Aust Vet J. 2009 Jan-Feb;87(1):66-9.
Uterine adenomyosis in an orang-utan (Pongo abelii/pygmaeus).
North Shore Veterinary Specialist Centre, Crows Nest, New South Wales 2065, Australia. firstname.lastname@example.org
A 48-year-old, multiparous, female hybrid orang-utan (Pongo abelii/pygmaeus) was investigated after a 3-year history of irregular and excessively heavy menstrual bleeding. Opportunistic pelvic examinations over a 2.5-year period were non-diagnostic. Medical therapy was not effective. A subtotal hysterectomy with bilateral salpingo-ovariectomy was performed. A pedunculated mass spanning 90% of the uterine lumen was seen grossly, and histopathology confirmed uterine adenomyosis. Adenomyosis is defined as the ectopic occurrence or diffuse implantation of endometrial tissue, including glands and stroma, into the myometrium. It is common in older, usually premenopausal, multiparous women and is frequently associated with other uterine pathology, including endometrial hyperplasia and leiomyomas. The most common clinical signs are dysmenorrhoea and heavy menstrual bleeding; however, up to 35% of women are asymptomatic. Diagnosis is difficult and requires myometrial sampling and an experienced pathologist. A hysterectomy in this case was diagnostic and curative. There have been few reports of uterine adenomyosis in non-human primates and none reported in an orang-utan. Uterine adenomyosis should be considered in the differential diagnosis in any multiparous, aged, non-human female primate with irregular and excessively heavy menstrual bleeding, and hysterectomy with bilateral salpingo-ovariectomy is recommended as a diagnostic and therapeutic solution.
J Clin Immunol. 2009 May;29(3):387-95. Epub 2009 Jan 27.
NF-kappaB decoy oligonucleotides suppress RANTES expression and monocyte chemotactic activity via NF-kappaB inactivation in stromal cells of ectopic endometrium.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, 368 North-Jiangdong Road, Nanjing, China. email@example.com
BACKGROUND: The nuclear factor kappa B (NF-kappaB) pathway is a critical mediator of regulated on activation, normal T cell expressed and secreted (RANTES) gene regulation and therefore represents a potential target for therapy of endometriosis-associated symptoms. OBJECTIVE: The objective of this study was to investigate the effect of NF-kappaB decoy oligonucleotides (ODNs) on NF-kappaB activation, RANTES expression, and monocyte chemotactic activity in ectopic endometrial stromal cells in vitro. METHODS: A specific sandwich enzyme-linked immunosorbent assay (ELISA) was used to quantify RANTES expression in ectopic and normal endometrial stromal cells stimulated by interleukin (IL)-1beta. Four hours after transfection of NF-kappaB decoy ODNs, 10 ng/ml IL-1beta was added to induce the ectopic endometrial stromal cells to secrete RANTES. The NF-kappaB activation, RANTES expression, and monocyte chemotactic activity in ectopic endometrial stromal cells were respectively evaluated by electrophoretic mobility shift assay, ELISA, and Boyden chambers. RESULTS: IL-1beta induced significantly higher levels (P < 0.05) of RANTES expression in a time-dependent manner in ectopic endometrial stromal cells compared with IL-1beta-untreated ectopic and normal endometrial stromal cells. The RANTES accounts for the majority (68%) of the monocyte chemotactic activity in conditioned media of ectopic endometrial stromal cells. In vitro transfection of NF-kappaB decoy ODNs dramatically decreased (P < 0.05) the NF-kappaB activation, RANTES expression, and monocyte chemotactic activity in IL-1beta-induced ectopic endometrial stromal cells. CONCLUSIONS: NF-kappaB decoy ODNs may exert anti-inflammatory effects in ectopic endometrial stromal cells via the suppression of NF-kappaB activation, RANTES expression, and monocyte chemotactic activity.
Fertil Steril. 2009 Jan 24. [Epub ahead of print]
Does endometrial integrin expression in endometriosis patients predict enhanced in vitro fertilization cycle outcomes after prolonged GnRH agonist therapy?
Colorado Center for Reproductive Medicine, Lone Tree, Colorado.
