Características clínicas en pacientes con menos de 12 folículos ováricos como hallazgo ecográfico / Clinical and ultrasound findings in patients with ovaries with a count of less than 12 follicles

Introducción y objetivos: Determinar los hallazgos clínicos y ecográficos en pacientes que presentan menos de 12 folículos ováricos. Método: Estudio observacional (cohorte histórica) con 505 pacientes seleccionadas mediante muestreo consecutivo, entre el 14 de enero del 2019 y el 15 de marzo del 2021, que consultan por diversas alteraciones ginecológicas. Se generan dos grupos de pacientes, las que presentaron uno a tres folículos en uno de los ovarios (n = 377) y las que presentaban 4 a 11 folículos (n = 128). Se midió como resultado primario la presencia de al menos un signo clínico de hiperandrogenismo. Resultados: De 505 pacientes analizadas, al comparar las que presentaron 4 a 11 folículos en uno de los ovarios (n = 377) con las que presentaban 1 a 3 folículos (n = 128), las primeras mostraron mayor presencia de signos de hiperandrogenismo, endometrio en fase lútea de mayor espesor y un patrón menstrual con uno a cuatro días de sangrado menstrual abundante, diferencias todas estadísticamente significativas (p < 0,05). Conclusión: En pacientes con 4 a 11 folículos en uno de sus ovarios, se observaron signos de hiperandrogenismo, similares al síndrome de ovario poliquístico.

Introduction and objectives: Determine the clinical and ultrasound findings in patients who present less than 12 ovarian follicles in the ultrasound count. Method: Observational study (historical cohort) with 505 patients selected by consecutive sampling, between January 14, 2019 and March 15, 2021, who consulted for different gynecological disorders. Two groups of patients were generated: those with 1 to 3 follicles in one of the ovaries (n = 377) and those with 4 to 11 follicles (n = 128). The primary outcome was the presence of at least one clinical sign of hyperandrogenism. Results: Of 505 patients analyzed, when comparing those who presented 4 to 11 follicles in one of the ovaries (n = 377) with those who presented 1 to 3 follicles (n = 128), the first group showed a greater presence of signs of hyperandrogenism, thicker endometrium in luteal phase and a menstrual pattern with one to four days of heavy menstrual bleeding, all differences were statistically significant (p < 0.05). Conclusion: In patients with 4 to 11 follicles in one of their ovaries, signs of hyperandrogenism, similar to polycystic ovary syndrome, were observed.

Prevalencia de endometritis crónica en mujeres infértiles establecida mediante histeroscopia y biopsia endometrial con CD138 / Prevalence of chronic endometritis in infertile women by hysteroscopy and endometrial biopsy with CD138

Resumen OBJETIVO: Determinar, mediante histeroscopia de evaluación y biopsia de endometrio, con análisis histológico endometrial e identificación de células plasmáticas con inmunohisdtoquímica con CD138 positiva, la prevalencia de endometritis crónica en pacientes infértiles. MATERIALES Y MÉTODOS: Estudio observacional, retrospectivo, efectuado de marzo de 2016 a noviembre del 2021 en el Centro de Reproducción Asistida de Saltillo (CREAS), Coahuila, México, en pacientes que consultaron por infertilidad. El diagnóstico de endometritis crónica se estableció mediante histeroscopia y biopsia de endometrio con inmunohistoquímica CD138. Se analizaron la prevalencia y precisión diagnóstica de la histeroscopia y la biopsia de endometrio. Además, la relación entre las características histeroscópicas específicas y la endometritis crónica confirmada por biopsia con CD138 positiva. RESULTADOS: La prevalencia de endometritis crónica por biopsia de endometrio CD138 positiva en las 170 pacientes estudiadas fue de 36% (n = 62) y por histeroscopia del 48.8% (n = 83), esta última con una sensibilidad del 48.3%, especificidad del 50.9%, valor predictivo positivo y negativo del 36.1 y 63.2%, respectivamente. En relación con las características histeroscópicas, la hiperemia endometrial tuvo una relación estadísticamente significativa con la prevalencia de endometritis crónica (p-value = 0.008; RM = 0.357; IC95%: 0.14-0.81) y con ≥ 2 características sugerentes de endometritis crónica (p-value = 0.015; RM = 3.63; IC95%: 1.15-12.69). CONCLUSIONES: En el procedimiento diagnóstico de la paciente infértil es importante descartar la endometritis crónica. Para ello es decisivo recurrir a herramientas diagnósticas, como la histeroscopia y confirmar el diagnóstico con una biopsia de endometrio con inmunohistoquímica CD138 positiva para que de esta manera pueda dirigirse el tratamiento.

Abstract OBJECTIVE: To determine the prevalence of chronic endometritis in infertile patients by evaluating hysteroscopy and endometrial biopsy with endometrial histologic analysis and identification of plasma cells by CD138-positive immunohistochemistry. MATERIALS AND METHODS: Observational, retrospective study performed from March 2016 to November 2021 at the Center for Assisted Reproduction of Saltillo (CREAS), Coahuila, Mexico, in patients who consulted for infertility. Chronic endometritis was diagnosed by hysteroscopy and endometrial biopsy with CD138 immunohistochemistry. The prevalence and diagnostic accuracy of hysteroscopy and endometrial biopsy were analysed. The association between specific hysteroscopic features and chronic endometritis confirmed by CD138-positive endometrial biopsy was also investigated. RESULTS: The prevalence of chronic endometritis by CD138-positive endometrial biopsy in the 170 patients studied was 36% (n = 62) and by hysteroscopy 48.8% (n = 83), the latter with a sensitivity of 48.3%, specificity of 50.9%, positive and negative predictive values of 36.1 and 63.2%, respectively. In relation to hysteroscopic features, endometrial hyperemia had a statistically significant relationship with the prevalence of chronic endometritis (p-value = 0.008; RM = 0.357; 95%CI: 0.14-0.81) and with ≥ 2 features suggestive of chronic endometritis (p-value = 0.015; RM = 3.63; 95%CI: 1.15-12.69). CONCLUSIONS: In the diagnostic process of infertile patients, it is important to exclude chronic endometritis. It is crucial to use diagnostic tools such as hysteroscopy and to confirm the diagnosis by endometrial biopsy with positive CD138 immunohistochemistry in order to guide treatment.

Netrina-1 en sangre como biomarcador para la detección del cáncer de endometrio / Serum Netrin-1 as a biomarker for Endometrium Cancer detection

RESUMEN Investigar la relación de la netrina-1 preoperatoria con factores clinicopatológicos y pronósticos importantes y los niveles de corte adecuados en pacientes con cáncer de endometrio. En este estudio prospectivo y observacional, el grupo de casos y el de controles se seleccionaron entre las pacientes que acudieron a la Clínica de Oncología Ginecológica. Se extrajeron 4 mL de sangre venosa en un tubo de bioquímica de cada paciente durante el período preoperatorio. Los valores de netrina para predecir la presencia de malignidad se analizaron mediante el análisis de la curva ROC (receiver operating characteristics). El valor de corte se calculó según el índice de Youden. En el estudio, el valor de corte de malignidad según el nivel de netrina fue determinado en 645,50 mg/dL en el análisis ROC (utilizando el índice de Youden). La probabilidad de malignidad en individuos con valores de netrina superiores a este punto de corte fue del 78,2% (IC 95%: 0,680 a 0,884). La sensibilidad de la netrina para mostrar la probabilidad de malignidad en este valor de corte fue del 87,5% y la especificidad del 63,6%. La netrina-1 puede ser un biomarcador potencial para la detección del cáncer de endometrio y la evaluación de su pronóstico.

ABSTRACT To investigate the relationship of preoperative netrin-1 with important clinicopathological and prognostic factors and appropriate cut-off levels in patients with endometrial cancer. In this prospective, observational study, the case and control group were selected among patients who applied to the Gynecological Oncology Clinic. Four mL of venous blood was drawn into a biochemistry tube from each patient during the preoperative period. Netrin values in predicting the presence of malignity were analyzed using ROC (receiver operating characteristics) curve analysis. The cut-off value was calculated according to the Youden index. In the study, the cut-off value of malignancy according to the netrin level was determined as 645.50 mg/dL in the ROC analysis (using the Youden index). The probability of malignancy in individuals with Netrin values above this cut-off was 78.2% (95% CI 0.680-0.884). The sensitivity of netrin in showing the probability of malignancy at this cut-off value was 87.5%, and the specificity 63.6%. Netrin-1 can be a potential biomarker for endometrial cancer detection and prognosis evaluation.

