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1.
Int J Cancer ; 133(10): 2383-91, 2013 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-23649867

RESUMEN

Rapid and reliable diagnosis of endometrial cancer (EC) in uterine aspirates is highly desirable. Current sensitivity and failure rate of histological diagnosis limit the success of this method and subsequent hysteroscopy is often necessary. Using quantitative reverse transcriptase-polymerase chain reaction on RNA from uterine aspirates samples, we measured the expression level of 20 previously identified genes involved in EC pathology, created five algorithms based on combinations of five genes and evaluated their ability to diagnose EC. The algorithms were tested in a prospective, double-blind, multicenter study. We enlisted 514 patients who presented with abnormal uterine bleeding. EC was diagnosed in 60 of the 514 patients (12%). Molecular analysis was performed on the remnants of aspirates and results were compared to the final histological diagnoses obtained through biopsies acquired by aspiration or guided by hysteroscopy, or from the specimens resected by hysterectomy. Algorithm 5 was the best performing molecular diagnostic classifier in the case-control and validation study. The molecular test had a sensitivity of 81%, specificity of 96%, positive predictive value (PPV) of 75% and negative predictive value (NPV) of 97%. A combination of the molecular and histological diagnosis had a sensitivity of 91%, specificity of 97%, PPV of 79% and NPV of 99% and the cases that could be diagnosed on uterine aspirate rose from 76 to 93% when combined with the molecular test. Incorporation of the molecular diagnosis increases the reliability of a negative diagnosis, reduces the need for hysteroscopies and helps to identify additional cases.


Asunto(s)
Neoplasias Endometriales/diagnóstico , Neoplasias Uterinas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Estudios de Casos y Controles , Método Doble Ciego , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía/métodos , Histeroscopía/métodos , Persona de Mediana Edad , Patología Molecular/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Adulto Joven
2.
J Low Genit Tract Dis ; 17(1): 12-6, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23222046

RESUMEN

OBJECTIVE: This study aimed to evaluate the impact of an educational intervention in lower genital tract pathology (LGTP) on the knowledge and skills acquired by the Spanish specialist residents. This didactic change was carried out under the auspices of the Asociación Española de Patología Cervical y Colposcopia and the Sociedad Española Ginecología y Obstetricia and its Resident Section. STUDY DESIGN: This is an observational, descriptive, and cross-sectional study. The survey was composed of 15 questions voluntarily answered by Spanish gynecology and obstetrics trainees. RESULTS: Compared with a previous survey, a substantial increase in the proportion of Spanish teaching hospitals with an LGTP unit (9/42 vs 47/59) has been detected while doubling the percentage of residents who acknowledge medium to high knowledge on this pathology. The same cannot be said about the handling capacity of vulvodynia registering a great improvement. CONCLUSIONS: Spanish scientific societies, concerned in the quality of LGTP training gained by their residents, have focused on the necessity of LGTP units. Our study confirms the usefulness of this performance in the new continued LGTP education.


Asunto(s)
Colposcopía/educación , Enfermedades de los Genitales Femeninos/diagnóstico , Enfermedades de los Genitales Femeninos/patología , Ginecología/educación , Obstetricia/educación , Estudios Transversales , Femenino , Humanos , Masculino , Garantía de la Calidad de Atención de Salud , España , Encuestas y Cuestionarios
3.
J Surg Oncol ; 106(1): 89-93, 2012 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-22258666

RESUMEN

BACKGROUND: The axillary reverse mapping (ARM) technique has been proposed to prevent arm lymphedema. We conducted this study to assess the feasibility of the technique and the outcomes of patients with neoadjuvant chemotherapy (NAC). METHODS: From July 2009 to May 2010, a prospective study was performed in 36 patients with breast cancer undergoing an ALND. The ARM technique was performed injecting 3 cm(3) of Patent Blue in the ipsilateral arm. Of the 36 patients, 29 patients received NAC previously to the ARM and 7 patients had an ALND and ARM performed as first treatment for positive axillary nodes. RESULTS: The identification rate of blue nodes was 83.3% (30 patients). Sentinel lymph node (SLN) was performed in 15 of 29 (42%) patients in the NAC group. Of these 15, two patients (13%) had a concordance between the blue and the hot node. Blue nodes were positive in 4 (13%) of the 30 patients. CONCLUSIONS: The ARM technique is feasible in patients undergoing NAC. Patients with extensive nodal involvement have increased risk of having positive blue nodes. More studies are needed to assess the subgroup of patients with positive axilla that may have the blue node spared without compromising the oncological treatment.


