Desfechos reprodutivos e de sobrevida em adolescente tratada com cirurgia preservadora de fertilidade por tumor borderline de ovário em estádio avançado: relato de caso e revisão da literatura / Reproductive and survival outcomes in an adolescent treated with fertility- sparing surgery for advanced stage borderline ovarian tumor: case report and review of the literature

Existem poucos dados na literatura sobre os resultados obstétricos e oncológicos de adolescentes com tumores borderline de ovário em estádio avançado trata- das com cirurgia preservadora da fertilidade. Uma adolescente de 15 anos com diagnóstico de tumor borderline de ovário estádio IIIc foi inicialmente tratada com tumorectomia ovariana bilateral e quimioterapia adjuvante com esquema de platina/taxano (seis ciclos). Durante o seguimento, foi submetida a outras três tumorectomias devido a tumor borderline de ovário (duas vezes) e cistadenoma ovariano (uma vez). Outra recidiva de tumor borderline de ovário ocorreu seis anos após o diagnóstico inicial, quando ela estava grávida; foi tratada com tumorecto- mia realizada durante a cesariana. Em sua última consulta ambulatorial, a mulher de 27 anos não apresentava evidência da doença e tinha um filho saudável. Mesmo em estádio avançado, a cirurgia de preservação da fertilidade foi segura e factível nessa paciente com tumor borderline de ovário.

There are few data in the literature regarding obstetric and oncological outcomes of adolescents with advanced-stage borderline ovarian tumors treated with fertility spa- ring surgery. A 15 years old adolescent who was diagnosed with a stage IIIc borderline ovarian tumor, was treated with bilateral ovarian tumorectomies and adjuvant chemotherapy with platinum/taxane regimen (six cycles). During follow up she was submitted to other three tumorectomies due to borderline ovarian tumor(twice) and ovarian cysta- denoma (once). Another borderline ovarian tumorrecurren- ce occurred six years after initial diagnosis, when she was pregnant; treated with tumorectomy performed during ce- sarean section. At her last outpatient visit, the 27-year-old woman had no evidence of disease and a had healthy child. Even at an advanced stage, fertility sparing surgery was safe and feasible in this patient with borderline ovarian tumor.

Características clínicas, diagnóstico e tratamento de mulher com síndrome de Meigs: relato de caso e revisão narrativa / Clinical characteristics, diagnosis and treatment of a woman with Meigs syndrome: case report and narrative review

O objetivo deste estudo é descrever o caso de mulher com síndrome de Meigs e apresentar a revisão narrativa sobre o tema. Paciente do sexo feminino, 30 anos, nulípara, encaminhada ao hospital por massa anexial e história prévia de drenagem de derrame pleural. Evoluiu com instabilidade hemodinâmica por derrame pleural hipertensivo à direita, sendo submetida a drenagem torácica, com citologia do líquido negativa. Após, foi submetida a laparotomia: realizada salpingo-ooforectomia esquerda. A congelação e a análise histopatológica diagnosticaram fibroma ovariano. A citologia ascítica foi negativa. CA-125 elevado, presença de derrames cavitários e exame de imagem suspeito podem mimetizar um cenário de neoplasia maligna de ovário em estágio avançado. Entretanto, na síndrome de Meigs clássica, o tratamento é cirúrgico, sendo o diagnóstico obtido por meio da análise histopatológica do tumor ovariano. O manejo da síndrome de Meigs clássica é cirúrgico e, após a remoção do tumor, o derrame pleural e a ascite desaparecem.

To describe a case of Meigs syndrome and present a narrative review of the condition. Female patient, 30 years old, nulliparous, referred to the hospital due to an adnexal mass and a previous drainage of pleural effusion. She developed hemodynamic instability due to a hypertensive right pleural effusion being submitted to chest drainage, with negative cytology of the fluid. She underwent laparotomy: Left salpingo-oophorectomy was performed and frozen section and histopathological analysis diagnosed an ovarian fibroma. Ascites cytology was negative. Elevated CA-125, presence of cavitary effusions, suspicious imaging exam can mimic a scenario of ovarian cancer at an advanced stage. However, in classical Meigs syndrome, treatment is surgical, and the diagnosis is obtained through histopathological analysis of the ovarian tumor. Classical Meigs syndrome' management is surgical. After tumor removal, pleural effusion and ascites resolve.

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.

Preoperative Differentiation of Benign and Malignant Non-epithelial Ovarian Tumors: Clinical Features and Tumor Markers.