Clinical Characteristics and Outcomes of a High-grade Endometrial Cancer Cohort Treated at Instituto Nacional de Câncer, Brazil / Características clínicas e desfechos de uma coorte de câncer endometrial de alto grau tratada no Instituto Nacional de Câncer, Brasil

Abstract Objective To analyze the outcomes of a cohort of patients with high-risk histologies of endometrial cancer (EC) treated at Instituto Nacional de Câncer (National Cancer Institute, INCA, in Portuguese), in Brazil. Materials and Methods We reviewed the medical records of patients with high-risk histologies of EC in any stage registered at INCA between 2010 and 2016 to perform a clinical and demographic descriptive analysis and to evaluate the outcomes in terms of recurrence and survival. Results From 2010 to 2016, 2,145 EC patients were registered and treated at INCA, and 466 had high-grade histologies that met the inclusion criteria. The mean age of the patients was 65 years, 44.6% were Caucasian, and 90% had a performance status of 0 or 1. The most common histology was high-grade endometrioid (31.1%), followed by serous carcinoma (25.3%), mixed (20.0%), carcinosarcoma (13.5%), and clear cell carcinoma (9.4%). Considering the 2018 Fédération Internationale de Gynécologie et d'Obstétrique (International Federation of Gynecology and Obstetrics, FIGO, in French) staging system, 44.8%, 12.4%, 29.8%, and 12.9% of the patient were in stages I, II, III or IV respectively. Age (> 60 years), more than 50% of myoinvasion, higher stage, poor performance status, serous and carcinosarcoma histologies, and adjuvant treatment were independent factors associated with recurrence-free survival (RFS) and overall survival (OS) in the multivariate analysis. Conclusion The current findings reinforced the international data showing poor outcomes of these tumors, especially for serous and carcinosarcomas and tumors with advanced stages, with shorter survival and high recurrence rates in distant sites, independently of the FIGO stage. Adjuvant therapy was associated with better survival.

Resumo Objetivo Analisar os desfechos de uma coorte de pacientes com câncer de endométrio (CE) e histologias de alto risco atendida no Instituto Nacional do Câncer (INCA) entre 2010 e 2016. Materiais e Métodos Foram revisados prontuários de pacientes com histologias de alto risco de CE em qualquer estágio cadastradas no INCA entre 2010 e 2016 para realizar uma análise descritiva clínica e demográfica e avaliar os resultados em termos de recorrência e sobrevida. Resultados De 2010 a 2016, 2.145 pacientes com CE foram cadastradas e atendidas no INCA, e 466 tinham histologias de alto grau e atendiam aos critérios de inclusão. A média de idade das pacientes foi de 65 anos, 44,6% eram brancas, e 90% tinham performance status de 0 ou 1. A histologia mais comum foi endometrioide de alto grau (31,1%), seguida de carcinoma seroso (25,3%), misto (20,0%), carcinossarcoma (13,5%) e carcinoma de células claras (9,4%). Considerando o estadiamento da Fédération Internationale de Gynécologie et d'Obstétrique (Federação Internacional de Ginecologia e Obstetrícia, FIGO, em francês) de 2018, 44,8%, 12,4%, 29,8% e 12,9% apresentaram estágios I, II, III ou IV, respectivamente. Idade (> 60 anos), mais de 50% de mioinvasão, estágio avançado, performance status ruim, histologias serosas e carcinossarcoma, e tratamento adjuvante foram fatores independentes associados à sobrevida livre de recorrência e sobrevida global na análise multivariada. Conclusão Os achados atuais reforçam os dados internacionais que demonstram o prognóstico ruim desses tumores, principalmente para as histologias serosas e carcinossarcomas e para estágios avançados, com menor sobrevida e altas taxas de recorrência à distância, independentemente do estágio da FIGO. A terapia adjuvante foi associada a melhor sobrevida.

Qualidade de vida e mapeamento de complicações: avaliação do linfonodo sentinela no câncer de endométrio / Quality of life and complications: evaluation of the sentinel lymph node in endometrial cancer

Objetivo: Avaliar a incidência das complicações pós-operatórias do estadiamento cirúrgico e qualidade de vida relacionada ao protocolo do linfonodo sentinela associado ou não à linfadenectomia sistemática no tratamento do câncer do endométrio. Métodos: Foi conduzida uma coorte prospectiva entre dezembro de 2017 e abril de 2022, incluindo mulheres com carcinoma de endométrio em estágio inicial presumido (doença restrita ao útero) e com estadiamento linfonodal, agrupadas em: Grupo LNS (somente pesquisa do linfonodo sentinela) e Grupo LNS+LND (linfonodo sentinela com adição de linfadenectomia sistemática). Foram incluídas pacientes com baixo e alto risco para metástase linfonodal. As pacientes de alto risco fazem parte do estudo ALICE (NCT03366051), um estudo prospectivo randomizado de não inferioridade. As pacientes foram avaliadas no pré-operatório, 1 mês, 6 e 12 meses, com aplicação de questionário de qualidade de vida (QQV) pelo EORTC QLQ-C30 e Cx24, avaliação clínica e perimetria para avaliar linfedema. Resultados: Foram incluídas 152 mulheres, sendo 113 (74,3%) no grupo LNS e 39 (25,7%) no grupo LNS+LND. Complicações cirúrgicas intraoperatórias ocorreram em 2 (1,3%) casos todas pertencentes ao grupo LNS+LND. Complicações cirúrgicas até 30 dias foram encontradas em 29 (19,1%) casos. As pacientes submetidas a LNS+LND apresentaram taxas gerais de complicações cirúrgicas mais altas em comparação com aquelas submetidas apenas a LNS (33,3% vs. 14,2%; p=0,011). O grupo LNS+LND apresentou maior tempo de cirurgia (p=0,001) e necessidade de UTI (p=0,001). A incidência de linfocele foi encontrada em 8 casos, apenas no grupo LNS+LND (0 vs. 20,5%; p<0,001). Para o linfedema de membros inferiores, não foi encontrada diferença entre os grupos pela avaliação perimétrica do grupo LNS comparado ao LNS+LND (23,2% vs. 13,3%; p= 0,25). O mesmo ocorreu para a avaliação clínica do linfedema, encontrado em 21,2% do grupo LNS e 33,3% do grupo LNS+LND (p=0,14). Entretanto, na avaliação de presença de linfedema pelo score de sintomas do EORTC, houve maior relato de linfedema no grupo LNS+LND (score 23,52) comparado ao grupo LNS (score 12,45) na avaliação de 12 meses (p=0,02). Além disso, encontramos associação entre avaliação clínica e linfedema relatado pelo paciente. O score médio de linfedema foi maior quando este foi detectado por exame clínico em 6 meses (30,10 vs. 7,8; p<0,001) e 12 meses (36,4 vs. 6,0; p<0,001), no entanto sem associação entre perimetria e avaliações clínicas (p=0,76). Em relação à avaliação global de qualidade de vida, não houve diferença entre os grupos aos 12 meses (p=0,21). Conclusões: Houve maior taxa geral de complicações para o grupo submetido a linfadenectomia sistemática, assim como maiores taxas de linfocele e linfedema pelo score de sintomas. Nenhuma diferença foi encontrada em relação à qualidade de vida entre os grupos LNS e LNS+LND

Objectives: To evaluate the incidence of postoperative complications of surgical lymph node staging procedures and quality of life related to the sentinel lymph node protocol associated or not with systemic lymphadenectomy in the treatment of endometrial cancer. Methods: A prospective cohort was conducted between December 2017 and April 2022. Women with presumed early-stage endometrial carcinoma (disease restricted to the uterus) and with lymph node staging were included, grouped as follows: SLN group (sentinel lymph node only) and SLN+LND Group (sentinel lymph node with addition of systematic lymphadenectomy). Patients with low and high risk for lymph node metastasis were included, and high-risk patients were part of the ALICE study (NCT03366051), a prospective randomized non-inferiority study. The patients were assessed preoperatively, 1 month, 6 and 12 months with the application of a quality-of-life questionnaire (QQL) using the EORTC QLQ-C30 and Cx24, clinical evaluation and perimetry to assess lymphedema. Results: 152 women were included, 113 (74.3%) women in the SLN group and 39 (25.7%) in the SLN+LND group. Intraoperative surgical complications occurred in 2 (1.3%) cases, all of them in the SLN+LND group. Surgical complications within 30 days were found in 29 (19.1%) cases. Patients undergoing SLN+LND had higher overall rates of surgical complications compared to women undergoing SLN alone (33.3% vs. 14.2%; p=0.011). The SLN+LND group had longer surgery time (p=0.001) and need for ICU (p=0.001). The incidence of lymphocele was found in 8 cases and only in the SLN+LND group (0 vs. 20.5%; p<0.001). For lower limbs lymphedema, no difference was found between the groups by the perimetric evaluation of the SLN group compared to the SLN+LND (23.2% vs. 13.3%; p=0.25). The same occurred for the clinical evaluation of lymphedema, being found in 21.2% for the SLN group and 33.3% for the SLN+LND group (p=0.14). However, when evaluating the presence of lymphedema using the EORTC symptom score, there was a higher number of lymphedema reports in the SLN+LND group (score 23.52) compared to the SLN group (score 12.45) at the 12-month evaluation (p=0.02). In addition, we found an association between clinical evaluation and lymphedema reported by the patient. The lymphedema score had a higher mean score when lymphedema was detected by clinical examination at 6 months (30.10 vs. 7.8; p<0.001) and 12 months (36.4 vs. 6.0; p<0.001), however with no association between perimetry and clinical evaluations (p=0.76). Regarding the overall assessment of quality of life, there was no difference between the groups at 12 months (p=0.21). Conclusions: There was a higher overall rate of complications for the group undergoing systematic lymphadenectomy, as well as higher rates of lymphocele and lymphedema according to the symptom score. No difference was found regarding quality of life between the LNS and LNS+LND groups

