Brazilian Guideline on Menopausal Cardiovascular Health ­ 2024 / Guía Brasileña de Salud Cardiovascular en el Climaterio y la Menopausia ­ 2024 / Diretriz Brasileira sobre a Saúde Cardiovascular no Climatério e na Menopausa ­ 2024

Women, who represent approximately half of the global population according to estimates as of January 2024, may experience signs and symptoms of menopause for at least one-third of their lives, during which they have a higher risk of cardiovascular morbidity and mortality. The effects of menopausal hormone therapy (MHT) on the progression of atherosclerosis and cardiovascular disease (CVD) events vary depending on the age at which MHT is initiated and the time since menopause until its initiation. Beneficial effects on CVD outcomes and all-cause mortality have been observed when MHT was initiated before the age of 60 or within 10 years after menopause. The decision regarding the initiation, dose, regimen, and duration of MHT should be made individually after discussing the benefits and risks with each patient. For primary prevention of postmenopausal chronic conditions, the combined use of estrogen and progestogen is not recommended in asymptomatic women, nor is the use of estrogen alone in hysterectomized women. Hormone-dependent neoplasms contraindicate MHT. For the treatment of genitourinary syndrome of menopause, vaginal estrogen therapy may be used in patients with known cardiovascular risk factors or established CVD. For women with contraindications to MHT or who refuse it, non-hormonal therapies with proven efficacy (antidepressants, gabapentin, and fezolinetant) may improve vasomotor symptoms. Compounded hormonal implants, or "bioidentical" and "compounded" hormones, and "hormone modulation" are not recommended due to lack of scientific evidence of their effectiveness and safety.

Mujeres, que representan aproximadamente la mitad de la población mundial según estimaciones de enero de 2024, pueden experimentar signos y síntomas de la menopausia durante al menos un tercio de sus vidas, durante los cuales tienen un mayor riesgo de morbilidad y mortalidad cardiovascular. Los efectos de la terapia hormonal de la menopausia (THM) en la progresión de la aterosclerosis y los eventos de enfermedad cardiovascular (ECV) varían según la edad en que se inicia la THM y el tiempo transcurrido desde la menopausia hasta su inicio. Se han observado efectos beneficiosos en los resultados de ECV y la mortalidad por todas las causas cuando la THM se inició antes de los 60 años o dentro de los 10 años posteriores a la menopausia. La decisión sobre la iniciación, dosis, régimen y duración de la THM debe tomarse individualmente después de discutir los beneficios y riesgos con cada paciente. Para la prevención primaria de condiciones crónicas en la posmenopausia, no se recomienda el uso combinado de estrógeno y progestágeno en mujeres asintomáticas, ni el uso de estrógeno solo en mujeres histerectomizadas. Las neoplasias dependientes de hormonas contraindican la THM. Para el tratamiento del síndrome genitourinario de la menopausia, se puede usar terapia estrogénica vaginal en pacientes con factores de riesgo cardiovascular conocidos o ECV establecida. Para mujeres con contraindicaciones a la THM o que la rechazan, las terapias no hormonales con eficacia demostrada (antidepresivos, gabapentina y fezolinetant) pueden mejorar los síntomas vasomotores. Los implantes hormonales compuestos, o hormonas "bioidénticas" y "compuestas", y la "modulación hormonal" no se recomiendan debido a la falta de evidencia científica sobre su efectividad y seguridad.

