Extragenital Endometriosis Research Articles

Bifocal endometriomas involving a Pfannenstiel incision. Clinical case

Endometrioma of the anterior abdominal wall (EAAW) is a rather rare variant of extragenital endometriosis, which in most cases occurs after obstetrical and gynecological procedures. EAAW presented predominantly as a single tumour‑like mass, and multiple ectopias were observed in only 1.9—5.6% of cases, exclusively after Pfannenstiel laparotomy. Here we present a clinical case of a 37‑year‑old patient who complained of the large tumour‑like nodules along the postoperative anterior abdominal wall scar, accompanied by severe cyclic, catamenial pain. Additionally, the patient noted an increase in tumour size during menstruation. Thirty‑three months ago, she underwent an elected cesarean section for obstetric indications. Based on ultrasonography and computed tomography scans, the presence of two EAAW in the corners of the postoperative scar was established: 46 × 32 × 31 mm and 14 × 18 × 13 mm, respectively. Both lesions were excised out without damaging their integrity. The fascial defect was replaced by synthetic polypropylene mesh. The diagnosis of EAAW was finally confirmed based on pathological (presence of endometrial glands and cytogenic stroma) and immunohistochemical (positive membrane expression of CD10 in cytogenic stroma, intense cytoplasmic expression of CK7 in endometrial glands, marked nuclear expression of progesterone (PR) and estrogen (ER‑α) receptors in endometrial glands and cytogenic stroma, proliferative activity index Ki‑67 — 2%) studies. At a follow‑up after 19 months, the patient was asymptomatic; according to physical examination and ultrasound scan, there was no evidence of recurrence. Abdominal wall endometriosis is a rare condition. Clinicians should be aware of this pathology, especially in women presenting with a painful mass near the scar of a previous obstetrical and gynecological surgery. Surgery is the best treatment modality for endometrioma, whereas its optimal volume is considered to be R0 resection with preservation of endometriomas’ integrity. The final diagnosis of EAAW requires pathological and immunohistochemical confirmation.

Features of epithelial-mesenchymal transition in ectopic endometrium in patients with extragenital endometriosis of various localizations. Observational study

Background. Epithelial-mesenchymal transition (EMT) is a conserved mechanism in the process of morphogenesis and organogenesis. EMT provides cells with migratory and invasive properties, which is a necessary condition for the formation of endometrioid heterotopias. Aim. To confirm the presence of EMT features in different types of endometriosis. Materials and methods. During a period of five years (2012–2017) we analyzed 43 cases of extragenital endometriosis: appendix (3 case), colon (5 cases), ileum (1 case), abdominal scar endometriosis after caesarean section (24 cases), and inguinal hernia (10 cases). The material was processed according to histological and immunohistochemical technique using monoclonal E-cadherin and polyclonal Vimentin antibodies to assess local invasiveness. Results. In peritoneal endometriosis, the ratio of E-cadherin to Vimentin expression was 10.3, in the colon = 9.1, in the appendix 8.6, in the ileum 5.5, in the hernial sac 4.2. Thus, in diffuse infiltrative forms of endometriosis, the lesion phenotype is characterized by low expression of E-cadherin, while expression of Vimentin is at a high level (p0.05). Conclusion. The results of our study confirmed involvement of the epithelial-mesenchymal transition process in the pathogenesis of extragenital endometriosis lesions, on the one hand, and they certify its invasive potential in these localizations, on the other hand.

The Expression of Kisspeptins and Matrix Metalloproteinases in Extragenital Endometriosis.

