Deep Infiltrating Endometriosis Lesions Research Articles

Associated ileocaecal location is a marker for greater severity of low rectal endometriosis.

To determine whether ileocaecal endometriosis (ICE) is a marker for low rectal endometriosis (LRE) severity. Retrospective cohort study. France. Analysis of 375 colorectal resections performed in women undergoing complete surgery for LRE from January 1995 to December 2015 in a university centre for endometriosis. Univariate and multivariate analysis of anatomical, postoperative clinical, and long-term outcomes according to presence of ICE. Mean number and type of deep infiltrating endometriosis (DIE) lesions, the existence of an associated endometrioma, and mean total American Society for Reproductive Medicine (ASRM) score. The prevalence of ICE was 25.6%. Primary end-point data showed that women with ICE had a significantly higher adjusted number of DIE lesions (OR = 1.43, 95% CI 1.02-3.03; P=0.048), higher prevalence of endometriomas (OR=1.91, 95% CI 1.04-3.51; P=0.044), more associated DIE sigmoid lesions (OR=2.12, 95% CI 1.07-3.91; P=0.025), and a higher mean total ASRM score (OR=2.07, 95% CI 1.12-4.14; P=0.025). Women with ICE resected during the surgical procedure for LRE did not have more adverse postoperative clinical outcomes than ICE-negative patients. Ileocaecal endometriosis was significantly associated with greater LRE severity. In a complete surgical resection strategy, combining resection of ICE and LRE did not appear to increase postoperative rates of complications, morbidity or recurrence, nor did it seem to impair long-term clinical outcomes. In women with low rectal endometriosis, 25% have an associated ileocaecal location that is a marker for severity.

Perineural invasion in endometriotic lesions contributes to endometriosis-associated pain

PurposeRecent studies have shown that abnormal distribution of pelvic nerves contributes to endometriosis-associated pain. However, the relationship between neurogenesis and pain severity in endometriosis still remains uncertain, which makes it an enigma for both gynecologists as well as neuropathologists. In this study, we tried to explore a special phenomenon, perineural invasion (PNI), in deep infiltrating endometriosis (DIE) and investigated the correlation between PNI- and DIE-associated pain.Patients and methodsThe study was conducted in the Department of Obstetrics and Gynecology of the First Affiliated Hospital of Sun Yat-sen University from June 2012 to January 2015. In total, 64 patients with DIE were enrolled. They received laparoscopically surgical resection of endometriotic lesions. The Kruskal–Wallis and Mann–Whitney tests were used for comparisons of enumeration data. Spearman rank correlation was used for linear analysis.ResultsImmunohistochemical analysis demonstrated that PNI was commonly found in DIE lesions. Patients were divided into PNI (+) group and PNI (−) group. The visual analog scale scores of dysmenorrhea, dyspareunia, and chronic pelvic pain were higher in PNI (+) group than in PNI (−) group. Also, we found significantly increased density of newly formed nerve fibers as well as microvessels in lesions of PNI (+) group. Further, double immunofluorescence showed a closely spatial nerve–vessel network in the endometriotic lesion of PNI (+) group. More importantly, correlation analysis revealed positive relation between the density of newly formed nerve fibers in the lesion and the density of microvessels in lesions of PNI (+) group.ConclusionThis study suggests that PNI in endometriotic lesions plays an important role in endometriosis-associated pain, mainly through a mechanism named “neuroangiogenesis”.

Dienogest therapy during the early stages of recurrence of endometrioma might be an alternative therapeutic option to avoid repeat surgeries.

