卵巣子宮内膜症性嚢胞の癌化におけるCD44v9と8-OHdGの発現

Aim: Expression of CD44 variant isoforms (CD44v) promotes the synthesis of reduced glutathione and contributes to reactive oxygen species defense through up-regulation of the intracellular antioxidant. The aim of the study was to investigate the expression of CD44v9 and oxidative DNA damage marker, 8-OHdG, in benign ovarian endometrioma (OE) and OE harboring clear cell carcinomas (CCC). Methods: A retrospective study was performed at the Department of Gynecology, Nara Medical University hospital from January 2006 to December 2012. Patients with histologically confirmed benign OE (n = 27) and OE harboring areas of CCC (n = 8) were selected. Tissue samples were immunohistochemically analyzed for the presence of CD44v9 and 8-OHdG using avidin-biotin complex method. Results: CD44v9 was located on the cell membrane of endometriotic epithelial cells and expressed in 88.9% (24/27) of benign OE tissues. Only 25.0% (2/8) of benign endometriotic lesions adjacent to CCC was found to stain weakly for CD44v9. Percentage of CD44v9 positive cells was 68.5 ± 20.2% (mean ± standard deviation) of benign OE, 16.7 ± 16.5% of CCC endometriotic tissue (P < 0.001). Compared to benign OE, CCC endometriotic tissue showed a significant increase in the proportion of 8-OHdG expression (77.3 ± 22.5% vs 94.9 ± 3.0%, P = 0.049). A significant negative correlation was observed between CD44v9 status and 8-OHdG nuclear expression (r = -0.458, P = 0.006). Conclusion: Alterations in CD44v9 and 8-OHdG may be associated with malignant transformation of benign OE.博士（医学）・乙第1452号・令和2年3月16日© 2019 Japan Society of Obstetrics and Gynecology.This is the peer reviewed version of the following article: [https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/jog.14093], which has been published in final form at [https://doi.org/10.1111/jog.14093]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

子宮内膜側に発症する (Subtypel) 子宮腺筋症は黄体ホルモン療法による多量性器出血の危険因子である

We aimed to retrospectively analyze the risk factors of a continuous dienogest (DNG) therapy for serious unpredictable bleeding in patients with symptomatic adenomyosis. This is a retrospective study based on data extracted from medical records of 84 women treated with 2 mg of DNG orally each day between 2008 and 2017. 47 subjects were excluded from the original analyses due to an inadequate subcategorization into subtype I and subtype II and a lack of hemoglobin levels. The influence of various independent variables on serious unpredictable bleeding was assessed. Of the 37 eligible patients who received the continuous DNG therapy, 14 patients experienced serious unpredictable bleeding. Univariate analysis revealed that the serious bleeding group had subtype I adenomyosis (P = 0.027). There was no correlation between age, parity, minimum hemoglobin level before treatment, previous endometrial curettage, and duration of DNG administration, or uterine or adenomyosis size and the serious bleeding. A DNG-related serious unpredictable bleeding is associated with the structural type of adenomyosis (subtype I) in patients with symptomatic adenomyosis.博士（医学）・甲第800号・令和3年9月29日© The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Preoperative plasma D-dimer level is a useful prognostic marker in ovarian cancer

A high pre-treatment plasma D-dimer level was recently identified as a poor prognostic factor in several malignancies. The aim of this study was to evaluate the prognostic significance of plasma D-dimer levels in epithelial ovarian cancer (EOC). Data of 199 patients were retrospectively analysed. The relationships between pre-treatment D-dimer levels and other clinical parameters and prognosis were evaluated. Univariate analysis identified age, pre-treatment plasma D-dimer level, massive ascites, residual tumours, pre-treatment CA125 level, histological type, and FIGO stage as predictors of overall survival. The multivariate analysis showed that a high pre-treatment plasma D-dimer level (p=.017), residual tumours (p < .001), and FIGO stage (p = .036) were independent risk factors of overall survival. Venous thromboembolism (VTE) did not influence overall survival (p=.091). High pre-treatment D-dimer levels are associated with a poor prognosis independent of VTE status in EOC patients, and might be a useful prognostic biomarker.Impact statement What is already known on this subject? In recent years, a high pre-treatment plasma D-dimer level has been identified as a prognostic factor in several malignancies, but only a handful of studies have assessed the role of pre-treatment plasma D-dimer levels in patients with EOC patients. Thus, the clinical significance and prognostic value of the plasma D-dimer level in EOC remain controversial, and there is also debate related to the association of the higher mortality rate among cancer patients with elevated D-dimer levels with VTE. What do the results of this study add? In our study, high pre-treatment D-dimer levels are associated with a poor prognosis independently of VTE in EOC patients. What are the implications of these findings for clinical practice and/or further research? The D-dimer level might emerge as a valuable prognostic biomarker, which will help doctors in the choice of initiating a more aggressive therapy, the combination of chemotherapy with anticoagulation therapy

Immunohistochemical expression of CD44v9 and 8-OHdG in ovarian endometrioma and the benign endometriotic lesions adjacent to clear cell carcinoma.

Aim: Expression of CD44 variant isoforms (CD44v) promotes the synthesis of reduced glutathione and contributes to reactive oxygen species defense through up-regulation of the intracellular antioxidant. The aim of the study was to investigate the expression of CD44v9 and oxidative DNA damage marker, 8-OHdG, in benign ovarian endometrioma (OE) and OE harboring clear cell carcinomas (CCC). Methods: A retrospective study was performed at the Department of Gynecology, Nara Medical University hospital from January 2006 to December 2012. Patients with histologically confirmed benign OE (n = 27) and OE harboring areas of CCC (n = 8) were selected. Tissue samples were immunohistochemically analyzed for the presence of CD44v9 and 8-OHdG using avidin-biotin complex method. Results: CD44v9 was located on the cell membrane of endometriotic epithelial cells and expressed in 88.9% (24/27) of benign OE tissues. Only 25.0% (2/8) of benign endometriotic lesions adjacent to CCC was found to stain weakly for CD44v9. Percentage of CD44v9 positive cells was 68.5 ± 20.2% (mean ± standard deviation) of benign OE, 16.7 ± 16.5% of CCC endometriotic tissue (P < 0.001). Compared to benign OE, CCC endometriotic tissue showed a significant increase in the proportion of 8-OHdG expression (77.3 ± 22.5% vs 94.9 ± 3.0%, P = 0.049). A significant negative correlation was observed between CD44v9 status and 8-OHdG nuclear expression (r = -0.458, P = 0.006). Conclusion: Alterations in CD44v9 and 8-OHdG may be associated with malignant transformation of benign OE.博士（医学）・乙第1452号・令和2年3月16日© 2019 Japan Society of Obstetrics and Gynecology.This is the peer reviewed version of the following article: [https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/jog.14093], which has been published in final form at [https://doi.org/10.1111/jog.14093]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.identifier:The journal of obstetrics and gynaecology research Vol.45 No.11 p.2260-2266 (2019 Nov)identifier:13418076identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3742identifier:The journal of obstetrics and gynaecology research, 45(11): 2260-226