Giant peritoneal loose body and its protein composition: a case report.

Peritoneal loose body (PLB) is a kind of lesions located in the abdominal cavity or pelvic cavity, which is rare and difficult to diagnose. The diameter of PLB is mostly 0.5-2.5 cm. Most PLBS are asymptomatic. Here we reported a case of giant PLB in the pelvis and analyzed its structure and protein composition. Surgical exploration revealed a white oval mass (4.5*4*3 cm) in the pelvic cavity. After the mass was removed, the symptoms of hematuria disappeared and the patient was discharged on the second postoperative day. Histochemical staining showed that PLB was mainly composed of collagen and scattered calcification. The protein components of PLB were detected by proteome analysis, and a variety of proteins related to collagen deposition and calcification were identified in PLB.

Distribution of smooth muscle actin and collagen in superficial peritoneal endometriotic lesions varies from the surrounding microenvironment.

RESEARCH QUESTION: Do different subtypes of superficial peritoneal endometriotic lesions exist, based on the presence and morphology of smooth muscle, collagen fibres and immune cell populations? DESIGN: A retrospective cohort study of 24 patients, from across the menstrual cycle, with surgically and histologically confirmed endometriosis. Immunofluorescence was used to delineate the CD10 stromal area of lesions (n = 271 lesions from 67 endometriotic biopsies), and then smooth muscle actin (SMA) positive tissue and immune cell populations (CD45+ and CD68+) were quantified within and adjacent to these lesions. Second harmonic generation microscopy was used to evaluate the presence and morphology of type-1 collagen fibres within and surrounding lesions. RESULTS: Overall, immune cell numbers and the area of SMA and collagen within endometriotic lesions tended to be low, but a spectrum of presentations significantly varied, particularly in the adjacent tissue microenvironment, based on lesion locations, the morphology of endometriotic gland profiles, or both. Lesions in which collagen fibres formed well aligned capsules around the CD10+ stromal border were identified compared with lesions in which collagen fibre distribution was random. Considerable inter- and intra-patient variability in the morphology of SMA and collagen was observed within and surrounding lesions. CONCLUSION: These data demonstrate considerable diversity in the presence of immune cells and morphology of SMA and collagen within, but even more so, surrounding endometriotic lesions, even within individual patients. This heterogeneity, especially within individual patients, presents a challenge to incorporating these cell and tissue types into any new endometriosis classification systems or prognostic approaches.

Extensive heterogeneity in the expression of steroid receptors in superficial peritoneal endometriotic lesions.

RESEARCH QUESTION: Is the expression of steroid hormone receptors (oestrogen receptor-α and progesterone receptor A/B) and proliferative markers (Bcl-2 and Ki67) uniform among superficial peritoneal endometriotic lesions? DESIGN: A retrospective cohort study of 24 patients with surgically and histologically confirmed endometriosis. Immunofluorescence was used to determine the proportion of oestrogen receptor-α (ERα), progesterone receptor A/B, Bcl-2 and Ki67 positive cells in 271 endometriotic lesions (defined as endometriotic gland profile/s within an individual region of CD10 stromal immunostaining from a single biopsy) from 67 endometriotic biopsies from 24 patients. Data were analysed to examine associations related to menstrual cycle stage, lesion location and gland morphology. RESULTS: Oestrogen receptor-α and progesterone receptor A/B expression in superficial peritoneal endometriotic lesions was extremely heterogeneous. Bcl-2 immunostaining in endometriotic lesions was also variable, whereas Ki67 immunostaining was minimal. Menstrual cycle stage associations were limited in steroid hormone receptor and Bcl-2 expression in lesions. Patterns in progesterone receptor A/B and Bcl-2 immunostaining were associated with lesion location. Bcl-2 was differentially expressed, based on lesion gland morphology. CONCLUSIONS: These data demonstrate considerable diversity in the expression of steroid hormone receptors and Bcl-2 between lesions, even within an individual patient.

Gene expression profiles separate endometriosis lesion subtypes and indicate a sensitivity of endometrioma to estrogen suppressive treatments through elevated ESR2 expression.

