Evaluation of tumor infiltrating lymphocytes as a prognostic biomarker in patients with ductal carcinoma in situ of the breast.

PURPOSE: To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence. METHODS: This retrospective cohort study included women aged 18 years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using Kaplan‒Meier curves, log-rank tests, and Cox regression models. RESULTS: A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2 months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence. CONCLUSION: In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.

Anthropometric, Metabolic, and Endocrine Parameters as Predictors of Estimated Average Glucose and Other Biomarkers of Dysglycemia in Women with Different Phenotypes of Polycystic Ovary Syndrome.

The aim of the study was to evaluate the efficacy of anthropometric, metabolic, and endocrine abnormalities as predictors of estimated average glucose and other biomarkers of dysglycemia in women with different phenotypes of polycystic ovary syndrome (PCOS). This cross-sectional study included 648 women with PCOS and 330 controls. A single protocol of investigation was applied for all subjects. PCOS women were divided by phenotypes according to the Rotterdam criteria. Biomarkers of dysglycemia were considered dependent variables and anthropometric, lipid, and hormone alterations as independent variables using univariate and multivariate logistic regressions. Univariate logistic regression analysis, controlled for age and BMI, showed that many biomarkers of dysglycemia could be predicted by anthropometric, lipid, and endocrine variables. Multivariate logistic models showed that in non-PCOS women estimated average glucose (eAG) was predicted by lower TSH levels (OR=0.39; p=0.045); fasting glucose was predicted by increased T (OR=2.3). For PCOS, phenotype A, eAG was predicted by decreased HDL-C (OR=0.17, p=0.023) and high levels of free estradiol (OR=7.1, p<0.001). Otherwise, in PCOS, phenotype D, eAG was predicted by higher levels of HDL-C. The current study demonstrated that eAG was poorly predicted by anthropometric, lipid, and hormone parameters. Nevertheless, without adding significant benefits, it was comparable with other established markers of dysglycemia in women with different PCOS phenotypes.

Brazilian Portuguese Translation and Validation of the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-IUGA revised.

INTRODUCTION AND HYPOTHESIS: Condition-specific sexual questionnaires are important patient-reported outcome measures. The aim of this study was to translate and validate the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire-International Urogynecology Association Revised (PISQ-IR) into Brazilian Portuguese and to clinically validate it in a Brazilian Portuguese-speaking population. METHODS: Translation and validation of the PISQ-IR was performed according to the International Urogynecological Association-recommended process and guidelines. For external validity, PISQ-IR subscales were compared with the clinical measures, Pelvic Organ Prolapse Quantification system (POP-Q) stage, pelvic floor muscle tone, and Oxford Grading Scale (Pearson correlations). Descriptive statistics, internal consistency (Cronbach's alpha coefficient), and test-retest reliability (interclass correlation coefficient) were calculated for all PISQ-IR subscales. RESULTS: A total of 120 sexually active and 106 not sexually active women were enrolled in the study between March 2015 and July 2019. Internal consistency was acceptable, with Cronbach's alpha values 0.60-0.80, except for the sexual arousal and orgasm, sexual arousal and partner-related issues, sexual arousal and condition-specific issues, global rating of sexual quality and condition impact subscales. PISQ-IR demonstrated good reliability (α > 0.6, CIC = 0.996). The agreement for each individual questionnaire item also individually presented substantial agreement between the assessments (κ 0.61-0.8). There was a correlation between PISQ-IR and POP, mixed, stress and fecal incontinence diagnosis and a positive correlation with pelvic floor muscle function according to the Oxford Scale in sexually active women. For sexually inactive women there was a correlation between PISQ-IR and mixed urinary symptoms. CONCLUSIONS: The Brazilian Portuguese version of PISQ-IR is a reliable and valid tool that can be easily used for the identification and assessment of sexual function in Brazilian Portuguese-speaking women with pelvic floor disorders.

Menstrual pattern in polycystic ovary syndrome and hypothalamic-pituitary-ovarian axis immaturity in adolescents: a systematic review and meta-analysis.