As mulheres, que representam cerca de metade da população mundial segundo estimativas de janeiro de 2024, podem sofrer com sinais e sintomas da menopausa durante pelo menos um terço de suas vidas, quando apresentam maiores risco e morbimortalidade cardiovasculares. Os efeitos da terapia hormonal da menopausa (THM) na progressão de eventos de aterosclerose e doença cardiovascular (DCV) variam de acordo com a idade em que a THM é iniciada e o tempo desde a menopausa até esse início. Efeitos benéficos nos resultados de DCV e na mortalidade por todas as causas ocorreram quando a THM foi iniciada antes dos 60 anos de idade ou nos 10 anos que se seguiram à menopausa. A decisão sobre o início, a dose, o regime e a duração da THM deve ser tomada individualmente após discussão sobre benefícios e riscos com cada paciente. Para a prevenção primária de condições crônicas na pós-menopausa, não se recomendam o uso combinado de estrogênio e progestagênio em mulheres assintomáticas nem o uso de estrogênio sozinho em mulheres histerectomizadas. Neoplasias hormônio-dependentes contraindicam a THM. Para tratamento da síndrome geniturinária da menopausa, pode-se utilizar terapia estrogênica por via vaginal em pacientes com fatores de risco cardiovascular conhecidos ou DCV estabelecida. Para mulheres com contraindicação à THM ou que a recusam, terapias não hormonais com eficácia comprovada (antidepressivos, gabapentina e fezolinetante) podem melhorar os sintomas vasomotores. Os implantes hormonais manipulados, ou hormônios "bioidênticos" "manipulados", e a 'modulação hormonal' não são recomendados pela falta de evidência científica de sua eficácia e segurança.

Etonogestrel-releasing subdermal contraceptive implant: Budget impact analysis based on the Brazilian private healthcare system.

High rates of unplanned pregnancies persist despite pharmacological developments and advancements in contraceptive methods. Here, we demonstrate that the etonogestrel-releasing subdermal contraceptive implant (IMP-ETN) may be an appropriate and cost-effective alternative to levonorgestrel-releasing intrauterine systems (LNG-IUSs) for women in Brazil. For our pharmacoeconomic analysis, we reviewed the literature on IMP-ETN regarding its acceptance, eligibility criteria, choice, relations with age, adverse events and, finally, the unmet need in the fee-for-service private healthcare sector. We considered qualitative observations in combination with quantitative analysis and performed a deterministic sensitivity analysis to investigate whether this technology can be self-sustainable over a period of five years. The target population for this analysis comprised 158,696 women. Compared with the continued use of LNG-IUSs, adopting the IMP-ETN can result in a cost avoidance of $ 7.640.804,02 in the first year and $ 82,455,254.43 in five years. Disseminating information among physicians will promote this change and strengthen the potential cost avoided by private health system payers. These savings can be used to improve other healthcare programs and strategies. Moreover, the principles of care can be promoted by improving and adapting healthcare systems and expanding treatment and follow-up strategies. This would also provide support to women's reproductive rights and improve their quality of life. Our results suggest that the IMP-ETN has a favorable cost-effectiveness profile. Given all its advantages and negative incremental cost impact over a period of five years, the IMP-ETN may be a more favorable alternative to LNG-IUSs. Therefore, it should be offered to beneficiaries with a private healthcare plan. This analysis overcomes previous barriers to the use of cost-benefit models, and our results may help balance decision-making by policymakers, technical consultants, and researchers.

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles / Padrões inflamatórios sistêmicos em pacientes com câncer de ovário: Análise de citocinas, quimiocinas e micropartículas

Abstract Objective To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. Materials and Methods We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. Results Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1β), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. Conclusion The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

Resumo Objetivo Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. Métodos Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. Resultados Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1β), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. Conclusão Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.

Systemic Inflammatory Patterns in Ovarian Cancer Patients: Analysis of Cytokines, Chemokines, and Microparticles.

OBJECTIVE: To compare the patterns of systemic inflammatory response in women with epithelial ovarian cancer (EOC) or no evidence of malignant disease, as well as to evaluate the profile of systemic inflammatory responses in type-1 and type-2 tumors. This is a non-invasive and indirect way to assess both tumor activity and the role of the inflammatory pattern during pro- and antitumor responses. MATERIALS AND METHODS: We performed a prospective evaluation of 56 patients: 30 women without evidence of malignant disease and 26 women with EOC. The plasma quantification of cytokines, chemokines, and microparticles (MPs) was performed using flow cytometry. RESULTS: Plasma levels of proinflammatory cytokines interleukin-12 (IL12), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α) interleukin-1 beta (IL-1ß), and interleukin-10 (IL-10), and C-X-C motif chemokine ligand 9 (CXCL-9) and C-X-C motif chemokine ligand 10 (CXCL-10) were significantly higher in patients with EOC than in those in the control group. Plasma levels of cytokine interleukin-17A (IL-17A) and MPs derived from endothelial cells were lower in patients with EOC than in the control group. The frequency of leukocytes and MPs derived from endothelial cells was higher in type-2 tumors than in those without malignancy. We observed an expressive number of inflammatory/regulatory cytokines and chemokines in the cases of EOC, as well as negative and positive correlations involving them, which leads to a higher complexity of these networks. CONCLUSION: The present study showed that, through the development of networks consisting of cytokines, chemokines, and MPs, there is a greater systemic inflammatory response in patients with EOC and a more complex correlation of these biomarkers in type-2 tumors.

