Comparative analysis of endometrial, vaginal, and gut microbiota in patients with and without adenomyosis.

INTRODUCTION: Alterations in microbiota composition have been implicated in a variety of human diseases. Patients with adenomyosis present immune dysregulation leading to a persistent chronic inflammatory response. In this context, the hypothesis that alterations in the microbiota may be involved in the pathogenesis of adenomyosis, by affecting the epigenetic, immunologic, and biochemical functions of the host, has recently been postulated. The aim of the present study was to compare the microbiota composition in the vagina, endometrium, and gut of individuals with and without adenomyosis. MATERIAL AND METHODS: Cross-sectional study including 38 adenomyosis patients and 46 controls, performed between September 2021 and October 2022 in a university hospital-based research center. The diagnosis of adenomyosis was based on sonographic criteria. Fecal, vaginal, and endometrial samples were collected. Study of the microbiota using 16S rRNA gene sequencing. RESULTS: Patients with adenomyosis exhibited a significant reduction in the gut microbial alpha diversity compared with healthy controls (Chao1 p = 0.012, Fisher p = 0.005, Observed species p = 0.005). Beta-diversity analysis showed significant differences in the compositions of both gut and vaginal microbiota between adenomyosis patients and the control group (Adonis p-value = 0.001; R2 = 0.03 and Adonis p-value = 0.034; R2 = 0.04 respectively). Specific bacterial taxa were found to be either overrepresented (Rhodospirillales, Ruminococcus gauvreauii group, Ruminococcaceae, and Actinomyces) or underrepresented in the gut and endometrial microbiota of adenomyosis patients compared with controls. Distinct microbiota profiles were identified among patients with internal and external adenomyosis phenotypes. CONCLUSIONS: The study revealed reduced gut microbiota diversity in adenomyosis patients, accompanied by distinct compositions in gut and vaginal microbiota compared with controls. Overrepresented or underrepresented bacterial taxa were noted in the gut and endometrial microbiota of adenomyosis patients, with variations in microbiota profiles among those with internal and external adenomyosis phenotypes. These findings suggest a potential association between microbiota and adenomyosis, indicating the need for further research to comprehensively understand the implications of these differences.

Nonsentinel Axillary Lymph Node Status in Clinically Node-Negative Early Breast Cancer After Primary Systemic Therapy and Positive Sentinel Lymph Node: A Predictive Model Proposal.

BACKGROUND: In clinically node-negative (cN0) early stage breast cancer (EBC) undergoing primary systemic treatment (PST), post-treatment positive sentinel lymph node (SLN+) directs axillary lymph node dissection (ALND), with uncertain impacts on outcomes and increased morbidities. PATIENTS AND METHODS: We conducted an observational study on imaging-confirmed cN0 EBC, who underwent PST and breast surgery that resulted in SLN+ and underwent ALND. The association among baseline/postsurgical clinic-pathological factors and positive nonsentinel additional axillary lymph nodes (non-SLN+) was analyzed with logistic regression. LASSO regression (LR) identified variables to include in a predictive score of non-SLN+ (ALND-predict). The accuracy and calibration were assessed, an optimal cut-point was then identified, and in silico validation with bootstrap was undertaken. RESULTS: Non-SLN+ were detected in 22.2% cases after ALND. Only progesterone receptor (PR) levels and macrometastatic SLN+ were independently associated to non-SLN+. LR identified PR, Ki67, and type and number of SLN+ as the most efficient covariates. The ALND-predict score was built based on their LR coefficients, showing an area under the curve (AUC) of 0.83 and an optimal cut-off of 63, with a negative predictive value (NPV) of 0.925. Continuous and dichotomic scores had a good fit (p = 0.876 and p = 1.00, respectively) and were independently associated to non-SLN+ [adjusted odds ratio (aOR): 1.06, p = 0.002 and aOR: 23.77, p < 0.001, respectively]. After 5000 bootstrap-adjusted retesting, the estimated bias-corrected and accelerated 95%CI included the aOR. CONCLUSIONS: In cN0 EBC with post-PST SLN+, non-SLN+ at ALND are infrequent (~22%) and independently associated to PR levels and macrometastatic SLN. ALND-predict multiparametric score accurately predicted absence of non-SLN involvement, identifying most patients who could be safely spared unnecessary ALND. Prospective validation is required.