OBJECTIVE: To evaluate the role of clinical features and preoperative measurement of cancer antigen 125 (CA125), human epididymis protein (HE4), and carcinoembryonic antigen (CEA) serum levels in women with benign and malignant non-epithelial ovarian tumors. METHODS: One hundred and nineteen consecutive women with germ cell, sex cord-stromal, and ovarian leiomyomas were included in this study. The preoperative levels of biomarkers were measured, and then surgery and histopathological analysis were performed. Information about the treatment and disease recurrence were obtained from the medical files of patients. RESULTS: Our sample included 71 women with germ cell tumors (64 benign and 7 malignant), 46 with sex cord-stromal tumors (32 benign and 14 malignant), and 2 with ovarian leiomyomas. Among benign germ cell tumors, 63 were mature teratomas, and, among malignant, four were immature teratomas. The most common tumors in the sex cord-stromal group were fibromas (benign) and granulosa cell tumor (malignant). The biomarker serum levels were not different among benign and malignant non-epithelial ovarian tumors. Fertility-sparing surgeries were performed in 5 (71.4%) women with malignant germ cell tumor. Eleven (78.6%) patients with malignant sex cord-stromal tumors were treated with fertility-sparing surgeries. Five women (71.4%) with germ cell tumors and only 1 (7.1%) with sex cord-stromal tumor were treated with chemotherapy. One woman with germ cell tumor recurred and died of the disease and one woman with sex cord-stromal tumor recurred. CONCLUSION: Non-epithelial ovarian tumors were benign in the majority of cases, and the malignant cases were diagnosed at initial stages with good prognosis. The measurements of CA125, HE4, and CEA serum levels were not useful in the preoperative diagnosis of these tumors.

OBJETIVO: Avaliar o papel das características clínicas e a medida pré-operatória dos níveis séricos de CA125, HE4, e CEA em mulheres com tumores de ovário não epiteliais benignos e malignos. MéTODOS: Cento e dezenove mulheres consecutivas com tumores ovarianos de células germinativas, do cordão sexual-estroma, e miomas ovarianos foram incluídas neste estudo. Os níveis pré-operatórios dos biomarcadores foram medidos, a cirurgia e a análise histopatológica foram realizadas. Informações sobre tratamento e recorrência da doença foram obtidas dos prontuários médicos das pacientes. RESULTADOS: Nossa amostra incluiu 71 mulheres com tumores de células germinativas (64 benignos e 7 malignos), 46 com tumores do cordão sexual-estroma (32 benignos e 14 malignos), e 2 com leiomiomas ovarianos. Entre os tumores benignos de células germinativas, 63 eram teratomas maduros, e, entre os malignos, quatro eram teratomas imaturos. Os tumores mais comuns do grupo do cordão sexual-estroma foram fibromas (benignos) e tumores de células da granulosa (malignos). Os níveis séricos dos biomarcadores não diferiram entre os tumores de ovário não epiteliais benignos e malignos. A cirurgia preservadora de fertilidade foi realizada em 5 (71,4%) mulheres com tumores malignos de células germinativas. Onze (78,6%) mulheres com tumores do cordão sexual-estroma malignos foram tratadas com cirurgia preservadora de fertilidade. Cinco (71,4%) mulheres com células germinativas e apenas 1 (7,1%) com tumor do cordão sexual-estroma foram tratadas com quimioterapia. Uma mulher com tumor de células germinativas recidivou e morreu da doença. Uma mulher com tumor do cordão sexual-estroma recidivou. CONCLUSãO: Os tumores de ovário não epiteliais foram benignos na maioria dos casos e os malignos foram diagnosticados em estágios iniciais, com bom prognóstico. A medida dos níveis séricos de CA125, HE4, e CEA não foram úteis no diagnóstico pré-operatório desses tumores.

Diagnostic Value of the Neutrophil/Lymphocyte Ratio, Platelet/Lymphocyte Ratio, and Thrombocytosis in the Preoperative Investigation of Ovarian Masses.

OBJECTIVE: To evaluate the diagnostic accuracy of cancer antigen 125 (CA125) and complete blood count (CBC) parameters, such as the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and thrombocytosis in patients with ovarian masses. METHODS: The present is a retrospective study conducted at a single tertiary hospital from January 2010 to November 2016. We included consecutive women referred due to suspicious adnexal masses. The CBC and CA125 were measured in the serum of 528 women with ovarian masses before surgery or biopsy. We evaluated the diagnostic performance of the NLR, PLR, platelets (PLTs), CA125, and the associations between them. We tested the clinical utility of the CBC parameters and CA125 in the discrimination of ovarian masses through decision curve analysis (DCA). RESULTS: The best balance between sensitivity and specificity was obtained by the associations of CA125 or PLTs ≥ 350/nL, with 70.14% and 71.66%, CA125 or PLTs ≥ 400/nL, with 67.30% and 81.79%, CA125 or PLR, with 76.3% and 64.87%, and CA125 or NLR, with 71.09% and 73.89% respectively. In the DCA, no isolated CBC parameter presented a higher clinical utility than CA125 alone. CONCLUSION: We showed that no CBC parameter was superior to CA125 in the prediction of the malignancy of ovarian tumors in the preoperative scenario.

