A narrative review for radiation oncologists to implement preoperative partial breast irradiation.

The strategy to anticipate radiotherapy (RT) before surgery, for breast cancer (BC) treatment, has recently generated a renewed interest. Historically, preoperative RT has remained confined either to highly selected patients, in the context of personalized therapy, or to clinical research protocols. Nevertheless, in the recent years, thanks to technological advances and increased tumor biology understanding, RT has undergone great changes that have also impacted the preoperative settings, embracing the modern approach to breast cancer. In particular, the reappraisal of preoperative RT can be viewed within the broader view of personalized and tailored medicine. In fact, preoperative accelerated partial breast irradiation (APBI) allows a more precise target delineation, with less variability in contouring among radiation oncologists, and a smaller treatment volume, possibly leading to lower toxicity and to dose escalation programs. The aim of the present review, which represents a benchmark study for the AIRC IG-23118, is to report available data on different technical aspects of preoperative RT including dosimetric studies, patient's selection and set-up, constraints, target delineation and clinical results. These data, along with the ones that will become available from ongoing studies, may inform the design of the future trials and representing a step toward a tailored APBI approach with the potential to challenge the current treatment paradigm in early-stage BC.Trial registration: The study is registered at clinicaltrials.gov (NCT04679454).

How to Perform Repeat Sentinel Node Biopsy Safely After a Previous Mastectomy: Technical Features and Oncologic Outcomes.

BACKGROUND: The latest National Comprehensive Cancer Network Breast Cancer Guidelines still discourage repeat sentinel node biopsy (SNB) after mastectomy, and the largest multicentric study available reports only 35 cases in the absence of previous axillary dissection (AD). METHODS: From January 2003 to November 2018, 89 patients of the European Institute of Oncology with local recurrence of breast cancer after mastectomy, free of distant metastases, with a clinically negative axilla and a negative axillary ultrasound, in absence of AD, underwent lymphatic mapping before wide local excision. RESULTS: During surgery, SNB was successful for 99% of the patients, with 14% being metastatic. Additional metastatic nodes removed by AD after a positive sentinel node occurred in 82% of cases. After a medium follow-up period of 3.7 years, the overall survival rate was 96.7%, and the disease-free survival rate was 84.4%. No axillary relapse after AD was recorded. One patient who refused human epidermal growth factor receptor 2 (HER2)-targeted treatment experienced ipsilateral axillary recurrence after a negative repeat SNB. The first axillary level was never directly irradiated because all the patients with positive repeat SNB underwent AD. For invasive luminal-like HER2-negative recurrences, the metastatic sentinel node was significantly associated with the choice to prescribe adjuvant chemotherapy (p = 0.003). CONCLUSIONS: In specialized centers, repeat axillary SNB for patients with local recurrence after mastectomy in the absence of previous AD can represent a safe option for detection and removal of occult axillary disease that would otherwise not be excised/irradiated to achieve better local control and could possibly influence the choice of adjuvant treatments.

Ten-year outcome results of cT4 breast cancer after neoadjuvant treatment.

BACKGROUND AND OBJECTIVES: cT4 breast cancer (BC) is classified as noninflammatory breast cancer (non-IBC) or inflammatory breast cancer (IBC). The outcome often is considered worse. The purpose of this study was to determine recurrence and outcomes in overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS) according to pathological complete response (pCR), and inflammatory status. METHODS: From 2000 to 2015 we selected 634 nonmetastatic cT4 BC patients treated with neoadjuvant therapy followed by surgery at the European Institute of Oncology. OS, IDFS, and DDFS were estimated with the Kaplan-Meier method. RESULTS: The median follow-up was 9.0 years. Twenty patients underwent only sentinel node biopsy (SNB), 13 SNB + AD, and 601 only AD. Considering the 614 patients with AD, only 2.5% of non-IBC patients reported pCR compared to 15% of IBC cases. Only two axillary recurrences were reported. Ten-year results were 52.3% (95% confidence interval [CI]: 47.8-56.5) for OS, 37.0% (95% CI: 32.6-41.3) for IDFS, and 49.8% (95% CI: 45.0-54.4) for DDFS. OS, IDFS, and DDFS were better in all BC with pCR (irrespective of inflammatory status). CONCLUSION: Our long-term results demonstrated that pCR significantly improves survival, reducing locoregional and distant recurrence risk in cT4 tumors with respect to patients with no pCR and according to inflammatory status of cT4 BC.

