BACKGROUND: The prevalence of endometriosis among women of reproductive age and the complexity of choosing the methods for its effective treatment necessitate the study of the clinical and morphological features of ovarian endometriosis in its recurrent course, as well as the search for available informative diagnostic and prognostic markers which allow identifying risk groups for relapse and form prevention methods. Endometriomas have a recurrence rate of 5055 % after treatment. AIM: The aim of this study was to conduct a comparative analysis of cell immune regulation features in recurrent ovarian endometriosis. MATERIALS AND METHODS: We studied clinical data, the value of peripheral immunocompetent blood cells, as well as morphological and immunohistochemical data of 196 patients operated on for endometrioid ovarian cysts, including 45 patients with a recurrent course of the disease and 151 women without relapse. Monoclonal mouse antibodies to T helpers (CD4), T killers (CD8), B lymphocytes (CD20), and macrophages (CD68) were used for immunohistochemical examination of the surgical material. Immunological examination of peripheral blood was performed by flow cytometry with the assessment of helper T lymphocyte, killer T lymphocyte and B lymphocyte subpopulations and their ratios. RESULTS: The recurrence rate of endometrioid ovarian cysts was 22.96%. Most patients (48.87%) relapsed 34 years after the first operation. In patients with recurrent endometrioma, we more often detected complaints of dyspareunia, dysmenorrhea, primary infertility and a history of operations on the uterine appendages unrelated to endometriosis in anamnesis, as well as the third degree of the pathological process. During morphological examination, the glandular-cystic variant and morphologically active lesions were detected more often in recurrent endometriosis compared to the relapse-free course. Cytotoxic T killers (CD8) and macrophages (CD68) were shown to be the predominant subpopulation of cells found in the inflammatory infiltrate of cytogenic stroma and endometrioid cyst capsule. More of them were detected in recurrent endometrioid cysts in the surgical material of both the first and second operations compared to the relapse-free course. B lymphocyte count was significantly higher in the cyst capsule with recurrent endometriosis than in cases of the relapse-free course. T helpers (CD4) were found only in the surgical material of an already diagnosed recurrence. Immunological examination of peripheral blood of patients with recurrent endometrioma revealed an increase in the total population of T lymphocytes due to a subpopulation of T helpers, the number of which per microliter exceeded the reference values. CONCLUSIONS: An increase in the number of free stromal cells in the foci of endometriosis with its recurrent course indicates the importance of hyperreactivity and the autoimmune mechanism in the chronization and progression of the disease.
BACKGROUND: One of the clinical course features of ovarian endometriosis is its recurrent nature, which leads to repeated operations and increased damage to the ovarian follicular apparatus. AIM: The aim of this study was to evaluate morphological and molecular features of recurrent endometrioid ovarian cysts in patients of reproductive age. MATERIALS AND METHODS: Morphological and immunohistochemical studies of the surgical material of 196 observations of endometrioid ovarian cysts were performed 23 observations of the first surgical intervention with further diagnosed relapse, 22 observations of repeated surgery and 151 observations of a relapse-free course of endometriosis. Monoclonal mouse antibodies to CD68, transforming growth factor -1, CD34, and -smooth muscle actin were used. RESULTS: CD68 (macrophage) expression was detected in lympho-macrophage infiltrates of the cytogenic stroma and endometrioid cyst capsule. Significantly greater values of the expression were obtained in recurrent endometrioid cysts in the surgical material of both the first (cytogenic stroma 31 [8; 53]%, capsule 23 [3; 42]%) and second operation (23 [12; 36] and 9 [5; 20]%, respectively) compared to the relapse-free course of the disease (8 [6; 9] and 2 [0; 4]%, respectively). The transforming growth factor -1 expression area in the endometrioid cyst capsule was significantly higher in the surgical material of both the first (22.8 [21.6; 24.8]%) and second operation (31.2 [30.5; 32.2]%) with recurrent endometriosis compared to cases with no relapse (12.7 [11.2; 13.9]%). But in the cytogenic stroma was it only detected in cases of repeated surgical endometrioid cyst treatment (18.7 [18.0; 19.7]%). The positive -smooth muscle actin expression area was higher in the surgical material of the second operation with recurrent endometriosis in both the cytogenic stroma (68.3 [66.3; 69.6]%) and endometrioma capsule (82.5 [80.5; 83.8]%). A large area of CD34 expression was also detected in the recurrent course of ovarian endometriosis in the surgical material of both the first (cytogenic stroma 34.8 [33.4; 35.8]%, capsule 52.6 [50.4; 55.0]%) and second operation (51.3 [49.0; 53.3] and 48.7 [46.7; 49.8]%, respectively). CONCLUSIONS: The recurrent course of ovarian endometriosis is characterized by more pronounced inflammation, angiogenesis, myofibroblast proliferation, and fibrogenesis, which indicates the importance of these pathological processes in the chronicity of the disease. Further study of the role of macrophages and the cascade of regenerative and reparative processes that they trigger is important for understanding the pathogenesis of endometriosis and searching for diagnostic markers of its recurrent course.