Long-term oncological outcomes of patients with negative sentinel lymph node in vulvar cancer. Comparative study with conventional lymphadenectomy.

INTRODUCTION: The aim of this study was to compare oncological outcomes and morbidity in patients with early-stage vulvar cancer with negative sentinel lymph node (SLN) biopsy vs negative inguinofemoral lymphadenectomy (IFL). MATERIAL AND METHODS: Study with retrospectively collected data in patients with squamous cell vulvar carcinomas ≤ 4 cm without suspected inguinofemoral lymph node metastases. Only patients with negative nodes after histopathology procedure were followed. Patients who underwent only SLN were compared with patients who underwent IFL ± SLN to compare recurrences, survival rates and morbidity. RESULTS: Ninety-three patients were eligible for follow up: 42 with negative SLN and 51 with negative IFL ± SLN. The median follow-up period was 60.4 months (range 6.7-160.7). The rate of isolated first groin recurrence was 4.8% in patients with negative SLN and 2.0% in patients with negative IFL ± SLN (P = 0.587) and the rates of first isolated local recurrence were 28.6% and 31.4%, respectively (P = 0.823). Only 1 patient (2.4%) in the group of negative SLN had distant recurrence. The disease-specific survival rate at 5 years was 83.3% in the negative SLN group and 92.2% in the negative IFL ± SLN group (P = 0.214). We observed a higher rate of wound breakdown and infection after IFL than SLN biopsy (17.6% vs 10.6%; P = 0.020) and lymphedema (33.3% vs 0%; P < 0.001). CONCLUSIONS: We report in the same population of patients with early-stage vulvar cancer that SLN biopsy does not have significantly higher rates of groin recurrences or lower survival rates compared with IFL. Moreover, the SLN procedure has less morbidity, which should encourage gynecologists to abandon IFL.

Clinical signs and diagnosis of fibroids from adolescence to menopause.

The aim of this review was to provide an updated assessment of the present diagnostic tools and clinical symptoms and signs to evaluate uterine fibroids (UFs) on the basis of current guidelines, recent scientific evidence, and a PubMed and Google Scholar search for peer-reviewed original and review articles related to clinical signs and diagnosis of UFs. Approximately 50%-75% of UFs are considered nonclinically relevant. When present, the most common symptoms are abnormal uterine bleeding, pelvic pain and/or bulk symptoms, and reproductive failure. Transvaginal ultrasound is recommended as the initial diagnostic modality because of its accessibility and high sensitivity, although magnetic resonance imaging appears to be the most accurate diagnostic tool to date in certain cases. Other emerging techniques, such as saline infusion sonohysterography, elastography, and contrast-enhanced ultrasonography, may contribute to improving diagnostic accuracy in selected cases. Moreover, artificial intelligence has begun to demonstrate its ability as a complementary tool to improve the efficiency of UF diagnosis. Therefore, it is critical to standardize descriptions of transvaginal ultrasound images according to updated classifications and to individualize the use of the different complementary diagnostic tools available to achieve precise uterine mapping that can lead to targeted therapeutic approaches according to the clinical context of each patient.

Evolution of breast conserving surgery-current implementation of oncoplastic techniques in breast conserving surgery: a literature review.