OBJETIVO: Comparar os padrões de resposta inflamatória sistêmica em mulheres com câncer epitelial de ovário (CEO) ou sem evidência de doença maligna, bem como avaliar o perfil de respostas inflamatórias sistêmicas em tumores dos tipos 1 e 2. Esta é uma forma não invasiva e indireta de avaliar tanto a atividade tumoral quanto o papel do padrão inflamatório durante as respostas pró- e antitumorais. MéTODOS: Ao todo, 56 pacientes foram avaliados prospectivamente: 30 mulheres sem evidência de doença maligna e 26 mulheres com CEO. A quantificação plasmática de citocinas, quimiocinas e micropartículas (MPs) foi realizada por citometria de fluxo. RESULTADOS: Os níveis plasmáticos das citocinas pró-inflamatórias interleucina-12 (IL12), interleucina-6 (IL-6), fator de necrose tumoral alfa (tumor necrosis factor alpha, TNF-α, em inglês), interleucina-1 beta (IL-1ß), e interleucina-10 (IL-10), e da quimiocina de motivo C-X-C 9 (CXCL-9) e da quimiocina de motivo C-X-C 10 (CXCL-10) foram significativamente maiores em pacientes com EOC do que nos controles. Os níveis plasmáticos da citocina interleucina-17A (IL17A) e MPs derivados de células endoteliais foram menores em pacientes com CEO do que no grupo de controle. A frequência de leucócitos e de MPs derivadas de células endoteliais foi maior nos tumores de tipo 2 do que naqueles sem malignidade. Observou-se um número expressivo de citocinas e quimiocinas inflamatórias/regulatórias nos casos de CEO, além de correlações negativas e positivas entre elas, o que leva a uma maior complexidade dessas redes. CONCLUSãO: Este estudo mostrou que, por meio da construção de redes compostas por citocinas, quimiocinas e MPs, há maior resposta inflamatória sistêmica em pacientes com CEO e correlação mais complexa desses biomarcadores em tumores de tipo 2.

Desafios do rastreamento do câncer de mama / Challenges of breast cancer screening

A mamografia é o método de eleição para o rastreamento do câncer de mama, sendo o único que demonstra redução de mortalidade na população de risco habitual. A periodicidade de realização e a idade de início do rastreamento mamográfico são um tema controverso na literatura. Entretanto, dados no nosso país apontam para uma porção significativa de neoplasia de mamas em mulheres abaixo dos 50 anos. A Federação Brasileira das Associações de Ginecologia e Obstetrícia (Febrasgo), a Sociedade Brasileira de Mastologia (SBM) e o Colégio Brasileiro de Radiologia e Diagnóstico por Imagem (CBR) concordam que o rastreamento mamográfico deveria ser realizado, anualmente, por todas as mulheres a partir de 40 anos de idade. No Brasil, há uma distribuição desigual de mamógrafos nas várias regiões. As políticas de rastreamento devem considerar essa desigualdade. A grande maioria dos serviços no Brasil realiza rastreamento oportunístico para o câncer de mama. A implantação de rastreamento organizado por faixa etária e estratificação de risco pode otimizar os custos do sistema público de saúde. Pacientes de alto risco precisam ser rastreadas de forma diferente das pacientes de risco habitual. Essas pacientes precisam ter acesso à ressonância magnética das mamas e também iniciar seu rastreamento em idade mais precoce. O protocolo abreviado da ressonância magnética para rastreamento de pacientes de alto risco para câncer de mama pode melhorar a adesão e o acesso dessas pacientes ao programa de rastreamento. A ultrassonografia das mamas não é método de rastreamento isoladamente. Entretanto, ela tem seu papel como método complementar à mamografia e à ressonância magnética em cenários específicos, bem como em substituição à ressonância magnética em pacientes com contraindicação ao uso desse método. As mamas densas possuem baixa sensibilidade para o rastreamento por mamografia

Human papillomavirus prevalence and frequency of sexually transmitted diseases in encarcered women by self-sampling approach.