BACKGROUND: Endometriosis is a common, gynaecological disease characterised by the presence of endometrial-like cells growing outside the uterus. Lesions appear at multiple locations, present with variation in appearance, size and depth of invasion. Despite hormones being the recommended first-line treatment, their efficacy, success and side effects vary widely amongst study populations. Current, hormonal medication for endometriosis is designed to suppress systemic oestrogen. Whether these hormones can influence the lesions themselves is not yet clear. Evidence of hormone receptor expression in endometriotic lesions and their ability to respond is conflicting. A variation in their expression, activation of transcriptional co-regulators and the potential to respond may contribute to their variation in patient outcomes. Identifying patients who would benefit from hormonal treatments remain an important goal in endometriosis research. METHODS: Using gene expression data from endometriosis lesions including endometrioma (OMA, n = 28), superficial peritoneal lesions (SUP, n = 72) and deeply infiltrating lesions (DIE, n = 78), we performed principal component analysis, differential gene expression and gene correlation analyses to assess the impact of menstrual stage, lesion subtype and hormonal treatment on the gene expression. RESULTS: The gene expression profiles did not vary based on menstrual stage, but could distinguish lesion subtypes with OMA significantly differentiating from both SUP and DIE. Additionally, the effect of oestrogen suppression medication altered the gene expression profile in OMA, while such effect was not observed in SUP or DIE. Analysis of the target receptors for hormonal medication indicated ESR2 was differentially expressed in OMA and that genes that correlated with ESR2 varied significantly between medicated and non-medicated OMA samples. CONCLUSIONS: Our results demonstrate of the different lesion types OMA present with strongest response to hormonal treatment directly through ESR2. The data suggests that there may be the potential to target treatment options to individual patients based on pre-surgical diagnoses.

The prognostic impact of peritoneal tumour DNA in gastrointestinal and gynaecological malignancies: a systematic review.

Peritoneal metastases from various abdominal cancer types are common and carry poor prognosis. The presence of peritoneal disease upstages cancer diagnosis and alters disease trajectory and treatment pathway in many cancer types. Therefore, accurate and timely detection of peritoneal disease is crucial. The current practice of diagnostic laparoscopy and peritoneal lavage cytology (PLC) in detecting peritoneal disease has variable sensitivity. The significant proportion of peritoneal recurrence seen during follow-up in patients where initial PLC was negative indicates the ongoing need for a better diagnostic tool for detecting clinically occult peritoneal disease, especially peritoneal micro-metastases. Advancement in liquid biopsy has allowed the development and use of peritoneal tumour DNA (ptDNA) as a cancer-specific biomarker within the peritoneum, and the presence of ptDNA may be a surrogate marker for early peritoneal metastases. A growing body of literature on ptDNA in different cancer types portends promising results. Here, we conduct a systematic review to evaluate the prognostic impact of ptDNA in various cancer types and discuss its potential future clinical applications, with a focus on gastrointestinal and gynaecological malignancies.

Do surgeons overestimate diaphragmatic peritoneal disease in interval debulking surgery of ovarian cancer?

INTRODUCTION: Cytoreductive surgery is a key point in ovarian cancer treatment. Substantial morbidity may be consecutive to this major radical surgery. However, the objective of no residual tumor (CC-0) had demonstrated its clear improvement of prognosis. Could macroscopically-driven interval debulking surgery (IDS) overestimate active cancer cells and be unnecessarily morbid? MATERIALS AND METHODS: This retrospective cohort study was conducted in Center Leon Berard Cancer Center between 2000 and 2018. We included women with advanced epithelial ovarian cancer who received neoadjuvant chemotherapy and underwent an IDS including resection of peritoneal metastases on the diaphragmatic domes. The primary endpoint was the pathological outcome of peritoneal resections of diaphragmatic domes. RESULTS: Peritoneal resections of diaphragmatic domes consisted of 117 patients. 75 patients required resection of nodules from the right cupola only, 2 patients from the left cupola only, and 40 patients bilaterally. Pathological analysis of the diaphragmatic domes found that 84.6% of samples demonstrated the presence of malignant cells, and only 12.8% found no tumor involvement. Pathology analysis could not be performed for 3 patients (2.6%) (vaporization). CONCLUSION: Surgical evaluation after neoadjuvant chemotherapy in ovarian cancer does not often overestimate peritoneal involvement by active carcinomatosis. Potential surgical morbidity due to peritoneal resection in IDS is admissible.

