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.

A phase 2 trial of short-course Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) at interval cytoreductive surgery (iCRS) for advanced ovarian cancer / Quimioterapia Intraperitoneal Hipertérmica (HIPEC) de curta duração ao tempo da cirurgia citorredutora de intervalo (iCRS) para câncer de ovário avançado: ensaio clínico de fase 2

ABSTRACT Objective: to report the final analysis of a phase 2 trial assessing the efficacy and safety of short-course hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with advanced epithelial ovarian cancer (EOC). Methods: this was an open-label, multicenter, single-arm trial of HIPEC in patients with advanced EOC who underwent interval cytoreductive surgery (iCRS) after neoadjuvant chemotherapy (NACT). HIPEC was performed as a concentration-based regimen of platinum-based chemotherapy for 30 minutes. Primary endpoint was the rate of disease progression occurring at nine months following iCRS plus HIPEC (PD9). Secondary endpoints were postoperative complications, time to start adjuvant chemotherapy, length of hospital and ICU stay, quality of life (QoL) over treatment, and ultimately 2-year progression-free survival (PFS) and overall survival (OS). Analysis was by intention-to-treat with final database lock for survival outcomes on February 23, 2021. Results: fifteen patients with stage III EOC were enrolled between February 2015 and July 2019, in four centers. The intention to treat PD9 was 6.7%. With a median follow-up of 33 months (IQR, 24.3-46.5), the median PFS was 18.1 months and corresponding 2-year rates of PFS and OS was 33.3% and 93.3%, respectively. Three patients (20%) experienced graded III complications. Median length of hospital and ICU stay was 5 (IQR, 4-6.5) and 1 (IQR, 1-1) days, respectively. Time to restart systemic chemotherapy was 39 (IQR, 35-49.3) days and no significant difference over time in QoL was observed. Conclusions: we demonstrate preliminary efficacy and safety of short-course HIPEC in patient with advanced EOC.

RESUMO Objetivo: apresentar a análise final de ensaio clínico de fase 2 que avaliou a eficácia e a segurança da quimioterapia intraperitoneal hipertérmica (HIPEC) de curta duração em pacientes com câncer epitelial de ovário avançado (EOC). Métodos: estudo aberto, multicêntrico, de braço único avaliando a HIPEC em pacientes com EOC avançado submetidos a cirurgia citorredutora de intervalo (iCRS) após quimioterapia neoadjuvante (NACT). A HIPEC foi realizada como regime baseado na concentração de cisplatina, perfundida por 30 minutos. O desfecho primário foi a taxa de progressão da doença 9 meses após a iCRS com HIPEC (PD9). Os desfechos secundários foram complicações pós-operatórias, tempo para iniciar a quimioterapia adjuvante, tempo de internação e permanência em UTI, qualidade de vida (QoL) ao longo do tratamento e, finalmente, sobrevida cumulativa livre de progressão (PSF) e global (OS) em 2 anos. As análises foram em intenção de tratar (ITT) com fechamento dos dados para análise da sobrevida em 23 de fevereiro de 2021. Resultados: quinze pacientes com EOC em estágio III foram incluídos no estudo entre fevereiro de 2015 e julho de 2019 em quatro centros recrutadores. A PD9 por ITT foi de 6,7%. Com acompanhamento mediano de 33 meses (IQR, 24,3-46,5), a PFS mediana foi de 18,1 meses e as taxas correspondentes de PFS e OS em 2 anos foram 33,3% e 93,3%, respectivamente. Três pacientes (20%) apresentaram complicações grau III. O tempo mediano de internamento hospitalar e em UTI foi de 5 (IQR, 4-6,5) e 1 (IQR, 1-1) dias, respectivamente. O tempo para reinício da quimioterapia sistêmica foi de 39 dias (IQR, 35-49,3) e não foi observada diferença significativa na QoL ao longo do tratamento. Conclusões: demonstrou-se eficácia e segurança preliminares da HIPEC de curta duração em pacientes com EOC avançado.

Tratamiento de tumores malignos epiteliales de ovario en estadios avanzados. Experiencia del Hospital Italiano de Buenos Aires / Treatment of advanced epithelial ovarian tumor. Hospital Italiano de Buenos Aires experience

Resumen El cáncer de ovario ocupa el tercer lugar en frecuencia entre los cánceres ginecológicos en Argentina. Existe un déficit de información de esta enfermedad en nuestro país respecto al tratamiento y evolución oncológica de las pacientes. El objetivo de nuestro trabajo fue evaluar los resultados perioperatorios y oncológicos, en pacientes con tumor epitelial de ovario con estadios avanzados. Presentamos una cohorte retrospectiva en la que se evaluó la supervivencia libre de enfermedad y la supervivencia global en pacientes con tumores epiteliales de ovario tratadas en el Hospital Italiano de Buenos Aires entre junio del 2009 a junio del 2017. De 170 pacientes incluidas en el estudio, 72 (42.4%) fueron tratadas con una cirugía de citorreducción primaria (CCP), mientras que 98 (57.6%) recibieron neoadyuvancia y luego cirugía del intervalo (CI). La tasa de citorreducción óptima fue de 75% y de 79% respectivamente. No se encontraron diferencias en los resultados perioperatorios, ni en las complicaciones graves entre ambos grupos. La mediana de SLE en el grupo de CCP fue de 2.5 años (IC 95% 1.6-3.1) mientras que en el grupo de CI fue de 1.4 (IC 95% 1.2-1.7) p < 0.001. La mediana de supervivencia global fue de 5.8 años en CCP, y de 3.5 años en CI. En pacientes adecuadamente seleccionadas la CCP presenta mejores resultados oncológicos a la neoadyuvancia y CI. La selección correcta de las pacientes para tratamiento primario es fundamental para definir la conducta terapéutica.