OBJECTIVE: To analyze differences in the menstrual pattern, age at menarche, and body mass index (BMI) in adolescents with Hypothalamic-Pituitary-Ovarian (HPO) axis immaturity and Polycystic Ovary Syndrome (PCOS) through a systematic review and meta-analysis. METHODS: The PubMed, EMBASE, Web of Science, Virtual Health Library, Scopus databases were searched using combinations of descriptors. Study quality was assessed using the Newcastle-Ottawa Scale. For data analysis, the results were grouped into PCOS group and NPCOS group (HPO axis immaturity). We performed a meta-analysis of raw data and the inverse variance method, employing the standardized mean difference, of the age at menarche and BMI of adolescents. RESULTS: Participants totaled 1,718 from nine selected studies. The meta-analysis showed that the PCOS group had a higher BMI than the NPCOS group (SMD 0.334; CI95% 0.073 - 0.595; p = .012). The degree of heterogeneity of the studies was approximately 40%. No significant difference in age at menarche (SMD - 0.027; CI95% -0.227 - 0.172; p = 0.790) and menstrual patterns was found, but amenorrhea was described only in adolescents with PCOS. CONCLUSIONS: The main characteristic in menstrual pattern that differentiated PCOS patients from girls with HPO axis immaturity was amenorrhea. Also, the BMI of PCOS patients was nearly one third higher than that of adolescents with HPO axis immaturity.

Pilot study of treatment of patients with deep infiltrative endometriosis with methotrexate carried in lipid nanoparticles.

OBJECTIVE: Previously, lipid nanoparticles (LDE) injected in women with endometriosis were shown to concentrate in the lesions. Here, the safety and feasibility of LDE carrying methotrexate (MTX) to treat deep infiltrating endometriosis was tested. DESIGN: Prospective pilot study. SETTING: Perola Byington Hospital Reference for Women's Health. SUBJECTS: Eleven volunteers (aged 30-47 years, BMI 26.15 ± 6.50 kg/m2) with endometriosis with visual analog scale pelvic pain scores (VAS) > 7 and rectosigmoid lesions were enrolled in the study. INTERVENTION: Three patients were treated with LDE-MTX at single intravenous 25 mg/m2 dose of MTX and eight patients with two 25 mg/m2 doses with 1-week interval. MAIN OUTCOME MEASURES: Clinical complaints, blood count, and biochemistry were analyzed before treatment and on days 90, 120, and 180 after LDE-MTX administration. Endometriotic lesions were evaluated by pelvic and transvaginal ultrasound (TVUS) before treatment and on days 30 and 180 after LDE-MTX administration. RESULTS: No clinical complaints related with LDE-MTX treatment were reported by the patients, and no hematologic, renal, or hepatic toxicities were observed in the laboratorial exams. FSH, LH, TSH, free T4, anti-Müllerian hormone, and prolactin levels were also within normal ranges during the observation period. Scores for deep dyspareunia (p < 0.001), chronic pelvic pain (p = 0.008), and dyschezia (p = 0.025) were improved over the 180-day observation period. There was a non-significant trend for reduction of VAS scores for dysmenorrhea. Bowel lesions by TVUS were unchanged. No clear differences between the two dose levels in therapeutic responses were observed. CONCLUSION: Results support the safety and feasibility of using LDE-MTX in women with deep infiltrating endometriosis as a novel and promising therapy for the disease. More prolonged treatment schemes should be tested in future placebo-controlled studies aiming to establish the usefulness of this novel nanomedicine approach.

Combined oral contraceptive use and obesity in women with polycystic ovary syndrome. A meta-analysis of randomized clinical trials.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogenous endocrine condition and combined oral contraceptives (COCs) have been demonstrated to be the first-line treatment to women who do not intend to become pregnant. The combination of COCs and PCOS may or may not amplify the risks of cardiovascular events. OBJECTIVE: To investigate whether surrogates for obesity may be influenced by the use of COCs containing different formulations in women with PCOS. METHOD: From January 2024 a literature search was conducted in Google Scholar and Pubmed databases using PCOS, COC, and obesity terms. Hand search of randomized clinical trials in the references of obtained manuscripts was also performed. After the exclusion of reviews and articles that did not fulfill eligibility criteria, compared the results obtained before and after the use of COCs in 13 randomized clinical trials (RCTs). Random-effects model was used to estimate the standardized mean differences (SMD) and standard errors (SE). Risk of bias was examined using the Rob2 tool. RESULT: Thirteen heterogeneous RCTs reported no difference in waist circumference with the use of different COC formulations (p = 0.714). On the contrary, body fat mass increased with the use of pill (p = 0.013). Waist triglyceride index and lipid accumulation product tended to be higher after the use of COCs (p = 0.073 and p = 0.064, respectively). CONCLUSION: Combined oral contraceptives with different formulations might increase fat mass accumulation in women with PCOS. Lipids may also be increased in PCOS users. Because some concerns about the quality and heterogeneity identified in various RCTs, caution should be taken before a definitive conclusion regarding the use of COCs and obesity.