OBJECTIVE: This study aimed to assess the sociodemographic and clinical profile of women deprived of their liberty and to identify the prevalence of sexually transmitted diseases and human papillomavirus through self-sampling samples. METHODS: This is an epidemiological, cross-sectional, observational, and descriptive study of the prevalence and correlation of the diagnosis of human papillomavirus infection in 268 encarcered women in Amazonas submitted to self-sampling from June 2019 to September 2020 using the genotyping analysis. Patients with positive and inconclusive results were evaluated by commercialized PCR to detect pathogens causing sexually transmitted diseases. The sample size used was based on a convenience sample. RESULTS: In 268 women, human papillomavirus DNA was detected in 87 (32.5%) of them. Sexually transmitted diseases were detected in 30 (34.48%) of the 87 women with a positive or inconclusive result for human papillomavirus. Women with more than three pregnancies had a higher risk of human papillomavirus detection (p=0.004). CONCLUSION: The prevalence of human papillomavirus and other sexually transmitted diseases in encarcered women in Amazonas is 32.5 and 34.48%, respectively. Most women were single (60.4%) and reported having had more than 15 partners (90.8%).

Provision of contraceptives by Brazilian general gynaecologists: a nationwide online survey.

OBJECTIVE: To assess the provision of contraceptives by Brazilian obstetricians and gynaecologists (Obst/Gyns) during medical consultation and associated factors. METHODS: An anonymous online survey was conducted with Obst/Gyns regarding age, gender, training, method counselling about and provision of long-acting reversible contraception (LARC). RESULTS: Of 16,000 Obst/Gyns, 610 (3.8%) answered the survey. After multiple regression analysis, female Obst/Gyns (reference) (OR male was 0.53 [95%CI 0.28-0.98], p = 0.044) and Obst/Gyns aged between 20 and 39 were more likely to provide an IUD. For hormonal-IUDs, Obst/Gyns who had had theoretical training in hormonal-IUD insertion (reference no training) (OR = 2.13 [95%CI 1.14-3.99], p = 0.018), those who work in a private facility or public hospital, and those that allowed more time during consultations (reference) (OR short time = 0.33 [95%CI 0.17-0.63], p < 0.001) were more likely to provide them. Obst/Gyns who were hands-on trained were more likely to provide subdermal implant (OR = 2.04 [95%CI 1.45-2.87], p < 0.001). CONCLUSIONS: There is a gap between theoretical and practical training received by this cohort of Obst/Gyns regarding LARCs, mainly contraceptive implants and hormonal-IUDs. The identification of barriers to offering contraceptives is essential to providing client-centred contraceptive care.

There is a gap between the theoretical and practical training received by Brazil-based Obst/Gyns regarding LARC methods, mainly subdermal implants and hormonal-IUDs. The identification of barriers is essential to providing client-centred contraceptive care.

The HOPE study: evaluating the impact of an online educational resource for heavy menstrual bleeding on the patient-physician dynamic.

The Heavy menstrual bleeding: Evidence-based Learning for best Practice (HELP) Group developed an educational website about heavy menstrual bleeding (HMB). The "HMB improving Outcomes with Patient counseling and Education" (HOPE) project examined the website's impact on women's knowledge, confidence, and consultations with healthcare providers (HCPs). HOPE was a quantitative online survey of gynecologists and women with HMB in Brazil. After an initial consultation, patients had unlimited access to the website and completed a survey. HCPs also completed a survey about the sconsultation. After a second consultation, HCPs and patients completed another survey. HCP surveys assessed their perception of patients' awareness, understanding, and willingness to discuss HMB. Patient surveys assessed their knowledge, experience, and confidence in discussing HMB. Forty HCPs recruited 400 women with HMB. Based on HCP perceptions at the first consultation, 18 percent of patients had "good knowledge" or "very good knowledge" of HMB, increasing to 69 percent after patients had visited the website. Before and after visiting the website, 34 percent and 69 percent of patients, respectively, regarded their HMB knowledge as "goo.d" Additionally, 17 percent of women reported their anxiety as "highest" during the first consultation; this decreased to 7 percent during the second consultation. After visiting the HELP website, patients' knowledge of HMB improved and they were less anxious.

