MAURICIO SIMOES ABRAO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina - Docente
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
16 resultados
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Agora exibindo 1 - 10 de 16
- Consensus on Recording Deep Endometriosis Surgery: the CORDES statement(aEuro)(2016) VANHIE, A.; MEULEMAN, C.; TOMASSETTI, C.; TIMMERMAN, D.; D'HOORE, A.; WOLTHUIS, A.; CLEYNENBREUGEL, B. Van; DANCET, E.; BROECK, U. Van den; TSALTAS, J.; RENNER, S. P.; EBERT, A. D.; CARMONA, F.; ABBOTT, J.; STEPNIEWSKA, A.; TAYLOR, H.; SARIDOGAN, E.; MUELLER, M.; KECKSTEIN, J.; PLUCHINO, N.; JANIK, G.; ZUPI, E.; MINELLI, L.; COOPER, M.; DUNSELMAN, G.; KOH, C.; ABRAO, M.; CHAPRON, C.; D'HOOGHE, T.Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. International expert consensus based on a systematic review of literature. Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here. This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. N/A.
- World Endometriosis Society consensus on the classification of endometriosis(2017) JOHNSON, Neil P.; HUMMELSHOJ, Lone; ADAMSON, G. David; KECKSTEIN, Jorg; TAYLOR, Hugh S.; ABRAO, Mauricio S.; BUSH, Deborah; KIESEL, Ludwig; TAMIMI, Rulla; SHARPE-TIMMS, Kathy L.; ROMBAUTS, Luk; GIUDICE, Linda C.STUDY QUESTION: What is the global consensus on the classification of endometriosis that considers the views of women with endometriosis? SUMMARY ANSWER: We have produced an international consensus statement on the classification of endometriosis through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometriosis. WHAT IS KNOWN ALREADY: Classification systems of endometriosis, developed by several professional organizations, traditionally have been based on lesion appearance, pelvic adhesions, and anatomic location of disease. One system predicts fertility outcome and none predicts pelvic pain, response to medications, disease recurrence, risks for associated disorders, quality of life measures, and other endpoints important to women and health care providers for guiding appropriate therapeutic options and prognosis. STUDY DESIGN, SIZE, DURATION: A consensus meeting, in conjunction with pre-and post-meeting processes, was undertaken. PARTICIPANTS/MATERIALS, SETTING, METHODS: A consensus meeting was held on 30 April 2014 in conjunction with the World Endometriosis Society's 12th World Congress on Endometriosis. Rigorous pre-and post-meeting processes, involving 55 representatives of 29 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 28 consensus statements were made. Of all, 10 statements had unanimous consensus, however none of the statements was made without expression of a caveat about the strength of the statement or the statement itself. Two statements did not achieve majority consensus. The statements covered women's priorities, aspects of classification, impact of low resources, as well as all the major classification systems for endometriosis. Until better classification systems are developed, we propose a classification toolbox (that includes the revised American Society for Reproductive Medicine and, where appropriate, the Enzian and Endometriosis Fertility Index staging systems), that may be used by all surgeons in each case of surgery undertaken for women with endometriosis. We also propose wider use of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project surgical and clinical data collection tools for research to improve classification of endometriosis in the future, of particular relevance when surgery is not undertaken. LIMITATIONS, REASONS FOR CAUTION: This consensus process differed from that of formal guideline development, although based on the same available evidence. A different group of international experts from those participating in this process may have yielded subtly different consensus statements. WIDER IMPLICATIONS OF THE FINDINGS: This is the first time that a large, global, consortium-representing 29 major stake-holding organizations, from 19 countries-has convened to systematically evaluate the best available evidence on the classification of endometriosis and reach consensus. In addition to 21 international medical organizations and companies, representatives from eight national endometriosis organizations were involved, including lay support groups, thus generating and including input from women who suffer from endometriosis in an endeavour to keep uppermost the goal of optimizing quality of life for women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The World Endometriosis Society convened