OBJECTIVE: To determine whether endometrial expression of the integrin alpha(v)beta(3) vitronectin can predict which endometriosis patient subgroup will benefit from pre-IVF cycle prolonged GnRH agonist (GnRHa) therapy. DESIGN: Prospective randomized institutional review board approved pilot trial. SETTING: Private assisted reproductive technology program. PATIENT(S): IVF candidates with regular menses, surgically confirmed endometriosis, and normal ovarian reserve. INTERVENTION(S): All patients underwent endometrial biopsy 9 to 11 days post-LH surge to evaluate alpha(v)beta(3) integrin expression. Patients were randomized either to receive depot leuprolide acetate 3.75 mg every 28 days for three doses before controlled ovarian hyperstimulation (COH) or to proceed directly to COH and IVF. Group 1: integrin-positive controls (N = 12); group 2: integrin-positive administered prolonged GnRHa (N = 8). Group A: integrin-negative controls (N = 7); group B: integrin-negative administered prolonged GnRHa (N = 9). MAIN OUTCOME MEASURE(S): COH responses, ongoing pregnancy and implantation rates. RESULTS: There were no significant effects of GnRH agonist treatment in either of the integrin expression strata regarding ongoing pregnancy or implantation rates, although these outcomes were more frequent in group 2 vs. 1 (62.5% vs. 41.6% and 35% vs. 20.6%, respectively). This effect may have because of limited sample size. The value of a negative integrin biopsy in predicting an ongoing pregnancy after prolonged GnRH agonist therapy was only 44.4%. CONCLUSION(S): Endometrial alpha(v)beta(3) integrin expression did not predict which endometriosis patients would benefit from prolonged GnRHa therapy before IVF.
Arch Gynecol Obstet. 2009 Sep;280(3):495-7. Epub 2009 Jan 24.
Appendiceal endometriosis presenting as perforated appendicitis: report of a case and review of the literature.
Department of General Surgery, Faculty of Medicine, Baskent University, Bahcelievler, Ankara, Turkey. firstname.lastname@example.org
While endometriosis is a common disorder in women of reproductive age, appendiceal endometriosis accounts for less than 1% of all pelvic endometriotic lesions. Involvement at this site may present as acute appendicitis and be diagnosed only upon postoperative histopathologic examination. We report such an occurrence of appendiceal endometriosis in a 40-year-old woman who presented with acute perforated appendicitis.
Hum Reprod. 2009 May;24(5):1133-41. Epub 2009 Jan 24.
Down-regulation of p21-activated kinase 1 by progestin and its increased expression in the eutopic endometrium of women with endometriosis.
Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, 388-1, Pungnap-2dong, Songpa-gu, Seoul 138-736, South Korea. email@example.com
BACKGROUND: P21-activated kinase 1 (Pak1) integrates various signaling pathways that are vital to cell survival and function. This study was performed to evaluate whether sex steroids may regulate the expression of Pak1 in endometrial cells as well as whether its expression is increased in the eutopic endometrium of women with endometriosis. METHODS: Following in vitro estradiol (E(2)) and/or medroxyprogesterone acetate (MPA) treatment of Ishikawa cells and endometrial stromal cells (ESCs), Pak1 protein was analyzed utilizing western blot analysis and immunocytochemistry. Immunohistochemistry was performed to evaluate Pak1 immunoreactivity semiquantitatively in women with endometriosis and in controls. To assess the role of Pak1 on endometrial cell viability, crystal violet assay was performed following transfection of Ishikawa cells with Pak1 small interfering RNA (siRNA). RESULTS: In vitro treatment with E(2) plus MPA or MPA alone led to a significant decrease of Pak1 protein in Ishikawa cells and ESCs (both P < 0.05 versus control). Immunohistochemistry also revealed that Pak1 protein is significantly decreased during the secretory phase in both epithelial and stromal cells in the control subjects (P < 0.001 and P < 0.01, respectively). The immunoreactivity of Pak1 in glandular cells was significantly increased in the eutopic endometrium of women with endometriosis compared with the controls during the secretory phase (P < 0.01). Crystal violet assay has shown that transfection of Ishikawa cells with Pak1 siRNA led to a significant decrease of cellular viability (P < 0.05). CONCLUSIONS: These findings suggest that Pak1 is down-regulated by progesterone during the secretory phase in normal endometrium and increased Pak1 activity during the secretory phase might lead to establishment of endometriosis.
Gynecol Endocrinol. 2009 Jan;25(1):39-52.
The role of iron in the pathogenesis of endometriosis.
Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, Japan. firstname.lastname@example.org
BACKGROUND: Endometriosis may cause symptoms including chronic pelvic pain and infertility, and increases susceptibility to the development of ovarian cancer. Genomic studies have started to delineate the wide array of mediators involved in the development of endometriosis. Understanding the mechanisms of endometriosis development and elucidating its pathogenesis and pathophysiology are intrinsic to prevention and the search for effective therapies. METHOD OF STUDY: The present article reviews the English language literature for biological, pathogenetic and pathophysiological studies on endometriosis. Several recent genomic studies are discussed in the context of endometriosis biology. RESULTS: Severe hemolysis occurring during the development of endometriosis results in high levels of free heme and iron. These compounds oxidatively modify lipids and proteins, leading to cell and DNA damage, and subsequently fibrosis development. Recent studies based on genome-wide expression analysis technology have noted specific expression of heme/iron-dependent mediators in endometriosis. The heme/iron-dependent signaling pathway of endometriosis, which is providing new insights into the regulation of inflammation, detoxification and survival, is discussed. CONCLUSION: Several important endometriosis-specific genes overlap with those known to be regulated by iron. Other genes are involved in oxidative stress. Iron has a significant impact on endometriotic-cell gene expression. This review summarizes recent advances in the heme/iron-mediated signaling and its target genes, outlines the potential challenges to understanding of the pathogenesis and pathophysiology of endometriosis, and proposes a possible novel model.
J Dairy Sci. 2009 Feb;92(2):621-5.
Short communication: Haptoglobin as an early indicator of metritis.
Faculty of Land and Food Systems, University of British Columbia, Vancouver, British Columbia, Canada.
The purpose of this study was to determine whether haptoglobin (Hp) could be used as a predictive measure for metritis. Cattle were grouped into 3 health categories based on the condition of vaginal discharge and body temperature after calving: severe metritis (n = 12), mild metritis (n = 32), and healthy (n = 23). Blood was collected and analyzed for Hp concentration on d -20 +/- 5, -6 +/- 2, -2 +/- 1, and d 0 relative to calving, and then every 3 d after calving until d +21. Cows with mild and severe metritis had greater Hp concentrations than healthy cows between d 0 and d +12. Mean (+/-SE) Hp concentrations peaked on d +3 in the cows with mild metritis (1.06 +/- 0.15 g/L) and on d +6 in cows with severe metritis (1.62 +/- 0.47 g/L). Mean concentrations for the healthy group were 0.58 +/- 0.12 g/L and 0.31 +/- 0.08 g/L on d +3 and d +6, respectively. Clinical signs of pathological discharge for the mildly and severely metritic cows did not occur until, on average, 8.6 +/- 3.9 d and 5.3 +/- 1.9 d after calving, respectively. Cows with Hp concentrations >or=1 g/L on d +3 were 6.7 times more likely to develop severe or mild metritis; this predictive threshold has a sensitivity of 50% and specificity of 87%. These results indicate that an acute phase inflammatory response precedes clinical metritis and that Hp screening may assist in the early detection of metritis, providing increased opportunities for early treatment and prevention.
J Dairy Sci. 2009 Feb;92(2):571-80.
Impact of hyperketonemia in early lactation dairy cows on health and production.
Department of Population Medicine, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada. email@example.com
Data from 1,010 lactating lactating, predominately component-fed Holstein cattle from 25 predominately tie-stall dairy farms in southwest Ontario were used to identify objective thresholds for defining hyperketonemia in lactating dairy cattle based on negative impacts on cow health, milk production, or both. Serum samples obtained during wk 1 and 2 postpartum and analyzed for beta-hydroxybutyrate (BHBA) concentrations that were used in analysis. Data were time-ordered so that the serum samples were obtained at least 1 d before the disease or milk recording events. Serum BHBA cutpoints were constructed at 200 micromol/L intervals between 600 and 2,000 micromol/L. Critical cutpoints for the health analysis were determined based on the threshold having the greatest sum of sensitivity and specificity for predicting the disease occurrence. For the production outcomes, models for first test day milk yield, milk fat, and milk protein percentage were constructed including covariates of parity, precalving body condition score, season of calving, test day linear score, and the random effect of herd. Each cutpoint was tested in these models to determine the threshold with the greatest impact and least risk of a type 1 error. Serum BHBA concentrations at or above 1,200 micromol/L in the first week following calving were associated with increased risks of subsequent displaced abomasum [odds ratio (OR) = 2.60] and metritis (OR = 3.35), whereas the critical threshold of BHBA in wk 2 postpartum on the risk of abomasal displacement was >or=1,800 micromol/L (OR = 6.22). The best threshold for predicting subsequent risk of clinical ketosis from serum obtained during wk 1 and wk 2 postpartum was 1,400 micromol/L of BHBA (OR = 4.25 and 5.98, respectively). There was no association between clinical mastitis and elevated serum BHBA in wk 1 or 2 postpartum, and there was no association between wk 2 BHBA and risk of metritis. Greater serum BHBA measured during the first and second week postcalving were associated with less milk yield, greater milk fat percentage, and less milk protein percentage on the first Dairy Herd Improvement test day of lactation. Impacts on first Dairy Herd Improvement test milk yield began at BHBA >or=1,200 micromol/L for wk 1 samples and >or=1,400 micromol/L for wk 2 samples. The greatest impact on yield occurred at 1,400 micromol/L (-1.88 kg/d) and 2,000 micromol/L (-3.3 kg/d) for sera from the first and second week postcalving, respectively. Hyperketonemia can be defined at 1,400 micromol/L of BHBA and in the first 2 wk postpartum increases disease risk and results in substantial loss of milk yield in early lactation.
