Vacuum-assisted excision: a safe minimally invasive option for benign phyllodes tumor diagnosis and treatment-a systematic review and meta-analysis.

Synopsis: This is a systematic review and meta-analysis comparing surgical excision with percutaneous ultrasound-guided vacuum-assisted excision (US-VAE) for the treatment of benign phyllodes tumor (PT) using local recurrence (LR) as the endpoint. Objective: To determine the frequency of local recurrence (LR) of benign phyllodes tumor (PT) after ultrasound-guided vacuum-assisted excision (US-VAE) compared to the frequency of LR after surgical excision. Method: A systematic review and meta-analysis [following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard] was conducted by comparing LR in women older than 18 years treated for benign PT by US-VAE compared with local surgical excision with at least 12 months of follow-up. Studies were retrieved from PubMed, Scopus, Web of Science, and Embase. The pooled effect measure used was the odds ratio (OR) of recurrence. Results: Five comparative prospective or retrospective observational studies published between January 1, 1992, and January 10, 2022, comparing surgical excision with percutaneous US-VAE for LR of benign PT met the selection criteria. Four were retrospective observational cohorts, and one was a prospective observational cohort. A total of 778 women were followed up. Of them, 439 (56.4%) underwent local surgical excision, and 339 (43.6%) patients had US-VAE. The median age of patients in the five studies ranged from 33.7 to 39 years; the median size ranged from 1.5 cm to 3.0 cm, and the median follow-up ranged from 12 months to 46.6 months. The needle gauge ranged from 7G to 11G. LR rates were not statically significant between US-VAE and surgical excision (41 of 339 versus 34 of 439; OR 1.3; p = 0.29). Conclusion: This meta-analysis suggests that using US-VAE for the removal of benign PT does not increase local regional recurrence and is a safe minimally invasive therapeutic option. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022309782.

The personal experience of female obstetricians and gynaecologists with contraceptive use influences the guidance and prescription of contraceptive methods: a web-survey.

OBJECTIVE: To evaluate the influence of the personal experience of female obstetricians and gynaecologists (Obst/Gyns) who utilise contraceptive methods on the provision of these methods. METHODS: An anonymous online web-based survey was carried out with female Obst/Gyns. The instrument contained questions about their current and previous contraceptive methods use, factors that influenced the choice and satisfaction with the ongoing method, as well as the occurrence of adverse events. They were also asked whether the experience of any adverse events influenced their decision in prescribing any particular contraceptive method. RESULTS: 476/9000 (5.3%) female Obst/Gyns answered the survey. The most common contraceptive in use was the 52-mg levonorgestrel-intrauterine device (52-mg LNG-IUD) (34%), followed by non-Long-Acting Reversible Contraception hormonal methods (21.2%). More than half of the respondents (57.6%) reported having some adverse effects and 18.7% reported that the personal experience of an adverse effect with the use of a contraceptive method influenced the prescription of that method. CONCLUSION: Half of female Obst/Gyns encountered adverse events linked to contraceptive usage. Additionally, almost one-fifth believe that their own encounter with adverse effects from a contraceptive method impacts their decision to prescribe the same method.

Almost one-fifth of the female obstetrics and gynaecologists that answered the online survey reported that the personal experience of an adverse effect with the use of a contraceptive method influenced the prescription of that method.

Fertility preservation in female cancer patients in Brazil: perceptions and attitudes of infertility specialists.

