Clinicopathological analysis of primary gastric (gastrointestinal)-type mucoglandular lesion of endometrium / 中华病理学杂志

Objective: To investigate the clinical and pathological features of primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium. Methods: Eight cases of primary gastric (gastrointestinal)-type mucoglandular lesions of endometrium diagnosed between 2014 to 2022 were retrieved from pathology archives of the Obstetrics and Gynecology Hospital Affiliated to Fudan University, Shanghai, China. The clinical history, pathological sections and follow-ups were analyzed. Results: The eight patients ranged in age from 35 to 67 years, with an average age of 55.5 years. Seven patients were examined for high-risk human papillary virus (HPV) before operation. Only one of them was positive for high-risk HPV52. No cervical mucinous lesions were found in any of the patients. Two cases were invasive gastric (gastrointestinal)-type adenocarcinoma, 2 cases were benign gastric (gastrointestinal)-type mucinous metaplasia, and the other 4 cases were atypical gastric (gastrointestinal)-type mucinous gland hyperplasia. Microscopically, tumor cells showed mucous epithelium with gastrointestinal differentiation. Immunophenotyping showed that MUC6 was diffusely or focally positive in 5 cases, CK20 and CDX2 were positive in 3 cases. And p16 was negative or focally positive in 5 cases and strongly positive in 1 case. ER was expressed in both benign and atypical lesions, and weakly positive or negative in the invasive adenocarcinoma. p53 showed mutant expression in one case and wild-type expression in the rest. HPV in situ hybridization was negative. Conclusions: Primary gastric (gastrointestinal)-type mucoglandular lesions of the endometrium show various forms of gastrointestinal differentiation, which are high-risk HPV independent. Morphology combined with immunohistochemistry is helpful for the diagnosis, which can only be made on exclusion of cervical gastrointestinal glandular lesion, gastrointestinal metastatic carcinoma and the mucinous subtype of endometrioid carcinoma.

Upregulation of h-TERT and Ki-67 in ectopic endometrium is associated with recurrence of endometriosis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

At present, endometriosis remains a worldwide health burden, with the main symptoms of dysmenorrhea, chronic pelvic pain, and infertility, markedly reducing the quality of life (de Ziegler et al., 2010). Although there is no proof that the disease is associated with high mortality, this disorder can significantly contribute to the deterioration of women's general well-being (McPeak et al., 2018). The main current treatment for endometriosis is surgery to remove endometriotic lesions; however, the recurrence rate following surgical treatment is as high as 21.5% at two years and 40.0%‍-‍50.0% at five years post-surgery (Koga et al., 2015). To prevent recurrence, adjuvant treatment with drugs after surgery is recommended to prolong relapse-free intervals. However, it is inconvenient for patients to continuously use such medications in terms of adverse effects and cost (Turk, 2002).

Accuracy of Transvaginal Ultrasound in the Diagnosis of Intrauterine Lesions / Acurácia da ultrasonografia tranvaginal no diagnóstico de lesões intrauterinas

Abstract Objective To evaluate the accuracy of transvaginal ultrasound in the diagnosis of intrauterine lesions, using hysteroscopy as the gold standard. Methods This was a prospective observational study with 307 patients. All patients underwent hysteroscopy after a previous transvaginal ultrasound to compare the results. The hysteroscopy was performed by experienced examiners, and transvaginal ultrasounds were performed in various public and private services, which is reflective of routine healthcare practices in obstetrics and gynecology. The sensitivity, specificity, and accuracy of the transvaginal ultrasound were calculated using hysteroscopy as the gold standard. The level of agreement between the two exams was calculated using the Kappa test. Results Themean age was 56.55±12.3 years. For endometrial polyps, we observed a sensitivity of 39.8%, specificity of 72.7%, accuracy of 52.8%, and Kappa index of 0.11 (p=0.025). For fibroids, the sensitivity was 46.7%, specificity was 95.0%, accuracy was 87.9%, and Kappa index was 0.46 (p<0.001). For endometrial thickening, the sensitivity was 68.7%, specificity was 41.7%, accuracy was 47.6%, and Kappa index was 0.06 (p=0.126). For endometrial atrophy, we found a sensitivity of 6.7%, specificity of 99.3%, accuracy of 90.2%, and Kappa index of 0.10 (p=0.006). For the other findings, the sensitivity was 15.6%, specificity was 99.6%, accuracy was 87.3%, and Kappa index was 0.23 (P<0.001). Conclusion Our study demonstrated a low level of accuracy of transvaginal ultrasound for the diagnosis of endometrial lesions, when performed by a non-experienced professional. Thus, it is important to consider the use of hysteroscopy to avoid unnecessary and inappropriate treatments.