Endometriosis is characterized by a condition where endometrial tissue grows outside the uterine cavity. The mechanisms of endometrium growth during endometriosis might be similar to the development of a tumor. The kisspeptin (KISS1) gene was initially discovered as a suppressor of metastasis. Matrix metalloproteinases (MMPs) and their inhibitors are described as factors in the early stages of endometriosis and tumor growth progression. We applied the quantitative polymerase chain reaction and the immunofluorescence method to investigate KISS1, its receptor (KISS1R), MMP-2, and MMP-9 in the eutopic and ectopic endometrium in women with and without endometriosis. We presume that the dysregulation of KISS1 and MMPs might contribute to endometriosis pathogenesis. Samples for the immunofluorescence study were collected from patients with a confirmed diagnosis of endometriosis in stages I-IV, aged 23 to 38 years old (n = 40). The cell line was derived from the endometrium of patients with extragenital endometriosis (n = 7). KISS1 and KISS1R expression are present in the ectopic endometrium of patients with extragenital endometriosis, as opposed to the control group where these proteins were not expressed. There is a decrease in KISS1 and KISS1R values at all stages of endometriosis. MMP-2 and MMP-9 genes express statistically significant increases in stages II, III, and IV of extragenital endometriosis. MMP synthesis increased in the last stages of endometriosis. We suppose that the KISS1/KISS1R system can be used in the future as a suppressive complex to reduce MMP-2 and MMP-9 expression and prevent endometrial cells from invading.

Umbilical endometriosis: A case report

Introduction: Cutaneous and umbilical involvement is very rare and represents only 0.5–1% in the various series. Its clinical diagnosis is difficult but it should be suspected in the presence of any bluish, painful umbilical nodule, sometimes with a brownish discharge, the evolution regulated by the menstrual cycle. Ultrasound of the abdominal wall points to the diagnosis of umbilical endometriosis despite the absence of characteristic signs on imaging. Wide surgical excision is the treatment of choice because of its resemblance to a primary tumor or metastasis. Case Report: We report the case of a 31-year-old female patient with no history of abdominal-pelvic surgery or trauma to the umbilicus, consulted for a painful umbilical swelling measuring approximately 1–2 cm diagnosed with umbilical endometriosis. Endometriosis of the umbilical wall is a rare condition, representing only 0.03–2% of extra-genital endometriosis. It is associated with pelvic endometriosis in 26% of cases. Its clinical diagnosis is difficult but it should be suspected in the presence of any bluish, painful umbilical nodule, sometimes with a brownish discharge, the evolution regulated by the menstrual cycle. Ultrasound of the abdominal wall with a high frequency probe is the initial, easily accessible examination that points to the diagnosis of umbilical endometriosis, but it is not pathognomonic. The formal diagnosis of umbilical endometriosis is only obtained with the help of histological examination. The presence of endometrial glands (epithelial cells) and a cytogenic chorion in the ectopic endometrial tissue is necessary to establish the histological diagnosis. In general, medical treatment with danazol, norethisterone, or luteinizing hormone-releasing hormone (LHRH) analogues is recommended before surgery. It would allow a reduction in the size of the endometriotic nodules. Conclusion: Umbilical endometriosis is a very rare form of extra-genital endometriosis. The diagnosis is made when a nodule is present with pain and catamenial bleeding. The diagnosis of certainty is based on a histological study.

Three-dimensional model for improvement of endometriosis care (3D-E).

Endometriosis affects approximately 10% of women of reproductive age and leads to significant morbidity and financial burden. Consequently, countries such as France and Germany are formulating strategies to combat endometriosis. In this study, we propose the implementation of our three-dimensional model (3D-E) to raise awareness about endometriosis and enhance timely diagnosis, treatment, and long-term care for affected patients. Based on the adapted Six Sigma Principle and the modified recommendation of Sales et al. for implementing evidence-based findings into a clinical routine, we first conducted a comprehensive investigation to identify risk factors leading to diagnostic delay of endometriosis. After identifying improvable factors, the applicable options were selected due to defined criteria such as integrability in the clinical routine, cost-effectiveness, and evidence-based-principle. Finally, solutions feasible for health care providers were integrated and the 3D-E model was established. Some of the main risk factors contributing to diagnostic delays are symptoms acceptance and misinterpreted symptoms, especially if presenting to nongynecologists in cases of extragenital endometriosis with atypical presentation. Therefore, we tried to sensitize colleagues (first dimension) with a review paper in Germany's largest medical journal and started an elective for medical students (second dimension) at our university. In order to involve additional health care professionals in endometriosis care (third dimension), we are preparing the concept of the EndoNurse. The 3D-E model is a relatively low-cost, comprehensive, and worldwide adaptable approach for facilitating knowledge transfer, sensitizing health care providers, and improving endometriosis diagnostics and therapy for patients with endometriosis who are in the center of the model.

