest imaging techniques and the most suitable biopsy method allows a better pre-operative diagnosis of the DCIS. Surgical treatment must be targeted to the patient and a multidisciplinary approach discussed in the Breast Unit centres.

Pre-graduation medical training including virtual reality during COVID-19 pandemic: a report on students' perception.

BACKGROUND: The Coronavirus Disease 19 (COVID-19) pandemic brought significant disruption to in-hospital medical training. Virtual reality simulating the clinical environment has the potential to overcome this issue and can be particularly useful to supplement the traditional in-hospital medical training during the COVID-19 pandemic, when hospital access is banned for medical students. The aim of this study was to assess medical students' perception on fully online training including simulated clinical scenarios during COVID-19 pandemic. METHODS: From May to July 2020 when in-hospital training was not possible, 122 students attending the sixth year of the course of Medicine and Surgery underwent online training sessions including an online platform with simulated clinical scenarios (Body Interact™) of 21 patient-based cases. Each session focused on one case, lasted 2 h and was divided into three different parts: introduction, virtual patient-based training, and debriefing. In the same period, adjunctive online training with formal presentation and discussion of clinical cases was also given. At the completion of training, a survey was performed, and students filled in a 12-item anonymous questionnaire on a voluntary basis to rate the training quality. Results were reported as percentages or with numeric ratings from 1 to 4. Due to the study design, no sample size was calculated. RESULTS: One hundred and fifteen students (94%) completed the questionnaire: 104 (90%) gave positive evaluation to virtual reality training and 107 (93%) appreciated the format in which online training was structured. The majority of participants considered the platform of virtual reality training realistic for the initial clinical assessment (77%), diagnostic activity (94%), and treatment options (81%). Furthermore, 97 (84%) considered the future use of this virtual reality training useful in addition to the apprenticeship at patient's bedside. Finally, 32 (28%) participants found the online access difficult due to technical issues. CONCLUSIONS: During the COVID-19 pandemic, online medical training including simulated clinical scenarios avoided training interruption and the majority of participant students gave a positive response on the perceived quality of this training modality. During this time frame, a non-negligible proportion of students experienced difficulties in online access to this virtual reality platform.

Machine Learning techniques in breast cancer prognosis prediction: A primary evaluation.

More than 750 000 women in Italy are surviving a diagnosis of breast cancer. A large body of literature tells us which characteristics impact the most on their prognosis. However, the prediction of each disease course and then the establishment of a therapeutic plan and follow-up tailored to the patient is still very complicated. In order to address this issue, a multidisciplinary approach has become widely accepted, while the Multigene Signature Panels and the Nottingham Prognostic Index are still discussed options. The current technological resources permit to gather many data for each patient. Machine Learning (ML) allows us to draw on these data, to discover their mutual relations and to esteem the prognosis for the new instances. This study provides a primary evaluation of the application of ML to predict breast cancer prognosis. We analyzed 1021 patients who underwent surgery for breast cancer in our Institute and we included 610 of them. Three outcomes were chosen: cancer recurrence (both loco-regional and systemic) and death from the disease within 32 months. We developed two types of ML models for every outcome (Artificial Neural Network and Support Vector Machine). Each ML algorithm was tested in accuracy (=95.29%-96.86%), sensitivity (=0.35-0.64), specificity (=0.97-0.99), and AUC (=0.804-0.916). These models might become an additional resource to evaluate the prognosis of breast cancer patients in our daily clinical practice. Before that, we should increase their sensitivity, according to literature, by considering a wider population sample with a longer period of follow-up. However, specificity, accuracy, minimal additional costs, and reproducibility are already encouraging.

Aggressive surgery for advanced ovarian cancer performed by a multidisciplinary team: A retrospective analysis on a large series of patients.

BACKGROUND: To evaluate the impact of extended surgical treatment performed by a team of gynecologists and general surgeons on postoperative morbidity and survival of patients with advanced ovarian cancer. METHODS: We collected data of 156 patients with advanced ovarian cancer stage IIb-III-IV according to International Federation of Gynecology and Obstetrics classification and treated with primary cytoreduction. End points were perioperative and postoperative complications and cancer-related survival. RESULTS: In 51 cases (51/156, 32.7%) a multivisceral resection was completed. Postoperative complications occurred in 52 cases (33.3%). The duration of the surgical procedure as well as the need for diaphragmatic peritonectomy were the factors independently associated with the development of postoperative complications. Five-year cancer-related survival rate was of 50.7%: only histotype and residual tumor resulted significantly associated. CONCLUSIONS: Our results highlight the importance of a team of gynecologists and general surgeons with specific interests and skills to achieve cytoreduction as rapidly as possible, even when it implies very complex maneuvers.