Background and Objective: De-escalation in breast cancer surgery has been a natural evolution since breast conserving surgery (BCS) was introduced in the early 1980s. From Halsted mastectomies to wide local excisions, we are facing nowadays the next trend in form of oncoplastic breast surgery. Oncoplastic breast surgery combines oncological principles with plastic surgery techniques to preserve the breast shape and appearance. The aim of this work is to review recent oncological and quality of live outcomes derived from oncoplastic techniques as well as offer a perspective about its implementation in breast cancer units. Methods: A literature review was conducted to explore the landscape of oncoplastic breast surgery. Key terms related to oncoplastic techniques and breast cancer were used in searches across databases such as PubMed, Embase and Cochrane Library. Inclusion criteria focused on recent articles discussing oncological and quality of life (QoL) outcomes, as well as perspectives on the role of oncoplastic surgery. Key Content and Findings: The research aims to contribute valuable insights into the efficacy and impact of oncoplastic surgery in the context of breast cancer treatment. In this new era of precision medicine, it is more than just healing patients; it is about improving their well-being. We ought to consider specific oncoplasty role in leading this paradigm shift. It is also relevant to define whether these new technical-demanding surgical options can be applied to all patients and if professional training performs adequately to current demands of personalized treatments. Conclusions: The global adoption of oncoplastic BCS is recommended due to its oncological safety and improvement in QoL compared to standard procedures. Emphasizing the need for skilled surgeons in complex cases, collaboration between breast surgeons and scientific societies is urged to certify ongoing educational training in oncoplastic techniques.

Laparoscopic Fertility-Sparing Management of Borderline Ovarian Tumors: Surgical and Long-Term Oncological Outcomes.

Objectives: To assess the long-term oncological safety of laparoscopic fertility-sparing surgery (FSS) in borderline ovarian tumors and the impact of laparoscopic surgical factors on recurrences. Primary outcomes were the recurrence rate and time to recurrence after laparoscopic FSS. Secondary outcomes were to evaluate the recurrence rate after a second laparoscopic surgery and to assess factors associated with the risk of relapse. Methods: This is a retrospective single-center observational study in a tertiary university-affiliated hospital. Thirty-four patients diagnosed with borderline ovarian tumors who underwent laparoscopic FSS were recruited. Patients were categorized into two groups: the adnexectomy group, including patients who underwent unilateral adnexectomy, and the cystectomy group, which included patients who underwent unilateral cystectomy, bilateral cystectomy, and unilateral adnexectomy with contralateral cystectomy. Results: Eleven relapses (32.3%) were observed during a median follow-up period of 116.1 [62.5-185.4] months. The recurrence rate was similar for patients who underwent cystectomy (6/19, 31.6%) and adnexectomy (5/15, 33.3%). Cystectomy led to a shorter time to first recurrence (36-month progression-free survival rates of 66% vs. 85%) and higher rates of capsular rupture (71.4% vs. 20%, p = 0.04) compared to adnexectomy. No deaths due to progression of disease were reported. Conclusions: Laparoscopic FSS for borderline ovarian tumors is a safe, long-term oncological option. Although the recurrence rate was similar in patients undergoing adnexectomy or cystectomy, the time to recurrence was shorter in cases treated with cystectomy. Further research is needed to identify eventual laparoscopic risk factors more strongly correlated with recurrence.

Surgical Management and Its Impact on Adjuvant Treatment in Recurrent Ipsilateral Breast Cancer: A Retrospective Cohort Study.

Background: Breast cancer (BC) recurrence, defined as the reappearance of cancer in the ipsilateral breast after primary treatment, poses significant challenges in clinical management. Despite advances in treatment, recurrence rates persist, ranging from 0.6 to 1.5% annually, reaching 10-15% at 20 years. This study aims to analyze the surgical and oncological characteristics of patients with BC recurrence. Methods: This retrospective study includes 56 patients diagnosed with recurrent BC between October 2018 and April 2022. Data were collected from a prospectively maintained surgical database. A descriptive analysis was performed on the initial BC, and the recurrence, including surgical complications, was classified using the Clavien-Dindo system. The success rates of selective sentinel lymph node (SLN) biopsies and aberrant drainages were assessed based on previous surgeries. Results: The cohort included 55 females and 1 male, with a median age of 65.3 years. The mean time to BC recurrence was 11.5 years. Among them, 26.8% underwent breast-conserving surgery, 41.1% had a mastectomy, 21.4% had a mastectomy with reconstruction, and 10.7% had an excision over a previous mastectomy. An SLN biopsy was performed in 78.6% of cases, with higher success rates in those without a previous axillary lymph node dissection (85.7% vs. 63.2%). Aberrant drainage was more frequent in patients with a previous ALND (44.4% vs. 20%). The median follow-up was 41.3 months, with 10.7% experiencing a second recurrence. Conclusions: Repeat breast-conserving surgery with re-irradiation for ipsilateral recurrence is feasible and does not significantly increase complications. SLN biopsy is valuable for restaging and tailoring adjuvant therapies, with ALND not being necessary if re-SLN biopsy shows no drainage. The management of aberrant drainage remains controversial.

