Trichostatin A-modified vaccine provides superior protection against ovarian cancer formation and development.

More attention has been paid to immunotherapy for ovarian cancer and the development of tumor vaccines. We developed a trichostatin A (TSA)-modified tumor vaccine with potent immunomodulating activities that can inhibit the growth of ovarian cancer in rats and stimulate immune cell response in vivo. TSA-treated Nutu-19 cells inactivated by X-ray radiation were used as a tumor vaccine in rat ovarian cancer models. Prophylactic and therapeutic experiments were performed with TSA-modified tumor vaccine in rats. Flow cytometry and ELISpot assays were conducted to assess immune response. Immune cell expression in the spleen and thymus were detected by immunohistochemical staining. GM-CSF, IL-7, IL-17, LIF, LIX, KC, MCP-1, MIP-2, M-CSF, IP-10/CXCL10, MIG/CXCL9, RANTES, IL-4, IFN-γ, and VEGF expressions were detected with Milliplex Map Magnetic Bead Panel immunoassay. TSA vaccination in therapeutic and prophylactic models could effectively stimulate innate immunity and boost the adaptive humoral and cell-mediated immune responses to inhibit the growth and tumorigenesis of ovarian cancer. This vaccine stimulated the thymus into reactivating status and enhanced infiltrating lymphocytes in tumor-bearing rats. The expression of key immunoregulatory factors were upregulated in the vaccine group. The intensities of infiltrating CD4+ and CD8+ T cells and NK cells were significantly increased in the vaccine group compared to the control group (P<0.05). This protection was mainly dependent on the IFN-γ pathway and, to a much lesser extent, by the IL-4 pathway. The tumor cells only irradiated by X-ray as the control group still showed a slight immune effect, indicating that irradiated cells may also cause certain immune antigen exposure, but the efficacy was not as significant as that of the TSA-modified tumor vaccine. Our study revealed the potential application of the TSA-modified tumor vaccine as a novel tumor vaccine against tumor refractoriness and growth. These findings offer a better understanding of the immunomodulatory effects of the vaccine against latent tumorigenesis and progression. This tumor vaccine therapy may increase antigen exposure, synergistically activate the immune system, and ultimately improve remission rates. A vaccine strategy designed to induce effective tumor immune response is being considered for cancer immunotherapy.

Sobreuso de ecografía transvaginal en un hospital universitario privado de Argentina: estudio de corte transversal / Transvaginal ultrasound overuse in a private university hospital in Argentina: a cross-sectional study

Introducción. Si bien contamos con recomendaciones basadas en la evidencia en contra de realizar tamizaje de cáncer ovárico con ecografía transvaginal debido a que aumenta el riesgo de resultados falsamente positivos y de cascadas diagnósticas, sin disminuir la mortalidad por esta enfermedad, su solicitud en mujeres sanas es frecuente. Sin embargo, no conocemos la magnitud de la implementación de esta práctica, que constituye un cuidado de bajo valor. Objetivo. Documentar el sobreuso de ecografías transvaginales realizadas en forma ambulatoria en un hospital universitario privado de Argentina. Métodos. Estudio de corte transversal de una muestra aleatoria de ecografías realizadas en forma ambulatoria durante 2017 y 2018. Mediante revisión manual de las historias clínicas, la solicitud de cada ecografía fue clasificada como apropiada cuando algún problema clínico justificaba su realización, o inapropiada cuando había sido realizada con fines de control de salud o por una condición clínica sin indicación de seguimiento ecográfico. Resultados. De un total de 1.997 ecografías analizadas, realizadas a 1.954 mujeres adultas (edad promedio 50 años),1.345 (67,4 %; intervalo de confianza [IC] 95 % 65,2 a 69,4) habían sido solicitadas en el contexto de un control de saludo sin un problema asociado en la historia clínica y otras 54 (8,3 %; IC 95 % 6,3 a 10,7), por condiciones de salud para las que no hay recomendaciones de realizar seguimiento ecográfico. Conclusiones. Esta investigación documentó una alta proporción de sobre utilización de la ecografías transvaginales en nuestra institución. Futuras investigaciones permitirán comprender los motivos que impulsan esta práctica y ayudarán a diseñar intervenciones para disminuir estos cuidados de bajo valor. (AU)