OBJETIVO: Avaliar a acurácia diagnóstica do antígeno de câncer 125 (cancer antigen 125, CA125, em inglês) e dos parâmetros do hemograma como as razões neutrófilo/linfócito (RNL), plaqueta/linfócito (RPL), e trombocitose em pacientes com massas ovarianas. MéTODOS: Este é um estudo retrospectivo realizado em um hospital terciário no período de janeiro de 2010 a novembro de 2016. Foram incluídas de forma consecutiva mulheres encaminhadas por massas anexiais suspeitas. Foram dosados hemogramas e CA125 no soro de 528 mulheres com massas ovarianas antes da cirurgia ou biópsia. Foram avaliados os desempenhos diagnósticos da RNL, da RPL, das plaquetas (PLQs) e do CA125, considerando-os isoladamente e associados entre si. Testamos a utilidade clínica dos parâmetros do hemograma e do CA125 na discriminação das massas ovarianas por análise de curva de decisão (ACD). RESULTADOS: Os melhores equilíbrios entre sensibilidade e especificidade foram obtidos por meio das associações do CA125 ou PLQs ≥ 350/nL, com 70,14% e 71,66%, CA125 ou PLQs ≥ 400/nL, com 67,30% e 81,79%, CA125 ou RPL, com 76,3% e 64,87%, e CA125 ou RNL, com 71,09% e 73,89%, respectivamente. CONCLUSãO: Na ACD, nenhum parâmetro do hemograma isolado se mostrou superior ao CA125 na predição de malignidade de tumores ovarianos no pré-operatório.

Influence of Gender and Undergraduate Course on the Knowledge about HPV and HPV Vaccine, and Vaccination Rate among Students of a Public University.

OBJECTIVE: To evaluate the knowledge related to human papillomavirus (HPV) infection and the rate of HPV vaccination among undergraduate freshmen and senior students of medicine, pharmacy, speech therapy, nursing and physical education in a Brazilian university. METHODS: A questionnaire concerning sociodemographic aspects, sexual background, and knowledge about HPV and its vaccine was filled out by 492 students. Three months later, a second questionnaire, concerning the new rate of vaccination, was applied to 233 students. RESULTS: Among the 290 women who answered the first questionnaire, 47% of the freshmen and 13% of the seniors stated they were not sexually active, as well as 11% of the 202 freshman and senior male students. Although the knowledge about HPV was higher among women, they reported a lower use of condoms. More than 83% of the women and 66% of the men knew that HPV can cause cervical cancer, but less than 30% of the students knew that HPV can cause vulvar, anal, penile and oropharyngeal cancer. Less than half of the students knew that HPV causes genital, anal and oropharyngeal warts. Comparing the students, the seniors had more knowledge of the fact that HPV is sexually transmitted, and that HPV infection can be asymptomatic. The rate of vaccination was of 26% for women, and of 8% for men, and it increased to 52% and 27% respectively among the 233 students evaluated in the second questionnaire. CONCLUSION: As almost half of freshman women declared being sexually inactive, the investment in public health information programs and easier access to the HPV vaccine seem to be a useful strategy for undergraduate students.

OBJETIVO: Avaliar o conhecimento sobre a infecção pelo vírus do papiloma humano (human papillomavirus, HPV, em inglês) e a taxa de vacinação entre estudantes calouros e veteranos do quarto ano dos cursos de medicina, farmácia, fonoaudiologia, enfermagem e educação física de uma universidade brasileira. MéTODOS: Um primeiro questionário sobre aspectos sociodemográficos, antecedentes sexuais e conhecimento sobre o HPV e sua vacina foi aplicado a 492 estudantes. Três meses depois, foi aplicado um novo questionário, a 233 estudantes, que avaliava a nova taxa de vacinação entre eles. RESULTADOS: Entre as 290 mulheres que responderam ao questionário, 47% das calouras e 13% das veteranas negaram início de atividade sexual. Entre os 202 calouros e veteranos do sexo masculino avaliados, essa taxa foi de 11%. Apesar de o conhecimento sobre o HPV ter sido maior entre as mulheres, elas declararam menor uso de preservativo. Mais de 83% das mulheres e 66% dos homens sabiam que o HPV causa câncer de colo de útero, mas menos de 30% de todos os alunos sabiam que o HPV pode causar câncer de vulva, ânus, pênis e orofaringe, e menos de 50% sabiam que o HPV pode causar verrugas genitais, anais e orofaríngeas. Comparando calouros e veteranos, houve um aumento no conhecimento de que o HPV é sexualmente transmitido, e de que sua infecção pode ser assintomática, entre os veteranos em comparação com os calouros. Pela taxa de vacinação analisada no segundo questionário, identificou-se que, antes do início da pesquisa, 26% das mulheres e 8% dos homens haviam sido vacinados, e, no momento da aplicação do segundo questionário, essas taxas subiram para 52% e 27%, respectivamente, entre os 233 alunos avaliados. CONCLUSãO: Quase metade das calouras relataram não ser sexualmente ativas, e a maioria delas ainda não era vacinada contra o HPV. O ingresso no Ensino Superior parece um momento oportuno para a realização de campanhas governamentais de conscientização e vacinação contra o HPV.