We aimed to evaluate whether hormonal therapy immediately after postsurgical recurrence of ovarian endometrioma controls disease progression and can be an alternative therapeutic option to avoid multiple repeat surgeries. We enrolled 146 patients treated for endometrioma at the University Hospital of Kyoto Prefectural University of Medicine between 2009 and 2015. After laparoscopic cystectomy using the stripping technique, opening of cul-de-sac obliterations and complete resection of the deep infiltrating endometriosis lesions, the patients either received no treatment (n = 83), oral contraceptives (OC; n = 32) or dienogest (DNG; n = 27), depending on their medical history. Four patients were excluded because they changed their regimens during the follow-up period. All patients were followed up every 3 months. Patients who developed recurrence of endometrioma immediately received DNG, OC or gonadotropin-releasing hormone agonist. Overall, 16 patients developed a recurrence of the endometrioma (12 in the nontreatment group, three in the OC group and one in the DNG group). The 11 patients with recurrence were treated with DNG immediately after the diagnosis of recurrent endometrioma. Among them, seven patients continued treatment with DNG (2 mg) for 24 months. After 24 months of treatment with DNG, complete resolution of recurrent endometrioma was achieved in four (57.1%) of seven patients. There was no improvement in the three patients who received OC and one patient who underwent secondary surgery. DNG therapy early after recurrence of postsurgical endometrioma appears to be viable for reducing the risk of repeated surgery.

Histological and Immunohistochemical Characterization of the Similarity and Difference Between Ovarian Endometriomas and Deep Infiltrating Endometriosis.

Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) have long been recognized to have different histology and, as such, postulated to be 2 separate disease entities. Few studies, however, have attempted to elucidate the causes for their differences. Making use of ectopic endometrial tissue samples from 25 and 20 women with OMA and DIE, respectively, and control endometrial tissue samples from 25 women without endometriosis, we conducted an immunohistochemical analysis to evaluate the expression of a group of carefully chosen markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM), fibrosis, vascularity, hormonal receptors, and proteins involved in epigenetic modifications. We found that both OMA and DIE lesions exhibited the same cellular changes consistent with EMT, FMT, SMM, and fibrosis as already shown in animal models. Compared to OMA, DIE lesions underwent more thorough and extensive EMT, FMT, and SMM and, consequently, displayed significantly higher fibrotic content but less vascularity. The 2 conditions also showed different expression levels of hormonal receptors. Both OMA and DIE lesions, especially the latter, showed significantly higher staining of enhancer of zeste homolog 2, H3K9me3, and H3K27me3 than that of control endometrium, suggesting progressive epigenetic changes concomitant with cellular ones. Finally, proteins that are known to be involved in fibrogenesis, such as thymocyte differentiation antigen 1 and peroxisome proliferator-activated receptor γ , were also aberrantly expressed under both conditions. The many similarities shared by both OMA and DIE indicate that the 2 conditions may actually share the same pathogenesis/pathophysiology. Their differences, however, suggest that the source of these differences may result from the different lesional microenvironments.

Female Sexual Function in Women with Suspected Deep Infiltrating Endometriosis.

To evaluate the quality of the sexual function of women with suspected deep infiltrating endometriosis. A cross-sectional, observational and prospective study was conducted between May 2015 and August 2016, in which 67 patients with deep infiltrating endometriosis, suspected or diagnosed, were assessed for epidemiological and clinical characteristics, such as pain level through a visual analog scale (VAS), features of deep infiltrating endometriosis lesions and score on the Female Sexual Function Index (FSFI) before the onset of treatment. The statistical analysis was performed using the software STATA version 12.0 (StataCorp LLC, College Station, TX, USA) to compare the variables through multiple regression analysis. The average age of the patients was 39.2 years old; most patients were symptomatic (92.5%); and the predominant location of the deep infiltrating lesions was on the rectosigmoid colon (50%), closely followed by the retrocervical region (48.3%). The median overall score on the FSFI was 23.4; in 67.2% of the cases the score was ≤ 26.5 (cutoff point for sexual dysfunction). Deep dyspareunia (p = 0.000, confidence interval [CI]: 0.64-0.83) and rectosigmoid endometriosis lesions (p = 0.008, CI: 0.72-0.95) showed significant correlation with lower FSFI scores, adjusted by bladder lesion, patients' age and size of lesions. Deep dyspareunia (p = 0.003, CI: 0.49-0.86) also exhibited significant correlation with FSFI pain domain, adjusted by cyclic bowel pain, vaginal lesion and use of gonadotropin-releasing hormone (GnRH) analog. These results reflect the influence of deep dyspareunia on the sexual dysfunction of the analyzed population. Most patients exhibited sexual dysfunction, and deep dyspareunia was the pelvic painful symptom that showed correlation with sexual dysfunction.

