Exploring cervical cancer mortality in Brazil: an ecological study on socioeconomic and healthcare factors.

OBJECTIVE: To evaluate the correlation between socioeconomic and healthcare factors and cervical cancer mortality rates, as well as the accessibility to prevention and treatment across Brazilian states and macroregions. The aim is to highlight the multifaceted challenge of addressing cervical cancer mortality, particularly in low- and middle-income countries. METHODS: This cross-sectional study analyzed public data from the Brazilian National Institute of Cancer (INCA), the National Institute of Geography and Statistics (IBGE), and the Brazilian Ministry of Health. Data were collected on indicators such as the Human Development Index (HDI), physician density, average household income, human papillomavirus (HPV) vaccine coverage, Pap smear screening rates, radiotherapy machine density, and non-White population rates by state and macroregion across Brazil. Spearman's rank correlation test and simple linear regression analysis were employed. RESULTS: Cervical cancer mortality rates are statistically lower in women with health insurance, positive self-perception of health, located in states with a higher HDI, per capita household income, density of physicians, and radiotherapy machines per 1000 inhabitants. In contrast, mortality rates proportionally increase according to poverty levels, as expected, and rates of non-White population. Considering public health, HDI scores significantly affected Pap smear test coverage, the number of radiotherapy machines, and HPV vaccine uptake. The North and the Southeast regions have, respectively, the lowest and the highest socioeconomic indicators, proportional to their mortality rates. No significant correlation was found between mortality rates and HPV vaccine or Pap smear coverage. CONCLUSIONS: Cervical cancer mortality in Brazil is significantly influenced by socioeconomic and healthcare disparities. This study provides a data-driven basis for public health strategies that address both medical and social determinants of health.

Non-hormonal and hormonal intrauterine contraception: survey of patients' perceptions in four Latin American countries.

OBJECTIVES: This study sought to understand women's perceived barriers to the use of hormonal and non-hormonal intrauterine contraception in Latin America. METHODS: We developed an online survey for women in Argentina, Brazil, Colombia and Mexico who were seeking contraception. The questions aimed at evaluating patient awareness of negative stories and statements, as well as perceived barriers to the copper intrauterine device (IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS). RESULTS: The survey was mailed to 2300 women. A total of 1953 responses were received from Argentina (n = 465), Brazil (n = 380), Colombia (n = 613) and Mexico (n = 495). More women reported having heard negative stories about the copper IUD than about the LNG-IUS. More women believed that the copper IUD, rather than the LNG-IUS, was suitable only for those who had already had children. More women believed that weight gain (14.3% vs. 38.2%; p < 0.001), mood swings (14.1% vs. 38.7%; p < 0.001) and infertility (16.3% vs. 19.9%; p = 0.016) were possible side effects of the LNG-IUS. By contrast, more women believed that abortion (36% vs. 22.7%; p < 0.001), pelvic infections (42.1% vs. 15.7%; p < 0.001) and ectopic pregnancy (43.5% vs 23.5%; p < 0.001) were side effects more associated with the copper IUD. More believed the copper IUD was associated with less pain during placement and removal compared with the LNG-IUS (42.8% vs. 31.2%; p < 0.001). The perception of increased risk of contracting a sexual transmitted disease did not differ between the methods (IUD vs. LNG-IUS, 21.7% vs. 20.3%; p = 0.388). CONCLUSIONS: Respondents to a web-based survey in four Latin American countries have misperceptions regarding the adverse effects and risks of intrauterine contraception, which may hamper the use of these safe and efficient contraceptive methods. Education about the true risks and benefits involved is fundamental to improving patient acceptance and compliance as well as reducing unplanned pregnancies and unsafe abortions.

Preoperative promestriene for hysteroscopy: a randomized clinical trial.

OBJECTIVE: Intraoperative complications of hysteroscopy, such as the creation of a false passage, cervix dilatation failure, and uterine perforation, may require suspension of the procedure. Some patients refuse a new procedure, which delays the diagnosis of a possible serious uterine pathology. For this reason, it is essential to develop strategies to increase the success rate of hysteroscopy. Some authors suggest preoperative use of topical estrogen for postmenopausal patients. This strategy is common in clinical practice, but studies demonstrating its effectiveness are scarce. The aim of this study was to evaluate the effect of cervical preparation with promestriene on the incidence of complications in postmenopausal women undergoing surgical hysteroscopy. METHODS: This is a double-blind clinical trial involving 37 postmenopausal patients undergoing surgical hysteroscopy. Participants used promestriene or placebo vaginally daily for 2 weeks and then twice a week for another 2 weeks until surgery. RESULTS: There were 2 out of 14 (14.3%) participants with complications in the promestriene group and 4 out of 23 (17.4%) participants in the placebo group (p=0.593). The complications were difficult cervical dilation, cervical laceration, and vaginal laceration. CONCLUSION: Cervical preparation with promestriene did not reduce intraoperative complications in postmenopausal patients undergoing surgical hysteroscopy.

