Endometriosis Tissue Research Articles

Ectopic Breast Tissue in the Scar Endometriosis: A Case Report

Endometriozis uterus dışında endometrial stroma ve glandların ektopik yerleşimidir. Skar endometriozisi bu tablonun nadir bir formudur. Endometriozis vucutta en sık pelvik organlarda bulunur. Ekstragenital endometriozis ise vücudun her yerinde olabilir ( 1-2 ).Ektopik meme dokusu konjenital bir anomali olup aksilladan kasığa kadar süt çizgisinin herhangi bir yerinde olabilir( 3 ).Bu olguda ektopik gebelik nedeniyle salpingoooferektomi yapılıp yedi ay sonra karın ön duvarında ağrılı şişlik nedeniyle opere edilen hastaya ait biyopsi materyalinde endometriozis odağı içinde ektopik meme dokusunun görülmesi sunulmaktadır.

A Method of Improving Representation of Endometriosis Ultrasound Data By Using Local Phase Tissue Signatures

Study Objective Endometriosis is a gynecological condition affecting 10-15% of women in their reproductive years. Early and accurate diagnosis requires the development of noninvasive, cost effective and safe imaging technology. Ultrasound could overcome some of the MRI challenges. However, noise, high inter- and intra-variability during ultrasound imaging reduces image quality and reproducible reading. Deep learning has increased its role in imaging analysis and has been applied to automatic ultrasound image analysis. The main objective is the investigation of how new computational methods, can improve the representation of endometriosis tissue in ultrasound data. Design We have developed computational method for processing B-mode ultrasound data. Our algorithms are based on the extraction of local phase tissue signatures, are intensity invariant. These features are not affected by the ultrasound transducer operating frequency, ultrasound machine settings, and the body mass index of the patient. Setting Clinical ultrasound sites. Patients or Participants The proposed computational methods will be validated on 3D ultrasound images obtained from the standard transvaginal ultrasound examinations. Interventions Both RF signals and B-mode data will be normalized to [-1, 1] and then rescaled to size (4096, 256, number of slices) using bilinear interpolation before inputting to our proposed networks. Training of the proposed CNNs will be achieved by investigating various methods based on gradient descent and variants such as adam, adagrad, adelta. Measurements and Main Results 100 B-mode US and RF US scans will be collected from each patient bringing the dataset size to 27,400 (B-mode and RF US). A sample size of 274 (137 healthy,137 diseased) subjects is sufficient to estimate a high Area Under the Curve. Conclusion New tissue signatures provide valuable information and improved representation of the endometriosis. Future work will involve the development of artificial intelligence, specifically methods based on deep learning, methods to derive models that yield individual-level accurate, early diagnosis in the context of endometriosis management.

Insight into epigenetics of human endometriosis organoids: DNA methylation analysis of HOX genes and their cofactors

To evaluate and compare the methylation pattern of Human Homeobox (HOX) clusters (A-D) and HOX cofactors in normal, eutopic, and ectopic endometrial tissues with ectopic and eutopic endometriosis organoids as advanced preclinical research models. A chromatin immunoprecipitation (ChIP) array containing 84 genes was used to analyze methylation levels of HOX clusters (A-D) and HOX cofactors in normal, eutopic, and ectopic endometrial biopsy specimens as well as ectopic and eutopic endometriosis organoids. Reproductive biomedicine and cell science research centers. Nine healthy women without endometriosis (control) and 16 women diagnosed with endometriosis. Ectopic endometrial lesions were obtained using a laparoscopic procedure, and eutopic and control endometrium biopsy specimens were obtained using pipelle sampling. Methylation levels of HOX clusters (A-D) and HOX cofactors in eutopic and ectopic endometrial biopsy specimens, as well as eutopic and ectopic endometriosis organoids and normal endometrium. Most HOX clusters (A-D) and HOX cofactors showed methylation alterations in ectopic/eutopic endometrial tissues and ectopic/eutopic endometriosis organoids compared with normal endometrium. These methylation alterations had the same pattern in ectopic/eutopic tissue biopsy specimens and ectopic/eutopic endometriosis organoids in most genes. A contrariwise methylation pattern was observed in 28 of 84 genes in the ectopic/eutopic tissue biopsy specimens and ectopic/eutopic endometriosis organoids. Because a conserved pattern of methylation alterations in endometriosis tissues and organoids was observed for most of the investigated genes (56 of 84), it can be concluded that endometriosis organoids maintain epigenetic changes. Therefore, our study suggests endometriosis organoids as a novel preclinical model to determine the epigenetic mechanisms that underlie endometriosis.

