Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: impact on axillary morbidity and survival-a propensity score cohort study.

PURPOSE: In patients with clinically lymph node-negative (cN0) breast cancer, performing sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) has been preferentially embraced in comparison to before NACT. However, survival outcomes associated with both strategies remain understudied. We aimed to compare the axillary lymphadenectomy (ALND) rate, disease-free survival (DFS), and overall survival (OS), between two strategies. METHODS: We included 310 patients in a retrospective observational study. SNLB was performed before NACT from December 2006 to April 2014 (107 cases) and after NACT from May 2014 to May 2020 (203 patients). An inverse probability of treatment weighting (IPTW) method was applied to homogenize both groups. Hazard ratios (HR) and odd ratios (OR) are reported with 95% confidence intervals (95%CI). RESULTS: The lymphadenectomy rate was 29.9% before NACT and 7.4% after NACT (p < 0.001), with an OR of 5.35 95%CI (2.7-10.4); p = .002. After 4 years of follow-up, SLNB after NACT was associated with lower risk for DFS, HR 0.42 95%CI (0.17-1.06); p = 0.066 and better OS, HR 0.21 CI 95% (0.07-0.67); p = 0.009 than SLNB before NACT. After multivariate analysis, independent adverse prognostic factors for OS included SLNB before NACT, HR 3.095 95%CI (2.323-4.123), clinical nonresponse to NACT, HR 1.702 95% CI (1.012-2.861), and small tumors (cT1) with high proliferation index, HR 1.889 95% (1.195-2.985). CONCLUSION: Performing SLNB before NACT results in more ALND and has no benefit for patient survival. These findings support discontinuing the practice of SLNB before NACT in patients with cN0 breast cancer.

Ovarian cancer relies on the PDGFRß-fibronectin axis for tumorsphere formation and metastatic spread.

High-grade serous ovarian cancer (HGSOC) is the deadliest gynecological malignancy. The most common form of metastatic spread of HGSOC is transcoelomic dissemination. In this process, detached cells from the primary tumor aggregate as tumorspheres and promote the accumulation of peritoneal ascites. This represents an early event in HGSOC development and is indicative of poor prognosis. In this study, based on tumorspheres isolated from ascitic liquid samples from HGSOC patients, ovarian cancer spheroid 3D cultures, and in vivo models, we describe a key signal for tumorsphere formation in HGSOC. We report that platelet-derived growth factor receptor beta (PDGFRß) is essential for fibronectin-mediated cell clustering of ovarian cancer cells into tumorspheres. This effect is mediated by the kinase NUAK family SNF1-like kinase 1 (NUAK1) and blocked by PDGFRß pharmacological or genetic inhibition. In the absence of PDGFRß, ovarian cancer cells can be provided with fibronectin by cancer-associated fibroblasts to generate chimeric spheroids. This work provides new insights that uncover potential targets to prevent peritoneal dissemination, the main cause of advanced disease in HGSOC patients.

Occupational exposure to pesticides and endometrial cancer in the Screenwide case-control study.

BACKGROUND: Endometrial cancer is the most common gynaecological tumour in developed countries and disease burden is expected to increase over the years. Identifying modifiable risk factors may help developing strategies to reduce the expected increasing incidence of these neoplasms. OBJECTIVE: This study evaluates the association between occupational exposure to pesticides and endometrial cancer using data from a recent case-control study in Spain. METHODS: The analyses included data from 174 consecutive incident endometrial cancer cases and 216 hospital controls frequency-matched by age. Data were collected through structured epidemiological questionnaires and exposure to pesticides was assessed using a Spanish job-exposure matrix (MatEmESp). RESULTS: Overall, 12% of controls and 18% of cases were occupationally exposed to pesticides. We observed a positive association between occupational exposure to pesticides and endometrial cancer (OR = 2.08; 95% CI = 1.13-3.88 compared to non-exposed). In general, exposures that occurred farther in the past were significantly associated with endometrial cancer. Exposure to insecticides, fungicides and herbicides were positively associated with endometrial cancer (OR = 2.08; 95% CI = 1.13-3.88, OR = 4.40; 95% CI = 1.65-13.33, and OR = 5.25; 95% CI = 1.84-17.67, respectively). The agricultural, poultry and livestock activities scenario was associated with endometrial cancer (OR = 4.16; 95% CI = 1.59-12.32), while the cleaning exposure scenario was not (OR = 1.22; 95% CI = 0.55-2.67). CONCLUSIONS: Assessment of occupational exposure to pesticides assessed using a Spanish job-exposure matrix revealed a positive association with endometrial cancer. The elucidation of the role of pesticide compounds on endometrial cancer should shed a light on the aetiology of this tumour.