Cirugía laparoscópica en pacientes con obesidad mórbida y cáncer de endometrio

Introducción: La cirugía, en pacientes con obesidad mórbida, como tratamiento del cáncer ginecológico supone un reto para el cirujano y el anestesiólogo, pues se asocia a un incremento de las complicaciones intra y posoperatorias. Objetivo: Describir los principales resultados con la cirugía laparoscópica, en pacientes con obesidad mórbida y adenocarcinoma de endometrio, tratadas en el Instituto Nacional de Oncología y Radiobiología (INOR) de la Habana, Cuba, en el período comprendido enero de 2019 a marzo de 2020. Método: Se realizó un estudio descriptivo, observacional y transversal, en 22 pacientes con índice de masa corporal mayor de 40 kg/m2 y diagnóstico de adenocarcinoma de endometrio, que fueron sometidas a cirugía laparoscópica. El dato primario fue obtenido a través de las historias clínicas, con los que se confeccionó una base de datos en una hoja de Microsoft Excel para sintetizar toda la información. Resultados: Predominó la edad entre 61 a 70 años. El adenocarcinoma endometrioide fue el más frecuente con el 77,27 %. El grado de diferenciación fue el bien diferenciado, infiltrando menos del 50 % del miometrio. El estadiamiento quirúrgico predominante fue el IA (72,72 %). El sangrado transoperatorio fue de 78,9 ± 5,7ml (rango 10 y 200 ml), la media del acto operatorio de 82 min (rango 75-132 min), y la estadía hospitalaria de menos de 24 horas (90,90 %). La conversión quirúrgica se realizó en el 4,54 % de los casos. Conclusiones: Las pacientes con obesidad mórbida pueden beneficiarse del abordaje laparoscópico para el tratamiento y la estatificación quirúrgica laparoscópica del carcinoma endometrial, lo que disminuye la morbilidad y la estadía hospitalaria.

Introduction: Surgery in morbidly obese patients as a treatment for gynecologic cancer is a challenge for surgeons and anesthesiologists, since it is associated with the processes of increasing intraoperative and postoperative complications. Objective: To describe the main results gained with the use of laparoscopic surgery in patients with morbid obesity and endometrial adenocarcinoma treated at the Instituto Nacional de Oncología y Radiobiología (INOR) of Havana, Cuba, from January 2019 to March 2020. Method: A descriptive, observational, cross-sectional study was carried out in 22 patients, with body mass index more than 40 kg/m2 and diagnosis of endometrial adenocarcinoma, who underwent laparoscopic surgery. The primary data was obtained from the medical records, which were used to create a database in a Microsoft Excel spreadsheet to synthesize all the information. Results: The predominant age group was between 61 and 70 years old. Endometrial adenocarcinoma was the most frequent cancer (77.27%). The degree of differentiation was well differentiated, infiltrating less than 50 % of the myometrium. The predominant surgical staging was IA (72.72%). Transoperative bleeding was 78.9 ± 5.7 ml (range between 10 and 200 ml), mean operative time was 82 min (range 75-132 min), and hospital stay was less than 24 hours (90.90%). Surgical conversion was performed in 4.54% of cases. Conclusions: Morbidly obese patients may benefit from the laparoscopic approach for the treatment and laparoscopic surgical staging of endometrial carcinoma, which decreases morbidity and hospital stay.

Introdução: A cirurgia, em pacientes com obesidade mórbida, como tratamento para o câncer ginecológico é um desafio para o cirurgião e para o anestesiologista, pois está associada ao aumento de complicações intra e pós-operatórias. Objetivo: Descrever os principais resultados da cirurgia laparoscópica, em pacientes com obesidade mórbida e adenocarcinoma endometrial, tratados no Instituto Nacional de Oncología y Radiobiología (INOR) em Havana, Cuba, no período de janeiro de 2019 a março de 2020. Método: A estudo descritivo, observacional e transversal realizado em 22 pacientes com índice de massa corporal superior a 40 kg/m2 e diagnóstico de adenocarcinoma de endométrio, submetidas à cirurgia laparoscópica. Os dados primários foram obtidos por meio dos prontuários, com os quais foi criado um banco de dados em uma planilha do Microsoft Excel para sintetizar todas as informações. Resultados: Predominou a idade entre 61 a 70 anos. O adenocarcinoma endometrioide foi o mais frequente com 77,27%. O grau de diferenciação foi bem diferenciado, infiltrando menos de 50% do miométrio. O estadiamento cirúrgico predominante foi IA (72,72%). O sangramento transoperatório foi de 78,9 ± 5,7 ml (variação de 10 e 200 ml), a média do ato cirúrgico foi de 82 min (variação de 75-132 min) e o tempo de internação foi inferior a 24 horas (90,90%). A conversão cirúrgica foi realizada em 4,54% dos casos. Conclusões: Pacientes com obesidade mórbida podem se beneficiar da abordagem laparoscópica para o tratamento e estadiamento cirúrgico laparoscópico do carcinoma endometrial, o que diminui a morbidade e o tempo de internação.

Sentinel Lymph Node Biopsy in Endometrial Cancer - A Systematic Review and Quality Assessment of Meta-Analyses / Biópsia do linfonodo sentinela no câncer de endométrio - Uma revisão sistemática e avaliação da qualidade de meta-análises

Abstract Objective To assess the quality of recent meta-analyses reviewing the diagnostic utility of sentinel node biopsy in endometrial cancer. Methods With the MeSH terms endometrial neoplasms and sentinel lymph node biopsy, PubMed and Embase databases were searched on October 21, 2020, and again on November 10, 2021, with meta-analysis and publication date filters set to since 2015. The articles included were classified with the A Measurement Tool to Assess Systematic Reviews (AMSTAR 2) assessment tool. Results The database searches found 17, 7 of which, after the screening, were selected for full review by the author, finally extracting six meta-analyzes for quality analysis. The rating with the AMSTAR 2 assessment tool found that overall confidence in their results was critically low. Conclusion This study found that the quality of recent meta-analyses on the utility of the staging of endometrial cancer with sentinel node biopsy, evaluated by the AMSTAR 2 assessment tool, is classified as critically low, and, therefore, these meta-analyses are not reliable in the summary of their studies.

Resumo Objetivo Avaliar a qualidade de meta-análises recentes que revisaram a utilidade diagnóstica da biópsia do linfonodo sentinela no câncer de endométrio. Métodos Com os termos MeSH endometrial neoplasms e =biópsia do linfonodo sentinela, as bases de dados PubMed e Embase foram pesquisadas em 21 de outubro de 2020 e novamente em 10 de novembro de 2021, com filtros de meta-análise e data de publicação configurados para desde 2015. Os artigos incluídos foram classificados com o instrumento de avaliação A Measurement Tool to Assess Systematic Reviews (AMSTAR 2). Resultados As pesquisas de banco de dados encontraram 17 artigos, sete dos quais, após a triagem, foram selecionados para revisão completa pelo autor, extraindo finalmente 6 meta-análises para análise de qualidade. A classificação com a ferramenta de avaliação AMSTAR 2 descobriu que a confiança geral em seus resultados era criticamente baixa. Conclusão Este estudo constatou que a qualidade de meta-análises recentes sobre a utilidade do estadiamento do câncer de endométrio com biópsia do linfonodo sentinela, avaliada pela ferramenta de avaliação AMSTAR 2, é classificada como criticamente baixa e, portanto, essas meta-análises não são confiáveis no resumo de seus estudos.

Tumor carcinoide de células caliciformes apendicular con metástasis endometrial

El tumor carcinoide de células caliciformes es una neoplasia mixta casi exclusiva del apéndice, con diferenciación neuroendocrina y mucinosa. La afección metastásica endometrial por carcinomas extragenitales, especialmente el tipo de células de anillo de sello, es rara. Se presenta un caso de tumor carcinoide de células caliciformes apendicular con metástasis endometrial. Se trató de paciente femenina de 70 años quien presentó sangrado genital. El examen ginecológico mostró sangrado genital en moderada cantidad de color rojo-marrón y cuello uterino endurecido. En la biopsia endometrial se halló nidos de células de anillo de sello. La impresión diagnóstica provisional fue carcinoma mal diferenciado de probable origen intestinal. Durante la intervención, el útero tenía consistencia pétrea, el apéndice cecal era fibrótico y engrosado y el epiplón engrosado con nódulos tumorales. Las secciones anatómicas del cuello y cuerpo uterino mostraron focos tumorales. En el apéndice cecal se encontró acúmulos de pequeño tamaño compuestos por células caliciformes. La inmunotinción fue positiva a sinaptofisina, CDX-2, EMA, CK20, CD56 focal. Estos hallazgos confirmaron el diagnóstico de tumor carcinoide de células caliciformes, un tumor caracterizado por infiltración de la pared apendicular por pequeños nidos o cordones de células caliciformes con mucina intracitoplasmática y expresión focal de marcadores neuroendocrinos. Estas neoplasias tienen un comportamiento más agresivo que los tumores neuroendocrinos. La metástasis endometrial es rara y puede ser confundida con un carcinoma primario de células de anillo de sello. Se debe considerar como diagnóstico diferencial después de excluir otros tumores primarios.