Abstract Ovarian cancer represents the third gynecological cancer in frequency in Argentina. There is a lack of information on this pathology in our country regarding the treatment and evolution of patients who suffer it. The aim of this study was to evaluate the perioperative and oncological results in patients with advanced epithelial ovarian tumor. We present a retrospective cohort in which we evaluated disease-free survival and overall survival in patients with epithelial ovarian tumor treated at the Hospital Italiano de Buenos Aires between June 2009 and June 2017. Of 170 patients included in the study, 72 (42.4%) received primary debulking surgery (CCP), while 98 (57.6%) received neoadjuvant therapy and interval surgery (CI). The optimal cyto-reduction rate was 75% and 79% respectively. No differences were found in perioperative outcomes, or in severe complications between the two groups. The median disease-free survival in the CCP group was 2.5 years (95% CI 1.6-3.1) while in the CI group it was 1.4 (95% CI 1.2-1.7) p < 0.001. The median overall survival was 5.8 years in CPP, and 3.5 years in CI. Faced with a meticulous selection by a group of experts, patients with advanced ovarian cancer treated with CCP present better oncological results than those who received neoadjuvant therapy and CI.

Clinical significance of p27 Kip1 expression in advanced ovarian cancer

Background: Ovarian cancer is the most common gynecological malignancy. In patients with advanced ovarian cancer, some biological parameters have prognostic implementations. P27kip1 is an inhibitor of a cycline-dependent kinase, its loss, can contribute to tumor progression. Objective: This study aimed to examine the importance of P27KIP1 protein in predicting the prognosis and response to neoadjuvant chemotherapy in patients with advanced ovarian epithelial cancer and to compare the outcomes of immunohistochemistry with Quantitative Real-time PCR. Patients and methods: We have studied P27KIP1expression by both immunohistochemistry and Quantitative Realtime PCR from 88 patients with advanced ovarian carcinomas undergone radical debulking surgery and received Paclitaxel followed by Cisplatin every 3 weeks for a total of 6 cycles. We also studied their association with both chemotherapy response and patient survival. Results: Nuclear expression of p27KIP1 protein was intense in 86 normal ovarian tissues and 42 of 88 carcinomas. The P27kip1mRNA expression level by qRT-PCR was very low in ovarian cancer tissues relative to its adjacent normal tissues. The results were statistically significant by both methods of determination. p27KIP1 expression was significantly related to good prognostic parameters as low stage tumors, differentiated tumors, absence of ascites, residual disease < 2 cm, and response to chemotherapy but not with histopathological type in case of determination by immunohistochemistry. Comparison of P27kip1 by both immunohistochemistry and qRTPCR with different prognostic parameters revealed no significant difference between both methods in the assessment of these parameters. In 4 years of follow-up, 20.5% of patients were alive without evidence of disease. 6.8% were alive with disease. The disease-related four -year survival rate for the whole group was 28.2%. In multivariate analysis, residual disease, histological type, tumor differentiation, ascites was of independent prognostic significance. Conclusion: In ovarian cancer, patients with loss of p27KIP1 expression are at a greater likelihood of disease progression, p27KIP1 may be used as a molecular marker to predict response to chemotherapy and prognosis. Both immunohistochemistry and qRT-PCR have equal reliability in the determination of p27 KIP1

Cáncer de Ovario: Tamizaje y diagnóstico imagenológico / Ovarian Cancer: Screening and imaging diagnosis

Resumen El cáncer de ovario se ha caracterizado por ser la neoplasia ginecológica de peor pronóstico. Lo anterior es consecuencia del curso silente de la enfermedad que ocasiona que la mayoría de las veces el diagnóstico se realice en etapas avanzadas. La información recolectada señala que los avances terapéuticos no han demostrado ser efectivos en mejorar la sobrevida de las pacientes con cáncer de ovario, lo cual orienta a la búsqueda constante de un método (o conjunto de éstos), que permita llevar a cabo el tamizaje y la detección temprana de dicha patología. Sin embargo, debido a que actualmente no se ha logrado identificar un método que sea costo-efectivo para el tamizaje, el mismo no se aplica a la población general y se reserva para casos específicos, como mujeres con antecedentes familiares de la enfermedad o que presentan síndromes hereditarios. Esta revisión incluye además información sobre las diferentes técnicas de imagen utilizadas tanto para el estudio y caracterización de masas anexiales, como para el estadiaje y pronóstico del cáncer de ovario. De las técnicas estudiadas, el ultrasonido (US) demostró ser la mejor opción para el abordaje inicial de masas anexiales; sin embargo, a la hora de realizar el estadiaje resultó ser inferior a la tomografía computarizada (TC) y la resonancia magnética (RM).