Association of Menopausal Status, Expression of Progesterone Receptor and Ki67 to the Clinical Response to Neoadjuvant Chemotherapy in Luminal Breast Cancer.

OBJECTIVE: To identify the biomarkers of response to neoadjuvant chemotherapy in early luminal breast cancer. METHODS: A cross-sectional study that included all patients with early or locally-advanced luminal breast cancer submitted to neoadjuvant chemotherapy between 2013 and 2014. Demographic, clinic and pathologic data were retrieved from patient records. The expressions of the estrogen receptor (ER), the progesterone receptor (PR), and Ki67 were analyzed by immunohistochemistry (IHC). The status of the human epidermal growth factor receptor 2 (HER2) was evaluated by IHC and fluorescent in situ hybridization (FISH). Independent predictors of clinic and pathologic response were evaluated by stepwise logistic regression models and receiver operating characteristic (ROC) curve analysis. RESULTS: Out of 298 patients identified, 115 were included in the analysis. Clinical complete response (cCR) was observed in 43.4% of the patients (49/113), and pathologic complete response (pCR) was observed in 7.1% (8/115) of the patients. The independent predictors of cCR were premenopausal status (p < 0.001), low PR expression (≤ 50% versus > 50%; p = 0.048), and Ki67 expression ≥ 14% (versus < 14%; p = 0.01). Patients with cCR were more commonly submitted to breast conserving surgery (34.7% versus 7.8%; p < 0.001). Increasing cut-off points for Ki67 expression were associated with an increase in specificity and a decrease in sensitivity to identify patients with cCR. CONCLUSION: Premenopausal status, lower PR expression and higher Ki67 expression were associated with a higher rate of cCR to neoadjuvant chemotherapy in luminal breast cancer.

OBJETIVO: Identificar biomarcadores de resposta à quimioterapia neoadjuvante em câncer luminal de mama. MéTODOS: Estudo transversal em que foram incluídas todas as pacientes com câncer luminal de mama em estádio inicial ou localmente avançado que foram submetidas a quimioterapia neoadjuvante nos anos de 2013 e 2014. Dados demográficos, clínicos e patológicos foram obtidos de prontuários médicos. As expressões de receptor de estrogênio (RE), de receptor de progesterona (RP), e de Ki67 foram avaliadas por imuno-histoquímica (IHQ). A expressão do receptor tipo 2 do fator de crescimento epidérmico humano (human epidermal growth factor receptor 2, HER2) foi avaliada por IHQ e hibridização in situ por imunofluorescência (HISI). Análises de regressão logística e de curva de característica de operação do receptor (COR) foram usadas para investigar fatores preditivos independentes de resposta clínica e patológica. RESULTADOS: De 298 pacientes identificadas, 115 foram incluídas na análise. Resposta clínica completa (RCc) foi observada em 43.4% das pacientes (49/113), e resposta patológica completa (RPc), em 7.1% (8/115). Os fatores preditivos independentes de RCc foram status menopausal (p < 0.001), baixa expressão de RP (≤ 50% versus > 50%; p = 0.048), e expressão de Ki67 ≥ 14% (versus < 14%; p = 0.01). Pacientes com RCc apresentaram maior probabilidade de serem submetidas a cirurgia conservadora da mama (34.7% versus 7.8%; p < 0.001). Aumento no ponto de corte para expressão de Ki67 foi associado a aumento da especificidade e redução da sensibilidade na identificação de pacientes com RCc. CONCLUSãO: Status premenopausal, baixa expressão de RP e maior expressão de Ki67 estiveram associados a maior taxa de RCc à quimioterapia neoadjuvante no câncer luminal de mama.

