Endometrial mesenchymal stromal/stem cells improve regeneration of injured endometrium in mice

BACKGROUND: The monthly regeneration of human endometrial tissue is maintained by the presence of human endometrial mesenchymal stromal/stem cells (eMSC), a cell population co-expressing the perivascular markers CD140b and CD146. Endometrial regeneration is impaired in the presence of intrauterine adhesions, leading to infertility, recurrent pregnancy loss and placental abnormalities. Several types of somatic stem cells have been used to repair the damaged endometrium in animal models, reporting successful pregnancy. However, the ability of endometrial stem cells to repair the damaged endometrium remains unknown. METHODS: Electrocoagulation was applied to the left uterine horn of NOD/SCID mice causing endometrial injury. Human eMSC or PBS was then injected into the left injured horn while the right normal horn served as controls. Mice were sacrificed at different timepoints (Day 3, 7 and 14) and the endometrial morphological changes as well as the degree of endometrial injury and repair were observed by histological staining. Gene expression of various inflammatory markers was assessed using qPCR. The functionality of the repaired endometrium was evaluated by fertility test. RESULTS: Human eMSC successfully incorporated into the injured uterine horn, which displayed significant morphological restoration. Also, endometrium in the eMSC group showed better cell proliferation and glands formation than the PBS group. Although the number of blood vessels were similar between the two groups, gene expression of VEGF-α significantly increased in the eMSC group. Moreover, eMSC had a positive impact on the regeneration of both stromal and epithelial components of the mouse endometrium, indicated by significantly higher vimentin and CK19 protein expression. Reduced endometrial fibrosis and down-regulation of fibrosis markers were also observed in the eMSC group. The eMSC group had a significantly higher gene expression of anti-inflammatory factor Il-10 and lower mRNA level of pro-inflammatory factors Ifng and Il-2, indicating the role of eMSC in regulation of inflammatory reactions. The eMSC group showed higher implantation sites than the PBS group, suggesting better endometrial receptivity with the presence of newly emerged endometrial lining. CONCLUSIONS: Our findings suggest eMSC improves regeneration of injured endometrium in mice.

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.

The role of KDR in intrauterine adhesions may involve the TGF-ß1/Smads signaling pathway

The aim of this study was to investigate the role of kinase-insert domain-containing receptor (KDR) in intrauterine adhesions (IUA) and its mechanism. The Case group consisted of 92 patients diagnosed with IUA, and the Control group included 86 patients with uterine septum who had normal endometrium verified with an uteroscope. In addition, 50 rats were randomly assigned into Control, Sham, Model, NC-siRNA, and KDR-siRNA groups. Rats in the Model, NC-siRNA, and KDR-siRNA groups were induced by uterine curettage and lipopolysaccharide (LPS) treatment to establish the IUA model. Then, immunohistochemistry was applied for detection of VEGF and KDR expression, HE staining was used for observation of the endometrial morphology and gland counting, Masson staining for measurement of the degree of endometrial fibrosis, and qRT-PCR and western blot for the expression of KDR, VEGF, MMP-9, as well as TGF-β1/Smads pathway-related proteins. Compared with the Control group, the mRNA and protein expressions of KDR were significantly higher in IUA endometrial tissues, and the expression of KDR was positively correlated to the severity of IUA. In addition, the injection of si-KDR increased the number of endometrial glands, reduced the area of fibrosis, inhibited mRNA and protein expression of KDR and VEGF, up-regulated the expression of MMP-9 and Smad7, and decreased the expression level of TGF-β1, p-Smad2, p-Smad3, and Smad4 in rats with IUA. Highly-expressed KDR was related to patients' severity of IUA, and silencing KDR may prevent the occurrence and development of IUA via TGF-β1/Smads signaling pathway and up-regulating the expression of MMP-9.