Anterior Focal Adenomyosis and Bladder Deep Infiltrating Endometriosis: Is There a Link?

Study ObjectiveTo evaluate the association between bladder deep infiltrating endometriosis (DIE) and anterior focal adenomyosis of the outer myometrium (aFAOM) diagnosed by preoperative magnetic resonance imaging (MRI). DesignAn observational, cross-sectional study using prospectively collected data (Canadian Task Force classification II-2). SettingSingle university tertiary referral center. PatientsAll nonpregnant women younger than 42 years who had undergone complete surgical exeresis of endometriotic lesions. For each patient a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding the surgery. Only women with preoperative standardized uterine MRI were retained for this study. InterventionsThirty-nine women with histologically proven bladder DIE and an available preoperative MRI were enrolled in the study. Patients were divided into 2 groups: women with aFAOM (aFAOM (+), n = 19) and women without aFAOM (aFAOM (–), n = 20). Both groups were compared for general characteristics, medical history, MRI findings, and disease severity. Measurements and Main ResultsNineteen patients (48.7%) with bladder DIE had aFAOM at preoperative MRI. The rate of associated diffuse adenomyosis was similar in the 2 groups (63.2% [n = 12] vs 73.7% [n = 14]; p = .48). The rate of an associated ovarian endometrioma (OMA) was significantly lower in the aFAOM (+) group (10.5% [n = 2] vs 40.0% [n = 8]; p = .03). There were fewer associated intestinal DIE lesions in the aFAOM (+) group compared with the aFAOM (–) group (26.3% vs 75.0%; p = .02), with lower involvement of the pouch of Douglas (26.3% vs 70%; p < .01). Total American Society for Reproductive Medicine score was significantly lower in the aFAOM (+) group (13.8 ± 12.2 vs 62.2 ± 46.2; p < .01). ConclusionaFAOM is present in only half of women with bladder DIE and appears to be associated with lower associated posterior DIE.

Treg and NK cells related cytokines are associated with deep rectosigmoid endometriosis and clinical symptoms related to the disease

The aim of this study was to evaluate Treg and NK cells related cytokines in deep infiltrating endometriosis lesions and its relationship with clinical symptoms of the disease. mRNA expression of Transforming Growth Factor Beta (TGFB), Interleukin (IL)10, Interferon Gamma (IFNG), IL7, and IL15 was analyzed by Real-Time PCR in eutopic endometrium and rectosigmoid lesions from 11 women with deep infiltrating endometriosis and in eutopic endometrium from 11 healthy women. IL10, IFNG, and IL7 expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from women with endometriosis. IL10 and TGFB expression was significantly higher in endometriotic bowel lesions than in eutopic endometrium from healthy women. In addition, TGFB and IL15 levels correlated positively with deep dyspareunia and cyclic dyschezia, respectively, while IL7 levels correlated negatively with dysmenorrhea. Deep infiltrating rectosigmoid endometriosis displays alterations in Treg and NK cells related cytokine, and TGFB, IL7 and IL15 expression is related with dyspareunia, dysmenorrhea and cyclic dyschezia, respectively, in patients with the disease.

Rectovaginal fistula following surgery for deep infiltrating endometriosis: Does lesion size matter?

ObjectiveThis study was performed to identify risk factors for postoperative rectovaginal fistula (PRF) in patients with deep infiltrating endometriosis (DIE).MethodsData were retrospectively obtained from the medical records of 104 patients with DIE, and statistical analysis was used to detect risk factors for PRF.ResultsFive of 104 (4.8%) patients developed PRF from 5 to 16 days postoperatively. The operative procedures included 84 (80.8%) superficial excisions, 6 (5.8%) full-thickness disc excisions, and 14 (13.5%) bowel resections. Most lesions were located in the cul-de-sac, and the mean lesion size was 2.6 cm (range, 0.5–7.0 cm). The univariate analysis showed that lesion location, larger lesion size, and surgical technique were statistically significant risk factors for PRF.ConclusionSurgical procedures should be very carefully executed in patients with DIE lesions of ≥4 cm.

