Int J Mol Med. 2010 Jan;25(1):17-23.
Immunohistochemical localization of inhibin and activin subunits, activin receptors and Smads in ovarian endometriosis.
Department of Obstetrics and Gynecology, Wakayama Medical University, School of Medicine, 811-1 Kimiidera Wakayama 641-0012, Japan. firstname.lastname@example.org.
We previously reported that activin A, not inhibin, was localized to endometrial tissues, and that the endometrium might be a major source of activin A during the menstrual cycle, using an immunohistochemical method. However, there are few detailed reports concerning the expression of inhibin subunits, activin receptors and Smad proteins in the ectopic endometrial tissues of endometriosis. In this study, our purpose was to evaluate the immunohistochemical localization of inhibin alpha-, betaA-subunits, activin A, activin receptor, and Smad proteins in ovarian endometriosis. Tissue samples from ovarian endometriosis were obtained from 13 women. Normal endometrial tissues were obtained during the proliferative phase from 5 premenopausal women without endometriosis who were undergoing a hysterectomy for the treatment of uterine cervical intraepithelial neoplasia 3. We examined the immunohistochemical localization of inhibin/activin alpha-, betaA-subunit, activin A, activin receptors types IA, IB, IIA, IIB, Smad2, Smad3 and Smad4 using an avidin-biotin-peroxidase complex technique. No immunostaining for the alpha-subunit of inhibin was observed in ovarian endometriosis and the normal endometrium. Positive immunostaining for the betaA-subunit of inhibin, activin A, activin receptors types IA, IB, IIA, IIB, Smad2, Smad3 and Smad4 was observed in ovarian endometriosis and the normal endometrium. In conclusion, these results suggest that activin A, but not inhibins, is produced by ovarian endometriosis and the normal endometrium, and that the activin signal transduction system exists in both ovarian endometriosis and the normal endometrium.
Am J Surg Pathol. 2009 Dec 2. [Epub ahead of print]
Endometriosis-associated Skeletal Muscle Regeneration: A Hitherto Undescribed Entity and a Potential Diagnostic Pitfall.
Institute of Pathological Anatomy and Histology, University of Perugia, Medical School, Perugia, Italy.
Skeletal muscle undergoes regeneration generally after an injury and in some cases it may mimic a malignant process. We observed these aspects in association with abdominal wall endometriosis and as no similar conditions were found in the literature this prompted us to study the main clinicopathologic and immunohistochemical profile of this phenomenon. Thirteen cases of abdominal wall endometriosis were retrieved from the files of our Institute. All original slides were reviewed to reveal the presence of skeletal muscle and 8 cases were enrolled for morphologic and immunohistochemical studies as follows: vimentin, desmin, myoglobin, myogenin, myoD1, CD56, S100, and p21. Histologically, in 4 of the 8 cases in the skeletal muscle adjacent to the endometriotic foci there was a proliferation of round cells with the typical appearance of maturing myoblasts. More peripherally, myotubes and early myocytes were present. This proliferation was florid in 1 case and focal in 3 cases. At immunohistochemical investigation, the less differentiated cells reacted with vimentin, desmin, S100, CD56, myoD1, and myogenin but not with myoglobin or p21. On the contrary, intermediately differentiated cells showed a progressive loss of vimentin, CD56, and myoD1 whereas they were positive for desmin, S100, myogenin, myoglobin, and p21. Terminally differentiated cells reacted only with desmin and myoglobin. This peculiar immunohistochemical profile was consistent with the immunophenotype of maturing myoblasts, confirmed the regenerative nature of the phenomenon and allowed differential diagnosis with other proliferations sharing a similar morphology. The expression of early differentiation markers was greatest in the islands of cells nearest to endometriosis, whereas in the more distant areas the markers of late differentiation prevailed. This gradient of expression suggests that muscle cells are stimulated by growth factors or other signals produced by the cycling endometrioid foci. In conclusion, we report a hitherto undescribed entity that may mimic a malignant process, especially when the reaction is florid or when endometriotic glands and stroma are not clearly evident, as during the examination of small biopsies, frozen sections, or cytology samples. Therefore, although the histologic diagnosis of endometriosis is usually straightforward, pathologists should be aware of the concomitant regenerative effects on skeletal muscle, which may represent a possible diagnostic pitfall.
Hum Reprod. 2009 Dec 1. [Epub ahead of print]
Nerve fibres in ovarian endometriotic lesions in women with ovarian endometriosis.
Department of Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
BACKGROUND Although nerve fibres are present in eutopic and ectopic endometrium, it is unclear whether they appear in ovarian endometriotic lesions. We investigated the presence of nerve fibres in ovarian endometriotic lesions and its correlation with clinical parameters in women with ovarian endometriosis. METHODS Histological sections of ovarian endometriotic lesions from 61 women with ovarian endometriosis (Stages II-IV) who underwent laparoscopic endometrioma cystectomy were stained immunohistochemically using a specific polyclonal rabbit anti-protein gene product 9.5 (PGP9.5) antibody to demonstrate myelinated and unmyelinated nerve fibres. RESULTS Nerve fibres stained with PGP9.5 were detected in ovarian endometriotic lesions in 31.1% of women, and most appeared in fibrotic interstitium of ovarian endometriotic lesions. The density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions in women with pain symptoms (n = 35) was higher than in women with no pain symptoms (n = 26, P = 0.039), although the percentage (positive cases/total) of PGP9.5-positive fibres did not differ. In women with pain symptoms, PGP9.5-positive fibres appeared in 40.0% of cases and the density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions was correlated with severity of pain symptoms (r = 0.466, P = 0.005). In women with no pain, PGP9.5-positive fibres were detected in only 5 (19.2%) women. Both the percentage and the density of PGP9.5-positive fibres in ovarian endometriotic lesions were associated with pelvic adhesions (chi(2) = 6.833, P = 0.009; Z = 2.442, P = 0.015, respectively) but not with disease severity. CONCLUSIONS PGP9.5-immunoactive nerve fibres in ovarian endometriotic lesions may be involved in the pathophysiology of pain generation and pelvic adhesion formation in women with ovarian endometriosis.