Oncological Outcomes of Nipple-Sparing Mastectomy: A Single-Center Experience of 1989 Patients.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly used in women with breast cancer who are not eligible for conservative surgery, but extensive outcome data are lacking and indications have not been established. OBJECTIVE: The aim of this study was to assess the oncological outcomes of NSM in a large series of patients with invasive or in situ breast cancer treated at a single center. METHODS: We analyzed 1989 consecutive women who had an NSM in 2003-2011, for invasive (1711 patients) or in situ cancer (278 patients) at the European Institute of Oncology, Italy, and followed-up to December 2016. Endpoints were local recurrences, recurrences in the nipple-areola complex (NAC), NAC necrosis, and overall survival (OS). RESULTS: After a median follow-up of 94 months (interquartile range 70-117), 91/1711 (5.3%) patients with invasive cancer had local recurrence (4.8% invasive disease, 0.5% in situ disease), and 11/278 (4.0%) patients with in situ disease had local recurrence (1.8% invasive disease, 2.2% in situ disease). Thirty-six (1.8%) patients had NAC recurrence, 9 with in situ disease (4 invasive and 5 in situ recurrences), and 27 with invasive disease (18 invasive and 9 in situ recurrences). NAC loss for necrosis occurred in 66 (3.3%) patients. There were 131 (6.6%) deaths, 109 (5.5%) as a result of breast cancer. OS at 5 years was 96.1% in women with invasive cancer and 99.2% in women with in situ disease. CONCLUSIONS: The findings in this large series, with a median follow-up of nearly 8 years, indicate that NSM is oncologically safe for selected patients. The rate of NAC loss was acceptably low.

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.

"This house believes that: Sentinel node biopsy alone is better than TAD after NACT for cN+ patients".

The increased use of neoadjuvant chemotherapy (NACT) has changed the approach to breast surgery. NACT allows de-escalation of surgery by both increasing breast conservation rates (up to 40%), the initial goal of this chemotherapy, and in particular it permits reduces axillary surgery. Furthermore, in relation to the molecular characteristics of the tumor we can have a pathological complete response (pCR) ranging from 20 to 80%. In clinically node positive (cN+) patients who converted to clinically node-negative (cN0) various prospective studies have demonstrated that the false negative rate (FNR) of the sentinel node biopsy (SNB) were higher than the acceptable 10% and strategies to reduce the FNR in cN + patients are being investigated. But all the effort to reduce the FNR does not have clinical prognostic significance. This has already been demonstrated in the literature in different randomized trials with long term follow up. The 10-year follow-up of our study confirmed our preliminary data that the use of standard SNB without the use of clip is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome. In fact, the axillary recurrences were less than 2%. Similar positive data with different follow up were also confirmed by other studies that used SNB alone without TAD. All these studies, with encouraging results on the follow up, confirm that SN surgery alone for selected patients who have an excellent response to NACT is rationale and not oncologically inferior to AD during a short- and long-term follow-up.

Is Nipple-Sparing Mastectomy Indicated after Previous Breast Surgery? A Series of 387 Institutional Cases.

BACKGROUND: Previous breast surgery does not represent an absolute contraindication for nipple-sparing mastectomy, although it may negatively interfere with surgical outcomes. The aim of the authors' study was to confirm the feasibility of nipple-sparing mastectomy after previous breast surgery, focusing on skin incisions and risk factors, complications, and oncologic outcomes. METHODS: The authors retrospectively identified 368 patients who underwent 387 nipple-sparing mastectomies and reconstruction after previous surgery (quadrantectomy, breast resection, augmentation and reduction mammaplasty, mastopexy) at the European Institute of Oncology from January of 2003 to November of 2017. Patterns of skin incisions (i.e., radial, hemiperiareolar, periareolar, vertical pattern, inframammary fold, Wise-pattern, and round-block) for primary surgery and for mastectomy, type of reconstruction, and radiotherapy have been recorded. The authors collected data regarding early and late complications and further operations (implant change, fat grafting) performed within 2 years to improve cosmetic outcomes. Oncologic follow-up has been reported for in-breast recurrences. RESULTS: Complete and partial nipple-areola complex necrosis occurred, respectively, in 2.8 percent and in 5.4 percent of cases. The authors recorded 5.4 percent failures resulting in implant removal. The analysis of risk factors for complications or for the need for further operations showed no significant association with skin incision for first surgery and mastectomy, use of the same skin incision, previous radiotherapy, or type of primary surgery. Five-year overall survival and disease-free survival were 99.1 and 93.8 percent, respectively. No nipple recurrence was recorded. CONCLUSIONS: The authors' results confirm that nipple-sparing mastectomy can be a safe surgical procedure after previous breast surgery. Surgical planning should be tailored to each patient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Predictors of positive axillary non-sentinel lymph nodes in breast cancer patients with positive sentinel lymph node biopsy after neoadjuvant systemic therapy.