Effects of preoperative magnetic resonance image on survival rates and surgical planning in breast cancer conservative surgery: randomized controlled trial (BREAST-MRI trial).

BACKGROUND: Breast magnetic resonance imaging (MRI) has high sensitivity in detecting invasive neoplasms. Controversy remains about its impact on the preoperative staging of breast cancer surgery. This study evaluated survival and surgical outcomes of preoperative MRI in conservative breast cancer surgery. METHODS: A phase III, randomized, open-label, single-center trial including female breast cancer participants, stage 0-III disease, and eligible for breast-conserving surgery. We compared the role of including MRI in preoperative evaluation versus radiologic exam routine with mammography and ultrasound in breast cancer conservative candidates. The primary outcome was local relapse-free survival (LRFS), and secondary outcomes were overall survival (OS), mastectomy rate, and reoperation rate. RESULTS: 524 were randomized to preoperative MRI group (n = 257) or control group (n = 267). The survival analysis showed a 5.9-years LRFS of 99.2% in MRI group versus 98.9% in control group (HR = 0.72; 95% CI 0.12-4.28; p = 0.7) and an OS of 95.3% in the MRI group versus 96.3% in the control group (HR = 1.37 95% CI 0.59-3.19; p = 0.8). Surgical management changed in 21 ipsilateral breasts in the MRI group; 21 (8.3%) had mastectomies versus one in the control group. No difference was found in reoperation rates, 22 (8.7%) in the MRI group versus 23 (8.7%) in the control group (RR = 1.002; 95% CI 0.57-1.75; p = 0.85). CONCLUSION: Preoperative MRI increased the mastectomy rates by 8%. The use of preoperative MRI did not influence local relapse-free survival, overall survival, or reoperation rates.

Hyperprolactinemia modifies extracellular matrix components associated with collagen fibrillogenesis in harderian glands of non- and pregnant female mice.

The harderian gland (HG) is a gland located at the base of the nictating membrane and fills the inferomedial aspect of the orbit in rodents. It is under the influence of the hypothalamic-pituitary-gonadal axis and, because of its hormone receptors, it is a target tissue for prolactin (PRL) and sex steroid hormones (estrogen and progesterone). In humans and murine, the anterior surface of the eyes is protected by a tear film synthesized by glands associated with the eye. In order to understand the endocrine changes caused by hyperprolactinemia in the glands responsible for the formation of the tear film, we used an animal model with metoclopramide-induced hyperprolactinemia (HPRL). Given the evidences that HPRL can lead to a process of cell death and tissue fibrosis, the protein expression of small leucine-rich proteoglycans (SLRPs) was analyzed through immunohistochemistry in the HG of the non- and the pregnant female mice with hyperprolactinemia. The SRLPs are related to collagen fibrillogenesis and they participate in pro-apoptotic signals. Our data revealed that high prolactin levels and changes in steroid hormones (estrogen and progesterone) can lead to an alteration in the amount of collagen, and in the structure of type I and III collagen fibers through changes in the amounts of lumican and decorin, which are responsible for collagen fibrillogenesis. This fact can lead to the impaired functioning of the HG by excessive apoptosis in the HG of the non- and the pregnant female mice with HPRL and especially in the HG of pregnancy-associated hyperprolactinemia.

A randomized trial comparing vaginal laser therapy and pelvic floor physical therapy for treating women with stress urinary incontinence.