Accuracy of Transvaginal Ultrasonography, Hysteroscopy and Uterine Curettage in Evaluating Endometrial Pathologies / Acurácia da ultrassonografia transvaginal, histeroscopia e curetagem uterina na avaliação de patologias endometriais

Abstract Objective To evaluate the accuracy of transvaginal ultrasonography, hysteroscopy and uterine curettage in the diagnosis of endometrial polyp, submucous myoma and endometrial hyperplasia, using as gold standard the histopathological analysis of biopsy samples obtained during hysteroscopy or uterine curettage. Methods Cross-sectional study performed at the Hospital Universitário de Brasília (HUB). Data were obtained from the charts of patients submitted to hysteroscopy or uterine curettage in the period from July 2007 to July 2012. Results One-hundred and ninety-one patients were evaluated, 134 of whom underwent hysteroscopy, and 57, uterine curettage. Hysteroscopy revealed a diagnostic accuracy higher than 90% for all the diseases evaluated, while transvaginal ultrasonography showed an accuracy of 65.9% for polyps, 78.1% for myoma and 63.2% for endometrial hyperplasia. Within the 57 patients submitted to uterine curettage, there was an accuracy of 56% for polyps and 54.6% for endometrial hyperplasia. Conclusion Ideally, after initial investigation with transvaginal ultrasonography, guided biopsy of the lesion should be performed by hysteroscopy, whenever necessary, in order to improve the diagnostic accuracy and subsequent clinical management.

Resumo Objetivo avaliar a acurácia da ultrassonografia transvaginal, da histeroscopia e da curetagem uterina no diagnóstico de pólipo endometrial, mioma submucoso e hiperplasia de endométrio, utilizando como padrão-ouro a análise histopatológica de amostras obtidas por biópsia realizada durante a histeroscopia ou a curetagem. Métodos estudo transversal realizado no Hospital Universitário de Brasília (HUB), cujas informações foram obtidas nos prontuários das pacientes que foram submetidas à histeroscopia ou curetagem uterina no período de julho de 2007 a julho de 2012. Resultados Foram avaliadas 191 pacientes, sendo que 134 foram submetidas à histeroscopia e 57 à curetagem uterina. Observou-se acurácia diagnóstica maior que 90% para todas as patologias avaliadas por histeroscopia, enquanto que por ultrassonografia transvaginal observou-se acurácia de 65,9% para pólipo, 78,1% para mioma e 63,2% para hiperplasia endometrial. Nas 57 pacientes submetidas a curetagem uterina, observou-se acurácia de 56% para pólipo e de 54,6% para hiperplasia endometrial. Conclusão Idealmente, após a investigação inicial com ultrassonografia transvaginal, deveria, sempre que necessário, ser realizada histeroscopia com biópsia guiada da lesão, o que melhoraria a acurácia diagnóstica e posterior conduta clínica.

Common Dysregulated Genes in Endometriosis and Malignancies / Genes comuns desregulados em endometriose e doenças malignas

Abstract Several authors have investigated the malignant transformation of endometriosis, which supports the hypothesis of the pre-neoplastic state of endometriotic lesions, but there are few data about the pathways and molecular events related to this phenomenon. This review provides current data about deregulated genes that may function as key factors in the malignant transition of endometriotic lesions. In order to do so, we first searched for studies that have screened differential gene expression between endometriotic tissues and normal endometrial tissue of women without endometriosis, and found only two articles with 139 deregulated genes. Further, using the PubMed database, we crossed the symbol of each gene with the terms related to malignancies, such as cancer and tumor, and obtained 9,619 articles, among which 444 were studies about gene expression associated with specific types of tumor. This revealed that more than 68% of the analyzed genes are also deregulated in cancer. We have also found genes functioning as tumor suppressors and an oncogene. In this study, we present a list of 95 informative genes in order to understand the genetic components that may be responsible for endometriosis' malignant transformation. However, future studies should be conducted to confirm these findings.