Goblet cell carcinoid tumor is an almost exclusive mixed neoplasm of the appendix with neuroendocrine and mucinous differentiation. Endometrial metastatic involvement by extragenital carcinomas, especially the signet ring cell type, is rare. A case of appendiceal goblet cell carcinoid tumor with endometrial metastasis is presented. This was a 70-year-old female patient who presented with genital bleeding. The gynecological examination showed moderate red-brown genital bleeding and hardened cervix. Endometrial biopsy reported nests of signet ring cells. The provisional diagnostic impression was poorly differentiated carcinoma of probable intestinal origin. During surgery, the uterus had a stony consistency, the cecal appendix was fibrotic and thickened, and the omentum was thickened with tumor nodules. Anatomical sections of the cervix and uterine body showed tumor foci. In the cecal appendix, small clusters composed of goblet cells were found. Immunostaining was positive for synaptophysin, CDX-2, EMA, CK20, focal CD56. These findings confirmed the diagnosis of goblet cell carcinoid tumor, a tumor characterized by infiltration of the appendiceal wall by small nests or cords of goblet cells with intracytoplasmic mucin and focal expression of neuroendocrine markers. These neoplasms have a more aggressive behavior than neuroendocrine tumors. Endometrial metastasis is rare and can be mistaken for a primary signet ring cell carcinoma. It should be considered as a differential diagnosis after other primary tumors have been excluded.

Effect of autologous platelet-rich plasma treatment on patients with thin endometrium / Efecto del tratamiento con plasma autólogo rico en plaquetas en pacientes con endometrio delgado

ABSTRACT Introduction: The success of frozen embryo transfer cycles depends on a delicate interaction between embryo quality and endometrium. Low pregnancy rates are associated with a thin endometrium. Objective: To evaluate the effect of autologous platelet-rich plasma treatment on patients with thin endometrium. Methods: In 34 patients with thin endometrium (< 7 mm), canceled in the previous frozen embryo transfer cycles, autologous platelet-rich plasma was prepared, from autologous peripheral vein blood; intrauterine infusion was given during hormone replacement therapy in frozen embryo transfer cycles. Frozen embryo transfer was performed when the endometrium thickness reached ≥ 7mm. Results: Six patients canceled the embryo transfer cycle due to endometrium thickness did not reach 7 mm; 28 patients got endometrial thickness ≥ 7 mm and performed frozen embryo transfer. The endometrial thickness was 7.5 ± 0.8 mm, which was significantly thicker than in the previous cycles (5.6 ± 0.79 mm) with p< 0.002, the implantation rate was 23.07 %, and the clinical pregnancy rate was 12/28 (42.8 %). Conclusion: Autologous platelet-rich plasma improves the endometrial thickness and the pregnancy rate outcomes in women with thin endometrium.

RESUMEN Introducción: El éxito de los ciclos de transferencia de embriones congelados depende de una delicada interacción entre la calidad del embrión y el endometrio. Las bajas tasas de embarazo están asociadas con un endometrio delgado. Objetivo: Evaluar el efecto del tratamiento con plasma rico en plaquetas autólogo en pacientes con endometrial delgado. Métodos: En 34 pacientes con endometrio delgado (< 7 mm) canceladas en los ciclos previos de transferencia de embriones congelados, se preparó plasma autólogo rico en plaquetas, a partir de sangre autóloga de venas periféricas; la infusión intrauterina se administró durante la terapia de reemplazo hormonal en los ciclos de transferencia de embriones congelados. La transferencia de embriones congelados se realizó cuando el grosor del endometrio alcanzó ≥ 7 mm. Resultados: En 6s pacientes se canceló el ciclo de transferencia embrionaria debido a que el grosor del endometrio no alcanzó los 7 mm; 28 pacientes obtuvieron un grosor endometrial ≥ 7 mm y realizaron transferencia de embriones congelados. El grosor del endometrio fue de 7,5 ± 0,8 mm, significativamente mayor que en los ciclos anteriores (5,6 ± 0,79 mm) con p< 0,002; la tasa de implantación fue de 23,07 % y la tasa de embarazo clínico fue de 12/28 (42,8 %). Conclusión: El plasma autólogo rico en plaquetas mejora el grosor endometrial y los resultados de la tasa de embarazo en mujeres con endometrio delgado.

Análisis del cáncer de endometrio en un hospital universitario de Ourense, España / Analysis of endometrial cancer in a university hospital in Ourense, Spain

Resumen OBJETIVO: Describir, de forma retrospectiva, el comportamiento del cáncer de endometrio en pacientes diagnosticadas en el Complexo Hospitalario Universitario de Ourense MATERIALES Y MÉTODOS: Estudio descriptivo, observacional y retrospectivo efectuado en el Complexo Hospitalario Universitario de Ourense entre septiembre de 2014 y enero de 2018. Criterio de inclusión: diagnóstico, tratamiento y seguimiento en nuestro centro. Criterio de exclusión: historia incompleta y diagnóstico o tratamiento en otro centro. Variables de estudio: tipo de tumor y de tratamiento. Se realizó un análisis descriptivo. Las posibles asociaciones se comprobaron mediante χ2, Fisher, t de Student y prueba de Mann-Whitney. RESULTADOS: Se estudiaron 149 pacientes, con edad media al diagnóstico de 69.38 años ± 9.6 años. El 86.6% (n = 129) de las pacientes estaban en la posmenopausia. El 68% (n = 101) eran obesas y el 54.7% (n = 81) hipertensas. El 54.7% (n = 81) se diagnosticaron en estadio IA. El 68.4% de los tumores grado 3 tuvieron infiltración miometrial mayor al 50%, el 28.6% grado 1 (p < 0.001). De las pacientes que recibieron radioterapia o braquiterapia el 46% estaba en estadios avanzados; 76% en estadio IB, 26% en estadio IA (p < 0.001). El 91.3% de los tumores estadio I fueron tipo I, en los estadios avanzados hubo 48.6% de tumores tipo I (p < 0.001). El 87.4% de los tumores grados 1 o 2 se encontraron en estadio I, un 45.2% de los tumores grado 3 en estadio I (p < 0.001). CONCLUSIONES: La mayoría de las pacientes tenía más de 60 años y eran diabéticas, hipertensas y obesas. El cáncer de endometrio suele diagnosticarse en estadios tempranos. La braquiterapia es la coadyuvancia más indicada.

Abstract OBJECTIVE: To retrospectively describe the behavior of endometrial cancer in patients diagnosed at the Complexo Hospitalario Universitario de Ourense. MATERIALS AND METHODS: Descriptive, observational and retrospective study in the Complexo Hospitalario Universitario de Ourense between September 2014 and January 2018. Inclusion criteria: diagnosis, treatment and follow-up in our center. Exclusion criteria: incomplete history and diagnosis or management in another center. Patient, tumor and treatment variables were collected. A descriptive analysis was performed. Possible associations were tested by Chi-square, Fisher, Student's t-test and Mann-Whitney test. RESULTS: 149 patients were studied, with mean age at diagnosis of 69.38 years ± 9.6 years. 86.6% (n = 129) of the patients were postmenopausal. 68% (n = 101) were obese and 54.7% (n = 81) hypertensive. 54.7% (n = 81) were diagnosed at stage IA. 68.4% of grade 3 tumors had myometrial infiltration greater than 50%, 28.6% grade 1 (p < 0.001). Of the patients who received radiotherapy or brachytherapy 46% were advanced stage; 76% stage IB, 26% stage IA (p < 0.001). 91.3% of stage I tumors were type I, in advanced stages there were 48.6% of type I tumors (p < 0.001). 87.4% of grade 1 or 2 tumors were stage I, 45.2% of grade 3 tumors were stage I (p < 0.001). CONCLUSIONS: Most patients were older than 60 years and were diabetic, hypertensive and obese. Endometrial cancer is usually diagnosed at early stages. Brachytherapy is the most indicated adjuvant.