BACKGROUND: The main method of endometrioid ovarian cyst treatment is considered surgery with further hormone therapy. However, the recurrence rate of endometriomas, even 57 years after combined treatment, can reach 50%. AIM: The aim of this study was to identify risk factors for recurrence of endometrioid ovarian cysts among women of reproductive age after combined treatment. MATERIALS AND METHODS: This study included 196 women operated on for ovarian endometriosis. We carried out a comparative analysis of the data between the study groups: the main group comprised 45 patients with a relapse of the disease; the comparison group consisted of 151 women without a relapse. Hematoxylin-eosin staining was used for morphological examination of the surgical material, and monoclonal mouse antibodies to Ki-67 and bcl-2 (DAKO, Denmark) were used for immunohistochemical examination. The construction of a statistical model for predicting the recurrence of ovarian endometriosis among women of reproductive age was carried out using multivariate binary logistic regression analysis in reverse stepwise mode. The influence of the independent variable on the likelihood of recurrence was determined using the odds ratio and its 95% confidence interval, with the sensitivity, specificity and diagnostic accuracy evaluated. RESULTS: A set of predictors has been identified that provides the greatest contribution to recurrence of ovarian endometriosis. Immunohistochemistry study showed that the level of Ki-67 protein was higher in the group with relapsed endometriomas compared to the non-recurrent course: in the epithelial lining of the cyst, 9.08 2.60 and 2.06 1.16%, respectively (p = 0.043); in the cytogenic stroma, 11.67 4.10 and 9.81 3.40%, respectively (p = 0.48). Bcl-2 expression was reduced in the epithelial lining of the cyst capsule in the main group in comparison with the material where there was no recurrence: 0.653 0.043 and 0.961 0.056%, respectively (p = 0.31). CONCLUSIONS: Of significance in predicting the risk of recurrence of ovarian endometriosis is a combination of four signs in one patient: primary infertility; pelvic organ surgery in history, unrelated to endometriosis; elevated levels of CA-125 oncoprotein and proliferative changes in cytogenic stroma cells, as well as increased expression of the Ki-67 antigen in the epithelial lining of the endometrioid cyst.