Resumo Vários autores têm estudado transformações malignas em endometriose que suportam a hipótese de um estado pré-neoplásico das lesões endometrióticas; contudo, existem poucos dados sobre as vias e eventos moleculares relacionados a este fenômeno. Esta revisão fornece dados atuais sobre genes desregulados que possam funcionar como fatores-chave para a transição maligna das lesões endometrióticas. Assim, inicialmente, estudos de expressão gênica diferencial em larga escala comparando tecido endometriótico e endométrio normal de mulheres sem endometriose foram procurados, e apenas dois artigos com 139 genes desregulados foram obtidos. Posteriormente, usando o banco de dados do PubMed, foram cruzados os símbolos de cada gene com termos relacionados à malignidade, como câncer e tumor, e 9.619 artigos foram obtidos, dos quais 444 eram estudos sobre expressão de genes associados a tipos específicos de tumor. Isto revela que mais de 68% dos genes analisados eram também desregulados em câncer. Também foram encontrados genes que funcionam como supressor tumoral e um oncogene. Este estudo apresenta uma lista de 95 genes informativos para compreender os componentes genéticos que possam ser responsáveis por transformações malignas na endometriose. Contudo, estudos futuros são necessários para confirmar estes achados.

Tamoxifeno y afecciones endometriales en pacientes con cáncer de mama / Tamoxifen and endometrial disease in patients with breast cancer

Los objetivos fueron evaluar la prevalencia de afecciones endometriales en pacientes tratadas con tamoxifeno (TAM) y analizar los aspectos epidemiológicos, ecográficos, histeroscópicos e histopatológicos. Desde enero de 1999 a diciembre 2008 se estudiaron 152 pacientes con cáncer de mama tratadas con TAM (20 mg/día), sintomáticas (con sangrado) o asintomáticas, pre y postmenopáusicas, incluidas en forma consecutiva. El diseño fue prospectivo y observacional. Los métodos diagnósticos usados fueron ecografía transvaginal, histeroscopía y biopsia. Las pacientes fueron seguidas durante 5 años con ecografía cada 12 meses e histeroscopia con biopsia en casos que lo justificaran. Edad: 62.76 ± 10.24 años y tiempo de tratamiento: 36.2 ± 19.9 meses. El adenocarcinoma se observó en 3/87 (3.45%) pacientes con factores de riesgo y en 1/65 (1.54%) sin ellos (RA: 1.91, IC 95% 1.88 a 1.94). Las afecciones benignas se hallaron en 148 pacientes (97.37% y los adenocarcinomas en 4 (2.63%),1 en un pólipo de aspecto benigno. Los 4 se observaron en mujeres postmenopáusicas (2 asintomáticas) con grosor endometrial igual o mayor a 16 mm. El riesgo de cáncer fue significativamente mayor en sintomáticas (2.36 versus 0.42 en asintomáticas). Tres adenocarcinomas se detectaron entre 24 y 48 meses del tratamiento. Recomendamos un seguimiento con ecografía transvaginal de las pacientes asintomáticas, resección de los pólipos evaluando factores de riesgo y tiempo de exposición, en especial luego de los 24 meses. Consideramos aceptable un cut-off = 10 mm en el grosor del endometrio en postmenopáusicas asintomáticas para realizar histeroscopía y biopsia.

The objectives were to evaluate prevalence of endometrial disease in patients treated with tamoxifen (TAM) and analyze the epidemiological, sonographic, hysteroscopic and histopathological findings. From January 1999 to December 2008, 152 breast cancer patients treated with TAM (20 mg/day), symptomatic (with bleeding) or asymptomatic, pre- and postmenopausal, were included consecutively in a prospective and observational follow-up study Diagnostic methods were (TV) transvaginal ultrasound, hysteroscopy and curettage biopsy. TV ultrasound was performed every 12 months for 12 to 60 months. The patients´ age were 62.76 years ± 10.24 the TAM-time: 36.24 ± 19. Adenocarcinoma was observed in 3/87 patients (3.45%) with risk factors and in 1/65 (1.54%) without them (RA 1.91, IC 95% 1.88-1.94). We found benign disease in 148 patients (97.37%) and adenocarcinomas in 4 (2.63%), one within a polyp. The 4 adenocarcinomas were detected in postmenopausal women (2 asymptomatic) with endometrial thicknesses equal or greater than 16 mm. The cancer risk was significantly increased in symptomatic (2.36 versus 0.42 in asymptomatic). Three adenocarcinomas were observed between 24 and 48 months of treatment. In conclusion, we suggest an adequate transvaginal ultrasound monitoring of asymptomatic patients treated with TAM, with removal of polyps, because atypia can be present hidden within, considerin risk factors and exposure time. We suggest as an acceptable cut-off = 10 mm in asymptomatic postmenopausal patients.

