Purpose: To evaluate the feasibility, early toxicity, and clinical outcomes of early-breast cancer patients in a single-arm, phase I/II study of an ultra-accelerated, four-fraction schedule of minimal breast irradiation (4f-AMBI) using a multicatheter, minimally-invasive, intraoperative tumor bed implant (MITBI) during breast-conserving surgery (BCS). Methods and materials: Eligible women aged >40 years with clinically and radiologically confirmed, unifocal invasive or in situ ¿3 cm tumors were considered as potential candidates for MITBI during BCS. After the pathology report, patients who met APBI criteria received ultra-accelerated four-fractions irradiation (6.2 Gy BID x 4fx over 2 days) with perioperative HDR-brachytherapy (PHDRBT). Early complications, toxicity, clinical outcomes, and cosmetic results were analyzed. Results: Of 89 patients initially implanted, 60(67.4%) were definitively included in the 4f-AMBI-protocol. The median age was 64.4 years; the median CTV was 32.1 cc (6.9-75.4 cc), and the external-V100 was 43.1 cc (12.87-107 cc), representing 5% of the breast tissue irradiated with a median CTV D90 of 6.2 Gy (5.6-6.28 Gy). The entire local treatment (BCS&MITBI-4f-AMBI) was completed at a median of 8 days (4-10 days). The rate of early complications was 11%. There were no major complications. Acute skin-subcutaneous G1 toxicity was reported in 11.7%, and late G1 toxicity on 36.7%. After a median follow-up of 27 months (11-51 months), the local, elsewhere, locoregional and distant-control rates were 100%, 98.3%, 100%, and 100% respectively. The early-cosmetic evaluation was excellent-good in 94.5% of patients evaluated. Conclusions: Ultra-accelerated, four-fraction, minimal breast irradiation (4f-AMBI) using a minimally-invasive tumor bed implant procedure is safe, dosimetrically feasible, and shows small irradiated volumes. This program provides low toxicity rates and excellent short-term clinical and cosmesis outcomes.

Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4 -> Dx4) followed by surgery +/- radiotherapy +/- hormonotherapy. Results: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p = 0.25), 16.6% versus 0% in luminal B (p = 0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p < 0.01). No grade > 3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-gamma production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-beta repertoire were detected in 67% of the patients with a drop in diversity index after treatment. Conclusion: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome.

Purpose: To evaluate our institutional experience of minimally invasive tumor bed implantation (MITBI) during breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) to deliver peri-operative high-dose-rate brachytherapy (PHDRBT) as accelerated minimal breast irradiation (AMBI) or anticipated boost (A-PHDRBT-boost). Material and methods: Patients older than 40, with clinical and radiological unifocal DCIS < 3 cm were considered potential candidates for accelerated partial breast irradiation (APBI) and were implanted during BCS using MITBI-technique. Patients who in final pathology reports showed free margins and no other microscopic tumor foci, received AMBI with PHDRBT (3.4 Gy BID in 5 days). Patients with adverse features received A-PHDRBT-boost with post-operative external beam radiotherapy (EBRT). Results: Forty-one patients were implanted, and 36 were treated and analyzed. According to final pathology, 24 (67%) patients were suitable for AMBI and 12 (33%) were qualified for A-PHDRBT-boost. Reoperation rate for those with clear margins was 16.6% (6/36); this rate increased to 33% (4/12) for G3 histology, and 66% (4/6) were rescued using AMBI. Early complications were documented in 5 patients (14%). With a median follow-up of 97 (range, 42-138) months, 5-year rates of local, elsewhere, locoregional, and distant control were all 97.2%. 5-year ipsilateral breast tumor recurrence rates (IBTR) were 5.6% (2/36), 8.3% (2/24) for AMBI, and 0% (0/12) for A-PHDRBT-boost patients. Both instances of IBTR were confirmed G3 tumors in pre-operative biopsies; no IBTR was documented in G1-2 tumors. Cosmetic outcomes were excellent/good in 96% of AMBI vs. 67% in A-PHDRBT-boost (p = 0.034). Conclusions: The MITBI-PHDRBT program allows selection of patients with excellent prognoses (G1-2 DCIS with negative margins and no multifocality), for whom AMBI could be a good alternative with low recurrence rate, decrease of unnecessary radiation, treatment logistics improvement, and over-treatment reduction. Patients whose pre-operative biopsy showed G3 tumor, presents with inferior local control and more risk of reoperation due to positive margins.

