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.

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.

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.

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.

Association between polymorphisms in xenobiotic detoxification-related genes with prognosis of epithelial ovarian cancer.

This study aimed to evaluate whether GSTM1 and GSTT1 (presents or nulls), GSTP1 c.313A>G and NQO2 c.-102A>C polymorphisms, involved in xenobiotic detoxification pathways, alter outcomes of epithelial ovarian cancer (EOC) patients. DNA from 84 EOC patients diagnosed at the University of Campinas Academic Hospital from January 1995 and July 2007 was analyzed by polymerase chain reaction and restriction fragment length polymorphism assays. The prognostic impact of genotypes of polymorphisms on progression-free survival and overall survival (OS) of EOC patients was examined using the Kaplan-Meier probability estimates and univariate and multivariate Cox proportional hazard ratio (HR) regression analyses. The significant results of Cox analyses were validated using a bootstrap resampling study (1000 replications). At 60 months of follow-up, lower OS was seen in patients with GSTT1 null genotype (50.0 vs. 76.7 %, P = 0.02) compared with the other genotype (Kaplan-Meier estimate). This outcome remained the same in univariate Cox analysis (HR 2.22, P = 0.02). After multivariate Cox analysis, patients with GSTT1 null (HR 2.11, P = 0.04, P bootstrap = 0.04) and NQO2 AA (HR 2.13, P = 0.03, P bootstrap = 0.04) genotypes were under greater risks of progressing to death when compared with those with others genotypes. Our data suggest, for the first time, that inherited abnormalities in xenobiotic detoxification pathway related to GSTT1 and NQO2 c.-102A>C polymorphisms act as independent prognostic factors for OS of EOC patients.

Molecular Subtypes of Breast Cancer Are Not Associated with the Clinical Under- or Overstaging of Breast Cancer.

Purpose to evaluate the agreement between the clinical and pathological stagings of breast cancer based on clinical and molecular features. Methods this was a cross-sectional study, in which clinical, epidemiological and pathological data were collected from 226 patients who underwent surgery at the Prof. Dr. José Aristodemo Pinotti Women's Hospital (CAISM/Unicamp) from January 2008 to September 2010. Patients were staged clinically and pathologically, and were classified as: understaged, when the clinical staging was lower than the pathological staging; correctly staged, when the clinical staging was the same as the pathological one; and overstaged, when the clinical staging was greater than the pathological staging. Results understaged patients were younger (52.2 years; p < 0.01) and more symptomatic at diagnosis (p = 0.04) when compared with correctly or overstaged patients. Clinicopathological surrogate subtype, menopausal status, parity, hormone replace therapy and histology were not associated with differences in staging. Women under 57 years of age were clinically understaged mainly due to underestimation of T (tumor staging) (p < 0.001), as were the premenopausal women (p < 0.01). Patients whose diagnosis was made due to clinical complaints, and not by screening, were clinically understaged due to underestimation of N (lymph nodes staging) (p < 0.001). Conclusion the study shows that the clinicopathological surrogate subtype is not associated with differences in staging, while younger women diagnosed because of clinical complaints tend to have their breast tumors understaged during clinical evaluation.

Molecular Subtypes of Breast Cancer Are Not Associated with the Clinical Under- or Overstaging of Breast Cancer / Subtipos moleculares de câncer de mama não estão associados ao subestadiamento ou ao superestadiamento do câncer de mama

Abstract Purpose to evaluate the agreement between the clinical and pathological stagings of breast cancer based on clinical and molecular features. Methods this was a cross-sectional study, in which clinical, epidemiological and pathological data were collected from 226 patients who underwent surgery at the Prof. Dr. José Aristodemo Pinotti Women's Hospital (CAISM/Unicamp) from January 2008 to September 2010. Patients were staged clinically and pathologically, and were classified as: understaged, when the clinical staging was lower than the pathological staging; correctly staged, when the clinical staging was the same as the pathological one; and overstaged, when the clinical staging was greater than the pathological staging. Results understaged patients were younger (52.2 years; p < 0.01) and more symptomatic at diagnosis (p = 0.04) when compared with correctly or overstaged patients. Clinicopathological surrogate subtype, menopausal status, parity, hormone replace therapy and histology were not associated with differences in staging. Women under 57 years of age were clinically understaged mainly due to underestimation of T ( tumor staging) (p < 0.001), as were the premenopausal women (p < 0.01). Patients whose diagnosis was made due to clinical complaints, and not by screening, were clinically understaged due to underestimation of N (lymph nodes staging) (p < 0.001). Conclusion the study shows that the clinicopathological surrogate subtype is not associated with differences in staging, while younger women diagnosed because of clinical complaints tend to have their breast tumors understaged during clinical evaluation.