In deep bioinformatic characterization of a novel fumarate hydratase variant FH c.199T > G; (p.Tyr67Asp) in hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a rare, autosomal dominant tumor predisposition syndrome characterized by variable development of multiple skin and uterus leiomyomas and aggressive forms of renal cell carcinoma (RCC). Mutations in fumarate hydratase (FH), one of the proteins in homologous recombination repair, precede the development of HLRCC with high penetrance. Considering the risk of early metastasis of RCC, FH has been included in mutation screening panels. The identification of a pathogenic FH variant guides the screening for tumors in the carriers. However, variants of uncertain significance (VUS) are frequent findings, limiting the clinical value of the mutation screening. Here, we describe the associated phenotype and an in-depth, multi-step Bioinformatic evaluation of the germline FH c.199T > G (p.Tyr67 > Asp) variant segregated in an HLRCC family. Evidence for FH c.199T > G; (p.Tyr67Asp) pathogenicity includes the variant segregation with the disease in three affected family members, its absence in populational databases, and the deep evolutionary conservation of the Tyr67 residue. At the protein level, this residue substitution causes the loss of molecular bonds and ionic interactions, affecting molecular dynamics and protein stability. Considering ACMG/AMP criteria, we propose the reclassification of the FH c.199T > G; (p.Tyr67Asp) variant to "likely pathogenic". In addition, the in-depth, in silico approach used here allowed us to understand how and why FH c.199T > G; (p.Tyr67Asp) could cause HLRCC. This could help in clinical management decisions concerning the monitoring of unaffected family members having this variant.

A phase II randomized clinical trial to assess toxicity and quality of life of breast cancer patients with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation in the context of COVID-19 crisis.

Purpose: This study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: In this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley-Smith formula. Results: Grade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema. Conclusion: HF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial registration: ClinicalTrials.gov, identifier NCT40155531.

Care after premenopausal risk-reducing salpingo-oophorectomy in high-risk women: Scoping review and international consensus recommendations.

Women at high inherited risk of ovarian cancer are offered risk-reducing salpingo-oophorectomy (RRSO) from age 35 to 45 years. Although potentially life-saving, RRSO may induce symptoms that negatively affect quality of life and impair long-term health. Clinical care following RRSO is often suboptimal. This scoping review describes how RRSO affects short- and long-term health and provides evidence-based international consensus recommendations for care from preoperative counselling to long-term disease prevention. This includes the efficacy and safety of hormonal and non-hormonal treatments for vasomotor symptoms, sleep disturbance and sexual dysfunction and effective approaches to prevent bone and cardiovascular disease.

Câncer de colo uterino na gestação / Cervical cancer in pregnancy

PONTOS-CHAVE • A incidência de câncer durante a gestação tem aumentado devido à tendência das mulheres em postergar a gravidez. O câncer de colo de útero é a terceira neoplasia mais comumente diagnosticada durante o período gestacional. • O rastreamento e o diagnóstico devem se dar como nas pacientes não gestantes; a citologia oncótica cervical é o exame obrigatório do pré-natal, e a colposcopia com biópsia pode ser realizada em qualquer período da gestação. • A gestação complicada pelo diagnóstico de um câncer deve sempre ser conduzida em centro de referência e por equipe multidisciplinar. • A interrupção da gestação em situações específicas, para tratamento-padrão, é respaldada por lei. • A quimioterapia neoadjuvante é uma alternativa segura de tratamento durante a gestação, para permitir alcançar a maturidade fetal. Apresenta altas taxas de resposta, sendo relatada progressão neoplásica durante a gestação em apenas 2,9% dos casos. O risco de malformações fetais decorrentes da quimioterapia é semelhante ao da população geral. Contudo, a quimioterapia está associada a restrição de crescimento intraútero, baixo peso ao nascer e mielotoxicidade neonatal. • Na ausência de progressão de doença, deve-se levar a gestação até o termo.