Clinical and sonographic impact of oral contraception in patients with deep endometriosis and adenomyosis at 2 years of follow-up.

Nowadays, combined oral contraceptives (COCs) are successfully employed for the treatment of endometriosis (END) and adenomyosis (AD) in a large proportion of patients. However, literature focusing on the clinical and sonographic response to treatment in the long-term follow-up of patients with deep endometriosis (DE) and AD is scarce. The aim of this study was to evaluate the changes in the symptoms and the sonographic exams at 12 and 24 months of follow-up in patients who had received a flexible extended COC regimen containing 2 mg of dienogest/30 µg ethinyl estradiol. This prospective, longitudinal, observational study included women diagnosed with DE and AD presenting no surgical indication and were candidates to treatment with COCs. The presence and severity of dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria were evaluated using the Numerical Rating Scale (NRS) at baseline, and at 12 and 24 months of treatment. Transvaginal ultrasound was also performed at these check points searching for criteria of AD and reporting the size of the DE nodules and ovarian endometriomas (OE). Sixty-four patients were included. A significant decrease in the number of patients with severe dysmenorrhea and non-menstrual pelvic pain was reported during follow-up. The mean NRS score for dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, dyschezia and dysuria was also significantly lower at follow-up. There was a significant reduction in the sonographic number and type of AD criteria during follow-up after treatment. Similarly, a significant decrease in the size of OE and uterosacral ligament involvement in DE was observed at the 12-month follow-up, with a further, albeit not statistically significant, decrease in the 12- to 24-month follow-up. Additionally, torus and rectosigmoid DE decreased in size, although the reduction was not statistically significant at any study point. This prospective study suggests a clinical and sonographic improvement after a flexible extended COC regimen in DE and AD patients, which was significant at 12 months of follow-up. The improvement was more evident in AD and OEs compared with DE. Further research with a longer follow-up, larger sample size and comparison with other treatments is needed.

Assessing vaginal wall thickness by transvaginal ultrasound in breast cancer survivors: A pilot study.

AIM: There is need for a straightforward objective measure to evaluate vaginal wall changes related to hypoestrogenism. The aim of this pilot study was to evaluate a transvaginal ultrasound procedure for the quantification of vaginal wall thickness in order to differentiate between healthy premenopausal women and postmenopausal women with genitourinary syndrome of menopause using ultra-low-level estrogen status as a model. METHODS: We performed a prospective, two-arm, cross-sectional pilot study comparing vaginal wall thickness measured by transvaginal ultrasound in postmenopausal breast cancer survivors using aromatase inhibitors with genitourinary syndrome of menopause (GSM group) and healthy premenopausal women (control or C group) from October 2020 to March 2022. After intravaginal introduction of 20 cm3 of sonographic gel, vaginal wall thickness was measured by transvaginal ultrasound in the anterior, posterior, and right and left lateral walls (four quadrants). The study methods followed the STROBE checklist. RESULTS: According to the results of a two-sided t-test, the mean vaginal wall thickness of the four quadrants in the GSM group was significantly less than that of the C group (2.25 mm vs 4.17 mm, respectively; p < 0.001). Likewise, the thickness of each of the vaginal walls (anterior, posterior, right and left lateral) statistically differed between the two groups (p < 0.001). CONCLUSION: Transvaginal ultrasound with intravaginal gel may be a feasible objective technique to assess genitourinary syndrome of menopause, showing clear differences in vaginal wall thickness between breast cancer survivors using aromatase inhibitors and premenopausal women. Possible correlations with symptoms or treatment response should be assessed in future studies.