Resumo Objetivo Avaliar a acurácia do ultrassom transvaginal para o diagnóstico de lesões intrauterinas, tendo a histeroscopia como padrão de referência. Métodos Foi realizado um estudo observacional prospectivo em 307 pacientes, submetidas à histeroscopia após ultrassonografia prévia para comparação dos resultados. A histeroscopia foi realizada por duas médicas com experiência, e os exames de ultrassom foram realizados em diversas fontes, públicas ou privadas, como ocorre no cotidiano da assistência à saúde em nosso meio. Foram avaliados sensibilidade, especificidade e acurácia, tendo a histeroscopia como padrão-ouro. O nível de concordância foi avaliado pelo teste de Kappa. Resultados A idade média foi de 56,55±12,3 anos. Os resultados para pólipo endometrial foram: sensibilidade 39.8%, especificidade 72,7%, acurácia de 52,8%, e índice Kappa 0,11 (p=0,025). Para mioma, sensibilidade 46,7%, especificidade 95,0%, acurácia 87,9%, e índice Kappa 0,46 (p<0,001). Para espessamento endometrial, sensibilidade 68,7%, especificidade 41,7%, acurácia 47,6%, e índice Kappa de 0,06 (p=0,126). Para atrofia, sensibilidade 6,7%, especificidade 99,3%, acurácia 90,2%, e índice Kappa 0,10 (p=0,006). Para outros achados, sensibilidade 15,6%, especificidade 99,6%, acurácia 87,3%, e índice Kappa 0,23 (p<0,001). Conclusão Nosso estudo demonstrou baixo nível de acurácia da ultrassonografia transvaginal para o diagnóstico de lesões endometriais, quando realizada por profissional não experiente. Assim, é importante considerar o uso da histeroscopia para evitar tratamentos desnecessários e inadequados.

Técnica morfométrica en el diagnóstico diferencial de hiperplasia endometrial compleja y adenocarcinoma endometroide. Matanzas; 2014-2015 / Morphometric technique in the differential diagnosis of complex endometrial hyperplasia and endometroid adenocarcinoma. Matanzas; 2014-2015

RESUMEN Introducción: la función del endometrio está regida por el eje hipotálamo hipofisario mediante las hormonas sexuales por lo que es vulnerable a los desórdenes de este sistema los que provocan diferentes trastornos funcionales que se traducen en alteraciones morfológicas. Es fundamental su estudio para el diagnóstico de patologías que son un problema de salud en la población femenina. Objetivo: determinar las diferencias morfométricas para el diagnóstico histopatológico diferencial entre la hiperplasia endometrial compleja, el adenocarcinoma endometrioide y en el endometrio proliferativo normal, en el municipio Matanzas, enero2014 -2015. Material y Métodos: se realizó un estudio observacional descriptivo de corte transversal y se aplicó morfometría a una muestra de 30 biopsias endometriales, con el objetivo de determinar las diferencias morfométricas para el diagnóstico histopatológico diferencial entre la hiperplasia endometrial compleja, el adenocarcinoma endometrioide y en el endometrio proliferativo normal. Resultados: el área total de la glándula fue la variable analizada que mostró mayores valores y reflejó marcadas diferencias entre la hiperplasia endometrial compleja, el adenocarcinoma endometrioide y el endometrio proliferativo normal, seguida por la altura del epitelio por tanto existen diferencias cuando se estudian variables que tiene en cuenta la morfología glandular. Conclusiones: existen diferencias morfométricas entre la hiperplasia endometrial y el adenocarcioma endometroide cuando se estudian variables que tienen en cuenta la morfología y arquitectura glandular (AU).

SUMMARY Introduction: the endometrium function is ruled by the pituitary- hypothalamus axis by means of sexual hormones; therefore it is vulnerable to the disorders of this system provoking different functional disorders resulting in morphological alterations. It is very important to study them for the sake of the diagnosis of diseases that are a health problem in female population. Objective: to determine the morphometric differences for the differential histopathological diagnosis among the complex endometrial hyperplasia, the endometrioid adenocarcinoma and the normal proliferative endometrium e, in the municipality of Matanzas, in the period January 2014-2015. Methods: a cross-sectional descriptive observational study was carried out applying morphometry to a sample of 30 endometrial biopsies, with the objective of determining the morphometric differences for the differential histopathological diagnosis among the complex endometrial hyperplasia, endometrial adenocarcinoma and normal proliferative endometrium. Results: the gland total area was the used variable showing more values and revealed stark differences among complex endometrial hyperplasia, endometrioid adenocarcinoma and normal proliferative endometrium, followed by the epithelium height; hence there are differences when variables are studied taking into account glandular morphology. Conclusions: there are morphometric differences between endometrial hyperplasia and endometrioid adenocarcinoma when there are studied variables taking into account glandular morphology and architecture (AU).

Regulatory T cells isolated from endometriotic peritoneal fluid express a different number of Toll-like receptors / Células T reguladoras isoladas do fluido peritoneal de mulheres com endometriose expressam um número diferente de receptores do tipo Toll

ABSTRACT Objective To analyze and compare the expression of Toll-like receptors by regulatory T cells present in the peritoneal fluid of patients with and without endometriosis. Methods Regulatory T cells were isolated from peritoneal fluid of women with and without endometriosis, collected during surgery, and mRNA was extracted for analysis of Toll-like receptors expression by reverse-transcriptase polymerase chain reaction. Results Patients with endometriosis presented regulatory T cells expressing a larger number and variety of Toll-like receptors when compared to regulatory T cells from patients in the Control Group. Toll-like receptor-1 and Toll-like receptor-2 in regulatory T cells were expressed in both groups. All other expressed Toll-like receptors types were only found in regulatory T cells from the Endometriosis Group. Conclusion Patients with endometriosis had peritoneal regulatory T cells expressing various Toll-like receptors types.