Background. Although we have evidence-based recommendations against screening for ovarian cancer with transvaginalultrasound because it increases the risk of false positive results and diagnostic cascades without reducing mortality from this disease, its request in healthy women is frequent. However, we do not know the magnitude of the implementation of this practice, which constitutes low-value care. Objective. To document the overuse of transvaginal ultrasounds performed on an outpatient basis in a private university hospital in Argentina. Methods. Cross-sectional study of a random sample of outpatient ultrasounds performed during 2017 and 2018. Through a manual review of the medical records, the request for each ultrasound was classified as appropriate when a clinical problem justified its performance or inappropriate when it was carried out for health control purposes or for a clinical condition that had no indication for ultrasound follow-up. Results. Of a total of 1997 ultrasounds analyzed, performed on 1954 adult women (average age 50 years), 1,345 (67.4 %;95 % confidence interval [CI] 65.2 to 69.4) had been requested in the context of a health check-up or without a documented problem in the medical history that would support its performance, and another 54 (8.3 %; 95 % CI 6.3 to 10.7), for health conditions for which there are no treatment recommendations to perform ultrasound follow-up. Conclusions. This research documented a high proportion of overuse of transvaginal ultrasound in our institution. Future research will allow us to understand the reasons that drive this practice and will help design interventions to reduce thislow-value care. (AU)

Breast and gynecologic cancers as a Brazilian health priority.

OBJECTIVE: Cancer imposes a profound burden on low- and middle-income countries where 65% of the global cancer deaths occurred in 2020. The objective of the present review was to describe female cancer epidemiology in Brazil, barriers to prevention, screening, and treatment, and to propose strategies to a better control. METHODS: For the process of literature search and scientific acquisition, we have utilized the terms "female cancer" AND "breast cancer," AND "cervical cancer" AND "endometrial cancer" AND "ovarian cancer" AND "Brazil" in PubMed. References of the articles included in this review were manually searched in order to identify relevant studies on the topic. The official Brazilian epidemiology data were extensively analyzed at the governmental site www.inca.gov.br. RESULTS: Considering cases of breast and gynecologic cancers together, 105,770 new cases are expected to be diagnosed yearly, positioning female cancer as the highest cancer incidence in Brazil. Female breast cancer is the most common and the leading cause of death from cancer in the female population in all regions of Brazil, except in the North, where cervical cancer ranks first. Cervical cancer, a preventable disease, corresponds to the third-most common neoplasia in women, with higher incidences in the North and Northeast regions of Brazil. An upward trend has been observed in endometrial cancer incidence, a tendency that follows the increase of its two most common risk factors: population aging and obesity. Ovarian cancer currently occupies the eighth position among female cancers in Brazil, but it is the most lethal gynecologic cancer. The main strategies to reduce female cancer mortality rates are the reduction of inequalities in healthcare services and the early diagnosis of cases. The lack of a specific national cancer program results in a reactive and unplanned approach to healthcare provision, ultimately leading to suboptimal resource utilization and higher expenditure. CONCLUSION: Analyzed together, breast and gynecologic cancers correspond to the leading cause of cancer in Brazil. A heterogeneous group, female cancer includes diseases with a high primary and secondary prevention potential. The organization of a female cancer program in Brazil prioritizing primary and secondary prevention strategies, such as adequate mammography screening and human papillomavirus vaccination coverage, could significantly improve female cancer control in the country.

Economic Modelling of Screen-and-Treat Strategies for Brazilian Women at Risk of Hereditary Breast and Ovarian Cancer.