INTRODUCTION: Female stress urinary incontinence (SUI) is considered a major public health issue. Physical therapy is an important conservative treatment; however, it is primarily limited by poor long-term compliance. Furthermore, surgical treatment entails significant risks. Therefore, new treatment techniques must be identified. OBJECTIVE: To compare the use of laser therapy and pelvic floor (PF) physical therapy for treating postmenopausal women with SUI. METHODS: This pilot study enrolled 40 women with a clinical and urodynamic diagnosis of SUI who were randomized into two groups: those who received erbium-doped yttrium-aluminum-garnet (Er:YAG) laser therapy implemented over three sessions with a 1-month interval (n = 20) and those who received physical therapy with supervision twice a week for 3 months (n = 20). In total, 16 women completed the treatment in each group. The patients were assessed for PF function using the modified Oxford scale and for pelvic organ prolapse using the Pelvic Organ Prolapse Quantification System. The 1-h pad test and quality of life questionnaires, King's Health Questionnaire (KHQ), and Incontinence Quality of Life (IQOL) were also administered. Patients were re-evaluated at 1, 3, 6, and 12 months after treatment. RESULTS: The mean patient age was 62.7 ± 9.1 and 57.9 ± 6.1 years, median Oxford score at baseline was 3 (2-4.5) and 4 (3-4), mean IQOL score was 79.8 ± 17 and 74.6 ± 18 for physical therapy group (PTG) and laser group (LG), respectively. For the amount of urine leak in the 1-h pad test evaluation, we found significance for the interaction of group and time points only for the Laser intragroup. The cure rate, that is, the rate of reaching an insignificant score in the pad test, at 6 and 12 months was 43.75% and 50% in PTG and 62.5% and 56.25% in the LG, respectively (p > 0.05). IQOL scores demonstrated considerable improvement in both groups (p > 0.05). Upon comparing the initial and follow-up results, the LG showed an improvement at all consultations, whereas the PTG showed improvements at 1, 3, and 6 months but not at 12 months after treatment. KHQ analysis revealed a considerable improvement in the quality of life (QOL) of patients over time, with no substantial difference between the groups. QOL comparison before and after treatment revealed that the vaginal LG improved more consistently in some domains. Only the PTG showed a significant increase in the mean Oxford score from pretreatment to 1 and 3 months after treatment (p < 0.001 and p = 0.002, respectively). However, no statistically significant difference was observed between the groups. CONCLUSION: Both treatments are safe and have a positive influence on the impact of UI on patients' QOL. The laser caused a greater reduction in the urinary loss, as measured using the weight of pad test, at 6-month and 12-month after treatment without difference with PTG at the end of the follow-up.

Comparison between anterior and posterior vaginal approach in apical prolapse repair in relation to anatomical structures and points of fixation to the sacrospinous ligament in fresh postmenopausal female cadavers.

INTRODUCTION AND HYPOTHESIS: The high prevalence of pelvic organ prolapse (POP) in women requires attention and constant review of treatment options. Sacrospinous ligament fixation (SSLF) for apical prolapse has benefits, high efficacy, and low cost. Our objective is to compare anterior and posterior vaginal approach in SSLF in relation to anatomical structures and to correlate them with body mass index (BMI). METHODS: Sacrospinous ligament fixation was performed in fresh female cadavers via anterior and posterior vaginal approaches, using the CAPIO®SLIM device (Boston Scientific, Natick, MA, USA). The distances from the point of fixation to the pudendal artery, pudendal nerve, and inferior gluteal artery were measured. RESULTS: We evaluated 11 cadavers with a mean age of 70.1 ± 9.9 years and mean BMI 22.4 ± 4.6 kg/m2. The mean distance from the posterior SSLF to the ischial spine, pudendal artery, pudendal nerve, and inferior gluteal artery were 21.18 ± 2.22 mm, 17.9 ± 7.3 mm, 19.2 ± 6.8 mm, and 18.9 ± 6.9 mm respectively. The same measurements relative to the anterior SSLF were 19.7 ± 2.7 mm, 18.6 ± 6.7 mm, 19.2 ± 6.9 mm, and 18.3 ± 6.7 mm. Statistical analysis showed no difference between the distances in the two approaches. The distances from the fixation point to the pudendal artery and nerve were directly proportional to the BMI. CONCLUSIONS: There was no difference in the measurements obtained in the anterior and posterior vaginal approaches. A direct correlation between BMI and the distances to the pudendal artery and pudendal nerve was found.

Skin-sparing mastectomy for the treatment of breast cancer.