Diagnóstico de precisão das lesões mamárias / Accurate diagnosis of breast lesions

PONTOS-CHAVE As lesões mamárias compreendem uma ampla variedade de diagnósticos que apresentam comportamentos diversos. As lesões mamárias podem ser classificadas como lesões benignas, de potencial de malignidade indeterminado (B3), carcinoma in situ e carcinoma invasor. Na era da medicina personalizada, individualizar e obter um diagnóstico preciso faz grande diferença no desfecho final da paciente, principalmente no caso do câncer de mama. Exames de imagem direcionados e de qualidade, métodos de biópsia adequadamente selecionados e análises de anatomopatologia convencional, imuno-histoquímica e até molecular são determinantes no diagnóstico e no manejo das pacientes.

Characteristics, prevalence and sources of stress in individuals who discontinue assisted reproductive technology treatments: a systematic review.

By considering the reasons behind discontinuing assisted reproductive technology (ART) treatment, several studies have indicated that 'stress' is an important issue, but the prevalence of stressors and stress responses, either acute or chronic, remains unclear. In this systematic review, we evaluated the characteristics, prevalence and causes of what was perceived and reported as 'stress' by couples who discontinued ART treatment. Electronic databases were systematically searched, and studies were considered eligible if they evaluated stress as a possible reason for ART discontinuation. Twelve studies were included, with 15,264 participants from eight countries. In all studies, 'stress' was assessed through generic questionnaires or medical records, not by validated stress questionnaires or biomarkers. The prevalence of 'stress' ranged from 11-53%. When the results were pooled, 'stress' was cited as a reason for ART discontinuation by 775 out of 2507 participants (30.9%). Clinical factors associated with worse prognosis, physical discomfort due to treatment procedures, family demands, time pressure and economic burden were identified as sources of 'stress' that contributed to ART discontinuation. Precisely knowing the characteristics of the stress associated with infertility is essential to devise preventive or supportive interventions to help patients to cope and endure the treatments. Further studies are necessary to investigate whether the mitigation of stress factors can reduce ART discontinuation rates.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer.

OBJECTIVE: The present study evaluated the profile of germline mutations present in patients who underwent genetic counseling for risk assessment for breast cancer (BC), ovarian cancer (OC), and endometrial cancer (EC) with a possible hereditary pattern. METHODS: Medical records of 382 patients who underwent genetic counseling after signing an informed consent form were analyzed. A total of 55.76% of patients (213/382) were symptomatic (personal history of cancer), and 44.24% (169/382) were asymptomatic (absence of the disease). The variables analyzed were age, sex, place of birth, personal or family history of BC, OC, EC, as well as other types of cancer associated with hereditary syndromes. The Human Genome Variation Society (HGVS) nomenclature guidelines were used to name the variants, and their biological significance was determined by comparing 11 databases. RESULTS: We identified 53 distinct mutations: 29 pathogenic variants, 13 variants of undetermined significance (VUS), and 11 benign. The most frequent mutations were BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T, and BRCA2 c.2T> G. Furthermore, 21 variants appear to have been described for the first time in Brazil. In addition to BRCA1/2 mutations, variants in other genes related to hereditary syndromes that predispose to gynecological cancers were found. CONCLUSION: This study allowed a deeper understanding of the main mutations identified in families in the state of Minas Gerais and demonstrates the need to assess the family history of non-gynecological cancer for risk assessment of BC, OC, and EC. Moreover, it is an effort that contributes to population studies to evaluate the cancer risk mutation profile in Brazil.