Comparison of the preventive effect of colchicine versus diphenhydramine, prednisolone, and a combination therapy on intraperitoneal adhesion bands: an experimental study in rats.

BACKGROUND: Peritoneal adhesion formation is an inevitable consequence of abnormal repair of the peritoneum following different peritoneal injuries of intra-abdominal operations with the subsequent morbidity that they represent. Vast efforts have been made to elucidate the cause and prevent the development of abdominal adhesions. The aim of our study is to compare the capability of colchicine versus diphenhydramine (DPH) and methylprednisolone (MP), and also prednisolone in adhesion prevention. METHODS: Sixty-one male Wistar stock rats were divided into four groups. The first group attended as the control group. Groups 2, 3, and 4 received oral combination of MP + DPH solution (20 mg/kg), colchicine (0.02 mg/kg), and prednisolone (1 mg/ kg), respectively. Adhesion bands were induced by standardized abrasion of the peritoneum through a midline laparotomy. All rats were sacrificed on the 15th-day post medication administration and the subjects underwent an exploratory laparotomy. The presence of adhesions was evaluated with the modified using Nair's classification. RESULTS: The proportion of the control group with substantial adhesion bands (73.3%) was significantly higher than that of the MP + DPH (13.3%), colchicine (33.3%), and prednisolone (31.3%) groups. There were significant differences between the scores of the control and the MP + DPH, colchicine, and prednisolone groups (P = 0.001, 0.028, and 0.019, respectively). There was no statistically significant difference to favor colchicine against MP + DPH (P = 0.390) or MP + DPH against prednisolone (P = 0.394). CONCLUSIONS: Both colchicine and combination of DPH + MP prevented postoperative abdominal adhesions separately in our study. However, the lowest adhesion formation rate was observed in the DPH + MP group, even lower than the prednisolone group.

The preventive effect of omega-3 fish oil on peritoneal adhesion formation.

INTRODUCTION: Postoperative peritoneal adhesions formed after abdominal surgery still continue to exist as an unresolved health problem. AIM: The aim of the present study is to examine whether omega -3 fish oil has a preventive effect on postoperative peritoneal adhesions. METHODS: Twenty-one female Wistar-Albino rats were separated into 3 groups (sham, control, and experimental group), each consisting of 7 rats. In sham group, only laparotomy was performed. Both in control and experimental group rats; the right parietal peritoneum and cecum were traumatized to form petechiae. Following this procedure, unlike the control group, the abdomen was irrigated with omega-3 fish oil in the experimental group. Rats were re-explored on the 14th postoperative day and adhesions were scored. Tissue samples and blood samples were taken for histopathological and biochemical analysis. RESULTS: None of the omega-3 fish oil given rats developed macroscopically postoperative peritoneal adhesion (P=0.005). Omega-3 fish oil formed an anti-adhesive lipid barrier on injured tissue surfaces. Microscopic evaluation revealed diffuse inflammation with excessive connective tissue and fibroblastic activity in control group rats while foreign body reactions were common in omega-3 given rats. The mean amount of hydroxyproline in samples from injured tissues was significantly lower in omega-3 given rats than in control rats. (P=0.004). CONCLUSION: Intraperitoneal application of omega-3 fish oil prevents postoperative peritoneal adhesions by forming an anti-adhesive lipid barrier on injured tissue surfaces. However, further studies are needed to determine whether this adipose layer is permanent or will be resorbed over time.

A Case of a Fixed Giant Peritoneal Loose Body outside the Peritoneum and near the Rectovesical Excavation.

