Presence Of Ectopic Endometrium Research Articles

P-283 Spatial transcriptomics identifies dysregulated pathways in adenomyosis proposing potential re-purposed lesion-specific treatments

Abstract Study question How does the transcriptome of adenomyosis lesions compare to the matched eutopic endometrium, and can they be targeted with lesion-specific treatments? Summary answer Adenomyosis lesions are transcriptionally distinct from matched eutopic endometrium, exhibiting upregulated cell motility pathways, increased cilia, and altered hormonal regulation, providing targets for lesion-specific treatments. What is known already Adenomyosis affects 10% of women of reproductive age and is caused by the presence of ectopic endometrium within the myometrium, causing heavy periods, chronic pain, and subfertility. The only definitive treatment is hysterectomy and there are no current fertility-sparing treatments available. Spatial transcriptomics allows interrogation of the transcriptome with spatial context, overcoming the limitations of bulk and sc-RNA sequencing technology. In the endometrium, spatial transcriptomics has providing insight into how cellular functions differ depending on their location and communication with neighbouring cells, however it has not yet been used to investigate adenomyosis. Study design, size, duration A retrospective observational study of ten women undergoing hysterectomy for heavy, painful periods, with a histological diagnosis of adenomyosis. All women were in the secretory phase of menstrual cycle and had not taken exogenous hormones for the preceding three months. Paired full-thickness endometrial and myometrial biopsies containing adenomyosis lesions were obtained from each woman. The presence of adenomyosis lesions was confirmed by the presence of endometrial glands and stroma >2.5mm from the endo-myometrial junction. Participants/materials, setting, methods Whole transcriptome profiling of the following regions of interest was performed: luminal epithelium, functionalis, basalis, and adenomyosis lesions, and immunofluorescent morphology markers were employed to identify epithelial, stromal, endothelial, and immune cells within each region. A generalised linear-mixed model was designed and unsupervised clustering, differential gene expression comparison, gene set enrichment analysis (GO and Reactome), ligand-receptor signalling, and in silico drug screening was performed. Statistical analyses were adjusted for a false discovery rate of (<0.05). Main results and the role of chance Adenomyosis lesions were more similar to endometrial basalis than functionalis, with 102 significantly DEG’s between adenomyosis lesions and endometrial basalis, and 282 significantly DEG’s between adenomyosis lesions and endometrial functionalis (adjusted p < 0.05). Adenomyosis lesion epithelium, stroma, and immune cells consistently revealed significantly downregulated DEG’s involved with cellular proliferation and apoptosis (FOS, JUNB, DUSP1) compared to the endometrium (adjusted p = 0.002). Pathway analysis revealed that adenomyosis lesion epithelium was positively enriched for terms relating to ciliation compared to the endometrium (adjusted p < 0.0001), and immunostaining confirmed an increased number of ciliated cells in adenomyosis lesions compared with eutopic endometrium in the same samples (n = 10, p < 0.01). Androgen receptor signalling was negatively enriched in the stroma of adenomyosis lesions compared to endometrial functionalis (adjusted P < 0.0001). Ligand-receptor signalling analysis revealed prominent crosstalk between endothelial-epithelial, and immune-epithelial cells in adenomyosis lesions, and a loss of stromal-epithelial cross-talk. TNFSF10 ligand from endothelial and immune cells showed high regulatory potential of gene receptors on epithelial cells known to be involved in cellular response to stress, regulation of growth, and apoptosis (DUSP1, DUSP5, EGR1, FOS, IER3, JUNB, PPP1R15A, SGK1). In-silico drug repurposing analysis revealed key compounds which may target adenomyosis lesions and spare the eutopic endometrium. Limitations, reasons for caution This is an observational study with a small sample size of ten which is a limitation, although is larger than the sample size of most published transcriptional studies of this type. Further validation work is needed to confirm the exploratory transcriptional findings outlined. Wider implications of the findings Fertility sparing, effective, lesion-specific treatments are urgently needed for women with adenomyosis. This study provides region and cell-type specific comparative transcriptional data between adenomyosis lesions and eutopic endometrium, identifying lesion-specific dysregulated pathways, insight into their biological relevance, and potential treatment targets to be trialled in future pre-clinical studies. Trial registration number Not applicable

Role of Betaglycan in TGF-β Signaling and Wound Healing in Human Endometriotic Epithelial Cells and in Endometriosis.