Abstract Ovarian cancer is the gynecological malignancy with the worst prognosis. Due to the silent course of the disease the diagnosis is made mainly in advanced stages. The literature reviewed showed that the therapeutic advances have not shown any major improvement in patient´s survival with ovarian cancer, therefore there is a constant research for a technique (or a set of them) that allows a proper screening and early detection of the disease. However, a cost effective method has not been found for screening, therefore it is not recommended for general population and it is reserved for specific cases, such as women with family history of ovarian cancer and with hereditary syndromes. This review also includes information about the different imaging techniques available not only for the study and characterization of neoplasms, but also for staging and prognosis of ovarian cancer. The ultrasound proved to be the best option for the initial approach of adnexal masses, however it has shown to be inferior for staging than CT-Scan and MRI.

Overexpression of long noncoding RNA PTPRG-AS1 is associated with poor prognosis in epithelial ovarian cancer

SUMMARY OBJECTIVE Long noncoding RNAs (lncRNAs) have been shown to play a critical role in tumor progression. Abnormal expression of LncRNA PTPRG antisense RNA 1 (PTPRG-AS1) has been reported in several tumors. Hence, we aimed to determine the expression and clinical significance of PTPRG-AS1 in epithelial ovarian cancer (EOC) patients. METHODS The expressions of PTPRG-AS1 were assessed in 184 pairs of EOC tumor specimens and adjacent normal tissues. The levels of target lncRNAs and GAPDH were examined using standard SYBR-Green methods. The relationships between the expressions of PTPRG-AS1 and the clinicopathological features were analyzed using the chi-square test. Multivariate analysis using the Cox proportional hazards model was performed to assess the prognostic value of PTPRG-AS1 in EOC patients. RESULTS We confirmed that the expressions of PTPRG-AS1 were distinctly higher in the EOC tissue compared with the adjacent non-tumor specimens (p < 0.01). Higher levels of PTPRG-AS1 in EOC patients were associated with advanced FIGO stage (p = 0.005), grade (p = 0.006), and distant metastasis (p = 0.005). Survival analyses revealed that patients with high expressions of PTPRG-AS1 had a distinctly decreased overall survival (p = 0.0029) and disease-free survival (p = 0.0009) compared with those with low expressions of PTPRG-AS1. Multivariate assays indicated that PTPRG-AS1 expression was an independent prognostic factor for both overall survival and disease-free survival in EOC (Both p < 0.05). CONCLUSIONS Our study suggests that PTPRG-AS1 may serve as a novel prognostic biomarker for EOC patients.

RESUMO OBJETIVO Sabe-se que RNAs longos não codificantes (lncRNAs) desempenham um papel crítico na progressão tumoral. A expressão anormal do RNA 1 anti-senso LncRNA PTPRG (PTPRG-AS1) já foi relatada em diversos tumores. Assim, buscamos determinar a expressão e significância clínica do PTPRG-AS1 em pacientes com câncer de ovário epitelial (COE). METODOLOGIA As expressões do PTPRG-AS1 foram avaliadas em 184 pares de amostras tumorais de COE e tecidos normais adjacentes. Os níveis de lncRNAs e GAPDH alvo foram examinados usando o método padrão de SYBR Green. As relações entre as expressões do PTPRG-AS1 e as características clínico-patológicas foram analisadas através do teste qui-quadrado. Uma análise multivariada utilizando o modelo de riscos proporcionais de Cox foi realizada para avaliar o valor prognóstico do PTPRG-AS1 em pacientes com COE. RESULTADOS Constatou-se que as expressões do PTPRG-AS1 foram nitidamente maiores nos tecidos de COE em relação aos espécimes adjacentes não tumorosos (p<0,01). Níveis mais elevados do PTPRG-AS1 em pacientes com COE foram associados a um estágio avançado de FIGO (p = 0,005), grau (p = 0,006) e metástases à distância (p = 0,005). As análises de sobrevida revelaram que pacientes com expressões elevadas do PTPRG-AS1 tiveram uma diminuição significativa da sobrevida global (p = 0,0029) e da sobrevida livre de doença (p = 0,0009) em relação àqueles com baixas expressões do PTPRG-AS1. As análises multivariadas indicaram que a expressão do PTPRG-AS1 foi um fator de prognóstico independente tanto para a sobrevida global quanto para a sobrevida livre de doença em pacientes com EOC (p < 0,05). CONCLUSÃO Nosso estudo sugere que o PTPRG-AS1 pode ser um novo biomarcador prognóstico para pacientes com COE.