Asunto(s)
Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Adulto , Anciano , Axila , Estudios de Factibilidad , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática/diagnóstico , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Biopsia del Ganglio Linfático Centinela/métodos
4.
J Low Genit Tract Dis ; 16(1): 34-8, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22126830

RESUMEN

OBJECTIVE: This study aimed to assess the risk of progression/persistence of squamous intraepithelial lesions (SILs) during pregnancy according to the age of the woman, the grade of the lesion, the type of human papillomavirus (HPV) infection, and the mode of delivery. MATERIALS AND METHODS: Eighty pregnant women with abnormal cytologic result at the first antenatal visit were evaluated. Postpartum cytologic and histologic findings were compared with the antepartum findings. RESULTS: There were 40 patients with low-grade SIL and 40 with high-grade SIL (HSIL). The overall regression rate was 32.5%. There were 19 patients 25 years or younger and 61 patients older than 25 years. The regression rate among younger patients was 52.6% versus 26.2% among those older than 25 years (relative risk [RR] = 2.01, 95% confidence interval [CI] = 1.10-3.66). The regression rate was 45% in the group of low-grade SIL and 20% in the group of HSIL (RR = 2.25, 95% CI = 1.11-4.57). In patients with HSIL, those older than 25 years had a 2-fold increased risk of progression/persistence than younger patients. High-risk HPV-positive samples were typed in 44 cases, 21 of which (47.7%) were positive for HPV-16. The regression rate was 9.5% for HPV-16-positive cases and 52.2% for HPV-16-negative cases (RR = 5.48, 95% CI = 1.39-21.68). The risk of progression or persistence of the lesion according to mode of delivery did not show significant differences (RR = 1.15, 95% CI = 0.82-1.63). CONCLUSIONS: Age of the patient older than 25 years, HSILs, and HPV type 16 infection are risk factors for the progression or persistence of intraepithelial lesions of the cervix in the postpartum period.


Asunto(s)
Infecciones por Papillomavirus/virología , Periodo Posparto , Complicaciones Neoplásicas del Embarazo/diagnóstico , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Adulto , Progresión de la Enfermedad , Femenino , Papillomavirus Humano 16/aislamiento & purificación , Humanos , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/patología , Embarazo , Complicaciones Neoplásicas del Embarazo/patología , Factores de Riesgo , Neoplasias del Cuello Uterino/diagnóstico , Adulto Joven , Displasia del Cuello del Útero/diagnóstico
5.
Int J Cancer ; 129(10): 2435-44, 2011 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-21207424

RESUMEN

Endometrial cancer (EC) is the most frequent of the invasive tumors of the female genital tract. Although usually detected in its initial stages, a 20% of the patients present with advanced disease. To date, no characterized molecular marker has been validated for the diagnosis of EC. In addition, new methods for prognosis and classification of EC are needed to combat this deadly disease. We thus aimed to identify new molecular markers of EC and to evaluate their validity on endometrial aspirates. Gene expression screening on 52 carcinoma samples and series of real-time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and noncarcinoma uterine aspirates were performed to identify and validate potential biomarkers of EC. Candidate markers were further confirmed at the protein level by immunohistochemistry and Western blot. We identified ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2 and DCN as differentially expressed in ECs. Furthermore, the differential expression of these biomarkers in primary endometrial tumors is correlated to their expression level in corresponding uterine fluid samples. Finally, these biomarkers significantly identified EC with area under the receiver-operating-characteristic values ranging from 0.74 to 0.95 in uterine aspirates. Interestingly, analogous values were found among initial stages. We present the discovery of molecular biomarkers of EC and describe their utility in uterine aspirates. These findings represent the basis for the development of a highly sensitive and specific minimally invasive method for screening ECs.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Endometriales/genética , Perfilación de la Expresión Génica , Líquidos Corporales/química , Neoplasias Endometriales/metabolismo , Femenino , Humanos , Reproducibilidad de los Resultados
6.
Ann Surg Oncol ; 18(2): 482-9, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-20839058