Histopathological findings of abdominal hysterectomies in patients presenting with heavy menstrual bleeding [HMB]

To determine the frequency of different histopathological findings in hysterectomy specimens in patients with heavy menstrual bleeding. Cross-sectional study This study was carried out in Gynae Unit III [Sandemen Provincial Teaching Hospital Quetta] from January 2009- December 2009. Two hundred abdominal Hysterectomy cases done for the treatment of heavy menstrual bleeding [HMB] were included in this study. An exclusion criteria was vaginal hysterectomies, abdominal hysterectomies done for complaints other than manorrhagia and malignancies. After hysterectomy specimen of uterus sent for histopathology. The age ranged from 30-55 years with maximum number [62.5%] of cases in 41-50 years of age group. The main presenting complaint of patients was heavy cyclical menstrual flow. Total abdominal Hysterectomies with bilateral salpingoophoroctomy done in 120patients, in 80 patients both ovaries conserved. There was no intra-operative complication. Mild post operative complications occurred in 15% of cases. There was no death. On histopathology leiomyoma was most common pathlogy found in 55% cases. No malignancy was detected on histopathology of the uterus. The study confirmed that benign diseases were more common in hysterectomy specimen performed for HMB. Uterine fibroids and adenomyosis are the most common benign conditions found in hysterectomy specimens on histopathological examination

Huge uterine-cervical diverticulum mimicking as a cyst.

Here we report an incidental huge uterine-cervical diverticulum from a total abdominal hysterectomy specimen in a perimenopausal woman who presented with acute abdominal pain. The diverticulum was mimicking with various cysts present in the lateral side of the female genital tract. Histopathological examination confirmed this to be a cervical diverticulum with communication to uterine cavity through two different openings. They can attain huge size if left ignored for long duration and present a diagnostic challenge to clinicians, radiologists, as well as pathologists because of its extreme rarity. Therefore, diverticula should also be included as a differential diagnosis. Its histopathological confirmation also highlights that diverticula can present as an acute abdomen, requiring early diagnosis with appropriate timely intervention. Immunohistochemistry CD 10 has also been used to differentiate it from a mesonephric cyst.

Efficacy of vitamin E and selenium for the prevention of intra-abdominal adhesions in rats: uterine horn models

OBJECTIVE: This study compares the efficacies of vitamin E and selenium, both individually and in combination, for the prevention of postoperative intra-abdominal adhesions in rats. METHODS: Forty-seven female rats were divided into five groups. The sham animals (S group, n = 7) were given only laparotomies and intraperitoneally received 0.9 percent NaCl (2 ml). In the 40 other rats, abrasions of the left uterine horn were performed, followed by intraperitoneal administration of either 2 ml 0.9 percent NaCl (C group), 10 mg vitamin E (vitamin E group), 0.2 mg/kg selenium (Se group) or 10 mg vitamin E with 0.2 mg/kg selenium (vitamin E + Se group), with 10 animals in each treatment group. RESULTS: Adhesion formation was significantly reduced in animals in the Se and vitamin E + Se groups (p<0.05). Tissue catalase and glutathione peroxidase activities did not significantly differ between the groups. However, catalase and glutathione peroxidase activities and reduced glutathione levels were slightly increased in the vitamin E, Se and vitamin E + Se groups. In the vitamin E group, malondialdehyde concentrations were significantly lower than in the C group (p<0.05), but no significant differences were present among the S, C, Se and vitamin E + Se groups. Levels of nitric oxide were significantly higher in the C group than in the other groups (p<0.01). CONCLUSION: Intraperitoneal administration of selenium or combined vitamin E and selenium appears to be effective in preventing intra-abdominal adhesion formation in rat models through the reduction of lipid peroxidation products.