A peritoneal loose body (PLB) is tissue completely separated from other intraperitoneal organs. It is rare and usually found incidentally during laparotomy, examination, or autopsy. PLBs are usually located free in the peritoneal cavity and not in the extraperitoneal space. They are thought to originate when epiploic appendices are released into the abdominal cavity after ischemic necrosis. We report a case of a giant PLB outside the peritoneal cavity, adjacent to the rectovesical excavation, that was identified preoperatively inan asymptomatic 83-year-old man undergoing evaluation for cholecystolithiasis. Computed tomography revealed a mass with well-defined margins in the rectovesical excavation. The mass (diameter, 60 mm) consisted of a calcified core and peripheral soft tissue and did not appear to invade adjacent organs. Although there were no symptoms or tumor growth over time, we scheduled a laparoscopic extraction for definitive diagnosis. On laparoscopic exploration, a white ovoid mass was found in the rectovesical excavation; there was no invasion of adjacent organs. We diagnosed a giant PLB. Postoperative recovery was uneventful. Most PLBs are asymptomatic and do not require surgery, except when symptoms are present, when the PLB is large, or when malignancy is suspected. PLB is rarely extraperitoneal and is usually freely mobile; however, in our patient, it was fixed and outside the abdominal cavity, near the rectovesical fossa. Although it could not be diagnosed preoperatively as being extraperitoneal, imaging findings were typical of PLB; thus, it was possible to remove the mass laparoscopically without bowel resection.

Robotic surgery in early and advanced ovarian cancer: Case selection for surgical staging and interval debulking surgery.

OBJECTIVE: During the last decade several case series have been published on robotic surgery in early and advanced stage ovarian cancer. Although most studies lack a significant oncological follow-up, more importantly criteria for patient selection for both robotic surgical staging (R-SS) and robotic interval debulking surgery (R-IDS) are not well defined. The objective of this study was to assess the surgical and oncological outcomes, using well-defined selection criteria, between robotic and open surgery in early and advanced stage ovarian cancer. STUDY DESIGN: Single-center retrospective case cohort study including 96 ovarian cancer patients. For early stage ovarian cancer, patients were selected for R-SS after laparoscopic salpingo-oophorectomy of a suspicious adnexal mass. For advanced stage ovarian cancer, only patients receiving neoadjuvant chemotherapy and IDS were included in the study. Exclusion criteria were the presence of residual peritoneal disease after NACT and/or patients requiring additional complex surgical procedures. RESULTS: For early stage ovarian cancer, similar median operative times were seen between R-SS and open surgical staging (O-SS), 132 min and 120 min respectively. Pelvic/para-aortic lymph node yield was similar between R-SS and O-SS, 22/11 nodes and 18/8 nodes respectively. Surgical upstaging occurred in 11.5% in the R-SS group and in 27.6% in the O-SS group. In advanced stage ovarian cancer, the BMI was significantly higher in the R-IDS group compared to the O-IDS group (27.8 vs 23.5; p =.006). The median follow was 52 months in the R-IDS group and 31 months in the O-IDS group. Recurrent disease occurred in 42.9% of the R-IDS group and in 45% of the O-IDS group. The length of hospitalization was significantly longer in the O-SS and O-IDS group (p <.00001). CONCLUSION: Patients with clinically early stage ovarian cancer, confirmed after laparoscopic removal of a suspicious adnexal mass, are candidates for R-SS whilst maintaining similar surgical and oncological outcome measures as O-SS. In advanced ovarian cancer, suitable candidates for R-IDS are those who receive NACT with good response and no residual peritoneal disease, especially in patients with a high BMI, but large prospective randomized trials with well-defined criteria are needed.

The preventive effect of omega-3 fish oil on the formation of peritoneal adhesions.

