Complexo hiperplasia endometrial cística/piometra em cadelas: fisiopatogenia, características clínicas e laboratoriais e abordagem terapêutica

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Aspectos clínicos, histopatológicos e expressão gênica do endométrio de cadelas acometidas por hiperplasia endometrial cística, mucometra e piometra

Pós-graduação em Cirurgia Veterinária - FCAV

Tratamento Clínico e Seguimento das Hiperplasias de Endométrio

Objetivos: avaliar a eficácia do acetato de medroxiprogesterona e do acetato de megestrol nas hiperplasias de endométrio. Métodos: foram incluídas, retrospectivamente 47 pacientes com sangramento uterino anormal, submetidas a curetagem uterina diagnóstica e/ou biópsia de endométrio, cujo achado histopatológico foi de hiperplasia de endométrio. Nas pacientes com hiperplasia sem atipia foi iniciado a terapêutica com acetato de medroxiprogesterona por via oral, na dose de 10 mg/dia durante 10-12 dias por mês. Nas com atipia, era utilizado o acetato de megestrol por via oral, dose de 160 mg/dia, uso contínuo. O período de tratamento variou de 3 a 18 meses. Biópsia de endométrio e/ou curetagem uterina de controle foram realizadas entre três e seis meses do início do tratamento e periodicamente para avaliar a resposta terapêutica. Resultados: foram analisadas 42 pacientes com hiperplasia endometrial sem atipia e cinco com atipia. A média de idade das pacientes foi de 49,5 ± 10,6 anos, sendo 70,2% com idade superior a 45 anos. O acetato de medroxiprogesterona foi eficaz em fazer regredir as hiperplasias sem atipias em 83,2% (35/42) e o acetato de megestrol em 80% (4/5) das hiperplasias com atipia. em 16,8% (7 casos) das hiperplasias sem atipia e em 20% (1 caso) das com atipia, ocorreu persistência das lesões, apesar do tratamento. em nenhum caso ocorreu progressão para câncer de endométrio, durante o período de seguimento que foi de 3 meses a 9 anos. No acompanhamento dessas pacientes, verificamos que 18 (38,3%) apresentaram amenorréia, em 12 (25,5%) ocorreu regularização do ciclo menstrual e 17 (36,2%) permaneceram com sangramento uterino anormal, sendo submetidas a histerectomia total abdominal. O exame anatomopatológico mostrou a persistência da lesão hiperplásica em oito casos, leiomioma em quatro, adenomiose em três, mio-hipertrofia uterina difusa em um caso e útero normal em outro, tendo havido regressão das lesões hiperplásicas nesses últimos nove casos. Conclusões: o tratamento das hiperplasias de endométrio com acetato de medroxiprogesterona e/ou acetato de megestrol, representa uma alternativa satisfatória para mulheres que desejam preservar o útero ou que tenham risco cirúrgico elevado. Entretanto, é necessário monitorização cuidadosa do endométrio, o que deve ser realizado pela avaliação dos sintomas, ultra-sonografia transvaginal e biópsia periódica.

Mummified papyraceous fetuses in the abdominal cavity of an elderly female dog with pyometra

This paper reports on a rare case of fetal papyraceous mummification after asymptomatic uterine rupture in an elderly female dog with pyometra. The patient had a history of mating six months before the examination but no apparent signs of gestation or parturition. Exploratory laparotomy was used to identify a rupture of the left uterine horn and the presence of cystic endometrial hyperplasia and pyometra. Two mummified papyraceous fetuses were observed in the abdominal cavity and had adhered to the spleen, pancreas, intestine and omentum. Ovariehysterectomy and corrective surgery were performed. The patient had remained healthy after uterine rupture until a new estrous cycle and the development of pyometra. Bitches that are 10 years old or more are predisposed to implantation failure, pregnancy or parturition problems and they should not be breed to avoid complications.

Imunolocalização e quantificação da proteína CYR61 no trato reprodutor de fêmeas caninas nas diferentes fases do ciclo estral, fêmeas pré-púberes e acometidas por piometra

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação hormonal, imunoistoquímica e da expressão gênica de receptores de estrógeno e progesterona em cadelas(Canis familiaris) nas diferentes fases do ciclo estral e com piometra

Pós-graduação em Medicina Veterinária - FMVZ

Satisfacción de la atención médica en el área del hospitalización del Departamento Gíneco -Obstetricia del Hospital José Carrasco Arteaga. 2014