Fibrosis as a key link in the morphogenesis of extragenital endometriosis

The clinical of extragenital endometriosis is variable and depends on the localization, while the leading manifestation is a pronounced pain syndrome, which in some cases can simulate various surgical pathologies. Materials and methods: A morphological and IHC study was performed in 82 cases of extragenital endometriosis of various localization. Research results: An IHC study showed positive expression of -SMA in fibrosis foci around and between endometriosis foci. The expression area of TGF-1 was different for the cytogenic stroma and the perifocally located connective tissue. Conclusions: Fibrosis is an integral component of the morphogenesis of endometrioid heterotopias, while the degree of its severity depends on the duration of the existence of endometriosis foci. Severe pain syndrome is probably associated with deformation of organs and tissues, compression of nerve endings due to fibrosis processes.

Endometriosis of the umbilical ring

Objective. To present a clinical case of diagnosis and surgical treatment of one of the forms of extragenital endometriosis – umbilical ring endometriosis.Materials and methods. A clinical case of patient M., 33 years old, female, with diagnosed and operated endometrial heterotopia in the projection of the soft tissues of the umbilical region.Results. The probable role of the migration theory of the pathogenesis of endometriosis is demonstrated due to the lack of a history of surgical treatment in this area.Conclusion. The migration theory of the pathogenesis of endometriosis can be explained by the mechanism of retrograde penetration of endometrial cells through blood and/or lymphatic vessels from the pelvic cavity.

Endometriosis of the surgical scar of the anterior abdominal wall. Case report

Endometriosis is the presence of tissue with morphological and functional features similar to endometrium outside the uterine cavity. Endometriosis affects approximately 10% of women worldwide, mostly of reproductive age. The rate of extragenital endometriosis is 0.33.5%. Diagnosis of endometriosis of the anterior abdominal wall is complex and includes analysis of clinical and medical history data, ultrasound, magnetic resonance imaging, and histological examination of the removed tissues. The article presents a clinical case of a large lesion of extragenital endometriosis localized in the subcutaneous fat of the anterior abdominal wall in a patient with a history of cesarean section. The main clinical manifestations of this disorder were cyclic pain during menstruation and an enlargement of the existing mass in the subcutaneous fat.

Gonadotropin-Releasing Hormone Antagonists-A New Hope in Endometriosis Treatment?

Endometriosis is a chronic disease, in which endometrial-like tissue is found outside the uterine cavity. Lesions are typically located in the true pelvis but can be found, in addition to extragenital endometriosis, in the respiratory system, the diaphragm, the pleura or the pericardium. As the extrauterine endometrial lesions undergo the menstrual cycle, they cause many symptoms, including pain, and besides infertility, they all mostly affect the quality of the patient's life. Pharmacological management of endometriosis significantly increases in importance either as a first-line treatment or as a complementary therapy after surgery. Yet, current research on antagonists of the gonadotropin-releasing hormone (GnRH) has revealed their potential benefits in endometriosis treatment. Their mechanism of action is to down-regulate the hypothalamic-pituitary-gonadal axis and therefore induce a hypoestrogenic state. The resulting reduction of estrogen levels prevents disease progression and diminishes the recurrence rate after surgical removal of endometriosis. The present review summarizes recent reports of the role oral GnRH antagonists have as a significant treatment option for pain reduction in endometriosis patients.

Rare Clinical Presentation of Postmenopausal Endometriosis: A New Perspective.