and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Mauricio Abrao is an advisor to Bayer Pharma, and a consultant to AbbVie and AstraZeneca; G David Adamson is the Owner of Advanced Reproductive Care Inc and Ziva and a consultant to Bayer Pharma, Ferring, and AbbVie; Deborah Bush has received travel grants from Fisher & Paykel Healthcare and Bayer Pharmaceuticals; Linda Giudice is a consultant to AbbVie, Juniper Pharmaceutical, and NextGen Jane, holds research grant from the NIH, is site PI on a clinical trial sponsored by Bayer, and is a shareholder in Merck and Pfizer; Lone Hummelshoj is an unpaid consultant to AbbVie; Neil Johnson has received conference expenses from Bayer Pharma, Merck-Serono, and MSD, research funding from AbbVie, and is a consultant to Vifor Pharma and Guerbet; Jrg Keckstein has received a travel grant from AbbVie; Ludwig Kiesel is a consultant to Bayer Pharma, AbbVie, AstraZeneca, Gedeon Richter, and Shionogi, and holds a research grant from Bayer Pharma; Luk Rombauts is an advisor to MSD, Merck Serono, and Ferring, and a shareholder in Monash IVF. The following have declared that they have nothing to disclose: Kathy Sharpe Timms; Rulla Tamimi; Hugh Taylor. TRIAL REGISTRATION NUMBER: N/A
- Reply: Should we also work on an international informed consent for endometriosis surgery?(2017) VANHIE, A.; MEULEMAN, C.; TOMASSETTI, C.; TIMMERMAN, D.; D'HOORE, A.; WOLTHUIS, A.; CLEYNENBREUGEL, B. Van; DANCET, E.; BROECK, U. Van den; TSALTAS, J.; RENNER, S. P.; EBERT, A. D.; CARMONA, F.; ABBOTT, J.; STEPNIEWSKA, A.; TAYLOR, H.; SARIDOGAN, E.; MUELLER, M.; KECKSTEIN, J.; PLUCHINO, N.; ZUPI, E.; DUNSELMAN, G.; ABRAO, M. S.; CHAPRON, C.; D'HOOGHE, T.
- Systematic evaluation of endometriosis by transvaginal ultrasound can accurately replace diagnostic laparoscopy, mainly for deep and ovarian endometriosis(2021) GONCALVES, Manoel Orlando; NETO, Joao Siufi; ANDRES, Marina Paula; SIUFI, Daniela; MATTOS, Leandro Accardo de; ABRAO, Mauricio S.STUDY QUESTION: What is the sensitivity and the specificity of preoperative transvaginal ultrasound with bowel preparation (TVUS-BP) compared to diagnostic laparoscopy (DL) for the identification of ovarian and deep sites of endometriosis? SUMMARY ANSWER: DL was able to detect retrocervical, ovarian, and bladder endometriosis with similar sensitivity and specificity as TVUS-BP, whereas for vaginal and rectosigmoid endometriosis, DL had lower sensitivity and specificity than TVUS-BP. WHAT IS KNOWN ALREADY: TVUS-BP is a non-invasive examination with good accuracy for diagnosing ovarian and deep endometriosis. DL is expensive and can lead to surgical complications. STUDY DESIGN, SIZE, DURATION: This prospective study included a total of 120 consecutive patients who underwent surgery for suspected endometriosis with preoperative imaging (TVUS-BP), including a video of the laparoscopic procedure, between March 2017 and September 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two radiologists performed preoperative TVUS-BP using the same protocol for diagnosing endometriosis. Two surgeons, who were blinded to the results of the preoperative imaging and clinical data, reviewed the surgical videos from the entry of the abdominal cavity until the surgeon finalized a complete and systematic review prior to beginning any dissection (considered as a DL). A data sheet was used by surgeons and radiologists to record the sites and size of disease involvement, the American Society for Reproductive Medicine (ASRM) stage, and the Enzian score. The surgical visualization of endometriosis lesions that were confirmed by histological analysis was the gold standard. MAIN RESULTS AND THE ROLE OF CHANCE: DL was able to detect retrocervical, ovarian, and bladder endometriosis with similar sensitivity and specificity as TVUS-BP. DL was not able to detect vaginal endometriosis (sensitivity and specificity 0%): this is compared to a sensitivity and specificity of 85.7% and 99.1%, respectively with the utilization of a preoperative TVUS-BP. In addition, DL was notably poor at detecting rectosigmoid endometriosis, with a sensitivity of 3.7-5.6%, and this compares to 96.3% sensitivity with utilization of a preoperative TVUS (P<0.001). For the ASRM stage, TVUS-BP results were highly correlated with the degree of endometriosis and pouch of Douglas (POD) obliteration (weighted Kappa of 0.867 and 0.985, respectively). For the Enzian score, there was a substantial correlation between TVUSP-BP and DL for compartment A (weighted Kappa = 0.827), compartment B (weighted Kappa = 