Primary broad ligament adenocarcinoma

Primary broad ligament carcinoma is a very rare occurrence with 28 reported cases worldwide, to date. The epidemiology, treatment strategy and prognosis are still uncertain because of the scarcity of cases. Currently, all broad ligament carcinomas are managed similar to epithelial ovarian cancer. We report the case of a 43-year-old female with a prolonged complaint of abdominal pain and intermittent urinary retention, requiring frequent catheterization. She was diagnosed with obstructive right hydroureteronephrosis. The abdominal Contrast Enhanced Computed Tomography (CECT) revealed a well-defined heterogeneous lesion of 2.1х3х3.2cm size in the right lateral and posterior wall of the cervix. An ultrasound (USG)-guided Fine Needle Aspiration Cytology (FNAC) of the mass was done and it was suspected to be malignant. The patient underwent total abdominal hysterectomy, right salpingo-oophorectomy, pelvic lymph-nodal sampling, and peritoneal washing. Histological examination depicted an endometrioid adenocarcinoma of the broad ligament. She received adjuvant chemotherapy, followed by hormonal therapy. It has been five years since her surgery, and she is now alive and disease free.

Diseño de un panel de citometría de flujo para muestras de sangre, ascitis y tejido ovárico / Design of a multicolored flow cytometry panel for blood, ascites and ovarian tissue samples

Introducción: El cáncer epitelial de ovario (CEO) ocupa el sexto lugar en incidencia y mortalidad a nivel mundial y en Cuba, el quinto en incidencia. Este cáncer es inmunogénicoy sus células malignas crecen en interacción conlas células inmunitarias. Su curso clínico depende del infiltrado inflamatorio acompañante del tumor. La citología e histopatología son los métodos diagnóstico de elección. Sin embargo, la citometría de flujo emerge como una tecnología de mayor sensibilidad, objetividad y rapidez. Objetivo: Diseñar un panel multicolor de citometría de flujo para inmunofenotipar el infiltrado linfocitario de tres tipos de muestras de pacientes con CEO. Métodos: Se realizó un diseño experimental, para la creación y evaluación de un panel multicolor de citometríade flujo, en el laboratorio de Inmunología del Instituto Nacional de Oncología y Radiobiología. El panel se diseñó en sangre de 3 sujetos sanos y se optimizó para sangre periférica en 33 sujetos sanos y, en sangre periférica, ascitis y tejido tumoral ovárico de tres pacientes con CEO. En cada muestra se inmunofenotiparon varias poblaciones linfocitarias. Resultados: Se seleccionaron 11 marcadores antigénicos para el inmunofenotipo, el panel quedó conformado por 4 tubos de citometría. La metodología se pudo aplicar a las muestras de ascitis y tejido tumoral sin interferencias, se obtuvieron porcentajes de las subpoblaciones linfocitarias dentro de los valores esperados. Conclusiones: El panel diseñado permitió inmunofenotipar linfocitos en distintos tipos de muestras de pacientes con CEO, con resultados confiables y reproducibles. Esta metodología puede extenderse a la realización de inmunofenotipaje en otras enfermedades(AU)

Introduction: Epithelial ovarian cancer occupies the 6th place in incidence and mortality in women worldwide. In Cuba, it occupies the 5th place in incidence in females. This cancer is immunogenic and its malignant cells grow in interaction with multiple cells from immune system. Its clinical course depends largely on the type of inflammatory infiltrate accompanying the tumor. Cytology and histopathology are gold standard as diagnostic methods. However, flow cytometry emerges as a technology with greater sensitivity, objectivity and speed. Objective: To design a multicolored flow cytometry panel to immunophenotype the lymphocytic infiltrate of three types of samples for patients with ovarian cancer. Methods: An experimental design was carried out in vitro for the creation and evaluation of a multicolored flow cytometry panel in the Immunology laboratory of the National Institute of Oncology and Radiobiology of Cuba. The panel was designed in the blood of three healthy subjects; then it was optimized for blood in 33 healthy volunteers and blood, ascites and ovarian tumor tissue, from three patients with epithelial ovarian cancer. Several lymphocytes lineages were immunophenotypedin each sample. Results: Eleven markers were selected for the immunophenotype and the panel was made up of four multiparameter cytometry tubes. The methodology created could be applied to the samples of ascites and tumor tissue without interferences and percentages of different lymphocyte subpopulations were obtained within the expected values. Conclusions: The designed panel allowed immunophenotyping of lymphocytes in different types of ovarian cancer patient samples and reliable and reproducible results were obtained. This methodology could be employed for others diseases(AU)

Supervivencia de pacientes con cáncer epitelial de ovario en el Instituto Nacional de Cancerología, resultados a partir del registro hospitalario de cáncer (2005-2014) / Survival of patients with epithelial ovarian cancer, results of the hospital-based cancer registry of the National Cancer Institute (2005-2014)