Association of menopausal status, expression of progesterone receptor and ki67 to the clinical response to neoadjuvant chemotherapy in luminal breast cancer / Associação de status menopausal, expressão de receptor de progesterona e de Ki67 à resposta clínica à quimioterapia neoadjuvante no câncer luminal de mama

Abstract Objective To identify the biomarkers of response to neoadjuvant chemotherapy in early luminal breast cancer. Methods A cross-sectional study that included all patients with early or locallyadvanced luminal breast cancer submitted to neoadjuvant chemotherapy between 2013 and 2014. Demographic, clinic and pathologic data were retrieved from patient records. The expressions of the estrogen receptor (ER), the progesterone receptor (PR), and Ki67 were analyzed by immunohistochemistry (IHC). The status of the human epidermal growth factor receptor 2 (HER2) was evaluated by IHC and fluorescent in situ hybridization (FISH). Independent predictors of clinic and pathologic response were evaluated by stepwise logistic regression models and receiver operating characteristic (ROC) curve analysis. Results Out of 298 patients identified, 115 were included in the analysis. Clinical complete response (cCR) was observed in 43.4% of the patients (49/113), and pathologic complete response (pCR) was observed in 7.1% (8/115) of the patients. The independent predictors of cCR were premenopausal status (p < 0.001), low PR expression (≤ 50% versus > 50%; p = 0.048), and Ki67 expression ≥ 14% (versus < 14%; p = 0.01). Patients with cCR were more commonly submitted to breast conserving surgery (34.7% versus 7.8%; p < 0.001). Increasing cut-off points for Ki67 expression were associated with an increase in specificity and a decrease in sensitivity to identify patients with cCR. Conclusion Premenopausal status, lower PR expression and higher Ki67 expression were associated with a higher rate of cCR to neoadjuvant chemotherapy in luminal breast cancer.

Resumo Objetivo Identificar biomarcadores de resposta à quimioterapia neoadjuvante em câncer luminal de mama. Métodos Estudo transversal em que foram incluídas todas as pacientes com câncer luminal de mama em estádio inicial ou localmente avançado que foram submetidas a quimioterapia neoadjuvante nos anos de 2013 e 2014. Dados demográficos, clínicos e patológicos foram obtidos de prontuários médicos. As expressões de receptor de estrogênio (RE), de receptor de progesterona (RP), e de Ki67 foram avaliadas por imuno-histoquímica (IHQ). A expressão do receptor tipo 2 do fator de crescimento epidérmico humano (human epidermal growth factor receptor 2, HER2) foi avaliada por IHQ e hibridização in situ por imunofluorescência (HISI). Análises de regressão logística e de curva de característica de operação do receptor (COR) foram usadas para investigar fatores preditivos independentes de resposta clínica e patológica. Resultados De 298 pacientes identificadas, 115 foram incluídas na análise. Resposta clínica completa (RCc) foi observada em 43.4% das pacientes (49/113), e resposta patológica completa (RPc), em 7.1% (8/115). Os fatores preditivos independentes de RCc foram status menopausal (p < 0.001), baixa expressão de RP (≤ 50% versus > 50%; p = 0.048), e expressão de Ki67 ≥ 14% (versus < 14%; p = 0.01). Pacientes com RCc apresentaram maior probabilidade de serem submetidas a cirurgia conservadora da mama (34.7% versus 7.8%; p < 0.001). Aumento no ponto de corte para expressão de Ki67 foi associado a aumento da especificidade e redução da sensibilidade na identificação de pacientes com RCc. Conclusão Status premenopausal, baixa expressão de RP e maior expressão de Ki67 estiveram associados a maior taxa de RCc à quimioterapia neoadjuvante no câncer luminal de mama.

Indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase expression in HPV infection, SILs, and cervical cancer.

BACKGROUND: Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in cervicovaginal samples from women with normal cervical epithelium or with different degrees of squamous intraepithelial lesions (SILs) and cervical cancer. METHODS: IDO expression was analyzed by immunocytochemistry in liquid-based cytology samples from 165 women, of whom 42 had cervical changes subclassified as low-grade SIL (n = 6), high-grade SIL (n = 30), or squamous cell carcinoma (SCC) (n = 6), and 123 had negative Papanicolaou smears. IDO and TDO expression also were analyzed by immunohistochemistry, and HPV and other genital pathogens were evaluated by polymerase chain reaction analysis. RESULTS: Low IDO expression was observed in normal cervical epithelium irrespective of HPV status. Increased numbers of IDO-positive squamous cells and IDO-positive leukocytes were observed in women with SIL or SCC. TDO expression was detected in leukocytes infiltrating the stroma around intraepithelial or invasive cervical lesions. Higher IDO levels were detected in organotypic epithelial cultures established from keratinocytes transduced with the HPV16 E6/E7 oncoproteins. CONCLUSIONS: The upregulation of IDO expression in leukocytes and squamous cells in HPV-associated SIL and SCC suggests that immunosuppressive mechanisms involving tryptophan metabolism may have a role in cervical carcinogenesis. Although previous studies have suggested the role of IDO in HPV pathogenesis, this is the first evidence of TDO involvement in the process. Furthermore, the current data emphasize the role of leukocytes, especially neutrophil-like cells, as an IDO source.

Interest In and Practices Related to Gynecologic Oncology among Members of the Brazilian Federation of Associations of Gynecology and Obstetrics.