Simple SummaryEndometriosis is a benign female disorder presumably caused by dislocation of endometrial tissue during menstruation most often into the pelvis and is mainly resulting in pain and infertility. Up to date the pathogenesis of endometriosis is still unclear and a non-invasive biomarker not available. One of the cytokines suggested to be involved in the pathogenesis are the transforming growth factor-betas 1-3, which signal via two high-affinity receptors and in the case of transforming growth factor-beta2 also via the co-receptor betaglycan. In this study, we have analyzed the involvement of betaglycan into transforming growth factor-beta signaling and the contribution to biological functions such as wound healing with an in vitro model. We demonstrated an interesting interaction of betaglycan with the transforming growth factor-betas 1-3 and vice versa. Remarkably, the co-receptor betaglycan in its soluble form reduced wound healing as well as secretion of transforming growth factor-betas. Although we found some hints that endocervical mucus levels are different between healthy subjects and cases with endometriosis it was not sufficient for a reliable non-invasive diagnosis of the disease. Taken together, our findings suggest a novel role for betaglycan in the pathogenesis of endometriosis. Endometriosis is characterized by the presence of ectopic endometrium most often in the pelvis. The transforming growth factor-beta (TGF-β) superfamily is also involved in the pathogenesis; however, betaglycan (BG, syn. TGF-β type III receptor) as an important co-receptor was not studied. We analyzed mainly BG ectodomain shedding because released soluble BG (sBG) often antagonizes TGF-β signaling. Furthermore, we studied the role of TGF-βs and BG in wound healing and evaluated the suitability of BG measurements in serum and endocervical mucus for non-invasive diagnosis of endometriosis. Evaluation of the BG shedding and signaling pathways involved as well as wound healing was performed with enzyme-linked immune assays (ELISAs), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), small interfering RNA (siRNA) knockdown, and scratch assays with human endometriotic epithelial cells. TGF-β1/2 stimulation resulted in a significant dose-dependent reduction in BG shedding in endometriotic cells, which was TGF-β/activin receptor-like kinase-5 (ALK-5)/mother against decapentaplegic homolog3 (SMAD3)- but not SMAD2-dependent. Inhibition of matrix metalloproteinases (MMPs) using the pan-MMP inhibitor GM6001 and tissue inhibitor of MMPs (TIMP3) equally attenuated BG shedding, signifying the involvement of MMPs in shedding. Likewise, recombinant BG moderately reduced the secretion of TGF-β1/2 and wound healing of endometriotic cells. TGF-β1 significantly enhanced the secretion of MMP2 and MMP3 and moderately promoted wound healing. In order to evaluate the role of BG in endometriosis, serum (n = 238) and mucus samples (n = 182) were analyzed. Intriguingly, a significant reduction in the levels of sBG in endocervical mucus but not in the serum of endometriosis patients compared to controls was observed. Collectively, these observations support a novel role for BG in the pathophysiology of endometriosis.

Ultrasound Imaging of Abdominal Wall Endometriosis: A Pictorial Review.

Endometriosis is a debilitating disease characterized by endometrial glands and stroma outside the endometrial cavity. Abdominal wall endometriosis (AWE) indicates the presence of ectopic endometrium between the peritoneum and the skin, including subcutaneous adipose tissue and muscle layers, often following obstetric and gynecological surgical procedures. AWE is a not infrequent gynecological surgical complication, due to the increasing number of cesarean sections worldwide. In this pictorial review, we discuss the importance of medical history and physical examination, including the main ultrasound features in the diagnosis of AWE.

Pathophysiologic mechanisms by which adenomyosis predisposes to postpartum haemorrhage and other obstetric complications

Adenomyosis is characterized by the presence of ectopic endometrium within the myometrium. This features lead to structural changes in the surrounding myometrium and endometrium resulting also in functional changes. Alterations in the myometrium are suspected to lead to defective remodeling of spiral arteries during the early stages of decidualization resulting in altered vascular resistance and defective placentation. These alterations could play a common part in the association between adenomyosis and major obstetric complications. Latest epidemiological studies show that adenomyosis is associated with preterm birth, preeclampsia, IUGR and increased caesarean section rates, but very little is known of any underlying mechanism linking postpartum hemorrhage and adenomyosis. It is our opinion that adenomyosis may increase the risk of postpartum hemorrhage through several mechanisms that will be further clarified.Women with adenomyosis may require specific management during pregnancy and may benefit from wider understanding of the pathological mechanisms associated with this disease process.