Rev Med Suisse. 2009 Oct 21;5(222):2085-6, 2088-90.
Endometriosis: review of the literature and clinical management.[Article in French]
Département de gynécologie et d’obstétrique, HUG, Geneva. email@example.com
Despite numerous studies, endometriosis remains unclear concerning the etiopathogenesis, the natural history and optimal treatment. It occurs preferentially in young women and may be associated with a series of painful symptoms very disabling, together with infertility and significant psychological problems. Because of the multiple consultations, operations and disability it can cause, endometriosis takes an increasing part in health costs. Delays between onset and diagnosis are still long, and it is important to diagnose as early as possible to stop this disease so as to maintain or restore fertility and quality of life for patients. That is why a careful listening and clinical examination with appropriate investigations will improve our global care.
Hum Reprod. 2009 Nov 26. [Epub ahead of print]
Influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with endometriosis.
Research Center, Hospital Universitario La Fe, Valencia, Spain.
BACKGROUND Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent benign gynaecological diseases. It has been suggested that both endometrial and peritoneal factors, related to angiogenesis and proteolysis, can be implicated in this disease. The aim of this study was to evaluate the influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with and without endometriosis. METHODS Endometrial cells were isolated, cultured and treated with endometriotic or normal peritoneal fluid. Vascular endothelial growth factor-A (VEGF-A), urokinase plasminogen activator (uPA), matrix metalloproteinase-3 (MMP-3) and their inhibitors including thrombospondin-1, plasminogen activator inhibitor-1 and MMP inhibitor type 1 (TIMP-1) mRNA levels were evaluated by quantitative RT-PCR, and protein levels were quantified by ELISA. RESULTS Peritoneal fluid from women with endometriosis induced an increase in VEGF-A and uPA protein and VEGF-A mRNA and uPA mRNA levels in endometrial cell culture from women with (P < 0.01) and without endometriosis (P < 0.05). The highest levels of VEGF-A and uPA were observed in endometrial cell cultures from patients with endometriosis and treated with peritoneal fluid from women with endometriosis. CONCLUSIONS Peritoneal fluid from women with endometriosis induced more VEGF and uPA expression in endometrial cell culture from women with endometriosis than did normal peritoneal fluid. Endometrial-peritoneal interactions increased angiogenic and proteolytic factors in endometrial cells, which could contribute to the development of endometriotic lesions.
Maturitas. 2009 Nov 27. [Epub ahead of print]
The place of dydrogesterone in the treatment of endometriosis and adenomyosis.
Department of Obstetrics and Gynecology, Ammerland Clinic GmbH, Academic Teaching Hospital of the University of Göttingen, Lange Strasse 28/D-26655 Westerstede, Germany.
Oral progestins have been reported to be effective in the treatment of endometriosis. The mode of action is still a matter of debate, but it may involve modulation of mitotic activity, local growth factors and growth factor receptors, as well as other paracrine mechanisms and anti-inflammatory reactions. Other treatments such as danazol and than GnRH-agonists are effective with regard to relief of symptoms and regression of the endometriotic implants, but are associated with high recurrence rates and a wide range of side effects. Progestins are therefore indicated in the symptomatic management of pain, bleeding disorders and other symptoms caused by endometriosis when long-term medication or repeated courses of treatment are indicated. The relationship between costs and efficacy is good, and the side effects are tolerable in most cases. Dydrogesterone is particularly suitable in cases where the woman desires to become pregnant and to prevent bleeding problems. Only very limited data are available concerning the use of progestins in adenomyosis and no conclusions can be drawn.
Prog Urol. 2009 Dec;19(11):850-7. Epub 2009 May 5.
Surgical management of urinary tract endometriosis: 12 cases.[Article in French]
Service d’urologie, CHU Jean-Bernard, 2, rue de la Milétrie, 86000 Poitiers, France.
OBJECTIVES: Our study aimed at evaluating, retrospectively, the outcome of the surgical management of urinary tract endometriosis. PATIENTS AND METHODS: Twelve women with a mean age of 36,4 were recruited between 1994 and 2007. They all had a histologically-proven and surgically-treated endometriosis of the urinary tract. RESULTS: Seven of them had a unilateral ureteric localization, two had a bilateral ureteric localization and three had a vesical localization. One patient with bladder nodules underwent a partial cystectomy and the two other patients with bladder localization underwent a transurethral resection. Out of the nine patients who had a ureteric localization of endometriosis, seven had a ureterectomy and re-implantation with bladder psoas hitching and had no recurrence. CONCLUSIONS: Our experience showed that ureterectomy and re-implantation with bladder psoas hitching is probably the best way of preventing recurrences in the case of urethral endometriosis. In the case of bladder endometriosis, transurethral resection did not appear as the most effective treatment although it remains an acceptable alternative, especially as far as premenopausal women or young women wishing to conceive are concerned.
Fertil Steril. 2009 Nov 26. [Epub ahead of print]
Cancers, infections, and endocrine diseases in women with endometriosis.
Program in Reproductive Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
OBJECTIVE: To assess the prevalence of patient-reported, physician-diagnosed comorbid conditions in women with endometriosis. DESIGN: Cross-sectional study of self-reported survey data. SETTING: Academic research. PATIENT(S): Four thousand three hundred thirty-one Endometriosis Association (EA) members reporting surgically diagnosed endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Self-reported, physician-diagnosed infectious diseases, cancers, and endocrine diseases. RESULT(S): Nearly two-thirds of women reported one or more of the assessed conditions. Recurrent upper respiratory infections and recurrent vaginal infections were common and more likely in women responding to the EA survey. Melanoma was reported by 0.7% (n=29), breast cancer by 0.4% (n=16), and ovarian cancer by 0.2% (n=10). While ovarian cancer and melanoma were significantly more common than in the general population, breast cancer was surprisingly less common. Addison’s disease and Cushing’s syndrome were rare (0.2% and 0.1%, respectively). CONCLUSION(S): Respondents reported a higher prevalence of recurrent upper respiratory or vaginal infections, melanoma, and ovarian cancer than the general population. These findings document other potential associations related to the immune system, which may help focus future research into this disease.
