0000000000188329
AUTHOR
Sylvia Mechsner
Immunohistochemical characterization of endometriosis-associated smooth muscle cells in human peritoneal endometriotic lesions
Background Smooth muscle cells (SMC) are common components of endometriotic lesions. SMC have been characterized previously in peritoneal, ovarian and deep infiltrating endometriotic lesions and adenomyosis. The aim of this retrospective study was to investigate the extent of differentiation in endometriosis-associated SMC (EMaSMC) in peritoneal endometriotic lesions. Methods We obtained biopsies from peritoneal endometriotic lesions (n = 60) and peritoneal sites distant from the endometriotic lesion (n = 60), as well as healthy peritoneum from patients without endometriosis (control tissue, n = 10). These controls were hysterectomy specimens from patients without endometriosis or adenomyos…
Abdominal Wall Endometriosis: Myofibroblasts as a Possible Evidence of Metaplasia: A Case Report
In this study, we report about a patient with extra-uterine endometriosis (EM) in the abdominal wall muscle with evident metaplasia based on the abundant alpha smooth muscle actin (ASMA)-expressing myofibroblasts. Laparotomy excision of the abdominal wall EM was done following ultrasonographic evidence of a hypodense swelling in the right rectus abdominis, which was confirmed by MRI. Immunohistochemistry staining for ASMA and collagen I was done, with the results confirming that endometriotic stromal cells expressed both. Anterior abdominal wall endometriosis was suspected because of the patient's history of recurrent EM combined with the cyclic nature of symptoms. MRI is useful in determin…
(Partial) loss of BAF250a (ARID1A) in rectovaginal deep-infiltrating endometriosis, endometriomas and involved pelvic sentinel lymph nodes
study hypothesis: Loss of protein BAF250a (ARID1A) expression is present in women with rectovaginal deep-infiltrating endometriosis (DIE) and endometriosis affecting the pelvic sentinel lymph nodes (PSLN). study finding: Partial loss of protein BAF250a was found in some of our patient samples, comprising all endometriosis entities, including rectovaginal DIE and endometriosis affecting the PSLN. what is known already: Loss of BAF250a (BRG-associated factor 250a)/ARIDIA (AT-rich interactive domain 1A) protein expression was identified among endometriosis-associated ovarian carcinomas and ovarian endometriosis, and this phenomenonwas described as a possible early event in the transformation o…
Optimized culture conditions for tissue explants of uterine leiomyoma
Background Uterine leiomyomas are the most common benign tumours in women, which arise from smooth muscle cells of the uterine myometrium and usually are multicentric. In spite of their frequency pathogenesis is widely unknown, mainly due to the absence of a suitable model system. We describe the systematic optimization of culturing leiomyoma tissue explants in an economical and effective ex vivo system. Methods Different concentrations of oxygen, different media, sera, hormones, and growth factor supplements were tested. Immunohistochemical stainings with antibodies against hormone receptors as well as specifying proliferation and apoptotic indices and real-time PCR were performed. Results…
Imbalance between sympathetic and sensory innervation in peritoneal endometriosis
To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n= 40) and healthy peritoneum (n= 12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleuki…
Neuroimmunomodulatory Alterations in Non-Lesional Peritoneum Close to Peritoneal Endometriosis
<b><i>Objectives:</i></b> An imbalance in the ratio of sensory to sympathetic nerve fibre (NF) density in peritoneal endometriotic lesions (pEL) has recently been demonstrated and leads to the assumption that this preponderance of the sensory pro-inflammatory milieu is a major cause of pain in endometriosis. Therefore, the density of sensory and sympathetic NFs was determined in distal unaffected peritoneum of endometriosis patients to be able to detect possible alterations in unaffected peritoneum. <b><i>Methods:</i></b> In serial pEL sections (n = 40), lesional and matching unaffected peritoneum as well as healthy peritoneum (HP) from patien…
Characterization of endometriosis-associated immune cell infiltrates (EMaICI)
Objective: To identify and characterize endometriosis-associated immune cell infiltrates (EMaICI). Furthermore, to define occurrence and size of EMaICI in various types of endometriosis. Methods: Immune cells were characterized in samples of 60 premenopausal women with histological proven endometriosis. Therefore, immunohistochemical staining with monoclonal antibodies for CD3, CD4, CD8, CD45RO, CD25, CD56, CD68, and CD20 on sections of paraffin-embedded endometriotic tissue was performed. Results: EMaICI were observed in all the types of endometriosis, and characterized as T lymphocytes (CD3+), helper T lymphocytes (CD4+), cytotoxic T lymphocytes (CD8+), antigen-experienced T lymphocytes”m…