RESUMEN

BACKGROUND: To assess the safety, feasibility, and impact on survival of extraperitoneal para-aortic lymphadenectomy in the staging of patients with bulky or locally advanced cervical cancer. MATERIALS AND METHODS: Between August 2001 and October 2009, 87 consecutive patients (median age 5 years) with bulky or locally advanced cervical cancer underwent extraperitoneal laparoscopic infrarenal aortic and common iliac dissection as a pretherapeutic staging procedure. Data on pathologic findings, details of surgery, postoperative complications, and disease status at follow-up were collected. RESULTS: The median operating time was 150 min (range 60-255 min). The mean (± standard deviation) para-aortic nodal yield was 15.5 ± 8.1 (range 4-62). In none of the patients, conversion to the transperitoneal approach or laparotomy was necessary. Histological examination revealed metastasis in 13 patients (macroscopic disease 10, microscopic disease 3). After a median follow-up of 33.4 months (range 13.3-65.9 months), 73.6% of patients were free of disease and 1.1% were alive with disease, 19.5% died from cervical cancer, and 3.3% died from other causes. After a follow-up of 3 years, no deaths or recurrences were documented, with an overall survival rate of 74.8% (95% CI 62.8%-83.4%) and disease-free survival of 86% (95% CI 74.7%-92.5%). There were no significant differences in overall survival and disease-free survival between patients with positive and negative para-aortic lymph nodes. CONCLUSION: The extraperitoneal laparoscopic para-aortic lymphadenectomy for pretherapeutic surgical staging in cervical cancer is a safe and feasible procedure that should be considered as a tool to identify lymph node positive patients who require extended-field radiation and/or chemotherapy.


Asunto(s)
Adenocarcinoma/patología , Carcinoma de Células Escamosas/patología , Laparoscopía , Escisión del Ganglio Linfático , Neoplasias del Cuello Uterino/patología , Adenocarcinoma/cirugía , Adulto , Anciano , Carcinoma de Células Escamosas/cirugía , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Persona de Mediana Edad , Estadificación de Neoplasias , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias del Cuello Uterino/cirugía , Adulto Joven
7.
Gynecol Oncol ; 120(3): 353-7, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21215440

RESUMEN

OBJECTIVE: The aim of this study was to investigate the feasibility of the sentinel lymph node (SLN) identification with SPECT/CT lymphoscintigraphy imaging in the early stage invasive cervical cancer in patients undergoing radical hysterectomy and pelvic lymphadenectomy. METHODS: Between March 2007 and June 2009, a prospective consecutive study was designed for SLN mapping. Twenty-two patients with cervical cancer FIGO stage IB1 (n=20) or stage IIA1 (n=2) underwent SLN identification with preoperative SPECT/CT and planar images (technetium-99m colloid albumin injection around the tumor) and posterior intraoperative detection with both blue dye and a handheld or laparoscopic gamma probe. Complete pelvic lymphadenectomy was performed in all cases by open (n=2) or laparoscopic (n=20) surgery. RESULTS: In the present series, a total of 35 SLN were detected with planar images and 40 SLN were identified and well located by SPECT/CT lymphoscintigraphy (median 2.0 nodes per patient). In 5/22 patients (22.7%) SPECT/CT procedure improves the number of localized SLN. Intraoperatively, 57 SLNs were identified, with a median of 3 SLNs per patient by gamma probe (a total of 53 hot nodes) and a median of 2 nodes per patient after blue dye injection (a total of 42 blue nodes). Microscopic nodal metastases (eight nodes, corresponding to four patients) were confirmed in 18.18% of cases; all these lymph nodes were previously detected as SLN. The remaining 450 nodes, including SLNs, following complete pelvic lymphadenectomy, were histologically negative. CONCLUSIONS: Sentinel lymph node detection is improved by SPECT/CT imaging because of the increased number of SLN detected and the better tridimensional anatomic location, allowing easier intra-operative detection with gamma probe and showing, in this series, a 100% negative predictive value.