RESUMO Objetivo Analisar e comparar a expressão de receptores do tipo Toll por células T reguladoras presentes no líquido peritoneal de pacientes com endometriose. Métodos Células T reguladoras foram isoladas do líquido peritoneal de mulheres com e sem endometriose, coletadas durante a cirurgia, e o RNAm foi extraído para análise da expressão de receptores do tipo Toll por reação em cadeia da polimerase com transcriptase reversa. Resultados Pacientes com endometriose apresentaram células T reguladoras expressando maior número e variedade de Toll por células quando comparadas com T reguladoras de pacientes do Grupo Controle. Receptores do tipo Toll-1 e receptores do tipo Toll-2 foram expressos em ambos os grupos. Todos os outros tipos de receptores Toll foram encontrados expressos apenas em células T reguladoras do grupo com endometriose. Conclusão Pacientes com endometriose apresentaram células T reguladoras peritoneais expressando vários tipos de receptores tipo Toll.

Thalidomide reduces cell proliferation in endometriosis experimentally induced in rats / A talidomida induz diminuição da proliferação celular em endometriose experimentalmente induzida em ratas

Abstract Objective To analyze the effect of thalidomide on the progression of endometriotic lesions experimentally induced in rats and to characterize the pattern of cell proliferation by immunohistochemical Proliferating Cell Nuclear Antigen (PCNA) labeling of eutopic and ectopic endometrium. Methods Fifteen female Wistar rats underwent laparotomy for endometriosis induction by resection of one uterine horn, isolation of the endometrium and fixation of a tissue segment to the pelvic peritoneum. Four weeks after, the animals were divided into 3 groups: control (I), 10mg/kg/day (II) and 1mg/kg/day (III) intraperitoneal thalidomide for 10 days. The lesion was excised together with the opposite uterine horn for endometrial gland and stroma analysis. Eutopic and ectopic endometrial tissue was submitted to immunohistochemistry for analysis of cell proliferation by PCNA labeling and the cell proliferation index (CPI) was calculated as the number of labeled cells per 1,000 cells. Results Group I showed a mean CPI of 0.248 ± 0.0513 in the gland and of 0.178 ± 0.046 in the stroma. In contrast, Groups II and III showed a significantly lower CPI, that is, 0.088 ± 0.009 and 0.080 ± 0.021 for the gland (p < 0.001) and 0.0945 ± 0.0066 and 0.075 ± 0.018 for the stroma (p < 0.001), respectively. Also, the mean lesion area of Group I was 69.2mm2, a significantly higher value compared with Group II (49.4mm2, p = 0.023) and Group III (48.6mm2, p = 0.006). No significant difference was observed between Groups II and III. Conclusion Thalidomide proved to be effective in reducing the lesion area and CPI of the experimental endometriosis implants both at the dose of 1mg/kg/day and at the dose of 10 mg/kg/day.

Resumo Objetivo Analisar o efeito da talidomida na progressão de lesões endometrióticas induzidas experimentalmente em ratas e caracterizar o padrão de proliferação celular pela marcação imunohistoquímica de Antígeno Nuclear de Célula Proliferativa (PCNA) no endométrio eutópico e ectópico. Métodos Quinze ratas Wistar foram submetidas a laparotomia para indução de endometriose por ressecção de um corno uterino, isolamento do endométrio e fixação de um segmento do tecido ao peritônio pélvico. Após quatro semanas, os animais foram divididos em 3 grupos: controle (I), 10 mg/kg/dia (II) e 1 mg/kg/dia (III) de talidomida intraperitoneal por um período de 10 dias. As lesões foram resseccionadas juntamente com o corno uterino oposto para análise da glândula endometrial e do estroma. O tecido endometrial eutópico e ectópico foi submetido à imunohistoquímica para análise da proliferação celular por marcação com PCNA e o índice de proliferação celular (CPI) foi calculado como o número de células marcadas por 1.000 células. Resultados O grupo I apresentou média de CPI de 0,248 ± 0,0513 na glândula e de 0,178 ± 0,046 no estroma. Em contraste, os grupos II e III apresentaram CPI significativamentemenor, isto é, 0,088 ± 0,009 e 0,080 ± 0,021 para a glândula (p < 0,001) e 0,0945 ± 0,0066 e 0,075 ± 0,018 para o estroma (p < 0,001), respectivamente. Além disso, a área de lesãomédia do Grupo I foi de 69,2mm2, valor significativamentemaior em relação ao Grupo II (49,4mm2, p = 0,023) e Grupo III (48,6mm2, p = 0,006). Não houve diferença estatisticamente significante entre os Grupos II e III. Conclusão A talidomida mostrou-se eficaz na redução da área da lesão e CPI dos implantes de endometriose experimental tanto na dose de 1mg/kg/dia quanto na dose de 10 mg/kg/dia.

Endometrial tuberculosis: hysteroscopic findings of a clinical case / Tuberculose endometrial: Achados histeroscópicos de um caso clínico

Abstract Endometrial tuberculosis is a rare diagnosis in the postmenopausal period, and it can mimic a carcinoma. The present article describes the case of a 54-year-old female patient with weight loss, abdominal pain, and ascites. An ultrasonography showed endometrial thickening, and a video hysteroscopy revealed a uterine cavity with formations with cotton aspect covering the entire endometrial surface and the tubal ostia. An anatomopathological evaluation diagnosed endometrial tuberculosis. The treatment was with a standardized therapeutic scheme (ethambutol, isoniazid, pyrazinamide and rifampicin), and the patient evolved with clinical improvement and normal uterine cavity at hysteroscopy. Considering the lack of pathognomonic hysteroscopic findings of the disorder, it is important to disclose the images of the case.