Accuracy and Survival Outcomes after National Implementation of Sentinel Lymph Node Biopsy in Early Stage Endometrial Cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has recently been accepted to evaluate nodal status in endometrial cancer at early stage, which is key to tailoring adjuvant treatments. Our aim was to evaluate the national implementation of SLN biopsy in terms of accuracy to detect nodal disease in a clinical setting and oncologic outcomes according to the volume of nodal disease. PATIENTS AND METHODS: A total of 29 Spanish centers participated in this retrospective, multicenter registry including patients with endometrial adenocarcinoma at preoperative early stage who had undergone SLN biopsy between 2015 and 2021. Each center collected data regarding demographic, clinical, histologic, therapeutic, and survival characteristics. RESULTS: A total of 892 patients were enrolled. After the surgery, 12.9% were suprastaged to FIGO 2009 stages III-IV and 108 patients (12.1%) had nodal involvement: 54.6% macrometastasis, 22.2% micrometastases, and 23.1% isolated tumor cells (ITC). Sensitivity of SLN biopsy was 93.7% and false negative rate was 6.2%. After a median follow up of 1.81 years, overall surivial and disease-free survival were significantly lower in patients who had macrometastases when compared with patients with negative nodes, micrometastases or ITC. CONCLUSIONS: In our nationwide cohort we obtained high sensitivity of SLN biopsy to detect nodal disease. The oncologic outcomes of patients with negative nodes and low-volume disease were similar after tailoring adjuvant treatments. In total, 22% of patients with macrometastasis and 50% of patients with micrometastasis were at low risk of nodal metastasis according to their preoperative risk factors, revealing the importance of SLN biopsy in the surgical management of patients with early stage EC.

Evaluation of somatic mutations in cervicovaginal samples as a non-invasive method for the detection and molecular classification of endometrial cancer.

BACKGROUND: The incidence of endometrial cancer is increasing worldwide. While delays in diagnosis reduce survival, case molecular misclassification might be associated with under- and over-treatment. The objective of this study was to evaluate genetic alterations to detect and molecularly classify cases of endometrial cancer using non-invasive samples. METHODS: Consecutive patients with incident endometrial cancer (N = 139) and controls (N = 107) from a recent Spanish case-control study were included in this analysis. Overall, 339 cervicovaginal samples (out of which 228 were clinician-collected and 111 were self-collected) were analysed using a test based on next-generation sequencing (NGS), which targets 47 genes. Immunohistochemical markers were evaluated in 133 tumour samples. A total of 159 samples were used to train the detection algorithm and 180 samples were used for validation. FINDINGS: Overall, 73% (N = 94 out of 129 clinician-collected samples, and N = 66 out of 90 self-collected samples) of endometrial cancer cases had detectable mutations in clinician-collected and self-collected samples, while the specificity was 80% (79/99) for clinician-collected samples and 90% (19/21) for self-collected samples. The molecular classifications obtained using tumour samples and non-invasive gynaecologic samples in our study showed moderate-to-good agreement. The molecular classification of cases of endometrial cancer into four groups using NGS of both clinician-collected and self-collected cervicovaginal samples yielded significant differences in disease-free survival. The cases with mutations in POLE had an excellent prognosis, whereas the cases with TP53 mutations had the poorest clinical outcome, which is consistent with the data on tumour samples. INTERPRETATION: This study classified endometrial cancer cases into four molecular groups based on the analysis of cervicovaginal samples that showed significant differences in disease-free survival. The molecular classification of endometrial cancer in non-invasive samples may improve patient care and survival by indicating the early need for aggressive surgery, as well as reducing referrals to highly specialized hospitals in cancers with good prognosis. Validation in independent sets will confirm the potential for molecular classification in non-invasive samples. FUNDING: This study was funded by a competitive grant from Instituto de Salud Carlos III through the projects PI19/01835, PI23/00790, and FI20/00031, CIBERESP CB06/02/0073 and CIBERONC CB16/12/00231, CB16/12/00234 (Co-funded by European Regional Development Fund. ERDF: A way to build Europe). Samples and data were provided by Biobank HUB-ICO-IDIBELL, integrated into the Spanish Biobank Network, and funded by the Instituto de Salud Carlos III (PT20/00171) and by Xarxa de Bancs de Tumors de Catalunya (XBTC) sponsored by Pla Director d'Oncologia de Catalunya. This work was supported in part by the AECC, Grupos estables (GCTRA18014MATI). It also counts with the support of the Secretariat for Universities and Research of the Department of Business and Knowledge of the Generalitat de Catalunya, and grants to support the activities of research groups 2021SGR01354 and 2021SGR1112.