OBJECTIVE: The present study aims to obtain basic demographic information, the level of interest and of training in gynecology oncology among Brazilian obstetricians and gynecologists (OB-GYNs) to create a professional profile. METHODS: An online questionnaire was sent to 16,008 gynecologists affiliated to the Brazilian Federation of Associations of Gynecology and Obstetrics (FEBRASGO, in the Portuguese acronym). We considered gynecologists dedicated to gynecologic oncology (OB-GYNs ONCO) those who self-reported that > 50% of their daily practice consists in working with women's cancer care. RESULTS: A total of 1,608 (10%) of 16,008 FEBRASGO members responded. The OB-GYNs are concentrated in the southern and southeastern states of Brazil. Gynecologic oncology was considered the 8th greatest area of interest in gynecology among the OB-GYNs. A total of 95 (5.9%) of the OB-GYNs were considered OB-GYNs ONCO. Obstetricians and gynecologists are actively engaged in cancer care: > 60% of them dedicate up to 25% of their daily practice to oncology. The role of the physicians in screening and prevention, diagnosis, in the treatment of precancerous lesions, and in low complexity surgical procedures is notably high. Gynecologists dedicated to gynecologic oncology in Brazil have a heterogeneous, nonstandardized and short training period in gynecologic oncology. These professionals had a more significantly role in performing medium- and high-complexity operations compared with OB-GYNs (65.2% versus 34%, and 47.3% versus 8.4%, respectively). CONCLUSION: The role of OB-GYNs and of OB-GYNs ONCO appears to be complementary. Obstetricians and gynecologists act more often in screening and prevention and in low-complexity surgical procedures, whereas OB-GYNs ONCO are more involved in highly complex cases. Strategies to raise standards in cancer training and to encourage the recognition of gynecologic oncology as a subspecialty should be adopted in Brazil.

OBJETIVO: O presente estudo tem como objetivo obter informações demográficas básicas, o nível de interesse e de treinamento em ginecologia oncológica entre obstetras e ginecologistas (OB-GYNs) brasileiros para criar um perfil destes profissionais. MéTODOS: Um questionário online foi enviado a 16.008 ginecologistas filiados à Federação Brasileira de Associações de Ginecologia e Obstetrícia (FEBRASGO). Nós consideramos ginecologistas dedicados à oncologia ginecológica (OB-GYNs ONCO) aqueles que referiram atuar em > 50% de sua prática diária com o tratamento do câncer feminino. RESULTADOS: Um total de 1.608 (10%) dos 16.008 membros da FEBRASGO responderam ao questionário. Os OB-GYNs estão concentrados nos estados do sul e sudeste do Brasil. A oncologia ginecológica foi considerada a 8ª área de maior interesse em ginecologia entre os OB-GYNs. Um total de 95 (5,9%) dos OB-GYNs foram considerados ginecologistas dedicados à oncologia ginecológica (OB-GYNs ONCO). Obstetras e ginecologistas estão ativamente envolvidos no tratamento do câncer: > 60% deles dedicam até 25% de sua prática diária à oncologia. O papel dos médicos na triagem e na prevenção, no diagnóstico, no tratamento de lesões pré-cancerosas e em procedimentos cirúrgicos de baixa complexidade é notavelmente alto. Ginecologistas dedicados à oncologia ginecológica no Brasil têm um período de treinamento em oncologia ginecológica heterogêneo, não padronizado e curto. Estes profissionais tiveram um papel mais significativo na realização de operações de média e alta complexidade em comparação com OB-GYNs (65,2% versus 34%, e 47,3% versus 8,4%, respectivamente). CONCLUSãO: Os papéis dos OB-GYN e dos OB-GYNs ONCO parecem ser complementares. Os OB-GYNs frequentemente atuam em triagem e prevenção e em procedimentos cirúrgicos de baixa complexidade, enquanto os OB-GYNs ONCO estão mais envolvidos em casos de mais alta complexidade. Estratégias para elevar os padrões de treinamento em oncoginecologia e incentivar o reconhecimento da oncologia ginecológica como uma subespecialidade devem ser adotadas no Brasil.

Diagnostic accuracy of shear wave elastography - Virtual touch™ imaging quantification in the evaluation of breast masses: Impact on ultrasonography's specificity and its ultimate clinical benefit.