BACKGROUND: Skin-sparing mastectomy (SSM) is a surgical technique that aims to maximize skin preservation, facilitate breast reconstruction, and improve cosmetic outcomes. Despite its use in clinical practice, the benefits and harms related to SSM are not well established. OBJECTIVES: To assess the effectiveness and safety of skin-sparing mastectomy for the treatment of breast cancer. SEARCH METHODS: We searched Cochrane Breast Cancer's Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP), and ClinicalTrials.gov on 9 August 2019. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-randomized or non-randomized studies (cohort and case-control) comparing SSM to conventional mastectomy for treating ductal carcinoma in situ (DCIS) or invasive breast cancer. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome was overall survival. Secondary outcomes were local recurrence free-survival, adverse events (including overall complications, breast reconstruction loss, skin necrosis, infection and hemorrhage), cosmetic results, and quality of life. We performed a descriptive analysis and meta-analysis of the data. MAIN RESULTS: We found no RCTs or quasi-RCTs. We included two prospective cohort studies and twelve retrospective cohort studies. These studies included 12,211 participants involving 12,283 surgeries (3183 SSM and 9100 conventional mastectomies). It was not possible to perform a meta-analysis for overall survival and local recurrence free-survival due to clinical heterogeneity across studies and a lack of data to calculate hazard ratios (HR).  Based on one study, the evidence suggests that SSM may not reduce overall survival for participants with DCIS tumors (HR 0.41, 95% CI 0.17 to 1.02; P = 0.06; 399 participants; very low-certainty evidence) or for participants with invasive carcinoma (HR 0.81, 95% CI 0.48 to 1.38; P = 0.44; 907 participants; very low-certainty evidence). For local recurrence-free survival, meta-analysis was not possible, due to high risk of bias in nine of the ten studies that measured this outcome. Informal visual examination of effect sizes from nine studies suggested the size of the HR may be similar between groups. Based on one study that adjusted for confounders, SSM may not reduce local recurrence-free survival (HR 0.82, 95% CI 0.47 to 1.42; P = 0.48; 5690 participants; very low-certainty evidence).  The effect of SSM on overall complications is unclear (RR 1.55, 95% CI 0.97 to 2.46; P = 0.07, I2 = 88%; 4 studies, 677 participants; very low-certainty evidence). Skin-sparing mastectomy may not reduce the risk of breast reconstruction loss (RR 1.79, 95% CI 0.31 to 10.35; P = 0.52; 3 studies, 475 participants; very low-certainty evidence), skin necrosis (RR 1.15, 95% CI 0.62 to 2.12; P = 0.22, I2 = 33%; 4 studies, 677 participants; very low-certainty evidence), local infection (RR 2.04, 95% CI 0.03 to 142.71; P = 0.74, I2 = 88%; 2 studies, 371 participants; very low-certainty evidence), nor hemorrhage (RR 1.23, 95% CI 0.47 to 3.27; P = 0.67, I2 = 0%; 4 studies, 677 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the risk of bias, imprecision, and inconsistency among the studies. There were no data available on the following outcomes: systemic surgical complications, local complications, explantation of implant/expander, hematoma, seroma, rehospitalization, skin necrosis with revisional surgery, and capsular contracture of the implant. It was not possible to perform a meta-analysis for cosmetic and quality of life outcomes due to a lack of data. One study performed an evaluation of aesthetic outcome after SSM: 77.7% of participants with immediate breast reconstruction had an overall aesthetic result of excellent or good versus 87% of participants with delayed breast reconstruction. AUTHORS' CONCLUSIONS: Based on very low-certainty evidence from observational studies, it was not possible to draw definitive conclusions on the effectiveness and safety of SSM for breast cancer treatment. The decision for this technique of breast surgery for treatment of DCIS or invasive breast cancer must be individualized and shared between the physician and the patient while considering the potential risks and benefits of available surgical options.

Vitamin D and in vitro fertilization: a systematic review.

