Patients With Endometriosis of the Rectosigmoid Have a Higher Percentage of Natural Killer Cells in Peripheral Blood

Study Objective: To estimate the concentration of natural killer (NK) cells in the peripheral blood in patients with and without endometriosis. Design: Case-control study (Canadian Task Force classification II-2). Setting: Tertiary referral hospital. Patients: One hundred fifty-five patients who had undergone videolaparoscopy were divided into 2 groups: those with endometriosis (n = 100) and those without endometriosis (n = 55). Interventions: The percentage of NK cells relative to peripheral lymphocytes was quantified at flow cytometry in 155 patients who had undergone laparoscopy. In addition to verifying the presence of endometriosis, stage of disease and the sites affected were also evaluated. Measurements and Main Results: The mean (SD) percentage of NK cells was higher (15.3% [9.8%]) in patients with endometriosis than in the group without the disease (10.6% [5.8%]) (p < .001). The percentage of NK cells was highest (19.8 [10.3%]) in patients with advanced stages of endometriosis and in those in whom the rectosigmoid colon was affected. In a statistical model of probability, the association of this marker (NK cells >= 11%) with the presence of symptoms such as pain and intestinal bleeding during menstruation and the absence of previous pregnancy yielded a 78% likelihood of the rectosigmoid colon being affected. Conclusion: Compared with patients without endometriosis, those with endometriosis demonstrate a higher concentration of peripheral NK cells. The percentage of NK cells is greater, primarily in patients with advanced stages of endometriosis involving the rectosigmoid colon. Therefore, it may serve as a diagnostic marker for this type of severe endometriosis, in particular if considered in conjunction with the symptoms. Journal of Minimally Invasive Gynecology (2012) 19, 317-324 (C) 2012 AAGL. All rights reserved.

Transvaginal ultrasonography with bowel preparation is able to predict the number of lesions and rectosigmoid layers affected in cases of deep endometriosis, defining surgical strategy

Successful surgical treatment of deep bowel endometriosis depends on obtaining detailed information about the lesions, prior to the procedure. The objective of this study was to determine the capability of transvaginal ultrasonography with bowel preparation (TVUS-BP) to predict the presence of one or more rectosigmoid nodules and the deepest bowel layer affected by the disease. A prospective study of 194 patients with clinical and TVUS-BP suspected deep endometriosis submitted to videolaparoscopy. Image data were compared with surgical and histological results. With respect to bowel nodule detection and presence of at least two rectosigmoid lesions, TVUS-BP had a sensitivity of 97 and 81%, specificity 100 and 99%, positive predictive value (PPV) 100 and 93% and negative predictive value (NPV) 98 and 96%, respectively. Regarding diagnosis of infiltration of the submucosal/mucosal layer, TVUS-BP had a sensitivity of 83%, specificity 94%, PPV 77%, NPV 96%. These findings show that TVUS-BP is an adequate exam for evaluating the presence of one or more rectosigmoid nodules and the deepest layer affected in deep infiltrating bowel endometriosis, confirming the importance of this technique for defining the most appropriate surgical strategy to be implemented.

Accuracy of magnetic resonance imaging for diagnosis and preoperative assessment of deeply infiltrating endometriosis

Objective: To evaluate the accuracy of preoperative magnetic resonance imaging (MRI) findings relative to surgical presence of deeply infiltrating endometriosis (DIE). Methods: This prospective study included 92 women with clinical suspicion of DIE. The MR images were compared with laparoscopy and pathology findings. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI for diagnosis of DIE were assessed. Results: DIE was confirmed at histopathology in 77 of the 92 patients (83.7%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of MRI to diagnose DIE at each of the specific sites evaluated were as follows: retrocervical space (89.4%, 92.3%, 96.7%, 77.4%, 90.2%); rectosigmoid (86.0%, 92.9%, 93.5%, 84.8%, 89.1%); bladder (23.1%, 100%,100%, 88.8%, 89.1%); ureters (50.0%, 100%, 95.5%, 95.7%); and vagina (72.7%, 100%, 100%, 96.4%, 96.7%). Conclusion: MRI demonstrates high accuracy in diagnosing DIE in the retrocervical region, rectosigmoid. bladder, ureters, and vagina. (C) 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Lid. All rights reserved.