BACKGROUND: Clinical evidence supports the use of genetic counselling and BRCA1/2 testing for women at risk for hereditary breast and ovarian cancer. Currently, screen-and-treat strategies are not reimbursed in the Brazilian Unified Healthcare System (SUS). The aim of this modelling study was to evaluate the cost effectiveness of a gene-based screen-and-treat strategy for BRCA1/2 in women with a high familial risk followed by preventive interventions compared with no screening. METHODS: Adopting the SUS perspective, a Markov model with a lifelong time horizon was developed for a cohort of healthy women aged 30 years that fulfilled the criteria for BRCA1/2 testing according to the National Comprehensive Cancer Network (NCCN) guideline. For women who tested positive, preventive options included intensified surveillance, risk-reducing bilateral mastectomy and bilateral salpingo-oophorectomy. The Markov model comprised the health states 'well', 'breast cancer', 'death' and two post-cancer states. Outcomes were the incremental costs per quality-adjusted life-year (QALY) and the incremental costs per life-year gained (LYG). Data were mainly obtained by a literature review. Deterministic and probabilistic sensitivity analyses were performed to assess the robustness of the results. RESULTS: In the base case, the screen-and-treat strategy resulted in additional costs of 3515 Brazilian reais (R$) (US$1698) and a gain of 0.145 QALYs, compared with no screening. The incremental cost-effectiveness ratio (ICER) was R$24,263 (US$21,724) per QALY and R$27,258 (US$24,405) per LYG. Applying deterministic sensitivity analyses, the ICER was most sensitive to the probability of a positive test result and the discount rate. In the probabilistic sensitivity analysis, a willingness to pay of R$25,000 per QALY gained for the screen-and-treat strategy resulted in a probability of cost effectiveness of 80%. CONCLUSION: Although there is no rigorous cost-effectiveness threshold in Brazil, the result of this cost-effectiveness analysis may support the inclusion of BRCA1/2 testing for women at high-risk of cancer in the SUS. The ICER calculated for the provision of genetic testing for BRCA1/2 approximates the cost-effectiveness threshold proposed by the World Health Organization (WHO) for low- and middle-income countries.

Salpingectomía oportunista: patrones de práctica en un grupo de ginecólogos colombianos / Opportunistic Salpingectomy: patterns of practice in a group of colombian gynecologists

INTRODUCCIÓN Y OBJETIVOS: El cáncer de ovario es la neoplasia de origen ginecológico más letal y el 90% de los casos son de origen epitelial. Se ha postulado el origen del cáncer epitelial de ovario (CEO) en las fimbrias de las trompas de Falopio, por lo cual, se ha sugerido la realización de la salpingectomía oportunista como método de prevención primaria. La presente investigación tiene como objetivo determinar la frecuencia con que los ginecólogos adscritos a la Federación Colombiana de Ginecología y Obstetricia (FECOLSOG) incluyeron salpingectomías oportunistas en su práctica clínica durante los años 2017-2018. MÉTODOS: Se realizó una encuesta a los ginecólogos adscritos a la FECOLSOG. Las variables analizadas incluyeron características demográficas, práctica profesional, método de prevención primaria de cáncer de ovario en pacientes de bajo riesgo y la realización o no de la salpingectomía oportunista y sus respectivas razones. Las variables cualitativas se analizaron con frecuencias absolutas y relativas, mientras que las cuantitativas con medidas de tendencia central y desviaciones estándar con el software STATA 13. RESULTADOS: De 1765 ginecólogos contactados, 353 contestaron la encuesta (tasa de respuesta del 20%). El 62.5% de estos realizan salpingectomía oportunista en su práctica ginecológica y de estos, el 75.2% lo hizo para prevenir cáncer de ovario. Entre las razones manifestadas por los especialistas para no realizar salpingectomía oportunista, el 12.5% no la consideraba un factor de protección frente al cáncer de ovario y un 14.4% consideraba que incrementaba el riesgo de falla ovárica temprana y morbilidad asociada. CONCLUSIÓN: Aunque existen controversias en su realización, la salpingectomía oportunista muestra ser una conducta adoptada por ginecólogos adscritos a FECOLSOG. Se requieren investigaciones futuras para determinar la efectividad de la salpingectomía e implementar estrategias de prevención del cáncer epitelial de ovario.