PURPOSE: Vitamin D (VD) action on calcium is well known, but its other properties, particularly in the human reproductive system, are not completely understood. This review aims at assessing the relationship between serum VD levels and IVF results. METHODS: A systematic review was carried out using MEDLINE, EMBASE, LILACS, Google scholar, the CAPES journal portal, and the Cochrane Library, as well as the descriptors "vitamin D" and "fertilization in vitro." The review was conducted by two authors following the PRISMA recommendations between September 2021 and February 2022. RESULTS: Eighteen articles were selected. Five of them showed a positive correlation between serum VD levels and IVF results, 12 lacked any association, and 1 exhibited a negative correlation. The 3 studies that assessed VD in the follicular fluid found a positive correlation between the serum and follicular levels. Non-Hispanic White patients seemed to suffer the consequence of vitamin D deficiency more than Asian patients. In one study alone in the VD-deficient group, there was a larger number of natural killer (NK) cells, B cells, a greater proportion of helper T cells/cytotoxic T cells (Th/Tc), and an association with a smaller number of mature oocytes. CONCLUSION: The association between serum VD levels and the post-IVF pregnancy rate is uncertain. However, VD levels might be more relevant in the White than in the Asian ethnicity and in the number of aspiration follicles, and they could act in the immune system having an impact both on embryo implantation and on pregnancy.

Gene Expression Profile of Uterine Leiomyoma from Women Exposed to Different Air Pollution Levels in Metropolitan Cities of Sao Paulo, Brazil.

Leiomyomas (LMs) are the most frequent uterine benign tumors, representing the leading cause of hysterectomy indications worldwide. They are highly associated with women's reproductive complications, and endocrine disruptors may influence their etiology. In this sense, air pollution represents a relevant hormonal disruptor that acts on key signaling pathways, resulting in tumor development and infertility. Our goal was to evaluate submucosal LM samples from patients living in the metropolitan and Sao Paulo city regions, focusing on genes involved in tumor development and infertility features. Twenty-four patients were selected based on their region of residence and clinical information availability. Several genes were differentially expressed between women living in metropolitan areas and Sao Paulo city. Significant associations were observed between BCL-2, DVL1, FGFR3, and WNT5b downregulation and contraceptive use in the samples from women living in Sao Paulo city. ESR1 and HHAT downregulation was associated with ethnicity. WNT5b and GREM were associated with LM treatment and related pathologies, respectively. In the samples from women living in other cities of the metropolitan region, abortion occurrence was associated with BMP4 upregulation. Although further studies may be necessary, our results showed that air pollution exposure influences the expression of genes related to LM development and female reproductive features.

The oncological safety of autologous fat grafting: a systematic review and meta-analysis.

OBJECTIVE: To present a systematic review of the literature and a meta-analysis evaluating the oncological safety of autologous fat grafting (AFG). SUMMARY BACKGROUND DATA: AFG for breast reconstruction presents difficulties during follow-up radiological exams, and the oncological potential of grafted fat is uncertain. Previous studies confirmed that the fatty tissue could be transferred under a good condition suitable would not interfere with mammographic follow-up, although the issue of oncological safety remains. METHODS: We reviewed the literature published until 01/18/2021. The outcomes were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). We included studies that evaluated women with breast cancer who undergone surgery followed by reconstruction with AFG. We synthesized data using the inverse variance method on the log-HR (log of the hazard ratio) scale for time-to-event outcomes using RevMan. We assessed heterogeneity using the Chi2 and I2 statistics. RESULTS: Fifteen studies evaluating 8541 participants were included. The hazard ratios (HR) could be extracted from four studies, and there was no difference in OS between the AFG group and control (HR 0.9, 95% CI 0.53 to 1.54, p = 0.71, I2 = 58%, moderate certainty evidence), and publication bias was not detected. The HR for DFS could be extracted from six studies, and there was no difference between the AFG group and control (HR 1.01, 95% CI 0.73 to 1.38, p = 0.96, I2 = 0%, moderate certainty evidence). The HR for LR could be extracted from ten studies, and there was no difference between the AFG group and control (HR 0.86, 95% CI 0.66 to 1.12, p = 0.43, I2 = 1%, moderate certainty evidence). CONCLUSION: According to the current evidence, AFG is a safe technique of breast reconstruction for patients that have undergone BC surgery and did not affect OS, DFS, or LR.

Hyaluronic acid and proliferation/cellular death amount in the female rats mammary gland after estroprogestative therapy.