Células-tronco: a resposta para os enigmas da patogênese da endometriose / Stem cells: the answer to the puzzles of the pathogenesis of endometriosis

A endometriose é uma doença crônica caracterizada pela presença de tecido endometrial ectópico. Esta doença frequentemente resulta em alta morbidade, incluindo dor pélvica crônica e infertilidade. A causa da endometriose é provavelmente multifatorial, sendo ainda objeto de muitos estudos. Fatores genéticos, ambientais e imunes estão possivelmente envolvidos na etiopatogenia desta doença, sendo especulada a associação com outros mecanismos. Nos últimos anos, alguns trabalhos têm demonstrado a presença de células-tronco/progenitoras no endométrio sadio; tais células possivelmente estão envolvidas na capacidade regenerativa desse tecido, assim como na patogênese de doenças ginecológicas proliferativas, como endometriose e carcinoma endometrial. Esta revisão avaliou as evidências disponíveis sobre a existência de células tronco/progenitoras endometriais e agrupou os resultados em uma hipótese de envolvimento dessas células na patogênese da endometriose. Foram selecionados os artigos mais relevantes sobre o tema. A identificação de células-tronco nos tecidos humanos e animais é presumida a partir da identificação de label retaining cells, células side population, marcadores de indiferenciação, potencial de clonogenicidade e diferenciação celular. A presença de supostas células-tronco no endométrio normal e ectópico foi demonstrada por alguns pesquisadores. Células endometriais no endométrio eutópico e em implantes endometrióticos, originadas a partir de células-tronco derivadas de medula óssea transplantada em humanos e de animais, também foram identificadas. Esses resultados sugerem que as células-tronco/progenitoras podem estar envolvidas na gênese da endometriose. No entanto, mais estudos são necessários para corroborar esta hipótese.

Endometriosis is a chronic disease characterized by the presence of ectopic endometrial tissue. This disease often results in high degree of morbidity, including chronic pelvic pain and infertility. Probably, the cause of endometriosis is multifactorial and it has been the object of many studies. Genetic, environmental and immune factors are possibly involved in the pathogenesis of this disease, and it is speculated that there are other mechanisms associated. In recent years, some studies have shown the presence of adult stem cells in the healthy endometrium. These cells are possible involved in the regenerative capability of endometrium and in the pathogenesis of proliferative gynecological diseases, such as endometriosis and endometrial carcinoma. This review evaluated the available evidence on the existence of stem/progenitor cells in the endometrium and gathered the results in an hypothesis of involvement of these cells in the pathogenesis of endometriosis. The most relevant articles about this subject were selected. The identification of stem cells in animal and human tissues is presumed from the identification of label retaining cells, side population cells, undifferentiation markers, besides the potential of clonogenesis and cellular differentiation. The presence of putative stem cells in the normal and ectopic endometrium was demonstrated by some researches. Endometrial cells in eutopic endometrium and endometriotic implants, originated from bone marrow-derived stem cells transplanted into humans and animals, have also been identified. These results suggest that stem/progenitor cells may be involved in the genesis of endometriosis. However, more studies are necessary to this hypothesis

Distribución de la patología quirúrgica del cuerpo uterino en mujeres chilenas sometidas a histerectomía en un hospital clínico universitario / Distribution of pathology in patients undergoing hysterectomy for uterine diseases in Chilean women in an academic centre

Antecedentes: La histerectomía es la cirugía ginecológica mundialmente más frecuente. Pocas series analizan la distribución de los hallazgos patológicos en histerectomizadas. Objetivos: Describir la distribución de la patología uterina originada en el endometrio, miometrio y estroma, en histerectomías efectuadas en un centro universitario. Determinar la frecuencia en que coexisten patologías, particularmente cáncer incidental en histerectomías por condiciones presuntamente benignas. Métodos: Estudio retrospectivo de todas las histerectomías efectuadas entre los años 1991 y 2005. Análisis descriptivo de la distribución de las enfermedades benignas y malignas originadas en el cuerpo uterino. Resultados: Se realizaron 5683 histerectomías. En 4275 úteros se diagnosticaron lesiones de origen no epitelial, principalmente leiomiomas uterinos y adenomiosis. En las 2070 piezas con lesiones epiteliales (endometrio) los hallazgos más prevalentes fueron atrofia, pólipo endometrial e hiperplasia glandular del endometrio. Hubo coexistencia de patología miometrial y endometrial en 905 piezas quirúrgicas. En 240 casos no hubo lesiones en la biopsia (4,2 por ciento). En el 1 por ciento de las histerectomías se encontró como hallazgo un cáncer ginecológico, siendo los dos diagnósticos más frecuentes asociados con esta situación, la metrorragia disfuncional perimenopáusica y el pólipo endometrial. Conclusiones: La distribución de los diagnósticos de la patología uterina es similar a la descrita por series internacionales. El hallazgo más común es el leiomioma uterino, frecuentemente asociado con adenomiosis. Se destaca el hallazgo incidental de cáncer de endometrio en histerectomizadas por metrorragia y/o pólipo endometrial; esto nos hace recomendar el uso rutinario del estudio biópsico preoperatorio en pacientes con metrorragia y de la biopsia contemporánea en casos de pólipo endometrial.