Resumen Objetivo: Proporcionar características demográficas y clínicas, así como estimaciones de supervivencia global a tres años de pacientes con cáncer epitelial de ovario (CEO) tratadas entre 2005 y 2014 en el Instituto Nacional de Cancerología de Colombia (INC). Métodos: Se incluyeron 783 pacientes diagnosticadas y tratadas por primera vez en el INC por CEO en los periodos 2005-2008, 2009-2011 y 2012-2014 sin un diagnóstico previo de otro cáncer. Se cruzaron datos del registro hospitalario de cáncer con bases de datos gubernamentales para obtener información de seguimiento. Utilizando el método Kaplan-Meier se estimó la probabilidad de sobrevivir a 36 meses a partir de la fecha de ingreso, evaluando diferencias en supervivencia entre grupos con la prueba de rango logarítmico. Se utilizaron modelos multivariados de riesgos proporcionales de Cox para evaluar: el efecto relativo de edad, el estadio clínico, el subtipo histológico y el tipo de tratamiento inicial en la supervivencia. Resultados: La probabilidad de supervivencia global a 36 meses fue de 56,5% (IC 95%: 53,0; 60,0), que se mantuvo estable en los tres periodos. La edad avanzada, el estadio clínico y el subtipo histológico afectaron significativamente la supervivencia global a tres años: 49,5% (IC 95%: 43; 55,6) para mujeres >59 años; 21,9% (IC 95%: 14,7; 29,2) para la enfermedad en estadio IV y 56,3% (IC 95%: 37,5; 54,3) para los tumores serosos. Las estimaciones de hazard fueron significativamente más altas en pacientes de 59 años o más (HR 1,54 (IC del 95%: 1,04 a 2,27)) y en cánceres con estadio avanzado (HR 13,47 (IC 95%: 7,92-22,92)); la cirugía más quimioterapia tuvo una reducción en el riesgo en comparación con otros tratamientos (HR 0,84 (IC 95% 0,52-1,36). Conclusiones: La supervivencia del cáncer epitelial de ovario se mantuvo estable con el tiempo. La variación se presentó en factores como: la edad, el estadio clínico y el primer tratamiento.

Abstract Aims: To provide demographical and clinical characteristics and estimations of 3-year overall survival of epithelial ovarian cancer (EOC) patients treated at the Colombian National Cancer Institute (INC) between 2005 and 2014. Methods: All 783 patients first treated at INC for EOC in the three periods: (2005-2008, 2009-2011, 2012-2014), without a prior cancer diagnosis, were included in this study. Follow-up was realized by cross-linkage with governmental databases using person identification numbers. Probability of surviving 36 months since the date of entry at INC was estimated using Kaplan-Meier methods, using the log-rank test to evaluate differences between groups. We used multivariate Cox proportional hazard models to evaluate the relative effect of age, clinical stage, histological subtype and treatment first on survival. Results: The overall survival probability at 36 months was 56.5% (95% CI: 53.0, 60.0), which was stable over time. Advanced age and clinical stage significantly affected 3-year overall survival, being 49.5°% (95°% CI: 43.4, 55.6) for age > 59, 21.9°% (95°% CI: 14.7, 29.2) for stage IV disease and 56.3% (95% CI: 37.5, 54.3) for serous tumors. Hazard ratios were significantly higher for patients aged 59 and over (HR 1.54 (95%CI 1.04-2.27)) and advanced stage cancers (HR 13.47 (95%CI 7.92-22.92)), whereas patients with surgery plus chemotherapy had a strongly reduced risks compared to other treatments (HR 0.84 (95%CI 0.52-1.36)). Conclusions: Survival of epithelial ovarian cancer was stable over time, with a variation according to age, clinical stage and first treatment.

Expresión de p53 en ovario y trompa uterina de tumores malignos epiteliales primarios del ovario / Ovary and fallopian tube expression of p53 in primary epithelial ovarian cancer

Introducción: la mutación en el gen TP53 se ha asociado con la oncogénesis de los tumores de ovario tipo II. Se ha propuesto que las mutaciones de p53 se inician en las células de la trompa uterina y después migran al ovario. El objetivo de este estudio es establecer la frecuencia de la expresión de p53 en ovario y trompa uterina en carcinoma epitelial primario de ovario. Materiales y métodos: estudio de corte transversal en tumores primarios epiteliales de ovario. Se evaluó la expresión de p53 por inmunohistoquímica en el ovario y en las trompas uterinas. Resultados: se incluyeron 45 pacientes con edad media de 55 años. Se estudiaron 24 casos de carcinomas serosos, 6 endometrioides, 5 mixtos, 3 de células claras, 3 carcinosarcomas, 2 carcinomas mucinosos y 2 indiferenciados. Se observó positividad fuerte y difusa en 68% de los tumores tipo II. En 52 hubo positividad en trompa uterina y ovario, 92% con compromiso bilateral. En 3 de estos casos se reconoció carcinoma intraepitelial tubárico con positividad de p53 en el área tumoral, no tumoral y en el carcinoma seroso. Conclusión: como se ha observado en estudios previos, el gen TP53 está involucrado en la oncogénesis de los tumores tipo II y se ha demostrado que existe una relación entre una mutación inicial de p53, seguida por STIL, STIC, evolucionando a un carcinoma seroso de ovario.