Endometriosis affects 2-5 % of postmenopausal women with menopause hormone therapy and is less common in women without treatment with exogenous estrogen or tamoxifen. Postmenopausal endometriosis has more unknown aspects in its pathogenesis and clinical manifestation than in the case of premenopausal patients. The aim of this review was to summarize the clinical presentation of rare cases of endometriosis, including deep infiltrating (DIE) and extragenital endometriosis, in women. The symptoms of endometriosis in the post-reproductive age are more heterogeneous than in women of childbearing age, often resembling symptoms of gastrointestinal tumors or urinary tract diseases. We summarize cases of endometriosis of the intestines, liver, pancreas, and stomach, as well as endometriosis of the urinary tract and skin, with non-gynecological manifestations. We also describe the pathogenesis of endometrial tissue activity in the context of reduced estrogen levels after menopause, which is also not clear, and demands more molecular and genetic studies. NAD+-dependent deacetylases called Sirtuins are metabolic sensors for maintaining body homeostasis. In the context of endometriosis, Sirtuins are being studied for their potential role in modulating inflammation, cell proliferation, and sex hormone sensitivity, but their role in postmenopausal endometriosis is not well researched. Treatment in postmenopausal women includes mostly for now surgery, depending on the location of the lesion, and aromatase inhibitors. The complete genetic and epigenetic profile in women post-reproductive age is needed to propose target therapy, especially in severe cases such as endometriosis that is deeply infiltrating and located outside the pelvis.

Spontaneous Umbilical Endometriosis: A Case Report

Endometriosis is a common gynecological entity that usually occurs in the pelvic organs. Umbilical endometriosis is a rare condition that accounts for 0.5-1% of all extragenital endometriosis. It usually arises secondary to prior surgery but may arise de novo as well. We report a case of this condition with the spontaneous occurrence, which was diagnosed preoperatively as umbilical granuloma. Umbilical endometriosis should be kept in differential diagnoses in women with umbilical lesions.

Endometrioza ombilicală

Umbilical endometriosis. Umbilical endometriosis (UE) is attributed to the rare forms of extragenital endometriosis presented in the literature through unique clinical trials or limited series. UE is a very rare condition with an estimated prevalence of <1% of all ectopic endometriosis. The first description of a primary umbilical endometrioma is credited to Villar in 1886, hence the term Villar’s nodule. UE is even more difficult to diagnose due to the extreme lack of clarity in clinical signs. Given the location of the given pathology, a differential diagnosis with other umbilical surgical diseases is necessary. A review of the literature of the last 10 years was generated based on PubMed and Google Scholar research, selecting some specific keywords. Several lesions can occur in the umbilical region, and endometriosis has to be ruled out even in patients without any surgery in their medical history. Surgery is the gold standard treatment for this condition. Considering the multitude of pathologies of the umbilical region that may look similar to EO, this condition must be considered in the differential diagnosis. Radical surgical excision is the preferred treatment aimed at preventing recurrence and reducing the risk of malignant transformation.

Extragenital Endometriosis in the Differential Diagnosis of Non- Gynecological Diseases.

Endometriosis is a chronic, benign disease that affects approximately 10% of women of childbearing age. Its characteristic clinical features are dysmenorrhea, dyschezia, dysuria, dyspareunia, and infertility. The manifestations of extragenital endometriosis (EE) are a diagnostic challenge, as this disease can mimic other diseases due to its unusual location with infiltration of various organs and corresponding symptoms. This review is based on publications retrieved by a selective search of the literature on the commonest extragenital sites of endometriosis, including the relevant current guideline. Current evidence on the treatment of extragenital endometriosis consists largely of cohort studies and cross-sectional studies. The treatment is either surgical and/or conservative (e.g., hormonal therapy). Gastrointestinal endometriosis is the most common form of EE, affecting the rectum and sigmoid colon in nearly 90% of cases and typically presenting with dyschezia. Urogenital endometriosis is the second most common form of EE. It affects the bladder in more than 85% of cases and may present with dysuria, hematuria, or irritable bladder syndrome. The diaphragm is the most common site of thoracic endometri - osis, potentially presenting with period-associated shoulder pain or catamenial pneumothorax. Endometriosis affecting a nerve often presents with sciatica. In abdominal wall endometriosis, painful nodules arise in scars from prior abdominal surgery. There is, as yet, no causally directed treatment for chronic endometriosis. The treatment is decided upon individually in discussion with the patient, in consideration of risk factors and after assessment of the benefits and risks. Timely diagnosis is essential.