EP26.05: Accuracy of transvaginal sonography in a series of patients operated of endometriosis

To determine the accuracy of transvaginal sonography (TVS) in pre-surgery evaluation of endometriosis. Taking into account the consensus opinion from the International Deep Endometriosis Analysis (IDEA) group, we performed a retrospective study collecting data from TVS exams carried out on 32 female candidates prior to the surgical procedure for endometriosis. Four specialised sonographers performed exams; the average time between ultrasound and surgery was 4'8 months. We evaluate the presence or the absence by TVS of endometrioma and deep infiltrating endometriosis (DIE) in anterior compartment and posterior compartment: rectovaginal septum (RVS), posterior vaginal fornix (PVF), uterosacral ligament (USL), rectosigmoid (RS) and Pouch of Douglas obliteration (POD obliteration). Data was assessed and compared with surgical and histological findings by calculating sensitivity, specificity and accuracy. Due to lack of data, DIE lesions in anterior compartment, RVS and PVF were collected but not evaluated. 32 women, average age of 36,2 years old, underwent TVS and surgery for endometriosis. The sensitivity, specificity and accuracy of TVS for the diagnosis of endometrioma and DIE were 91% (95%CI 76-100), 79% (95%CI 37-100), 84% (95%CI 70-98) and 75% (95%CI 46-100), 95% (95%CI 83-100), 87,5% (95%CI 74-100), respectively. In 30% of endometriomas TVS revealed association with DIE. Results concerning DIE and POD obliteration are expressed in table1. TVS is an accurate and non-invasive test for detection and pre-surgical description of endometriomas and DIE, contributing to the management plan for surgery. Our results resemble those published in prospective studies. Further evaluation of data in our centre would be necessary in order to obtain more valuable outcomes. EP26.05: Table 1. Sensitivity, specificity and accuracy values for DIE and POD obliteration

Value of the 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. A pilot study

ObjectiveThe non-invasive diagnosis of endometriosis remains challenging. Recent data suggested that somatostatin might be involved in its pathogenesis. High sensitive visualization of somatostatin receptors expression is possible using PET-CT imaging after the administration of a 68Ga-labeled somatostatin analog (DOTATATE) that will bind to the somatostatin receptor sub-types 2 and 5. The aim of the present study was to assess the usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. Study designThis is a prospective, single center pilot study. A pre operative 68Ga-DOTATATE PET-CT was performed in all of the patients who presented with suspected endometriosis and who were scheduled for a laparoscopy. Surgical endometriosis staging and histopathological analysis, including somatostatin receptors SST1, 2 and 5 immunohistochemistry (IHC) of removed specimens, were confronted to the results of the 68Ga-DOTATATE PET-CT. Results12 patients were included in this study. 68Ga-DOTATATE PET-CT performed pre operatively showed increased pathologic uptake in four patients with a deep infiltrating endometriosis (DIE) recto-vaginal lesion and in another patient with an adenomyoma. Expression of SST1, 2 and 5 receptors in surgical specimens was confirmed by IHC in these five lesions. Neither superficial peritoneal endometriosis, nor ovarian endometrioma were found to show an increased pathologic uptake on 68Ga-DOTATATE PET-CT. IHC analysis confirmed that SST1, 2, and 5 receptors were not present in these lesions. ConclusionThe results observed in this small size series of patients seem to confirm expression of somatostatin receptors only in recto-vaginal DIE and focal adenomyosis lesions. The usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of this entity is uncertain. Future research should concentrate on studying the role of somatostatin in the pathogenesis of DIE.

Local upregulation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 ion channels in rectosigmoid deep infiltrating endometriosis.