Int J Gynaecol Obstet. 2009 Nov 25. [Epub ahead of print]
Triptorelin improves intestinal symptoms among patients with colorectal endometriosis.
Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Italy.
Fertil Steril. 2009 Nov 25. [Epub ahead of print]
In vitro effects of atorvastatin on lipopolysaccharide-induced gene expression in endometriotic stromal cells.
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
OBJECTIVE: To investigate the in vitro effects of atorvastatin on lipopolysaccharide (LPS)-induced gene expression in endometrial-endometriotic stromal cells. DESIGN: In vitro experimental study using flow cytometry, ELISA, semiquantitative reverse transcriptase polymerase chain reaction, and Western blot. SETTING: Postgraduate Institute of Medical Education and Research. PATIENT(S): Twenty-five women undergoing laparoscopy (n = 10) and laparotomy (n = 15). INTERVENTION(S): Endometriotic cyst wall (group I) and endometrial biopsy (group II) collection. MAIN OUTCOME MEASURE(S): The endometrial-endometriotic stromal cells were isolated from ectopic (group I) and eutopic (group II) endometrium by established methods, cultured, and stimulated with LPS (1 mug/mL), followed by atorvastatin treatment in a time- and dose-dependent manner to investigate the effects of LPS on proliferation (Ki-67) and expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), receptor for advanced glycation end products (RAGE), extracellular newly identified RAGE binding protein (EN-RAGE), peroxisome proliferator activated receptor-gamma (PPAR-gamma), and liver X receptor-alpha (LXR-alpha) genes in endometrial-endometriotic stromal cells and on levels of insulin-like growth factor binding protein-1 (IGFBP-1) and 17beta-E(2) in endometrial-endometriotic stromal cell culture supernatant. RESULT(S): Significant inhibition of Ki-67 and LPS-induced expression of inflammatory and angiogenic genes (COX-2, VEGF, RAGE, and EN-RAGE) was observed in atorvastatin-treated endometrial-endometriotic stromal cells. In contrast, a significant dose- and time-dependent increase in expression of anti-inflammatory genes (PPAR-gamma and LXR-alpha) and levels of IGFBP-1 was observed after atorvastatin treatment in both the groups. However, atorvastatin treatment had no effect on 17beta-E(2) levels in endometrial/endometriotic stromal cell culture supernatant. CONCLUSION(S): The data of the present study provide new insights for the implication of atorvastatin treatment for endometriosis in humans.
Int J Surg. 2009 Nov 24. [Epub ahead of print]
Umbilical endometriosis: A radical excision with laparoscopic assistance.
Department of Obstetrics and Gynecology, University of Milan, Fondazione Policlinico Mangiagalli e Regina Elena, Via Commenda 12, 20122 Milano, Italy.
BACKGROUND: Umbilical endometriosis represents the most common site of cutaneous endometriosis. Although its treatment is typically surgical, in literature the approach used is variable and extends from diathermocoagulation to omphalectomy. Such superficial treatments for umbilical endometriosis can predispose the patient to a relapse of the disease. We here present seven cases of umbilical endometriosis treated with radical surgery with a laparoscopically-assisted approach, with a complete and long-term disease-free follow-up. CASES: Seven cases of umbilical endometriosis, four of which relapsing from a prior superficial treatment, were treated radically with a laparoscopically-assisted approach, with a long-term disease-free follow-up. CONCLUSION: Although a medical treatment can be considered, the treatment of choice in these patients should be that of excisional surgery so as to avoid lesion relapse and the risk of oncogenic transformation. Despite umbilical endometriosis is a rare finding, this relatively small case series treated by laparoscopically-assisted omphalectomy shows a complete resolution of the lesion and symptoms along with good aesthetic results at a long-term follow-up.
Sangyo Eiseigaku Zasshi. 2009 Nov 27. [Epub ahead of print]
Regional Differences in Prevalence of Anemia Found by Periodic Health Checkups at Workplaces.
Department of Environmental and Preventive Medicine, Hyogo College of Medicine.
Anemia-related blood examinations are included in examinations for periodic health checkups at workplaces designated by the Industrial Safety and Health Law in Japan. The aim of this study was to determine whether there were regional differences in the prevalence of anemia in workers and, if so, to investigate possible reasons for the differences. Relationships between prevalence of anemia found by periodic health checkups and some common factors related to anemia in each prefecture of Japan were investigated by ecological regression analysis using Spearman’s rank correlation coefficient. There were regional differences in the prevalence of anemia in the prefectures of Japan (5.1-11.7%), and high prevalence was observed in prefectures in the northeastern district, such as Iwate, Akita and Yamagata Prefectures, and in Fukui, Shimane and Nagasaki Prefectures. Prevalence of anemia in each prefecture was significantly correlated with the prevalence of hypertension, dyslipidemia, liver dysfunction, abnormality in ECG, hyperglycemia or glucosuria at health checkups in each prefecture. Prevalence of anemia in each prefecture was significantly correlated with the percentage of patients receiving therapy for anemia in each prefecture but not with the prevalence of myoma uteri, endometriosis uteri or mortality of uterus cancer in each prefecture. There was also no significant correlation of the prevalence of anemia with the prevalence of iron-deficiency anemia or dietary iron intake in each prefecture. The prevalence of anemia in each prefecture showed significant positive correlations with the ratio of female population to total population and the ratio of female workers to total workers in each prefecture; it also showed a significant negative correlation with the ratio of the number of large-sized workplaces (300 or more workers) to the number of workplaces with 50 or more workers in each prefecture. A considerable regional difference in the prevalence of anemia was found by periodic health checkups at workplaces, and we consider that this difference is not due to regional differences in the incidence of diseases causing genital bleeding in women but to regional difference in the ratio of female workers to total workers and the status of health control at the workplace, which depends on size of the workplace.