Cost-effectiveness analysis of molecular testing in minimally invasive samples to detect endometrial cancer in women with postmenopausal bleeding.

INTRODUCTION: New approaches are being developed to early detect endometrial cancer using molecular biomarkers. These approaches offer high sensitivities and specificities, representing a promising horizon to develop early detection strategies. OBJECTIVE: To evaluate the effectiveness and cost-effectiveness of introducing molecular testing to detect endometrial cancer in women with postmenopausal bleeding compared to the current strategy using the national healthcare service perspective. METHODS: A Markov model was developed to assess the two early detection strategies. The model predicts the number of hysterectomies, lifetime expectancy, quality-adjusted life-years, endometrial cancer prevalence and incidence, mortality from endometrial cancer and the lifetime cost of screening, diagnosis, and treatment. Strategies were compared using the incremental cost-effectiveness ratio. RESULTS: The molecular strategy reduces 1.9% of the overall number of hysterectomies and the number of undetected cancer cases by 65%. Assuming a molecular test cost of 310€, the molecular strategy has an incremental cost of -32,952€ per QALY gained, being more effective and less expensive than the current strategy. CONCLUSIONS: The introduction of molecular testing to diagnose endometrial cancer in women presenting postmenopausal bleeding provides more health benefit at a lower cost, and therefore has the potential to be cost-effective.

Management of the axilla in postmenopausal patients with cN0 hormone receptor-positive/HER2-negative breast cancer treated with neoadjuvant endocrine therapy and its prognostic impact.

PURPOSE: To evaluate the differences in nodal positivity if the sentinel lymph node biopsy (SLNB) is performed before or after neoadjuvant endocrine therapy (NET) in breast cancer patients, and its impact on prognosis. METHODS: A retrospective cohort study was performed in a single center including 91 postmenopausal cases with clinically node-negative and hormone receptor-positive/HER2-negative (HR + /HER2-) breast cancer, treated with NET and SLNB. SLNB was done pre-NET until 2014, and post-NET thereafter. Axillary lymph node dissection (ALND) was indicated only in SLNB macrometastasis, although in selected elderly patients, it was omitted. Kaplan-Meier survival curves were estimated in relation to the status of the axilla, and the differences assessed using the log-rank test. RESULTS: Between December 2006 and March 2022, SLNB was performed pre-NET in 14 cases and post-NET in 77. Both groups were similar in baseline tumor and patient characteristics. SLNB positivity was similar regardless of whether SLNB was performed before (5/14, 35.7%) or after NET (27/77, 37%), with 2/14 SLN macrometastases in the pre-NET cohort and 17/77 in the post-NET cohort. Only three patients (18.7%) with SLN macrometastasis had > 3 positive nodes following ALND. The 5-year overall survival and distant disease-free survival were 92.4% and 94.8%, respectively, with no significant differences according to SLNB status (p 0.5 and 0.8, respectively). CONCLUSION: SLN positivity did not differ according to its timing (before or after NET). Therefore, NET has no effect on lymph node clearance. Furthermore, the prognosis is good regardless of the axillary involvement. Therefore, factors other than axillary involvement may affect the prognosis in these patients.