Linfoma no Hodgkin primario de vagina o cuello uterino. Un diagnóstico en ocasiones incierto: a propósito de un caso / Primary non-Hodgkin´s lymphoma of vagina or cervix. A diagnosis sometimes uncertain: about a case

Resumen ANTECEDENTES: La afectación primaria del aparato genital femenino por un linfoma no Hodgkin es excepcional, se reporta en 0.2 a 1.1% de los casos. Los órganos afectados con más frecuencia son los ovarios, seguidos del cuello uterino; el endometrio y la vagina son los menos aquejados. Debido a su baja frecuencia aún no se llega a un consenso del tratamiento más adecuado de estos linfomas; hasta ahora, por lo general, se ha individualizado para cada caso en concreto. CASO CLÍNICO: Paciente de 29 años que consultó por sangrado genital anómalo e incapacidad para la inserción de tampones vaginales. En la exploración se encontró una masa pélvica, palpable a través de la vagina, que impresionaba al infiltrar toda la luz vaginal y la parte media e izquierda de la vulva. En los estudios de imagen se objetivó una gran masa pélvica de hasta 10 centímetros que parecía depender del cuello del útero y que se extendía e infiltraba el canal vaginal, la vulva y el tercio inferior de la vejiga. El reporte anatomopatológico de la biopsia fue: infiltración de pared vaginal por un linfoma no Hodgkin B difuso de células grandes. Se le indicaron seis ciclos de quimioterapia con ciclofosfamida, vincristina, adriamicina y prednisona con los que se consiguió la remisión metabólica completa. CONCLUSIÓN: El diagnóstico del linfoma genital primario puede resultar complejo por la posibilidad de simular una neoplasia ginecológica. En casos de enfermedad avanzada, la manifestación clínica más frecuente es el sangrado genital anómalo. El esquema de tratamiento más aceptado en la actualidad es con rituximab-ciclofosfamida, vincristina, adriamicina, prednisona seguido de radioterapia de consolidación.

Abstract BACKGROUND: Primary involvement of the female genital tract by non-Hodgkin's lymphoma is exceptional, reported in 0.2 to 1.1% of cases. The most frequently affected organs are the ovaries, followed by the cervix; the endometrium and vagina are the least affected. Due to their low frequency, there is still no consensus on the most appropriate treatment of these lymphomas; until now, it has generally been individualized for each specific case. CLINICAL CASE: A 29-year-old female patient consulted for abnormal genital bleeding and inability to insert vaginal tampons. On examination a pelvic mass was found, palpable through the vagina, which impressed by infiltrating the entire vaginal lumen and the middle and left side of the vulva. Imaging studies showed a large pelvic mass of up to 10 centimeters that appeared to be dependent on the cervix and that extended and infiltrated the vaginal canal, the vulva and the lower third of the bladder. The anatomopathological report of the biopsy was: infiltration of the vaginal wall by diffuse large cell non-Hodgkin's B lymphoma. She was prescribed six cycles of chemotherapy with cyclophosphamide, vincristine, adriamycin and prednisone with which complete metabolic remission was achieved. CONCLUSION: The diagnosis of primary genital lymphoma can be complex because of the possibility of simulating a gynecologic neoplasm. In cases of advanced disease, the most frequent clinical manifestation is abnormal genital bleeding. The most accepted treatment scheme at present is rituximab-cyclophosphamide, vincristine, adriamycin, prednisone followed by consolidation radiotherapy.

Cáncer sincrónico de ovario y cúpula vaginal. Reporte de un caso y revisión de la bibliografía / Synchronous ovarian and vaginal vault cancer. Report of a case and review of the literature

Resumen INTRODUCCIÓN: El cáncer sincrónico es poco frecuente y de origen incierto. Se caracteriza por diferentes lesiones malignas que afectan dos o más zonas del aparato reproductor al mismo tiempo o en un lapso menor a un año; la combinación ovario y endometrio es la más frecuente. OBJETIVO: Reportar un caso de cáncer ginecológico sincrónico, tumor maligno de células de la granulosa de ovario y carcinoma de células escamosas en la cúpula vaginal; además, revisar la bibliografía al respecto. CASO CLÍNICO: Paciente de 47 años, con histerectomía total por miomatosis y una lesión de gran tamaño que ocupaba el espacio pélvico y comprimía el techo vesical. Acudió a consulta debido a un sangrado genital abundante, pérdida de peso y de orina en forma involuntaria. En el examen físico se evidenció una lesión friable en la cúpula vaginal de 3 cm. Se decidieron la ooforectomía izquierda y la extirpación tumoral. La biopsia y la inmunohistoquímica de las lesiones reportó un tumor maligno de células de la granulosa del adulto localizado en el ovario, y un carcinoma de células escamosas en la cúpula vaginal. Se indicó quimioterapia y en la actualidad la paciente permanece sin recidiva de la enfermedad y en seguimiento oncológico. CONCLUSIÓN: El cáncer sincrónico es poco frecuente, de ahí que se disponga de poca información. Gracias al acierto del diagnóstico y de la conducta terapéutica a seguir, luego de 24 meses la paciente del caso no ha tenido signos de recidiva de la enfermedad; continúa en seguimiento oncológico conforme a los protocolos establecidos.

Abstract INTRODUCTION: Synchronous cancer in gynecology is a rare entity, of uncertain etiology, consisting of different malignant lesions affecting two or more areas of the female reproductive system, at the same time or within a period of less than 1 year, the combination of ovary and endometrium being the most frequent. OBJECTIVE: to report a case of synchronous gynecological cancer, malignant granulosa cell tumor of the ovary and squamous cell carcinoma of the vaginal vault and in view of the infrequency of the case to review the literature. CLINICAL CASE: 47 years old patient, who underwent total hysterectomy for uterine myomatosis plus right oophorectomy for showing ovarian tumor during surgery, the histopathological report reported malignant granulosa cell tumor, abdomino-pelvic tomography was requested, which reported a large pelvic space occupying lesion (LOE) with compression of the bladder roof. She came to our office for the first time due to abundant genital bleeding, weight loss and involuntary urine loss, physical examination revealed a friable lesion in the vaginal vault of 3cm, surgical intervention was decided where a left oophorectomy and tumor pruning were performed, Biopsy and immunohistochemistry of lesions with report of malignant granulosa cell tumor of adult granulosa cells in the ovary and squamous cell carcinoma in the vaginal vault, referred to medical oncology who applied chemotherapy and currently the patient is without recurrence of the disease and in oncological follow-up. CONCLUSION: Synchronous cancer is an infrequent pathology, where much information remains to be investigated to better understand this entity. We present the first reported case of synchronous ovarian granulosa cell tumor cancer with vaginal vault cancer. Fortunately our patient 24 months after completing her treatment shows no signs of recurrence of the disease and will be followed up according to the established oncologic protocols.

Tratamiento laparoscópico de una paciente con un leiomioma uterino gigante cavitado, con cambio degenerativo mucomixoide / Laparoscopic treatment of a patient with a cavitated giant uterine leiomyoma with mucomyxoid degenerative change

Resumen INTRODUCCIÓN: Un leiomioma con cambios degenerativos poco frecuentes es un desafío diagnóstico difícil de diferenciar de sus homólogos malignos, si se pretende fundamentarlo solo en lo advertido en las imágenes. CASO CLÍNICO: Paciente de 40 años de edad, enviada al servicio de Cirugía de mínima invasión en marzo del 2021 debido al aumento del perímetro abdominal, disminución del apetito y disnea de medianos esfuerzos. El ultrasonido abdomino-pélvico reportó que el útero estaba aumentado de tamaño, con miomas intramurales de medianos elementos. El endometrio heterogéneo. El ovario derecho tenía un quiste complejo, gigante, de 276 mm x 250 mm x 276 mm, con volumen de 10 000 cc. Además, esplenomegalia, hidronefrosis derecha y litiasis renal izquierda. Los marcadores tumorales se reportaron normales. En la cirugía por laparoscopia se observó un tumor que ocupaba toda la cavidad abdominal de 40 x 30 cm, adherido a la pared posterior del útero, con ambos ovarios sin alteraciones, sin líquido libre; se procedió a la histerectomía total. CONCLUSIONES: Los cambios degenerativos en los leiomiomas uterinos pueden distorsionar la estructura habitual del tumor y reflejarla en imágenes típicas de una tumoración quística de ovario; en el estudio inicial esto representa un desafío para el cirujano y debe considerarse parte del diagnóstico diferencial de las masas anexiales. En la paciente del caso, con cirugía de mínima invasión, se consiguió la resección completa de la pieza, a pesar del tamaño aumentado, con menores riesgos de complicaciones en la herida y menos dolor posoperatorio; las incisiones son pequeñas y con desenlaces estéticos favorables y menos días de estancia intrahospitalaria.