Resumo Objetivo avaliar a concordância entre o estadiamento clínico e patológico do câncer de mama em função das características clínicas e moleculares das pacientes. Métodos estudo de corte transversal, sendo coletados dados clínicos, epidemiológicos e anátomo-patológicos de 226 pacientes operadas no Hospital da Mulher Prof. Dr. José Aristodemo Pinotti (Centro de Atenção Integral à Saúde da Mulher - CAISM/ Unicamp), de janeiro de 2008 a setembro de 2010. As pacientes foram estadiadas clínica e patologicamente e classificadas como: subestadiadas, quando o estadiamento clínico foi menor do que o patológico; corretamente estadiadas, quando o estadiamento clínico foi equivalente ao patológico; e superestadiadas, quando o estadiamento clínico foi maior do que o patológico. Resultados as pacientes subestadiadas eram mais jovens (52,2 anos; p < 0,01) e sintomáticas ao diagnóstico (p = 0,04) do que as pacientes corretamente estadiadas ou superestadiadas. O subtipo clinico-patológico, o status menopausal, a paridade, a terapia de reposição hormonal e a histologia não foram associados com a diferença no estadiamento. Detectamos que as mulheres com menos de 57 anos de idade foram clinicamente subestadiadas principalmente devido à subestimação do T (p < 0 ,001), assim como as mulheres na pré-menopausa (p < 0,01). Por outro lado, as pacientes cujo diagnóstico foi realizado por queixa clínica, e não rastreamento, foram clinicamente subestadiadas devido à subestimação do N (p < 0,001). Conclusão o estudo nos mostra que o subtipo clinico-patológico não está associado a diferenças de estadiamento, enquanto mulheres mais jovens, e que tiveram seu diagnóstico por queixa clínica, tendem a ter seus tumores mais frequentemente subestadiados.

Cysts within Otherwise Probably Benign Solid Breast Masses and the Risk of Malignancy.

Objective The objective of this study is to assess whether the largest cyst diameter is useful for BI-RADS ultrasonography classification of predominantly solid breast masses with an oval shape, circumscribed margins, and largest axis parallel to the skin, which, except for the cystic component, would be likely classified as benign. Methods This study received approval from the local institutional review board. From March 2009 to August 2014, we prospectively biopsied 170 breast masses from 164 women. We grouped the largest cyst and mass diameters according to histopathological diagnoses. We used Student's t-test, linear regression, and the area under the receiver operating characteristic curve (AUC) for statistical assessment. Results Histopathological examination revealed 143 (84%) benign and 27 (16%) malignant masses. The mean largest mass diameter was larger among malignant (mean ± standard deviation, 34.1 ± 16.6 mm) than benign masses (24.7 ± 16.7 mm) (P < 0.008). The mean largest cyst diameter was also larger among malignant (9.9 ± 7.1 mm) than benign masses (4.6 ± 3.6 mm) (P < 0.001). Agreement between measurements of the largest mass and cyst diameters was low (R(2) = 0.26). AUC for the largest cyst diameter (0.78) was similar to the AUC for the largest mass diameter (0.69) (p = 0.2). A largest cyst diameter < 3, ≥ 3 to < 11, and ≥ 11 mm had a positive predictive value of 0, 15, and 52%, respectively. Conclusion A largest cystic component < 3 mm identified within breast masses that show favorable characteristics may be considered clinically inconsequential in ultrasonography characterization. Conversely, masses with a largest cystic component ≥ 3 mm should be classified as BI-RADS-US category 4.

Cysts within Otherwise Probably Benign Solid Breast Masses and the Risk of Malignancy / Cistos no interior de nódulo mamários benignos: risco de malignidade

