Awareness of the Causes Leading to Surgical Ablation of Ovarian Function in Premenopausal Breast Cancer-A Single-Center Analysis.

Background and Objectives: Ovarian surgical ablation (OSA) in estrogen receptor-positive (ER+) breast cancer is usually performed to halt ovarian function in premenopausal patients. Since alternative pharmacological therapy exists and few studies have investigated why surgery is still performed, we aimed to analyze the reasons for the use of OSA despite the remaining controversy. Materials and Methods: Premenopausal ER+ breast cancer patients treated at a tertiary center (2005-2011) were selected, and patients with germline mutations were excluded. Results: Seventy-nine patients met the inclusion criteria. Globally, the main reasons for OSA included: continued menstruation despite hormone therapy with or without ovarian medical ablation (OMA) (34.2%), patient informed choice (31.6%), disease progression (16.5%), gynecological disease requiring surgery (13.9%), and tamoxifen intolerance/contraindication (3.8%). In women aged ≥45 years, patient choice was significantly more frequently the reason for OSA (47.4% versus 17.1% (p = 0.004)). For those aged <45 years, salvation attempts were significantly more frequent as compared to older women (26.8% versus 5.3% (p = 0.01)). In 77.8% of women undergoing OSA with menstrual cycle maintenance, surgery was performed 1-5 years after diagnosis, while surgery was performed earlier (0-3 months after diagnosis) in patients undergoing OSA as an informed choice (56.0%), as a salvation attempt (53.8%), or due to gynecological disease (63.6%). The leading reason for OSA in women previously undergoing OMA was continued menstruation (60.0%). Conclusions: This study suggests a possible failure of pharmacological ovarian suppression and reinforces the need for shared decision-making with patients when discussing treatment strategies, although validation by further studies is warranted due to our limited sample size.

Impact of gestational weight gain on obstetric and neonatal outcomes in obese diabetic women.

BACKGROUND: Both obesity and gestational diabetes mellitus are increasing in prevalence, being a major health problem in pregnancy with independent and additive impact on obstetrics outcomes. It is recognized that inadequate gestational weight gain is an independent risk factor for pregnancy-related morbidity. The aim of this study was to evaluate the effect of gestational weight gain on obstetric and neonatal outcomes in obese women with gestational diabetes. METHODS: Retrospective multicenter study of obese women with gestational diabetes. The assessed group was divided into three categories: women who gained below (<5 kg), within (5-9 kg) and above (>9 kg) the 2009 Institute of Medicine recommendations. Maternal and neonatal outcomes were compared and adjusted odds ratios calculated controlling for confounders. RESULTS: Only 35,1 % of obese women with gestational diabetes (n = 634) achieved the recommended gestational weight gain; 27,8 % (n = 502) gained below and 37,1 % (n = 670) above the recommendations. There was a positive correlation between gestational weight gain and neonatal birthweight (r = 0,225; p < 0,001). Gestational weight gain below recommendations was associated with lower odds for cesarean section, even adjusting for birthweight [aOR = 0,67 (0,54-0,85); p < 0,001]; lower odds for large for gestational age neonates [aOR = 0,39 (0,28-0,57); p < 0,001] and macrosomia [aOR = 0,34 (0,21-0,55); p < 0,001]. Excessive weight gain, even adjusting for birthweight, was associated with higher odds for cesarean section [aOR = 1,31 (1,07-1,61); p = 0,009], low Apgar score [aOR = 4,79 (1,19-19,21); p = 0,027], large for gestational age neonates [aOR = 2,32 (1,76-3,04); p < 0,001] and macrosomia [aOR = 2,39 (1,68-3,38); p < 0,001]. CONCLUSIONS: In obese women with gestational diabetes, a reduced gestational weight gain (<5 kg) is associated with better obstetric and neonatal outcomes than an excessive or even an adequate weight gain. Therefore, specific recommendations should be created since gestational weight gain could be a modifiable risk factor for adverse obstetric outcomes.

Marking Techniques for Targeted Axillary Dissection Among Patients With Node-Positive Breast Cancer Treated With Neoadjuvant Chemotherapy.