Introduction: a TP53 gene mutation has been associated with the oncogenesis of type II ovary tumors. Mutations of the p53 gene in the fallopian tube cells which migrate to the ovary have been proposed as an alternative origin. This study focuses on establishing the frequency of p53 ovary and uterine tube expression in primary epithelial ovarian cancer. Materials and Methods: a cross-sectional study on primary epithelial ovarian tumors. Expression of p53 in the ovary and uterine tubes was assessed using immunohistochemistry. Results: 45 patients, median age 55 years, were included. Twenty-four (24) cases of serous carcinomas, 6 endometrioid carcinomas, 5 mixed carcinomas, 3 clear-cell carcinomas, 3 carcinosarcomas, 2 mucinous carcinomas and 2 undifferenciated tumors were studied. Positivity was strong and diffuse in 68% of type II tumors. Positivity was detected in the tubes and ovaries in 52 cases, 92% with bilateral compromise. Intraepithelial tube carcinoma was recognized in 3 cases with p53 positivity in the tumor, outside the tumor and in the serous carcinoma. Conclusion: as observed in previous studies, TP53 gene is involved in the oncogenesis of type II tumors and a correlation between the initial p53 mutations followed by STIL, STIC progressing to an ovary serous carcinoma has been demonstrated.

Carcinoma de ovario en paciente con mutación del gen BRCA1. Diagnóstico tras biopsia de adenopatía cervical, en el contexto de un síndrome paraneoplásico cutáneo / Ovarian carcinoma in a patient with a BRCA1 gene mutation. Diagnosis after biopsy of cervical adenopathy, in the context of a cutaneous paraneoplastic syndrome

RESUMEN El cáncer epitelial de ovario representa uno de los tumores ginecológicos más letales ya que más del 75% de las pacientes son diagnosticadas en estadío avanzado. Aún no se ha demostrado que la realización de pruebas y exámenes pélvicos rutinarios haya reducido la mortalidad, no existiendo actualmente, un cribado eficaz para su diagnóstico precoz. Aunque la sintomatología metastásica extraperitoneal más común es el derrame pleural, las linfadenopatías neoplásicas a nivel supraclavicular aparecen hasta en el 4% de casos, generalmente asociándose a un mal pronóstico. La identificación de una adenopatía supraclavicular se relaciona hasta en un 58-83% de los casos, con el hallazgo de una tumoración maligna. Por otro lado, la dermatomiositis del adulto puede tener un origen paraneoplásico en un 15-25% de las ocasiones, siendo el cáncer de mama y de ovario la etiología más frecuente en la población femenina. Las pacientes portadoras de mutaciones en los genes BRCA 1 y 2 tienen un aumento del riesgo de padecer neoplasias de mama y ovario. En aquellas afectas de un cáncer de ovario y portadoras de una mutación en los genes BRCA, no se debería plantear una cirugía profiláctica de rutina sobre la mama, al menos en los primeros 5 años tras el diagnóstico de la neoplasia ovárica. Presentamos el caso de una paciente portadora de una mutación germinal del gen BRCA 1, que debuta con un cáncer de ovario, tras el estudio de una adenopatía neoplásica de cuello, biopsiada en el contexto de un síndrome paraneoplásico cutáneo.

ABSTRACT Epithelial ovarian cancer represents one of the most lethal gynecological tumors, since more than 75% of affected women are diagnosed at an advanced stage. However, studies have not demonstrated yet that performing routine pelvic exams and tests had reduced mortality in ovarian cancer, and currently there is no effective screening for early diagnosis. The most common extraperitoneal metastatic symptomatology of ovarian cancer is pleural effusion, but there are other, like neoplastic lymphadenopathies at supraclavicular level, described in up to 4% of cases and generally related to a poor prognosis. The identification of a supraclavicular adenopathy is associated with the finding of a malignant tumor in 58-83% of the cases. On the other hand, adult dermatomyositis can have a paraneoplastic origin in 15-25% of patients, being breast and ovarian cancer the most frequent etiology in the female population. Patients with BRCA 1 and 2 genes mutations have an increased risk of breast and ovarian malignancies. In those affected by an ovarian cancer and carriers of a mutation in the BRCA genes, routine prophylactic surgery should not be considered on the breast, at least in the first 5 years after the diagnosis of ovarian neoplasia. We present the case of a patient with a germinal mutation of the BRCA 1 gene, who debuts with an ovarian cancer, after the study of a neoplastic adenopathy of neck, biopsied in the context of a cutaneous paraneoplastic syndrome.

Homologous recombination deficiency in ovarian cancer: a review of its epidemiology and management

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.

Acute Abdomen Secondary to Ruptured Epithelial Ovarian Cancer during Pregnancy: The Relevance of Teamwork / Abdome agudo secundário à ruptura do câncer do ovário epitelial durante a gravidez: a importância do trabalho em equipe

Abstract Acute abdomen secondary to epithelial ovarian cancer rupture during pregnancy is a rare event. Our aim is to present how the work of a coordinated multidisciplinary team in a case of ruptured epithelial ovarian cancer during pregnancy is feasible to obtain the best results possible. A 34-year-old woman during the 37th week of her first gestation presented with an acute abdomen. During laparotomy, a ruptured 16.5-cm left ovarian tumor was detected; the tumor was extirpated and sent to pathologic evaluation. In the meantime, a Kerr cesarean section was performed, and a healthy female neonate was born. The tumor was diagnosed as a cystadenocarcinoma; therefore, the family and the combined surgical team (obstetricians and a surgical oncologist) decided to complete a definitive radical ovarian cancer surgery: hysterectomy, right salpingooophorectomy, lymphadenectomy, omentectomy and appendectomy. The patient's postoperative evolution was uneventful, and she was sent to adjuvant chemotherapy.

