Acute Diffuse Peritonitis Due to Spontaneous Rupture of an Infected Endometrioma: A Case Report

Background. Endometriosis is defined as a chronic, inflammatory, estrogen-dependent gynaecologic disease. It affects approximately 5–10% of reproductive-age women worldwide. Ovarian endometriosis is the most frequent form of this condition. Endometriotic cysts are found in about 17–44% of women diagnosed with endometriosis. It is well known, that ovarian endometriomas can cause infertility and chronic pelvic pain. Enlarging cysts can also cause ovarian torsion. In addition, ovarian endometriosis slightly increases the risk for ovarian cancer. The rupture of endometriotic ovarian cysts is an exceptional complication. According to the literature, the prevalence is less than 3% among women with endometriosis. The rupture of an ovarian endometrioma can cause acute peritonitis, which can lead to sepsis, septic shock and can be lethal. The occurrence of abscesses within an ovarian endometrioma is an extremely rare complication. Generally, the origin of infected endometriotic ovarian cysts is related to the previous invasive procedures involving pelvic organs or the use of intrauterine devices. Also, ovarian abscesses can be caused by the hematogenous or lymphatic spread of bacteria. Although, the literature points out that infection of endometriotic ovarian cysts can develop spontaneously. In these rare cases, reservoir and route of infection remains an enigma.Case report. A 49-year-old female was brought to the emergency room with severe generalized lower abdominal pain (6/10) and three days lasting fever. Abdominal examination revealed diffuse abdominal pain with anterior abdominal wall muscle tension. Painful solid masses were felt on both sides of the uterus during the pelvic examination. Cystic masses were detected in both ovaries during transvaginal sonography. Computer tomography (CT) of the abdomen and pelvis revealed abnormal changes in both ovaries. A small amount of free fluid was found in the pelvic cavity along with thickened pelvic peritoneum. Suspecting acute peritonitis and bilateral tubo-ovarian abscesses, surgical treatment was performed. Lower midline laparotomy with bilateral adnexectomy and abdominal lavage with 4000 ml normal saline were done. The outcome of peritonitis was evaluated using the Mannheim peritonitis index (MPI=17 – low risk of morbidity and mortality). The histopathological examination revealed the diagnosis of bilateral endometriotic cysts complicated with acute inflammation, with associated acute inflammation of both fallopian tubes. Microbiological cultures from the purulent fluid were negative.Conclusions. Although the occurrence of abscesses within an ovarian endometrioma is an extremely rare finding in clinical practice, it has to be considered by gynaecologists because it might result in a surgical emergency that can be life-threatening. Being aware of the risk factors of abscesses within an endometrioma can lead to an early diagnosis of this rare condition and help to avoid serious complications.

Absorbable Hemostatic Particles to Reduce the Damage on the Follicular Reserve After Ovarian Endometriomas Stripping

Objective: to reduce the surgical damage to the ovarian reserve, after stripping of ovarian endometrioma, of the necrotic type given by the electrohaemostasis or ischemic type given by the suture. Design: perform haemostasis on ovarian parenchyma with topical haemostatic agents. Materials and methods: we used Arista AH which is a powder made up of microporous polysaccharide hemospheres that act by osmotic action and accelerate the natural coagulation process. We used Arista AH in 27 women with mono- or bilateral ovarian endometriosis. Results: in all treated cases we obtained a rapid and optimal haemostasis. There were no post-surgical complications related to haemostatic defects. Three months after the surgery, we checked the Antral Follicle Count (AFC) with a trans-vaginal ultrasound probe. AFC in 24 women with full follow-up gave the following results: unilateral endometrioma – AFC between 5 and 8 (MV: 6.3), bilateral endometriomas – the AFC between 5 and 7 (MV: 5.8). Conclusions: The use of Arista AH powder allows highly effective hemostasis and is easy to use, fully respecting the residual ovarian parenchyma after stripping.