Endometriosis lesions that compromise the rectum deeper than the inner muscularis layer have more than 40% of the circumference of the rectum affected by the disease

Study Objective: To estimate the relationship between the depth of lesions of rectal endometriosis and the percentage of the circumference of the bowel segment affected by the disease. Design: A prospective pathologic analysis of 45 surgical specimens of bowel endometriosis obtained by laparoscopic segmental resection of the rectosigmoid (Canadian Task Force classification II-1). Setting: Tertiary referral hospital. Patients: forty-five patients were submitted to a segmental resection of the rectum due to endometriosis between July 2004 and September 2006. Interventions: Morphometric aspects of endometriotic lesions were analyzed, such as size and thickness of the lesion, deepest layer of bowel affected by lesion, and percentage of circumference of bowel affected by endometriosis. Measurements and Main Results: Results showed that in lesions that reached the submucous layer of the bowel, the circumference affected was 31.6% greater than in lesions that reached only the outer muscular layer, whereas in lesions that reached the mucous layer, the circumference affected was 52.5% greater than in those that reached the outer muscular layer of the bowel. In addition, 89.3% of lesions with an affected circumference greater than 40% were those affecting the submucous or mucous layers of the bowel. These results suggest that when a lesion reaches these 2 deepest layers of the rectosiamoid, risk increases that the circumference affected will be greater than 40% (relative risk = 1.5; 95% CI: 1.0-2.3; p =.03). Conclusion: In endometriotic lesions affecting the rectosigmoid beyond the inner muscular layer of the bowel wall, more than 40% of the circumference of the rectosigmoid is affected by the disease, confirming the recommendation of segmental resection of the bowel for this form of the disease.

Findings of Pelvic Endometriosis at Transvaginal US, MR Imaging, and Laparoscopy

Endometriosis is a common multifocal gynecologic disease that manifests during the reproductive years, often causing chronic pelvic pain and infertility. It may occur as invasive peritoneal fibrotic nodules and adhesions or as ovarian cysts with hemorrhagic content. Although findings at physical examination may be suggestive, imaging is necessary for definitive diagnosis, patient counseling, and treatment planning. The imaging techniques that are most useful for preoperative disease mapping are transvaginal ultrasonography (US) after bowel preparation, and magnetic resonance (MR) imaging. Initial transvaginal US is a reliable technique for detecting rectosigmoid endometriotic lesions. MR imaging is indicated as a complementary examination in complex cases of endometriosis with extensive adhesions and ureteral involvement. Peritoneal endometriotic implants are typically hypoechoic on transvaginal US images and demonstrate low signal intensity on T2-weighted MR images. Endometriotic implants most commonly are found in retrocervical and rectosigmoid sites, followed by the vagina, bladder, and ureters. Cysts with low-level internal echoes and echogenic peripheral foci at transvaginal US are suggestive of endometriomas. MR imaging has high specificity for identifying endometriomas, which are characterized by high signal intensity on T1-weighted images and low signal intensity on T2-weighted images. Correlation of the radiologic imaging features of endometriotic lesions with their laparoscopic appearances may help improve individual proficiency in the radiologic diagnosis of endometriosis. Supplemental material available at http:// radiographics.rsna.org/lookup/suppl/doi: 10.1148/rg.314105193/-/DC1. (C) RSNA, 2011 radiographics.rsna.org

Pain Threshold And Sleep Quality In Women With Endometriosis.