Resumo O abdome agudo secundário à ruptura do câncer do ovário epitelial durante a gravidez é um evento raro. Nosso objetivo é apresentar como o trabalho de uma equipe multidisciplinar coordenada em um caso de ruptura do câncer de ovário epitelial durante a gravidez é viável para obter os melhores resultados possíveis. Umamulher de 34 anos de idade, durante a 37a semana de sua primeira gestação, apresentou um abdome agudo. Durante a laparotomia, foi detectado um tumor ovariano esquerdo com ruptura de 16,5 cm; O tumor foi extirpado e enviado para avaliação patológica. Enquanto isso, uma cesariana de Kerr foi feita, e uma recém-nascida saudável nasceu. O tumor foi diagnosticado como um cistoadenocarcinoma; então, a família e a equipe cirúrgica combinada (obstetras e oncologista cirúrgico) decidiram concluir uma cirurgia radical definitiva do câncer de ovário: histerectomia, salpingo-ooforectomia direita, linfadenectomia, omentectomia e apendicectomia. A evolução pós-operatória da paciente foi sem intercorrências, e ela foi enviada para quimioterapia adjuvante.

Caracterización de las pacientes con cáncer de ovario. Hospital Gineco-Obstétrico "Ramón González Coro" 2001-2013 / Characterization of patients with ovarian cancer. Gyneco-obstetric Hospital "Ramón González Coro" 2001-2013

Introducción: actualmente en Cuba y en todo el mundo, el cáncer de ovario representa la octava causa más importante de neoplasias malignas en la mujer, pero es la cuarta causa relacionada con la mortalidad. Objetivo: identificar el comportamiento por tipos histológicos y por tratamientos del cáncer de ovario. Materiales y métodos: se realizó un estudio descriptivo, retrospectivo, de pacientes con cáncer de ovario, atendidas en el Hospital "Ramón González Coro", La Habana. En el período comprendido entre enero de 2001 a julio de 2013. Las unidades de análisis fueron las historias clínicas de las 98 pacientes que se estudiaron. Resultados: se observó que 69,3 % tenían entre 31 y 60 años de edad. La edad promedio del grupo completo fue 48,2 años, la mitad de las pacientes no refirieron antecedentes patológicos. La paridad promedio fue 1,3. En 3,1 % tenían antecedentes de una neoplasia maligna confirmada y tratada, 14,3 % poseían antecedentes familiares maternos de neoplasia maligna; siendo el motivo de consulta más frecuente el "dolor en bajo vientre" (40,8 %). No hubo asociación significativa entre los estadios (FIGO) y el tipo de cáncer. Conclusiones: los resultados obtenidos se comportan, en general, de acuerdo a patrones epidemiológicos reportados internacionalmente, aunque la frecuencia de cáncer epitelial fue menor que la referida en la literatura consultada. La mayoría de los cánceres estudiados estaban en estadios I y III (AU).

Background: currently in Cuba and around the world, the ovarian cancer represents the eighth most important cause of malignant neoplasia in women, but it is the fourth cause related with mortality. Objective: identifying behavior by histological types and by ovarian cancer treatment. Materials and methods: a descriptive, retrospective study was carried out in patients with ovarian cancer attended in the Hospital "Ramón González Coro", Havana, in the period between January 2001 and July 2013. The analysis units were the clinical records of the 98 studied patients. Outcomes: it was observed that 69.3 % were aged 31-60 years. The average age of the entire group was 48.2 years; half of the patients did not refer pathological antecedents. The average parity was 1.3. 3.1 % had antecedents of confirmed and treated malignant neoplasia; 14.3 % had maternal antecedents of malignant neoplasia, being the most frequent motive of consultation "pain in the low womb" (40.8 %). There was not significant association between the stages (FIGO) and the cancer type. Conclusions: the obtained results behave, in general, according to the epidemiological patterns internationally reported, though the frequency of the epithelial cancer was lower than the one referred in the consulted literature. Most of the studied cancers were in stages I and III (AU).

Prognostic Value of ADAMTS Proteases and Their Substrates in Epithelial Ovarian Cancer

Background: ADAMTS are metalloproteases with disintegrin and thrombospondin motifs. They are secreted proteases playing a role in biological processes such as inflammation, angiogenesis, and urogenital development. ADAMTS have specific substrates, such as the proteoglycans (PG) versican, aggrecan, and brevican. Despite data indicating a role of ADAMTS in tumor invasion and metastases, effects played by these molecules in cancer progression are still controversial. In ovarian cancer, the importance of ADAMTS gene mutations was recently described and related to chemotherapy outcome. Objective: To analyze protein levels of ADAMTS-1, -4, and -5, and TIMP-3 in human ovarian cancer classified as benign, borderline, or malignant. We also assessed the expression of the ADAMTS substrates aggrecan, brevican, and versican in these neoplasms. Correlations between overall survival and protein expression were performed. Methods: Tumors were classified according to the WHO Classification of Tumors of Female Reproductive Organs. Protein and PG expression was studied by immunohistochemistry. Differences in labeling were analyzed by percent measurements of stained areas. Results: ADAMTS-1, ADAMTS-5, and its tissue inhibitor TIMP-3 are increased in borderline and malignant tumors compared to benign neoplasms. Aggrecan and versican levels were increased in malignant subtypes compared to benign ovarian cancer. Higher ADAMTS-1, TIMP-3, and versican expression was associated with a shorter overall survival. Conclusions: Comparison of protease, TIMP-3, and substrate expression showed that in malignant tumors all ADAMTS and TIMP-3 expression levels were significantly raised compared to the substrates studied.