Transient Receptor Potential Vanilloid 1 (TRPV1) and Transient Receptor Potential Ankyrin 1 (TRPA1) expressed mainly by primary sensory neurons function as major nociceptive integrators. They are also present on the rat endometrium in an oestrogen-regulated manner. TRPV1 is upregulated in peritoneal and ovarian endometriosis patients, but there is no information about TRPA1 and their pathophysiological significances. In this study, patients undergoing laparoscopic surgery were investigated: severe dysmenorrhoea due to rectosigmoid deep infiltrating endometriosis (n = 15), uterine fibroid-induced moderate dysmenorrhoea (n = 7) and tubal infertility with no pain (n = 6). TRPA1 and TRPV1 mRNA and protein expressions were determined by quantitative polymerase chain reaction and semi-quantitative immunohistochemistry from the endometrium samples taken by curettage. Results were correlated with the clinical characteristics including pain intensity. TRPA1 and TRPV1 receptors were expressed in the healthy human endometrium at mRNA and protein levels. Sparse, scattered cytoplasmic TRPA1 and TRPV1 immunopositivities were found in the stroma and epithelial layers. We detected upregulated mRNA levels in deep infiltrating endometriosis lesions, and TRPV1 gene expression was also elevated in autocontrol endometrium of deep infiltrating endometriosis patients. Histological scoring revealed significant TRPA1 and TRPV1 difference between deep infiltrating endometriosis stroma and epithelium, and in deep infiltrating endometriosis epithelium compared to control samples. Besides, we measured elevated stromal TRPV1 immunopositivity in deep infiltrating endometriosis. Stromal TRPA1 and TRPV1 immunoreactivities strongly correlated with dysmenorrhoea severity, as well TRPV1 expression on ectopic epithelial cells and macrophages with dyspareunia. Epithelial TRPA1 and stromal TRPV1 immunopositivity also positively correlated with dyschezia severity. We provide the first evidence for the presence of non-neuronal TRPA1 receptor in the healthy human endometrium and confirm the expression of TRPV1 channels. Their upregulations in rectosigmoid deep infiltrating endometriosis lesions and correlations with pain intensity suggest potential roles in pathophysiological mechanisms of the disease.

Total circulating microparticle levels are increased in patients with deep infiltrating endometriosis.

Are the levels of total circulating cell-derived microparticles (cMPs) and circulating tissue factor-containing microparticles (cMP-TF) increased in patients with endometriosis? The levels of total cMP, but not cMP-TF, were higher in patients with endometriosis, and these were attributed to higher levels in patients with deep infiltrating endometriosis (DIE). Previous studies have reported elevated levels of total cMP in inflammatory conditions as well as higher levels of other inflammatory biomarkers in endometriosis. Increased expression of tissue factor (a transmembrane receptor for Factor VII/VIIa) in eutopic and ectopic endometrium from patients with endometriosis has been described. There is no previous data regarding total cMP and cMP-TF levels in patients with endometriosis. A prospective case-control study including two groups of patients was carried out. The E group included 65 patients with surgically confirmed endometriosis (37 with DIE lesions) and the C group comprises 33 women without surgical findings of any form of endometriosis. Patients and controls were recruited during the same 10-month period. Controls were the next patient without endometriosis undergoing surgery, after including two patients with endometriosis. Venous blood samples for total cMP and cMP-TF determinations were obtained at the time of surgery, before anesthesia at a tertiary care center. To assess total cMP, an ELISA functional assay was used and cMP-TF activity in plasma was measured using an ELISA kit. Total cMP levels in plasma were higher in the E group compared with the C group (P < 0.0001). The subanalysis of endometriosis patients with DIE or with ovarian endometriomas without DIE showed that total cMP levels were higher in the DIE group (P = 0.001). There were no statistically significant differences in cMP-TF levels among the groups analyzed. This is a preliminary study in which the sample size was arbitrarily decided, albeit in keeping with previous studies analyzing cMP in other inflammatory diseases and other biomarkers in endometriosis. The control group included patients with other pathologies as well as healthy controls, and blood samples were taken at different phases of the cycle. Elevated total cMP levels in DIE patients may reflect an inflammatory and/or procoagulant systemic status in these patients. Further studies are warranted to confirm our findings and to assess the role of cMP levels in the pathophysiology of DIE. This study was supported in part by a grant from FIS-PI11/01560 and FIS-PI11/00977 within the 'Plan Nacional de I + D + I' and co-funded by the 'ISCIII-Subdirección General de Evaluación' and 'Fondo Europeo de Desarrollo Regional (FEDER)' and by the grant 'Premi Fi de Residència Emili Letang 2015' from the Hospital Clínic of Barcelona. The authors have no competing interests to disclose.