Rare extragenital endometriosis: pathogenesis and therapy

Background: In the context of extragenital endometriosis, the gastrointestinal, urinary tract, abdominal wall, and thorax localizations are considered relatively frequent, while the umbilical, inguinal, sciatic nerve, liver, and pancreas are instead “rare”. Methods: Online searches were carried out in PubMed database of the last 20 years for these terms: extragenital endometriosis, umbilical endometriosis, inguinal endometriosis, sciatic nerve endometriosis, hepatic and pancreatic endometriosis. The following exclusion criteria were used: (1) Personal surgical history unspecified. (2) Nonspecific histological diagnosis for each type of endometriosis examined. (3) Inability to distinguish between the personal series of the author and the case reports described. (4) Proceedings of scientific meetings were not included. Tables that are easy to consult were compiled. Results: 810 titles were found among which 162 studies were selected for reading in full text and finally 114 papers were included, which met the objective of the revision. The so-called “rare” forms of extragenital endometriosis show an unsuspected frequency, an extreme variability of presentation, and uncertain treatment guidelines. Discussion: Gynecologists, general surgeons, and neurologists should be well acquainted with these pathologies to avoid confusing diagnostic paths and to set up adequate therapies.

Diagnostic value of occult haemolacria

To study tears for occult (latent) haemolacria in women and compare the representativeness of the main methods of tear examination. Tear samples from 72 women aged between 18 and 46 years were evaluated using two methods: microscopic and chemical with reagent test strips. In the follicular phase of the menstrual cycle, erythrocytes in tears were detected in 59.1% (13) subjects, which was significantly higher (χ2=4.2, p=0.041) compared to the luteal phase - erythrocytes were detected in 40.9% (9) women. The proportion of women in the luteal phase of the cycle who had single epithelial cells in the tear (76.9%) was significantly lower (χ2=5.2, p=0.022) than in women in the follicular phase (83.9%). The predictive value of the chemical method was 0.53 of that of the microscopic one. Microscopically, blood was detected in 30.6% of tear samples, while chemically - in 16.7%. An associative relationship was found between occult haemolacria in women and a diagnosis of endometriosis (K=0.75, p≤0.05). The proportion of women with erythrocytes in tears determined with the chemical method was 41.7% in patients with endometriosis, which was significantly higher (χ2=6.5, p=0.011) than 11.7% in women without endometriosis. Fluctuations of hormones during the menstrual cycle are reflected in tear composition, manifested as an increase in the number of epithelial cells in the luteal phase, and erythrocytes in the follicular phase. Erythrocytes found in a tear amid accumulations of epithelial cells, their glandular atypia and neutrophilic infiltration in patients with endometriosis may indicate the manifestation of extragenital endometriosis. The microscopic method turned out to be more sensitive in detecting occult haemolacria, and additionally it provided information about other cells. At the same time, the chemical method, which was relatively diagnostically informative, faster and technically simpler, can be used for screening.

Endometriosis. Case report

Extragenital endometriosis (EGE) is the rarest variant of endometrioid disease. This is a process in which a benign growth of tissue similar to the endometrium in morphological and functional properties occurs outside the uterine cavity. The manifestation of the disease has an erased course characteristic of other diseases and patients are more likely to end up in non-core departments, which is accompanied by errors in treatment tactics. According to the data of T.V. Dresvyanskaya et al., the frequency of EGE is 68% of the number of all cases of detection of endometrioid disease. The article presents a case of successful surgical treatment of EGE of rare localization.

