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Antonio Pellicer - One of the best experts on this subject based on the ideXlab platform.
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Surgical treatment of rectovaginal Endometriosis with rectal involvement
Gynecological Surgery, 2011Co-Authors: Vicente Payá, Juan José Hidalgo-mora, Cesar Diaz-garcia, Antonio PellicerAbstract:Rectovaginal Endometriosis (RVE) is one of the most serious and incapacitating forms of presentation of this disease. Traditionally, medical treatment has not been considered effective for the majority of patients, being surgery the only reasonable and therapeutic choice in these cases. This exposes patients to a potentially serious morbidity, thus a careful evaluation should be done by a surgical board considering the impact of the disease as well as the quality of life of the patients. The main surgical techniques used are the shaving of the rectal wall affected by the endometriosic implants, the discoid excision of the front rectal wall, and the segmental intestinal resection, and there is no consensus concerning which is the most effective and suitable between them. The bibliography published in the last 10 years relating to the surgical treatment of RVE is being reviewed with the intention of updating the knowledge base about the topic and looking for common ground between different studies, allowing us to come closer to reaching a consensus about treatment for this pathology.
Osamu Matsubara - One of the best experts on this subject based on the ideXlab platform.
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Loss of ARID1A protein expression occurs as an early event in ovarian clear-cell carcinoma development and frequently coexists with PIK3CA mutations
Modern Pathology, 2012Co-Authors: Sohei Yamamoto, Masashi Takano, Hitoshi Tsuda, Seiichi Tamai, Osamu MatsubaraAbstract:ARID1A is a recently identified tumor suppressor gene that is mutated in ∼50% of ovarian clear-cell carcinomas. This mutation is associated with loss of ARID1A protein expression as assessed by immunohistochemistry. The present study aimed at determining the timing of the loss of ARID1A protein expression during the development of ovarian clear-cell carcinoma and assessing its relevance in correlation to PIK3CA gene mutations. A total of 42 clear-cell carcinoma cases with adjacent putative precursor lesions (Endometriosis-associated carcinoma cases ( n =28) and (clear-cell) adenofibroma-associated carcinoma cases ( n =14)) were selected and subjected to immunohistochemical analysis for ARID1A protein expression and direct genomic DNA sequencing of exons 9 and 20 of the PIK3CA gene. ARID1A immunoreactivity was deficient in 17 (61%) of the 28 Endometriosis-associated carcinomas and 6 (43%) of the 14 adenofibroma-associated carcinomas. Among the precursor lesions adjacent to the 23 ARID1A-deficient carcinomas, 86% of the non-atypical Endometriosis (12 of 14) and 100% of the atypical Endometriosis (14 of 14), benign (3 of 3), and borderline (6 of 6) clear-cell adenofibroma components were found to be ARID1A deficient. In contrast, in the 19 patients with ARID1A-intact carcinomas, all of the adjacent precursor lesions retained ARID1A expression regardless of their types and cytological atypia. Analysis of 22 solitary endometrioses and 10 endometrioses distant from ARID1A-deficient carcinomas showed that all of these lesions were diffusely immunoreactive for ARID1A. Among the 42 clear-cell carcinomas, somatic mutations of PIK3CA were detected in 17 (40%) tumors and majority (71%) of these were ARID1A-deficient carcinomas. These results suggest that loss of ARID1A protein expression occurs as a very early event in ovarian clear-cell carcinoma development, similar to the pattern of PIK3CA mutation recently reported by our group, and frequently coexists (not mutually exclusive) with PIK3CA mutations.