Management of infertile women with pelvic endometriosis: a literature review

Endometriosis is a condition that affects women's fertility. Several mechanisms are involved in this process: anatomical changes, mechanical, immune or inflammatory factors, ovarian reserve alterations... There are different types of strategies to treat endometriosis-related infertility: medical treatment, surgical treatment and/or techniques of medically assisted procreation. We tried to consider various therapeutic strategies depending on the stage of the disease in order to offer appropriate management to patients with endometriosis who wish to become pregnant: we reviewed 58 articles between 1985 to 2016 searching in medline using the key words «endometriosis and infertility» and «infertility and endometriosis treatment». And we divided the patients in subgroups mild and severe endometriosis, in vitro fertilization (IVF) versus surgery in deep infiltrating endometriosis (DIE) and others. Surgery appears to be the chief treatment for minimal to mild endometriosis in a context of infertility. Concerning deep infiltrating endometriosis, data in insufficient to decide on the best treatment although surgery associated with IVF seems to bring clinical benefit. Regarding optimal management of infertility - in case of stage III or IV endometriosis, there is yet no consensus. A multidisciplinary approach is essential in order to consider the various treatment options and provide optimum care and individualized to patients according to different parameters (patient age, degree of damage and location of DIE lesions, presence or absence of ovarian failure or other factors associated with subfertility, male infertility factors in the couple...). Indeed, optimal care of patients should be multidisciplinary and personalized.

Laparoscopic Radical Trachelectomy for Posterior DIE (Deep Infiltrating Endometriosis) Involving Sacral Nerve Roots

DIE (deep infiltrating endometriosis) lesions involving somatic nerves are rare. Here we presented a case with posterior DIE lesions infiltrating the whole Lt uterosacral ligament all the way deep to pre-sacral region, destructing the inferior hypogastric plexus (pelvic plexus), involving sacral nerve roots (S2, S3), causing severe periodic pelvic and anal pain.

Urocortin and corticotrophin-releasing hormone receptor type 2 mRNA are highly expressed in deep infiltrating endometriotic lesions

Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) are the most severe forms of endometriosis, but different pathogenetic mechanisms and clinical symptoms distinguish these two forms. Corticotrophin-releasing hormone (CRH) and urocortin (Ucn) are endometrial neuropeptides involved in tissue differentiation and inflammation. The expression of CRH, Ucn, Ucn2, CRH-receptors (type-1 and type-2) and inflammatory enzymes phospholipase-A2 group IIA (PLA2G2A) and cycloxygenase-2 (COX2) were evaluated in OMA (n = 22) and DIE (n = 26). The effect of CRH or Ucn on COX2 mRNA expression was evaluated in cultured human endometrial stromal cells. In DIE lesions, CRH, Ucn and CRH-R2 mRNA levels were significantly higher than in OMA (P < 0.01, P < 0.001 and P < 0.05, respectively); DIE lesions showed a higher expression of COX2 (P < 0.01) and PLA2G2A (P < 0.05) mRNA than OMA, which was positively correlated with CRH-R2 mRNA expression (P < 0.05). Intense immunostaining for CRH and Ucn was shown in DIE. Treatment of cultured endometrial stromal cells with Ucn significantly increased COX2 mRNA expression (P < 0.01); this effect was reversed by the CRH-R2 antagonist astressin-2B. In DIE, DIE lesions highly express neuropeptide and enzyme mRNAs, supporting a strong activation of inflammatory pathways.