Cáncer serosopélvico de alto grado: evidencia sobre su origen en la trompa de Falopio / High-grade serous pelvic cancer: evidence of its origin in the fallopian tube

Cáncer epitelial de ovario es una enfermedad altamente letal. Constituye la quinta causa de muerte por cáncer en mujeres a nivel mundial. El subtipo histológico más frecuente es el carcinoma seroso de alto grado. Este es el responsable de la alta letalidad de la enfermedad. Se presenta evidencia que respalda el origen tubario de este tipo histológico desde lesiones precursoras. A partir de estos datos se ha establecido que el cáncer tradicionalmente conocido como cáncer ovárico seroso de alto grado, el cáncer de trompa de Falopio y el carcinoma peritoneal primario, corresponden a una misma entidad nosológica: cáncer seroso pélvico de alto grado. Se revisa además la evidencia disponible para establecer que la salpingectomía podría constituir una medida de prevención para este tipo de cáncer.

Epithelial ovarian cancer is a highly lethal disease. It is the 5th cause of cancer death in women worldwide. The most common histologic subtype is the high-grade serous carcinoma. This is the responsible for the high lethality of the disease. Evidence supporting the tubal origin of this histological type from precursor lesions is presented. From these data it has been established that cancer traditionally known as serous high-grade ovarian cancer, cancer of the fallopian tube and primary peritoneal carcinoma, correspond to a single disease entity: pelvic serous high-grade cancer. We also check the available evidence to establish that the salpingectomy could be a preventive measure for this type of cancer.

Cáncer epitelial avanzado de ovario en un grupo de pacientes colombianas / Advanced epithelial ovarian cancer in a group of colombian patients

Objetivo: Describir la experiencia de 14 años del Instituto Nacional de Cancerología de Colombia en el tratamiento de los estados avanzados de cáncer epitelial de ovario. Métodos: Estudio observacional retrospectivo tipo serie de casos que incluyó pacientes con cáncer epitelial de ovario en estados III y IV, las cuales fueron llevadas a tratamiento primario en el Instituto Nacional de Cancerología entre el 1 de enero de 1997 y el 31 de diciembre de 2011. Resultados: Se identificación 119 pacientes para el período de interés. Con una mediana de edad de 56 años, la mayoría de pacientes presentó compromiso en el estado funcional (63,9%) e hipoalbuminemia (82,4%). El tipo histológico más frecuente fue el adenocarcinoma seroso (62,2%), y el grado histológico mal diferenciado ocurrió en el 63,3% de los casos. Un 94,1% de los pacientes presentó compromiso de superficies peritoneales, con afectación de abdomen superior en un 38,7% y enfermedad extraabdominal un 29,4%. Se tuvo como intención de tratamiento la cirugía primaria más quimioterapia adyuvante en el 89,1% de las pacientes, logrando una citorreducción óptima en el 25,2% de los casos. El 29% presentó progresión durante el tratamiento y en un 57% se registró recaída. La mediana de supervivencia libre de enfermedad fue de 16,61 meses, y la de supervivencia global, de 28,93 meses. Conclusiones: Las pacientes con cáncer epitelial de ovario avanzado de nuestro medio se presentan con alta carga tumoral y con un comportamiento agresivo de la enfermedad reflejado en un pobre resultado oncológico.

Objective: To describe fourteen years of experience of in the treatment of advanced stages of epithelial ovarian cancer in the National Cancer Institute of Colombia. Methods: A retrospective observational case series including patients with epithelial ovarian cancer in stages III and IV, who received primary treatment in National Cancer Institute of Colombia between January 1st, 1997 and December 31th, 2011. Results: A total of 119 patients were identified durin the study period. With a median age of 56 years, most patients showed functional status compromise (63.9%) and hypolbuminemia (82.4%). The most common histological type was serous adenocarcinoma (62.2%) and there was poorly differentiated histological grade in 63.3% of cases. Almost all (94.1%) patients had peritoneal surfaces compromise with involvement of the upper abdomen in 38.7% and extra-abdominal disease in 29.4%. Treatment with primary surgery plus adjuvant chemotherapy was performed on 89.1%, achieving optimal cytoreduction in 25.2%; 29% of cases showed progression during treatment, and 57% of them relapsed. The median disease-free survival was 16.61 months, and the overall survival was 28.93 months. Conclusions: In our setting, patients with advanced epithelial ovarian cancer have a high tumor burden and aggressive behavior of the disease, reflected in a poor oncological outcome.