An Integrated Approach for the Early Detection of Endometrial and Ovarian Cancers (Screenwide Study): Rationale, Study Design and Pilot Study.

Screenwide is a case-control study (2017−2021) including women with incident endometrial and ovarian cancers (EC and OC), BRCA1/2 and MMR pathogenic variant carriers, and age-matched controls from three centers in Spain. Participants completed a personal interview on their sociodemographic factors, occupational exposure, medication, lifestyle, and medical history. We collected biological specimens, including blood samples, self-collected vaginal specimens, cervical pap-brush samples, uterine specimens, and, when available, tumor samples. The planned analyses included evaluation of the potential risk factors for EC/OC; evaluation of molecular biomarkers in minimally invasive samples; evaluation of the cost-effectiveness of molecular tests; and the generation of predictive scores to integrate different epidemiologic, clinical, and molecular factors. Overall, 182 EC, 69 OC, 98 BRCA pathogenic variant carriers, 104 MMR pathogenic variant carriers, and 385 controls were enrolled. The overall participation rate was 85.7%. The pilot study using 61 samples from nine EC cases and four controls showed that genetic variants at the variant allele fraction > 5% found in tumors (n = 61 variants across the nine tumors) were detected in paired endometrial aspirates, clinician-collected cervical samples, and vaginal self-samples with detection rates of 90% (55/61), 79% (48/61), and 72% (44/61) by duplex sequencing, respectively. Among the controls, only one somatic mutation was detected in a cervical sample. We enrolled more than 800 women to evaluate new early detection strategies. The preliminary data suggest that our methodological approach could be useful for the early detection of gynecological cancers.

The Impact of Surgical Practice on Oncological Outcomes in Robot-Assisted Radical Hysterectomy for Early-Stage Cervical Cancer, Spanish National Registry.

This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed by the European Society of Gynaecological Oncology (ESGO). The top 5 of 10 centers in Spain and Portugal were included in the analysis. The hospitals were divided into group A (n = 118) and group B (n = 97), with recurrence rates of <10% and >10%, respectively. After balancing both groups using the propensity score, the ORs for all events were higher and statistically significant for group B (recurrences OR = 1.23, 95% CI = 1.13-1.15, p-value = 0.001; death OR = 1.10, 95% CI = 1.02-1.18, p-value = 0.012; disease-specific mortality ORr = 1.11, 95% CI = 1.04-1.19, p-value = 0.002). A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed among the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes not only after robot-assisted surgery, but also after laparoscopies and open surgeries in the treatment of cervical cancer.

Prophylactic incisional negative pressure wound therapy for gynaecologic malignancies.

Wound complications are an important cause of postoperative morbidity among patients with gynaecologic malignancies. We evaluated whether the placement of closed-incisional negative pressure therapy (ciNPT) at the time of laparotomy for gynaecologic cancer surgery reduced wound complication rates. A retrospective cohort study with primary wound closure performed by a gynaecologic oncologist was carried out. We evaluated two cohorts of patients who underwent surgery in 2017 with standard closure and patients who underwent surgery in 2019 with the placement of prophylactic ciNPT. Postoperative outcomes were examined. A total of 143 patients were included, 85 (59.4%) vs 58 (40.6%) with standard closure and ciNPT, respectively. The total complication rate in our sample was 38.71%. The rate of surgical complications in patients treated with ciNPT was 6.9% compared with 31.8% (P = .000) in patients treated with standard closure. In the analysis of complications, a significant reduction in infections (17.1%), seromas (15.4%), and wound dehiscence (17.1%) were observed when ciNPT was applied. The median hospital stay was 8 vs 6 days in the standard closure vs ciNPT groups (P = .048). The use of the prophylactic ciNPT following a laparotomy may decrease wound complications and hospital stays in oncological patients. ciNPT could be considered as part of clinical practice in patients at high risk of wound complications, such as patients with gynaecological malignancies.

Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

PURPOSE: To find a group of cN2 patients or patients with high axillary burden who become ypN0 after neoadjuvant chemotherapy (NACT) and who may benefit from avoiding a lymphadenectomy. METHODS: A retrospective observational cohort study was conducted with 221 clinically staged N2 patients or patients with at least 3 suspicious lymph nodes found by ultrasound at diagnosis. The predictive factors for ypN0 analysed were age, MRI-determined tumour size, histological subtype, the Nottingham histologic grade, surrogate molecular subtype, ki-67 and vascular invasion when present. Clinical and radiological responses after NACT were also evaluated. Univariate and multivariate analyses by logistic regression were performed. Distant disease-free survival (DDFS) was calculated in relation to the status of the axillary lymph nodes after NACT. RESULTS: After NACT, 89 patients (40.3%) had axillary pathologic complete response (pCR) (ypN0) and 132 (59.7%) had residual axillary disease (ypN+). Molecular surrogate subtype, Ki-67 expression, and the clinical and radiological responses to NACT were the only independent factors associated with ypN0. Axillary pCR was observed more often in HER2-positive and triple-negative tumours than in luminal ones (OR 7.5 and 3.6, respectively). DDFS was 88.7% (95% CI 80.7-96.7%) for ypN0 and 56.2% (95% CI 32.1-80.3%) for ypN+ (p = 0.09). CONCLUSIONS: In HER2-positive and triple-negative breast cancer patients staged as cN2 or with high axillary burden before NACT, a sentinel lymph node biopsy after NACT could be recommended if there is a clinical and radiological response.

Risk Factors for Recurrence after Robot-Assisted Radical Hysterectomy for Early-Stage Cervical Cancer: A Multicenter Retrospective Study.

This retrospective analysis aimed to assess the risk factors for recurrence in patients diagnosed with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) undergoing robot-assisted radical hysterectomy in Spain and Portugal between 2009 and 2018. A second primary objective was to audit the oncological outcomes according to quality indicators (QI) proposed by the European Society of Gynecology Oncology (ESGO). The study population included 239 women. After a median follow-up of 51 months, recurrence occurred in 26 patients (10.9%). Independent factors for recurrence were clinical tumor size > 20 mm (hazard ratio (HR) 2.37), adenocarcinoma as histological type (HR 2.51), positive pelvic lymph nodes (HR 4.83), tumor grade 2 (HR 4.99), tumor grade 3 (HR 8.06), and having not performed sentinel lymph node biopsy (SLNB) (HR 4.08). All 5 QI selected were surpassed by our results. In patients with early-stage cervical cancer undergoing robotic radical hysterectomy, clinicians should be aware that tumor grade 2 and 3, tumor size > 20 mm, adenocarcinoma, positive pelvic nodes, and lack of performance of SLNB are risk factors for recurrence. Fulfillment of QI targets of the ESGO might be considered as an objective oncological outcome indicator supporting the minimally invasive approach for early-stage cervical cancer treatment.

Study of the fetal and maternal microbiota in pregnant women with intrauterine growth restriction and its relationship with inflammatory biomarkers: A case-control study protocol (SPIRIT compliant).

In general terms, fetal growth restriction (FGR) is considered the impossibility of achieving the genetically determined potential size. In the vast majority of cases, it is related to uteroplacental insufficiency. Although its origin remains unknown and causes are only known in 30% of cases, it is believed to be related to an interaction of environmental and genetic factors with either a fetal or maternal origin. One hypothesis is that alterations in the gastrointestinal microbiota composition, and thus alteration in the immune response, could play a role in FGR development. We performed an observational, prospective study in a subpopulation affected with FGR to elucidate the implications of this microbiota on the FGR condition.A total of 63 fetuses with FGR diagnosed in the third trimester as defined by the Delphi consensus, and 63 fetuses with fetal growth appropriate for gestational age will be recruited. Obstetric and nutritional information will be registered by means of specific questionnaires. We will collect maternal fecal samples between 30 to 36 weeks, intrapartum samples (maternal feces, maternal and cord blood) and postpartum samples (meconium and new-born feces at 6 weeks of life). Samples will be analyzed in the Department of Biochemistry and Molecular Biology II, Nutrition and Food Technology Institute of the University of Granada (UGR), for the determination of the gastrointestinal microbiota composition and its relationship with inflammatory biomarkers.This study will contribute to a better understanding of the influence of gastrointestinal microbiota and related inflammatory biomarkers in the development of FGR.Trial registration: NCT04047966. Registered August 7, 2019, during the recruitment stage. Retrospectively registered. Ongoing research.