0.670), and compartment C (weighted kappa = 0.814). LIMITATIONS, REASONS FOR CAUTION: The number of participants included may be a limitation in this study and, as the evaluators were blinded to the physical exam, the DL accuracy could be underestimated. As biopsies of pelvic organs were obtained only if there was a suspicion of endometriosis, the gold standard was not always applicable. This aspect could underestimate the prevalence of lesions and overestimate the sensitivity and the specificity of both the TVUS-BP and the DL. WIDER IMPLICATIONS OF THE FINDINGS: Preoperative TVUS-BP was accurate in identifying all sites of ovarian and deep endometriosis that were evaluated. It had significantly higher sensitivity than DL in detecting rectosigmoid endometriosis and predicting intraoperative ASRM staging and the Enzian score. These results suggest that TVUS-BP can replace DL for the diagnosis and treatment planning for patients with ovarian and deep endometriosis.
conferenceObject SPIRIT long-term extension study: two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain(2022) BECKER, C.; AS-SANIE, S.; ABRAO, M. S.; BROWN, E.; FERREIRA, J. C. Arjona; WAGMAN, R. B.; WANG, F.; PERRY, J. S.; JOHNSON, N.; GIUDUCE, L. C.- B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice(2019) RICCIO, L. G. C.; JELJELI, M.; SANTULLI, P.; CHOUZENOUX, S.; DORIDOT, L.; NICCO, C.; REIS, F. M.; ABRAO, M. S.; CHAPRON, C.; BATTEUX, F.STUDY QUESTION: What are the effects of B lymphocyte inactivation or depletion on the progression of endometriosis? SUMMARY ANSWER: Skewing activated B cells toward regulatory B cells (Bregs) by Bruton's tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect. WHAT IS KNOWN ALREADY: A polyclonal activation of B cells and the presence of anti-endometrial autoanti bodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear. STUDY DESIGN, SIZE, DURATION: This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation. PARTICIPANTS/MATERIALS, SETTING, METHODS: After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA. MAIN RESULTS AND THE ROLE OF CHANCE: Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinibtreated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: It is still unclear whether B cell depletion by the anti-CD20 or inactivation by Ibrutinib can prevent establishment and/or progression of endometriosis in humans. WIDER IMPLICATIONS OF THE FINDINGS: Further investigation may contribute to clarifying the role of B cell subsets in human endometriosis.
- Common chromosomal imbalances and stemness-related protein expression markers in endometriotic lesions from different anatomical sites: the potential role of stem cells(2012) SILVEIRA, Cassia G. T.; ABRAO, Mauricio S.; DIAS JR., Joao A.; COUDRY, Renata A.; SOARES, Fernando A.; DRIGO, Sandra A.; DOMINGUES, Maria A. C.; ROGATTO, Silvia R.Endometriosis is a multifactorial gynecological disease characterized by the presence of functional endometrium-like tissue in ectopic sites. Several studies have focused on elucidating the immunological, endocrine, environmental and genetic factors involved in endometriosis. However, its pathogenesis is still unclear. High-resolution comparative genomic hybridization was applied to screen for genomic imbalances in laser microdissected stromal and epithelial cells from 20 endometriotic lesions and three samples of eutopic endometrium derived from eight patients. The expression of seven stemness-related markers (CD9, CD13, CD24, CD34, CD133, CD117/c-Kit and Oct-4) in endometrial tissue samples was evaluated by immunohistochemistry. Samples of eutopic endometrium showed normal genomic profiles. In ectopic tissues, an average of 68 genomic imbalances was detected per sample. DNA losses were more frequently detected and involved mainly 3p, 5q, 7p, 9p, 11q, 16q, 18q and 19q. Many of the genomic imbalances detected were common to endometriotic stroma and epithelia and also among different endometriotic sites from the same patient. These findings suggested a clonal origin of the endometriotic cells and the putative involvement of stem cells. Positive immunostaining for CD9, CD34, c-Kit and Oct-4 markers was detected in isolated epithelial and/or stromal cells in eutopic and ectopic endometrium in the majority of cases. The presence of shared genomic alterations in stromal and epithelial cells from different anatomical sites of the same patient and the expression of stemness-related markers suggested that endometriosis arises as a clonal proliferation with the putative involvement of stem cells.