Background: Hysterectomy is the most frequently performed gynecologic procedure worldwide. Few studies have been done to analysis the distribution of pathological findings in hysterectomies. Objectives: To determine the distribution of epithelial and non-epithelial pathology in patients undergoing hysterectomy for uterine disease in an academic centre. To establish what is the percentage and the etiology of concurrent pathologies and the incidence of unexpected cancer within patients undergoing surgery for a presumably benign condition. Methods: A retrospective study was done of all the patients undergoing hysterectomy between 1991 and 2005. In addition a descriptive analysis of the distribution of benign and malignant conditions originated in the uterine corpus was done highlighting the occurrence of incidental cancer among different preoperative diagnosis. Results: During the period, 5683 hysterectomies were performed. In 4275 cases a non-epithelial pathology was found, mainly, fibroids and adenomyosis. In 2070 cases endometrial pathology was diagnosed: atrophy, polyps and hyperplasia as the most prevalent findings. In 905 cases myometrial and endometrial pathology of uterine corpus coexists. In 240 cases any pathology was found (4.2 percent). In 1 percent of hysterectomies an incidental gynecological cancer was found, and the two conditions more frequently associated were metrorrhagia and polyps. Conclusions: The distribution of etiologies for the uterine pathology, is similar to other international series. The most common finding is fibroid frequently associated to adenomyosis. It is important to highlight the incidental finding of endometrial cancer among patients operated on by metrorrhagia and/or polyps. Based on this, we recommend the routine use of preoperative biopsy in patients with metrorrhagia and frozen section biopsy in those with polyps.

Morphometric evaluation of endometrial blood vessels.

Five hundred endometrial specimens were studied to document the changes in blood vessels in various phases of menstrual cycle, menstrual disturbances and in unexplained infertility. Sixty-three cases were taken as control and 437 cases as study group which included cases of dysfunctional uterine bleeding (DUB), endometrial polyps, fibroids, adenomyosis, infertility and atrophic endometrium. Using light microscopy, the vascular morphology was studied. The blood vessels were concentrated more in basal layer in the proliferative phase and in functional layer in the secretory phase. Cases of complex hyperplasia and pill endometrium had significantly higher vessel concentration. Congestion and dilatation of blood vessels were significantly higher in cases of DUB. The present study showed a positive correlation between endometrial angiogenesis and menstrual disorders. The alteration in blood vessel morphology has significant role in prognosis and in various anti-angiogenic therapies.

Correlación de la histeroscopia y biopsia dirigida en el estudio del engrosamiento endometrial patológico por ultrasonido / Correlation of hysteroscopy and directed biopsy in the study of pathological endometrial thickening by ultrasound