Abstract INTRODUCTION: A leiomyoma with rare degenerative changes is a diagnostic challenge difficult to differentiate from its malignant counterparts, if it is intended to be based only on imaging findings. CLINICAL CASE: 40-year-old female patient referred to the Minimally Invasive Surgery service in March 2021 due to increased abdominal perimeter, decreased appetite and dyspnea on medium exertion. Abdomino-pelvic ultrasound reported that the uterus was enlarged, with medium-element intramural fibroids. The endometrium was heterogeneous. The right ovary had a complex, giant cyst, 276 mm x 250 mm x 276 mm, with a volume of 10,000 cc. In addition, splenomegaly, right hydronephrosis and left renal lithiasis. Tumor markers were reported normal. Laparoscopic surgery showed a tumor occupying the entire abdominal cavity measuring 40 x 30 cm and attached to the posterior wall of the uterus, with both ovaries unaltered, with no free fluid; total hysterectomy was performed. CONCLUSIONS: Degenerative changes in uterine leiomyomas can distort the usual tumor structure and reflect it in images typical of an ovarian cystic tumor; in the initial study this represents a challenge for the surgeon and should be considered part of the differential diagnosis of adnexal masses. In the case patient, with minimally invasive surgery, complete resection of the specimen was achieved, despite the increased size, with less risk of wound complications and less postoperative pain; the incisions are small and with favorable esthetic outcomes and fewer days of in-hospital stay.

Cáncer de endometrio: tratamiento quirúrgico en un hospital comunitario de España / Endometrial cancer: surgical treatment in a community hospital in Spain

Resumen OBJETIVO: Exponer los desenlaces quirúrgicos de las pacientes intervenidas por cáncer de endometrio, analizar si existen puntos de mejora en nuestra práctica clínica y aportar más datos a la evidencia publicada, para ayudar al avance en el tratamiento quirúrgico de las pacientes con esta enfermedad MATERIALES Y MÉTODOS: Estudio observacional, descriptivo y retrospectivo llevado a cabo en la Unidad de Oncología Ginecológica del Hospital Regional Virgen Macarena de Sevilla, España, entre junio de 2013 y febrero de 2020. Se reunieron los reportes quirúrgicos de pacientes intervenidas por alguna afección endometrial premaligna o maligna. Variables de estudio: edad, IMC, cirugías previas, diagnóstico histopatológico y estadio, vía de acceso quirúrgico y terapia coadyuvante. Se exponen los desenlaces relacionados con complicaciones quirúrgicas y tasa de curación, así como el tiempo de intervención, vía de acceso quirúrgico y estancia hospitalaria. RESULTADOS: Se estudiaron 250 pacientes, la mayoría (76%) con diagnóstico de adenocarcinoma endometrioide de endometrio. La vía de acceso quirúrgico más utilizada fue la laparoscopia (51.6%), con un porcentaje de complicaciones intraoperatorias del 10% y posoperatorias del 9.2%. El 88.4% de las pacientes permanece viva y libre de enfermedad después del tratamiento, con recaídas solo en el 11.6% y 8% de fallecimientos. CONCLUSIONES: El tratamiento inicial de elección, en pacientes con hiperplasia con atipias o cáncer de endometrio en estadios tempranos, es la cirugía, mediante histerectomía, doble anexectomía y en algunos casos linfadenectomía asociada. La elección de la vía quirúrgica de acceso debe individualizarse a las condiciones particulares de cada paciente. La laparoscopia ofrece múltiples ventajas, es una técnica en auge y cada día más practicada.

Abstract OBJECTIVE: To expose the surgical outcomes of patients operated on for endometrial cancer, to analyze if there are points of improvement in our clinical practice and to contribute more data to the published evidence, to help advance the surgical treatment of patients with this disease. MATERIALS AND METHODS: Observational, descriptive, and retrospective study carried out in the Gynecologic Oncology Unit of the Virgen Macarena Regional Hospital of Seville, Spain, between June 2013 and February 2020. Surgical reports of patients operated on for any premalignant or malignant endometrial condition were collected. Study variables: age, BMI, previous surgeries, histopathological diagnosis and stage, surgical access route and adjuvant therapy. Outcomes related to surgical complications and cure rate are presented, as well as operation time, surgical access route and hospital stay. RESULTS: 250 patients were studied, the majority (76%) with a diagnosis of endometrioid endometrial adenocarcinoma. The most used surgical access route was laparoscopy (51.6%), with a percentage of intraoperative complications of 10% and postoperative complications of 9.2%. 88.4% of patients remain alive free of disease after treatment, with relapses in only 11.6% and 8% deaths. CONCLUSIONS: The initial treatment of choice in patients with hyperplasia with atypia or early-stage endometrial cancer is surgery, by hysterectomy, double adnexectomy and in some cases associated lymphadenectomy. The choice of surgical approach must be individualized to the conditions of each patient. Laparoscopy offers multiple advantages; it is a technique that is on the rise and is being used more and more frequently.

Factores predictores de recurrencia del cáncer de endometrio / Predictors of the endometrium cancer recurrence

Resumen OBJETIVO: Determinar qué factores favorecen la predicción de recurrencia de cáncer de endometrio en diferentes estadios de la enfermedad. MATERIALES Y MÉTODOS: Estudio retrospectivo efectuado en un grupo de pacientes con cáncer de endometrio atendidas entre el 2017 y 2020 en el Hospital Juan Ramón Jiménez de Huelva, España. Variables de análisis: edad, grado de diferenciación tumoral, invasión miometrial, estadio posquirúrgico e infiltración al espacio linfovascular, en todas las pacientes con recidiva. El análisis estadístico se procesó en el programa SPSS v23. Habiéndose realizado un análisis de Kolmogorov- Smirnov y tras haber obtenido un resultado no normal, se utilizó la prueba de χ2 para los datos categóricos paramétricos, e independientemente se aplicó la prueba U de Mann Whitney para los datos no paramétricos. Los valores de p < 0.01 se consideraron estadísticamente significativos. RESULTADOS: Se reunieron 9 pacientes con recidiva tumoral y seguimiento de 5 años luego del diagnóstico primario. Conforme al análisis estadístico no se encontró una relación de dependencia entre las variables recidiva e invasión miometrial (χ2 = 4.780; p = 0.092), recidiva y grado tumoral (χ2 = 7.765; p = 0.051) y recidiva y el estadio posquirúrgico (χ2 = 10.200, p = 0.070). Por el contrario, se observó relación de dependencia entre las variables afectación ganglionar e infiltración al espacio linfovascular positiva (χ2 = 9.954, Cc = 0.235, p < 0.01). En todas las pacientes se evaluó la infiltración al espacio linfovascular. Ésta fue negativa en 141 casos y 4 de estos casos tuvieron recurrencia de la enfermedad. 5 de 9 pacientes con recurrencia de la enfermedad tenían infiltración al espacio linfovascular positiva. CONCLUSIONES: Lo aquí encontrado muestra que más de la mitad de las pacientes con recurrencia de la enfermedad tuvieron infiltración al espacio linfovascular. Cuando ésta fue negativa hubo una reducción del riesgo de 2.8% de padecer una recurrencia.

Abstract OBJECTIVE: To determine which factors favor the prediction of endometrial cancer recurrence at different stages of the disease. MATERIALS AND METHODS: Retrospective study performed in a group of patients with endometrial cancer attended between 2017 and 2020 at the Juan Ramón Jiménez Hospital in Huelva, Spain. Analysis variables: age, degree of tumor differentiation, myometrial invasion, post-surgical stage and infiltration to the lymphovascular space, in all patients with recurrence. The statistical analysis was processed in SPSS v23. Having performed a Kolmogorov-Smirnov analysis and having obtained a non-normal result, a 2 test was used for parametric categorical data, and independently the Mann Whitney U test was used for non-parametric data. Values of p < 0.01 were considered statistically significant. RESULTS: Nine patients with tumor recurrence and 5-year follow-up after primary diagnosis were collected. According to the statistical analysis, no dependency relationship was found between the variables recurrence and myometrial invasion (χ2 = 4.780; p = 0.092), recurrence and tumor grade (χ2 = 7.765; p = 0.051) and recurrence and post-surgical stage (χ2 = 10.200, p = 0.070). In contrast, a dependency relationship was observed between the variables nodal involvement and positive lymphovascular space infiltration (χ2 = 9.954, Cc = 0.235, p < 0.01). The existence of infiltration of the lymphovascular space was evaluated in all patients. This was negative in 141 cases and 4 of these cases had disease recurrence. 5 of 9 patients with disease recurrence had positive lymphovascular space infiltration. CONCLUSIONS: The findings here show that more than half of the patients with disease recurrence have infiltration to the lymphovascular space and, in addition, if the infiltration to the lymphovascular space is negative, there is a 2.8% reduced risk of recurrence.