Pathogenesis Based Diagnosis and Treatment of Endometriosis

Understanding the pathophysiology of endometriosis is changing our diagnosis and treatment. Endometriosis lesions are clones of specific cells, with variable characteristics as aromatase activity and progesterone resistance. Therefore the GE theory postulates GE incidents to start endometriosis, which thus is different from implanted endometrium. The subsequent growth in the specific environment of the peritoneal cavity is associated with angiogenesis, inflammation, immunologic changes and bleeding in the lesions causing fibrosis. Fibrosis will stop the growth and lesions look burnt out. The pain caused by endometriosis lesions is variable: some lesions are not painful while other lesions cause neuroinflammation at distance up to 28 mm. Diagnosis of endometriosis is made by laparoscopy, following an experience guided clinical decision, based on history, symptoms, clinical exam and imaging. Biochemical markers are not useful. For deep endometriosis, imaging is important before surgery, notwithstanding rather poor predictive values when confidence limits, the prevalence of the disease and the absence of stratification of lesions by size, localization and depth of infiltration, are considered. Surgery of endometriosis is based on recognition and excision. Since the surrounding fibrosis belongs to the body with limited infiltration by endometriosis, a rim of fibrosis can be left without safety margins. For deep endometriosis, this results in a conservative excision eventually with discoid excision or short bowel resections. For cystic ovarian endometriosis superficial destruction, if complete, should be sufficient. Understanding pathophysiology is important for the discussion of early intervention during adolescence. Considering neuroinflammation at distance, the indication to explore large somatic nerves should be reconsidered. Also, medical therapy of endometriosis has to be reconsidered since the variability of lesions results in a variable response, some lesions not requiring estrogens for growth and some being progesterone resistant. If the onset of endometriosis is driven by oxidative stress from retrograde menstruation and the peritoneal microbiome, medical therapy could prevent new lesions and becomes indicated after surgery.

Effectiveness of NLRP3 Inhibitor as a Non-Hormonal Treatment for Ovarian Endometriosis

Background Endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects 10% of women of reproductive age. Ovarian endometriosis (OE) is the most common lesion in endometriosis and may cause infertility in addition to dysmenorrhea. Hormonal treatments for endometriosis suppress ovulation; hence, they are not compatible with fertility. The inflammasome is a complex that includes Nod-like receptor (NLR) family proteins that sense pathogen-/danger‐associated molecular patterns and homeostasis-altering molecular processes. It has been reported that the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing (NLRP) 3 inflammasome, which contributes to the activation of interleukin-1 beta (IL-1β), might be related to the progression of endometriosis. Therefore, the aim of the present study was to evaluate non-hormonal therapies for OE, such as the inhibitors of the NLRP3 inflammasome. Methods The expression of NLRP3 was measured in the eutopic endometrium (EM) of patients with/without endometriosis and OE and stromal cells derived from the endometrium of patients with endometriosis and OE (endometrial stromal cells [ESCs] and cyst-derived stromal cells [CSCs]). The effect of an NLRP3 inhibitor (MCC950) on ESC and CSC survival and IL-1β production was evaluated. We then administered MCC950 to a murine model of OE to evaluate its effects on OE lesions and ovarian function. Results NLRP3 gene and protein expression levels were higher in OE and CSCs than in EM and ESCs, respectively. MCC950 treatment significantly reduced the survival of CSCs but not that of ESCs. Moreover, MCC950 treatment reduced the co-localization of NLRP3 and IL-1β in CSCs and IL-1β concentrations in CSC supernatants. In the murine model, MCC950 treatment reduced OE lesion size compared to phosphate-buffered saline treatment (89 ± 15 vs. 49 ± 9.3 mm3 per ovary; P < 0.05). In addition, IL-1β and Ki67 levels in the OE-associated epithelia and oxidative stress markers of granulosa cells were reduced in the MCC950-treated group. Conclusions These results indicate that NLRP3/IL-1β is involved in the pathogenesis of endometriosis and that NLRP3 inhibitors may be useful for suppressing OE and improving the function of ovaries with endometriosis.

Clinical significance of predictive and diagnostic indices of fetal pathology associated with placental insufficiency in women with endometriosis