Objectives To perform an external validation of the diagnostic performance of the three-step strategy proposed by the International Ovarian Tumor Analysis (IOTA) group for classifying adnexal masses as benign or malignant, when ultrasound is performed by non-expert sonographers in the first two steps. The second objective was to assess the diagnostic performance of an alternative strategy using simple-rules risk (SRR), instead of simple rules (SR), in the second step. Methods This was a prospective observational study conducted at two university hospitals, from September 2015 to August 2017, of consecutive patients diagnosed with an adnexal mass. All women were evaluated by ultrasound using the IOTA three-step strategy. Non-expert sonographers performed the first step (use of simple descriptors to classify the masses) and the second step (use of SR if the mass could not be classified in the first step); masses that could not be classified in the first two steps were categorized by an expert sonographer based on their subjective assessment (third step). The reference standard was histological diagnosis in patients who underwent surgery or at least 12 months of follow-up in cases managed expectantly. The sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios and overall accuracy of the IOTA three-step strategy were estimated. Furthermore, we evaluated retrospectively an alternative two-step strategy using SRR in the second step to categorize the masses not classifiable with simple descriptors, classifying the lesions as being of low, intermediate or high risk for malignancy. The diagnostic performance of this strategy was estimated by calculating its sensitivity and specificity, assuming surgical intervention for intermediate-or high-risk lesions. Results The study included 283 patients (median age, 48 (range, 18-90) years), of whom 165 (58.3%) were premenopausal and 118 (41.7%) postmenopausal. Two hundred and sixteen (76.3%) women underwent surgery (154 benign and 62 malignant masses) and 67 (23.7%) were managed expectantly with serial ultrasound follow-up for at least 12 months. All expectantly managed masses were considered benign because no sonographic changes suggestive of malignancy were observed during follow-up. Simple descriptors could be applied in 126 (44.5%) masses. Of the remaining 157 lesions, 112 (39.6%) could be characterized using SR. Therefore, 238 (84.1%) masses could be classified by non-expert sonographers in the first two steps. Of the remaining 45 (15.9%) masses, all could be classified by an expert sonographer. Overall sensitivity, specificity, LR+ and LR- of the IOTA three-step strategy were 95.2%, 97.7%, 42.1 and 0.05, respectively. The diagnostic accuracy was 97.2%. Following the two-step strategy using SRR in the second step, of the 157 lesions not classified with simple descriptors, 42, 38 and 77 presented low, intermediate or high risk for malignancy, respectively. Based on this method, 210 women would have undergone surgical treatment. The sensitivity and specificity of this two-step strategy were 98.4% and 63.8%, respectively. Conclusions The IOTA three-step strategy shows high accuracy for discriminating between benign and malignant adnexal lesions when used by non-expert sonographers. An alternative strategy using the SRR calculator in the second step might improve on this diagnostic performance by decreasing the number of surgical interventions and increasing sensitivity.

Objective To assess the diagnostic performance of a three-step strategy proposed by the International Ovarian Tumor Analysis (IOTA) Group for discriminating between benign and malignant adnexal masses. Methods This was a prospective observational study, performed at two tertiary-care university hospitals, of women diagnosed with an adnexal mass on transvaginal or transabdominal ultrasound between December 2012 and December 2014. Women were scheduled for an ultrasound evaluation, which was initially performed by non-expert examiners. The examiner had to classify the mass using `simple descriptors¿ (first step) and, if not possible, using `simple rules¿ (second step). For inconclusive masses, an expert examiner classified the mass according to their subjective impression (third step). Masses were managed expectantly, with serial follow-up examinations, or surgically, according to ultrasound findings and clinical symptoms. Histology was used as the reference standard. Masses that were managed expectantly with at least 1 year of follow-up were considered as benign for analytical purposes. Women with less than 1 year of follow-up were not included in the study. Results Six hundred and sixty-six women were included (median age, 41 (range, 18¿81)¿years) of whom 514 were premenopausal and 152 were postmenopausal. Based on the three-step strategy, 362 women had surgical removal of the mass (53 malignant and 309 benign), 71 masses resolved spontaneously and 233 persisted. Four hundred and forty-eight (67.3%) of 666 masses could be classified using simple descriptors and, of the 218 that could not, 147 (67.4%) were classified using simple rules. Of the remaining 71 masses, the expert examiner classified 45 as benign, 12 as malignant and 14 as uncertain. Overall sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of the three-step strategy were 94.3%, 94.9%, 18.6 and 0.06, respectively. Conclusion The IOTA three-step strategy, based on the sequential use of simple descriptors, simple rules and expert evaluation, performs well for classifying adnexal masses as benign or malignant.