Gestagenes in the treatment of endometriosis: efficiency, safety, bioequivalence, transferability

Endometriosis is a chronic disease that requires long-term treatment, the goal of which is effectively use drugs and avoids repeated surgical interventions.The quality of patients’ life depends on the varying degrees of symptoms such as pelvic pain, dyspareunia, dysmenorrhea. Endometriosis causes infertility and perinatal complications. The symptoms of endometriosis often affect psychological and social well-being, and threaten the relationships, sexuality and mental health of women. Women with endometriosis have high levels of anxiety, depression, and other psychiatric disorders that can aggravate the severity of their pain.The existing statistics on the endometriosis incidence is underestimated given the diagnostic difficulties. So far, there are no final, only generally an accepted method of treating endometriosis, and in most cases, treatment is only eliminates the symptoms. Today, it is desirable to take a conservative approach to treatment, avoiding surgery, and hormone therapy is recommended to relieve pain associated with endometriosis. An individual approach is important in the management of patients with endometriosis, taking into account the reproductive plans and needs of woman. Medical treatment methods should be used as much as possible, for example, dienogest 2 mg (in particular, Savis drug). Dienogest is a derivative of 19-nortestosterone, which has an antiproliferative effect on the endometriosis foci.Savis is a drug specially formulated for the endometriosis treatment. Savis may be prescribed to relieve symptoms before and after surgery to prevent relapse. The safety profile of dienogest has been studied and data is constantly accumulating, given the popularity of its prescription.The effectiveness of dienogest should be assessed primarily by its effect on pain and quality of life, on maintaining fertility, and on the possibility of avoiding or postponing surgery. This is important for various forms of endometriosis: endometriomas, extragenital endometriosis, adenomyosis.

Persistent dysuria in women: etiological diagnostics and treatment

INTRODUCTION: Dysuria is a painful urination combined with its frequency and/or difficulty. Dysuria is observed in many urological diseases and is one of the most common reasons for treatment for urological cause.
 AIM: The aim of the study is to identify the etiological factors of dysuria in women and to evaluate a personalized approach to their treatment.
 MATERIALS AND METHODS: We analyzed the data of 368 women with chronical cystitis. The inclusion criteria for the study were the presence of dysuria (painful and frequent urination more than 8 times a day with or without difficulty), the prescription of urination disorders over one year old and age 18 and over. All patients underwent a comprehensive urological examination to identify the causes of urinary disorders.
 RESULTS: The Bacterial cystitis was confirmed only in 78 (21.2%) patients among all 368 women. In the remaining 290 (78.8%) patients, the causes of persistent dysuria were other diseases: bladder leukoplakia in 154 (41.8%), bladder pain syndrome/interstitial cystitis in 38 (10.3%), viral cystitis in 34 (9.3%), paraurethral formations in 29 (7.9%), neurogenic urinary dysfunction bladder in 25 (6.8%), urethral pain syndrome in 5 (1.4%) patients. Dysuria was also caused by postradiation cystitis (2 patients), secondary stones in the urinary bladder (2 patients), and one patient had extragenital endometriosis.
 CONCLUSIONS: The variety of reasons for the development of persistent dysuria in women requires careful examination of patients. Treatment should be carried out only after accurate verification of the diagnosis.

VP05.21: A case of piriformis syndrome in extragenital endometriosis

VP05.21: A case of piriformis syndrome in extragenital endometriosis

Mesenchymal Stromal Cells Isolated from Ectopic but Not Eutopic Endometrium Display Pronounced Immunomodulatory Activity In Vitro.

A comparative analysis of the cell surface markers and immunological properties of cell cultures originating from normal endometrium and endometrioid heterotopias of women with extragenital endometriosis was carried out. Both types of cell cultures expressed surface molecules typical of mesenchymal stromal cells and did not express hematopoietic and epithelial markers. Despite similar phenotype, the mesenchymal stromal cells derived from the two sources had different immunomodulation capacities: the cells of endometrioid heterotopias but not eutopic endometrium could suppress dendritic cell differentiation from monocytes as well as lymphocyte proliferation in allogeneic co-cultures. A comparative multiplex analysis of the secretomes revealed a significant increase in the secretion of pro-inflammatory mediators, including IL6, IFN-γ, and several chemokines associated with inflammation by the stromal cells of ectopic lesions. The results demonstrate that the stromal cells of endometrioid heterotopias display enhanced pro-inflammatory and immunosuppressive activities, which most likely impact the pathogenesis and progression of the disease.