Predictive factors for omitting lymphadenectomy in patients with node-positive breast cancer treated with neo-adjuvant systemic therapy.

A pathologic complete response (pCR) in the axilla occurs in 30%-40% of patients with initially node-positive breast cancer after neo-adjuvant chemotherapy (NACT). Debate persists about whether to perform systematic axillary lymphadenectomy (ALND) in patients with initial node-positive disease and clinical complete response after NACT. We aimed to identify predictive factors of axillary pCR (ypN0) after NACT. This retrospective study analyzed data for all patients with initial biopsy-proven node-positive disease who underwent ALND after NACT between June 2008 and December 2016 at our institution. Clinical and pathologic features, recurrence and specific mortality rates were compared between patients who achieved an axillary pCR and those who did not (ypN0 vs ypN+, respectively). A total of 331 patients were included, of whom 128 (38.7%) became ypN0 after NACT. Among patients with >2 suspicious axillary lymph nodes before treatment, 54 (38%) achieved ypN0 status. The independent predictors of ypN0 were Ki-67 > 30 (OR 1.98; 95% CI, 1.146-3.381), HER2 positivity (OR 2.6; 95% CI, 1.354-5.108), nonluminal molecular-like subtype (OR 4.15; 95% CI, 2.068-5.108), and clinical complete response, defined as negative clinical and ultrasonographic findings (OR 2.8; 95% CI, 1.110-7.081). After a mean follow-up of 61 months, distant disease-free and overall survival rates were higher in patients with ypN0 disease (HR 4.14; 95% CI, 2.03-8.43) than ypN+ patients. Complete clinical response and the presence of nonluminal molecular-like subtypes independently predicted ypN0. Patients meeting these criteria might be suitable form omitting ALND and just performing targeted axillary procedures to patients meeting these criteria.

The Evolving Microbiome from Pregnancy to Early Infancy: A Comprehensive Review.

Pregnancy induces a number of immunological, hormonal, and metabolic changes that are necessary for the mother to adapt her body to this new physiological situation. The microbiome of the mother, the placenta and the fetus influence the fetus growth and undoubtedly plays a major role in the adequate development of the newborn infant. Hence, the microbiome modulates the inflammatory mechanisms related to physiological and pathological processes that are involved in the perinatal progress through different mechanisms. The present review summarizes the actual knowledge related to physiological changes in the microbiota occurring in the mother, the fetus, and the child, both during neonatal period and beyond. In addition, we approach some specific pathological situations during the perinatal periods, as well as the influence of the type of delivery and feeding.

Assessment of ovarian reserve and reproductive outcomes in BRCA1 or BRCA2 mutation carriers.