A Dietary Intervention to Lower Serum Levels of IGF-I in BRCA Mutation Carriers.

BACKGROUND: Insulin-like growth factor I (IGF-I) and other markers of insulin resistance (IRm) might influence the penetrance of BRCA gene mutation. In a demonstration project on BRCA mutation carriers we tested the effect of the 'Mediterranean diet', with moderate protein restriction, on serum levels of IGF-I and IRm. METHODS: BRCA mutation carriers, with or without breast cancer, aged 18⁻70 years and without metastases were eligible. After the baseline examinations, women were randomized to an active dietary intervention or to a control group. The intervention group attended six full days of life-style intervention activities (cookery classes followed by lunch, sessions of walking for 45 min and nutritional conferences) over the next six months. RESULTS: 213 BRCA mutation carriers completed the six-month study. Women in the intervention group (110) showed major changes in all the parameters under study. They significantly lost weight (p < 0.001), fat mass (p = 0.002), with reduced hip circumference (p = 0.01), triglycerides (p = 0.02) and IGF-I (p = 0.02) compared with controls. They also had a significantly higher levels of insulin-like growth factor-binding protein 3 (IGFI-BP3) (p = 0.03) and a lower IGF-I/IGFI-BP3 ratio (p = 0.04). The reduction of serum levels of IGF-I was significantly associated with the reduction in the consumption of animal products (p = 0.04). CONCLUSIONS: Women in the intervention group showed significant improvements in IGF-I and in other IRm that might influence the penetrance of BRCA mutations.

Wound healing and postsurgical complications in breast cancer surgery: a comparison between PEAK PlasmaBlade and conventional electrosurgery - a preliminary report of a case series.

PURPOSE: PEAK PlasmaBlade is a recent and distinctive type of electrosurgical device. Previous studies have already documented some meaningful advantages of this device over conventional electrosurgery. This study compared the use of PEAK PlasmaBlade to standard electrosurgery in mastectomy and breast conservative surgery. The purpose was to test the impact of PEAK PlasmaBlade on the wound-healing process and on postsurgical complications in breast cancer surgery. METHODS: Sixty patients undergoing breast cancer surgery were enrolled. The PEAK PlasmaBlade was used for 20 of those. A standard electrosurgical device was used for the other 40 patients. The 2 groups were homogenous in age, body mass index, comorbidities and type of surgery. We recorded wound complications, serum drainage amount and duration of stay, blood loss, time of surgery, length of hospital stay, and total number of medications required. RESULTS: The 2 groups were not significantly different in terms of patient characteristics. A statistically significant reduction in incidence of seroma was observed in the PEAK group: only 10% versus 37.5% of the patients in the conventional electrosurgery group developed this complication (Fisher exact test, P = 0.034). CONCLUSION: Seroma is the most important wound complication in breast surgery. The research of new instruments that might reduce its incidence is desirable. In order to validate or deny the results of this study, it is necessary to enroll more subjects and to consider the impact of this device on axillary lymph node dissection.

Metachronous bilateral ectopic breast carcinoma: a case report.

An incomplete regression of the mammary line during embryogenesis occurs in 0.2-6% of the population, which may result in the presence of ectopic breast tissue (EBT). The development of a carcinoma in the EBT is a rare event. The authors present a case report of a 76-year-old female patient, with a lobular carcinoma in an abdominal wall EBT submitted to surgery and adjuvant chemotherapy.

Early Versus Delayed Source Control in Open Abdomen Management for Severe Intra-abdominal Infections: A Retrospective Analysis on 111 Cases.

BACKGROUND: Time to source control plays a determinant prognostic role in patients having severe intra-abdominal infections (IAIs). Open abdomen (OA) management became an effective treatment option for peritonitis. Aim of this study was to analyze the correlation between time to source control and outcome in patients presenting with abdominal sepsis and treated by OA. METHODS: We retrospectively analyzed 111 patients affected by abdominal sepsis and treated with OA from May 2007 to May 2015. Patients were classified according to time interval from first patient evaluation to source control. The end points were intra-hospital mortality and primary fascial closure rate. RESULTS: The in-hospital mortality rate was 21.6% (24/111), and the primary fascial closure rate was 90.9% (101/111). A time to source control ≥6 h resulted significantly associated with a poor prognosis and a lower fascial closure rate (mortality 27.0 vs 9.0%, p = 0.04; primary fascial closure 86 vs 100%, p = 0.02). We observed a direct increase in mortality (and a reduction in closure rate) for each 6-h delay in surgery to source control. CONCLUSION: Early source control using OA management significantly improves outcome of patients with severe IAIs. This damage control approach well fits to the treatment of time-related conditions, particularly in case of critically ill patients.