Purpose: To assess the safety, feasibility, and efficacy of free-hand intraoperative multicatheter breast implant (FHIOMBI) and perioperative high-dose-rate brachytherapy (PHDRBT) in early breast cancer. Methods and Materials: Patients with early breast cancer candidates for breast conservative surgery (BCS) were prospectively enrolled. Patients suitable for accelerated partial breast irradiation (APBI) (low or intermediate risk according GEC-ESTRO criteria) received PHDRBT (3.4 Gy BID × 10 in 5 days). Patients not suitable for APBI (high risk patients according GEC-ESTRO criteria) received PHDRBT boost (3.4 Gy BID × 4 in 2 days) followed by whole breast irradiation. Results: From June 2007 to November 2014, 119 patients were treated and 122 FHIOMBI procedures were performed. Median duration of FHIOMBI was 25 minutes. A median of eight catheters (range, 4-14) were used. No severe intraoperative complications were observed. Severe early postoperative complications (bleeding) were documented in 2 patients (1.6%), wound healing complications in 3 (2.4%), and infection (mastitis or abscess) in 2 (1.6%). PHDRBT was delivered as APBI in 88 cases (72.1%) and as a boost in 34 (27.8%). The median clinical target volume T was 40.8 cc (range, 12.3-160.5); median D90 was 3.32 Gy (range, 3.11-3.85); median dose homogeneity index was 0.72 (range, 0.48-0.82). With a median followup of 38.4 months (range, 8.7-98.7) no local, elsewhere, or regional relapses were observed; there was only one distant failure in PHDRBT boost. No major (acute or late) RTOG grade 3 or higher were documented in any of the 119 patients treated with PHDRBT. Cosmetic outcome in APBI patients was excellent or good in (87.0%) and fair or poor in (11.9%) while in boost patients was excellent or good in (76.4%) and fair in (23.5%). Conclusion: The FHIOMBI-PHDRBT program does not add complications to conservative surgery. It allows precise selection of APBI patients and offers excellent results in disease control and cosmetics. It also offers logistic advantages because it dramatically shortens the time of local treatment and avoids further invasive procedures.

Levator avulsion is associated with lower manometric squeeze pressure (p¿=¿0.032).

ObjectiveTo evaluate the contribution of three-dimensional (3D) power Doppler angiography (3D-PDA) to the differential diagnosis of adnexal masses. MethodsThis was a prospective study in women diagnosed with a persistent adnexal mass and subsequently scheduled for surgery in a tertiary university hospital. All women were evaluated by transvaginal/transrectal ultrasound according to a predetermined three-step protocol, with transabdominal ultrasound being performed in some cases. First, morphological evaluation of the mass was performed using gray-scale pattern recognition' (first step). Lesions diagnosed as having a benign pattern were considered as being at low risk of malignancy whereas tumors with solid components, ascites and/or signs of carcinomatosis were considered as being at high risk of malignancy. In both cases no further test was performed and a decision regarding clinical management, either for follow-up or surgery, was taken. Tumors with solid components but without signs of ascites or carcinomatosis were considered as being at intermediate risk of malignancy. These lesions were assessed by two-dimensional (2D) PDA to evaluate tumor vascularity (color score) (second step). Solid tumors with a color score of 1 or 2 were considered as benign and no further test was performed, while tumors with a color score of 2, 3 or 4 within solid components or a color score of 3 or 4 in the case of a solid tumor were considered as malignant. The latter group underwent 3D-PDA a

To determine the degree of confidence of students regarding obstetric examination before and after training with simulators, and assess their satisfaction with the use of simulation as a tool for acquiring skills. METHODS:Training groups involved 10 students per lecturer. Students learned how to perform Leopold's manoeuvres and measure uterine height with a simulator. The instructor supervised each physical exam. Surveys by those students who had previously done an internship at the Department of Obstetric & Gynecology were not taken into account. RESULTS:Students' confidence in performing the procedures improved significantly (p¿0.001) after the intervention.

Introduction: Accelerated partial breast irradiation (APBI) with multicatheters after lumpectomy for breast cancer (BC) may be an alternative to whole breast irradiation in selected patients. The aim is to show our 5 year experience. Method: Between June 2007 and June 2012, 87 BC patients have been evaluated for APBI. Inclusion criteria were: age over 40 years, unifocal tumour, infiltrating ductal or intraductal carcinoma, tumour size smaller than 3 cm and no lymph node involvement. Complications, cosmetic results and local and distant recurrences were evaluated. Results: Treatment was completed in 48 patients and contraindicated in 39. The average age of treated patients was 59 years. Operating time was 123. min with 9 implanted catheters in each patient. No complications were observed during surgery or radiotherapy. Patients were discharged from hospital after 4 days. Tumour size was 11. mm. Of these, 35 were infiltrating ductal and 13 intraductal carcinomas. A total of 44 patients received adjuvant treatment. Mean follow-up was 22 months with no evidence of local or distant recurrence. The cosmetic outcome was good or excellent in 66% of cases. Conclusions: APBI with multicatheter placed after lumpectomy for BC is feasible and safe but requires a strict selection of patients.