Inhibitory effect of resveratrol on the growth and angiogenesis of human endometrial tissue in an In Vitro three-dimensional model of endometriosis

Endometriosis is a chronic estrogen-dependent disorder and one of the most common causes of infertility in women. Resveratrol (RES) is a polyphenolic and phytoestrogenic compound with anti-oxidative, anti-inflammatory, anti-angiogenic, and anti-estrogenic properties. The aim of the present study was to investigate the effect of different concentrations of RES on human endometrial growth and angiogenesis in an in vitro three-dimensional (3D) model of endometriosis.Human endometrial tissues of endometriosis (endometriotic) and normal (endometrial) subjects (n = 9/groups) were biopsied in sterile conditions and cut into 1 × 2 mm pieces. Tissue fragments of each biopsy were given concentrations of 0 (control), 10, 50, 100 and 200 μM RES for 21 days in 3D culture condition using fibrin as an extracellular matrix. Scoring methods were used for tissue changes, including; cellular invasion, monolayer formation and angiogenesis. Nitric oxide (NO) was measured using Griess's reaction, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the apoptotic gene expression.The mean of growth scores of endometriotic and endometrial tissue showed a significant dose dependent inhibition (P < 0.05). The levels of NO also significantly decreased in different groups. Apoptotic genes (P53, Bax, Bcl2 and caspase 3) and Sirt1 showed a significant increase in various concentrations of RES in both tissues (P < 0.05).RES exert dose- and time-dependent inhibitory effects on human endometrial tissue, and its higher doses suggested it as a natural supplement to inhibit the growth and treatment of endometriosis.

Using Raman Spectroscopy to Investigate the Molecular Level Characteristics of Endometriosis

Endometriosis is a benign gynecologic disorder. It is particularly common among young women and may make pregnancy difficult. In this study molecular level characterization of endometriosis tissues were performed using Raman spectroscopy in combination with multivariate statistical analysis. Three hundred sixty six Raman spectra recorded from different points of seventy two tissue samples, taken from the cyst walls of twelve patients were examined. Principle component analysis (PCA) followed by linear discriminant analysis (LDA) were performed on the Raman data, and the samples were then classified into three groups: severe, moderate, and weak endometriosis. In the severe endometriosis group, the relative band intensities of DNA were increased. Moreover, increase in pyrrole moieties and kynurenine were seen. The results show that endometriosis severity correlates to increase in DNA concentration, and degradation of tryptophan due to increased indoleamine-pyrrole 2,3-dioxygenase (IDO) activity, and an increase in kynurenine concentration and pyrrole intermediate. It is concluded that Raman spectroscopy is capable of providing a quick diagnosis, ahead of the pathology result being reported.

Oestrogen induces epithelial-mesenchymal transition in endometriosis via circ_0004712/miR-148a-3p sponge function.

Endometriosis is a common, chronic gynaecologic disease affecting up to 10% of women in their reproductive age and leading to pain and infertility. Oestrogen (E2)‐induced epithelial‐mesenchymal transition (EMT) process has been considered as a key factor of endometriosis development. Recently, the dysregulated circular RNAs (circRNAs) have been discovered in endometriosis tissues. However, the molecular mechanism of circRNAs on the E2‐induced EMT process in endometriosis is still unknown. Here, we demonstrated that circ_0004712 up‐regulated by E2 treatment in endometrial epithelial cells. Knock‐down the expression of circ_0004712 significantly suppressed E2‐induced cell migration activity. Meanwhile, we identified miR‐148a‐3p as a potential target miRNA of circ_0004712. Inhibited the expression of miR‐148a‐3p could recovered the effect of circ_0004712 knock‐down in E2‐treated endometrial epithelial. Furthermore, Western blot assay showed that E2 treatment could increase the expression and activity of β‐catenin, snail and N‐cadherin and reduce the expression of E‐cadherin. The expression and activity of β‐catenin pathway were recovered by circ_0004712 knock‐down or miR‐148a‐3p overexpression. Altogether, the results demonstrate that circ_0004712/miR‐148a‐3p plays an important role in E2‐induced EMT process in the development of endometriosis, and the molecular mechanism may be associated with the β‐catenin pathway. This work highlighted the importance of circRNAs in the development of endometriosis and provide a new biomarker for diagnosis and therapies.