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.

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.

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%).

High-Grade Transformation in Adenoid Cystic Carcinoma of the Bartholin Gland: Case Report.

INTRODUCTION: In the present study, we report a case of primary adenoid cystic carcinoma (ACC) of the Bartholin gland with high-grade transformation (HGT). Adenoid cystic carcinoma of the Bartholin gland is a rare tumor and HGT has only been reported in head and neck tumors. CASE REPORT: A 77-year-old woman with a non-ulcerated vulvar lesion on the topography of the right Bartholin gland. The patient was submitted to tumor resection followed by V-Y island flap and adjuvant radiotherapy. The histopathological examination revealed primary ACC of the Bartholin gland, with areas of HGT and extensive perineural invasion. The immunohistochemical study with p53 showed a diffuse and strong positive reaction in areas with HGT. After 24 months of follow-up, the patient presented distant metastases and died, despite having undergone to chemotherapy. CONCLUSION: As far as we know, this case is the first description in the literature of HGT in ACC of the Bartholin gland, and HGT appears to be associated with tumor aggressiveness.

INTRODUçãO: Este estudo relata o caso de um carcinoma adenoide cístico (CAC) de glândula de Bartholin com transformação de alto grau. O CAC de glândula de Bartholin é um tumor raro, e sua transformação de alto grau é relatada somente em tumores de cabeça e pescoço. RELATO DE CASO: Paciente de 77 anos de idade, do sexo feminino, com lesão vulvar não ulcerada na topografia da glândula de Bartholin direita. A paciente foi submetida a ressecção do tumor e realização de retalho em V-Y, seguidas de radioterapia adjuvante. O exame histopatológico revelou CAC primário de glândula de Bartholin, com áreas de transformação de alto grau e invasão perineural. O estudo imunohistoquímico com p53 mostrou reação positiva difusa e intensa em áreas com transformação de alto grau. Após 24 meses de seguimento, a paciente apresentou metástases à distância e faleceu, apesar de ter sido submetida a quimioterapia. CONCLUSãO: Pelo que sabemos, este caso é a primeira descrição na literatura de transformação de alto grau em CAC de glândula de Bartholin, e a transformação de alto grau parece estar associada à agressividade do tumor.

Hormone therapy after risk-reducing surgery in patients with BRCA1/BRCA2 mutation: evaluation of potential benefits and safety.

Women with mutations in the BRCA 1 and 2 genes are at increased risk for ovarian and breast cancer and therefore candidates for risk-reducing surgery, including salpingo-oophorectomy and mastectomy. Risk-reducing salpingo-oophorectomy (RRSO) is considered the most effective prophylactic measure for ovarian cancer prevention in this group of patients. This procedure involves loss of ovarian function and induced menopause. Estrogen therapy is the most effective treatment for controlling vasomotor symptoms and improving the quality of life of climacteric women. However, the potential hormonal stimulation of these tumors and the risk of breast cancer are a concern regarding the safety of hormone replacement therapy (HRT) in this population. This article aims to review the current evidence regarding the potential benefits and safety of HRT after RRSO.

Apoptosis-related gene expression can predict the response of ovarian cancer cell lines to treatment with recombinant human TRAIL alone or combined with cisplatin.