Resumo A tuberculose endometrial é um diagnóstico raro na pós-menopausa e podemimetizar um carcinoma. O presente artigo descreve o caso de uma paciente de 54 anos com perda de peso, dor abdominal e ascite. A ultrassonografia mostrou espessamento endometrial, e a histeroscopia por vídeo revelou uma cavidade uterina com formações que apresentavam aspecto de algodão cobrindo toda a superfície endometrial e os óstios tubários. Uma avaliação anatomopatológica diagnosticou tuberculose endometrial. O tratamento foi com esquema terapêutico padronizado (etambutol, isoniazida, pirazinamida e rifampicina), e a paciente evoluiu com melhora clínica e cavidade uterina normal na histeroscopia. Considerando a falta de achados histeroscópicos patognomônicos do distúrbio, é importante divulgar as imagens do caso.

Downregulation of lncrna uca1 as a diagnostic and prognostic biomarker for ovarian endometriosis

SUMMARY OBJECTIVE: Ovarian endometriosis seriously affects the quality of life of females, and long non-coding RNA lncRNA urothelial carcinoma-associated 1 (UCA1) plays pivotal roles in the pathogenesis of various ovarian diseases. However, the involvement of lncRNA UCA1 in ovarian endometriosis remains unknown to date. Therefore, the present study aims to study the role of UCA1 in ovarian endometriosis. METHODS: A total of 98 patients with ovarian endometriosis and 28 healthy females were included. The expression of lncRNA UCA1 in ectopic and eutopic endometrium tissues of ovarian endometriosis patients and controls was detected using qRT-PCR. A ROC curve analysis was performed to evaluate the diagnostic values of serum lncRNA UCA1 for ovarian endometriosis. Patients were followed up for 2 years after discharge, and the recurrence of ovarian endometriosis was recorded. RESULTS: The expression level of lncRNA UCA1 was significantly higher in ectopic endometrium tissues than in paired eutopic endometrium tissues for most of the patients. The serum lncRNA UCA1 level showed no significant correlations with either patients' age or living habits. After the treatment, the serum lncRNA UCA1 level increased, and serum levels of lncRNA UCA1 on the day of discharge were significantly lower in patients with recurrence than those in patients without recurrence. Conclusion: The downregulation of lncRNA UCA1 is involved in the pathogenesis of ovarian endometriosis and may serve as a promising diagnostic and prognostic biomarker for the disease.

RESUMO OBJETIVO: A endometriose ovariana afeta seriamente a qualidade de vida das mulheres, e o carcinoma urotelial 1 de urcélio de RNA não codificador longo 1 (UCA1) desempenha um papel crucial na patogênese de várias doenças ovarianas. No entanto, o envolvimento do lncRNA UCA1 na endometriose ovariana permanece desconhecido até o momento. Portanto, o presente estudo tem como objetivo estudar o papel do UCA1 na endometriose ovariana. Métodos: Um total de 98 pacientes com endometriose ovariana e de 28 mulheres saudáveis foi incluído. A expressão de lncRNA UCA1 em tecidos de endométrio ectópico e eutópico de pacientes com endometriose ovariana e controles foi detectada por qRT-PCR. A análise da curva ROC foi realizada para avaliar os valores diagnósticos do lncRNA UCA1 sérico para endometriose ovariana. Os pacientes foram acompanhados por dois anos após a alta, e a recorrência da endometriose ovariana foi registrada. RESULTADOS: O nível de expressão do lncRNA O UCA1 foi significativamente maior nos tecidos do endométrio ectópico do que nos tecidos do endométrio eutópico pareados para a maioria dos pacientes. O nível sérico de UCA1 foi diminuído com a progressão da endometriose ovariana. O soro UCA1 pode ser usado para diagnosticar com precisão a endometriose ovariana. O nível sérico de UCA1 não apresentou correlações significativas com a idade ou com os hábitos de vida dos pacientes. Após o tratamento, o nível sérico do lncRNA UCA1 foi aumentado, e os níveis séricos de lncRNA UCA1 no dia da alta foram significativamente menores nos pacientes com recidiva do que naqueles sem recorrência. CONCLUSÃO: A regulação negativa do lncRNA UCA1 está envolvida na patogênese da endometriose ovariana e pode servir como um promissor biomarcador diagnóstico e prognóstico para a doença.