Invasive breast cancer with axillary lymph node (LN) invasion is a continuing problem worldwide. The morbidity associated with axillary LN dissection along with the high rate of nodal downstaging after neoadjuvant chemotherapy (NACT) made the standard treatment shift towards less invasive surgery. Sentinel lymph node biopsy (SLNB) after NACT is associated with high false-negative rates (13%-14%). To overcome this problem, it was concluded that the positive nodes should first be indicated with image-detectable markers and then removed together with SLNB: targeted axillary dissection (TAD). This review aims to describe and evaluate the different marking techniques for TAD in patients with node-positive breast cancer treated with NACT, namely: clip placement and guidewire localization; clip placement and 125I-labelled radioactive seed localization; clip placement and skin mark; clip placement and intraoperative ultrasound; tattooing with a sterile black carbon suspension; magnetic seeds; radar and infrared light technology localization. Targeted axillary dissection techniques have shown false-negative rates below 9% and identification rates above 95%. The most studied technique is guidewire localization, as it is also the oldest one. However, according to data gathered from this review, some newer techniques have shown to be very promising due to their statistical results and management factors.

The impact of anemia on treatment management and clinical outcomes of women hospitalized for uterine leiomyomas.

OBJECTIVES: Uterine leiomyomas are the most common benign gynecological tumors. Symptomatic leiomyomas represent a major cause of hospitalization, particularly those associated with abnormal uterine bleeding (AUB) and anemia. The aim of this study was to identify predictors of anemia in women hospitalized due to uterine leiomyomas and evaluate its impact on treatment management and clinical outcomes. MATERIAL AND METHODS: Population-based retrospective study of women hospitalized for uterine fibroids in public hospitals in mainland Portugal between 2010 and 2015. Data were extracted from the national database of the Central Administration of the Portuguese Health System. Comparative and multivariable logistic regression analysis was performed to assess outcomes. RESULTS: A total of 36 295 patients were hospitalized due to uterine leiomyomas during this period. Of those, 11.5% presented with anemia. Age, obesity, intramural type of leiomyoma and AUB are independent predictors of anemia (p < 0.001, AUC 0.7056). Anemia was associated with a high risk of inpatient hospitalization (OR: 5.161, 95% CI: 4.376-6.085), urgent admission (OR: 1.953, 95% CI: 1.797-2.121), radical surgical approach (OR: 2.559, 95% CI: 2.298-2.849), laparoscopic hysterectomy (OR: 1.575, 95% CI: 1.393-1.780) and intra- and post-operative complications (OR: 5.285, 95% CI: 4.332-6.448). It was also associated with longer hospital stays (p < 0.001). These outcomes were more pronounced in acute anemic patients. CONCLUSIONS: Anemia has a significant impact on treatment approaches and clinical outcomes of women hospitalized for uterine leiomyomas. Age, obesity, intramural leiomyomas and AUB are some predictors of anemia that could represent a risk-stratification opportunity, allowing for its prompt identification and correction, therefore improving patient care.

One Step Nucleic Acid Amplification (OSNA) Lysate Samples Are Suitable to Establish a Transcriptional Metastatic Signature in Patients with Early Stage Hormone Receptors-Positive Breast Cancer.

The One Step Nucleic Acid Amplification (OSNA) is being adopted worldwide for sentinel lymph nodes (SLNs) staging in breast cancer (BC). As major disadvantage, OSNA precludes prognostic information based on structural evaluation of SLNs. Our aim is to identify biomarkers related to tumor-microenvironment interplay exploring gene expression data from the OSNA remaining lysate. This study included 32 patients with early stage hormone receptors-positive BC. Remaining OSNA lysates were prepared for targeted RNA-sequencing analysis. Identification of differentially expressed genes (DEGs) was performed by DESeq2 in R and data analysis in STATA. The results show that, in metastatic SLNs, several genes were upregulated: KRT7, VTCN1, CD44, GATA3, ALOX15B, RORC, NECTIN2, LRG1, CD276, FOXM1 and IGF1R. Hierarchical clustering analysis revealed three different clusters. The identified DEGs codify proteins mainly involved in cancer aggressiveness and with impact in immune response. The overexpression of the immune suppressive genes VTCN1 and CD276 may explain that no direct evidence of activation of immune response in metastatic SLNs was found. We show that OSNA results may be improved incorporating microenvironment-related biomarkers that may be useful in the future for prognosis stratification and immunotherapy selection. As OSNA assay is being implemented for SLNs staging in other cancers, this approach could also have a wider utility.

Isolated torsion of a fallopian tube: an uncommon cause of abdominal pain in an 11-year-old.

This report describes a rare case of isolated fallopian tube torsion (IFTT) in a premenarchal 11-year-old girl. The patient presented with subacute abdominal pain, associated with nausea and vomiting. Sonographic findings revealed left tube enlargement with free intraperitoneal fluid. Doppler mapping was not unequivocal. During exploratory laparoscopy, a large pelvic necrotic mass was found to be a twisted left fallopian tube. After detorsion, salpingectomy was performed and the patient recovered promptly, showing no complications 3 months post operation. IFTT should be considered as a differential diagnosis of lower abdominal pain in adolescent girls with normal-appearing ovaries on ultrasound. Conservative management for fertility preservation is the ideal approach. Therefore, avoiding delay in laparoscopy is crucial.