Objetivo. Determinar el grado de satisfacción de las pacientes con la atención médica y de enfermería recibida en el Área de Hospitalización del Departamento de Gineco - Obstetricia del Hospital José Carrasco Arteaga. Metodología. Con un diseño descriptivo de corte transversal se recopiló información de 628 pacientes ingresadas a los servicios de Ginecología y Obstetricia entre marzo y mayo del 2014. Se analizó edad, instrucción, estado civil, residencia, diagnóstico al ingreso, al egreso y procedimiento realizado en los dos servicios y grado de satisfacción de las pacientes con el personal médico y el personal de enfermería. Resultados. Las pacientes del servicio de Ginecología representaron el 26.11 %, con un promedio de edad de 41.46 ± 11.41 años y las de Obstetricia el 73.89 % con una edad media de 28.62 ± 6.12 años. La instrucción más frecuente fue la secundaria, en la mayoría casadas y residen en el área urbana. El diagnóstico ginecológico más frecuente al ingreso y al egreso fue la hiperplasia endometrial con el 26.1 % en ambos casos. En el área Obstétrica, el embarazo a término sin complicaciones representó más del 50% de los diagnósticos tanto al ingreso como al egreso. La histerectomía fue el procedimiento ginecológico realizado con mayor frecuencia (25 %). La cesárea es el procedimiento obstétrico más frecuente (45.26 %). Conclusiones. Se obtienen valoraciones altas en la satisfacción de la atención médica en más del 65 % de las pacientes encuestadas tanto del personal médico como del personal de enfermería.

Diagnóstico situacional del servicio de ginecología del Hospital Nacional Especializado de Maternidad Dr. Raúl Arguello Escolán, Enero a Diciembre 2013

Se plantea la realización de este estudio basado en el servicio de Ginecología. De esta manera la institución será capaz de elaborar planes para la solución de sus problemas y/o necesidades, permitiendo que todos el personal que labora en el servicio de ginecología lo utilicen como un instrumento más, para elaborar, indagar, profundizar, integrar y crear una propuesta de transformación de la situación de salud de área de trabajo, en la que cada miembro del personal sea un participe activo para mejorar el proceso salud-enfermedad de cada paciente que ingresa a dicho servicio. Objetivo: realizar el diagnóstico situacional del servicio de ginecología del Hospital Nacional Especializado de Maternidad “Dr. Raúl Arguello Escolán” de Enero-Diciembre 2013. Metodología: se realizó un estudio descriptivo, del funcionamiento del servicio de ginecología. Se utilizaron para el estudio los expedientes clínicos y datos proporcionados por el departamento de estadística, además de la información de carácter administrativo facilitado por el jefe del servicio de ginecología del Hospital Nacional Especializado de Maternidad. Utilizando variables como edad, sexo, ingresos, egresos, procedimientos realizados, tasas de mortalidad y los recursos humanos y físicos con los que cuenta dicho servicio. Conclusión: de acuerdo a los datos obtenidos durante la realización del diagnóstico situacional, se puede concluir lo siguiente: la mayoría de pacientes ingresados durante el periodo de estudio se encuentran predominantemente en los rangos de edades, de 41 a 50 años, lo cual es explicable por el tipo de patologías más comunes atendidas en dicho servicio, se determinaron las causas más comunes de ingreso y egreso del servicio de ginecología, demostrándose que las 5 primeras patologías son las mismas para ambas situaciones como lo son: Leiomioma uterino, prolapso útero vaginal completo, hiperplasia endometrial, tumor benigno de ovario, carcinoma in situ del cuello uterino, igualmente es de recalcar que no siempre el diagnóstico de ingreso es el mismo que al egreso, lo cual permite la modificación de las otras 5 restantes causas de egreso tomadas en cuenta y se determinó que durante el año 2013 en el servicio se llevaron a cabo 1426 procedimientos, siendo los tres principales: las histerectomías abdominales totales, histerectomía vaginal total, dilatación y legrado de útero.

Causas de hemorragia uterina anormal en mujeres de 35 a 50 años que acudieron al departamento de ginecología en el Hospital José Carrasco Arteaga desde junio-diciembre del 2014

ANTECEDENTES: La hemorragia uterina anormal (HUA) es un problema común de mujeres en edad reproductiva, perimenopáusica y menopausia, por lo cual se realizó el presente estudio para conocer las causas de la hemorragia uterina anormal en nuestra población además de sus características demográficas y consecuencia del sangrado. OBJETIVO GENERAL: Determinar las diferentes causas del sangrado uterino anormal en mujeres de 35 a 50 años del departamento de gineco-obstetricia del hospital José Carrasco Arteaga en el periodo de junio-diciembre del 2014. METODOLOGÍA: Es un estudio cuantitativo descriptivo donde se indagó las historias clínicas de pacientes con diagnósticos de hemorragia uterina anormal en el Hospital “José Carrasco Arteaga”, del departamento de Ginecología en el periodo junio-diciembre 2014. La recolección de variables fue procesada, elaborada y codificada en el programa SPSS. RESULTADOS: Se identificaron 178 casos, con una media de 43,47 años, de la región urbana (88,8%), la mayor frecuencia fue empleadas formal(72,5%), casadas (60,1%), con una media de gestas de 3, 91% con Papanicolaou en el ultimo año, 65,7% no tuvo planificación familiar, el principal diagnóstico fue hiperplasia endometrial (41%), segundo Leiomioma (36,7%), y el principal tratamiento fue: legrado (46,1%), seguida de histerectomía (43,3%), y 27,5% presento anemia moderada, a continuación, anemia leve (11,8%) y grave (9,6%). CONCLUCIONES: La causa más frecuente de hemorragia uterina anormal fue hiperplasia endometrial y el tipo de tratamiento escogido fue el legrado intrauterino