Fertil Steril. 2009 Nov 23. [Epub ahead of print]
A multidisciplinary, minimally invasive approach for complicated deep infiltrating endometriosis: a case report.
Minimally Invasive Gynecological Surgery Unit, Reproductive Medicine Unit, S. Orsola Hospital, University of Bologna, Italy.
OBJECTIVE: To present a case of complicated deep infiltrating endometriosis managed by a multidisciplinary minimally invasive approach. DESIGN: Case report. SETTING: Tertiary care university hospital. PATIENT: A 32-year-old woman with deep infiltrating endometriosis involving the rectovaginal septum, the rectum, and the left ureter, complicated by silent left renal function loss. INTERVENTION(S): Laparoscopic left nephrectomy, ureterectomy, excision of a left ovarian endometrioma, removal of a large rectovaginal nodule, and segmental bowel resection with minilaparotomic end-to-end anastomosis. MAIN OUTCOME MEASURE(S): Multidisciplinary diagnosis and minimally invasive surgical approach to deep infiltrating endometriosis involving the rectum and the urinary tract. RESULT(S): Collaboration between gynecologists, urologists, and colorectal surgeons enabled a successful management of the case in one surgical intervention providing minor risk of complications, shorter hospital stay, and faster functional recovery. CONCLUSION(S): Deep infiltrating endometriosis is a global pathology that may involve different structures. A multidisciplinary, minimally invasive approach should be recommended to achieve appropriate disease management.
Obstet Gynecol Surv. 2009 Dec;64(12):830-42.
Ureteral and vesical endometriosis. Two different clinical entities sharing the same pathogenesis.
Department Chair, Department of Obstetrics and Gynecology, Istituto Luigi Mangiagalli, University of Milan, Italy. firstname.lastname@example.org
Ureteral or vesical endometriotic lesions affect about 1% of women with endometriosis. The diagnosis may be difficult when specific symptoms are lacking. A delay in diagnosis can lead to significant morbidity. An adequate comprehension of the circumstances in which ureteral and vesical endometriosis present or should be suspected, aided by advances in imaging techniques and laparoscopic surgery, may allow a significant progress in the treatment of these conditions. The pathogenesis, diagnosis, and treatment of ureteral and vesical endometriosis are reviewed, with the aim of increasing the degree of awareness of the clinicians and helping in devising an adequate clinical management plan for the lesser understood aspects of the disease.
Expert Opin Ther Pat. 2009 Dec;19(12):1771-85.
Luteinizing hormone-releasing hormone antagonists.
Eötvös Loránd University, Hungarian Academy of Sciences, Research Group of Peptide Chemistry, Budapest, Pázmány P. stny. 1/A, Hungary. email@example.com
BACKGROUND: Luteinizing hormone-releasing hormone (LH-RH) plays a central role in the vertebrate reproduction by regulating gonadal activity. Based on its binding to pituitary LH-RH receptors, as well as to LH-RH receptors expressed on cancer cells, LH-RH agonists and antagonists have been developed for different therapeutic applications. OBJECTIVE/METHOD: Here we give an overview of the most relevant LH-RH antagonists and their therapeutic applications. Recently patented compounds as well as drug formulations and dosage are presented. CONCLUSION: LH-RH antagonists have found clinical applications in in vitro fertilization, benign prostatic hyperplasia, endometriosis and in the treatment of hormone-dependent tumors. Work in progress is focused on further development of both peptidic and orally active non-peptidic LH-RH antagonists.
Diagn Cytopathol. 2009 Nov 23. [Epub ahead of print]
Papanicolaou tests associated with cervical mucosal endometriosis: An analysis of cellular features and comparison to endocervical adenocarcinoma in situ.
Department of Anatomic Pathology, Cleveland Clinic, Cleveland, Ohio.
Endometrium directly sampled from endocervical mucosal endometriosis can mimic endocervical adenocarcinoma in situ (AIS) in Papanicolaou (Pap) tests. We analyzed a series of Pap tests to investigate the cellular features of mucosal endometriosis and to assess the utility of stroma and apoptotic bodies in the differential diagnosis with AIS. Pap test samples from patients known to have endocervical mucosal endometriosis were compared with samples containing AIS. Pap tests from patients with mucosal endometriosis had lesional cells in 13 (62%) cases which includes glandular and stromal cells (10 cases), stroma only (two cases), and glandular cells only (one case). Three (23%) cases had gland-stromal aggregates. Three (23%) cases had mitotic figures and two (15%) had apoptotic bodies. By comparison, only one (8%) AIS case had endometrial-type stroma. Seven (58%) AIS cases had apoptotic bodies and three (25%) had mitotic figures. We conclude that Pap tests from patients with mucosal endometriosis usually (62%) have lesional cells. These lesional cells almost always include stroma, which is useful in the differential diagnosis with AIS. We identified stroma significantly more often in endometriosis cases (92%) than in AIS cases (8%). Pathologists should look for endometrial stroma when considering an interpretation of directly sampled endometrium. In the absence of stroma, AIS should be considered. Diagn. Cytopathol. 2010. (c) 2009 Wiley-Liss, Inc.
Eur Radiol. 2009 Nov 21. [Epub ahead of print]
Appearance of abdominal wall endometriosis on MR imaging.
Department of Radiology, Endometriosis Center VUMC, VU Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands, firstname.lastname@example.org.