Adherence to Mediterranean Diet and Metabolic Syndrome in BRCA Mutation Carriers.

BACKGROUND: Insulin resistance is associated with higher breast cancer (BC) penetrance in BRCA mutation carriers. Metabolic syndrome (MetS), an insulin resistance syndrome, can be reversed by adhering to the Mediterranean diet (MedDiet). In a dietary intervention trial on BRCA mutation carriers, we evaluated adherence to the MedDiet, and the association with the MetS, by analyzing data from the Mediterranean Diet Adherence Screener (MEDAS). METHODS: BRCA mutation carriers, with or without BC, aged 18 to 70 years, were eligible for the trial. After the baseline examinations, women were randomized to a dietary intervention or to a control group. Both groups completed the MEDAS at baseline and at the end of the dietary intervention. RESULTS: A total of 163 women completed the 6 months of dietary intervention. Compared with controls, the women in the intervention group significantly reduced their consumption of red meat ( P < .01) and commercial sweets ( P < .01) and their MEDAS score rose significantly (+1.3 vs +0.55, P = .02). The number of MetS parameters decreased with increasing points of adherence to the MEDAS score ( P = .01). In the intervention group, there was a significant association with the greater reduction of MetS. CONCLUSION: BRCA mutation carriers in the intervention group experienced greater improvement in their MedDiet and MetS parameters.

Antibiotic prophylaxis in thyroid surgery.

Use of antibiotic prophylactic (AP) in clean surgery is still controversial. We reviewed the literature of the last 10 years to identify the best way to approach the use of prophylactic antibiotic in thyroid surgery. In thyroid surgery, it is a highly controversial topic primarily due to the lack of evidence in "support" of or "against" antibiotic use. In this review, the authors analyze the literature on the use of AP in thyroid surgery in order to evaluate if the available data support or contradict this use routinely.

Right-Sided versus Left-Sided Colectomies for Cancer: Surgical Outcomes and Novel Considerations.

INTRODUCTION: The aim of this study is to compare short-term outcomes of right versus left colectomies performed as a form of cancer treatment. MATERIALS AND METHODS: This study includes 305 consecutive patients with adenocarcinoma treated by laparoscopic or open colectomy. Right colectomy has been compared with left colectomy. The study endpoints were the first flatus day, the first evacuation day, the first day of postoperative solid oral diet intake, and the postoperative hospital stay length. RESULTS: There were 140 (45.9%) right colectomies and 165 (54.1%) left colectomies performed. The cut-off values for the considered (median) endpoints were three, five, four, and eight days, respectively. The first day of postoperative solid oral diet intake and the length of postoperative hospital stay are significantly associated with the type of resection. CONCLUSIONS: The colon cancer patients treated by right-sided colectomy assumed a solid oral diet and presented a longer postoperative hospital stay compared with the patients treated by left-sided colectomy.

Seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up.

Seventh tumor-node-metastasis (TNM) classification for gastric cancer, published in 2010, introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity, due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases, positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however, its search in clinical practice is still far from being routinely performed, as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently, many controversies on lymph node staging are still ongoing, with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world.

Current Developments and Unusual Aspects in Gastrointestinal Surgical Stapling.

Stapling devices are used in gastrointestinal, gynecologic, thoracic, and many other surgeries to resect organs, transect tissues, and anastomose different structures. These devices became widely accepted standard practice in many gastrointestinal operations, especially since the successful advent of minimally invasive surgery. Despite the relevant advantages related to the use of a surgical stapler, we must also consider that these instruments may be at risk of failure. When any component fails, the patient is at risk of operative morbidity. Gastrointestinal surgical stapling technique still needs refinement in order to increase its reliability. Staple line reinforcement has been widely used and seems to effectively reduce anastomotic complications. Literature provides us with examples of studies supporting both bleeding and leakage reduction after staple line reinforcement, but high-quality evidence is not available to date. Semi-absorbable and nonabsorbable materials have been the earliest available. The use of bioabsorbable staple line reinforcement materials has recently become more widespread, and these materials are more widely used these days. Powered staplers were made available to the market some time ago and represent a rather unheard of aspect of endosurgical stapling. Despite powered staples being supposedly convenient compared with manual ones only one relevant article was found when searching the U.S. National Library of Medicine for "powered stapler." New surgical stapling devices are constantly developed and introduced on the market. Results with such devices depend on the stapler features but also surely vary according to the surgeon experience.