- mRNA levels of low-density lipoprotein receptors are overexpressed in the foci of deep bowel endometriosis(2017) GIBRAN, Luciano; MARANHAO, Raul C.; TAVARES, Elaine R.; CARVALHO, Priscila O.; ABRAO, Mauricio S.; PODGAEC, SergioSTUDY QUESTION: Is mRNA expression of LDL receptors altered in deep bowel endometriotic foci? SUMMARY ANSWER: mRNA expression of LDL receptors is up-regulated in deep bowel endometriotic foci of patients with endometriosis. WHAT IS KNOWN ALREADY: Several studies have demonstrated the overexpression of low-density lipoprotein receptors in various tumour cell lines and endometriosis has similar aspects to cancer, mainly concerning the pathogenesis of both diseases. This is the first study we know of to investigate lipoprotein receptors expression in deep endometriosis with bowel involvement. STUDY DESIGN, SIZE, DURATION: During 2014-2015, an exploratory case-control study was conducted with 39 patients, including 20 women with a histological diagnosis of deep endometriosis compromising the bowel and 19 women without endometriosis who underwent laparoscopic tubal ligation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Peripheral blood samples were collected on the day of surgery for lipid profile analysis, and samples of endometrial tissue and of bowel endometriotic lesions were also collected. The tissue samples were sent for histopathological analysis and for LDL-R and LRP-1 gene expression screening using quantitative real-time PCR. MAIN RESULTS AND THE ROLE OF CHANCE: Patients with deep endometriosis had lower LDL-cholesterol than patients without the disease (119 +/- 23 versus 156 +/- 35; P = 0.001). Gene expression analysis of LDL receptors revealed that LDL-R was more highly expressed in endometriotic lesions when compared to the endometrium of the same patient but not more than in the endometrium of women without endometriosis (0.027 +/- 0.022 versus 0.012 +/- 0.009 versus 0.019 +/- 0.01, respectively; P < 0.001). LRP-1 was more highly expressed in endometriotic lesions, both when compared with the endometrium of the same patient and when compared with the endometrium of patients without the disease (0.307 +/- 0.207 versus 0.089 +/- 0.076 and versus 0.126 +/- 0.072, respectively; P < 0.001). The study also showed that LDL-R gene expression in the endometrium of women with endometriosis was higher during the secretory phase of the menstrual cycle (P = 0.001). LRP-1 gene expression was increased during the secretory phase in the endometrium of women without the disease (P = 0.008). LIMITATIONS, REASONS FOR CAUTION: In the endometriotic lesions, the presence of fibrosis is substantial, restricting access to the stromal and glandular components of the lesion. Despite that, we found that LDL receptor mRNA was overexpressed. Future studies may perform laser microdissection to isolate the area of interest in the target tissue, excluding fibrosis contamination. WIDER IMPLICATIONS OF THE FINDINGS: This study supports the feasibility of LDL-R targeted therapy in the treatment of deep endometriosis.
conferenceObject Sustained efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT 52-week data(2021) AS-SANIE, S.; GIUDICE, L.; ABRAO, M. S.; WILK, K.; MEHEDINTU, C.; BECKER, C.; FERREIRA, J. C. Arjona; WAGMAN, R. B.; WANG, F.; WARSI, Q. A.; NEIL, J.- Reply: Biochemical markers for endometriosis: a long way to go(2014) BORRELLI, G. M.; ABRAO, M. S.; MECHSNER, S.