Estudo imuno-histoquímico e classificação molecular dos adenocarcinomas de endométrio com expressão heterogênea dos genes de reparo do DNA / Immunohistochemical study and molecular classification of endometrial adenocarcinomas with heterogeneous expression of DNA repair genes

Introdução: O carcinoma endometrial (CE) foi classificado pelo sistema de Bokhman em tipos I e II com base em observações clínicas e epidemiológicas. O tipo I corresponde aos tumores de baixo grau e o tipo II aos tumores de alto grau. Adicionalmente, estudos recentes propuseram que a classificação também fosse baseada em aspectos histológicos e moleculares com base nos dados do TCGA (The Cancer Genome Atlas). Foram identificados quatro grupos moleculares distintos de CE: (1) com mutações no POLE (fenótipo "ultramutado"), (2) "alto número de cópias" (mutações em TP53), (3) !baixo número de cópias" (em que os tumores não apresentam nenhuma das alterações descritas nos outros tipos) e (4) tumores com predomínio de instabilidade de microssatélites. A imunohistoquímica (IHC) para proteínas do gene de reparo é usada para identificar a deficiência de genes de reparo do DNA (Mismatch Repair ­ MMR) associada à instabilidade de microssatélites(MSI). A coloração nuclear positiva representa a expressão retida de proteínas MMR, enquanto a perda completa representa deficiência de MMR. O padrão de expressão heterogênea (HEP), ou seja, concomitância em um mesmo espécime de áreas positivas e totalmente negativas tem sido observada em CE. No presente momento, as principais diretrizes determinam que a presença de HEP seja interpretada como expressão retida de proteínas MMR. Não há, porém, consenso quanto à classificação e interpretação de HEP, nem conhecimento do impacto da classificação de HEP como subtipo molecular diferente em relação às características clínicas e prognósticas. Objetivos: realizar a classificação molecular dos casos de CE com HEP das proteínas relacionadas aos genes de reparo do DNA e comparação do perfil molecular entre áreas positivas e negativas no estudo imunohistoquímico. Materiais e Métodos: De janeiro/2007 a dezembro/2017 foram identificados 356 casos de CE, 16 deles com HEP. A classificação molecular foi feita com base no protocolo PROMISE para CE. Cada área (expressão retida ou perdida) foi macrodissecada e o status molecular foi avaliado separadamente quanto ao status MSI (Idylla), metilação do promotor MLH1 (NGS - ponto de corte para positividade ≥ 15%), status POLE (NGS) e status p53 (IHC). Variáveis clínicas e patológicas também foram avaliadas e correlacionadas com cada caso. Resultados: A histologia endometrioide foi predominante (15 casos), bem como ausência de invasão linfovascular (11 casos), ausência de padrão MELF (10 casos), graus FIGO 1 e 2 (13 casos), invasão miometrial < 50% (13 casos) e estadiamento T1 (13 casos). Todos os pacientes estavam vivos e sem evidência de doença no último acompanhamento, exceto por um caso, cujo status de sobrevida era desconhecido. Dois casos que seriam descritos como apresentando expressão retida de proteínas relacionadas a genes de reparo do DNA por IHC apresentaram-se na análise molecular com instabilidade de microssatélites(MSI-H). Nos casos de HEP, a proteína MSH6 foi a maisfrequentemente envolvida (9 casos, 7 isolados). A proteína MLH1 apresentou-se alterada em 6 casos, sendo a única proteína associada a co-alterações (com MSH6 e PMS2). Seis casos apresentaram-se metilados por MLH1, padrão encontrado tanto em áreas com perda quanto em áreas com retenção das proteínas relacionadas a MMR por IHC e dois casos apresentaram metilação em apenas uma das áreas. Em relação ao status de POLE, 6 casos apresentaram mutação, 2 com mutações tanto em áreas com perda quanto em áreas com retenção de expressão, 3 apenas na área com perda e 1 apenas na área com retenção. Dois casos apresentam padrão aberrante de p53 (MSH6 alterados) em ambas as áreas. Conclusão: em pacientes portadoras CE e com tumores apresentando HEP a correlação entre a IHC e os achados moleculares é heterogênea e o diagnóstico entre casos com retenção ou das proteínas relacionadas a MMR não é factível apenas com realização de IHC. A análise molecular deve ser realizada em todos os casos de CE com HEP para determinar adequadamente as característicasintrínsecas de cada tumor. Devido à raridade desse achado, esta proposta é financeiramente viável e tem o potencial de mudar a prática clínica em um subconjunto de pacientes, permitindo tratamentos inovadores. HEP deve ser relatado como um padrão distinto e não considerado como uma expressão sinônimo de expressão retida de proteínas MMR em CE.

Introduction: Endometrial adenocarcinoma is classified by the Bokhman system in type I and II based on clinical and epidemiological observations, whereas the type I represents low grade tumors and type II high grade tumors. Additionally, a classification based on histological aspects and molecular profile has been proposed. The TCGA (The Cancer Genome Atlas) identified four molecular groups of endometrial adenocarcinomas: (1) mutations in POLE ("ultramutated" phenotype), (2) "high copy number" (mutations in TP53), (3) "low number of copies " (in which the tumors do not exhibit any of the changes described in the other types) and (4) tumors with predominance of microsatellite instability. In a small number of patients, heterogeneous staining is observed in the evaluation protein expression for mismatch repair genes. Objectives: to evaluate and perform the molecular classifications of cases of endometrial carcinoma with heterogeneous staining by IHC of proteins related to mismatch repair genes and comparison of the molecular profile of positive and negative areas in the IHC study. Cases and Methods: From January/2007 to December/2017 354 cases with EC were identified, 16 of those with HEP. Molecular classification was made based on the PROMISE protocol for EC. Each area (retained and lost expression) was macrodissected and molecular status was evaluated separately regarding MSI status (Idylla), MLH1 promoter methylation (NGS - cutoff for positivity ≥ 15%), POLE status (NGS) and p53 status (IHC). Clinical and pathologic variables were also evaluated and correlated with each case. Results: Endometrioid histology was predominant (15 cases), as absent lymphovascular invasion (11 cases), absence of MELF pattern (10 cases), FIGO Grade 1 and 2 (13 cases), and T1 stage (13 cases). All patients were alive and disease-free at the last follow-up. Two cases that would be described as retained by IHC presented in the molecular analysis as MSI-H. In HEP cases MSH6 was more frequent (9 cases, 7 isolated). MLH1 was altered in 6 cases, and wasthe only protein associated with co-alterations (with MSH6 and PMS2). Six cases were MLH1 methylated, found both in lost and retained areas. As POLE status, there were 6 mutated cases, 2 of those with mutations both in lost and retained areas, and 3 the lost area. Two cases had p53 aberrant pattern (MSH6 altered), that was seen both in the retained and in the lost areas. Conclusion: Correlation between IHC and molecular findings is heterogeneous, and determination between retained or lost expression of MMR proteins by IHC when HEP occurs, however feasible, does not represent the actual molecular alterations. Thus, molecular analysis should be performed every case to adequately determine the intrinsic features of each tumor. Due to the rarity of this finding, this is financially viable and has the potential to change clinical practice in a subset of patients. HEP should be reported as a distinct pattern, and not considered as a synonym expression of retained expression of MMR proteins in EC.

Nueva clasificación molecular del carcinoma de endometrio: impacto en el diagnóstico histopatológico, tratamiento y pronóstico / New molecular classification of endometrial carcinoma: impact on histopathological diagnosis, treatment, and prognosis / Nova classificação molecular do carcinoma de endométrio: impacto no diagnóstico histopatológico, tratamento e prognóstico

Introducción. El carcinoma de endometrio es una patología heterogénea a nivel patogénico, histopatológico y molecular. En los últimos años se han sumado esfuerzos para esclarecer y aumentar el conocimiento de las bases moleculares, logrando así dividir las pacientes en cuatro subgrupos descritos por el Atlas del Genoma del Cáncer (TCGA, por sus siglas en inglés), obteniéndose valiosa información que afecta el diagnóstico, tratamiento y pronóstico de las pacientes con esta enfermedad. El objetivo de la siguiente revisión es exponer la nueva clasificación molecular del carcinoma de endometrio, así como discutir las ventajas que esta trae a la hora de estratificar a las pacientes y tomar decisiones terapéuticas. División de los temas tratados. Se realizó una búsqueda bibliográfica no sistemática en las bases de datos PubMed, Cochrane y Medline desde el año 2014 hasta el 2020 sobre el carcinoma de endometrio y su clasificación molecular. Se expone de manera concreta y actualizada el contexto histórico, los diferentes subgrupos moleculares y cómo estos impactan en el manejo de las pacientes. Conclusiones. El carcinoma de endometrio es una enfermedad heterogénea a nivel histopatológico, clínico y molecular. Con la nueva clasificación y los estudios prospectivos se podrán crear nuevas estrategias que permitan brindar mejores protocolos diagnósticos y terapéuticos.

Introduction. Endometrial carcinoma is a heterogeneous pathology in pathologenic, histopathological, and molecular terms. Over the last years, efforts have been made to clarify and increase knowledge of molecular bases, as such dividing patients into four subgroups described by the The Cancer Genome Atlas (TCGA), obtaining valuable information that affects the diagnosis, treatment, and prognosis of patients with this disease. The objective of this review is to exhibit the new molecular classification of endometrial carcinoma, and to discuss its advantages when stratifying patients and making therapeutic decisions. Division of Covered Topics. A non-systematic bibliographical search was carried out in the PubMed, Cochrane, and Medline databases from 2014 to 2020, on endometrial carcinoma and its molecular classification. The historical context, different molecular subgroups and how these impact patient handling are shown in a concrete and updated way. Conclusions. Endometrial carcinoma is a heterogeneous disease in histopathological, clinical, and molecular terms. With the new classification and the prospective studies, new strategies can be created to provide better diagnostic and therapeutic protocols.