Risk factors for irreversible unilateral loss of renal function in patients with deep endometriosis.

Deep endometriosis (DE) can be more aggressive than other types of endometriosis, and may even lead to irreversible severe complications such as complete unilateral loss of renal function. We aimed to describe the clinical and radiologic characteristics of DE patients diagnosed with irreversible unilateral loss of renal function due to unilateral ureteral stenosis and evaluate risk factors for developing this loss. This retrospective cohort study included 436 patients who underwent laparoscopic DE surgery. We evaluated two groups of patients according to preserved (Non-Renal Loss Group; n = 421) or irreversible unilateral damaged renal function (Renal Loss Group; n = 15). Preoperative epidemiologic variables, clinical characteristics, radiologic findings and surgical treatments of all the patients were collected. The Renal Loss Group had a higher infertility rate and a higher proportion of asymptomatic patients. The following radiological variables showed statistically significant differences between the two groups: mean endometrioma diameter, the presence of intestinal DE and negative sliding sign. Multivariate analysis showed that infertility, being asymptomatic, having intestinal DE or torus uterinus/uterosacral ligament DE and a negative sliding sign significantly increased the risk of loss of renal function. Therefore, among patients with these clinical and/or radiological variables, severe urinary tract obstruction should be specifically ruled out.

Effect of Fractional Carbon Dioxide vs Sham Laser on Sexual Function in Survivors of Breast Cancer Receiving Aromatase Inhibitors for Genitourinary Syndrome of Menopause: The LIGHT Randomized Clinical Trial.