Possibility of Targeting Claudin-2 in Therapy for Human Endometrioid Endometrial Carcinoma.

Claudin-2 (CLDN-2) is a leaky-type tight junction protein, and its overexpression increases tumorigenesis of some types of cancer cells. In the present study, to examine the possibility of targeting CLDN-2 in the therapy for endometrioid endometrial adenocarcinoma, we investigated the regulation and role of CLDN-2 in endometriosis and endometrioid endometrial adenocarcinoma. In endometrioid endometrial adenocarcinoma tissues, marked upregulation of CLDN-2 was observed together with malignancy, while in endometriosis tissues, a change in the localization of CLDN-2 was observed. In cells of the endometrial adenocarcinoma cell line Sawano, which highly express CLDN-2, downregulation of CLDN-2 induced by the siRNA upregulated the epithelial barrier and inhibited cell migration. Furthermore, the downregulation of CLDN-2 affected the cell cycle and inhibited cell proliferation. In Sawano cells cultured with high-glucose medium, CLDN-2 expression was downregulated at the mRNA and protein levels. The high-glucose medium upregulated the epithelial barrier, cell proliferation, and migration, and inhibited cell invasion. The histone deacetylase (HDAC) inhibitor tricostatin A (TSA), which has antitumor effects, downregulated CLDN-2 expression, cell proliferation, invasion, and migration, and upregulated the epithelial barrier. The mitochondrial respiration level, an indicator of cancer metabolism, was downregulated by CLDN-2 knockdown and upregulated by the high-glucose condition. Taken together, these results indicated that overexpression of CLDN-2 closely contributed to the malignancy of endometrioid endometrial adenocarcinoma. Downregulation of CLDN-2 via the changes of the glucose concentration and treatment with HDAC inhibitors may be important in the therapy for endometrial cancer.

Analysis of mRNA expression and DNA methylation level of RAC1 gene encoding focal adhesion molecule in endometrial and peritoneal endometriosis

Focal adhesion molecules involve in cellular migration, attachment, and play a role in endometriosis pathomechanisms. Recent studies showed that the expression of RAC1, a gene encoded focal adhesion molecule, was predominantly found in endometriosis. As gene expression may be regulated by DNA methylation. Therefore, this study aimed to analyze promoter methylation level of RAC1 gene and mRNA expression in endometrial and peritoneal endometriosis tissues. This study using 20 endometrial and 9 peritoneal tissues from the same patients and 20 normal endometrial. The DNA and RNA from samples were isolated, DNA was converted using sodium bisulfite and amplified using Methyl Specific Polymerase Chain Reaction (MSP) method. The methylation level was determined by the intensity measurement of the bands that arose in gel electrophoresis using ImageJ software, whereas mRNA expression level was measured by Reverse Transcription-quantitative PCR (RT-qPCR) method. The mRNA expression level of RAC1 gene in peritoneal endometriosis increased compared to normal endometrium, as well as compared to endometrial endometriosis, but there was no significant difference in endometrial endometriosis compared to normal. Promoter hypermethylation level of RAC1 gene in peritoneal endometriosis was significantly different compared to normal endometrium, however not significant to endometrial endometriosis. Methylation level of its gene in endometrial endometriosis shown no significant difference compared to normal. There was association between promoter hypermethylation level and its mRNA expression in endometrial endometriosis (R= 0.014; p=0.952). The elevation of mRNA expression of RAC1 gene plays a role in endometrial cell migration to peritoneum, and associated with promoter hypermethylation level of its gene.