Correlación clínica, imagenológica e histológica en patología endometrial: experiencia en el hospital Dr. Francisco Antonio Rísquez (2006-2016) / Clinical, imaging and histological correlation in endometrial pathology: experience in the hospital Dr. Francisco Antonio Rísquez (2006-2016)

Para el estudio y diagnóstico de la patología endometrial se cuenta con el ultrasonido transvaginal y la biopsia de endometrio. Objetivo: Determinar la correlación clínica, ultrasonográfica e histológica en patología endometrial, en pacientes tratadas en el Servicio de Cirugía del Hospital Dr. Francisco Antonio Rísquez, entre 2006 y 2016. Métodos: Estudio retrospectivo, transversal. Se incluyeron las pacientes intervenidas quirúrgicamente por patologías uterinas, que contaron con información completa en la historia clínica. Se utilizó estadística descriptiva, sensibilidad, especificidad y coeficiente de correlación. Resultados: El grupo etario más afectado fue el de 41 a 50 años, con 62,73 %, el motivo de consulta más frecuente fue sangrado genital con 52 casos (47,3 %), 52 pacientes (47,3 %) presentaron sangrado menstrual abundante y 40 (36,4 %) refirieron sangrado abundante y prolongado. Ecográficamente, el diagnóstico más frecuente fue leiomiomatosis uterina (87 casos, 79,1 %). La línea endometrial estuvo entre 1,3 y 11,3 mm en 80,9 %; en 54 casos (49,1 %) la biopsia de endometrio reportó secretor sin atipia. No se observó correlación estadística entre la clínica y la biopsia de endometrio (p=0,478 Kappa=0,00). La correlación estadística entre el ultrasonido y la biopsia de endometrio fue casi perfecta (p=0,000 Kappa=0,947) y entre la biopsia preoperatoria y la definitiva fue moderada (p=0,000 Kappa 0,542). La sensibilidad del ultrasonido es de 100 % y especificidad de 90,91 %. Conclusiones: La sensibilidad y especificidad del ultrasonido respecto a la biopsia de endometrio fue elevada. La frecuencia de patología endometrial en la biopsia endometrial fue baja(AU)

For the study and diagnosis of endometrial pathology it has with transvaginal ultrasound and endometrial biopsy. Objective: To determine the correlation of clinical, ultrasound and histological endometrial pathology in patients treated in the service of surgery of the Hospital Dr. Francisco Antonio Rísquez, between 2006 and 2016. Methods: Retrospective, cross-sectional study. Included patients surgically treated by uterine pathologies, which counted with complete information in the medical record. We used descriptive statistics, sensitivity, specificity, and correlation coefficient. Results: The most affected age group was that of 41 to 50 years, in 62,73%, the reason for more frequent consultation was bleeding genital with 52 cases (47.3%), 52 patients (47.3%) they had heavy menstrual bleeding and 40 (36.4%) abundant and prolonged bleeding was referred. Ecograficamente, the most frequent diagnosis was uterine leiomyomatosis (87 cases, 794.1%). The endometrial line was between 1.3 and 11.3 mm 80.9%; in 54 cases (49.1%) the endometrial biopsy reported secretory without atypia. No statistical correlation between the clinic and the endometrial biopsy was observed (p = 0, 478 Kappa = 0, 00). The statistical correlation between ultrasound and endometrial biopsy was almost perfect (p = 0, 000 Kappa = 0, 947) and between preoperative biopsy and the final was moderate (p = 0, 0000,542 Kappa). The sensitivity of ultrasound is 100% and specificity of 90.91%. Conclusions: The sensitivity and specificity of ultrasound for endometrial biopsy was high. The frequency of endometrial pathology in endometrial biopsy was low(AU)

Increased expression levels of metalloprotease, tissue inhibitor of metalloprotease, metallothionein, and p63 in ectopic endometrium: an animal experimental study / Aumento nos níveis de expressão de metaloprotease, inibidor tecidual das metaloproteases, metalotioneina e p63 em endométrio ectópico: um estudo experimental animal

Abstract Objective To characterize the patterns of cell differentiation, proliferation, and tissue invasion in eutopic and ectopic endometrium of rabbits with induced endometriotic lesions via a well- known experimental model, 4 and 8 weeks after the endometrial implantation procedure. Methods Twenty-nine female New Zealand rabbits underwent laparotomy for endometriosis induction through the resection of one uterine horn, isolation of the endometrium, and fixation of tissue segment to the pelvic peritoneum. Two groups of animals (one with 14 animals, and the other with15) were sacrificed 4 and 8 weeks after endometriosis induction. The lesion was excised along with the opposite uterine horn for endometrial gland and stroma determination. Immunohistochemical reactions were performed in eutopic and ectopic endometrial tissues for analysis of the following markers: metalloprotease (MMP-9) and tissue inhibitor of metalloprotease (TIMP-2), which are involved in the invasive capacity of the endometrial tissue; and metallothionein (MT) and p63, which are involved in cell differentiation and proliferation. Results The intensity of the immunostaining for MMP9, TIMP-2, MT, and p63 was higher in ectopic endometria than in eutopic endometria. However, when the ectopic lesions were compared at 4 and 8 weeks, no significant difference was observed, with the exception of the marker p63, which was more evident after 8 weeks of evolution of the ectopic endometrial tissue. Conclusion Ectopic endometrial lesions seem to express greater power for cell differentiation and tissue invasion, compared with eutopic endometria, demonstrating a potentially invasive, progressive, and heterogeneous presentation of endometriosis.