Revealing the enigma of coagulation in endometriosis: the risk of thrombosis and the role of antithrombotic treatment

Endometriosis is a chronic inflammatory disease of women of reproductive age that is defined by the presence of ectopic endometrium. The pathophysiology of the disease is poorly understood, however platelet activation play a crucial role in initiation of inflammation and fibrinogenesis, which in term further activate the coagulation cascade. The relationship between inflammation and coagulation motivated researchers to study whether patients are in a hypercoagulable state and if endometriosis represent an independent risk factor for venous thromboembolism or cardiovascular risk. This review article focuses on the role of coagulation, the risk of thrombosis and a possible beneficial effect of antithrombotic-treatment.

Expression Pattern of Mitogen-inducible Gene 6 in Relation to the Extracellular Signal-regulated Kinase Pathway and Redox Status in Patients with Endometriosis

Background: Endometriosis is a gynecological disorder characterized by the presence of ectopic endometrium outside the uterus. It is a multi-factorial disease, where different processes facilitate the implantation and survival of ectopic endometrial tissue. 
 The Aim: This study aims to evaluate the levels of the expression patterns of mitogen-inducible gene 6 (Mig-6) in eutopic and ectopic endometrial tissues of endometriosis patients and their relevance to the levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) and redox status.
 Methods: Relative gene expression levels of Mig-6 and the levels of pERK1/2 were assessed in endometrial tissues of control group and in both eutopic and ectopic endometrial tissues of endometriosis patients .Serum levels of total protein thiols and total protein carbonyls were also assessed in endometriosis and control groups.
 Results: Relative gene expression levels of Mig- 6 showed significant lower values in endometriosis group as compared to control group, and they were associated with significant increase in pERK 1/2 levels and altered redox status.
 Conclusion: These data, signified a significant role of downregulated Mig-6 expression, and activated ERK 1/2 signaling in the pathogenesis of endometriosis. Moreover, it suggested that oxidative stress indicated by high protein carbonyls level contributes to the pathogenesis of endometriosis and that protein thiols have a defensive role against oxidative stress.

High Expression of High-Mobility Group Box 1 in Menstrual Blood: Implications for Endometriosis.

Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosis is not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor ( VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid ( P < .001 for both). RAGE was expressed in both normal and ectopic endometrium. Administration of 1000 ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF production in ESCs relative to the control ( P < .05). These results suggest that menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.

Galectin-1 overexpression in endometriosis and its regulation by neuropeptides (CRH, UCN) indicating its important role in reproduction and inflammation.

Endometriosis is an inflammatory disease of women of reproductive age featured by the presence of ectopic endometrium and is strongly related to infertility. Galectins, carbonhydrate-binding proteins, have been found to have pro- or anti-inflammatory roles in the reproductive tract and in pathological conditions concerning infertility. Galectin-1, which is expressed at endometrium and decidua, plays a major role in implantation and trophoblast invasion. Also, the neuropeptides, corticotropin releasing hormone (CRH) and urocortin (UCN) and their receptors are expressed in eutopic and ectopic endometrium showing a differential expression pattern in endometriotic women compared to healthy ones. The aim of this study was to examine the galectin-1 expression in endometriotic lesions and compare its expression in eutopic endometrium of endometriotic and healthy women. Furthermore, we examined the effect of CRH and UCN in galectin-1 expression in Ishikawa cell line and macrophages and investigated the implication of CRHR1 in these responses. Eutopic and ectopic endometrium specimens, Ishikawa cell line and mice macrophages were used. Immunohistochemistry and western blot analysis were performed in order to identify galectin-1 expression in ectopic and eutopic endometrium of women with and without endometriosis and the regulatory effect of CRH and UCN on galectin-1 expression. This study presents for the first time that galectin-1 is overexpressed in endometriotic lesions compared to eutopic endometrium of endometriotic women and is more abundantly expressed in eutopic endometrium of disease women compared to healthy ones. Furthermore, it is shown that CRH and UCN upregulate galectin-1 expression in Ishikawa cell line and macrophages and this effect is mediated through CRHR1. These results suggest that galectin-1 might play an important role in endometriosis pathology and infertility profile of women suffering from endometriosis by being at the same time regulated by CRH and UCN interfering in the immune disequilibrium which characterizes this pathological condition.

Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects

Endometriosis is a common benign pathology, characterised by the presence of endometrial tissue outside the endometrial cavity with a prevalence of 10-15% in reproductive-aged women. The pathogenesis is not completely understood, and several theories have been proposed to explain the aetiology. Our group has recently described the presence of ectopic endometrium in a consistent number of human female foetuses analysed by autopsy, reinforcing the hypothesis that endometriosis may be generated by defects during the organogenesis of the female reproductive trait. Herein, in order to identify, at molecular level, changes involved in the disease, we compared the transcriptional profiling of ectopic endometrium with the corresponding eutopic one. Statistical analyses lead us to identify some genes specifically deregulated in the ectopic endometrium, that are involved in gonad developmental process or in wound healing process. Among them, we identified BMP4 and GREM1. BMP4 was never associated before to endometriosis and is involved in the mesoderm-Müllerian duct differentiation. GREM1 is needed for the initial step of the ureter growth and perhaps could possibly be involved in Müller ducts differentiation. These molecules might be related to the endometriosis aetiology since we showed that their expression is not related to the menstrual cycle phase both at RNA and at protein levels. These data support the theory that embryological defects could be responsible of the endometriosis generation.

Defective myometrial spiral artery remodelling as a cause of major obstetrical syndromes in endometriosis and adenomyosis

Endometriosis and adenomyosis are characterized by the presence of ectopic endometrium, but are also associated with functional and structural changes in the eutopic endometrium and inner myometrium. Alterations in the inner myometrium occurring in women with endometriosis and adenomyosis may be at the root of a defective remodelling of the myometrial spiral arteries from the onset of decidualization and result in vascular resistance and increased risk of defective deep placentation. The association of major obstetrical syndromes and different types of defective remodelling of the myometrial spiral arteries has been well documented. The possibility of a link between both endometriosis and adenomyosis and some major obstetric syndromes remains controversial because of at least two factors: first, changes of the inner myometrium are frequently present in women with endometriosis but the diagnosis requires high-resolution imaging such as magnetic resonance which is not routinely performed and second, patients with endometriosis are frequently subjected to prolonged hormone suppressive therapy. Indeed, there is evidence that pre-treatment with a Gonadotropin Releasing-Hormone analogue can improve the uterine microenvironment and implantation rate following IVF in infertile patients with endometriosis.

Hepatic endometrioma: a case report and review of the literature: report of a case

Hepatic endometriosis has an extremely rare occurrence characterized by the presence of ectopic endometrium in the liver. A diagnosis of hepatic endometriosis is established after surgery. A 51-year-old multiparous female was referred to our unit for investigation of a liver tumor. The patient reported a 6-month history of epigastric pain and vomiting. She had undergone conservative hysterectomy for uterine leiomyomas several years earlier. The results of liver function tests and the levels of tumor markers (CA 19.9, CEA, CA125, αFP) were normal. Radiological imaging (USS, CT and MRI) suggested the presence of liver cystadenoma, liver cystadenocarcinoma or cystic metastasis of the liver in the left liver lobe extending to the diaphragm with left hepatic vein compression. Laparotomy was performed. The intraoperative frozen sections suggested a diagnosis of endometriosis. Anatomical resection was performed, including left lobectomy with diaphragm resection. The final histology confirmed the presence of hepatic endometrioma without malignant transformation. Fourteen cases of hepatic endometrioma have been described in the medical literature. We herein report the 15th case. Making a preoperative diagnosis of hepatic endometriosis is very difficult, despite conducting a complete investigation, in the absence of clinical and radiological characteristics. The diagnosis is made according to a histological examination of the whole surgical sample.

Use of a murine endometriosis interna model for the characterization of compounds that effectively treat human endometriosis.

Endometriosis is a chronic, estrogen-dependent disease characterized by the presence of ectopic endometrium either in the pelvic cavity (endometriosis externa) or within the uterus (endometriosis interna, adenomyosis). Key symptoms are pelvic pain, dysmenorrhea and infertility. Established rodent animal models used for drug research in endometriosis have certain limitations. Since rodents do not menstruate, they cannot develop endometriosis externa spontaneously, but they suffer from endometriosis interna. There is growing evidence that human endometriosis externa and interna represent two faces of the same disease. Both are estrogen-dependent and respond to similar treatment paradigms. Here, we addressed the question whether a murine endometriosis interna model may also be suitable for the characterization of drugs employed in human endometriosis. We examined the effects of danazol, Faslodex and cetrorelix in SHN mice that developed endometriosis interna after pituitary grafting. The GnRH antagonist cetrorelix and the estrogen receptor antagonist Faslodex, which negatively interfered with estrogen-mediated signaling, completely inhibited endometriosis interna, whereas danazol, an androgenic progestin, showed significant therapeutic activity in the majority of SHN mice. We conclude that this murine endometriosis interna model may be a valuable complement to established endometriosis externa models to support drug research in human endometriosis.