Asunto(s)
Biopsia del Ganglio Linfático Centinela/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Tomografía Computarizada por Rayos X/métodos , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias del Cuello Uterino/mortalidad
8.
Int Urogynecol J ; 22(12): 1543-7, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21732099

RESUMEN

INTRODUCTION AND HYPOTHESIS: This study was conducted to evaluate the effectiveness and safety of retropubic suburethral slings (TVT) to treat recurrent stress urinary incontinence (SUI) after transobturator tape (TOT) failure. METHODS: A descriptive study was performed among women with recurrent SUI treated at the Vall d'Hebron University Hospital between January 2006 and December 2009. All women were preoperatively evaluated to rule out complications of the first sling. Urodynamic testing was performed before and after the TOT procedure in all cases. Postoperative follow-up was performed at 1, 6, and 12 months and yearly thereafter. Outcomes were classified as cured, improved, or failed. RESULTS: Twenty-three women were operated on over the study period. The median time to reoperation was 12 months (range 6 to 34 months) and the median follow-up time was 36.1 months (range 7.8 to 60.2 months). Overall cure and improvement rates were 86.4% at 12 and 24 months and 75% at 36 months. Failure was found not to be related to time between both sling surgeries. Two cases of bladder perforation were recorded (8.7%). Postoperative complications were slight and self-limited. De novo urgency occurred in five cases (21.7%). CONCLUSIONS: TVT has been found to be effective to treat recurrent SUI after TOT failure in the present series with slight side effects.


Asunto(s)
Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/prevención & control , Incontinencia Urinaria de Esfuerzo/terapia , Anciano , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Prevención Secundaria , Cabestrillo Suburetral/efectos adversos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Incontinencia Urinaria de Esfuerzo/fisiopatología , Urodinámica/fisiología
9.
J Minim Invasive Gynecol ; 18(5): 555-68, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21783432

RESUMEN

Laparoscopic radical hysterectomy is one surgical procedure currently performed to treat gynecologic cancer. The objective of this review was to update the current knowledge of laparoscopic radical hysterectomy in early invasive cervical cancer. Articles indexed in the MEDLINE database using the key words "Laparoscopic radical hysterectomy" and "Cancer of the cervix" were reviewed. Studies of laparoscopic radical hysterectomy for treatment of early cervical cancer with a minimum study population of 10 patients were selected. The laparoscopic approach was associated with less surgical morbidity (surgical bleeding) and with shorter length of hospital stay, although the duration of the operation may be longer. Laparoscopic radical hysterectomy with endoscopic pelvic lymphadenectomy, and paraaortic lymphadenectomy if needed, is a safe surgical option for treatment and staging of early invasive cervical cancer considering surgical risk, intraoperative bleeding, intraoperative and postoperative complications, and patient recovery. It is important to respect the learning curve. Surgical advances including new laparoscopic instrumentation and, in particular, use of robotics will contribute to reducing the duration of the operation and to facilitating learning and teaching of the procedure.


Asunto(s)
Histerectomía/métodos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Neoplasias del Cuello Uterino/cirugía , Femenino , Humanos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología
10.
Ann Surg Oncol ; 17(1): 235-9, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19777186