A new application to one-step nucleic acid amplification-discarded sample in breast cancer: Preliminary results.

The one-step nucleic acid amplification (OSNA) assay is a molecular method used for detecting breast cancer (BC) metastasis in sentinel lymph nodes (SLNs). However, this method has a major disadvantage, since it prevents tissue structure analysis, while only one molecular marker can be evaluated, namely cytokeratin 19 mRNA. The aim of the present study was to evaluate whether an OSNA-discarded sample could be suitable for the gene expression analysis of the SLN microenvironment. The remaining intermediate phase of the centrifuged SLN homogenate obtained from the OSNA assay of samples from two patients with BC was used for mRNA extraction. Subsequently, the expression of five genes, namely forkhead box, cluster of differentiation 4 and three control genes, was determined by reverse transcription-quantitative PCR analysis. The results demonstrated that high-quality RNA was extracted. Therefore, this RNA may be used for gene expression analyses to predict novel molecular biomarkers associated with immuno-inflammatory microenvironment.

National trends and determinants of hospitalization for uterine leiomyomas - Portuguese public database analysis from 2000 to 2015.

OBJECTIVE: To determine the trends of hospitalization (inpatients and outpatients) for uterine leiomyomas in Portugal, over a period of fifteen years. STUDY DESIGN: We perform a population- and register-based retrospective study of women who were hospitalized with a primary diagnosis of uterine fibroid in public hospitals in continental Portugal, in the period between January 1, 2000 and December 31, 2015. Patient data regarding hospital codes, admission and discharge dates, patient age, diagnosis, procedures and complications were extracted from the national database of Administração Central do Sistema de Saúde (ACSS). All calculations were performed with the STATA software, version 13.1. Categorical data were analysed by the χ2 test and the means of continuous variables were analysed with Student's t-test. Statistical significance was set at p < 0.05. RESULTS: Between 2000 and 2015, 102 476 patients were admitted to public hospitals in Portugal due to uterine leiomyomas. The majority were admitted to hospital for surgery: 73.6 % for hysterectomy and 13.0 % for myomectomy. During this period, the definitive treatment (hysterectomy) decreased from 83.2% to 63.0% (p < 0.001), with a change towards more conservative treatments such as myomectomies (6.4% to 22.6%, p < 0.001). Additionally, in women submitted to hysterectomy, laparoscopic and vaginal routes increased (1.1%-11.5%, p < 0.001 and 2.1%-4.0%, p < 0.001; respectively). Globally, there was a 14.3 % reduction in hospitalizations due to uterine fibroids and an increase in the outpatient rate (from 3.1% to 22.1%). The mean number of hospitalization days for inpatients also decreased (from 6.3 ± 4.1-4.0 ± 3.0, p < 0.001). Regarding urgently hospitalized women, 11.8 % required a blood transfusion. In women submitted to surgical procedures, 0.5 % had an intraoperative complication and 2.3 % a post-operative complication, directly related to the surgical procedure. CONCLUSION: There was a reduction in hospitalizations due to uterine fibroids and a change towards more conservative treatments.

Metformin in gestational diabetes mellitus: predictors of poor response.

OBJECTIVE: Metformin can be regarded as a first-line treatment in gestational diabetes mellitus (GDM) due to its safety and effectiveness. However, a proportion of women do not achieve adequate glycemic control with metformin alone. We aim to identify predictors of this poor response to metformin. DESIGN AND METHODS: Retrospective multicentre cohort study of women with GDM who started metformin as first-line treatment. The assessed cohort was divided into a metformin group and metformin plus insulin group. Biometric and demographic characteristics, glycemic control data, obstetric, neonatal and postpartum outcomes were compared between groups and analysed in order to identify predictors of poor response to metformin. Data were analysed using STATA, version 13.1. RESULTS: Of the 388 women enrolled in the study, 135 (34.8%) required additional insulin therapy to achieve the glycemic targets. Higher age (aOR: 1.08 (1.03-1.13), P = 0.003), higher pre-pregnancy body mass index (BMI) (1.06 (1.02-1.10), P = 0.003) and earlier introduction of metformin (0.89 (0.85-0.94), P < 0.001) were independent predictors for insulin supplementation. Regarding all the analysed outcomes, only cesarean delivery rates and postpartum glucose levels were higher in women requiring insulin supplementation. CONCLUSIONS: Although almost 35% of women did not achieve adequate glycemic control with metformin, insulin supplementation was not associated with poor neonatal outcomes. Higher age, higher pre-pregnancy BMI and earlier introduction of metformin could be used as predictors of poor response to metformin.