OBJECTIVE: Abdominal wall endometriosis (AWE) is defined as endometrial tissue that is superficial to the peritoneum. AWE is often difficult to diagnose, mimicking a broad spectrum of diseases. The aim of this study was to describe the appearance of AWE on magnetic resonance (MR) imaging. METHODS: We present ten patients with AWE (12 lesions) in which MR imaging was used for diagnosis. MR imaging included T2-weighted imaging and T1-weighted imaging with fat suppression. To assess the value of diffusion-weighted imaging (DWI) in endometriosis, four patients underwent additional DWI. The apparent diffusion coefficient (ADC) was calculated using b values of 50, 400, 800 and 1,200 s/mm(2). RESULTS: In most cases, the lesion was located ventral or dorsal to the aponeurosis of the rectus oblique muscle (n = 6) or in the rectus abdominis (n = 5). MR of AWE lesions showed isointense or slightly hyperintense signal compared with muscle on T2-weighted images and showed isointense or slightly hyperintense signal compared with muscle on T1-weighted images with foci of high signal intensity, indicative of haemorrhage. The mean ADC value of AWE was 0.93 x 10(-3)/mm(2)/s. CONCLUSION: MR imaging seems to be useful in determining the location and depth of infiltration in surrounding tissue preoperatively.
Int Urogynecol J Pelvic Floor Dysfunct. 2009 Nov 21. [Epub ahead of print]
Intravesical lignocaine in the diagnosis of bladder pain syndrome.
Pushpawati Singhania Research Institute, Press Enclave Road, Sheikh Sarai, Phase II, New Delhi, 17, India, email@example.com.
INTRODUCTION AND HYPOTHESIS: To differentiate between the pain originating from urinary bladder and that due to other pelvic organs, using intravesical instillations of 2% lignocaine solution. METHODS: Twenty-two women with pelvic pain received intravesical instillation of 20 ml of 2% lignocaine solution. The intensity of pain was recorded by using visual analogue scale (VAS) just before, at 2, 10 and 20 min after intravesical instillation. Women who experienced a drop in the VAS score by 50% were termed as responders. All these women underwent cystoscopy under anaesthesia. RESULTS: Fifteen out of 22 (68.18%) women experienced a substantial reduction in the pain. Thirteen out of these 15 women had features suggestive of BPS/IC on cystoscopy. Out of the seven non-responders, two women were found to have endometriosis, four were diagnosed as pelvic inflammatory disease and one had diverticulitis. CONCLUSIONS: Intravesical lignocaine appears to be useful in excluding patients with pelvic pain originating from organs other than the urinary bladder.
Patient Prefer Adherence. 2009 Nov 3;3:205-11.
Examining the efficacy, safety, and patient acceptability of the etonogestrel implantable contraceptive.
Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Contraceptive implants provide long-acting, highly effective reversible contraception. The etonogestrel implant (ENG implant) is a single rod implant that offers three years of efficacy. The ENG implant was designed to provide contraceptive efficacy by inhibiting ovulation and Pearl Index scores reported for this method are similar to other long-acting reversible contraception as well as similar to sterilization. The implant has been shown to be safe during breast feeding and may improve symptoms of dysmenorrhea and endometriosis. Irregular bleeding patterns can be expected with the device’s use and should be addressed in order to decrease rates of discontinuation.
Reprod Sci. 2009 Nov 20. [Epub ahead of print]
Regulation of Monocyte Chemotactic Protein-1 Expression in Human Endometrial Endothelial Cells by Sex Steroids: A Potential Mechanism for Leukocyte Recruitment in Endometriosis.
The main aim of this study is to describe the in vivo temporal and spatial expression of monocyte chemotactic protein 1 (MCP-1) in human endometrial endothelial cells (HEECs) and to compare the in vitro regulation of MCP-1 expression by sex steroids in HEECs from women with or without endometriosis. Eutopic endometrial tissues and endometriosis implants were grouped according to the menstrual cycle phase and were examined by immunohistochemistry for MCP-1 expression. No significant difference was observed for MCP-1 immunoreactivity in the endothelial cells of eutopic endometrium of women with endometriosis when compared to endometrium of women without endometriosis and to endometriosis implants. For in vitro studies, the purity of cultured HEECs (90%-95%) was confirmed by immunocytochemistry using endothelium-specific markers CD31 and CD146. The effects of estradiol (5 x 10(-8) mol/L), progesterone (10(-7) mol/L), or both on MCP-1 messenger RNA (mRNA) and protein levels were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and enzyme-linked immunosorbent serologic assay (ELISA), respectively. Sex steroids did not have significant effect on MCP-1 mRNA and protein expression in HEECs from women without endometriosis. However, we observed that the sex steroid treatment stimulated MCP-1 mRNA and protein expression in HEECs from women with endometriosis (P < .05). We postulate that the stimulation of chemokine expression by sex steroids in the endometrial endothelial cells in women with endometriosis may play a central role in recruiting mononuclear cells, therefore contributing to the inflammatory aspect of endometriosis.
Menopause Int. 2009 Dec;15(4):169-74.
Endometriosis: associations with menopause, hormone replacement therapy and cancer.
Department of Gynaecology, Saint Mary’s University Hospital, CMMC NHS Trust, Hathersage Road, Manchester M13 0JH, UK. Manisha.Palep-Singh@cmft.nhs.uk
Endometriosis is an estrogen-dependent condition and is characterized by the presence of ectopic endometrial tissue. The pathogenesis of this condition remains an enigma. Endometriosis has well known associations with menopause both in terms of secondary outcomes from medical and surgical therapy in premenopausal women, as well as a natural occurrence/recurrence of the disease in women going through menopause naturally. This review article aims to discuss the current day modalities of management of endometriosis with their pros and cons especially in the context of menopause and cancer.