Objective: Fertility preservation is a priority in oncology for female cancer patients. However, there is a lack of communication between infertility specialists and oncologists. This study aimed to evaluate infertility specialists' perceptions and experiences regarding fertility preservation. Methods: Conduct an online survey to profile infertility specialists. Participants were infertility affiliated with the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO). The specialists received an online survey, which response rate were 30.9%, most of whom were in southern and southeastern. The survey consisted on 14 questions about the infertility specialists' location, techniques in clinical practice, treatment successful rate, patients idea, etc. Results: The average experience in human reproduction were 15.5 ± 10.2 years (mean ± standard deviation, range 1-40). Among reproductive-aged female cancer patients recommended for fertility preservation, 60.3 ± 28.8% (range 10-100%) underwent preservation procedures. Main barriers were cost (41%), oncologists' knowledge or acceptance (35%) and accessibility (9%). Most infertility specialists (58%) considered 40 years the limit for fertility preservation. Leukemia, lymphoma, breast and ovarian cancers were prioritized for fertility preservation, while lung, thyroid, gastric, and brain cancers were less relevant. Conclusion: This is the first Brazilian study about infertility specialists' perceptions on oncology patients access to fertility preservation. These patients primarily receive treatment in the public health system, while infertility specialists mainly work in the private healthcare. This healthcare mode is currently fragmented, but integrating these experts is enhancing patient access to fertility preservation. Studies on this topic are still warranted.

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.

Fertility preservation in female cancer patients in Brazil: perceptions and attitudes of infertility specialists

Objective: Fertility preservation is a priority in oncology for female cancer patients. However, there is a lack of communication between infertility specialists and oncologists. This study aimed to evaluate infertility specialists' perceptions and experiences regarding fertility preservation. Methods: Conduct an online survey to profile infertility specialists. Participants were infertility affiliated with the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO). The specialists received an online survey, which response rate were 30.9%, most of whom were in southern and southeastern. The survey consisted on 14 questions about the infertility specialists' location, techniques in clinical practice, treatment successful rate, patients idea, etc. Results: The average experience in human reproduction were 15.5 ± 10.2 years (mean ± standard deviation, range 1-40). Among reproductive-aged female cancer patients recommended for fertility preservation, 60.3 ± 28.8% (range 10-100%) underwent preservation procedures. Main barriers were cost (41%), oncologists' knowledge or acceptance (35%) and accessibility (9%). Most infertility specialists (58%) considered 40 years the limit for fertility preservation. Leukemia, lymphoma, breast and ovarian cancers were prioritized for fertility preservation, while lung, thyroid, gastric, and brain cancers were less relevant. Conclusion: This is the first Brazilian study about infertility specialists' perceptions on oncology patients access to fertility preservation. These patients primarily receive treatment in the public health system, while infertility specialists mainly work in the private healthcare. This healthcare mode is currently fragmented, but integrating these experts is enhancing patient access to fertility preservation. Studies on this topic are still warranted.

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.

Abordagem da anemia em situações específicas na mulher: importância e evidências para a tomada de decisão / Specific Anemia Management in Women: Significance and Evidence-Based Decision-Making

A Organização Mundial de Saúde estima que aproximadamente 30% das mulheres na menacme apresentam anemia ferropriva, com implicações significativas para a saúde e a qualidade de vida delas. A anemia é definida com base nos níveis de hemoglobina e pode variar em gravidade. Essa condição resulta em comprometimento da capacidade de transporte de oxigênio, exigindo mecanismos compensatórios do organismo. Além disso, pacientes que enfrentam perda sanguínea aguda e crônica e distúrbios hemorrágicos estão em risco elevado de desenvolver anemia. O Programa Patient Blood Management (PBM) surge como uma abordagem centrada no paciente, enfocando deficiência de ferro, anemia, coagulopatia e perda de sangue. O Patient Blood Management propõe a otimização da gestão do sangue do paciente, evitando transfusões desnecessárias e promovendo uma abordagem mais conservadora. Este artigo aborda a relevância da deficiência de ferro durante a gestação e a menacme, bem como as estratégias de tratamento no período pré-operatório. A suplementação de ferro, seja por via oral ou endovenosa, é fundamental para tratar a anemia ferropriva, enquanto as hemotransfusões são reservadas para casos mais graves. A abordagem sistemática da anemia é crucial para garantir melhores desfechos em cirurgias ginecológicas e no período gestacional. A suplementação de ferro, principalmente via intravenosa, surge como uma opção terapêutica eficaz e rápida, enquanto a hemotransfusão, apesar de útil em situações específicas, apresenta riscos associados que devem ser cautelosamente avaliados.

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.

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.

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.