Eutopic endometrium from women with endometriosis does not exhibit neurotrophic properties
The role of neurotrophins in eutopic endometrium from endometriosis-patients was investigated in a prospective study using immunofluorescence-staining, Western blot and a neuronal growth assay. The nerve growth factor is expressed in primary endometrial cell culture from women with and without endometriosis. Western blot analysis of endometrial biopsies or uterine fluid from patients with and without endometriosis shows no difference in the neurotrophin expression. We could not find a difference between patients with and without endometriosis with regards to the neurite outgrowth of sensory ganglia when treated with conditioned cultured medium or uterine fluid. This result refutes the assum…
High Lymph Vessel Density and Expression of Lymphatic Growth Factors in Peritoneal Endometriosis
To investigate the occurrence of lymph vessels and lymphangiogenic growth factors in peritoneal lesions, we performed immunohistochemical staining of peritoneal lesions of 37 patients with antibodies against podoplanin (D2-40), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), prospero homeobox protein 1 (Prox-1), vascular epithelial growth factor (VEGF)-C/VEGF-D. Overall, 10 lesions were double stained against D2-40 and von Willebrand factor. The lymph vessel density in peritoneal lesion was significantly higher in comparison with healthy peritoneum. All lymph vessel makers could be detected, whereby the lymph vessel density of LYVE-1- and Prox-1-positive lymph vessels was signi…
Laparoscopic Neuronavigation for Deep Lateral Pelvic Endometriosis: Clinical and Surgical Implications
Abstract Study Objective To evaluate the clinical presentation and surgical outcome in patients with deep lateral pelvic endometriosis (dLPE). Design A retrospective multicentric study (Canadian Task Force classification II-2). Setting University tertiary referral centers. Patients One hundred forty-eight women with deep infiltrating endometriosis (DIE). Interventions Laparoscopic excision of DIE. Disease distribution was classified as follows: central pelvic endometriosis (CPE) when DIE involved 1 of the following anatomic sites: cervix, vagina, uterosacral ligaments, rectum, bladder, or pelvic peritoneum; superficial lateral pelvic endometriosis when parametria, ureters, or hypogastric pl…
How to understand the complexity of endometriosis-related pain
Pain is the most important symptom in patients with endometriosis, and its management is truly challenging. Due to the different localization of the endometriotic lesions in the pelvis, patients suffer from visceral and somatic pain or both at the same time. There are specific and unspecific symptoms characterized by endometriosis. Specific symptoms include dysmenorrhea, cyclic and acyclic pelvic pain, dyschezia, dysuria and dyspareunia. There is also a wide range of unspecific symptoms, such as unspecific bowel and bladder complaints, the emission of pain in the legs, vegetative concomitants like vomiting, emesis, gastric disorders, headaches, dizziness, painful ovulation, irregular pelvic…
Laparoscopic Sentinel Lymph Node Detection After Hysteroscopic Injection of Technetium-99 in Patients With Endometrial Cancer
Background and Objectives Endometrial cancer (EC) has an increasing incidence worldwide. Despite the unequivocal prognostic importance of nodal status, systematic lymphadenectomy is associated to elevated morbidity. Sentinel lymph node (SLN) biopsy is designed to avoid extensive nodal dissection and provide crucial oncologic information. The goal of this prospective study was to determine the feasibility, safety, and accuracy of laparoscopic SLN biopsy in EC obtained through hysteroscopic injection of technetium-99 (Tc-99). Methods From January 2008 to December 2012, a total of 42 women with EC were included in the study. We injected 20 mBq of Tc-99 hysteroscopically underneath the tumor mi…
Reduced Sympathetic Innervation in Endometriosis is Associated to Semaphorin 3C and 3F Expression
Endometriosis is a chronic inflammatory disease and one of the most common causes of pelvic pain. The mechanisms underlying pain emergence or chronic inflammation during endometriosis remain unknown. Several chronic inflammatory diseases including endometriosis show reduced amounts of noradrenergic nerve fibers. The source of the affected innervation is still unclear. Semaphorins represent potential elicitors, due to their known role as axonal guidance cues, and are suggested as nerve repellent factors in different chronic inflammatory diseases. Therefore, semaphorins might influence the progress of neuroinflammatory mechanisms during endometriosis. Here, we analyzed the noradrenergic inner…
Arrangement of myofibroblastic and smooth muscle-like cells in superficial peritoneal endometriosis and a possible role of transforming growth factor beta 1 (TGFβ1) in myofibroblastic metaplasia.