LncRNA SNHG4 promotes the increased growth of endometrial tissue outside the uterine cavity via regulating c-Met mediated by miR-148a-3p

Long noncoding RNAs (lncRNAs) modulate endometriosis. The current study investigated the mechanisms and effects of SNHG4 on endometriosis. The qRT-PCR was conducted to examine the miR-148a-3p and SNHG4 expressions in endometriosis tissues. The 5-ethynyl-2′-deoxyuridine incorporation assay and 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay were used to measure the rate of cell proliferation. The association between miR-148a-3p, SNHG4 and c-Met was confirmed via bioinformatical approach and luciferase reporter gene assay. Also, the function of SNHG4 on the growth of endometriotic lesions was investigated in vivo. The SNHG4 expression was considerably upregulated in endometriosis tissues, whereas the level of miR-148a-3p expression was reduced. In addition, SNHG4 can be considered as ceRNAs that bind miR-148a-3p and rise the proliferation activity of HESCs by downregulating miR-148a-3p. Furthermore, silencing SNHG4 could downregulate the c-Met level by enhancing miR-148a-3p expression, and finally inhibiting endometriosis development in vivo. LncRNA SNHG4 promotes the increased growth of endometrial tissue outside the uterine cavity via regulating c-Met mediated by miR-148a-3p, which may be used as diagnostic biomarker as well as molecular target in the treatment of endometriosis.

MiR-17-5p mitigates endometriosis by directly regulating VEGFA

Endometriosis is a common disease in women, which impairs the quality of life in patients. Recently, accumulating evidences reported that miRNAs play an essential role in diagnosis and treatment of endometriosis. However, the regulatory mechanism of miRNAs has not been fully explored. The expression of miR-17-5p and VEGFA was detected using qRT-PCR. The protein level of VEGFA was measured via Western blot. Cell proliferation was determined by CCK-8 assay. Cell migration and invasion were measured via transwell assay. The relationship of miR-17-5p and VEGFA were verified via luciferase reporter assay. Then miR-17-5p was remarkably down-regulated in endometriosis tissues, serums and cells, and overexpression of miR-17-5p inhibited cell proliferation, migration and invasion in endometriosis. Results showed that VEGFA was significantly up-regulated in endometriosis tissues and cells and acted as a target of miR-17-5p. Moreover, miR- 17-5p negatively regulated VEGFA expression in endometriosis. Otherwise, up-regulation of VEGFA improved cell proliferative, migrated and invasive ability in ECSCs with transfection of miR-17-5p mimics group. Our data showed miR-17-5p inhibits cell proliferation, migration and invasion in endometriosis by directly repressing VEGFA expression.

Bioinformatic analysis reveals the importance of epithelial-mesenchymal transition in the development of endometriosis

Background: Endometriosis is a frequently occurring disease in women, which seriously affects their quality of life. However, its etiology and pathogenesis are still unclear. Methods: To identify key genes/pathways involved in the pathogenesis of endometriosis, we recruited 3 raw microarray datasets (GSE11691, GSE7305, and GSE12768) from Gene Expression Omnibus database (GEO), which contain endometriosis tissues and normal endometrial tissues. We then performed in-depth bioinformatic analysis to determine differentially expressed genes (DEGs), followed by gene ontology (GO), Hallmark pathway enrichment and protein-protein interaction (PPI) network analysis. The findings were further validated by immunohistochemistry (IHC) staining in endometrial tissues from endometriosis or control patients. Results: We identified 186 DEGs, of which 118 were up-regulated and 68 were down-regulated. The most enriched DEGs in GO functional analysis were mainly associated with cell adhesion, inflammatory response, and extracellular exosome. We found that epithelial-mesenchymal transition (EMT) ranked first in the Hallmark pathway enrichment. EMT may potentially be induced by inflammatory cytokines such as CXCL12. IHC confirmed the down-regulation of E-cadherin (CDH1) and up-regulation of CXCL12 in endometriosis tissues. Conclusions: Utilizing bioinformatics and patient samples, we provide evidence of EMT in endometriosis. Elucidating the role of EMT will improve the understanding of the molecular mechanisms involved in the development of endometriosis.