Pain is a common complaint in women with endometriosis and can be influenced by many variables, including sleep disorders; however, no data are available on the sleep quality of women with endometriosis or on the correlation between sleep quality and pain. The 510 volunteers included in this study were divided into two groups: 257 women with a laparoscopic and histopathological diagnosis of endometriosis and 253 women with no history of endometriosis and no endometriosis-related symptoms. The volunteers answered two questionnaires: the Post-Sleep Inventory to evaluate sleep quality and the International Physical Activity Questionnaire to assess their level of physical activity. Pain was evaluated using a visual analogue scale (VAS) and women were also submitted to a physical examination, during which their pain threshold was assessed at 20 different body sites. Sleep quality was significantly poorer in women with endometriosis compared to women without the disease. The pain threshold was significantly lower in the greater trochanter and abdomen in women with endometriosis when compared to women without the disease; however, there was no difference in VAS pain score between the groups. The higher the VAS pain score, the lower the Post-Sleep Inventory score. Additionally, there was a significant positive correlation between the pain threshold at some body sites and sleep quality. Sleep quality was poorer and the pain threshold at certain body sites was lower in the group of women with endometriosis.

Reduction Of Blood Nitric Oxide Levels Is Associated With Clinical Improvement Of The Chronic Pelvic Pain Related To Endometriosis.

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Stem cells in endometrium and their role in the pathogenesis of endometriosis

The human endometrium is a dynamic tissue that undergoes cycles of growth and regression with each menstrual cycle. Adult progenitor stem cells are likely responsible for this remarkable regenerative capacity; these same progenitor stem cells may also have an enhanced capacity to generate endometriosis if shed in a retrograde fashion. The progenitor stem cells reside in the uterus; however, less-committed mesenchymal stem cells may also travel from other tissues such as bone marrow to repopulate the progenitor population. Mesenchymal stem cells are also involved in the pathogenesis of endometriosis and may be the principle source of endometriosis outside of the peritoneal cavity when they differentiate into endometriosis in ectopic locations. Finally, besides progenitor stem cells, recent publications have identified multipotent stem cells in the endometrium. These multipotent stem cells are a readily available source of cells that are useful in tissue engineering and regenerative medicine. Endometrial stem cells have been used to generate chondrocytes, myocytes, neurons, and adiposites in vitro as well as to replace dopaminergic neurons in a murine model of Parkinson`s disease.

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model

Objective: To analyze the antiangiogenic effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib on the growth of endometrial implants in a rat model of peritoneal endometriosis. Design: Pharmacologic interventions in an experimental model of peritoneal endometriosis. Setting: Research laboratory in the Federal University of Rio de Janeiro. Animal(s): Twenty female Sprague-Dawley rats with experimentally induced endometriosis. Intervention(s): After implantation and establishment of autologous endometrium onto the peritoneum abdominal wall, rats were randomized into groups and treated with parecoxib or the vehicle by IM injection for 30 days. Main Outcome Measure(s): Vascular density, the expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1, the distribution of activated macrophages, the expression of COX-2, and the prostaglandin concentration in the endometriotic lesions treated with parecoxib were analyzed. Result(s): The treatment significantly decreased the implant size, and histologic examination indicated mostly atrophy and regression. A reduction in microvessel density and in the number of macrophages, associated with decreased expression of VEGF and Flk-1, also were observed. The treatment group showed a low concentration of prostaglandin E(2). Conclusion(s): These results suggest that the use of COX-2 selective inhibitors could be effective to suppress the establishment and growth of endometriosis, partially through their antiangiogenic activity. (Fertil Steril (R) 2010; 93: 2674-9. (C) 2010 by American Society for Reproductive Medicine.)