INTRODUCTION AND OBJECTIVES: Ovarian cancer is the most lethal gynecological malignancy and 90% of cases are of epithelial origin. Recently, different investigations attribute their origin to the fimbriae of the fallopian tubes, reason why it has been suggested to perform elective salpingectomy for the prevention of high-grade adenocarcinoma, its most frequent histological variant. This research aims to determine the frequency with which gynecologists from the Colombian Federation of Gynecology and Obstetrics (FECOLSOG) included this procedure in their clinical practice during the years 2017-2018. METHODS: A survey was sent electronically to the gynecologists assigned to FECOLSOG on three different occasions with an interval of 15 days between them. The variables analyzed included demographic characteristics, professional practice, primary prevention method of Ovarian Cancer in low-risk patients and the performance or not of elective salpingectomy with their respective reasons. Qualitative variables were analyzed with absolute and relative frequencies, while quantitative variables with measures of central tendency and standard deviations with STATA 13 software. RESULTS: From 1765 gynecologists contacted at least once via email, 353 answered the survey, indicating a response rate of 20%. 62.5% perform elective salpingectomy in their gynecological practice and of these, 75.2% do so to prevent ovarian cancer. Among the reasons for not practicing salpingectomy, 12.5% ​​do not consider it a protective factor for ovarian cancer, and 14.4% believe that it increases the risk of early ovarian failure and morbidity. CONCLUSION: Elective salpingectomy is a promising procedure as a preventive measure against epithelial ovarian cancer. Although there are controversies regarding its performance, salpingectomy seems to be a common practice amongst gynecologists from FECOLSOG, and seems to have higher recurrence within this field. Future research is required to determine the effectiveness of salpingectomy and thus, implement the best strategies for ovarian cancer prevention.

SEOM clinical guidelines in hereditary breast and ovarian cancer (2019).

Mutations in BRCA1 and BRCA2 high penetrance genes account for most hereditary breast and ovarian cancer, although other new high-moderate penetrance genes included in multigene panels have increased the genetic diagnosis of hereditary breast and ovarian cancer families by 50%. Multigene cancer panels provide new challenges related to increased frequency of variants of uncertain significance, new gene-specific cancer risk assessments, and clinical recommendations for carriers of mutations of new genes. Although clinical criteria for genetic testing continue to be largely based on personal and family history with around a 10% detection rate, broader criteria are being applied with a lower threshold for detecting mutations when there are therapeutic implications for patients with breast or ovarian cancer. In this regard, new models of genetic counselling and testing are being implemented following the registration of PARP inhibitors for individuals who display BRCA mutations. Massive sequencing techniques in tumor tissue is also driving a paradigm shift in genetic testing and potential identification of germline mutations. In this paper, we review the current clinical criteria for genetic testing, as well as surveillance recommendations in healthy carriers, risk reduction surgical options, and new treatment strategies in breast cancer gene-mutated carriers.

Epidemiologia de cáncer de ovario colombia 2009- 2016 / Epidemiology of ovarian cancer colombia 2009- 2016

Resumen Introducción el cáncer es una de las enfermedades más temidas por la humanidad y el tumor maligno de ovario no es la excepción. Se caracteriza por su alta agresividad y por presentar síntomas inespecíficos, además de no contar, hasta el momento, con pruebas de tamizaje que permitan una detección precoz, convirtiéndose en uno de los cánceres femeninos con alta mortalidad ocupando el séptimo lugar a nivel mundial. Objetivo Medir la prevalencia, mortalidad y la letalidad asociadas al cáncer de ovario entre 2009 a 2016 en la población colombiana. Método se realizó un estudio descriptivo, transversal, ecológico. A partir de una base de datos en el RIPS de SISPRO y DANE se seleccionaron las mujeres con diagnóstico de tumor maligno de ovario. Resultados se hallaron 36.798 mujeres con diagnóstico de cáncer de ovario, la edad media fue de 63 años con una prevalencia de 31,66 por 100.000 mujeres, en los departamentos de Antioquia, Santander, y Bogotá. Se estimó una tasa de mortalidad de 3,9 por 100.000 mujeres, predominio en educación básica primaria, y régimen de seguridad social contributivo. La letalidad fue de 15,75%. Conclusiones En Colombia la prevalencia, mortalidad y letalidad entre 2009 a 2016 presentó una tendencia al incremento, predominio en casadas, bajo nivel educativo y menor acceso a los servicios de salud. En virtud de lo anteriormente expuesto, se abre la posibilidad de establecer prioridades sanitarias, diseño de futuras estrategias en prevención de la enfermedad en salud pública, detención precoz y con la consecuente disminución de la mortalidad.

Incidence of intraepithelial fallopian tube neoplasias in mexican women over 40 years of age that underwent elective hysterectomy.