AIMS: To evaluate the concentration of hyaluronan acid and proliferation/cellular death in mammary gland of ovariectomized female rat after estroprogestative therapy. MATERIALS AND METHODS: Forty ovariectomized female rats were divided into four groups with 10 animals/each: OG (vehicle); EG: (Estradiol, 7 days of treatment), PG (Progesterone acetate, 23 days of treatment), and EPG: (Estradiol, 7 days of treatment, and next Progesterone acetate, 23 days of treatment). Twenty-four hours after the last treatment, all animals were euthanized, the mammary gland removed, then, a fragment was immersed in acetone to quantifying of the hyaluronan acid biochemical method (ELISA-Like fluorometric assay), and a fragment fixed for 24 h in 10% formaldehyde in phosphate-buffered saline (PBS) processed for immunohistochemistry method for detection of the cell marker proliferation (Ki67) and cellular marker death by DNA fragmentation the TUNEL method. RESULTS: The estradiol-treatment alone (EG) or associated with progesterone (EPG) affected the concentration of hyaluronan acid, increased cell proliferation, and decreased cell death compared to OG and PG (p < .05) in the mammary tissue. CONCLUSIONS: Our results suggest that the excessive reduction of HA in mammary tissue, as occurred with progesterone treatment, can lead to a breakdown of the extracellular matrix. These changes may be indicative of mammary pathology such as the development of tumor.

Etonogestrel-releasing contraceptive implant in a patient using thalidomide for the treatment of erythema nodosum leprosum: a case report.

INTRODUCTION: Thalidomide is an immunomodulatory drug and first choice in the treatment of erythema nodosum leprosum. Given its teratogenic potential, it is essential that an effective contraceptive method is used, especially a long-acting reversible contraceptive (LARC) method. The subdermal etonogestrel (ENG)-releasing implant is an adequate method due to the high effectiveness and long-term use. However, interaction between thalidomide and ENG has not been well documented. Concern arises because thalidomide interacts with cytochrome P450 (CYP450) enzymes that metabolize sexual steroids. AIM: We aimed to study the effectiveness and safety of the ENG-implant in a thalidomide user. METHODS: Case report of a sexually active 21-year-old patient with both Hansen's disease and leprosy reaction type 2 treated with thalidomide requiring effective contraception. Follow-up was up to 36 months after implant placement. RESULTS: Contraception with ENG-implant was effective and safe, based on clinical parameters (reduction of menstrual flow and cervical mucus thickening) and laboratory parameters (gonadotropins and sexual steroids). CONCLUSION: To the best of our knowledge, this is the first case reported which presents a patient in simultaneous use of thalidomide and ENG-implant. Although this case report preliminary supports effectiveness and safety of ENG-implant as a contraceptive option in women using thalidomide, rigorous drug-drug interaction research is needed to better characterize the interaction between thalidomide and the ENG-implant.

Impact of the prolactin levels in breast cancer: a systematic review and meta-analysis.

Prolactin (PRL) acts stimulating the mammary glands development, and its deregulation has been associated to the emergence of several types of tumors, including breast cancer. Breast cancer represents the most prevalent malignancy in women, and the second cause of death in several countries. This tumor can be arise due to several molecular alterations, among them PRL has been the object of increasing interest from researchers worldwide. OBJECTIVE: To assess the association between elevated levels of plasma prolactin and breast cancer development. METHODS: A total of 158 studies were found in search databases (48 from PubMed, 69 from Scopus, 88 from Cochrane, 25 from Embase and 10 retrieved from the gray literature) after removing duplicates. Of these, 104 studies were excluded after title and abstract reading, and 54 studies were then read in full, of which only 14 were selected for this review because they had evaluated the association between PRL and breast cancer. Meta-analysis was carried out using the relative risk (RR), mean and standard deviation, confidence interval (95% CI), and the total number of patients for each study. Fixed- and random-effect models were used as applicable and, for the analysis. RESULTS: The meta-analysis showed a positive association between elevated levels of PRL and breast cancer occurrence (RR 1.26; 95%CI 1.15-1.37). Additionally, the patient sub-group analyses showed a positive association between PRL and invasive breast cancer (1.42; 1.24-1.60), ER+/PR+ (1.49; 1.23-1.75), and post-menopausal status (1.29; 1.16-1.43). CONCLUSION: The results showed a positive association between plasma prolactin levels and breast cancer, especially in women with ER+/PR + tumors, of post-menopausal age and those with invasive cancer.

Hyperestrogenemia resulting from a granulosa cell tumor and causing pulmonary thromboembolism: a case report.