<br><b>Introduction:</b> Postoperative peritoneal adhesions that form after abdominal surgery still continue to exist as an unresolved health problem.</br> <br><b>Aim:</b> The aim of the study is to examine whether omega-3 fish oil has a preventive effect on postoperative peritoneal adhesions.</br> <br><b>Material and methods:</b> Twenty-one female Wistar albino rats were separated into 3 groups (sham, control and experimental), each consisting of 7 rats. In the sham group, only laparotomy was performed. In both the control and experimental group rats, the right parietal peritoneum and cecum were traumatised to form petechiae. Following this procedure, the abdomen was irrigated with omega-3 fish oil in the experimental group. The rats were re-explored on the 14^th postoperative day and any adhesions were scored. Tissue samples and blood samples were taken for histopathological and biochemical analysis.</br> <br><b>Results:</b> None of the rats that were administered omega-3 fish oil developed macroscopic postoperative peritoneal adhesions (P = 0.005). The omega-3 fish oil formed an anti-adhesive lipid barrier on the injured tissue surfaces. Microscopic evaluation revealed diffuse inflammation with excessive connective tissue and fibroblastic activity in the control group rats, while foreign body reactions were common in the omega-3 rats. The mean amount of hydroxyproline in samples from injured tissues was significantly lower in the omega-3 rats than in the control rats (P = 0.004).</br> <br><b>Conclusion:</b> Intraperitoneal application of omega-3 fish oil prevents postoperative peritoneal adhesions by forming an anti-adhesive lipid barrier on injured tissue surfaces. However, further studies are needed to determine whether this adipose layer is permanent or will be resorbed over time.</br>.

[Omental infarction, unusual cause of abdominal pain]. / Infarto omental, causa poco común de dolor adbominal.

INTRODUCTION: Omental infarction describes ischemic torsion of the distal portion of the omentum and constitutes an infrequent cause of acute abdominal pain in childhood of which few cases are known. Objec tive: To analyze through a clinical case the characteristics and management of this pathology, to consider this entity in the differential diagnosis of acute abdominal pain. CLINICAL CASE: An 11-year- old child consulted the emergency department due to a 48-hour history of continuous abdominal pain, which had progressively increased. On the physical examination, the patient presented pain in the right side of the abdomen and the epigastric area, with no signs of peritoneal irritation, and was overweight (BMI 91st percentile). Biochemical analysis showed a slight increase in c-reactive protein (CRP) 41.31 mg/L (reference value < 3.0 mg/L) without leukocytosis and normal ultrasound study, without visualization of the appendix. Due to persistent pain, increased CRP, and absence of appen dix visualization in the ultrasound, the study was completed with an abdomen and pelvis CT scan which showed trabeculation of the fat of the anterior right subhepatic space, thus diagnosing omental infarction. The patient was hospitalized for conservative management with analgesia, anti-inflamma tory drugs, and fluid therapy, presenting good evolution in the first 48 hours. CONCLUSION: Omental infarction is an infrequent cause of acute abdominal pain in childhood. Imaging studies play a funda mental role in the differential diagnosis of this entity with other clinical conditions of similar course, thus avoiding unnecessary surgical interventions.

Pancreatic herniation: a large pancreatic mass concealed within the intrathoracic cavity.

Cancer of unknown primary is a challenging entity. We present an elderly woman with metastatic cancer of unknown primary despite comprehensive imaging and immunohistochemical analysis. Based on a thorough history, a gastrointestinal source was suspected and a diagnosis of pancreatic cancer concealed within a type IV hiatal hernia was made using multimodal imaging. On review of prior imaging, due to the highly complex anatomy within our patient's hiatal hernia, the pancreatic mass was retroactively noted. While initial imaging may detect metastatic disease, identifying the primary malignancy requires a thorough history and physical examination, multimodal imaging where malignancy is suspected, and immunohistochemical analysis of metastatic deposits. Herniation of pancreatic cancer has not been previously described in the literature and serves as an important reminder of the importance of multimodal imaging in patients with significantly complex anatomy.

A network pharmacology approach to explore active compounds and pharmacological mechanisms of a patented Chinese herbal medicine in the treatment of endometriosis.