OBJETIVO: Correlacionar la histeroscopia con la biopsia dirigida en pacientes pre y postmenopáusicas con engrosamiento endometrial patológico al ultrasonido. MÉTODO: Estudio retrospectivo de 265 pacientes derivadas por engrosamiento endometrial patológico en la ecografía transvaginal y evaluadas mediante histeroscopia con biopsia dirigida. RESULTADOS: 68,7% de las pacientes presentaron un aspecto histeroscópico benigno, 15,1% normal, 10,6% potencialmente maligno y 5,6% maligno. Los diagnósticos anátomo patológicos más frecuentes fueron: pólipo endometrial (n=92; 34,7%), endometrio proliferativo/secretor (n=84; 31,7%) y mioma submucoso (n=38; 14,3%). Todos los cánceres endometriales (n=9) se presentaron en mujeres postmenopáusicas sin TRH y con endometrio 11 mm. La correlación entre histeroscopia y anatomía patológica para diagnóstico de patología benigna tuvo una sensibilidad y especificidad de 90,7% (95% IC 85,2 - 94,3) y 65,4% (95% IC 55,8 - 73,8); valor predictivo positivo y negativo fue de 80,2% (95% IC 73,8 - 85,4) y 82% (95% IC 72,3 - 88,7). Para diagnóstico de hiperplasia endometrial la sensibilidad y especificidad fue 60% (95% IC 31,3 - 83,2) y 91,4% (95% IC 87,3 - 94,2); el valor predictivo positivo y negativo fue de 21,4% (95% IC 10,7 - 39,5) y 98,3% (95% IC 95,7 - 99,3). Para diagnóstico de cáncer endometrial la sensibilidad y especificidad fue de 95% (95% IC 65,5 - 99,5) y 97,9% (95% IC 95,2 - 99); el valor predictivo positivo y negativo fue de 63,3% (95% IC 38,7 - 82,5) y 99,7% (95% IC 98,1 - 99,8). CONCLUSIÓN: El 85% de las pacientes con engrosamiento endometrial presentaron una histeroscopia alterada (benigna, potencialmente maligna o maligna), confirmada en 80% de los casos por anatomía patológica. En un centro con experiencia la histeroscopia normal puede hacer innecesaria la biopsia. El aspecto potencialmente maligno a la histeroscopia puede ser un sobrediagnóstico, por lo que la anatomía patológica es imprescindible. ...

OBJECTIVE: Comparison of hysteroscopy with biopsy in pre- and post -menopausic patients with endometrial thickening on ultrasound. METHODS: Retrospective study of 265 patients with pathologic endometrial thickening on transvaginal ultrasound and evaluated with hysteroscopy and biopsy. RESULTS: 68.7% of the patients had benign hysteroscopy results, 15.1% were normal, 10.6% were potentially malignant, and 5.6% were malignant. The most frequent biopsy results were: endometrial polyp (n= 92, 34.7%), proliferate / secretor endometrium (n= 84, 31.7%), and submucosal myoma (n=38, 14.3%). All of the endometrial cancers (n= 9) were in post- menopausic women, with no history of hormone replacement therapy and with endometrial thickening 11mm. Sensitivity and specificity for hysteroscopy in comparison to biopsy for diagnosing benign pathology were 90.7% (95% CI 85.2 - 94.3) and 65.4% (95% CI 55.8 - 73.8), and the positive and negative predictive values were 80.2% (95% CI 73.8 - 85.4) and 81.9% (95% CI 72.3 - 88.7). Sensitivity and specificity for hysteroscopy in comparison to biopsy for diagnosing endometrial hyperplasia were 60% (95% CI 31.3 - 83.2) and 91.4% (95% CI 87.3 - 94.2), the positive and negative predictive values were 21.4% (95% CI 10.7 - 39.5) and 98.3% (95% CI 95.7 - 99.3). Sensitivity and specificity for hysteroscopy in comparison to biopsy for diagnosing endometrial cancer were 95% (95% CI 65.5 - 99.5) and 97.9% (95% CI 95.2 - 99), positive and negative predictive values were 63.3% (95% CI 38.7 - 82.5) and 99.7% (95% CI 98.1 - 99.8). CONCLUSION: 85% of the patients with endometrial thickening had an abnormal hysteroscopy result, which latter were confirmed in 80% of the cases with biopsy. In a center with experience, a normal hysteroscopy result can make biopsy unnecessary. Potentially malignant hysteroscopys tend to be over diagnosed, making biopsy fundamental. All endometrial cancers were detected by hysteroscopy in our study.