Estrogen modulates platelet activation and aggregation, and it increases the levels of the von Willebrand factor, factors II, VII, VIII, and X, and of fibrinogen, all of which increase the risk for thromboembolism. We report the case of a 59-year-old woman, postmenopausal for 4 years, not using hormone replacement therapy, who was admitted into the emergency room with shortness of breath and increased abdominal volume. After physical examination and imaging and biochemical tests, she was diagnosed with pulmonary thromboembolism and a large left adnexal tumor. The patient was promptly received full anticoagulation therapy for the pulmonary thromboembolism. High levels of estradiol (810.4 pg/mL), anti-Mullerian hormone (16.39 ng/mL), inhibin (11250 pg/mL), and suppressed FSH (<0.16 IU/L) led to a suspicion of granulosa-cell tumor. After clinical stabilization, she underwent to an exploratory laparotomy with total hysterectomy and bilateral adnexectomy to treat the pelvic tumor. Pathologic report confirmed a granulosa-cell tumor.

Effects of clinical and metabolic variables and hormones on the expression of immune protein biomarkers in the endometrium of women with polycystic ovary syndrome and normal-cycling controls.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) are at an elevated risk of endometrial cancer, which may be associated with the continuous proliferative state caused by the interaction between hormones and metabolic factors. OBJECTIVE: To investigate the impact of hormones and metabolic factors in the proliferation and death of endometrium during the proliferative phase. METHODS: Cross-sectional study with 11 women with PCOS and eight normal-cycling non-PCOS controls at the Federal University of the State of Rio de Janeiro from February 2011 to June 2019. Clinical, biochemical, and hormonal data were collected to analyze their influence on the expression of biomarkers related to the endometrial tissue breakdown. Hysteroscopy and endometrial biopsies were conducted, and the endometrial samples underwent immunohistochemistry for markers of apoptosis B-cell lymphoma 2 (BCL2), cleaved caspase-3 (CASP3), fas cell surface death receptor (FAS), FAS ligand (FASLG), BCL2 associated X (BAX), marker of proliferation Ki-67 (MKI67), and cell death using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL). RESULTS: CASP3 and TUNEL expressions were lower in both stroma and endometrium gland of PCOS women than in controls. MKI67 and homeostasis indexes (BCL2/BAX; FASLG/FAS) in the endometrium of the PCOS group were significantly higher. Body mass index (BMI) values were positively correlated with the expression of MKI67 and MKI67/TUNEL ratio in the endometrial stroma compartment. Fasting insulin levels were positively correlated with the expression of BCL2, and DHEA-S levels were negatively correlated with the expression of CASP3 of women with PCOS. CONCLUSION: BMI, insulin, and DHEA-S influence the endometrial homeostasis breakdown in PCOS in the endometrium stroma.

Impacts of bariatric surgery in health outcomes and health care costs in Brazil: Interrupted time series analysis of multi-panel data.

BACKGROUND: The increasing burden of obesity generates significant socioeconomic impacts for individuals, populations, and national health systems worldwide. The literature on impacts and cost-effectiveness of obesity-related interventions for prevention and treatment of moderate to severe obesity indicate that bariatric surgery presents high costs associated with high effectiveness in improving health status referring to certain outcomes; however, there is a lack of robust evidence at an individual-level estimation of its impacts on multiple health outcomes related to obesity comorbidities. METHODS: The study encompasses a single-centre retrospective longitudinal analysis of patient-level data using micro-costing technique to estimate direct health care costs with cost-effectiveness for multiple health outcomes pre-and post-bariatric surgery. Data from 114 patients who had bariatric surgery at the Hospital of Clinics of the University of Sao Paulo during 2018 were investigated through interrupted time-series analysis with generalised estimating equations and marginal effects, including information on patients' characteristics, lifestyle, anthropometric measures, hemodynamic measures, biochemical exams, and utilisation of health care resources during screening (180 days before) and follow-up (180 days after) of bariatric surgery. RESULTS: The preliminary statistical analysis showed that health outcomes presented improvement, except cholesterol and VLDL, and overall direct health care costs increased after the intervention. However, interrupted time series analysis showed that the rise in health care costs is attributable to the high cost of bariatric surgery, followed by a statistically significant decrease in post-intervention health care costs. Changes in health outcomes were also statistically significant in general, except in cholesterol and LDL, leading to significant improvements in patients' health status after the intervention. CONCLUSIONS: Trends multiple health outcomes showed statistically significant improvements in patients' health status post-intervention compared to trends pre-intervention, resulting in reduced direct health care costs and the burden of obesity.