OBJETIVO: O presente estudo avaliou o perfil de mutações germinativas presentes em pacientes submetidas a aconselhamento genético para avaliação de risco para câncer de mama (CM), câncer de ovário (OC) e câncer de endométrio (CE) com possível padrão hereditário. MéTODOS: Foram analisados os prontuários de 382 pacientes que realizaram aconselhamento genético após consentimento informado. Um total de 55,76% dos pacientes (213/382) eram sintomáticos (história pessoal de câncer), e 44,24% (169/382) eram assintomáticos (ausência da doença). As variáveis analisadas foram idade, sexo, naturalidade, história pessoal ou familiar de CM, OC, CE bem como outros tipos de câncer associados a síndromes hereditárias. As diretrizes de nomenclatura da Human Genome Variation Society (HGVS) foram usadas para nomear as variantes e seu significado biológico foi determinado pela comparação de 11 bancos de dados. RESULTADOS: Identificamos 53 mutações distintas: 29 variantes patogênicas, 13 variantes de significado indeterminado e 11 benignas. As mutações mais frequentes foram BRCA1 c.470_471delCT, BRCA1 c.4675 + 1G > T e BRCA2 c.2T > G. Além disso, 21 variantes parecem ter sido descritas pela primeira vez no Brasil. Além das mutações BRCA1/2, foram encontradas variantes em outros genes relacionados a síndromes hereditárias que predispõem a cânceres ginecológicos. CONCLUSãO: Este estudo permitiu conhecer melhor as principais mutações identificadas nas famílias do estado de Minas Gerais e demonstra a necessidade de avaliar a história familiar de câncer não ginecológico para avaliação do risco de CM, OC e CE. Além disso, é um esforço que contribui com estudos populacionais para avaliar o perfil de mutações de risco para câncer no Brasil.

Eating habits, anthropometry, lifestyle, and hypertension of a group of non-village indigenous women in Amazon, Brazil

SUMMARY OBJECTIVE: The aim of this study was to describe the anthropometric characteristics, eating habits, and lifestyle of non-village indigenous women living in Manaus, AM, and their association with hypertension. METHODS: This cross-sectional (descriptive-analytical) study was carried out from January 2020 to December 2021 using a questionnaire for clinical, sociodemographic, and behavioral data. Non-pregnant women who belonged to Parque das Tribos for more than a year, declared themselves indigenous, and were over 18 years of age were included in the study. RESULTS: In total, 21 ethnicities were identified, and 95 indigenous women were evaluated. The average age group was 36±12.1 years, the average height was 157 cm, and the body mass index was 28.8 kg/m2. The prevalence of systemic arterial hypertension was ±40%, and 68.5% had excess weight, with 29.1% having class I obesity. In all, 35.8% consumed a lot of salt, sugar, and industrialized foods, and 88.4% were sedentary. CONCLUSION: Much of the sample presented excess weight, and almost all were sedentary. More than one-third had unappropriated eating habits. Hypertension was present in more than one-third of these indigenous women. There was an association between higher body mass index and hypertension. Knowing the characteristics of this group of non-village indigenous women may help determine the best health approach. The data demonstrate the necessity of preventive measures.

Preservação da fertilidade em pacientes com câncer ginecológico / Fertility preservation in gynecologic cancer patients

CONTEXTO CLÍNICO O câncer ginecológico afeta diretamente a fertilidade, pois o tratamento consiste na remoção cirúrgica do sistema reprodutor e/ou na sua exposição a agentes gonadotóxicos. Entretanto, pacientes em estádios iniciais e que estejam dentro de critérios estabelecidos podem ser tratadas com cirurgias conservadoras da fertilidade, com resultados oncológicos equivalentes aos dos tratamentos tradicionais. As técnicas de preservação da fertilidade, como criopreservação de oócitos, embriões e tecido ovariano, também podem ser oferecidas em algumas situações. A American Society of Clinical Oncology (ASCO) publicou recomendações sobre a preservação de fertilidade, com o objetivo de aumentar a conscientização sobre o tema, e, juntamente com a American Society for Reproductive Medicine (ASRM), recomenda que pacientes em idade fértil com câncer passem por aconselhamento reprodutivo. Essas pacientes apresentam menores taxas de arrependimento, mesmo quando optam por desistir do tratamento conservador. O interesse na preservação da fertilidade aumentou nas últimas décadas, tanto pelo fato de as mulheres postergarem a gestação como pelo aumento da incidência de câncer em jovens. A taxa de incidência de todos os cânceres aumentou 29% entre 1973 e 2015 em adolescentes e adultos jovens de ambos os sexos. O câncer de colo uterino, em mulheres de 20-29 anos, aumentou anualmente em uma média de 10,3% entre 2000 e 2009. A omissão em orientar pacientes com câncer sobre as possibilidades de preservação da fertilidade pode gerar questionamentos futuros; em alguns países. isso já se configura má prática médica.