INTRODUCTION: The clinical impact on fertility in carriers of BRCA1 and BRCA2 mutations remains unclear. The aim of this study was to assess ovarian reserve as measured by anti-mullerian hormone levels in BRCA1 or BRCA2 mutation carriers, as well as to investigate the impact of anti-mullerian hormone levels on reproductive outcomes. METHODS: The study involved a cohort of women who tested positive for BRCA1 and BRCA2 screening or were tested for a BRCA1 or BRCA2 family mutation. Blood samples were collected for anti-mullerian hormone analysis and the reproductive outcomes were analyzed after a mean follow-up of 9 years. Participants were classified into BRCA mutation-positive versus BRCA mutation-negative. Controls were healthy relatives who tested negative for the family mutation. All patients were contacted by telephone to collect data on reproductive outcomes. Linear regression was used to predict anti-mullerian hormone levels by BRCA status adjusted for a polynomial form of age. RESULTS: Results of anti-mullerian hormone analysis and reproductive outcomes were available for 135 women (BRCA mutation-negative, n=66; BRCA1 mutation-positive, n=32; BRCA2 mutation-positive, n=37). Anti-mullerian hormone curves according to BRCA status and adjusted by age showed that BRCA2 mutation-positive patients have lower levels of anti-mullerian hormone as compared with BRCA-negative and BRCA1 mutation-positive. Among the women who tried to conceive, infertility was observed in 18.7% of BRCA mutation-negative women, in 22.2% of BRCA1 mutation-positive women, and in 30.8% of BRCA2 mutation-positive women (p=0.499). In the multivariable analysis, there were no factors independently associated with infertility. DISCUSSION: BRCA2 mutation-positive carriers showed more diminished anti-mullerian hormone levels than BRCA1 mutation-positive and BRCA mutation-negative women. However, these differences do not appear to have a negative impact on reproductive outcome. This is important to consider at the time of reproductive counseling in women with BRCA1 or BRCA2 mutations.

Mejora coste efectiva en diagnóstico de cáncer endometrial con la incorporación del análisis molecular GynEC(R)-Dx / Cost-effective improvement in endometrial cancer diagnosis by the incorporation of molecular analysis

Objetivo: estimar el número de exploraciones evitables al comparar un algoritmo diagnóstico clásico de la metrorragia posmenopáusica (MPM) frente a un algoritmo que incorpore un test molecular como GynEC(R)-Dx. Material y métodos: estudio de cohortes, prospectivo y aleatorizado por centros realizado en mujeres que presentaron MPM. Las pacientes fueron aleatorizadas a seguir un algoritmo de estudio de MPM clásico vs GynEC(R)-Dx. Se registraron variables demográficas y se comparó el uso de recursos tales como biopsias, ecografías, histeroscopias y visitas entre ambos grupos. Adicionalmente se revalidó la sensibilidad (S), especificidad (E), valor predictivo positivo (VPP) y valor predictivo negativo (VPN) del test. Resultados: se incluyeron un total de 94 pacientes, 51 en grupo clásico y 43 en grupo GynEC(R)-Dx. En el grupo clásico se realizaron 95 exploraciones más respecto al grupo de GynEC(R)-Dx clasificadas en: 11 biopsias, 17 ecografías, 24 histeroscopias y 89 visitas. En el grupo GynEC(R)-Dx se realizaron 92 exploraciones innecesarias consideradas "fuera de protocolo". En la revalidación se observó una S 100%, E 92.5%, VPP 50%, VPN 100%. Conclusiones: la incorporación de un test molecular como GynEC(R)-DX para el estudio de la metrorragia posmenopáusica permite disminuir el número de exploraciones y visitas respecto a los algoritmos convencionales

Objective: The histopathology remains the gold standard to diagnose endometrial cancer (EC) from endometrial biopsy. Molecular tests have recently emerged as a useful tool to classify EC according to its prognosis. However, there is currently no published protocol that includes molecular diagnosis of postmenopausal women with abnormal uterine bleeding (AUB). We hypothesized that the incorporation of a molecular test in the management of postmenopausal women with AUB improves the cost-efectiveness of the diagnostic process. Material and methods: We present a prospective study performed in postmenopausal women who presented AUB between 2009-2014. Seven centers recruited the patients. Three of them follow the classical diagnosis algorithm (group 1) and four centers follow the one that incorporates a molecular test (Gynec(R)-Dx) performed on the remnants of aspirates (group 2). In group 2, when both the endometrial biopsy and the molecular test were negative, the consequent explorations were considered as "out of procotol". Clinical data, number of biopsies, ultrasounds, hysteroscopies and visits were compared between groups. In addition, the sensitivity (S), specificity (E), positive and negative predictive values (PPV and NPV) of the molecular test were calculated. Results: 94 patients were recruited. 51 vs 43 women were included in the classical and the molecular algorithm respectively. There were no differences in age, BMI, parity, use of tamoxifen or hormonal treatment. The detailed outcomes of explorations between classical vs molecular group are shown in Table 1. 324 vs 229 explorations were performed respectively (table 2). In the molecular group, 92 explorations were considered "out of protocol". The test validations showed a 100% S, 92.5% E, 50% PPV and 100% NPV. Conclusions: According to our results, the incorporation of a molecular test for the diagnosis of EC in postmenopausal women who complained with AUB reduces the number of explorations. Consequently, the molecular algorithm is more cost-effective than conventional algorithms