High serum follistatin levels in women with ovarian endometriosis

Follistatin is an activin-binding protein produced by several tissues, including endometrium and endometriotic implants. We aimed to quantify follistatin in patients with ovarian endometriosis and investigate its value as a diagnostic marker. Women undergoing laparoscopic excision of ovarian endometrioma (n = 52) or other benign ovarian cysts (n = 52) were studied, plus women with non-ovarian endometriosis (n = 11) and healthy controls (n = 27). Serum was collected from all subjects, and peritoneal and cystic fluid from a subset with endometrioma. Follistatin was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of follistatin to detect endometrioma was evaluated by receiver operating characteristic (ROC) curve and compared with cancer antigen (CA)-125. Serum follistatin was increased in women with ovarian endometrioma (2080 +/- 94 pg/ml) compared with controls (545 +/- 49 pg/ml, P < 0.001), other benign ovarian cysts (795 +/- 60 pg/ml, P < 0.001) or non-ovarian endometriosis (1271 +/- 115 pg/ml, P < 0.001). Cystic fluid showed a higher concentration of follistatin (9850 +/- 4461 pg/ml) than peritoneal fluid (1885 +/- 261 pg/ml, P < 0.001) and serum (P < 0.001). Follistatin levels detected 48/52 cases of endometrioma (92% sensitivity) at 1433 pg/ml cut-off, corresponding to 92% specificity. CA-125 detected only 44% of endometriomas with 90% specificity. ROC curve comparison showed follistatin was more accurate than CA-125 to discriminate women with endometrioma either from controls or women with other benign ovarian cysts (P < 0.0001). Serum follistatin is increased in women with endometriosis and allows clear distinction between endometrioma and other benign ovarian cysts. Follistatin has the sensitivity and specificity to become a useful clinical marker of ovarian endometrioma.

Endometriosis of the ureter and bladder are not associated diseases

Objective: To verify whether bladder and ureter endometriosis had the same clinical features and disease behavior. Design: Case-control study. Setting: Multidisciplinary group in Sao Paulo, Brazil. Patient(s): A total of 690 patients were submitted to laparoscopy with histologically diagnosis of endometriosis between July 1999 and December 2006. Twelve of these patients had lesions affecting the ureter and 26 had lesions affecting the bladder. A control group consisted of 652 patients in whom endometriosis was not affecting either the ureter or the bladder. Intervention(s): None. Main Outcome Measure(s): Clinical and surgical features of patients with ureteral or bladder endometriosis. Result(s): No patients with ureteral endometriosis had lesions affecting the bladder. Compared with the control group, patients with ureteral endometriosis had more advanced disease (Stages III and IV) according to the American Society of Reproductive Medicine (ASRM) staging classification (100% vs. 65.5%); they also had more retrocervical (83.3% vs. 21.6%) and rectum-sigmoid lesions (91.7% vs. 17.9%). Compared with the control group, more patients with bladder endometriosis had cyclic dysuria and/or hematuria (34.6% vs. 9.8%), more advanced stages of the disease (88.4% vs. 65.5%), and an association with endometriosis of the rectum-sigmoid (65.3% vs. 17.9%). Conclusion(s): Ureter endometriosis is not associated with the bladder disease; however, it is associated with advanced ASRM stages and with retrocervical and rectum-sigmoid lesions. (Fertil Steril (R) 2009;91:1662-7. (C)2009 by American Society for Reproductive Medicine.)

Interleukin-12 but not interieukin-18 is associated with severe endometriosis

Objective: To evaluate interleukin (IL)-12 and IL-18 levels in the serum and peritoneal fluid of women with and without endometriosis. Design: Cross-sectional survey. Setting: University hospital. Patients: Interleukin-12 and IL-18 levels were compared in 105 patients submitted to laparoscopy because of symptoms suggestive of endometriosis (pain and/or infertility). The disease was confirmed in 72 patients (study group), while in 33 patients findings were not compatible with endometriosis (control group). Intevention(s): Blood sample and peritoneal fluid were obtained from patients during videolaparoscopy. Main Outcome Measure(s): The levels of IL-12 and IL-18 in peripheral blood and peritoneal fluid were determined and compared with the stage and site of the disease and histologic classification. Result(s): IL-12 levels measured in peritoneal fluid were higher inpatients with endometriosis compared with the control group. A significant increase in IL-12 levels was found when the more advanced stages of the disease were compared with the initial stages. No statistically significant differences were found in IL-18 levels, either in serum or in peritoneal fluid samples. Conclusion(s): Patients with severe endometriosis have higher IL-12 levels irrespective of IL-18 levels, suggesting that in this disease an alternative pathway is involved in induction of the Th1 immune response. (Fertil Steril (R) 2009;91:320-4. (C)2009 by American Society for Reproductive Medicine.)