OBJECTIVES: The objectives of this study were to determine the sensitivity of ovarian cancer (OC) cell lines (TOV-21G and SKOV-3) to cisplatin and to the recombinant human TRAIL (rhTRAIL), and to evaluate the expression profile of TNFRSF10B, TNFRSF10C, TP53TG5, MDM2, BAX, BCL-2 and CASPASE-8 genes and their participation in the resistance/susceptibility mechanism of these tumor cell lines. METHODS: To determine the IC50 values associated with Cisplatin and rhTRAIL, inhibition of cell growth was observed using MTT assays in two human OC cell lines (SKOV-3 and TOV-21G). The analysis of gene expression was performed using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Both cell lines had different susceptibility profiles to the tested drugs. In the SKOV-3 cell line, the IC50 values for cisplatin and for rhTRAIL were 270.83 ug/mL and 196.5 ng/mL, respectively. The same concentrations were used for TOV-21G. Different gene expression profiles were observed in each tested cell line. CASPASE-8 and TNFRSF10B expression levels could predict the response of both the cell lines to rhTRAIL alone or the response to a combination of rhTRAIL and cisplatin. In addition, we observed a relationship between BCL-2 and BAX expression that may be helpful in estimating the proliferation rate of the OC cell lines. CONCLUSION: SKOV-3 and TOV-21G respond differently to cisplatin and rhTRAIL exposure, and expression of CASPASE-8 and TNFRSF10B are good predictors of responses to these treatments.

Gynecological Surgery and COVID-19: What is the Impact and How Should I Manage it?

It is estimated that around 28 million surgeries will be postponed or canceled worldwide as a result of this pandemic, causing a delay in the diagnosis and treatment of more than 2 million cancer cases. In Brazil, both the National Health Agency (ANS) and National Health Surveillance Agency (ANVISA) advised the postponement of elective and non-essential surgeries, causing a considerable impact on the number of surgical procedures that decreased by 33.4% in this period. However, some women need treatment for various gynecological diseases that cannot be postponed. The purpose of this article is to present recommendations on surgical treatment during the COVID-19 pandemic.

Estima-se que cerca de 28 milhões de cirurgias sejam postergadas ou canceladas no mundo em decorrência desta pandemia, causando atraso no diagnóstico e tratamento de mais de 2 milhões de casos oncológicos. No Brasil, tanto a ANS (Agencia Nacional de Saúde) como a ANVISA (Agencia Nacional de Vigilância Sanitária) orientaram o adiamento das cirurgias eletivas e não essenciais, tendo um impacto considerável no número de procedimentos cirúrgicos com diminuição de 33,4% neste período no Brasil. No entanto, algumas mulheres necessitam de tratamento para várias doenças ginecológicas, algumas das quais não podem ser adiadas. O objetivo deste artigo é apresentar recomendações sobre o tratamento cirúrgico durante a pandemia de COVID-19.

Association of insulin-like growth factor II mrna-binding protein 3 (IMP3) expression with prognostic and morphological factors in endometrial cancer

Abstract Objective Endometrial cancer (EC) is a heterogeneous disease with recurrence rates ranging from 15 to 20%. The discrimination of cases with a worse prognosis aims, in part, to reduce the length of surgical staging in cases with a better prognosis. This study aimed to evaluate the association between Insulin-like growth factor II mRNA-binding protein 3 (IMP3) expression and prognostic and morphological factors in EC. Methods This retrospective, cross-sectional, analytical study included 79 EC patients - 70 endometrioid carcinoma (EEC) and 9 serous carcinoma (SC) - and 74 benign endometrium controls. IMP3 expression was evaluated by immunohistochemistry-based TMA (Tissue Microarray), and the results were associated with morphological and prognostic factors, including claudins 3 and 4, estrogen and progesterone receptors, TP53, and KI67. Results IMP3 expression was significantly higher in SC compared to EEC in both extent (p<0.001) and intensity (p=0.044). It was also significantly associated with worse prognostic factors, including degree of differentiation (p=0.024, p<0.001), staging (p<0.001; p<0.001) and metastasis (p=0.002; p<0.001). IMP3 expression was also significant in extent (p=0.002) in endometrial tumors compared with controls. In addition, protein TP53 and KI67 showed significant associations in extent and intensity, respectively. Conclusion IMP3 expression was associated with worse prognostic factors studied. These findings suggest that IMP3 may be a potential biomarker for EC poorer prognosis.

Preoperative promestriene for hysteroscopy: a randomized clinical trial

SUMMARY OBJECTIVE: Intraoperative complications of hysteroscopy, such as the creation of a false passage, cervix dilatation failure, and uterine perforation, may require suspension of the procedure. Some patients refuse a new procedure, which delays the diagnosis of a possible serious uterine pathology. For this reason, it is essential to develop strategies to increase the success rate of hysteroscopy. Some authors suggest preoperative use of topical estrogen for postmenopausal patients. This strategy is common in clinical practice, but studies demonstrating its effectiveness are scarce. The aim of this study was to evaluate the effect of cervical preparation with promestriene on the incidence of complications in postmenopausal women undergoing surgical hysteroscopy. METHODS: This is a double-blind clinical trial involving 37 postmenopausal patients undergoing surgical hysteroscopy. Participants used promestriene or placebo vaginally daily for 2 weeks and then twice a week for another 2 weeks until surgery. RESULTS: There were 2 out of 14 (14.3%) participants with complications in the promestriene group and 4 out of 23 (17.4%) participants in the placebo group (p=0.593). The complications were difficult cervical dilation, cervical laceration, and vaginal laceration. CONCLUSION: Cervical preparation with promestriene did not reduce intraoperative complications in postmenopausal patients undergoing surgical hysteroscopy.