Importance: Survivors of breast cancer present more severe symptoms of genitourinary syndrome of menopause (GSM) than patients without history of breast cancer. Recently, new treatments, such as vaginal laser therapy, have appeared, but evidence of their efficacy remains scarce. Objective: To assess the safety and efficacy of carbon dioxide (CO2) vs sham vaginal laser therapy after 6 months of follow-up in survivors of breast cancer with GSM receiving aromatase inhibitors. Design, Setting, and Participants: This prospective double-blind sham-controlled randomized clinical trial with two parallel study groups was performed during October 2020 to March 2022 in a tertiary referral hospital. Survivors of breast cancer using aromatase inhibitors were assessed for eligibility, and eligible patients were randomized into the 2 treatment groups. Follow-up was conducted at 6 months. Data were analyzed in July 2022. Interventions: All patients from both groups were instructed to use the first-line treatment (FLT) based on nonhormonal moisturizers and vaginal vibrator stimulation. Patients for each group were allocated to 5 monthly sessions of fractional CO2 laser therapy (CLT) or sham laser therapy (SLT). Main Outcomes and Measures: The primary outcome was sexual function, evaluated through Female Sexual Function Index (FSFI) score. Other subjective measures of efficacy included a visual analog scale of dyspareunia, vaginal pH, a Vaginal Health Index, quality of life (assessed via Short-Form 12), and body image (assessed with the Spanish Body Image Scale). Objective measures of efficacy included vaginal maturation index, vaginal epithelial elasticity (measured in Pascals) and vaginal epithelial thickness (measured in millimeters). Measures were assessed before and after the intervention. Tolerance (measured on a Likert scale), adverse effects, and estradiol levels were recorded. Results: Among 211 survivors of breast cancer assessed, 84 women were deemed eligible and 72 women (mean [SD] age, 52.6 [8.3] years) were randomized to CLT (35 participants) or SLT (37 participants) and analyzed. There were no statistically significant differences between groups at baseline. At 6 months, both groups showed improvement in FSFI (mean [SD] score at baseline vs 6 months: CLT, 14.8 [8.8] points vs 20.0 [9.5] points; SLT, 15.6 [7.0] points vs 23.5 [6.5] points), but there was no significant difference between CLT and SLT groups in the improvement of sexual function evaluated through the FSFI test overall (mean [SD] difference, 5.2 [1.5] points vs 7.9 [1.2] points; P = .15) or after excluding women who were not sexually active (mean [SD] difference, 2.9 [1.4] points vs 5.5 [1.1] points; P = .15). There were also no differences between improvement of the 2 groups at 6 months of follow-up in the other assessed subjective outcomes, including dyspareunia (mean [SD] difference, -4.3 [3.4] vs -4.5 [2.3]; P = .73), Vaginal Health Index (mean [SD] difference, 3.3 [4.1] vs 5.0 [4.5]; P = .17), body image (mean [SD] difference, -3.7 [4.5] vs -2.7 [4.8]; P = .35), and quality of life (mean [SD] difference, -0.3 [3.6] vs -0.7 [3.2]; P = .39). Similarly, there were no differences in improvements in objective outcomes, including vaginal pH (mean [SD] difference, -0.6 [0.9] vs -0.8 [1.2]; P = .29), vaginal maturation index (mean [SD] difference, 10.2 [17.4] vs 14.4 [17.1]; P = .15), vaginal epithelial thickness (mean [SD] difference, 0.021 [0.014] mm vs 0.013 [0.012] mm; P = .30), vaginal epithelial elasticity (mean [SD] difference, -1373 [3197] Pascals vs -2103 [3771] Pascals; P = .64). There were significant improvements in the overall analysis regardless of group in many outcomes. The 2 interventions were well tolerated, but tolerance was significantly lower in the CLT group than the SLT group (mean [SD] Likert scale score, 3.3 [1.3] vs 4.1 [1.0]; P = .007). No differences were observed in complications or serum estradiol levels. Conclusions and Relevance: In this randomized clinical trial, vaginal laser treatment was found to be safe after 6 months of follow-up, but no statistically significant differences in efficacy were observed between CLT and SLT. Trial Registration: ClinicalTrials.gov identifier: NCT04619485.

Analysis of Local Recurrence Risk in Ductal Carcinoma In Situ and External Validation of the Memorial Sloan Kettering Cancer Center Nomogram.

BACKGROUND: Adjuvant radiotherapy and hormonotherapy after breast-conserving surgery (BCS) in ductal carcinoma in situ (DCIS) have been shown to reduce the risk of local recurrence. To predict the risk of ipsilateral breast tumor relapse (IBTR) after BCS, the Memorial Sloan Kettering Cancer Center (MSKCC) developed a nomogram to analyze local recurrence (LR) risk in our cohort and to assess its external validation. METHODS: A historical cohort study using data from 296 patients treated for DCIS at the Hospital Clínic of Barcelona was carried out. Patients who had had a mastectomy were excluded from the analysis. RESULTS: The mean age was 58 years (42-75), and the median follow-up time was 10.64 years. The overall local relapse rate was 13.04% (27 patients) during the study period. Actuarial 5- and 10-year IBTR rates were 5.8 and 12.9%, respectively. The external validation of the MSKCC nomogram was performed using a multivariate logistic regression analysis on a total of 207 patients, which did not reach statistical significance in the studied population for predicting LR (p = 0.10). The expression of estrogen receptors was significantly associated with a decreased risk of LR (OR: 0.25; p = 0.004). CONCLUSIONS: In our series, the LR rate was 13.4%, which was in accordance with the published series. The MSKCC nomogram did not accurately predict the IBTR in this Spanish cohort of patients treated for DCIS (p = 0.10).

Vaginal laser therapy for genitourinary syndrome of menopause - systematic review.