BACKGROUND: In recent years, an important role in the pathogenesis of adenomyosis has been assigned to invasive properties of the cells of the basal layer of the endometrium, which provide them with the capacity to grow into the underlying layers of the myometrium. AIM: The aim of this study was to evaluate the invasive and migratory properties of the ectopic and heterotopic endometrium in patients with adenomyosis. MATERIALS AND METHODS: We performed clinical, morphological and immunohistochemical analyses of the surgical material of 98 patients with adenomyosis. Immunohistochemical study was carried out according to the standard avidin-biotin method, using mouse monoclonal antibodies to estrogen receptors, matrix metalloproteinase type 9, vimentin, and fibronectin (DAKO, Denmark) as primary immune sera. RESULTS: The maximum number of estrogen receptors in both the proliferation and secretion phases was found in the endometrial glands and superficially located endometrioid heterotopias. A weaker expression of this marker was also found in the cells of the cytogenic stroma. In the foci of adenomyosis, located in the deep layers of the myometrium, the expression of estrogen receptors in the epithelial and stromal components of heterotopias varied in a wide range from 0 to 100%. The most pronounced expression of matrix metalloproteinase type 9 was characteristic of the epithelial component of superficial endometrioid heterotopias. In the foci of adenomyosis, located in the deep parts of the myometrium, a pronounced expression of matrix metalloproteinase type 9 was preserved in the proliferation phase, and its significant decrease was found in the secretion phase. The glands of the eutopic endometrium were also characterized by a more significant level of matrix metalloproteinase type 9 expression in the proliferation phase in comparison with the secretion phase. A pronounced expression of vimentin was detected in the epithelium of the glands of both superficial and deep foci of adenomyosis, as well as in the eutopic endometrium (100%). In the cytogenic stroma, the largest area of vimentin expression was found in the eutopic endometrium and superficially located endometrioid heterotopias. However, its value significantly decreased in the foci of adenomyosis located in the deep parts of the myometrium. The largest area of fibronectin expression was characteristic of the cytogenic stroma of superficial adenomyosis foci. CONCLUSIONS: The displacement of elements of the eutopic endometrium into the thickness of the myometrium and further progression of adenomyosis is provided by two parallel pathogenetic mechanisms, namely, invasive growth due to matrix metalloproteinase type 9 activation and epithelial cell migration due to the epithelial-mesenchymal transition.
BACKGROUND: Postoperative scar endometriosis is diagnosed in 0.031.5% of women and is 0.424.0% of the total number of endometriosis lesions. The increase in the frequency of surgical delivery and the difficulties of early clinical diagnosis determine the relevance of clinicopathologic analysis of postoperative scar endometriosis. AIM: The aim of this study was to conduct a comprehensive comparative analysis of the clinical course, diagnostic criteria, results of surgical and combined treatment, as well as morphological and morphofunctional features of postoperative scars endometriosis. MATERIALS AND METHODS: We analyzed complaints, anamnesis, general clinical, gynecological and instrumental examination data, as well as results of the morphological examination of the surgical material from 21 patients with postoperative scar endometriosis. Immunohistochemical study of the surgical material was performed according to the avidin-biotin complex method using monoclonal mouse antibodies to alpha-smooth muscle actin (Dako, Denmark). RESULTS: The average age of patients with postoperative scar endometriosis was about 33.6 6.3 years. In 19 out of 21 patients (90.47%), this pathology occurred in the scar after caesarean section. The main clinical manifestation of the disease was pain syndrome. All patients complained of periodic pain in the area of the postoperative scar, which worsened on the eve and during menstruation. According to its nature and intensity, the patients characterized the pain as dull (33.3%), aching (14.3%), paroxysmal (19.1%), or twitching (33.3%). In some cases (28.6%), the pain syndrome was accompanied by nausea and vomiting. Many women (71.4%), in addition to the pain, noted the appearance of dark brown (bloody) discharge from the scar during menstruation. In macro- and microscopic examination, postoperative scar endometriosis foci formed nodes of different sizes without a clear capsule. This was due to proliferation of connective tissue fields found in all observations with a large number of collagen fibers located around and between heterotopias. Immunohistochemical study of postoperative scar endometriosis revealed perifocal proliferation of myofibroblasts, which surrounded endometrioid heterotopias in the form of couplings and was characterized by positive expression of alpha-smooth muscle actin. Concentric myofibroblast proliferates in the form of nodules were found in the cytogenic stroma of endometriosis foci. CONCLUSIONS: Early diagnosis and treatment of endometriosis are important in terms of preventing the fibrosis and sclerosis of the affected tissues and organs, which lead to their deformation and dysfunction.
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