Purpose: Superficial peritoneal endometriotic (pEM) lesions are composed of endometrial glands and stroma, in addition to a third component—myofibroblasts and smooth muscles (SM)-like cells. The latter develops secondary to a metaplasia. In this study, we characterised the third component cells in pEM according to differentiation markers in different micro-compartments. Furthermore, a possible effect of TGFβ1 on myofibroblastic metaplasia in endometriotic epithelial cells was studied. Methods: Seventy-six premenopausal patients were included. Peritoneal biopsies were excised from EM patients (n = 23), unaffected peritoneum (peritoneum from EM patients but without EM components, n = 5/23) an…
Pain Mechanisms in Peritoneal Diseases Might Be Partially Regulated by Estrogen
To identify factors influencing the differential pain pathogenesis in peritoneal endometriosis (pEM) and peritoneal carcinomatosis in ovarian cancer (pOC), we undertook an experimental study. Tissue samples of 18 patients with pEM, 15 patients with pOC, and 15 unaffected peritoneums as controls were collected during laparoscopy or laparotomy. Immunohistochemical stainings were conducted to identify nerve fibers and neurotrophins in the tissue samples. Additionally, 23 pEM fluids, 25 pOC ascites fluids, and 20 peritoneal fluids of patients with myoma uteri as controls were collected. In these fluids, the expression of neurotrophins was evaluated. The effects of peritoneal fluids and ascites …
Evidence of neurotrophic events due to peritoneal endometriotic lesions
To investigate the neurotrophic properties of endometriosis, as well as the involvement of neurotrophic factors in the development of chronic pelvic pain in patients with endometriosis, we performed a prospective clinical study. The presence of neurotrophins was investigated in the peritoneal fluid (PF) of patients with peritoneal endometriotic lesions or adenomyosis, as well as from women with non-endometriotic adhesions and from women without endometriosis/adenomyosis/adhesions. The PF from patients with peritoneal endometriotic lesions was divided in three groups: asymptomatic endometriosis, minimal pain and severe pain. PF from patients with adenomyosis or with non-endometriotic adhesio…
Influence of nerve growth factor in endometriosis-associated symptoms
To investigate the role of the nerve growth factor (NGF) in the development of dysmenorrhea/pelvic pain in patients with endometriosis, we performed a prospective, clinical, blind study. Peritoneal fluids (PFs) were obtained from patients with histologically proven endometriosis. Patients with endometriosis were divided into 7 different groups depending on their preoperative pain score and symptomatology: patients with no pain, patients with minimal pain (dysmenorrhea, pelvic pain, or both), and patients with severe pain (dysmenorrhea, pelvic pain, or both) and were used for the neuronal growth assay with cultured chicken dorsal root ganglia (DRG) and for Western blot analyses. Dorsal root …
Ultramicro-trauma in the endometrial-myometrial junctional zone and pale cell migration in adenomyosis
Objective To determine if ultrastructural tissue trauma occurs in the junctional zone in uteri in adenomyosis. Design A case-control experimental study. Setting Endometriosis research center. Patient(s) Twelve uteri with adenomyosis, and 9 uteri without adenomyosis, were gained during laparoscopy-assisted vaginal hysterectomy. Intervention(s) Transmission electron microscopic study of the junctional zone, as well as immunohistochemical staining for epithelial cadherin, and van Gieson staining and immunofluorescence for CD45 and CD68. Main Outcome Measure(s) Analysis of the electron microscopy photos and the immunoreactive scores of the staining. Result(s) The inner myometrial muscle fibers …
Myofibroblasts Are Evidence of Chronic Tissue Microtrauma at the Endometrial-Myometrial Junctional Zone in Uteri With Adenomyosis.
Background Adenomyosis (AM) uteri exhibit hyperperistalsis. The latter causes a chronic tissue trauma at the endometrial-myometrial junctional zone (EMJZ). Upon tissue trauma, microdehiscences in the myometrium facilitate the translocation of basal endometrial fragments into the myometrium. There, a metaplasia (mediated by transforming growth factor β1 [TGFβ1] and connective tissue growth factor [CTGF]) occurs and AM lesions develop. The abundance of myofibroblasts in a tissue hallmarks metaplasia and points to a tissue microtrauma. Materials and methods To study if myofibroblasts-as an evidence of tissue microtrauma-are more abundant at EMJZ in AM-uteri, a case-control experimental study w…
Possible Role of the Posterior Compartment Peritonectomy, as a Part of the Complex Surgery, Regarding Recurrence Rate, Improvement of Symptoms and Fertility Rate in Patients with Endometriosis, Long-Term Follow-Up.