Abstract Objective The objective of this study is to assess whether the largest cyst diameter is useful for BI-RADS ultrasonography classification of predominantly solid breast masses with an oval shape, circumscribed margins, and largest axis parallel to the skin, which, except for the cystic component, would be likely classified as benign. Methods This study received approval from the local institutional review board. From March 2009 to August 2014, we prospectively biopsied 170 breast masses from 164 women. We grouped the largest cyst and mass diameters according to histopathological diagnoses. We used Student's t-test, linear regression, and the area under the receiver operating characteristic curve (AUC) for statistical assessment. Results Histopathological examination revealed 143 (84%) benign and 27 (16%) malignant masses. The mean largest mass diameter was larger among malignant (mean standard deviation, 34.1 16.6 mm) than benign masses (24.7 16.7 mm) (P < 0.008). The mean largest cyst diameter was also larger among malignant (9.9 7.1 mm) than benign masses (4.6 3.6 mm) (P < 0.001). Agreement between measurements of the largest mass and cyst diameters was low (R2 = 0.26). AUC for the largest cyst diameter (0.78) was similar to the AUC for the largest mass diameter (0.69) ( p = 0.2). A largest cyst diameter < 3, 3 to < 11, and 11 mm had a positive predictive value of 0, 15, and 52%, respectively. Conclusion A largest cystic component < 3 mm identified within breast masses that show favorable characteristics may be considered clinically inconsequential in ultrasonography characterization. Conversely, masses with a largest cystic component 3 mm should be classified as BI-RADS-US category 4.

Resumo Objetivo Avaliar se o maior diâmetro do cisto é útil para a classificação ultrassonográfica BI-RADS de nódulos mamários predominantemente sólidos, com forma oval, margens circunscritas e maior eixo paralelo à pele que, exceto pela presença do componente cístico, seriam classificados como provavelmente benignos. Métodos Este estudo foi aprovado pelo Comitê de Ética local. De março de 2009 a agosto de 2014, 170 nódulos mamários de 164 mulheres foram prospectivamente biópsiados. As medidas do maior diâmetro do maior cisto e do maior diâmetro do nódulo foram agrupados de acordo com os diagnósticos histopatológicos. O teste t de Student, a regressão linear e a área sob a curva ROC (AUC) foram utilizados para a avaliação estatística. Resultados O exame histopatológico revelou 143 (84%) nódulos benignos e 27 (16%) nódulos malignos. A média da medida do maior diâmetro dos nódulos foi maior entre os nódulos malignos (média desvio padrão, 34,1 16,6 mm) do que nos nódulos benignos (24,7 16,7 mm) (p < 0,008). A média do maior diâmetro do maior cisto também foi maior entre os nódulos malignos (9,9 7,1 mm) do que nos nódulos benignos (4,6 3,6 mm) (p < 0,001). A concordância entre as medidas dos maiores diâmetros dos nódulos e do maior diâmetro do maior cisto foi baixa (R2 = 0,26). A AUC do maior diâmetro do maior cisto (0,78) foi semelhante à AUC do maior diâmetro do nódulo (0,69) (p = 0,2). Os maiores diâmetros dos maiores cistos medindo < 3; 3 e < 11; e 11 mm tiveram um valor preditivo positivo de 0, 15 e 52%, respectivamente. Conclusão Componentes císticos < 3 mm identificados dentro de nódulos mamários que apresentam as demais características provavelmente benignas podem ser considerados clinicamente irrelevantes na caracterização ultrassonográfica. Por outro lado, nódulos que apresentam um componente cístico medindo 3 mm devem ser classificadas na categoria BI-RADS-US 4.

Vascular endothelial growth factor (VEGF) polymorphism and increased risk of epithelial ovarian cancer.

INTRODUCTION: Angiogenesis (AG) is essential for epithelial ovarian cancer (EOC) development. Vascular endothelial growth factor (VEGF), encoded by the VEGF gene, and endostatin, the product of the COL18A1 gene, act as a potent promoter and an inhibitor of AG, respectively. In the present study, we tested whether VEGF C936T and COL18A1 D104N polymorphisms alter the risk of EOC. METHODS: Genomic DNA from 131 EOC patients and 137 controls were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ (2) or Fisher's exact test and logistic regression analysis. RESULTS: The frequency of the VEGF 936CC genotype was higher in patients than in controls (84.8% vs. 75.3%, P = 0.03). Individuals with respective genotypes had a 1.98 (95% CI 1.04-3.78)-fold increased risk of EOC than those with the remaining genotypes. An excess of VEGF 936CC plus COL18A1 DN genotype was seen in patients when compared to controls (48.6% vs. 30.5%); however, only a tendency toward a statistically significant difference in genotype frequencies was found in the study (P = 0.06), reflecting a trend toward an increased risk of 2.44 for EOC in carriers of the combined genotype. CONCLUSION: Our data present, for the first time, preliminary evidence that VEGF C936T alone or combined with the COL18A1 D104N polymorphism of AG constitutes an important inherited EOC determinant.