RESUMEN

BACKGROUND: Sentinel lymph node (SLN) biopsy has been shown to be both accurate and feasible for women who receive neoadjuvant chemotherapy (NAC). This study was designed to evaluate the ability of intraoperative assessment to predict metastasis in the sentinel node after NAC and to compare it with patients not treated with NAC. METHODS: Thirty-seven patients with invasive breast cancer and SLN biopsy after NAC and 461 patients with invasive breast cancer not treated with NAC were included in the study. The SLN was identified by the gamma probe and sent to pathology for frozen (FS) and H&E paraffin-sections. If the SLN was negative by H&E paraffin-sections, then immunohistochemistry was performed. RESULTS: The sensitivity of FS in the NAC group ranged from 78.5% for micro and isolated tumor cells to 100% for macrometastasis. The sensitivity of FS in the non-NAC group ranged from 82% for micro and isolated tumor cells to 97.4% for macrometastasis. There were no statistically differences between the sensitivities of FS in the two groups. Nine (64.2%) of the 14 patients in the NAC group with metastasis to the SLN had other non-SLN metastasis. CONCLUSIONS: After NAC, FS is an effective method for detecting macrometastasis in the SLN. As in the adjuvant setting, the sensitivity of FS is lower for SLN micro and sub-micrometastasis. Intraoperative FS of the SLN after NAC is indicated to avoid a second surgery because 60% of patients with a positive SLN will have additional positive axillary nodes.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Terapia Neoadyuvante , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/cirugía , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/secundario , Carcinoma Ductal de Mama/cirugía , Carcinoma Lobular/tratamiento farmacológico , Carcinoma Lobular/secundario , Carcinoma Lobular/cirugía , Femenino , Secciones por Congelación , Humanos , Periodo Intraoperatorio , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Metástasis Linfática , Persona de Mediana Edad , Estudios Prospectivos , Biopsia del Ganglio Linfático Centinela , Resultado del Tratamiento
11.
Tumori ; 96(4): 629-32, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20968147

RESUMEN

We describe the case of a pregnant woman diagnosed with breast cancer at 26 weeks' gestation. The tumor was positive for estrogen and progesterone receptors and negative for overexpression of c-erbB-2 protein. Neoadjuvant FAC (fluorouracil, adriamycin, cytoxan) chemotherapy was started at 29 weeks' gestation. At 37 weeks, delivery was induced and the patient gave born to a healthy female baby weighing 2350 g, after which she was given a further cycle of chemotherapy and weekly paclitaxel. Clinical and radiological remission was achieved. Resection of the breast tissue showed complete pathological response and negative lymph nodes. This case illustrates how the integrated work of different specialists can obtain excellent oncological and obstetrical results in the care of pregnant women with breast cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Complicaciones Neoplásicas del Embarazo/patología , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias de la Mama/metabolismo , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Paclitaxel/administración & dosificación , Embarazo , Complicaciones Neoplásicas del Embarazo/metabolismo , Resultado del Embarazo , Tercer Trimestre del Embarazo , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Inducción de Remisión , Resultado del Tratamiento
12.
Arch Gynecol Obstet ; 282(1): 63-7, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20405294

RESUMEN

PURPOSE: The association between cervical cancer and uterine prolapse is rare and sparsely represented in literature, despite the high incidence of the latter. The suitable treatment in this clinical situation is not defined. The objective of this article is to review published cases about this clinical condition. METHODS: We report a case of cervical cancer in prolapsed uterus treated with radical hysterectomy performed totally by laparoscopic approach, and review other case reports published about this clinical condition. RESULTS: We present the first case reported in literature in our knowledge of cervical cancer in prolapsed uterus treated with radical hysterectomy performed totally by laparoscopic approach. Treatments previously reported are vaginal hysterectomies with adjuvant radiotherapy or concomitant chemo-radiotherapy. CONCLUSIONS: Radical hysterectomy can be correctly performed totally by laparoscopic approach even when cervical cancer is associated with severe uterine prolapse.


Asunto(s)
Adenocarcinoma/cirugía , Histerectomía/métodos , Neoplasias del Cuello Uterino/cirugía , Prolapso Uterino/cirugía , Adenocarcinoma/patología , Biopsia , Femenino , Humanos , Laparoscopía , Escisión del Ganglio Linfático , Imagen por Resonancia Magnética , Persona de Mediana Edad , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología , Prolapso Uterino/patología
13.
J Proteome Res ; 8(10): 4676-84, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19691290