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Accumulative copy number increase of MET drives tumor development and histological progression in a subset of ovarian clear-cell adenocarcinomas
Modern Pathology, 2012Co-Authors: Sohei Yamamoto, Masashi Takano, Hitoshi Tsuda, Seiichi Tamai, Kosuke Miyai, Osamu MatsubaraAbstract:Our previous study demonstrated that, among ovarian carcinomas, amplification of the MET gene and overexpression of MET specifically and commonly occur in clear-cell adenocarcinoma histology. This study was conducted to address how these alterations contribute to development and progression of this highly chemoresistant form of ovarian cancer. We histologically reviewed 21 previously described MET amplification-positive clear-cell adenocarcinoma cases, and selected 11 tumors with synchronous Endometriosis and 2 tumors with adjacent clear-cell adenofibroma (CCAF) components. Using double in situ hybridization and immunohistochemistry, copy number alterations of the MET gene and levels of MET protein expression were analyzed in these putative precursor lesions and the corresponding invasive carcinoma components in this selected cohort. All of the non-atypical precursor lesions analyzed (ie, non-atypical endometrioses and the benign CCAFs) were negative for MET gain. However, low-level (≥3 MET copies in ≥10% and ≥4 MET copies in 10–40% of tumor cells) gain of MET was detected in 4 (40%) of the 10 atypical endometrioses and 1 of the 2 borderline CCAFs. Moreover, high-level (≥4 MET copies in ≥40% of tumor cells) gain of MET were detected in five (50%) of the atypical endometrioses. In 4 (31%) of the 13 cases enrolled, intratumoral heterogeneity for MET gain was documented in invasive carcinoma components, wherein all the relatively differentiated carcinoma components showed low-level gain of MET and all the corresponding poorly differentiated carcinomas showed high-level gain. The overall incidence of MET overexpression gradually increased from the precursors of non-atypical form (0%), through those of atypical form (67%) and the relatively differentiated carcinoma components (92%), to the poorly differentiated carcinoma components (100%). These results suggest that accumulative MET gene copy number alterations causing MET overexpression are associated with higher tumor grade and might drive the development and progression of the MET amplification-positive ovarian clear-cell adenocarcinoma.
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pik3ca mutation is an early event in the development of Endometriosis associated ovarian clear cell adenocarcinoma
The Journal of Pathology, 2011Co-Authors: Sohei Yamamoto, Masashi Takano, Hitoshi Tsuda, Seiichi Tamai, Keichi Iwaya, Osamu MatsubaraAbstract:Clear cell adenocarcinoma (CCA), a highly lethal histological subtype of ovarian carcinoma, is a type of human cancer with a high frequency of activating mutations in the PIK3CA gene. In this study, we aimed to determine how these mutations contribute to tumour development of CCAs. Exons 9 and 20 of the PIK3CA gene were analysed by direct genomic DNA sequencing of 23 CCAs with synchronous putative precursor lesions (ie Endometriosis adjacent to carcinoma, with or without cytological atypia) and their mutational statuses were compared. Somatic mutations of the PIK3CA gene were detected in 10/23 (43%) carcinomas and in all cases the type of mutation was H1047R in the kinase domain. The identical H1047R mutation was also detected in the coexisting endometriotic epithelium, adjacent to the CCAs, in nine of ten (90%) cases. Moreover, in six of the nine lesions, the H1047R mutation was identified even in the endometrioses lacking cytological atypia. These findings provide evidence that mutations of the PIK3CA gene occur in the putative precursor lesions of CCA, strongly suggesting that they are very early events in tumourigenesis, probably initiating the malignant transformation of Endometriosis. A specific kinase inhibitor to mutated PIK3CA may potentially be an effective therapeutic reagent against these carcinomas. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Expression of platelet-derived growth factors and their receptors in ovarian clear-cell carcinoma and its putative precursors
Modern Pathology, 2008Co-Authors: Sohei Yamamoto, Kazuya Kudoh, Kenichi Furuya, Masashi Takano, Tsunekazu Kita, Hitoshi Tsuda, Seiichi Tamai, Osamu MatsubaraAbstract:Recent studies have shown that platelet-derived growth factors and their receptors are frequently co-expressed in ovarian cancers. Herein, we investigated the role of the platelet-derived growth factor pathway in the development of ovarian clear-cell adenocarcinoma, a highly chemoresistant form of ovarian cancer. Immunohistochemical expression of platelet-derived growth factor receptor- α and receptor- β , platelet-derived growth factor A-chain and B-chain was examined in 31 cases of clear-cell adenocarcinoma and 56 coexisting putative precursor lesions: 17 non-atypical and 19 atypical endometrioses, and 10 non-atypical and 10 atypical clear-cell adenofibroma components. Twenty-one solitary endometrioses were also examined. Vascular endothelial cells were always positive for all the markers examined, and were used as positive controls. The frequencies of positivity for platelet-derived growth factor receptor- α and receptor- β , and platelet-derived growth factor A-chain increased in accordance with higher cytologic atypia in the putative precursors: 71, 47, and 59% in the 17 non-atypical endometrioses, 84, 73, and 84% in the 19 atypical endometrioses, 0% each in the 10 non-atypical clear-cell adenofibromas, 100, 90, and 90% in the 10 atypical clear-cell adenofibromas, and 97, 97, and 100% in the 31 clear-cell adenocarcinomas, respectively. Positivity for platelet-derived growth factor B-chain increased in accordance with increased atypia in clear-cell adenofibroma: 0% in non-atypical clear-cell adenofibromas, 30% in atypical clear-cell adenofibromas, and 60% in coexisting carcinomas. However, in contrast, positivity for platelet-derived growth factor B-chain decreased in accordance with increased atypia in Endometriosis coexisting with clear-cell adenocarcinomas: 35% in non-atypical endometrioses, 11% in atypical endometrioses, and 5% in coexisting carcinomas. Platelet-derived growth factor receptor- α and receptor- β , and their ligands A-chain and B-chain were positive in 14, 29, 19, and 62% of the solitary endometrioses, respectively. These results indicate activation of the platelet-derived growth factor pathway in ovarian clear-cell adenocarcinomas and suggest biological differences between carcinomas that arise in association with clear-cell adenofibroma vs Endometriosis.