Adenomyosis: Usual and Unusual Imaging Manifestations, Pitfalls, and Problem-solving MR Imaging Techniques

Adenomyosis is a common nonneoplastic gynecologic disease characterized by the presence of ectopic endometrium within the myometrium. On T2-weighted magnetic resonance (MR) images, typical adenomyosis appears as an ill-demarcated low-signal-intensity lesion with uterine enlargement. However, various physiologic or pathologic states such as amount of functional endometrial tissue, phase of the menstrual cycle, endogenous hormonal abnormality, and exogenous hormonal stimulation may affect the MR imaging appearance of adenomyosis and may result in a tumorlike appearance. Problem-solving MR imaging techniques used in diagnosis of adenomyosis include diffusion-weighted imaging, susceptibility-weighted imaging, hydrogen 1 MR spectroscopy, cine MR imaging, and high-resolution MR imaging at 3 T. Adenomyotic lesions that show high signal intensity relative to the outer myometrium on T2-weighted images mimic malignancies such as leiomyosarcoma and endometrial stromal sarcoma. In these cases, a relatively high apparent diffusion coefficient at diffusion-weighted imaging and a low choline peak at MR spectroscopy are suggestive of a benign lesion. Small hemorrhagic foci suggestive of an adenomyotic lesion are well demonstrated as signal voids at susceptibility-weighted imaging. Cine MR imaging is useful in differentiating transient myometrial contraction from focal adenomyosis. High-resolution MR imaging at 3 T demonstrates anatomically detailed structures and may improve diagnostic accuracy in differentiating adenomyosis from its mimics, such as low-grade endometrial stromal sarcoma.

Combined proteomic and RNA microarray analysis after TRIzol extraction of eutopic endometrium for endometriosis biomarker discovery

OBJECTIVE: Endometriosis (endo) is an important gynaecological disease defined by the presence of ectopic endometrium (EM) outside the uterus and associated with pelvic pain and infertility. In this study we evaluated for the first time the feasibility of EM TRIzol extraction to obtain both a protein and mRNA fraction of sufficient quality from the same EM sample in order to perform combined proteomic analysis and mRNA microarray.DESIGN: Proteomic analysis of TRIzol-extracted eutopic endometrium.MATERIALS AND METHODS: Endometrial tissues were obtained during the late luteal phase (day 23-26) from 16 patients including controls with a normal pelvis (n=5) and patients with endometriosis (n=11) including minimal-mild (n=5) and moderate-severe (n=6) disease according to ASRM classification. We used Surface Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry (SELDI-TOF-MS): all samples were measured in duplicates on CM10 and IMAC30 protein chips in low molecular weight (CHCA) and high molecular weight (SPA). All mass peaks were used as input for a Least Squares Support Vector Machine (LS-SVM). Next, Leave one out cross validation (LOO-CV) was used to estimate independent test set performance.RESULTS: Profiling of endometrial samples by using different ProteinChip surfaces showed differential expression of proteins and peptides in the range between 7 - 17 kDa depending on chip and matrix type. The LOO-CV performance of the LS-SVM models indicated an Area under the ROC curve (AUC) between 85%-100% (depending on chip and matrix type) for the diagnosis of endometriosis. These results will be discussed in relationship to the mRNA microarray results obtained on the same EM samples (Sherwin et al, 2008).CONCLUSIONS: Protein profiling using ProteinChip array after TRIzol preparation is feasible and reproducible and allows combined proteomic analysis and mRNA microarray on the same EM sample. OBJECTIVE: Endometriosis (endo) is an important gynaecological disease defined by the presence of ectopic endometrium (EM) outside the uterus and associated with pelvic pain and infertility. In this study we evaluated for the first time the feasibility of EM TRIzol extraction to obtain both a protein and mRNA fraction of sufficient quality from the same EM sample in order to perform combined proteomic analysis and mRNA microarray. DESIGN: Proteomic analysis of TRIzol-extracted eutopic endometrium. MATERIALS AND METHODS: Endometrial tissues were obtained during the late luteal phase (day 23-26) from 16 patients including controls with a normal pelvis (n=5) and patients with endometriosis (n=11) including minimal-mild (n=5) and moderate-severe (n=6) disease according to ASRM classification. We used Surface Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry (SELDI-TOF-MS): all samples were measured in duplicates on CM10 and IMAC30 protein chips in low molecular weight (CHCA) and high molecular weight (SPA). All mass peaks were used as input for a Least Squares Support Vector Machine (LS-SVM). Next, Leave one out cross validation (LOO-CV) was used to estimate independent test set performance. RESULTS: Profiling of endometrial samples by using different ProteinChip surfaces showed differential expression of proteins and peptides in the range between 7 - 17 kDa depending on chip and matrix type. The LOO-CV performance of the LS-SVM models indicated an Area under the ROC curve (AUC) between 85%-100% (depending on chip and matrix type) for the diagnosis of endometriosis. These results will be discussed in relationship to the mRNA microarray results obtained on the same EM samples (Sherwin et al, 2008). CONCLUSIONS: Protein profiling using ProteinChip array after TRIzol preparation is feasible and reproducible and allows combined proteomic analysis and mRNA microarray on the same EM sample.