RESUMEN

Tumor invasion defines the transition between tissue-restricted carcinomas, related to good outcome as optimal surgery becomes possible, and metastatic tumors associated with poor prognosis and a dramatic decrease in survival. In endometrial cancer, myometrial infiltration represents a determinant parameter highly valuable in prognosis. To date, the identification of proteins involved in endometrial carcinoma invasion has been essentially conducted by immunohistochemical methods, without a global perception on the invasive front. Laser microdissection presents nowadays limitations to the profound spatiotemporal regulation from both the tumor and the surrounding stroma occurring at the invasive front. In this work, we attempted an alternative proteomic approach to characterize specific components of the tumor invasive front or its reactive stroma, by comparing the invasive area of an endometrial carcinoma with the noninvasive superficial tumor area and normal tissue from the same patients. This strategy led us to identify proteins involved in cellular morphology, assembly and movement, differentially expressed at the invasive front, as well as pathways like cell-to-cell signaling and interaction and a modulated response to oxidative stress as events related to endometrial carcinoma invasion. In conclusion, we could identify new players of myometrial infiltration by applying a subtractive proteomic approach to the endometrial carcinoma invasion front.


Asunto(s)
Neoplasias Endometriales/metabolismo , Invasividad Neoplásica , Proteoma/análisis , Proteómica/métodos , Anciano , Análisis por Conglomerados , Electroforesis en Gel Bidimensional , Femenino , Histocitoquímica , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Oxidorreductasas actuantes sobre Donantes de Grupo CH-CH/metabolismo , Proteínas/análisis , Reproducibilidad de los Resultados , Transducción de Señal , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa-1
14.
Carcinogenesis ; 30(8): 1288-97, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19443906

RESUMEN

Endometrial cancer, the most common gynecological malignancy in western countries, is characterized by a favorable prognosis. Nonetheless, deep myometrial invasion correlates with more undifferentiated tumors, lymph-vascular invasion, node involvement and decreased global survival. We have described previously the Ets family member ERM/ETV5 specifically upregulated in endometrial endometrioid carcinoma (EEC) associated with myometrial infiltration. To understand the role of this transcription factor during myometrial infiltration, we analyzed by two-dimension differential gel electrophoresis (2D-DIGE) technology those proteins whose expression was altered in endometrial cell lines stably overexpressing ERM/ETV5. Pathway analysis pointed to actin regulation and transforming growth factor beta and progesterone signaling as processes regulated by ERM/ETV5. In addition, we characterized the specific upregulation of the nuclear dehydrogenase/reductase Hep27 as well as its ERM/ETV5-dependent mitochondrial localization. Further functional studies demonstrated a protective role of Hep 27 against apoptosis induced by oxidative stress. Overall, the ETV5-related proteomic approach performed in the Hec-1A cell line reinforces a role of this transcription factor in the regulation of the migratory and invasive tumor behavior and points to a modulated response to oxidative stress associated with the promotion of invasion in endometrial cancer. Unraveling the molecular events in EEC associated with the initiation of tumor invasion would represent an obvious improvement in the pursuit of rational targets for the onset of metastasis. This knowledge would also be a valuable tool for the molecular stratification of patients since myometrial affectation determines an increase in the rate of recurrence after a first surgical treatment and a decrease in 5 year survival.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Proteínas de Unión al ADN/metabolismo , Neoplasias Endometriales/metabolismo , Estrés Oxidativo , Proteómica , Factores de Transcripción/metabolismo , Alcohol Deshidrogenasa/antagonistas & inhibidores , Alcohol Deshidrogenasa/genética , Alcohol Deshidrogenasa/metabolismo , Oxidorreductasas de Alcohol , Apoptosis , Western Blotting , Carbonil Reductasa (NADPH) , Inmunoprecipitación de Cromatina , Electroforesis en Gel Bidimensional , Neoplasias Endometriales/patología , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Técnicas para Inmunoenzimas , Invasividad Neoplásica , Proteínas Nucleares/antagonistas & inhibidores , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Progesterona/metabolismo , ARN Interferente Pequeño/farmacología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Fracciones Subcelulares , Factor de Crecimiento Transformador beta/metabolismo , Células Tumorales Cultivadas , Regulación hacia Arriba
15.
Int J Cancer ; 125(2): 257-63, 2009 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-19384951