BACKGROUND: Modern achievements of pharmacology, surgery and reproductive medicine have determined an increase in the implementation of reproductive function in endometriosis of various localization. The onset of pregnancy in presence of impaired endometrial receptivity and progesterone resistance, pro-inflammatory and pro-thrombotic status, abnormal functioning of the immune system, structural changes in the reproductive organs leads to impaired formation of the embryo (feto) placental system, early reproductive losses, complicated pregnancy and adverse perinatal outcomes. In this regard, the endometriosis and pregnancy issue requires close study and specific proposals to optimize pregnancy management. AIM: The aim of this study was to develop predictive (PIs) and diagnostic (DIs) indices of placenta-associated fetal pathology in pregnant women with endometriosis, to determine their prognostically and diagnostically significant parameters. MATERIALS AND METHODS: This prospective study in the dynamics of gestation included a comprehensive clinical and laboratory examination of 175 pregnant women with endometriosis (100 subjects with adenomyosis and 75 subjects with ovarian endometriosis). To develop PIs and DIs, two comparison groups with fetal pathology due to placental insufficiency were retrospectively identified, depending on the location of endometriosis. Group I consisted of 49 pregnant women with adenomyosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia; Group II comprised 29 pregnant women with ovarian endometriosis and placental insufficiency isolated from other pregnancy complications, accompanied by growth retardation and/or chronic fetal hypoxia. The control group (Group III) included 30 healthy pregnant women with a normal course of gestation. The examination was performed at 10-14 weeks, 20-24 weeks, and 28-34 weeks of gestation and included an assessment of placental insufficiency markers such as placental growth factor (PlGF), placental -1-microglobulin (PAMG-1), tumor necrosis factor (TNF), lymphocytes with membrane receptor FasR (L CD95+), C-reactive protein, placental alkaline phosphatase (PAPh), and fetal hemoglobin (HbF). The information value of individual parameters and indices was determined by ROC analysis, odds ratio, and clinical epidemiology tests. RESULTS: Pregnancy in presence of endometriosis in 100% of cases was complicated by placental insufficiency of varying severity (with fetal pathology in 81.5% of cases), the frequency of which had statistically significant differences between the groups of pregnant women with adenomyosis and ovarian endometriosis (2 = 4.06, p = 0.04). To predict growth retardation and / or chronic fetal hypoxia, we have developed PI I (PlGF / TNF 100) and PI II (PAMG-1 / PlGF 100), which characterize the state of placental angio-and vasculogenesis depending on systemic inflammatory response level. For early diagnosis of fetal pathology, we have proposed DI I (CRP / PAPh 100), DI II (HbF / PlGF 100) and DI III (L CD95+ / PAPh 100), which allow for diagnosing placental alterations with impaired placental energy supply due to an increase in inflammatory status. Evaluation of prognostic and diagnostic significance of PIs and DIs showed that the most informative tools are PI I (Se = 86.1%, Sp = 80.5%) and DI I (Se = 88.3%, Sp = 83.7%). CONCLUSIONS: The use of PIs allows for risk stratification of pregnant women from the 1st trimester of gestation to address the issue of the prevention method. The clinical capabilities of DIs optimize obstetric tactics for the timely prescription of therapy for placental insufficiency and targeted diagnosis of fetal pathology. Pregnant women with endometriosis should be classified as a high perinatal risk group, and therefore the proposed PIs and DIs should be included in the dynamic examination complex.

FEATURES OF FUNCTION OF PATIENTS WITH OVARIAN ENDOMETRIOSIS

По всему миру эндометриоз занимает третье место в структуре всех гинекологических заболеваний. Эндометриоз ассоциированное бесплодие встречается практически у 45% женщин, страдающих эндометриозом. До настоящего времени вопрос о эффективности видов терапии наружного генитального эндометриоза остается открытым. Многие годы основным методом лечения было хирургическое лечение эндометриоза. В дальнейшем была обоснована комбинированная терапия эндометриоза, включающая в себя хирургическое лечение с последующей гормонотерапией. В настоящее время определены четкие показания к оперативному лечению эндометриоза, в то же время недостаточно конкретизирована дальнейшая тактика ведения пациенток One of the priorities of the state policy of the Republic of Kazakhstan is the protection of reproductive health and improving the medical and demographic situation. To date, one of the urgent problems of modern gynecology is endometriosis. The disease occurs in almost 90% of women with chronic pelvic pain and infertility. Every year there is a steady increase in the incidence of endometriosis in all countries of the continent. For many years, the main treatment has been the surgical treatment of endometriosis. In the future, combination therapy of endometriosis was substantiated, including surgical treatment followed by hormone therapy. In the future, combined therapy of endometriosis was justified, including surgical treatment followed by hormone therapy. Currently, clear indications for surgical treatment of endometriosis have been determined, while the further management of patients has not been sufficiently specified

N-Acyl Dopamines Induce Apoptosis in Endometrial Stromal Cells from Patients with Endometriosis

Endometriosis is characterized by the formation and development of endometrial tissues outside the uterus, based on an imbalance between proliferation and cell death, leading to the uncontrolled growth of ectopic foci. The potential target for the regulation of these processes is the endocannabinoid system, which was found to be involved in the migration, proliferation, and survival of tumor cells. In this paper, we investigated the effect of endocannabinoid-like compounds from the N-acyl dopamine (NADA) family on the viability of stromal cells from ectopic and eutopic endometrium of patients with ovarian endometriosis. N-arachidonoyldopamine, N-docosahexaenoyldopamine, and N-oleoyldopamine have been shown to have a five-times-more-selective cytotoxic effect on endometrioid stromal cells. To study the mechanisms of the toxic effect, inhibitory analysis, measurements of caspase-3/9 activity, reactive oxygen species, and the mitochondrial membrane potential were performed. It was found that NADA induced apoptosis via an intrinsic pathway through the CB1 receptor and downstream serine palmitoyltransferase, NO synthase activation, increased ROS production, and mitochondrial dysfunction. The higher selectivity of NADA for endometriotic stromal cells and the current lack of effective drug treatment can be considered positive factors for further research of these compounds as possible therapeutic agents against endometriosis.