OBJECTIVES: To evaluate the diagnostic performance and the clinical benefit of Shear-Wave Elastography - Virtual Touch™ Imaging Quantification (SWE-VTIQ) as a complement to ultrasonography (US). METHODS: From October 2016 through Jun 2017, B-mode US and SWE-VTIQ were prospectively performed in 396 breast masses in 357 women who consented to undergo this study. Quantitative elastography values were recorded: Vmax (maximum elasticity), Vmean (median elasticity), Vratio(max) (ratio of Vmax and surrounding parenchyma) and Vratio(mean) (ratio of Vmean and surrounding parenchyma). The histopathology of the lesions was considered the reference standard for benign or malignant definition. The performance of the four elastographic parameters was evaluated trough sensitivity, specificity and AUC. The parameter with the best performance was tested in six different diagnostic approaches defined based on clinical practice. RESULTS: Of the 396 masses, 122 (30.8%) were benign and 274 (69.2%) were malignant. All SWE parameters were significantly higher in malignant masses (all p < 0.01). Vmax and Vratio(max) performed significantly better then Vratio(mean) (p = 0.01 and p = 0.03, respectively). SWE-VTIQ improved US specificity in all diagnostic approaches, except when applied to BI-RADS 3 lesions. SWE-VTIQ reduced the false positive rate in 25% if applied only to BI-RADS 4A masses, maintaining a high sensitivity (98.9%, 95% confidence interval 97.1-100%) and a negative predictive value of 95.5%. When applied to BI-RADS 4A and 4B masses, SWE-VTIQ reduced the false positive rate in 54.4%. However, 13 malignant cases would be missed in this approach (4.7% of all malignant cases). CONCLUSIONS: SWE-VTIQ increases US specificity when applied to BI-RADS 4 A lesions, significantly reducing unnecessary interventions and preserving the diagnosis of malignant lesions. When applied also to BI-RADS® 4B lesions, SWE-VTIQ increases the number of false negative cases, which should be evaluated with caution.

Clinical Features and Management of Women with Borderline Ovarian Tumors in a Single Center in Brazil.

OBJECTIVE: The aim of the present study was to describe and analyze data of 57 women with borderline ovarian tumors (BOTs) regarding histological characteristics, clinical features and treatment management at the Department of Obstetrics and Gynecology of the Universidade Estadual de Campinas (Unicamp, in the Portuguese acronym). METHODS: The present retrospective study analyzed data obtained from clinical and histopathological reports of women with BOTs treated in a single cancer center between 2010 and 2018. RESULTS: A total of 57 women were included, with a mean age of 48.42 years old (15.43-80.77), of which 30 (52.63%) were postmenopausal, and 18 (31.58%) were < 40 years old. All of the women underwent surgery. A total of 37 women (64.91%) were submitted to complete surgical staging for BOT, and none (0/57) were submitted to pelvic or paraortic lymphadenectomy. Chemotherapy was administered for two patients who recurred. The final histological diagnoses were: serous in 20 (35.09%) cases, mucinous in 26 (45.61%), seromucinous in 10 (17.54%), and endometrioid in 1 (1.75%) case. Intraoperative analyses of frozen sections were obtained in 42 (73.68%) women, of which 28 (66.67%) matched with the final diagnosis. The mean follow-up was of 42.79 months (range: 2.03-104.87 months). Regarding the current status of the women, 45 (78.95%) are alive without disease, 2 (3.51%) are alive with disease, 9 (15.79%) had their last follow-up visit > 1 year before the performance of the present study but are alive, and 1 patient (1.75%) died of another cause. CONCLUSION: Women in the present study were treated according to the current guidelines and only two patients recurred.

OBJETIVO: O objetivo do presente estudo foi descrever uma série de 57 mulheres com tumores borderline de ovário (TBO) em relação às características histológicas, clínicas, e ao manejo do tratamento realizado no Departamento de Obstetrícia e Ginecologia da Universidade Estadual de Campinas (Unicamp). MéTODOS: O presente estudo retrospectivo analisou dados obtidos dos registros clínicos e histopatológicos de mulheres com TBO tratadas em um único centro oncológico de 2010 a 2018. RESULTADOS: Um total de 57 mulheres foram incluídas, com uma média de idade de 48,42 anos (15,43­80,77), das quais 30 (52,63%) eram menopausadas, e 18 (31,58%) tinham < 40 anos. Todas as mulheres foram operadas. Um total de 37 mulheres (64,91%) foram submetidas a cirurgia de estadiamento completo para TBO, e nenhuma foi submetida a linfadenectomia pélvica ou paraórtica. O tratamento com quimioterapia foi administrado em duas pacientes que recidivaram. Os diagnósticos histológicos finais foram: seroso em 20 mulheres (35,09%), mucinoso em 26 (45,61%), seromucinoso em 10 (17,54%) e endometrióide em 1 (1,75%). A avaliação histológica intraoperatória foi realizada em 42 (73,68%) das mulheres, das quais 28 (66,67%) foram compatíveis com os diagnósticos finais. O tempo médio de seguimento foi de 42,79 meses (variando de 2,03 a 104,87 meses). Em relação ao status atual das mulheres, 45 (78.95%) estão vivas sem doença, 2 (3,51%) estão vivas com doença, 9 (15.79%) tiveram a última consulta de seguimento há > 1 ano antes da realização do presente estudo, mas estão vivas, e 1 paciente faleceu por outra causa. CONCLUSãO: As mulheres do presente estudo foram tratadas de acordo com as recomendações atuais e apenas duas mulheres apresentaram recorrência.