Immunohistochemical Investigation of Metastasis-Related Chemokines in Deep-Infiltrating Endometriosis and Compromised Pelvic Sentinel Lymph Nodes.

Endometriosis is a prevalent benign disease, despite sharing several similarities with malignancies, such as the possibility of lymphatic spread. In malignancies, chemokines play a sovereign role in the process of metastasis. Metastasis-related chemokine axes have not yet been assessed in deep-infiltrating endometriosis (DIE), and this investigation was the aim of our study. The expression of these chemokines was investigated by immunohistochemistry in rectovaginal DIE lesions and in matched pelvic sentinel lymph nodes (PSLNs) of patients with endometriosis (n = 27), and their expression in the eutopic endometrium (EE) of endometriosis-free women (n = 20) was used as controls. Their staining pattern in rectovaginal DIE, in endometriotic lesions affecting the PSLN as well as in the EE of patients without endometriosis was characterized for the first time. Overall, these chemokines were highly expressed in DIE and endometriosis in PSLN. Chemokines might be involved in the spread of endometriosis and should be further investigated.

Expression of microtubule associated protein 2 and synaptophysin in endometrium: high levels in deep infiltrating endometriosis lesions

To assess whether healthy endometrium, eutopic endometrium, and endometriotic lesions express nerve growth factor (NGF), microtubule-associated protein 2 (MAP-2), and synaptophysin (SYP). Molecular study in tissue extracts. University hospital. A group of women (n = 70), divided as [1] healthy controls (n = 30) and [2] with endometriosis (n = 40), was included. From the healthy control group an endometrial specimen was collected by hysteroscopy (proliferative phase, n = 16; secretive phase, n = 14). Endometriotic and endometrial specimens were collected from women undergoing laparoscopic surgery for endometriosis, endometrioma (OMA) (n = 20), or deep infiltrating endometriosis (DIE) (n = 20). To assess expression of NGF, MAP-2, and SYP messenger RNA (mRNA) levels in endometrium and in endometriosis by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and protein localization by immunofluorescence. Cultures of human endometrial stromal cells were used to evaluate the effect of tumor necrosis factor (TNF)-α on NGF and SYP. Endometrial tissue from control expressed mRNA for NGF, MAP-2, and SYP, without any difference between proliferative and secretive phase. The DIE and OMA lesions showed the highest NGF mRNA expression, significantly higher than in eutopic endometrium and control. In DIE lesions SYP mRNA expression was higher than in OMA or in eutopic endometrium or controls. Immunofluorescence analysis of NGF, MAP-2, and SYP showed a slightly more intense positive signal in endometriotic lesions. Exposure to TNF-α increased NGF and SYP mRNA expression in endometrial culture cells. The present study revealed the presence of two selected neuronal markers, MAP-2 and SYP mRNAs and protein expression, in eutopic endometrium and in endometriotic lesions.

Pathogenetic Mechanisms of Deep Infiltrating Endometriosis.

Endometriosis is a benign gynecologic disease, affecting women of reproductive age associated with chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. Ovarian endometrioma (OMA), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) are, till now, recognized as major phenotypes. The discussion is to know whether they share the same pathogenetic mechanisms. Till today, DIE is recognized as the most severe clinical form of endometriosis and has a complex clinical management. The DIE lesions have been considered in the present article, without distinguishing between the anterior (bladder) or the posterior (vagina, uterosacral ligaments, rectum, and ureter) compartment. The present knowledge indicates that hormonal function (estrogen and progesterone receptors) and immunological factors, such as peritoneal macrophages, natural killer cells, and lymphocytes, are critically altered in DIE. The aggressive behavior of DIE may be explained by the highly decreased apoptosis (nuclear factor kappa-light-chain-enhancer of activated B cells [NF-kB], B-cell lymphoma 2 [Blc-2], and anti-Mullerian hormone) and by the increased proliferation activity related to oxidative stress (NF-kB, reactive oxygen species, extracellular regulated kinase (ERK), advanced oxidation protein product). Invasive mechanisms are more expressed (matrix metalloproteinases and activins) in DIE in comparison to the OMA and SPE. Correlated with the increased invasiveness are the data on very high expression of neuroangiogenesis (nerve growth factor, vascular endothelial growth factor, and intercellular adhesion molecule) genes in DIE. Therefore, at the present time, several of the DIE pathogenetic features result specific in comparison to other endometriosis phenotypes, pleading for the existence of a specific entity. These evidence of specific pathogenetic features of DIE may explain the more severe symptomatology related to this form of endometriosis and suggest possible future target medical treatments.