AIM: To assess the rate of positive non-sentinel lymph nodes (non-SLNs) after neoadjuvant systemic therapy (NAST) in breast cancer (BC) following positive sentinel lymph node biopsy (SLNB). MATERIALS AND METHODS: From institutional database, 265 consecutive patients receiving NAST for cT1-3, any N, M0 BC between 2001 and 2018 were identified. Patients presented clinically negative axilla before surgery and were candidate for SLNB. Following metastatic SLNB, completion axillary lymph node dissection (AxLND) was performed. Non-SLNs rate was investigated using multivariate (MV) logistic regression models. The distribution of non-SLNs across the axilla was observed. RESULTS: Positive non-SLNs were found in 62.3% of cases and showed no correlation with SLN metastasis size. At MV, statistically significant variables associated with non-SLNs were older age (p = 0.025), clinically positive lymph nodes (p = 0.002), SLN extracapsular extension (ECE, p = 0.001), and higher ratio of positive SLNs/total SLNs (p = 0.016). ECE and higher nodal ratio were independent predictors of III axillary level positivity. By categorizing patients in intermediate- and high-risk groups using the study variables, positive non-SLNs were found in the range of 23-56% across the three axillary levels, rates which did not support radiotherapy volume de-escalation. The III axillary level lower involvement (6.3%) was better identified with the RAPCHEM trial criteria based on the ypN status after AxLND. CONCLUSIONS: Involved non-SLNs rate following positive SLNB after NAST is nearly double the rate observed after primary surgery, supporting some intervention on the axilla. If AxLND is limited to I and II level, the involvement of the III level up to 31% of the cases seems to require some additional treatment, while the omission in selected cases needs further investigation.

Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up.

INTRODUCTION: In patients with positive lymph nodes (cN+) prior to neoadjuvant treatment (NAT), which convert to a clinically negative axilla (cN0) after treatment, the use of sentinel node biopsy (SNB) is still debatable, since the false-negative rate (FNR) is significantly high (12.6-14.2%). The objective of this retrospective mono-institutional study, with a long follow-up, aimed to evaluate the outcome in patients undergoing NAT who remained or converted to cN0 and received SNB independent of target axillary dissection (TAD) or the removal of at least 3 sentinel nodes (SNs). METHODS: This study analyzed 688 consecutive cT1-3, cN0/1/2 patients, operated at the European Institute of Oncology, Milan, from 2000 to 2015 who became or remained cN0 after NAT and underwent SNB with a least one SN found. Axillary dissection (AD) was not performed if the SN was negative. Nodal radiotherapy (RT) was not mandatory. RESULTS: Axillary failure occurred in 1.8% of the initially cN1/2 patients and in 1.5% of the initially cN0 patients. After a median follow-up of 9.2 years (IQR 5.3-12.3), the 5- and 10-year overall survival (OS) were 91.3% (95% CI, 88.8-93.2) and 81.0% (95% CI, 77.2-84.2) in the whole cohort, 92.0% (95% CI, 89.0-94.2) and 81.5% (95% CI, 76.9-85.2) in those initially cN0, 89.8% (95% CI, 85.0-93.2) and 80.1% (95% CI, 72.8-85.7) in those initially cN1/2. CONCLUSION: The 10-year follow-up confirmed our preliminary data that the use of standard SNB is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome.

[The assessment of nurses satisfaction for an organization that values posts and professional responsibilities]. / Contributi valutazione della soddisfazione per l'organizzazione basata sulla valorizzazione di posizioni funzionali, tra gli infermieri del Policlinico S. Orsola-Malpighi.

UNLABELLED: To assess the effectiveness of a new organizational model for professional development, that assigns and financially rewards 12 positions that encompass specific responsibilities (such as responsible of Evidence based Nursing; expert in pressure ulcers, responsible of the newly employed nurses), nurses' satisfaction was measured. METHOD: From November to December 2003 the MC Closey Muller Satisfaction Questionnaire was administered to all the nurses in service in the wards. Levels of satisfaction of nurses with and without specific responsibilities were compared. The answers for each item are on a five points Likert scale. RESULTS: The questionnaire was administered to 1.167 nurses (58.9% of the nurses of the hospital); 602 were assigned positions with specific responsibilities. Overall, nurses with positions assigned were more satisfied (2.76 vs 2.61, p.0.01) and statistically significant differences were obtained for 14/31 items of the scale, and for 5/8 subscales. CONCLUSIONS: The results obtained, although the level of satisfaction is lower compared to other studies, confirm the strategy of professional development adopted in the Hospital. The analysis of results for each position allowed some reflections and to identify strategies to improve the organizational support to some positions.