G protein-coupled estrogen receptor 1 expression in normal myometrium, leiomyoma, and adenomyosis tissues of premenopausal women

To verify the different expression of G protein-coupled estrogen receptor 1 (GPER1) among normal uterine, leiomyoma, and adenomyosis tissues. Normal uterine, leiomyoma, and adenomyosis tissue samples were obtained from women aged 35–52 years from a tertiary university hospital. The tissue samples were subjected to immunohistochemical, Western blot, and reverse-transcription polymerase chain reaction (RT-PCR) analyses of GPER1. GPER1 protein expression was confirmed in the tissues by immunohistochemical and Western blot analyses and compared with GPER1 mRNA levels using RT-PCR. GPER1 was detected in the tissue samples of leiomyoma and adenomyosis, which are estrogen-dependent diseases. GPER1 expression was similar between normal uterine and leiomyoma tissues but was reduced in adenomyosis tissue. The level of phosphorylated extracellular signal-regulated kinases 1/2 was lower and higher in leiomyoma and adenomyosis tissues, respectively, than in normal tissue, but the differences among the groups were not statistically significant. Our immunohistochemical, Western blot, and RT-PCR results suggest that GPER1 expression is involved in cell proliferation in leiomyoma and in cell invasion and migration in adenomyosis. Functional studies of GPER1 involving larger sample sizes should be performed to confirm the adenomyosis and leiomyoma disease mechanisms and eventually to develop new therapeutic interventions for these diseases.

Focal Adhesion Kinase-Mediated Sequences, Including Cell Adhesion, Inflammatory Response, and Fibrosis, as a Therapeutic Target in Endometriosis.

Endometriosis has several distinguishing features in the ectopic endometrium, including chronic inflammation and fibrosis. According to the retrograde menstruation theory, endometriotic cells are derived from eutopic endometrial cells, and adhesion of endometrial cells to the extracellular matrix can be the initial step in the development of endometriosis. Therefore, we hypothesized that cell adhesion, which mediates a sequence of events in the development of endometriosis triggering inflammatory responses and tissue fibrosis could be a possible therapeutic target for endometriosis. We found co-upregulation of focal adhesion kinase (FAK) and monocyte chemoattractant protein-1 (MCP-1) in the endometriotic tissues compared with that in the normal endometrium. MCP-1 secretion was significantly higher in the endometriotic stromal cells than in the eutopic endometrial stromal cells. Furthermore, co-culture of U937 cells and endometriotic stromal cells upregulated secretion of transforming growth factor-β1 (TGF-β1). A FAK inhibitor significantly inhibited the secretion of MCP-1 in the endometriotic stromal cells and TGF-β1 in the co-culture with macrophages. FAK inhibitor treatment in the murine endometriosis model demonstrated a decrease in the formation of endometriotic lesions as well as the expression of MCP-1 and TGF-β1. Our results suggest that the FAK-mediated sequential development of endometriosis, including inflammatory response and tissue fibrosis, can be a new therapeutic target in endometriosis.

Nanoparticle-Based Platform for Activatable Fluorescence Imaging and Photothermal Ablation of Endometriosis.

Endometriosis is a painful disorder where endometrium-like tissue forms lesions outside of the uterine cavity. Intraoperative identification and removal of these lesions are difficult. This study presents a nanoplatform that concurrently delineates and ablates endometriosis tissues using real-time near-infrared (NIR) fluorescence and photothermal therapy (PTT). The nanoplatform consists of a dye, silicon naphthalocyanine (SiNc), capable of both NIR fluorescence imaging and PTT, and a polymeric nanoparticle as a SiNc carrier to endometriosis tissue following systemic administration. To achieve high contrast during fluorescence imaging of endometriotic lesions, nanoparticles are constructed to be non-fluorescent prior to internalization by endometriosis cells. In vitro studies confirm that these nanoparticles activate the fluorescence signal following internalization in macaque endometrial stromal cells and ablate them by increasing cellular temperature to 53 ° C upon interaction with NIR light. To demonstrate in vivo efficiency of the nanoparticles, biopsies of endometrium and endometriosis from rhesus macaques are transplanted into immunodeficient mice. Imaging with the intraoperative Fluobeam 800 system reveals that 24 h following intravenous injection, nanoparticles efficiently accumulate in, and demarcate, endometriotic grafts with fluorescence. Finally, the nanoparticles increase the temperature of endometriotic grafts up to 47 °C upon exposure to NIR light, completely eradicating them after a single treatment.