OBJECTIVE: Endometriosis is a common benign disease in women of reproductive age. Qu's formula (QUF) is a patented Chinese herbal medicine for treating endometriosis that has been proven to be effective in treating and preventing the recurrence of endometriosis. This study is aimed to discover its molecular mechanism and to explore the potential drug targets. METHODS: A QUF target and endometriosis-related gene set was identified by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases and five disease-gene databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, and a protein-protein interaction (PPI) network was established to discover the potential mechanism. MalaCards was searched for targets and signaling pathways related to endometriosis, and the search results were also used to identify the key factors in QUF. Molecular docking was performed to visualize the interactions between the effective molecules and proteins encoded by critical genes. Cell experiments and molecular dynamics (MD) simulations were used to further validate the therapeutic effects of the active compounds in QUF on endometriosis. RESULTS: A compound-target network with 117 nodes (94 genes and 23 active compounds) and 224 edges was generated. The results of GO and KEGG analyses indicated that QUF could act by regulating the immune response, apoptosis and proliferation, oxidative stress, and angiogenesis. VEGFA, CXCL8, CCL2, IL1B and PTGS2 were selected for molecular docking analysis from two critical subnetworks with high correlation scores in MalaCards, and the active compounds of QUF had binding potential and high affinity for them. The mRNA expression levels of CCL2, IL1B and PTGS2 significantly decreased after treatment with quercetin. MD simulations showed that the combinations of quercetin and these proteins were relatively stable. CONCLUSION: The network pharmacological strategy integrates molecular docking to unravel the molecular mechanism by which QUF protects against endometriosis. Our findings not only confirm the clinical effectiveness of QUF but also provide a foundation for further experimental study.

Immunoregulation by type I interferons in the peritoneal cavity.

The peritoneal cavity, a fluid-containing potential space surrounding the abdominal and pelvic organs, is home to a rich network of immune cells that maintain tissue homeostasis and provide protection against infection. However, under pathological conditions such as peritonitis, endometriosis, and peritoneal carcinomatosis, the peritoneal immune system can become dysregulated, resulting in nonresolving inflammation and disease progression. An enhanced understanding of the factors that regulate peritoneal immune cells under both homeostatic conditions and in disease contexts is therefore required to identify new treatment strategies for these often life-limiting peritoneal pathologies. Type I interferons (T1IFNs) are a family of cytokines with broad immunoregulatory functions, which provide defense against viruses, bacteria, and cancer. There have been numerous reports of immunoregulation by T1IFNs within the peritoneal cavity, which can contribute to both the resolution or propagation of peritoneal disease states, depending on the specifics of the disease setting and local environment. In this review, we provide an overview of the major immune cell populations that reside in the peritoneal cavity (or infiltrate it under inflammatory conditions) and highlight their contribution to the initiation, progression, or resolution of peritoneal diseases. Additionally, we will discuss the role of T1IFNs in the regulation of peritoneal immune cells, and summarize the results of laboratory studies and clinical trials which have investigated T1IFNs in peritonitis/sepsis, endometriosis, and peritoneal carcinomatosis.

Keratin Granulomas in the Peritoneum on Frozen Section: A Case Report with Multiple Suspects and the Search for the Culprit.

Keratin granulomas in the peritoneum are a rare finding with multiple etiologies and can be especially challenging for both the pathologist and the surgeon when these lesions are grossly visible. We report a case of a unique frozen section diagnostic scenario of evaluation of keratin granulomas in the peritoneum of a 47-year-old woman in the setting of multiple potential culprits: endometrial endometrioid adenocarcinoma following fertility sparing treatment, and a concurrent dermoid cyst. We discuss the various etiologies of keratin granulomas in the peritoneum, mechanism of their formation, diagnostic significance, as well as implications of fertility sparing treatments. To the best of our knowledge, this is the only case of keratin granulomas in the peritoneum with multiple distinct potential pathologic culprits as well the only case following fertility sparing treatment.

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.

PGE2 and Thrombin Induce Myofibroblast Transdifferentiation via Activin A and CTGF in Endometrial Stromal Cells.