Nipple-sparing and skin-sparing mastectomy: Review of aims, oncological safety and contraindications.

Skin-sparing (SSM) and nipple-sparing (NSM) mastectomies are relatively new conservative surgical approaches to breast cancer. In SSM most of the breast skin is conserved to create a pocket that facilitates immediate breast reconstruction with implant or autologous graft to achieve a quality cosmetic outcome. NSM is closely similar except that the nipple-areola complex (NAC) is also conserved. Meta-analyses indicate that outcomes for SSM and NSM do not differ from those for non-conservative mastectomies. Recurrence rates in the NAC after NSM are acceptably low (0-3.7%). Other studies indicate that NSM is associated with high patient satisfaction and good psychological adjustment. Indications are carcinoma or DCIS that require mastectomy (including after neoadjuvant chemotherapy). NSM is also suitable for women undergoing risk-reducing bilateral mastectomy. Tumor not less than 2 cm from the NAC is recommended, but may be less important than no evidence of nipple involvement on mandatory intraoperative nipple margin assessment. A positive margin is an absolute contraindication for nipple preservation. Other contraindications are microcalcifications close to the subareolar region and a positive nipple discharge. Complication rates are similar to those for other types of post-mastectomy reconstructions. The main complication of NSM is NAC necrosis, however as surgeon experience matures, frequency declines. Factors associated with complications are voluminous breast, ptosis, smoking, obesity, and radiotherapy. Since the access incision is small, breast tissue may be left behind, so only experienced breast surgeons should do these operations in close collaboration with the plastic surgeon. For breast cancer patients requiring mastectomy, NSM should be the option of choice.

Group B Streptococcus detection in pregnant women via culture and PCR methods.

INTRODUCTION:: Group B Streptococcus (GBS), a source of neonatal infection, colonizes the gastrointestinal and genitourinary tracts of pregnant women. Routine screening for maternal GBS in late pregnancy and consequent intrapartum antibiotic prophylaxis have reduced the incidence of early-onset GBS neonatal infection. The aim of this study was to evaluate the performance of PCR, compared to culture (gold standard), in GBS colonization screening of pregnant women, and to establish the prevalence of GBS colonization among this population. METHODS:: Vaginal introitus and perianal samples were collected from 204 pregnant women, between the 35th and 37th weeks of pregnancy, at the Obstetrics and Gynecology Unit of the University of Caxias do Sul General Hospital between June 2008 and September 2009. All samples were cultured after enrichment in a selective medium and then assayed by culture and PCR methods. RESULTS:: The culture and PCR methods yielded detection rates of vaginal/perianal GBS colonization of 22.5% and 26%, respectively (sensitivity 100%; specificity 95.6%; positive and negative predictive values 86.8% and 100%, respectively). A higher prevalence of GBS colonization was detected in the combined vaginal and perianal samples by both culture and PCR assay analyses. CONCLUSIONS:: PCR is a faster and more efficient method for GBS screening, allowing for optimal identification of women who should receive intrapartum antibiotic prophylaxis to prevent newborn infection.

[Evaluation of 2 tools for measuring the risk of falls among patients]. / Valutazione di due strumenti di misura del rischio di cadute dei pazienti.

To select a risk assessment tool to predict which elderly inpatients will fall, two widely used risk assessment scales (Conley and Stratify) were compared to evaluate their sensibility and specificity. A sample of 2651 patients were included in the survey (1620 evaluated with the Conley; 1181 with the Stratify and 173 with both scales). One hundred and 33 patients fell during the hospital stay (5% of the sample but 1% of all the hospital admissions). Both scales show low values of sensibility (0.69 Conley and 0.20 Stratify) or specificity (0.41 Conley and 0.87 Stratify) with a likely hood ratio of 1.18 and 1.55 respectively. Neither scale is more predictive for stratifying at risk patients. The Conley scale is more sensible in discriminating at risk patients but its use must be accompanied by the clinical assessment of the patients.