AIMS: The incidence of intraepithelial neoplasia in the fallopian tubes of women over 40 years of age who had undergone elective hysterectomy was assessed at the Aguascalientes Women's Hospital. METHODS: An observational, prospective, descriptive study was carried out at the Aguascalientes Women's Hospital on female patients over 40 years of age who underwent elective hysterectomy between July and October 2017. In these 4 months, 85 patients underwent elective hysterectomy. RESULTS: In this study, 85 patients who received a hysterectomy for non-oncological reasons were analyzed. Salpinx alterations compatible with intraepithelial neoplasia in the Fallopian tubes were found in 2.4% of the patients studied. CONCLUSIONS: The incidence of intraepithelial neoplasia in the fallopian tubes of high-risk patients at the Aguascalientes Women's Hospital is 2.4%. Prophylactic salpingectomy is a simple procedure and has the potential to decrease the risk of high-grade ovarian cancer. In premenopausal patients, total abdominal hysterectomy with bilateral salpingectomy should be the procedure most often performed.

Cost effectiveness of the cancer prevention program for carriers of the BRCA1/2 mutation.

OBJECTIVE: To analyze the cost effectiveness of the diagnostic program for the germline mutation in BRCA1/2 genes and of preventative strategies for the relatives of patients diagnosed with ovarian cancer associated with this mutation. METHODS: The study analyzed the cost effectiveness by developing an analysis of the Markov decision process from the perspective of the National Health System. The strategies compared reflect upon the adoption of genetic testing and preventative strategies for relatives or the usual care currently proposed. The incremental cost-effectiveness ratio was expressed in terms of cost per case avoided. The sensitivity analysis was performed in a univariate and deterministic manner. RESULTS: The study showed increments for effectiveness and for costs when performing genetic testing and adopting prophylactic measures for family members. The incremental cost-effectiveness ratio was estimated at R$908.58 per case of cancer avoided, a figure considered lower than the study's cost-effectiveness threshold (R$7,543.50). CONCLUSIONS: The program analyzed should be considered a cost-effective strategy for the national situation. Studies in various other countries have reached similar conclusions. One possible ramification of this research might the need to perform a budgetary-impact analysis of making the program one of the country's health policies.

Gynecological-endocrinological aspects in women carriers of BRCA1/2 gene mutations.

Women carriers of mutations in the genes BRCA1 and BRCA2 coding for tumor suppressor proteins are at high risk of developing breast and ovarian cancers. Hereditary breast and ovarian cancers due to BRCA pathogenic mutations occur at earlier ages: mean age 43 years at diagnosis of breast cancer for BRCA1 mutations; onset of ovarian cancer up to 10-21% by age 50 years. Preventive strategies are then defined in the reproductive years. The National Comprehensive Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin with the affected cancer individual (BRCA1/2 full sequencing); then, family members should be tested for the specific gene mutation found. A woman known to be a carrier needs a strict specific surveillance strategy to achieve early diagnosis. The NCCN proposes breast imageneological surveillance beginning at age 25 years; ovarian surveillance beginning at age 30-35 years. Concomitantly, risk-reducing strategies should be analyzed: surgical or pharmacological. When prophylactic bilateral salpingo-oophorectomy is performed before menopause, estrogen replacement therapy could be required. For BRCA, we review the risks of cancer in mutations carriers, criteria for genetic testing, surveillance and risk-reduction strategies, and the safety of prescribing hormone therapy when needed.

Catalysts towards cancer risk management action: A longitudinal study of reproductive-aged women with BRCA1/2 mutations.

Deleterious mutations in BRCA1 or BRCA2 genes increase a woman's lifetime risk of breast and ovarian cancer. Risk management guidelines endorse early detection and prevention behaviors. Despite expressed intent, uptake of these measures remains low. This longitudinal, qualitative study integrated retrospective and prospective data to distinguish factors shaping intent to act from those that are catalysts to taking action to reduce cancer risk. Twelve BRCA1/2 mutation-positive women participating in the National Cancer Institute's Breast Imaging Study aged 18-35 completed two semi-structured interviews three years apart. Researchers completed focused coding to identify points of behavioral intent and action and contextual factors acting as catalysts upon participant narratives. All women shared only two action steps: seeking information about cancer risk and completing genetic testing. The constellation of action steps created a unique action trajectory that was defined, with precise ideas about risk perception and clear behavioral response, or iterative, in which unanticipated life events shifted the speed, accessibility, or order in which risk management and family planning goals were prioritized, planned, or executed. Factors shifting action steps included salient, unanticipated life events, such as infertility, insurance/financial constraints, birth of the last child, or a relative's cancer diagnosis. Focus on cancer morbidity may obfuscate how women prioritize actions, and ignore varied pragmatic, relational, and social factors affecting how intended actions are completed, particularly during the reproductive years. We recommend providers update patients' risk management plans at each visit to assess readiness for next steps and reduce reluctance to discuss, or guilt associated with, change.