BACKGROUND: Genitourinary syndrome of menopause (GSM) can have a great impact on the quality of life (QOL), and affects between 53.8% and 90% of postmenopausal women. The literature suggests that vaginal laser therapy could be an effective treatment for GSM symptoms, but its efficacy and safety have not been established and international societies do not endorse its use. Despite that, there has been an increase in the use of vaginal laser therapy globally over the last decade. OBJECTIVE: The objective of this review is to evaluate the literature which assesses the efficacy and safety of the vaginal laser therapy in the treatment of GSM. METHODS: A comprehensive literature search was conducted electronically using Embase and PubMed to retrieve studies assessing evidence for the efficacy and safety of vaginal laser therapy for GSM or vulvovaginal atrophy up to June 2021. RESULTS: A total of 64 studies were finally included in the review. There were 10 controlled intervention studies, 7 observational cohort and cross-sectional studies and 47 before-after studies without a control group. CONCLUSION: Vaginal laser seems to improve scores on the Visual Analogue Scale (VAS), Female Sexual Function Index (FSFI) and Vaginal Health Index (VHI) in GSM over the short term. Safety outcomes are underreported and short-term. Further well-designed clinical trials with sham-laser control groups and evaluating objective variables are needed to provide the best evidence on efficacy.

Aquaporin-4-Positive Triple-Negative Breast Cancer Presenting with Paraneoplastic Neuromyelitis Optica Spectrum Disorder.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory central nervous system disorder that preferentially affects the optic nerve and the spinal cord. Although NMOSD is more commonly an idiopathic autoimmune condition associated with antibodies against aquaporin-4 (AQP4)-IgG, the disease may also occur as a paraneoplastic syndrome in rare instances. In these cases, the expression of AQP4 by the tumor is likely the trigger of the autoimmune response. CASE PRESENTATION: We describe the case of a 32-year-old woman who presented with progressive tetraparesis, cranial involvement, respiratory failure, and spinal cord MRI compatible with longitudinally extensive transverse myelitis, few days after being diagnosed with a T3N1M0 triple-negative right breast cancer. Due to the history of concurrent breast cancer and after ruling out metastatic spinal cord involvement, the possibility of a paraneoplastic origin was raised. AQP4-IgG were found in the serum and CSF by cell-based assay, confirming the diagnosis of NMOSD. The patient was treated with corticosteroids, plasma exchange, and rituximab. Concomitantly, breast cancer therapy was started with an adapted neoadjuvant chemotherapy scheme based on carboplatin and paclitaxel. An initial slight improvement slowed down; so, a right mastectomy with lymphadenectomy was performed. Expression of AQP4 was demonstrated in the tumor. The patient presented a significant neurological improvement after combined treatment regaining muscular balance and strength in upper and lower extremities. CONCLUSION: NMOSD may have a paraneoplastic origin associated with breast cancer and the importance of its early detection since the combination of tumoral and immunosuppressive therapy may improve the patient's prognosis.

Genitourinary Syndrome of Menopause: Current Treatment Options in Breast Cancer Survivors - Systematic Review.

Breast cancer survivors (BCS) usually receive treatments which lead to persistent oestrogen suppression, which may cause atrophic vaginitis in a large proportion of these women. The most effective treatments for vulvovaginal atrophy (VVA) are based on local oestrogen therapy. However, these treatments are restricted in BCS due to the controversy over their use in women who had hormone-dependent tumours. Therefore, it is common to find untreated symptoms that affect sexual function and quality of life in BCS, thereby leading to the discontinuation of anti-oestrogenic treatments. This systematic review aims to discuss the current treatment options available for the genitourinary syndrome of menopause (GSM) in BCS. A comprehensive literature search was conducted electronically using Embase and PubMed to retrieve studies assessing treatment options for GSM or VVA in BCS up to April 2020. Studies evaluating treatments in different BCS cohorts were excluded. A total of 29 studies were finally included in the review. Non-hormonal treatments are the first-line treatment for VVA, but when these are not effective for symptom relief, other options can be considered, such as local oestrogen, erbium laser or CO2 laser and local androgens. The present data suggest that these therapies are effective for VVA in BCS; however, safety remains controversial and a major concern with all of these treatments.