Transvaginal ultrasound for diagnosis of deeply infiltrating endometriosis

Deeply infiltrating endometriosis is the clinical form of the disease that is generally associated with conditions of more intense pain and may require more complex surgical management, consequently resulting in greater risks to the patient. In recent years, various investigators have confirmed the usefulness of methods such as magnetic resonance imaging (MRI), transrectal ultrasound and transvaginal ultrasound (TVUS) for the diagnosis of deep endometriotic lesions. The objectives of the present study are to describe the method used to perform TVUS for the detection of deeply infiltrating endometriosis, and to discuss the clinical benefits that the data obtained may offer clinicians providing care for patients suspected of having this type of endometriosis. (C) 2008 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Vascular density and distribution of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) are significantly higher in patients with deeply infiltrating endometriosis affecting the rectum

Objective: To analyze vascular density and immunolocalization of angiogenic vascular endothelial growth factor (VEGF) and its receptor Flk-1 in the proliferative and secretory eutopic human endometrium. and in three different sites of endometriosis: the ovary, bladder, and rectum. Design: Prospective study. Setting: University hospital. Patient(s): Thirty women with endometriosis (10 ovarian, 1.0 bladder, 10 rectal) and 32 control women (10 proliferative endometrium, 10 secretory endometrium, 4 normal ovary, 4 normal bladder, 4 normal rectum). Intervention(s): Normal endometrial samples were obtained from women during laparoscopic ablation of subserous myoma, and biopsy specimens of endometriosis were obtained from patients undergoing surgery for the diagnosis and treatment of endometriosis. Normal tissues of ovary, bladder, and rectum were obtained from these organs beside the lesions of endometriosis. Main Outcome Measure(S): Blood vessels were quantified according to the number of von Willebrand factor-positive endothelial cells. The VEGF and Flk-1 distribution were evaluated semiquantitatively by immunohistochemical staining. Result(s): More blood vessels were found in cases of endometriosis, particularly rectal endometriosis, compared with the respective control samples and with the eutopic endometrium, and they were localized in endometrial stroma around the glands. The VEGF and Flk-1 expression levels were also higher in cases of endometriosis, especially rectal endometriosis. Conclusion(s): Vascularization and VEGF and Flk-1 expression are significantly higher in deeply infiltrating endometriosis affecting the rectum, reinforcing the hypothesis that antiangiogenesis therapy may constitute a new modality of treatment, especially in cases of deep endometriosis involving the rectum.

Transvaginal US after Bowel Preparation for Deeply Infiltrating Endometriosis: Protocol, Imaging Appearances, and Laparoscopic Correlation

Deeply infiltrating endometriosis (DIE) is a common gynecologic disease that is characterized by a difficult and delayed diagnosis. Radiologic mapping of the DIE lesion sites is crucial for case management, patient counseling, and surgical planning. Transvaginal ultrasonography (US) is the initial imaging modality for investigating DIE and has been the focus of several recent studies. DIE typically manifests at imaging as hypoechogenic nodules throughout the affected sites and thickening of the intestinal wall, with some lesions showing a mixed pattern due to cystic areas. Transvaginal US performed after bowel preparation improves the ability to diagnose intestinal lesions and provides invaluable details, including which layers of the intestine are affected and the distance between the lesion and the anal border. It is vital that radiologists be familiar with the technical aspects of this modality and with the US manifestations of DIE lesions. Transvaginal US performed after bowel preparation should be the first-line imaging modality for the evaluation of women with suspected endometriosis. (C) RSNA, 2010 . radiographics.rsna.org