Short report: Follow-up of Bahamian women with a BRCA1 or BRCA2 mutation.

PURPOSE: We sought to determine to what extent the knowledge of carrying a BRCA1 or BRCA2 mutation influences the uptake of preventive surgeries in Bahamian women, including bilateral salpingo-oophorectomy and bilateral mastectomy. PATIENTS AND METHODS: The study population consisted of 78 female residents of the Bahamas for whom a BRCA1 or BRCA2 mutation had been detected between 2004 and 2014. The mean age of the 78 participants at the time of genetic testing was 46 years (age range 22-73 years). The mean time of follow-up was 4.4 years. RESULTS: Of the 78 study participants, 19 women had a bilateral salpingo-oophorectomy (24%). Seven out of 37 patients who had unilateral breast cancer chose to remove the unaffected contralateral breast (19%). Three of 13 patients with no history of breast cancer chose to have a prophylactic bilateral mastectomy (23%). CONCLUSION: Preventive surgery is an acceptable option for a significant proportion of Bahamian women with a BRCA1 or BRCA2 mutation. It will be important to identify and reduce barriers to preventive surgery in the Bahamas in order that the benefit of getting testing can be fully realized.

Rastreamento do câncer de ovário / Screeening for ovarian cancer

Introdução: O câncer de ovário é uma das neoplasias com maior mortalidade no mundo. Esse dado se deve ao estágio avançado em que o tumor se encontra quando é diagnosticado. Em virtude disso, muitas pesquisas buscam métodos eficientes de rastreio para um diagnóstico e tratamento precoces. Métodos: Foi realizada a revisão sobre paciente com alto risco de câncer de ovário utilizando como base de dados o Pubmed, do qual foram selecionados artigos dos últimos 5 anos, com foco em revisões sobre rastreio e manejo dessas pacientes. Foi realizado consulta ao livro "Ginecologia básica e avançada" do Serviço de Ginecologia do Hospital São Lucas da PUCRS e aos sites do INCA e NCCN. Resultados: Nas análises reunidas, observou-se resultados desfavoráveis à realização dos exames para rastreio de câncer de ovário em paciente de baixo risco. Os estudos que mostram benefício intervencionista são os que avaliam o manejo cirúrgico em pacientes de alto risco para o desenvolvimento dessa neoplasia. Conclusão: Concluímos com a pesquisa realizada que não há evidências que justifiquem a aplicação de teste de rastreio para câncer de ovário para pacientes de baixo risco. Todavia, a cirurgia de salpingo-ooforectomia redutora de risco é recomendada em paciente com alto risco por apresentar significativa redução de mortalidade.

Introduction: Ovarian cancer is a very aggressive neoplasms. This is due to the advanced stage in which the tumor is found when it is diagnosed. As a result, many researches seek efficient screening methods for early diagnosis and treatment. Methods: The review was carried out on patients at high risk of ovarian cancer using a database Pubmed, from which articles were selected from the last 5 years, focusing on reviews on the screening and management of these patients. A consultation was made to the book "Ginecologia Básica e Avançada" of the Gynecology departament of the Hospital São Lucas da PUCRS and to the websites of INCA and NCCN. Results: In the analyzes, unfavorable results were observed in the ovarian cancer screening in a low-risk patient. Studies that show interventional benefit are those that evaluated the surgical management in patients at high risk for the development of this neoplasia. Conclusion: It was observed in the analysis that the studies still do not exist evidence that justify the application of screening test for ovarian cancer for patients of low risk. However, risk-reducing salpingo-oophorectomy surgery is recommended in a high-risk patient because of a significant reduction in mortality.