Maternal educational level and the risk of persistent post-partum glucose metabolism disorders in women with gestational diabetes mellitus.

AIMS: Gestational diabetes mellitus (GDM) occurs in 5-15% of pregnancies, and lower maternal educational attainment has been associated with higher risk of GDM. We aimed to determine if maternal education level is associated with persistent post-partum glucose metabolism disorders in women with GDM. METHODS: Retrospective cohort study of women with GDM followed in 25 Portuguese health institutions between 2008 and 2012. Educational attainment was categorised into four levels. Prevalence of post-partum glucose metabolism disorders (type 2 diabetes mellitus, increased fasting plasma glucose or impaired glucose tolerance) was compared and adjusted odds ratios calculated controlling for confounders using logistic regression. RESULTS: We included 4490 women diagnosed with GDM. Educational level ranged as follows: 6.8% (n = 307) were at level 1 (≤ 6th grade), 34.6% (n = 1554) at level 2 (6-9th grade), 30.4% (n = 1364) at level 3 (10-12th grade) and 28.2% (n = 1265) at level 4 (≥ university degree). At 6 weeks post-partum re-evaluation, 10.9% (n = 491) had persistent glucose metabolism disorders. Educational levels 1 and 2 had a higher probability of persistent post-partum glucose metabolism disorders when compared to level 4 (OR = 2.37 [1.69;3.32], p < 0.001 and OR = 1.39 [1.09;1.76], p = 0.008, for level 1 and 2, respectively), an association that persisted in multivariable logistic regression adjusting for confounders (level 1 OR = 2.25 [1.53;3.33], p < 0.001; level 2 OR = 1.43 [1.09;1.89], p = 0.01). CONCLUSIONS: Persistent post-partum glucose metabolism disorders are frequent in women with GDM and associated with lower maternal educational level. Interventions aimed at this risk group may contribute towards a decrease in prevalence of post-partum glucose metabolism disorders.

Hysterectomies in Portugal (2000-2014): What has changed?

OBJECTIVE: To describe conditions regarding hysterectomies during the past 15 years in Portugal. STUDY DESIGN: Nationwide retrospective study of women who underwent hysterectomy in Portuguese public hospitals in the period between 2000 and 2014. Patient data regarding hospital codes, geography, patient age, indications, operative techniques, associated procedures, complications, admission dates, discharge dates and 30-day postoperative readmissions were extracted from the national database with information regarding all public hospitals in Portugal. For calculation of hysterectomy rates, the total number of women was found using the Statistics Portugal website. Data were analysed using STATA version 13.1. RESULTS: A total of 166 177 hysterectomies were performed between 2000 and 2014 in public hospitals in Portugal. The overall rate of hysterectomy decreased 19.3% (from 212/100 000 to 171/100 000 women per year). The average age of women at time of hysterectomy increased from 51.6±11.4 to 55.2±12.3years (p<0.001). There was an increase in laparoscopic [1.2%-9.5%, p<0.001] and vaginal route [13.3%-21.2%, p<0.001], with a consequent decrease in laparotomic route [85.5%-69.1%, p<0.001]. There was a change in the pattern of indications for hysterectomy; however, uterine fibroids remain the major indication for hysterectomy [45.3%-37.6%, p<0.001]. In women with hysterectomy for benign pathology, the rate of bilateral adnexectomy decreased from 71.0% to 51.9% (p<0.001) and the rate of bilateral salpingectomy increased from 1.0% to 15.1% (p<0.001). The mean number of hospitalization days decreased from 7.1±6.1 (in 2000-2004) to 5.4±5.0 (in 2010-2014) (p<0.001). Globally, the rate of complications increased from 3.3% in 2000-2004 to 3.6% in 2010-2014 (p<0.01). CONCLUSION: In Portugal, the rate of hysterectomies decreased in the last 15 years with an increase in age at the time of the procedure and a change towards less invasive routes. Uterine fibroids remain the major indication for hysterectomy. Additionally, we noted a significant shift towards more concomitant bilateral salpingectomy (and less bilateral adnexectomy) during hysterectomy for benign indications, according to the evidence suggesting the fallopian tube as the origin of ovarian cancer.