Analysis of DNA methylation and its correlation with mRNA expression of epidermal growth factor receptor encoding for cytoskeleton regulating protein in peritoneal endometriosis tissue

It has been known that the EGFR have the role for regulation the cytoskeleton activity and its expression increased in endometriosis tissue. The aim of this study was to evaluate the DNA methylation of the EGFR gene that might cause the alteration of its mRNA expression in peritoneal endometriosis tissue. Samples were peritoneal endometriosis tissue from 20 endometriosis patients and 20 female of non-endometriosis patients. The DNA methylation of the EGFR gene was analyzed by the method of Methylation Specific PCR and ImageJ software, while its expression of mRNA were analyzed by the method of qRT-PCR. The DNA methylation in the EGFR gene in peritoneal endometriosis tissues increased compared to normal endometrial tissues (peritoneal endometriosis tissue = 56%, normal endometriosis tissue = 19%). The expression of mRNA EGFR gene in endometriosis peritoneal tissues was 1.341 fold increased relative to normal endometrium. There is no significant correlation between the DNA methylation with expression of mRNA EGFR (p = 0.947 and r = -0.016). Increasing of EGFR mRNA expression in endometriosis tissue that was not caused by alteration of its DNA methylation, have to play a role in the pathogenesis of endometriosis.

The Suppression Effect of Kebar Extract on Endometriosis Lesion MDA and TNF -a Independent to VEGF A Study in Endometriosis Mice Mode

Background: The pathogenesis of endometriosis remains unclear, and involves multifactorial etiologies. The increase in oxidative stress is known to be associated with this disease. Oxidative stress increases angiogenesis and supports the proliferation of endometriosis tissue in the peritoneal cavity. Kebar grass, a medicinal plant, is expected to increase antioxidant defense resulting in decreased oxidative stress, inflammation, angiogenesis, and reduced endometrial tissue implants.&#x0D; &#x0D; Objective: To investigate the effects of Kebar grass extract administration to MDA serum levels, TNF-a and VEGF expression, and the extension of the endometriotic lesions in mice model.&#x0D; &#x0D; Methods: This study was experimentally designed. It was conducted in the Department of Obstetrics Gynecology, Faculty of Medicine Diponegoro, University and Faculty of Veterinary Medicine, Airlangga University. Twenty-one mice were divided into three groups: the first group is control of 7 untreated endometriosis mice model, the second group consisted of 7 mice injected with leuprolide acetate 1mg/kgBB single dose, and the last group consisted of 7 mice fed with Kebar grass extract 3mg/day for 14 days. MDA serum level was measured by spectrophotometry, TNF-a and VEGF expression by IHC using Rammele Scale Index (ImmunoReactive Score), whereas the extension of the endometriotic lesions was measured using computerize tracing.&#x0D; &#x0D; Results: Both Kebar grass extract and leuprolide acetate administration significantly decrease MDA serum levels in endometriosis mice model, compare with the control group, (0.09±0.02 nmol, 0.11±0.07 nmol, and 0.30±0.06 nmol, respectively; p=0.001). TNF-α expression of the group treated with Kebar grass extract was lower than leuprolide acetate and control group (2.43±1.521 %, 4.86±0.458 %, and 7.26±2.898 %, respectively; p=0.002). However, there was no significant difference in VEGF expression among study groups (4.34±2.40 %, 5.11±1.95 %, and 7.40±3.49 % respectively; p=0.116). Finally, the extension of the endometriotic lesions of the mouse models administered with Kebar grass extract and leuprolide acetate was smaller than the control group (0 mm2, 4.54±7.75 mm2, and 34.80±13.09 mm2 respectively; p=0.005).&#x0D; &#x0D; Conclusion: Kebar grass extract has the effect of decreasing MDA serum levels and reducing TNF-α expression, resulted in smaller endometriotic lesions in mice, even though it does not affect VEGF expression.&#x0D; &#x0D; Keywords: malondialdehyde, tumour necrosis factor alpha, vascular endothelial growth factor, endometriotic lesion, kebar grass extract, endometriosis mouse