Endometriosis is characterized by inflammation and fibrotic changes. Our previous study using a mouse model showed that proinflammatory factors present in peritoneal hemorrhage exacerbated inflammation in endometriosis-like grafts, at least in part through the activation of prostaglandin (PG) E2 receptor and protease-activated receptor (PAR). In addition, menstruation-related factors, PGE2 and thrombin (P/T), a PAR1 agonist induced epithelial-mesenchymal transition (EMT) of endometrial cells under hypoxia. However, the molecular mechanisms by which P/T induce development of endometriosis have not been fully characterized. To investigate the effects of P/T, RNA extracted from endometrial stromal cells (ESCs) treated with P/T were subjected to RNA sequence analysis, and identified activin A, FOS, and GATA2 as upregulated genes. Activin A increased the expression of connective tissue growth factor (CTGF) and mesenchymal marker genes in ESCs. CTGF induced the expression of fibrosis marker type I collagen, fibronectin, and α-smooth muscle actin (αSMA), indicating fibroblast to myofibroblast transdifferentiation (FMT) of ESCs. In addition, activin A, FOS, GATA2, CTGF, and αSMA were localized in endometriosis lesions. Taken together, our data show that P/T induces changes resembling EMT and FMT in ectopic ESCs derived from retrograde menstruation, and that these are associated with fibrotic changes in the lesions. Pharmacological means that block P/T-induced activin A and CTGF signaling may be strategies to inhibit fibrosis in endometriotic lesions.

Associations between body mass index and the surgical phenotype and location of endometriotic lesions.

RESEARCH QUESTION: Is there a relationship between body mass index (BMI) and endometriotic lesions, specifically surgical phenotype and lesion location? DESIGN: An observational retrospective cohort study at the Royal Women's Hospital, Melbourne, Australia, including 471 histologically confirmed endometriosis patients. Statistical analyses included multivariate logistic regression and multivariate modelling, correcting for multiple testing. Outcomes were the presence or absence of surgically classified lesion phenotypes, as per revised American Society for Reproductive Medicine criteria including superficial or deep, peritoneal or ovarian, and adhesions (Study I); and lesions at specific anatomical locations (including pelvic side wall, uterosacral ligament, pouch of Douglas, ovarian, uterovesical fold, bladder, and pararectal endometriosis) (Study II). RESULTS: In Study I, patients with higher BMI were more likely to have superficial peritoneal lesions (odds ratio [OR] 1.070, 95% confidence interval [CI] 1.004-1.144; P = 0.044), and less likely to have deep ovarian lesions (OR 0.928, 95% CI 0.864-0.993; P = 0.034). In Study II, patients with higher BMI were less likely to have uterovesical fold lesions (OR 0.927, 95% CI 0.867-0.985; P = 0.021) or anterior compartment lesions (OR 0.940, 95% CI 0.888-0.989; P = 0.023). After correcting for multiple testing, the relationship between BMI and lesion phenotypes did not persist (P > 0.01). CONCLUSIONS: This analysis does not conclusively support an influence of BMI on endometriotic lesion phenotype based on surgical classification or location. Further investigation of the physiological disturbances underlying BMI and the promotion of endometriotic lesion phenotypes and their location is warranted, but any effect is likely to be small.

Exosomes and their cargo are important regulators of cell function in endometriosis.

Endometriosis is a chronic oestrogen-dependent gynaecological disorder characterized by non-menstrual pelvic pain, infertility and the extrauterine growth of endometrial-like glands and stroma. It has been noted that the eutopic endometrium of women with endometriosis is functionally distinct from that of women without endometriosis. Moreover, ectopic endometrial implants are functionally different from the eutopic endometrium of women with endometriosis. However, the mechanisms directing these differences are ill-defined. It is proposed here that small membrane-bound extracellular vesicles called exosomes are important vehicles in the protection and transport of signalling molecules central to the dysregulation of endometrial function in women with endometriosis. Therefore, a critical review of the literature linking exosomes and their cargo to the pathobiology of endometriosis was conducted. Circulating peritoneal fluid and endometrial cell exosomes contained long non-coding RNA, miRNA and proteins involved in histone modification, angiogenesis and immune modulation that differed significantly in women with endometriosis compared with controls. Moreover, experimental evidence supports a role for exosomes and their cargo in angiogenesis, neurogenesis, immune modulation and endometrial stromal cell invasion. It is therefore suggested that exosomes play an important role in the pathophysiology of endometriosis.