A Metabolomic Approach to Predict Breast Cancer Behavior and Chemotherapy Response.

Although the classification of breast carcinomas into molecular or immunohistochemical subtypes has contributed to a better categorization of women into different therapeutic regimens, breast cancer nevertheless still progresses or recurs in a remarkable number of patients. Identifying women who would benefit from chemotherapy could potentially increase treatment effectiveness, which has important implications for long-term survival. Metabolomic analyses of fluids and tissues from cancer patients improve our knowledge of the reprogramming of metabolic pathways involved in resistance to chemotherapy. This review evaluates how recent metabolomic approaches have contributed to understanding the relationship between breast cancer and the acquisition of resistance. We focus on the advantages and challenges of cancer treatment and the use of new strategies in clinical care, which helps us comprehend drug resistance and predict responses to treatment.

Exosome-mediated breast cancer chemoresistance via miR-155 transfer.

Breast cancer remains the most prevalent cause of cancer mortality in woman worldwide due to the metastatic process and therapy resistance. Resistance against cancer therapy is partially attributed to cancer stem cells (CSCs). These cells arise from epithelial cells undergoing epithelial-to-mesenchymal transition (EMT) and might be responsible for tumor recurrence. In this study, we reported the relevance of miR-155 upregulation in chemoresistant cells associated with EMT. Notably, we found miR-155 induction in exosomes isolated from CSCs and resistant cells, followed by resistant cells' exosome transfer to the recipient sensitive cells. Functionally, miR-155 mimic assay showed an enrichment in miR-155 from exosome concomitant with miR-155 exosome transfer to breast cancer cells. In parallel to these effects, we also observed EMT change in miR-155 transfected cells. The chemoresistance phenotype transfer to sensitive cells and the migration capability was analyzed by MTT and scratch assays and our results suggest that exosomes may intermediate resistance and migration capacity to sensitive cells partly through exosome transfer of miR-155. Taken together, our findings establish the significance of exosome-mediate miR-155 chemoresistance in breast cancer cells, with implications for targeting miR-155 signaling as a possible therapeutic strategy.

VEGF gene polymorphisms and outcome of epithelial ovarian cancer patients.

AIM: Since VEGF polymorphisms were associated with variable protein production, we analyzed herein their roles in outcome of epithelial ovarian cancer (EOC) patients. METHODS: Genotypes of 85 patients with primary EOC were identified in DNA by real-time PCR. Progression-free survival and overall survival were analyzed using Kaplan-Meier method, univariate Cox model and bootstrap resampling study. RESULTS: At 60 months of follow-up, progression-free survival was shorter in patients with VEGF c.-2578 CC genotype compared with others (52.7 vs 82.2%; p = 0.04). Those patients had 2.15 more chance of presenting disease progression than others (p = 0.04); bootstrap study validated the result (p = 0.03). CONCLUSION: Our data suggest that VEGF c.-2578C>A polymorphism acts as a prognostic factor in EOC.

Exosomes-mediate microRNAs transfer in breast cancer chemoresistance regulation.

Breast cancer is the most common and fatal type of cancer in women worldwide due to the metastatic process and resistance to treatment. Despite advances in molecular knowledge, little is known regarding resistance to chemotherapy. One highlighted aspect is the DNA damage response (DDR) pathway that is activated upon genotoxic damage, controlling the cell cycle arrest or DNA repair activation. Recently, studies have showed that cancer stem cells (CSCs) could promote chemoresistance through DDR pathway. Furthermore, it is known that the epithelial-mesenchymal transition (EMT) can generate cells with CSCs characteristics and therefore regulate the chemoresistance process. The exosomes are microvesicles filled with RNAs, proteins and microRNAs (miRNAs) that can be released by many cell types, including tumor cells and CSCs. The exosomes content may be cell-to-cell transferable and it could control a wide range of pathways during tumor development and metastasis. A big challenge for modern medicine is to determine the reasons why patients do not respond to chemotherapy treatments and also guide the most appropriate therapy for each one. Considering that the CSCs are able to stimulate the formation of a more aggressive tumor phenotype with migration and metastasis ability, resistance to treatment and disease recurrence, as well as few studies capable to determine clearly the interaction of breast CSCs with its microenvironment, the present review summarize the possibility that exosomes-mediate miRNAs transfer and regulate chemoresistance in breast tumor cells and CSCs, to clarify the complexity of breast cancer progression and therapy.