Diagnosis, Surgical treatment and Postoperative outcomes of Hepatic Endometriosis: A systematic review

Background: Endometriosis is a chronic estrogen dependent disorder characterized by the presence of endometrial-like tissue and stroma in extra-uterine locations. Hepatic endometriosis (HE) is one of the rarest forms of extrapelvic endometriosis. The objective of our systematic review was to summarize the existing evidence on HE with special consideration to the natural history, the diagnosis and the surgical treatment. Materials and Methods: Three electronic databases were systematically searched for articles published up to January 2019. All appropriate observational studies and case reports addressing cases of women with HE were considered eligible for inclusion in the present systematic review. Results: A total of 28 studies (24 case reports and 4 case series) which comprised 33 patients with a mean age of 39.1 years who were diagnosed with HE were included. Ten (62.5%) were nulliparous and 25 (75.7%) were women were of reproductive age while 20 women were premenopausal (60.6%) and 13 (39.4%) were postmenopausal. Thirteen patients (41.9%) had a history of pelvic endometriosis of various sites and 16 (50%) had a history of prior gynecologic surgery. Abdominal pain was the primary symptom in 29 patients (87.8%). Six patients underwent a preoperative diagnostic procedure with biopsy or fine needle aspiration. In 2 of them histology revealed endometrial tissue but diagnosis of endometriosis was not clear. Sixteen women (50%) underwent cyst excision and pericystectomy while the remaining underwent minor or major hepatectomies (n=8/32, 25% and n=8/32, 25%, respectively). One case of bile leak was recorded. Conclusions: Preoperative diagnosis of HE is challenging, regardless, it should be considered in the differential diagnosis of a hepatic mass especially in premenopausal women with a history of endometriosis of other sites. According to our review, hepatic resections for HE in selected patients are safe and present with favorable outcomes with regards to recurrence.

Natural history, Diagnosis, Surgical treatment and Postoperative outcomes of Hepatic Endometriosis: A systematic review

Background: Endometriosis is a chronic estrogen dependent disorder characterized by the presence of endometrial-like tissue and stroma in extra-uterine locations. Hepatic endometriosis (HE) is one of the rarest forms of extrapelvic endometriosis. The objective of our systematic review was to summarize the existing evidence on HE with special consideration to the natural history, the diagnosis and the surgical treatment. Materials and Methods: Three electronic databases were systematically searched for articles published up to January 2019. All appropriate observational studies and case reports addressing cases of women with HE were considered eligible for inclusion in the present systematic review. Results: A total of 28 studies (24 case reports and 4 case series) which comprised 33 patients with a mean age of 39.1 years who were diagnosed with HE were included. Ten (62.5%) were nulliparous and 25 (75.7%) were women were of reproductive age while 20 women were premenopausal (60.6%) and 13 (39.4%) were postmenopausal. Thirteen patients (41.9%) had a history of pelvic endometriosis of various sites and 16 (50%) had a history of prior gynecologic surgery. Abdominal pain was the primary symptom in 29 patients (87.8%). Six patients underwent a preoperative diagnostic procedure with biopsy or fine needle aspiration. In 2 of them histology revealed endometrial tissue but diagnosis of endometriosis was not clear. Sixteen women (50%) underwent cyst excision and pericystectomy while the remaining underwent minor or major hepatectomies (n=8/32, 25% and n=8/32, 25%, respectively). One case of bile leak was recorded.Tabled 1Main characteristics of the included patientsTotal patients32AgeMean age ±SD (years)39.7±8.9518-45 years N(%)24 (75)>45 years N(%)8 (25)ParityNulliparous N(%)10/16 (62.5)Multiparous N(%)6/16 (37.5)Menopausal statusPremenopausal N(%)19 (59.4%)Postmenopausal N(%)13 (40.6%)History of pelvic endometriosis N(%)11/30 (36.7)Previous pelvic ob/gyn surgery N(%)16/32 (50%)Disease related symptoms/examination/ imagingAbdominal Pain28Asymptomatic4Nausea and vomit4Palpable mass7Ascites and jaundice1Abnormal liver function3intra- and postoperative outcomesType of surgeryCyst excision/ pericystectomy N(%)16 (48.4%)Minor hepatectomy N(%)8 (25.8)Major hepatectomy N(%)8 (25.8)Surgical ApproachOpen N(%)28 (87.5)Laparoscopic N(%)4Postoperative complicationsBile leak N(%)1Recurrence N(%)1 Open table in a new tab Conclusions: Preoperative diagnosis of HE is challenging, regardless, it should be considered in the differential diagnosis of a hepatic mass especially in premenopausal women with a history of endometriosis of other sites. According to our review, hepatic resections for HE in selected patients are safe and present with favorable outcomes with regards to recurrence.