RESUMEN

Endometrial carcinoma is the most common malignancy of the female genital tract in industrialized countries. Metastasis is the major cause of endometrial cancer deaths. Therefore, there is a vital need for clinically relevant in vivo models allowing the elucidation of the molecular and cellular mechanisms underlying metastatic behavior. In this study, we describe an innovative experimental orthotopic model of human endometrial carcinoma. Implantation in the bifurcation of the uterine horns resulted in tumors integrated into the myometrial compartment, which can be used and further exploited for the study of in vivo angiogenesis, myometrial invasion, and the metastatic capacity of endometrial cancer cells. This orthotopic model also represents a suitable tool to analyze how tumorigenesis and distant metastasis of endometrial cancer might be influenced by gene alteration, by modulating its expression in the original cancer cell line. One of the candidate genes implicated in endometrial cancer is the transcription factor RUNX1. The over-expression of RUNX1 in the endometrial cancer cell line HEC1A and the transplantation of these cells to the uterus of nude mice were associated specifically with distant metastasis in the lung. RUNX1 plays a role in the establishment of metastases in endometrial cancer. Translated to the clinics, these models would be equivalent to an advanced undifferentiated carcinoma with node affectation (stage IIIC) and distant metastasis (stage IVB). These patients would be candidates for adjuvant therapy, not efficient until today, and therefore, our models are actually suitable for the design and evaluation of experimental therapies.


Asunto(s)
Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética , Neoplasias Endometriales/patología , Metástasis de la Neoplasia/genética , Animales , Secuencia de Bases , Línea Celular , Cartilla de ADN , Femenino , Humanos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
16.
Cancer Res ; 67(14): 6753-9, 2007 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-17638886

RESUMEN

We have described recently the Ets family transcription factor, ERM/ETV5, specifically up-regulated in endometrioid endometrial carcinoma (EEC) and associated with myometrial infiltration. Ets family members have been correlated to tumor progression by up-regulating the expression of matrix-degrading proteases. In the present study, we investigated the possibility that in EEC, ERM/ETV5 may act by inducing the expression of genes involved in extracellular matrix remodeling. Unraveling the molecular events associated with the initiation of tumor invasion would represent an obvious improvement for EEC patients. The overexpression of ERM/ETV5 induced scattering in the endometrial cancer cell line Hec-1A, correlating to increased matrix metalloproteinase-2 (MMP-2) gelatinase activity. Both chromatin immunoprecipitation and reversion experiments with RNA interference and specific MMP-2 inhibitor showed a functional link between ERM/ETV5 overexpression and MMP-2 activation. The increased MMP-2 activity associated with overexpressed ERM/ETV5 in a mouse model conferred invasive capacity to endometrial tumors. Orthotopically implanted overexpressing ERM/ETV5 tumors presented a more aggressive and infiltrative pattern of myometrial invasion. Finally, the specific localization of ERM/ETV5 and MMP-2 at the invasive front of myometrial infiltrating human endometrial carcinomas further reinforced the hypothesis of a role for ERM/ETV5 in the early steps of endometrial dissemination. Taken together, these results lead us to propose that in EEC, ERM/ETV5 acts through MMP-2 gelatinolytic activity to confer invasive capabilities, associated with an initial switch to myometrial infiltration. They also postulate ERM/ETV5 as a valuable marker for patient stratification and a transcription pathway that should be evaluated for therapies specifically targeting the initial steps of EEC dissemination.


Asunto(s)
Proteínas de Unión al ADN/biosíntesis , Neoplasias Endometriales/metabolismo , Regulación Neoplásica de la Expresión Génica , Metaloproteinasa 2 de la Matriz/metabolismo , Miometrio/metabolismo , Factores de Transcripción/biosíntesis , Animales , Secuencia de Bases , Línea Celular Tumoral , Neoplasias Endometriales/patología , Activación Enzimática , Femenino , Regulación Enzimológica de la Expresión Génica , Humanos , Ratones , Datos de Secuencia Molecular , Invasividad Neoplásica
17.
Gynecol Oncol ; 110(3 Suppl 2): S33-5, 2008 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-18538379