Pólipos endometiiales: manejo con histeroscopia quirúrgica y correlación histológica / Endometrial polyps: management with surgical hysteroscopy and histological correlation

Se presenta la experiencia quirúrgica en 160 pacientes con diagnóstico ecográfico de pólipo endometrial. Se evalúan las características epidemiológicas, clínicas y la correlación histológica. La edad promedio fue de 50 años, se analizaron las variables diferenciándolas en premenopáusicas o post menopáusicas, y presencia de síntomas. En todos los subgrupos la incidencia fue igualmente alta para los pólipos endometriales, seguida en frecuencia por los leiomiomas, hiperplasia endometrial y endometrio proliferativo, entre otros. Se encontraron 3 casos de adenocarcinoma endometrial, todos en el subgrupo de las pacientes postmenopáusicas sintomáticas. El procedimiento fue bien tolerado, y sin complicaciones. Destacamos a la histeroscopia como el estándar dorado por su alta sensibilidad y especificidad en el diagnóstico de pólipo endometrial.

The surgical experience in 160 patients with echographic diagnostic of endometrial polyps, are analyzed. Clinical and pathological characteristics are evaluated. The patient average age was 50 years old; variables were analyzed differentiating them in pre menopausal or post menopausal, according to the presence of symptoms. In all sub-groups the incidence was equally high for the endometrial polyps, followed in frequency by leiomyomas, endometrial hyperplasia and endometria proliferative among others. Three cases of endometrial adenocarcinoma were found, all in the sub-group of the symptomatic post menopausal patients. The procedure was well tolerated, without complications. We emphasized the hysteroscopy procedure as the gold standard by its high sensitivity and specificity in the endometrial polyp diagnosis.

value of transvaginal sonography performed before diagnostic hysteroscopy for the evaluation of uterine cavity in infertile women

Hysteroscopy have gained general acceptance as a method for the investigation of infertility. The main advantage of hysteroscopy is the capability of inspecting the uterine cavity. Transvaginal sonography [TVS] is a noninvasive modality that provide excellent imaging of the uterus and of endometrial abnormalities. The present study was designed to evaluate the use of TVS as the initial diagnostic procedure before hysteroscopy for detecting intrauterine disorders. Seventy-eight infertile women were examined by TVS and diagnostic hysteroscopy in the late follicular phase of the menstrual cycle and the results were compared. The uterine cavity abnormalities were present in 19.2% of the infertile females involved in the study. The Transvaginal scnography had 87.5% sensitivity, 100% specificity for detecting endometrial polyps while it had 100% sensitivity and 100% specificity for detecting other intrauterine cavity abnormalities including intrautcrine adhesions, uterine septae and submucosal myomas. Examination of the uterine cavity is an integral part of any thorough evaluation of an infertile woman. Tranavaginal sonography, when performed during the follicular phase, can detect most uterine cavity abnormalities. It was an accurate tool in the identification of intrauterine adhesions, uterine septae and submucosal fibroids

Correlation of endometrial ultrasonography and endometrial histopathology in patients with postmenopausal bleeding.

A retrospective study of 49 cases with persistent postmenopausal vaginal bleeding undergoing hysterectomy in the absence of postoperatively evident diagnosis of genital malignancy was carried out. Normal endometrium was the source of bleeding in 24 cases (48.9%) while 11 cases (22.4%) had evidence of endometritis. Endometrial hyperplasia and polyps were present in 12 cases (24.4%). Two cases were found to have malignancy in the surgical specimen, which were not evident on pre-operative endometrial biopsy. However, there was high degree of suspicion of malignancy in these 2 cases based on the endometrial histopathology and ultrasonographic endometrial thickness. By careful correlation of clinical findings, endometrial histopathology and ultrasound measurement of endometrial thickness, most cases with postmenopausal bleeding can be managed conservatively.

Sonohisterografía: citología endometrial por lavado aspirativo de cavidad / Sonohysterography: endometrial cytology by lavage-aspiration of cavity

Se presenta la introducción del estudio de la citología endometrial como complemento a la Sonohisterografía. La recuperación del líquido endocavitorio por aspiración, resulta un excelente complemento al procedimiento pues permite un adecuado diagnóstico en un 70,8 por ciento de las pacientes.