Alan J. Hunter - One of the best experts on this subject based on the ideXlab platform.
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Thoracic Endometriosis Unmasked by Ovarian Hyperstimulation for in vitro Fertilization
Journal of General Internal Medicine, 2012Co-Authors: Stephanie A. C. Halvorson, Mari A. Ricker, Alan F. Barker, Phillip E. Patton, Rebecca A. Harrison, Alan J. HunterAbstract:Thoracic Endometriosis syndrome is a well-described, rare manifestation of Endometriosis. We present a case of a 35-year old woman undergoing controlled ovarian stimulation prior to in vitro fertilization (IVF) who developed bilateral hemorrhagic pleural effusions. She was initially diagnosed with ovarian hyperstimulation syndrome, a complication of infertility therapy; however, she was later found to have occult thoracic Endometriosis. We describe ovarian hyperstimulation syndrome and review the manifestations of thoracic Endometriosis syndrome. Although Endometriosis is a hormone-dependent disease, the rate of IVF complications related to Endometriosis is low.
Vicente Payá - One of the best experts on this subject based on the ideXlab platform.
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Surgical treatment of rectovaginal Endometriosis with rectal involvement
Gynecological Surgery, 2011Co-Authors: Vicente Payá, Juan José Hidalgo-mora, Cesar Diaz-garcia, Antonio PellicerAbstract:Rectovaginal Endometriosis (RVE) is one of the most serious and incapacitating forms of presentation of this disease. Traditionally, medical treatment has not been considered effective for the majority of patients, being surgery the only reasonable and therapeutic choice in these cases. This exposes patients to a potentially serious morbidity, thus a careful evaluation should be done by a surgical board considering the impact of the disease as well as the quality of life of the patients. The main surgical techniques used are the shaving of the rectal wall affected by the endometriosic implants, the discoid excision of the front rectal wall, and the segmental intestinal resection, and there is no consensus concerning which is the most effective and suitable between them. The bibliography published in the last 10 years relating to the surgical treatment of RVE is being reviewed with the intention of updating the knowledge base about the topic and looking for common ground between different studies, allowing us to come closer to reaching a consensus about treatment for this pathology.
Loïc Marpeau - One of the best experts on this subject based on the ideXlab platform.
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Is painful rectovaginal Endometriosis an intermediate stage of rectal Endometriosis
Fertility and sterility, 2007Co-Authors: Horace Roman, Alexis Gromez, Patrick Hochain, N Marouteau-pasquier, Jean-jacques Tuech, Benoit Resch, Loïc MarpeauAbstract:Objective To compare the history of pain complaints of women presenting rectovaginal and rectal Endometriosis to show that rectovaginal locations may progress to a rectal involvement of the disease. Design Retrospective comparative study. Setting Department of Gynecology and Obstetrics, University Hospital Rouen, France. Patient(s) Thirty-two patients with rectovaginal Endometriosis and 16 patients with rectal involvement. Intervention(s) Standardized questionnaires recording the clinical history of painful deep Endometriosis up to diagnosis. Main Outcome Measure(s) Length of time from onset of pain to diagnosis, types of pain, disability related to the pain, and number of physicians consulted before the diagnosis was made. Result(s) Women with rectal Endometriosis had an earlier onset of dysmenorrhoea. The age of dysmenorrhoea and the length of time between the onset of the first pain to the first time that the Endometriosis was suspected were significantly increased in women with rectal Endometriosis. Pain during defecation was more frequent in patients with rectal Endometriosis. Women consulted an average of three physicians before the Endometriosis diagnosis was suggested. A nongynecologist physician made the diagnosis of rectovaginal and rectal Endometriosis in respectively 26% and 31% of cases. Conclusion(s) Rectal Endometriosis is associated with an earlier onset and a longer history of painful symptoms until the diagnosis was made when compared with rectovaginal Endometriosis locations. These observations support the hypothesis that rectovaginal location may be an intermediate stage of rectal Endometriosis.