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.

Germline Mutations Landscape in a Cohort of the State of Minas Gerais, Brazil, in Patients Who Underwent Genetic Counseling for Gynecological and Breast Cancer / Cenário de mutações germinativas em uma coorte do estado de Minas Gerais, Brasil, em pacientes submetidas ao aconselhamento genético para câncer ginecológico e de mama

Abstract 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.

Resumo 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.

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.

Immunohistochemical WWOX Expression and Association with Angiogenesis, p53 Expression, Cell Proliferation and Clinicopathological Parameters in Cervical Cancer.

OBJECTIVE: The current study evaluated the expression of WW domain-containing oxidoreductase (WWOX), its association with clinicopathological features and with p53, Ki-67 (cell proliferation) and CD31 (angiogenesis) expression in patients with invasive cervical squamous cell carcinoma (ICSCC). To the best of our knowledge, no other study has evaluated this association. METHODS: Women with IB stage-ICSCC (n = 20) and women with uterine leiomyoma (n = 20) were prospectively evaluated. Patients with ICSCC were submitted to type B-C1 radical hysterectomy and pelvic lymphadenectomy. Patients in the control group underwent vaginal hysterectomy. Tissue samples were stained with hematoxylin and eosin for histological evaluation and protein expression was detected by immunohistochemistry studies. RESULTS: The WWOX expression was significantly lower in the tumor compared with the expression in the benign cervix (p = 0.019). The WWOX expression was inversely associated with the CD31 expression in the tumor samples (p = 0.018). There was no association between the WWOX expression with the p53 expression (p = 0.464) or the Ki-67 expression (p = 0.360) in the samples of invasive carcinoma of the cervix. There was no association between the WWOX expression and tumor size (p = 0.156), grade of differentiation (p = 0.914), presence of lymphatic vascular invasion (p = 0.155), parametrium involvement (p = 0.421) or pelvic lymph node metastasis (p = 0.310) in ICSCC tissue samples. CONCLUSION: The results suggested that WWOX may be involved in ICSCC carcinogenesis, and this marker was associated with tumor angiogenesis.

OBJETIVO: O presente estudo avaliou a expressão do WWOX, sua associação com características clinicopatológicas e com a expressão do p53, ki-67 (proliferação celular) e CD31 (angiogênese) em pacientes com carcinoma invasivo de células escamosas do colo uterino, ou simplesmente câncer do colo uterino (CCE). MéTODOS: Foram avaliadas prospectivamente pacientes com CCE no estágio IB (n = 20) e mulheres com mioma uterino, no grupo controle (n = 20). As pacientes com CCE foram submetidas à histerectomia radical e à linfadenectomia pélvica do tipo B-C1. As mulheres no grupo-controle foram submetidas à histerectomia vaginal. As amostras de tecido foram coradas com hematoxilina e eosina para avaliação histológica e a expressão das proteínas foi detectada por imuno-histoquímico. RESULTADOS: A expressão do WWOX foi significativamente menor no tumor quando comparada com sua expressão no colo do útero benigno (p = 0,019). A expressão tumoral de CD31 foi inversamente associada à expressão de WWOX (p = 0,018). Sua expressão não foi associada à expressão tumoral de p53 e Ki-67 em pacientes com CCE (p = 0,464 e p = 0,360, respectivamente). Não houve associação entre a expressão de WWOX e o tamanho do tumor (p = 0,156), grau de diferenciação (p = 0,914), presença de invasão vascular linfática (p = 0,155), comprometimento do paramétrio (p = 0,421) ou metástase dos linfonodos pélvicos (p = 0,310) em pacientes com CCE. CONCLUSãO: Os resultados sugeriram que o WWOX pode estar envolvido na carcinogênese do CICECU e esse marcador foi associado à angiogênese tumoral.

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.

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.

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

SUMMARY 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%).