The effect of melatonin on the activity of nucleolar organizer districts in women with ovarian endometriosis

Aim. To study the activity of ribosomal synthesis in women with ovarian endometriosis and its relationship with melatonin levels. Materials and methods. The study included 52 women with ovarian endometriosis. All patients were admitted to the gynecological department of the Clinic of the Southern State Medical University of the Russian Federation for surgical treatment. The paper uses the classification of ovarian endometriosis L. V. Adamyan (1998). During the study, 3 groups were formed: 1 group-stage 1 (n = 8), 2 group – stage 2 (n = 29), 3 group- stage 3 (n = 15).There were no patients with stage 4 ovarian endometriosis. Anamnesis was collected in all women, therapeutic and diagnostic laparoscopy, 6-SOMT was determined in the morning portion of urine, the activity of nucleolar organizer areas in the tissue of endometrioid foci of the ovaries was determined. Statistical data processing was performed using the IBM SPSS Statistics 19 software package. Results. In women with ovarian endometriosis, the lowest level of melatonin in the urine is observed at 1 and 3 stages. In patients with 1 stage ovarian endometriosis, its level was 41.14 ± 1.80 ng / ml; in group 2 – 71.16 ± 2.19 ng/ml, in group 3 – 54.01 ± 1.33 ng / ml (p = 0.048, p1-2 < 0.001, p2-3 = 0.046, p1-3 = 0.062). The main complaint in patients with stage 1 endometriosis was infertility – 8 (100%). The level of melatonin in the urine was significantly reduced in all groups of patients with ovarian endometriosis and infertility, independently of the stage. In patients with 1 stage ovarian endometriosis with low melatonin levels, proliferative diseases of the uterus (uterine fibroids, endometrial polyps, endometrial hyperplasia) are more common in the anamnesis. The number of intranuclear and extranuclear argentaffin inclusions, as well as their combination (INC + ENC) was significantly higher in stage 3 of ovarian endometriosis than in 1 and 2 stages. In endometriosis of the ovaries, a decrease in the level of melatonin in the urine correlates with an increase in the number of cells with a high degree of ribosomal synthesis activity. Conclusion. In women with endometriosis, the lowest values of melatonin were found at stage 1, especially in the presence of infertility, as well as in the common process. The activity of nucleolar organizers, which characterizes the intensity of ribosomal synthesis and the severity of proliferation, was significantly increased in the epithelial cells of ovarian endometriomas at stage 3, while an inverse relationship was revealed between the level of melatonin and the activity of nucleolar organizers.

HE4 might be a more useful tumor biomarker to detect malignancy in patients with ovarian endometrioma when malignancy is suspected

Objective To analyze the utility of carbohydrate antigen (CA)125 and human epididymis protein 4 (HE4) to detect malignancy in women with ovarian endometriosis, when ovarian cancer is suspected and ultrasonography results are inconclusive. Methods Women who underwent surgery between 2015 and 2019 for ovarian endometriosis or for adnexal masses, with a final diagnosis of ovarian carcinoma (clear cell and endometrioid) were included in this retrospective study. The women were divided into three groups: ovarian endometriosis (OE), ovarian carcinoma without endometriosis (OC), and ovarian carcinoma with endometriosis (OC + E). Adnexal masses were assessed preoperatively by transvaginal ultrasonography according to the International Ovarian Tumor Analysis (IOTA) simple rules, and CA125 and HE4 blood levels were obtained. Results Of 208 women, 45 had malignancy, 16 in the OC + E group and 29 in the OC group. According to transvaginal ultrasonography, 13 were classified as undetermined risk of malignancy: OC group: 3, OE group: 3, and OC + E group: 7. When we compared the tumor biomarkers, significant differences in HE4 but not in CA125 levels were found between the groups. Conclusions When ovarian malignancy is suspected in patients with ovarian endometriosis, HE4 is a more useful tumor biomarker to diagnose OC when ultrasonography results are inconclusive.