Mol Cell Endocrinol. 2009 Nov 20. [Epub ahead of print]
17betaE(2) promotes cell proliferation in endometriosis by decreasing PTEN via NFsmall ka, CyrillicB-dependent pathway.
Department of Obstetrics & Gynecology, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong 250021, People’s Republic of China.
The objective of this study was to explore the mechanism of phosphatase and tensin homolog (PTEN) loss in endometriosis. We found that aberrant PTEN expression and Mitogen-activated protein kinases (MAPK)/ERK, Phosphoinositide 3-kinase (PI3K)/AKt, and nuclear factor-kappaB (NFsmall ka, CyrillicB) signaling overactivities coexisted in endometriosis. In vitro, 17beta-estradiol rapidly activated the 3 pathways in endometriotic cells and specific inhibitions on the 3 pathways respectively blocked 17beta-estradiol-induced cell proliferation. 17beta-estradiol suppressed PTEN transcription and expression in endometriotic cells which was abolished by specific NFsmall ka, CyrillicB inhibition. Conclusion(s): Total/nuclear PTEN loss and MAPK/ERK, PI3K/AKt, and NFsmall ka, CyrillicB signal overactivities coexist in endometriosis. In vitro, 17beta-estradiol can promotes cell proliferation in endometriosis by activating PI3K/AKt pathway via an NFsmall ka, CyrillicB/PTEN-dependent pathway. For the first time we propose the possibility of the presence of a positive feedback loop: 17beta-estradiol–>high NFsmall ka, CyrillicB–>low PTEN–>high PI3K–>high NFsmall ka, CyrillicB, in endometriosis, which may finally promote the proliferation of ectopic endometrial epithelial cells and in turn contributes to the progression of the disease.
Fertil Steril. 2009 Nov 18. [Epub ahead of print]
Growth differentiation factor 9 concentration in the follicular fluid of infertile women with endometriosis.
Department of Obstetrics and Gynecology, Dr. Soetomo Hospital, Faculty of Medicine, University of Airlangga, Surabaya, Indonesia.
This study evaluated the level of growth differentiation factor 9 (GDF-9) in the follicular fluid of infertile women with endometriosis. The presence of GDF-9 in follicular fluid of preovulatory follicle was confirmed by Western blotting method in the band of 53 kDa, and GDF-9 concentration in women with severe endometriosis was lower than in those without.
Fertil Steril. 2009 Nov 18. [Epub ahead of print]
Immunohistochemical detection of aquaporin expression in eutopic and ectopic endometria from women with endometriomas.
Department of Gynecology and Obstetrics, Women’s Hospital, Zhejiang University Medical College. Zhejiang Province, Hangzhou City, China.
OBJECTIVE: To investigate the expression of aquaporin (AQP) in eutopic and ectopic endometrial tissues from women with endometriomas. DESIGN: Controlled laboratory research. SETTING: Hospital-based unit for gynecology and obstetrics and research laboratories. PATIENT(S): Premenopausal women undergoing laparoscopy for endometriomas. INTERVENTION(S): Endometrial biopsy samples obtained from 70 women with endometriomas. MAIN OUTCOME MEASURE(S): Semiquantitative analysis by immunohistochemistry. RESULT(S): Aquaporins 2, 5, and 8 were mainly located in luminal and glandular epithelia. The frequency of positive immunostaining for aquaporins 2, 5, and 8 decreased in ectopic compared with eutopic endometria. Aquaporins 2, 5, and 8 were found at a low frequency in the endometria in early proliferative phases but at a higher frequency in late proliferative and secretory phases. There were no significant differences in the menstrual cycle of the proliferative phase and secretory phase in the two groups. CONCLUSION(S): Aquaporins 2, 5, and 8 were expressed with greater frequency in eutopic endometrial cells than inectopic endometrial cells, suggesting that eutopic endometrial cells have stronger migration activity than ectopic endometrial cells in women with endometriosis.
Fertil Steril. 2009 Nov 18. [Epub ahead of print]
Endometriosis fertility index: the new, validated endometriosis staging system.
Fertility Physicians of Northern California, Palo Alto and San Jose, California.
OBJECTIVE: To develop a clinical tool that predicts pregnancy rates (PRs) in patients with surgically documented endometriosis who attempt non-IVF conception. DESIGN: Prospective data collection on 579 patients and comprehensive statistical analysis to derive a new staging system-the endometriosis fertility index (EFI)-from data rather than a priori assumptions, followed by testing the EFI prospectively on 222 additional patients for correlation of predicted and actual outcomes. SETTING: Private reproductive endocrinology practice. PATIENT(S): A total of 801 consecutively diagnosed and treated infertile patients with endometriosis. INTERVENTION(S): Surgical diagnosis and treatment followed by non-IVF fertility management. MAIN OUTCOME MEASURE(S): The EFI and life table PRs. RESULT(S): A statistically significant variable used to create the EFI was the least function score (i.e., the sum of those scores determined intraoperatively after surgical intervention that describe the function of the tube, fimbria, and ovary on both sides). Sensitivity analysis showed that the EFI varies little, even with variation in the assignment of functional scores, and predicted PRs. CONCLUSION(S): The EFI is a simple, robust, and validated clinical tool that predicts PRs after endometriosis surgical staging. Its use provides reassurance to those patients with good prognoses and avoids wasted time and treatment for those with poor prognoses.
J Int Med Res. 2009 Sep-Oct;37(5):1389-95.
Expression of Steroidogenic Factor 1 (SF-1) and Steroidogenic Acute Regulatory Protein (StAR) in Endometriosis is Associated with Endometriosis Severity.
Department of Obstetrics and Gynaecology, Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China.