RESUMEN

During the last years, and coinciding with the beginning of the concomitant treatment with radio-chemotherapy, a better control of local cervical cancer has been reached, although failures in the systemic control of the illness have been more frequent. One of the main causes is not treating the illness at the level of the para-aortic lymph nodes, basically because their affectation is unknown and because imaging tests have a high percentage of false negative results. At this time, it is when laparoscopic para-aortic lymphadenectomy arises, in order to be able to know the extension of the illness better before treatment. A extraperitoneal laparoscopic approach is described in order to reduce complications derived from a possible extended irradiation. Between August 2001 and October 2007, a total of 69 patients with bulky and locally advanced cervical cancer (FIGO stages IB2, IIA > 4 cm and IIB-IVA) underwent extraperitoneal laparoscopic lymphadenectomy for surgical staging. Extraperitoneal aortic lymphadenectomy by laparoscopic approach is a technique with low morbidity. Special laparoscopic material is not required and if it is performed by a team trained in technical endoscopics it is not difficult. Radio-chemotherapy treatment began immediately after laparoscopy because of its minimal aggression.


Asunto(s)
Neoplasias del Cuello Uterino/cirugía , Adolescente , Adulto , Anciano , Femenino , Humanos , Escisión del Ganglio Linfático/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Resultado del Tratamiento , Neoplasias del Cuello Uterino/patología
18.
Acta Obstet Gynecol Scand ; 87(2): 232-9, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18231894

RESUMEN

BACKGROUND: A clinical cohort study of 254 women undergoing trans-obturator surgery for stress urinary incontinence was conducted to assess the efficacy of the trans-obturator suburethral tape (TOT) after a follow-up of 1 year (251 evaluable patients) and 2 years (62 patients). RESULTS: Seventy-five patients had previous gynaecologic surgery. Overall cure and improvement rates were 82% at 6 and 12 months, and 90% at 24 months. The most favourable results were obtained in patients with occult incontinence and urethral hypermobility. The relative risk (RR) for failure in patients with a history of gynaecologic surgery was 3.3 (95% CI: 1.1-14.7). There were 8 cases of bladder perforation (3.1%) during the learning phase with the TOT procedure, 20 of urinary retention (7.9%) - in 1 patient the tape was released after 12 days of insertion - and 3 of tape erosion (1.2%). CONCLUSION: Results are encouraging but should be substantiated on a larger series over a longer follow-up.


Asunto(s)
Cabestrillo Suburetral , Incontinencia Urinaria de Esfuerzo/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Complicaciones Intraoperatorias , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Muestreo , Resultado del Tratamiento , Uretra/fisiopatología , Vejiga Urinaria/lesiones , Retención Urinaria/etiología , Infecciones Urinarias/etiología , Urodinámica/fisiología , Prolapso Uterino/cirugía , Vagina/lesiones
19.
Acta Obstet Gynecol Scand ; 87(7): 723-30, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18607826

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the safety and feasibility of extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected lymph node recurrence of gynecological cancers. DESIGN: Descriptive study. SETTING: Unit of Gynecologic Oncology of an acute-care teaching hospital in Barcelona, Spain. POPULATION: Between December 2002 and October 2007, eight women underwent extraperitoneal laparoscopic paraaortic lymphadenectomy for suspected lymph node recurrence, detected by magnetic resonance image (MRI), computed tomography (CT) scan or 18F-fluorodeoxyglucose positron emission tomography (PET) scanning. The suspicious nodes were removed through an extraperitoneal laparoscopic approach. RESULTS: The median age of patients was 66.5 years (range: 54-74). The median operating time was 157.5 minutes (range: 120-240). The median blood loss was 112.5 mL (range: 50-150). The mean nodal yield was 9.4+/-4.72 (range: 1-16). There were no intraoperative or postoperative complications. The median hospital stay was two days. Histological examination revealed metastasis in seven of eight patients. CONCLUSIONS: The extraperitoneal laparoscopic paraaortic lymphadenectomy for lymph node recurrence of gynecological cancers is a safe and feasible procedure which should be considered where there is isolated involvement of retroperitoneal lymph nodes. This procedure is a minimally invasive technique that allows an excellent approach to the paraaortic lymph nodes.


Asunto(s)
Neoplasias de los Genitales Femeninos/patología , Laparoscopía , Escisión del Ganglio Linfático/métodos , Anciano , Aorta Abdominal , Diagnóstico por Imagen , Estudios de Factibilidad , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía
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