Resumo Objetivo Caracterizar o padrão de diferenciação celular, proliferação e invasão tecidual em endométrio eutópico e ectópico de coelhas com lesões de endometriose induzidas por um modelo experimental 4 e 8 semanas após o procedimento de implantação endometrial. Métodos Vinte e nove coelhas fêmeas Nova Zelândia foram submetidas a laparotomia para indução de endometriose através da ressecção de um dos cornos uterinos, isolamento do endométrio e fixação do tecido no peritônio pélvico. Dois grupos de animais (14 animais em um grupo e 15 animais no outro) foram sacrificados 4 e 8 semanas após a indução da endometriose. A lesão foi excisada junto com o corno uterino contralateral para determinação da presença de glândulas e de estroma endometrial. Reações de imunohistoquímica foram realizadas no tecido endometrial eutópico e ectópico para análise dos seguintes marcadores: metaloprotease (MMP9) e inibidor tecidual da metaloprotease 2 (TIMP-2), os quais estão envolvidos na capacidade de invasão do tecido endometrial; e metalotioneina (MT) e p63, os quais estão envolvidos na diferenciação e proliferação celular. Resultados A intensidade da imunomarcação para MMP9, TIMP-2, MT e p63 foi mais alta nos endométrios ectópicos do que nos endométrios eutópicos. Contudo, quando as lesões foram comparadas entre 4 e 8 semanas, nenhuma diferença foi observada, com exceção do marcador p63, o qual foi mais evidente depois de 8 semanas de evolução do tecido endometrial ectópico. Conclusão Lesões endometriais ectópicas parecem expressar maior poder de diferenciação celular e de invasão tecidual comparadas com endométrios eutópicos, demonstrando o potencial de invasão, de progressão e de apresentação heterogênea da endometriose.

Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits

PURPOSE: To investigate the efficacy of intralesional 20% aspirin injection for treatment of experimental peritoneal endometriosis. Methods: Peritoneal endometriosis was experimentally induced in forty adult nulligravid female rabbits. On day 30 post-endometriosis induction, rabbits were randomly divided to assess early (10 days) and late (20 days) effects of intralesional injection of physiological saline solution (control groups) in comparison to intralesional injection of 20% bicarbonate aspirin solution (experimental groups) as follows: control group 1 (10 days, n=10); control group 2 (20 days, n=10); experimental group 3 (10 days, n=10); experimental group 4 (20 days, n=10). Resected tissues, including endometriosis foci, were qualitatively (general morphology and signs of inflammatory cells infiltrate, necrosis and apoptosis) and quantitatively (remaining endometriosis area) assessed by histopathological analysis. Results: Extensive necrosis, hemorrhage, apoptosis, and fibrosis were observed in the experimental groups 3 and 4. Groups 1 and 2 presented typical endometrial tissue cysts, respectively. Groups 3 and 4 showed sparse endometrial tissue foci and no endometrial tissue, respectively. Quantitative analysis revealed that aspirin-treated groups 3 and 4 had significantly (p<0.05) smaller remaining endometriosis area, compared to control groups 1 and 2. Conclusion: Intralesional 20% aspirin injection caused total destruction of peritoneal endometriosis foci in rabbits.

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice

PURPOSE: To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. METHODS: BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. RESULTS: Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. CONCLUSION: There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

Carcinoma epidermoide de cuello uterino con extensión superficial a endometrio / Squamous cell carcinoma of the cervix with superficial extension to the endometrium

El cáncer de cuello uterino es la neoplasia más frecuente del tracto genital femenino, que en su forma avanzada puede invadir localmente a tejido paracervical, vagina, vejiga y recto. Se presenta un caso, muy poco frecuente, de carcinoma cervical con extensión endometrial como neoplasia in situ, en una paciente de 76 años y que se manifestó clínicamente como piometra.

Cervical cancer is the most common malignant tumor of the female genital tract, which in its advanced stage can invade locally paracervical tissue, vagina, bladder and rectum. A case extremely rarely is reported of cervical carcinoma with in situ carcinoma involving to endometrium in a patient of 76 years old and clinically manifested as pyometra.

Dismenorrea membranácea durante la menarquia / Membranous dysmenorrhea during menarche

La dismenorrea membranosa se caracteriza por dolor menstrual acompañado de la expulsión de la mucosa endometrial en forma de grandes fragmentos, e incluso en una única pieza, con la forma del molde de la cavidad uterina. Se presenta el caso de una paciente con expulsión de un gran molde de endometrio durante la menarquia. Se presentan las imágenes del molde endometrial íntegro de la cavidad uterina y el estudio anatomopatológico.

Membranous dysmenorrheal consist of menstrual pain accompanied by the expulsion of endometrial mucosa in the form of large fragments or even in one piece with the shape of the uterine cavity. We present the case of a patient with expulsion of endometrial during menarche. The pictures of endometrial piece, the shape of the uterine cavity and anatomo-pathological study has presented.

Adiponectin effect on nitric oxide secretion by normal and endometriotic human endometrial stromal cells: in vitro study / Efecto de la adiponectica sobre la secreción de óxido nítrico por células estromales de endometrio humano, normales y con endometriosis: estudio in vitro

Endometriosis is an estrogen-dependent disease in reproductive age women. Adiponectin and Nitric oxide (NO) have an important role in physiologic functions especially in human reproductive system. Levels of NO increased in the endometriosis patients but serum adiponectin levels decreased in woman with endometriosis. The aim of this study was to determine adiponectin effect on nitric oxide secretion by cultured normal and endometriotic human endometrial stromal cells. In this experimental study, normal (n= 10) and endometriotic endometrial biopsies (n= 10) were taken in sterile condition. Stromal cells isolated and cultured in in DMEM/ F12 medium and treated with adiponectin concentrations (0, 10, 100, and 200 ng/ml) for 24 and 48 hours. NO assay was done on their supernatants by Greiss method. Data was analyzed by one way ANOVA and p<0.05 was considered significant. There was significant difference between endometriosis groups in NO secretion in all dose of adiponectin and time (p<0.05). In normal groups there was significant difference in 48 hours (p<0.05) but no significant change in 24 hours (p>0.05). Adiponectin effects nitric oxide secretion of cultured human endometriotic stromal cells.