Introdução. O carcinoma de endométrio é uma patologia heterogênea no nível patogênico, histopatológico e molecular. Nos últimos anos, foram feitos esforços para esclarecer e aumentar o conhecimento das bases moleculares, conseguindo dividir as pacientes em quatro subgrupos descritos pelo Atlas do Genoma do Câncer (TCGA, por suas siglas em inglês), obtendo informações valiosas que afetam o diagnóstico, o tratamento e o prognóstico das pacientes com esta doença. O objetivo da seguinte revisão é apresentar a nova classificação molecular do carcinoma de endométrio, bem como discutir as vantagens que ela traz no momento de estratificar as pacientes e tomar decisões terapêuticas. Divisão dos tópicos abordados. Uma pesquisa bibliográfica não sistemática foi realizada nas bases de dados PubMed, Cochrane e Medline de 2014 a 2020 sobre o carcinoma de endométrio e sua classificação molecular. São apresentados de forma concreta e atualizada o contexto histórico, os diferentes subgrupos moleculares e como esses têm impacto no tratamento das pacientes. Conclusões. O carcinoma de endométrio é uma doença heterogênea no nível histopatológico, clínico e molecular. Com a nova classificação e estudos prospectivos, novas estratégias podem ser desenvolvidas para fornecer melhores protocolos diagnósticos e terapêuticos.

Apresentação não usual de dois casos de uso de dispositivoIntrauterino hormonal - Mirena® / Two cases of unusual presentation of hormonal levonorgestrel intrauterine system - Mirena®

Os contraceptivos intrauterinos contendo levonorgestrel, Mirena®, amplamente utilizados na ginecologia contemporânea como método eficaz de contracepção e controle de distúrbios menstruais, mostrou reduzir as taxas de câncer de endométrio. Além disso, complicações como perfuração e migração são raras, exigindo intervenção rápida. Descrição: Dois casos atípicos acerca do uso de dispositivo intrauterino hormonal, o primeiro trata de migração do dispositivo para a cavidade abdominal, após 1 ano e 8 meses da inserção, sem perfuração, com retirada videolaparoscópica. O segundo é um caso de câncer primário de endométrio em paciente com 3 anos de uso de Mirena®. Discussão: A migração do dispositivo intrauterino é uma complicação rara, pouco relatada na literatura, a abordagem videolaparoscópica é a preferencial e foi realizada no caso em questão. O dispositivo intrauterino hormonal também está relacionado à diminuição das taxas de câncer de endométrio e, inclusive, é usado como método preventivo em mulheres de alto risco. Após revisão de literatura, apenas seis casos similares foram descritos. Conclusão: O dispositivo hormonal intrauterino, apesar de seguro, pode implicar apresentações raras, como migração e perfuração, que exigem conhecimento e agilidade da equipe profissional. O segundo caso apresentado é um evento raro, que faz atentar para mulheres com padrão hemorrágico incomum em uso do Mirena®. (AU)

Intrauterine contraceptives containing levonorgestrel, Mirena®, widely used in contemporary gynecology as an effective method of contraception and control of menstrual disorders, have shown to reduce rates of endometrial cancer. In addition, complications such as perforation and migration are rare, requiring rapid intervention. Description: Two atypical cases about the use of intrauterine hormonal device, the first deals with migration of the device to the abdominal cavity, after 1 year and 8 months of insertion, without perforation, with videolaparoscopic withdrawal. The second is a case of primary endometrial cancer in a patient with 3 years of use of Mirena®. Discussion: Migration of the intrauterine device is a rare complication, little reported in the literature, the videolaparoscopic approach is the preferred one and was performed in the case in question. The hormonal intrauterine device is also related to the decreased rates of endometrial cancer and is also used as a preventive method in high-risk women. After reviewing the literature, only six similar cases were described. Conclusion: The intrauterine hormonal device, although safe, may imply rare presentations, such as migration and perforation, which require knowledge and agility of the professional team. The second case presented is a rare event, which makes it aware for women with an unusual hemorrhagic pattern to use Mirena®. (AU)

Screening of Variants in the Transcript Profile of Eutopic Endometrium from Infertile Women with Endometriosis during the Implantation Window / Rastreio de variantes no perfil de tanscritos do endométrio eutópico de mulheres inférteis com endometriose durante a janela de implantação

Abstract Objective Abnormalities in the eutopic endometrium of women with endometriosis may be related to disease-associated infertility. Although previous RNA-sequencing analysis did not show differential expression in endometrial transcripts of endometriosis patients, other molecular alterations could impact protein synthesis and endometrial receptivity. Our aim was to screen for functional mutations in the transcripts of eutopic endometria of infertile women with endometriosis and controls during the implantation window. Methods Data from RNA-Sequencing of endometrial biopsies collected during the implantation window from 17 patients (6 infertile women with endometriosis, 6 infertile controls, 5 fertile controls) were analyzed for variant discovery and identification of functional mutations. A targeted study of the alterations found was performed to understand the data into disease's context. Results None of the variants identified was common to other samples within the same group, and no mutation was repeated among patients with endometriosis, infertile and fertile controls. In the endometriosis group, nine predicted deleterious mutations were identified, but only one was previously associated to a clinical condition with no endometrial impact. When crossing the mutated genes with the descriptors endometriosis and/or endometrium, the gene CMKLR1 was associated either with inflammatory response in endometriosis or with endometrial processes for pregnancy establishment. Conclusion Despite no pattern of mutation having been found, we ponder the small sample size and the analysis on RNA-sequencing data. Considering the purpose of the study of screening and the importance of the CMKLR1 gene on endometrial

Resumo Objetivo Anormalidades no endométrio eutópico de mulheres com endometriose podem estar relacionadas à infertilidade associada à doença. Embora a análise prévia de sequenciamento de RNA não tenha evidenciado expressão diferencial em transcritos endometriais de pacientes com endometriose, outras alterações moleculares poderiam afetar a síntese de proteínas e a receptividade endometrial. Nosso objetivo foi rastrear mutações funcionais em transcritos de endométrios eutópicos de mulheres inférteis com endometriose e de controles durante a janela de implantação. Métodos Os dados do sequenciamento de RNA de biópsias endometriais coletados durante a janela de implantação de 17 pacientes (6 mulheres inférteis com endometriose, 6 controles inférteis, 5 controles férteis) foram analisados para a descoberta de variantes e a identificação de mutações funcionais. Um estudo direcionado das alterações encontradas foi realizado para compreender os dados no contexto da doença. Resultados Nenhuma das variantes identificadas foi comuma outras amostras dentro do mesmo grupo, assim como nenhuma mutação se repetiu entre pacientes com endometriose, controles inférteis e férteis. No grupo de endometriose, foram identificadas nove mutações deletérias preditas, mas apenas uma foi previamente associada a uma condição clínica sem impacto endometrial. Ao cruzar os genes mutados com os descritores endometriose e/ou endométrio, o gene CMKLR1 foi associado a resposta inflamatória na endometriose e a processos endometriais para estabelecimento da gravidez. Conclusão Apesar de nenhum padrão de mutação ter sido encontrado, ponderamos o pequeno tamanho da amostra e a análise dos dados de sequenciamento de RNA. Considerando o objetivo do estudo de triagem e a importância do gene CMKLR1 na modulação endometrial, este poderia ser um gene candidato para estudos adicionais que avaliem mutações no endométrio eutópico de pacientes com endometriose.

Hemorragia de vías digestivas altas por presentación atípica de adenocarcinoma endometrial metastásico en el estómago. Tipificación diagnóstica con recursos endoscópicos / Upper gastrointestinal bleeding due to atypical presentation of metastatic endometrial adenocarcinoma in the stomach. Diagnostic typing with endoscopic resources

Resumen El cáncer de endometrio es la neoplasia ginecológica maligna más frecuente en el sexo femenino. Su presentación metastásica se limita principalmente a los órganos vecinos y ganglios cercanos, y es infrecuente la invasión al tubo digestivo superior. En el presente artículo se presenta una paciente que ingresó al servicio de urgencias con cuadro de hemorragia de vías digestivas altas, enfocado inicialmente como un tumor estromal gastrointestinal (GIST) de la pared gástrica, pero que luego de la realización de una adecuada historia clínica, complementada con imágenes diagnósticas y avances ecoendoscópicos, se logró el diagnóstico de metástasis de cáncer de endometrio.

Abstract Endometrial cancer is the most common gynecologic malignancy in women. Its metastatic presentation is mainly limited to neighboring organs and nearby lymph nodes, and infiltration of the upper digestive tract is uncommon. This case report depicts a patient admitted to the emergency department with upper gastrointestinal bleeding symptoms. Initially, a gastrointestinal stromal tumor (GIST) of the gastric wall was suspected, but endometrial cancer metastasis was discovered after a thorough medical examination, diagnostic imaging, and echoendoscopes.