Progesterone and estradiol receptors and Ki-67 in the superficial and deep infiltrating endometriosis

ABSTRACT Introduction: Endometriosis is a hormone-dependent disease characterized by ectopic presence of endometrial tissue responsive to ovarian steroids. Estrogen and progesterone are the main regulators of endometrial tissue, and the expression of receptors of these hormones in the ectopic tissue seems to be related to the pathophysiology of the disease. Ki-67 is a marker of tissue proliferation and an important marker of epithelial kinetics. Endometriosis can be classified as superficial, in the peritoneum, and deep, when it extends into ligaments and other organs. Objective: Our objective was to analyze the expression of estrogen and progesterone receptors and Ki-67, through immunohistochemistry, in different sites of endometriosis tissues (superficial peritoneal/ovarian endometriosis and deep infiltrating endometriosis). Casuistic and methods: We studied nine patients; five with superficial and four with deep endometriosis. Statistical correlation was performed with the Shapiro-Wilk test (significance level of 5%) and linear correlation analysis using Spearman’s non-parametric test (significance of 1%). There was a correlation of Spearman between the estrogen receptor variable and Ki-67 in patients with superficial endometriosis. There was also a correlation between the variables estrogen receptor and progesterone receptor in patients with deep endometriosis. Results: Contrary to what was found for superficial endometriosis, there is linear increase of the variables, with a strong and positive correlation coefficient. This demonstrates that the variation of estrogen receptors can be explained in 99.1% by the same variation of progesterone receptors in deep endometriosis. Conclusion: It is possible to infer that other factors are involved in the response to hormonal variations for superficial and deep endometriosis.

Hyperbaric Oxygen (HBO) Reduce Expression of Hypoxia Inducible Factor-1 Alpha (HIF-1 alpha) and Endometriotic Tissue Size in Mice Model of Endometriosis

Hypoxia in endometriosis will increase the expression of Hypoxia Inducible Factor-1alpha (HIF1alpha) and its expression could be decreased by Hyperbaric Oxygen (HBO). This study aimed to analyze the effect of HBO 2.4 ATA for 3x30 minutes per day for 10 days on the expression of HIF-1 alpha and endometriotic tissue size on mice model of endometriosis. This study was an experimental laboratory study with a separate pretest-posttest control group design. The mice were divided into three groups, the first was a pretest control group (which describes the condition after endometrium transplantation), the second was the endometriotic group that received hyperbaric oxygen, and the third was the endometriotic group that did not receive hyperbaric oxygen therapy. The endometriosis implant size in the peritoneal tissue was assessed and the immunohistochemistry examination was conducted to determine the expression of HIF-1 alpha. The endometriosis tissue size was reduced in the HBO group compared to the control and nonHBO group. The lowest expression of HIF-1 alpha was significantly found in HBO over the other group. The decrease of HIF1 alpha expression mediates the reduction of size endometriotic tissue due to the therapy of HBO.