La endometriosis es una enfermedad dependiente de estrógenos que se presenta en mujeres en edad reproductiva. La adiponectina y el óxido nítrico (ON) tienen un papel importante en las funciones fisiológicas, especialmente en el sistema reproductivo humano. Los niveles de ON aumentan en los pacientes con endometriosis, pero los niveles de adiponectina en suero disminuyen. El objetivo fue determinar el efecto de la adiponectina sobre la secreción de ON por las células estromales de endometrio humano, tanto normales como con endometriosis, en medio de cultivo. En este estudio experimental, las células estromales de endometrio normales (n= 10) y las biopsias de endometrio con endometriosis (n= 10) se tomaron en condiciones de esterilidad. Las células estromales fueron aisladas y cultivadas en un medio DMEM/F12, y se sometieron a distintas concentraciones de adiponectina (0, 10, 100, y 200 ng/ml) durante 24 y 48 horas. El ensayo con ON se realizó a los sobrenadantes obtenidos por el método de Greiss. Los datos recolectados fueron analizados por ANOVA de una vía y un valor p<0,05 se consideró significativo. Entre los grupos con endometriosis, en referencia a la secreción de ON, no hubo diferencia significativa en todas las dosis de adiponectina y los tiempos estipulados (p<0,05). En los grupos normales, hubo diferencia significativa a las 48 horas (p<0,05), pero ningún cambio significativo a las 24 horas (p>0,05). La adiponectina tiene efectos sobre la secreción de óxido nítrico por las células estromales endometriales humanas en cultivo.

Dysfunctional uterine bleeding - a clinicopathological study of 215 cases, Hadhramout -Yemen

Introduction: Dysfunctional uterine bleeding is one of the most common causes for the gynecological patients. This was a retrospective study of different patterns of endometrial pathology and to correlate the histopathology of endometrium with clinical parameters

Material and Methods: This reterospective study was carried out on 215 females over the age of 20 years with DUB at our laoratory sent by gynecologist from Universal Hospital and Al-Amal private clinic, during October 2011 to September 2013

Results: the most common age group presenting of DUB was in age group of 40-49 years [40.50%]. DUB was most frequently seen in grand multipara [75.8%]. Menorrhagia was the predominant bleeding pattern [43.7%]. The normal physiological endometrium [proliferative and secretory endometrium] was the commonest endometrial histopathological diagnosis [51.1%], followed by endometrial hyperplasia [26%]. There were statistically significant relationship between the parity and the bleeding patterns and between endometrial histopathological diagnosis and the parity age and the patterns of bleeding [P value<0.05]

Conclusion: DUB predominantly affects women of 40-49 years old. DUB is common in grand multiparous women and menorrhagia is the most common presenting bleeding pattern. Proliferative and secretory endometrium followed by endometrial hyperplasia is the major endometrial histopathological findings. The parity is significant correlated with bleeding patterns and endometrial histopathological diagnosis; grand multiparous women can be presented with any patterns of bleeding mainly menorrhagia with endometrial hyperplasia. The endometrial histopathological diagnosis was significantly related to age, the majority of endometrial hyperplasia are in age >/= 50 years

morphological study of atypical uterine bleeding

To find out the Histopathological pattern of Endomyometrium in atypical uterine bleeding [AUB], also to study organic causes of AUB. A prospective, descriptive study. This study was conducted at the Departments of Pathology and Gynaecology and Obstetrics, Bolan Medical College Complex Hospital Quetta from January 2011 to January 2013. Specimens were received as endometrial curettage and hysterectomy specimens from patients hospitalized in the dept. of Gynaecology and Obstetrics of BMC Complex Hospital Quetta. This study included 300 women's presenting with AUB, irrespective of age and parity. A detailed clinical history followed by physical examination was also carried out in each patients to exclude systemic causes like psychological upsets and early pregnancy states and also exclude general physical abnormalities. After grossing and H and E staining all the sections were studied by group of pathologists. A Total 300 cases were studied, including 100 endometrial curetting's and 200 uteri in patients of atypical uterine bleeding at Bolan Medical Complex Hospital Quetta. The ages of these patients ranged from 20-69 years. Maximum numbers of cases were in age groups 40-49 years. Chronic endometritis [7 out of 100] 7% and the cystic hyperplasia [9 out of 100] 9% were the most important causes of atypical uterine bleeding in endometrial curetting's. No case of endometrial carcinoma was diagnosed in this series. The histological study of hysterectomy specimen revealed multiple leiomyoma's [135 out of 200] 67.5% and adenomyosis [38 out of 200] 19% as the commonest causes of atypical uterine bleeding. [2 out of 200] 1% case of leiomyosarcoma and [1 out of 200] 0.5% case of choriocarcinoma were diagnosed suggesting a lower frequency of uterine malignancy in our study. In conclusion leiomyoma's and adenomyosis are most important causes of AUB after 3[rd] decade of life. Fortunately the frequency of uterine malignancy [excluding cervix] including endometrial carcinoma is much low in our setup as compared to western studies