This study was designed to investigate the levels of expression of steroidogenic factor 1 (SF-1) and steroidogenic acute regulatory protein (StAR) in endometriosis, and to explore the association between these two factors and the menstrual cycle and the severity of endometriosis. Levels of SF-1 and StAR protein were evaluated using immunohistochemistry in 38 cases of endometriosis with ectopic endometria and in 25 normal endometria (controls). The SF-1 and StAR protein levels were significantly higher in ectopic endometria than in normal endometria. There was a significant correlation between the level of SF-1 and StAR in ectopic endometriotic tissues. It is concluded that protein levels of SF-1 and StAR are upregulated in ectopic endometria and are significantly correlated with the severity of endometriosis.
Bioorg Med Chem Lett. 2009 Oct 25. [Epub ahead of print]
Improving the developability profile of pyrrolidine progesterone receptor partial agonists.
Kallander LS, Washburn DG, Hoang TH, Frazee JS, Stoy P, Johnson L, Lu Q, Hammond M, Barton LS, Patterson JR, Azzarano LM, Nagilla R, Madauss KP, Williams SP, Stewart EL, Duraiswami C, Grygielko ET, Xu X, Laping NJ, Bray JD, Thompson SK.
Department of Chemistry, Metabolic Pathways Centre for Excellence in Drug Discovery, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein.
Eur J Obstet Gynecol Reprod Biol. 2009 Nov 17. [Epub ahead of print]
Massive ascites, pleural effusion, and diaphragmatic implants in a patient with endometriosis.
IRCAD/EITS and Strasbourg University Hospitals, Faculty of Medicine, Strasbourg, France.
Fertil Steril. 2009 Nov 14. [Epub ahead of print]
Patients’ report on how endometriosis affects health, work, and daily life.
Department of Microbiology, Ponce School of Medicine, Ponce, Puerto Rico.
The objective of this study was to assess the burden of endometriosis by obtaining patient-reported outcome data describing the experience of living with this disease. Survey data from 107 women with self-reported, surgically diagnosed endometriosis showed that living with this disease may be characterized by physical limitations that disrupt health, work, and daily life.
Acta Obstet Gynecol Scand. 2009;88(10):1066-7.
Obstetrics in October and endometriosis.
Abdom Imaging. 2009 Nov 19. [Epub ahead of print]
Diagnosis of deep infiltrating endometriosis: accuracy of magnetic resonance imaging and transvaginal 3D ultrasonography.
Department of Diagnostic Imaging, Campus Bio-Medico University of Rome, Rome, Italy.
PURPOSE: To compare two different imaging modalities, magnetic resonance (MR), and three-dimensional sonography (3DUS), in order to evaluate the specific role in preoperative work-up of deep infiltrating endometriosis. MATERIALS AND METHODS: 33 women with endometriosis underwent 3DUS and MR followed by surgical and histopathological investigations. Investigators described the disease extension in the following sites: torus uterinus and uterosacral ligaments (USL), vagina, rectovaginal-septum, rectosigmoid, bladder, ovaries. Results were compared with surgical and histopathological findings. RESULTS: Ovarian and deep pelvic endometriosis were found by surgery and histology in, respectively, 24 (72.7%) and 22 (66.6%) of the 33 patients. Sensitivity and specificity values of 3DUS for the diagnosis of endometrial cysts were 87.5% and 100%, respectively; those of MRI were 96.8% and 91.1%, respectively. Sensitivity and specificity of 3DUS for the diagnosis of deep infiltrating endometriosis in specific sites were: USL 50% and 94.7%; vagina 84% and 80%; rectovaginal-septum 76.9% and 100%; rectosigmoid 33.3% and 100%; bladder 25% and 100%. Those of MR were: USL 69.2% and 94.3%; vagina 83.3% and 88.8%; rectovaginal-septum 76.4% and 100%; restosigmoid 75% and 100%; bladder 83.3% and 100%. CONCLUSIONS: MR accurately diagnoses deep infiltrating endometriosis; 3DUS accurately diagnoses deep infiltrating endometriosis in specific locations.
Gynecol Obstet Invest. 2009 Nov 17;69(2):73-77. [Epub ahead of print]
Efficacy of Gonadotropin-Releasing Hormone Agonist and an Extended-Interval Dosing Regimen in the Treatment of Patients with Adenomyosis and Endometriosis.
Department of Obstetrics and Gynecology, First Municipal Hospital Affiliated to Guangzhou Medical College, Guangzhou, PR China.
Aims: To determine the effects of gonadotropin-releasing hormone agonist (GnRH-a) and an extended-interval dosing regimen in the treatment of patients with adenomyosis and endometriosis. Methods: This was a prospective observational study in the setting of a hospital outpatient clinic. Seventy women suffering from adenomyosis and endometriosis were randomly divided into 2 groups: extended-interval dosing (experimental group) and conventional dosing (control group). Methods: Patients in the experimental group received a 4-dose regimen (triptorelin 3.75 mg by intramuscular injection every 6 weeks for a total of 4 doses). The patients in the control group received a conventional regimen (1 injection every 4 weeks for a total of 6 doses). The main outcome measures were relief and recurrence of dysmenorrhea and related climacteric symptoms, reduction of uterine volume, and serum levels of 17-beta-oestradiol (E(2)), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Results: The reliving rate of dysmenorrhea was 100% in patients treated with both the new regimen and the convention regimen after 6 months. The uterine volume was reduced 37.6% and 39.2%, respectively. And the levels of LH, FSH and E(2) were decreased significantly (p < 0.001). The E(2 )levels were reduced to the postmenopausal level. The hormone profile of the experimental group was similar to that of the control group (p > 0.05). Conclusion: The use of the extended-interval dosing regimen of triptorelin depot in patients with adenomyosis or endometriosis results in a consistent hypo-oestrogenised state, which is similar to that achieved by the conventional regimen. The new regimen reduces the cost of treatment. Copyright © 2009 S. Karger AG, Basel.
Gynecol Oncol. 2009 Nov 16. [Epub ahead of print]
When ‘never-events’ occur despite adherence to clinical guidelines: The case of venous thromboembolism in clear cell cancer of the ovary compared with other epithelial histologic subtypes.