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE) : a randomised trial

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed centrally and independently from other study procedures via a computer generated, web-based system (providing concealment of the next assigned treatment) using stratified permuted blocks of 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer.

Inhibition of activated fibroblast growth factor receptor 2 in endometrial cancer cells induces cell death despite PTEN abrogation

KRAS activation and PTEN inactivation are frequent events in endometrial tumorigenesis, occurring in 10% to 30% and 26% to 80% of endometrial cancers, respectively. Because we have recently shown activating mutations in fibroblast growth factor receptor 2 (FGFR2) in 16% of endometrioid endometrial cancers, we sought to determine the genetic context in which FGFR2 mutations occur. Analysis of 116 primary endometrioid endometrial cancers revealed that FGFR2 and KRAS mutations were mutually exclusive, whereas FGFR2 mutations were seen concomitantly with PTEN mutations. Here, we show that shRNA knockdown of FGFR2 or treatment with a pan-FGFR inhibitor, PD173074, resulted in cell cycle arrest and induction of cell death in endometrial cancer cells with activating mutations in FGFR2. This cell death in response to FGFR2 inhibition occurred within the context of loss-of-function mutations in PTEN and constitutive AKT phosphorylation, and was associated with a marked reduction in extracellular signal-regulated kinase 1/2 activation. Together, these data suggest that inhibition of FGFR2 may be a viable therapeutic option in endometrial tumors possessing activating mutations in FGFR2, despite the frequent abrogation of PTEN in this cancer type.

Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

FGFR2 as a molecular target in endometrial cancer

Although molecularly targeted therapies have been effective in some cancer types, no targeted therapy is approved for use in endometrial cancer. The recent identification of activating mutations in fibroblast growth factor receptor 2 (FGFR2) in endometrial tumors has generated a new avenue for the development of targeted therapeutic agents. The majority of the mutations identified are identical to germline mutations in FGFR2 and FGFR3 that cause craniosynostosis and hypochondroplasia syndromes and result in both ligand-independent and ligand-dependent receptor activation. Mutations that predominantly occur in the endometrioid subtype of endometrial cancer, are mutually exclusive with KRAS mutation, but occur in the presence of PTEN abrogation. In vitro studies have shown that endometrial cancer cell lines with activating FGFR2 mutations are selectively sensitive to a pan-FGFR inhibitor, PD173074. Several agents with activity against FGFRs are currently in clinical trials. Investigation of these agents in endometrial cancer patients with activating FGFR2 mutations is warranted.

Timing of births and endometrial cancer risk in Swedish women

While a protective long-term effect of parity on endometrial cancer risk is well established, the impact of timing of births is not fully understood. We examined the relationship between endometrial cancer risk and reproductive characteristics in a population-based cohort of 2,674,465 Swedish women, 20–72 years of age. During follow-up from 1973 through 2004, 7,386 endometrial cancers were observed. Compared to uniparous women, nulliparous women had a significantly elevated endometrial cancer risk (hazard ratio [HR] = 1.32, 95% confidence interval [CI], 1.22–1.42). Endometrial cancer risk decreased with increasing parity; compared to uniparous women, women with ≥4 births had a HR=0.66 (95% CI, 0.59–0.74); p-trend < 0.001. Among multiparous women, we observed no relationship of risk with age at first birth after adjustment for other reproductive factors. While we initially observed a decreased risk with later ages at last birth, this appeared to reflect a stronger relationship with time since last birth, with women with shorter times being at lowest risk. In models for multiparous women that included number of births, age at first and last birth, and time since last birth, age at last birth was not associated with endometrial cancer risk, while shorter time since last birth and increased parity were associated with statistically significantly reduced endometrial cancer risks. The HR was 3.95 (95%CI; 2.17–7.20; p-trend=<0.0001) for women with ≥25 years since a last birth compared to women having given birth within 4 years. Our findings support that clearance of initiated cells during delivery may be important in endometrial carcinogenesis. Keywords: endometrial carcinoma, parity, registry, reproductive factors