Histopathological evaluation of uterine curettings in patients with abnormal uterine bleeding

The main objective of the present study is to determine the histopathological patterns and diagnostic value of endometrial curettings in patients presenting with abnormal uterine bleeding. A prospective study. This study was conducted at Department of Pathology Liaquat University of Medical and Health Sciences Jamshoro during March 2010 to February 2011. A total of 100 cases of endometrial curettage were processed for routine staining with Haematoxylin and Eosin and slides were evaluated for histopathological diagnosis. The results showed that patient's age ranged between 40-52 years and most of the patients about 77%presented with menorrahgia. The histological findings showed normal phase [Proliferative and Secretory phase] of menstrual cycle in 52% of cases followed by simple hyperplasia without atypia 23%, chronic endometritis 13%,polyp 2%, tuberculous endometritis 2%, anovulatory cycle 1%, anovulatory cycle with chronic endometrits 1%,atrophic changes 1%, atypical complex hyperplasia 2% and malignancy in 3% of cases. The Simple hyperplasia23% and chronic endometritis 13% were the commonest pathological alteration. The accidental findings of organic lesions including polyps and malignancy in 5% cases focused the diagnostic importance of curettage in patients presenting with abnormal uterine bleeding. It is concluded that simple hyperplasia without atypia and chronic endometritis are most important causes of abnormal uterine bleeding in the perimenopausal age groups

Achados histeroscópicos na cavidade endometrial após ablação endometrial / Hysteroscopic appearance of the endometrial cavity after endometrial ablation

OBJETIVO: Verificar o aspecto da cavidade uterina após a ablação endometrial histeroscópica, a prevalência de sinéquias após o procedimento e, com isso, avaliar a importância da histeroscopia realizada no pós-operatório dessas pacientes. MÉTODOS: Foram avaliados, retrospectivamente, os laudos dos exames de 153 pacientes que haviam sido submetidas à histeroscopia ambulatorial após ablação do endométrio devido a sangramento uterino anormal de causa benigna, no período entre janeiro de 2006 e julho de 2011. As pacientes foram divididas em dois grupos: HIST≤60 (n=90), com pacientes submetidas ao exame no período de 40 a 60 dias após o procedimento, e grupo HIST>60 (n=63), das que foram examinadas entre 61 dias e 12 meses. RESULTADOS: No grupo HIST≤60, 30% das pacientes apresentavam algum grau de sinéquia; aderências grau I foram descritas em 4,4%; grau II em 6,7%; grau IIa em 4,4%; grau III em 7,8%; e 2,2% apresentavam grau IV. No HIST>60, sinéquias foram descritas em 53,9% dos casos, 3,2% tinham sinéquias grau I; 11,1%, grau II; 7,9%, grau IIa; 15,9%, grau III; e 4,8%, grau IV. Hematometra foi descrito em 2,2% dos casos do HIST≤60 e em 6,3% no HIST>60. CONCLUSÕES: A cavidade uterina de pacientes submetidas à histeroscopia ambulatorial até 60 dias após a ablação endometrial mostrou menor número de sinéquias quando comparada com as cavidades uterinas de pacientes que foram submetidas ao exame após 60 dias. Acompanhamento em longo prazo é necessário para avaliar plenamente o impacto da histeroscopia ambulatorial após a ablação endometrial. .

PURPOSE: To examine the aspect of the uterine cavity after hysteroscopic endometrial ablation, to determine the prevalence of synechiae after the procedure, and to analyze the importance of hysteroscopy during the postoperative period. METHODS: The results of the hysteroscopic exams of 153 patients who underwent outpatient hysteroscopy after endometrial ablation due to abnormal uterine bleeding of benign etiology during the period from January 2006 to July 2011 were retrospectively reviewed. The patients were divided into two groups: HIST≤60 (n=90) consisting of patients undergoing the exam 40-60 days after the ablation procedure, and the group HIST>60 (n=63) consisting of patients undergoing the exam between 61 days and 12 months after the procedure. RESULTS: In the HIST≤60 group, 30% of the patients presented some degree of synechiae: synechiae grade I in 4.4% of patients, grade II in 6.7% , grade IIa in 4.4%, grade III in 7.8%, and grade IV in 2.2%. In the HIST>60 group, 53.9% of all cases had synechiae, 3.2% were grade I, 11.1% grade II, 7.9% grade IIa, 15.9% grade III, and 4.8% grade IV. Hematometra was detected in 2.2 % of all cases in group HIST≤60 and in 6.3% of all cases in group HIST>60. CONCLUSIONS: The uterine cavity of the patients submitted to diagnostic hysteroscopy up to 60 days after endometrial ablation showed significantly fewer synechiae compared to the uterine cavity of patients who underwent the exam after 60 days. Long-term follow-up is necessary to fully evaluate the importance of outpatient hysteroscopy after endometrial ablation regarding menstrual patterns, risk of cancer and prevalence of treatment failure. .