Division of Gynecologic Oncology, University of Virginia Health Systems, PO Box 800712, Charlottesville, VA 22903, USA.
OBJECTIVE.: To determine the incidence of clinically significant venous thromboembolism (VTE) in women diagnosed with clear cell carcinoma of the ovary (CCC-O) interpreted in the context of Centers for Medicare and Medicaid Services (CMS) ‘never-events.’ METHODS.: Using the institutional pathology Tumor Registry at the Massachusetts General Hospital (MGH), all women diagnosed with a CCC-O from 1994 to 2004 were identified. Controls with epithelial ovarian cancer of other histologies were matched for stage, age and year of diagnosis. Medical records were abstracted and pathology reviewed. All patients had surgical staging and/or cytoreductive surgery by a Gynecologic Oncologist at the MGH. All patients received appropriate peri- and post-operative prophylaxis with subcutaneous heparin and/or sequential compression devices. VTE was diagnosed with standard imaging techniques when clinical suspicion arose. RESULTS.: Fifty-eight (58) women were diagnosed with CCC-O during the study period, 43 of whom had complete data available for analysis. Patients with Stage I or II disease comprised 70% of the patients. The mean age of the cohort was 55 and the mean weight 71 kg. Eighty-six (86) age, stage, and year of diagnosis matched controls were selected. The majority of controls had serous tumors (47%) with the remainder being endometrioid (33%), mucinous (14%), transitional cell (2%), sarcoma (2%) and mixed (2%). CCC-O was often seen in association with endometriosis 70% compared with 22% of controls (p<0.0001). Overall, 18 of 43 CCC-O patients (42%) had VTE while only 19 of 86 control patients (22%) had VTE (p=0.024, OR=2.5 CI 1.1504-5.60). The rate of VTE was not influenced by weight or smoking. In the CCC-O patients, seventeen percent (17%) of VTE was diagnosed at presentation while 50% was diagnosed postoperatively and 33% at the time of disease recurrence or progression. Overall, including cases and controls, late stage disease was more likely associated with VTE (18 of 39, 46%) vs. early stage disease (19 of 90, 21%), p=0.004. CONCLUSIONS.: Women with CCC-O have a 2.5-times greater risk of disease related VTE than women with other histologies of epithelial ovarian cancer despite adherence to prophylactic guidelines. Given the high rate of VTE postoperatively as well as with disease recurrence, one should consider indefinite therapeutic anticoagulation in women with CCC-O. The case of CCC-O is one example of the impracticality of payment denial for ‘never-events,’ as VTE arises despite best efforts at prevention.
Arch Gynecol Obstet. 2009 Nov 17. [Epub ahead of print]
Decreased expression of Beclin 1 in eutopic endometrium of women with adenomyosis.
Department of Gynecology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88, Jiefang Road, Hangzhou, Zhejiang, China.
PURPOSE: Researchers have launched a new area of febrile investigations on the autophagy-related gene Beclin 1. Our aim is to investigate whether Beclin 1 expression is altered in eutopic endometrium of women with adenomyosis and its association with clinical characteristics. METHODS: We collected tissue samples from the eutopic endometria of 30 women with adenomyosis and 32 healthy women undergoing surgery for benign indications. We cultured the stromal cells of the eutopic endometria. Beclin 1 expression of the cultured stromal cells and tissues was assessed by reverse transcription polymerase chain reaction and western blot analysis. RESULTS: Beclin 1 messenger RNA (mRNA) expression in cultured stromal cells of eutopic endometria and endometrial tissues of women with adenomyosis was significantly lower than that of controls (P < 0.05). Beclin 1 protein expression in cultured stromal cells of eutopic endometria and endometrial tissues of adenomyosis was also significantly lower compared with that of controls (P < 0.01). Beclin 1 protein expression in eutopic endometrial tissues was negatively correlated with serum CA125 (r = -0.307, P = 0.015), and pelvic pain (r = -0.542, P = 0.000). CONCLUSIONS: The study revealed Beclin 1 mRNA and protein expression were significantly decreased in eutopic endometria of women with adenomyosis. Moreover, Beclin 1 was negatively correlated with serum CA125 and pelvic pain. Beclin 1 might contribute to the pathogenesis and progression of endometriosis. Further research on autophagy of adenomyosis is required.
Rev Assoc Med Bras. 2009 Sep-Oct;55(5):611-6.
Bowel endometriosis: a benign disease?[Article in Portuguese]
Departamento de Obstetrícia e Ginecologia, FM, USP.
Endometriosis is generally assumed to be a benign disease, but it is estimated that 1% of cases are associated with cancer, especially when both conditions are present in the ovary. Extra-ovarian lesions in the rectovaginal septum, colon, bladder, vagina and peritoneum were already associated with malign neoplasia. Several characteristics of endometrial tissue are very similar to the neoplasia phenotype. Endometriosis itself typically behaves as a neoplasia process, spreading over adjacent stroma and being associated with distant lesions. This is an update on the diagnostic, clinical, and therapeutic knowledge of, management of bowel implants of endometrial tissue, as well as the relation with neoplastic processes to better understand its benign nature or eventual potential for malignancy.
Cases J. 2009 Aug 12;2:6438.
Endometriosis presenting as an acute groin swelling: a case report.
INTRODUCTION: Many conditions present as groin swellings, in both the elective and emergency setting. The management of these conditions varies widely, thus a prompt and accurate diagnosis is important. CASE PRESENTATION: A 27 year old female presented with an acute painful swelling in her right groin. A preliminary diagnosis of an incarcerated femoral hernia led to urgent surgical exploration. Histology of the excised tissue showed appearances consistent with endometriosis. CONCLUSION: Endometriosis is an unusual cause of an acute groin mass, which should be considered as a differential diagnosis in women of childbearing age.