Susceptibility-weighted magnetic resonance imaging for the evaluation of deep infiltrating endometriosis: preliminary results.

Knowledge of the precise sites of deep infiltrating endometriosis (DIE) lesions is essential for preoperative workup and treatment. Susceptibility-weighted imaging (SWI) has high sensitivity for blood products and have recently been applied in abdominal imaging. To determine the value of SWI in the diagnosis of DIE. Forty-three clinically suspected DIE patients with sonographically diagnosed ovarian endometriomas who had tenderness or palpable nodule(s) on rectovaginal examination were referred to pelvic magnetic resonance imaging (MRI) including SWI. Two patients were excluded from the study because of low quality of SWI series. Twenty-eight patients who were offered laparoscopic endometriosis surgery (LES) preferred medical treatment over surgical approach. Thirteen out of 41 participants had LES. Lesions were evaluated for their locations, signal intensities on T1-weighted (T1W) and T2-weighted (T2W) images, and presence of signal voids on SWI using 3T MRI and correlated with LES findings. A total of 18 endometriosis foci were laparoscopically removed from 13 patients. DIE lesions removed at laparoscopy were located at the uterosacral ligament (9/18), rectovaginal region (4/18), retrocervical region (2/18), and fallopian tubes (3/18). Eleven out of 18 (61%) DIE foci were detected by their high-signal intensities on T1W images whereas 16 out of 18 (89%) DIE foci were detected by signal voids on SWI. SWI imaging with its high sensitivity to blood products, contributes to the diagnosis of DIE by depicting different phases of hemorrhage not seen by conventional MRI sequences.

Use of hormonal therapy is associated with reduced nerve fiber density in deep infiltrating, rectovaginal endometriosis.

To study the density of nerve fibers in cases of deep infiltrating endometriosis (DIE) of the rectovaginal septum in relation to various clinical factors. A research laboratory-based study. A tertiary center together with a research laboratory. Archived DIE tissue samples from 45 women operated upon for rectovaginal septum DIE were re-examined histologically, and by immunohistochemistry. The effect of progestogens or combined oral contraceptives on the density of nerve fibers, and the expression of nerve growth factor (NGF) and its high-affinity receptor (tyrosine kinase receptor A, Trk-A). The use of hormonal therapy was associated with reduced densities of sympathetic, parasympathetic and sensory nerve fibers in DIE lesions. Density of total nerve fibers (with pan-neuronal marker PGP9.5) was significantly lower (p < 0.05) in lesions collected from hormone-treated women (8.6/mm², 4.2-20.8/mm²; median density, from 25th to 75th quartiles) compared with that in lesions from untreated women (24.9/mm², 11.2-34.9/mm²). DIE lesions stained strongly for NGF and its receptor Trk-A. Expression of NGF, but not of Trk-A, was significantly reduced during use of hormonal therapy. Use of hormonal therapy was associated with significantly reduced nerve fiber density in DIE lesions. This may be an important mechanism of action of hormonal therapy for controlling DIE pain symptoms. The expression of estrogen-regulated NGF and its receptor was only partially suppressed during the use of hormonal therapy, suggesting that local estrogen action is often maintained during conventional hormonal therapy in cases of DIE.