ABSTRACT Study Objective Beside the pain, there are 2 further problems in the management of endometriosis: the high recurrence rate (10% per year) and the high rate of impaired fertility. The objective of this study was to investigate the pathogenesis of these 2 factors. Design This is a retrospective cohort study, and the aim is to evaluate the complete excision of endometriotic lesions, including the posterior compartment of the peritoneum, with regard to postoperative outcome, focusing on relieving pain, increasing fertility rate, and decreasing recurrence rate. Setting Charite-University Clinic, Department of Gynaecology, Endometriosis research Centre. Patients Fifty-four patients were …
Overexpression of nerve growth factor in peritoneal fluid from women with endometriosis may promote neurite outgrowth in endometriotic lesions
To investigate the role of the nerve growth factor (NGF) in the endometriosis-associated innervation in the development of endometriosis- associated symptoms, 41 peritoneal fluid samples (PF) from patients with surgically and histologically proven endometriosis and 20 PF from patients with other gynecologic conditions were analyzed with Western blot and a novel in vitro model using dorsal root ganglia (DRG) to show neuronal outgrowth; endometrial cells also were analyzed. The results suggest that the PF of endometriosis patients and endometriotic lesions have neurotropic properties, because the Western blot analysis and the cell culture stainings showed NGF expression, and the neurite outgr…
When and how should peritoneal endometriosis be operated on in order to improve fertility rates and symptoms? The experience and outcomes of nearly 100 cases
Abstract Purpose To analyze the follow-up results of patients suffering from symptomatic early-stage endometriosis after a consistent laparoscopic peritoneal stripping of the altered peritoneum (peritoneal endometriosis and surrounding inflamed tissue) was performed. This type of endometriosis is resistant to medical therapy and/or impairs fertility. Methods Using our prospectively maintained database, we were able to identify all symptomatic women with the suspicion of only peritoneal endometriosis who underwent laparoscopy at our endometriosis center over a period of 5 years. All procedures were carried out in a standardized fashion by one single surgeon, who is highly experienced in mini…
Laparoscopic En Bloc Right Diaphragmatic Peritonectomy for Diaphragmatic Endometriosis According to the Sugarbaker Technique
Abstract Study Objective To evaluate the feasibility of a novel laparoscopic procedure for complete eradication of diaphragmatic endometriosis (DE). Design A retrospective multicenter study (Canadian Task Force Classification II-2). Setting University tertiary referral centre. Patients A consecutive series of 9 women with DE. Interventions Laparoscopic en bloc eradication using Sugarbaker's peritonectomy technique with or without diaphragmatic resection for DE. All surgical procedures were performed by the same surgeon in 2 tertiary referral centers (Charite University, Berlin, Germany, and Catholic University of the Sacred Heart, Foundation John Paul II, Campobasso, Italy). Measurements an…
Immunohistochemical Investigation of Metastasis-Related Chemokines in Deep-Infiltrating Endometriosis and Compromised Pelvic Sentinel Lymph Nodes
Endometriosis is a prevalent benign disease, despite sharing several similarities with malignancies, such as the possibility of lymphatic spread. In malignancies, chemokines play a sovereign role in the process of metastasis. Metastasis-related chemokine axes have not yet been assessed in deep-infiltrating endometriosis (DIE), and this investigation was the aim of our study. The expression of these chemokines was investigated by immunohistochemistry in rectovaginal DIE lesions and in matched pelvic sentinel lymph nodes (PSLNs) of patients with endometriosis (n = 27), and their expression in the eutopic endometrium (EE) of endometriosis-free women (n = 20) was used as controls. Their stainin…
Post-operative management and follow-up of surgical treatment in the case of rectovaginal and retrocervical endometriosis.
Abstract Introduction Deep infiltrating endometriosis (DIE) affects between 3.8% and 37% of all endometriosis patients, mostly affecting rectovaginal septum or retrocervical space and characterized by the severe endometriosis-related complaints. Nowadays, generally managed with surgery. However, this is associated with a risk of postoperative complications. To better evaluate intra- and postoperative complications and outcomes for rectovaginal (RVE) and retrocervical endometriosis (RCE), the preoperative management should be accurately described and compared. Methodology This is a cohort retrospective study performed at the Endometriosis Centre of Charité-University Clinic, Berlin. 34 patie…