Have maternal or paternal ages any impact on the prenatal incidence of genomic copy number variants associated with fetal structural anomalies?

The objective of this study was to determine whether maternal or paternal ages have any impact on the prenatal incidence of genomic copy number variants (CNV) in fetuses with structural anomalies. We conducted a non-paired case-control study (1:2 ratio) among pregnancies undergoing chromosomal microarray analysis (CMA) because of fetal ultrasound anomalies, from December 2012 to May 2020. Pregnancies with any pathogenic copy number variant (CNV), either microdeletion or microduplication, were defined as cases. Controls were selected as the next two pregnancies with the same indication for CMA but with a normal result. Logistic regression was used, adjusting by use of assisted reproductive technology (ART) and parental smoking. Stratified analysis was performed according to CNV type (de novo/inherited and recurrent/non-recurrent). The study included 189 pregnancies: 63 cases and 126 controls. Mean maternal age in cases was 33.1 (SD 4.6) years and 33.9 (SD 6.0) years in controls. Mean paternal mean age was 34.5 (SD 4.8) years in cases and 35.8 (SD 5.8) years in controls. No significant differences in maternal or paternal age were observed, neither in stratified analysis according to the CNV type. Moreover, the proportion of cases were not significantly different between non-advanced and advanced ages, either considering paternal or maternal ages. The presence of pathogenic CNV at CMA in fetuses with structural anomalies was not found to be associated with advanced paternal or maternal age.

HE4 might be a more useful tumor biomarker to detect malignancy in patients with ovarian endometrioma when malignancy is suspected.

OBJECTIVE: To analyze the utility of carbohydrate antigen (CA)125 and human epididymis protein 4 (HE4) to detect malignancy in women with ovarian endometriosis, when ovarian cancer is suspected and ultrasonography results are inconclusive. METHODS: Women who underwent surgery between 2015 and 2019 for ovarian endometriosis or for adnexal masses, with a final diagnosis of ovarian carcinoma (clear cell and endometrioid) were included in this retrospective study. The women were divided into three groups: ovarian endometriosis (OE), ovarian carcinoma without endometriosis (OC), and ovarian carcinoma with endometriosis (OC + E). Adnexal masses were assessed preoperatively by transvaginal ultrasonography according to the International Ovarian Tumor Analysis (IOTA) simple rules, and CA125 and HE4 blood levels were obtained. RESULTS: Of 208 women, 45 had malignancy, 16 in the OC + E group and 29 in the OC group. According to transvaginal ultrasonography, 13 were classified as undetermined risk of malignancy: OC group: 3, OE group: 3, and OC + E group: 7. When we compared the tumor biomarkers, significant differences in HE4 but not in CA125 levels were found between the groups. CONCLUSIONS: When ovarian malignancy is suspected in patients with ovarian endometriosis, HE4 is a more useful tumor biomarker to diagnose OC when ultrasonography results are inconclusive.

Genitourinary Syndrome of Menopause Assessment Tools.

New therapeutic options are being considered to treat genitourinary syndrome of menopause (GSM), such as vaginal laser, ospemifene, or prasterone, but there is no explicit agreement in the scientific community for its use. Some concerns have arisen on how to evaluate the improvement of GSM symptoms. In 2003, the FDA suggested possible end points for this purpose: change in severity of symptoms, change in vaginal pH, and change in vaginal maturation index (VMI). Contrarily, the most common assessment tools used to quantify severity and improvement of GSM nowadays are the visual analog scale of GSM symptoms, the vaginal health index, and the female sexual function index. In our opinion, subjective and objective variables to evaluate GSM can be differentiated, and not many of the considered objective outcomes are used in the recent literature assessing GSM. There is the possibility that some therapies present only subjective improvement, giving place to a possible placebo effect that is not being evaluated. To conclude, there is a demand to evaluate whether vaginal pH and VMI are enough to assess objectively GSM changes or new objective approaches should be audited.