Reducing postoperative catheterisation after anterior colporrhaphy from 48 to 24 h: a randomised controlled trial.

INTRODUCTION AND HYPOTHESIS: There is a distinct lack of literature on postoperative management after anterior colporrhaphy (AC). Our traditional postoperative protocol consisted of 24 h of indwelling catheterisation followed by 24 h of self-intermittent catheterisation. We hypothesised that a new protocol consisting of only 24 h of indwelling catheterisation might produce better results without additional complications. METHODS: From April 2014 to July 2017, all candidates for AC were randomised to catheter removal 24 or 48 h after surgery. The primary outcome was the postoperative urinary retention (POUR) rate. Secondary outcomes included: asymptomatic bacteriuria (AB), urinary tract infection (UTI) and postoperative pain after 24 h. RESULTS: A total of 79 patients were recruited. Thirty-seven and 40 patients were randomised to follow the 48-h protocol and the 24-h protocol respectively. There were no significant differences in relation to the POUR rate: 3 patients (8.1%) vs 1 (2.5%) in the 48-h vs the 24-h group respectively (p = 0.346). The UTI rate was 2 (8.1%) vs 0 patients respectively (p = 0.139) and the postoperative AB rate was 3 (9.1%) vs 0 patients (p = 0.106). In the postoperative pain evaluation, the visual analogue scale score was significantly higher in the 48 h group (0.35 vs 0.13, p = 0.02). CONCLUSIONS: According to our results, reducing the catheterisation from 48 to 24 h after AC does not increase the risk of POUR and decreases the rate of UTI, AB and postoperative pain. This new postoperative management protocol of pelvic floor surgery would improve postoperative outcomes and shorten the stay in hospital.

The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer Patients. Results, and the Advantages and Disadvantages of Both Procedures.

BACKGROUND: In patients with breast cancer who are candidates for neoadjuvant therapy (NAT), the timing of when to perform sentinel lymph node biopsy (SLNB) remains under discussion. The aim of this study was to compare the advantages and disadvantages of SLNB performed before and after NAT. PATIENTS AND METHODS: One hundred seventy-two patients, T1c to T3 and N0 (clinically and according to ultrasound) candidates for NAT were included. We compared the outcomes of 2 groups: (1) 122 patients of whom SLNB was performed before NAT (pre-NAT) from December 2006 to April 2014; and (2) 50 patients with SLNB performed after NAT (post-NAT) from May 2014 to July 2016. RESULTS: Both groups were homogeneous in baseline patient characteristics. The SLNB was positive in 50 patients [41.7%] (33 macrometastases [66%] and 17 micrometastases [34%]) versus 6 patients [12%] (5 macrometastases [83.3%] and 1 micrometastases [16.7%]) in pre- and post-NAT groups, respectively. The lymphadenectomy was performed in 34 patients [28.3%] versus 4 patients [8%], with an odds ratio of 3.48 (95% confidence interval, 1.3-9.3). The recurrences in the pre-NAT group after a median follow-up of 62 months were 12 systemic, 2 local and systemic, and none axillary. In the post-NAT group were no recurrences after a median follow-up of 16 months. Finally, SLNB after NAT reduces the delay in starting NAT from 24 to 14 days (medians; P < .001) and the identification of the SLNB was in 122 patients [100%] versus 49 patients [98%]. CONCLUSION: SLNB performed after NAT significantly reduces the rate of lymphadenectomies without any increase in recurrences at early follow-up. Furthermore, it allows systemic treatment to be started earlier without interfering in the SLNB identification rate.