Group B Streptococcus detection in pregnant women via culture and PCR methods

Abstract INTRODUCTION: Group B Streptococcus (GBS), a source of neonatal infection, colonizes the gastrointestinal and genitourinary tracts of pregnant women. Routine screening for maternal GBS in late pregnancy and consequent intrapartum antibiotic prophylaxis have reduced the incidence of early-onset GBS neonatal infection. The aim of this study was to evaluate the performance of PCR, compared to culture (gold standard), in GBS colonization screening of pregnant women, and to establish the prevalence of GBS colonization among this population. METHODS: Vaginal introitus and perianal samples were collected from 204 pregnant women, between the 35th and 37th weeks of pregnancy, at the Obstetrics and Gynecology Unit of the University of Caxias do Sul General Hospital between June 2008 and September 2009. All samples were cultured after enrichment in a selective medium and then assayed by culture and PCR methods. RESULTS: The culture and PCR methods yielded detection rates of vaginal/perianal GBS colonization of 22.5% and 26%, respectively (sensitivity 100%; specificity 95.6%; positive and negative predictive values 86.8% and 100%, respectively). A higher prevalence of GBS colonization was detected in the combined vaginal and perianal samples by both culture and PCR assay analyses. CONCLUSIONS: PCR is a faster and more efficient method for GBS screening, allowing for optimal identification of women who should receive intrapartum antibiotic prophylaxis to prevent newborn infection.

[Quality of life and related factors among climacteric women from south Brazil]. / Qualidade de vida e fatores asociados em mulheres climatéricas residentes na região sul do Brasil.

OBJECTIVE: This study aimed to evaluate the quality of life in climacteric and associated factor among women from Southeast Brazil. PATIENTS AND METHOD: A cross-section study of 506 women aged between 45 and 60 years old attended at a university climacteric clinic from South Brazil from June to October 2002. Hysterectomized women, as well as hormonal therapy or hormonal contraceptive users were excluded. The quality of life was evaluated by the Women's Health Questionnaire (WHQ). Statistical analysis was performed with multiple linear regression analysis. RESULTS: The average of the age among the studied women was 51.3 (+/- 4.5) years old. About 15.4% were premenopausal, 34.4% perimenopausal and 50.2% postmenopausal women. The quality of life showed up deteriorated among the studied women. The factors related with quality of life were: the educational level (p < 0.01), the confirmation of smoking in the last year (p < 0.01), regular physical activity (p < 0.01), the confirmation of previous co-morbidities (p < 0.01) and the menopausal status (p < 0.01). A higher educational level, as well as the confirmation of regular physical activity led to a significant increase on their life quality. Smoking and previous clinical co-morbidities were responsible for the lower scores of quality of life. The pre-menopause was associated with a higher life quality level if compared to peri and post menopause. No differences in relation to the scores of life were identified among the perimenopausal and postmenopausal women. CONCLUSIONS: Nevertheless the menopausal status showed up associated to the quality of life, the results of the study pointed out that the climacteric is not just influenced by biological factors, but also by psychosocial and cultural factors.

Endometriose e infertilidade: Videolaparascopia e/ou fertilização in vitro / Endometriosis and infertility: Videolaparoscopy and/or in vitro fertilization

A endometriose é caracterizada por implante e crescimento de tecido endometrial fora da cavidade uterina. Afeta mulheres em idade reprodutiva e tem sido observada em 5% à 10% das pacientes submetidas a laparotomias ginecológicas. Podemos encontrar desde pacientes assintomáticas, até quadros de dor pélvica crônica, dismenorréia, dispareunia e infertilidade. Tendo em vista que pacientes com endometriose tem cerca de vinte vezes mais chances de serem inférteis se comparadas às que não tem a doença, direcionamos nosso estudo para a revisão da literatura na escolha do melhor tratamento para a endometriose quando a única manifestação é a infertilidade. Após descartar o fator masculino, devemos avaliar a gravidade da doença, a idade da paciente e a duração da infertilidade. O diagnóstico definitivo só pode ser realizado por meio de visão direta e biópsia dos focos de endometriose, portanto devemos considerar o tratamento cirúrgico laparoscópico como primeiro passo na terapêutica. Em pacientes com endometriose mínima ou leve a ablação das lesões associadas à adesiólise é o tratamento de escolha. A fertilização in vitro (FIV) parece ser abordagem adequada nos casos de coexistência de outros fatores de infertilidade e/ou falha de outras abordagens terapêuticas, além dos casos de endometriose grave com distorção da cavidade pélvica. No tratamento das pacientes com endometriose e infertilidade devemos levar em consideração a presença ou não de fator masculino ou outro fator concominante, gravidade da doença, idade da paciente e duração da infertilidade.