Spontaneous adenomyosis in the chimpanzee (Pan troglodytes): a first report and review of the primate literature: Case Report

Adenomyosis is a non-neoplastic condition characterized by the presence of ectopic endometrium in the myometrium with hyperplasia of adjacent smooth muscle. Common symptoms in women include debilitating pelvic pain and abnormal uterine bleeding, and the condition has been paradoxically associated with both multiparity and subfertility. Adenomyosis spontaneously occurs in humans and some non-human primates, including the baboon and macaque, where it has been associated with primary infertility and the presence of endometriosis. No cases of adenomyosis have been previously reported in Pongidae such as gorilla, orangutan or chimpanzee. We here describe two cases of naturally occurring adenomyosis in the chimpanzee (Pan troglodytes) and briefly review the literature regarding the presence of adenomyosis in non-human primate species.

Diagnosis and investigation of endometriosis

Currently there is lively debate about what constitutes the diagnosis of endometriosis. Recent research and clinical studies have led some experts to consider that the presence of ectopic endometrium may be physiological. They argue that endometriosis should be defined as the combination of local destruction or symptoms associated with the finding of ectopic endometrium 1. This confusion makes it difficult for the practising clinician to be clear as to what visual findings of endometriosis need treatment in which patient. It is necessary to be aware that endometriosis can be found in many lesions not previously thought to contain the disease and that small amounts of the disease may be very common in the menstruating woman. There is also evidence that endometriosis progresses from active to inactive disease and that these stages can be recognised visually. Therefore, the diagnosis should combine verification of the presence of the disease with recognisable symptoms and signs before the causality of endometriosis is accepted. Currently the main technique for investigation is laparoscopy. There are, however, possibilities of non-invasive diagnosis using ultrasonography, radioisotopes and serum CA-125 concentrations but these are still in development. Finally, the diagnosis of extra-pelvic endometriosis can present some problems and these are discussed.

Surgically induced endometriosis does not alter peritoneal factors in the rabbit model

It was the purpose of this study to examine the cause and effect relationship between alterations in peritoneal factors and the presence of ectopic endometrium in the rabbit model. Forty rabbits had autologous endometrial or omental (control) tissue surgically implanted. Peritoneal fluid (PF) volume, macrophage number, and macrophage activation, as well as the number of implants with adhesions, were compared with values obtained during the initial surgery. The effect of hormonal treatment on these factors was evaluated at a third laparotomy. There was a significant increase (P less than 0.05) of adhesions in animals with endometrial implants. Peritoneal fluid volume, macrophage number, or macrophage activation were not increased in rabbits with endometrial implants as compared with controls, nor was there a response to hormonal manipulation. These results demonstrate that PF volume, macrophage number, and macrophage activation are not altered by endometrial implants in the rabbit model. This suggests that the increase in these peritoneal factors in women with endometriosis may not be caused exclusively by the presence of ectopic endometrial tissue.

Endometriosis

Endometriosis, a condition defined by the presence of ectopic endometrium, is a disorder of increasing incidence and a significant cause of gastroenterologic distress in young women. Although clinical manifestations vary considerably depending upon the anatomic extent of disease, characteristic abdominal complaints and typical physical findings continue to be associated with misdiagnosis and delayed recognition of gastrointestinal involvement. The authors of this paper review the medical literature concerning endometriosis of the digestive tract--emphasizing modes of presentation, risk factors, diagnostic testing, complications, and therapy. Greater familiarity with the disease and heightened awareness of its sequellae are needed and prerequisite to improved medical management.