J Magn Reson Imaging. 2009 Feb;29(2):365-70.
Diagnosis of complete cul-de-sac obliteration (CCDSO) by the MRI jelly method.
Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan. firstname.lastname@example.org
PURPOSE: To evaluate the usefulness of MRI jelly method (jelly method). MATERIALS AND METHODS: Fifty-five patients (32.7 +/- 5 years old) with endometriosis, treated with laparoscopic surgery between January and June 2005 with preoperative MRI using the jelly method. In imaging by the jelly method, 50 mL of jelly used for ultrasound was injected into the vagina, and 150 mL of jelly diluted twice with tap water was injected into the rectum. MRI were inspected for the following seven findings: (Finding 1) Uterine position (anteflexion or retroflexion); (Finding 2) Thickness of the posterior uterine wall (adenomyosis uteri); (Finding 3) Ascites in the Douglas’ pouch; (Finding 4) Elevated posterior uterine fornix; (Finding 5) Thickening of the “Haustra”; (Finding 6) Elevated anterior rectal wall; and (Finding 7) Douglas’ pouch lesion visualized as a high-intensity area on a T1-weighted image. The latter four findings were enhanced with the jelly method. These seven findings were examined for their correlations with video findings of adhesion during surgery. RESULTS: CCDSO was present in 30 of 55 patients. These seven findings had accuracies of 69.1%, 70.9%, 72.7%, 74.5%, 56.4%, 83.6%, and 81.8% respectively. Findings 6 and 7 showed high accuracy. CONCLUSION: These two findings could only be obtained using the jelly method, indicating the usefulness of this method for diagnosing CCDSO.
Cochrane Database Syst Rev. 2009 Jan 21;(1):CD005997.
Hormone therapy for endometriosis and surgical menopause.
Obstetrics & Gynaecology, KFNGH, PO Box 57374, Riyadh, Saudi Arabia, 11574. email@example.com
BACKGROUND: Endometriosis is characterized by the presence of ectopic endometrial tissue that might lead to many distressing and debilitating symptoms. Despite available studies supporting standard hormone therapy for women with endometriosis and post-surgical menopause, there is still a concern that estrogens may induce a recurrence of the disease and its symptoms. OBJECTIVES: This review aimed to look at pain and disease recurrence in women with endometriosis who used hormone therapy for post-surgical menopause. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialized Register (March 2008), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1966 to March 2008), EMBASE (1980 to March 2008), and references lists of articles. Relevant journals and conference proceedings were handsearched. SELECTION CRITERIA: Randomized controlled trials studying hormone therapy for women with endometriosis in post-surgical menopause. DATA COLLECTION AND ANALYSIS: Review authors assessed the eligibility of trials and their quality. MAIN RESULTS: Two studies fulfilled our inclusion criteria. One trial compared the nonstop transdermal application of 17beta-estradiol (0.05 mg/day) combined with cyclic medroxy progesterone acetate (10 mg per day) for 12 days per month in women with a conserved uterus with nonstop tibolone (2.5 mg/day). The second trial used sequential administration of estrogens and progesterone with two 22 cm(2) patches applied weekly to produce a controlled release of 0.05 mg/day. Micronized progesterone was administered orally (200 mg/day) for 14 days with a 16-day interval free of treatment. Pain and dyspareunia The first trial reported recurrence of pain in the estrogen and progesterone arm in 4/10 of women compared with 1/11 in the tibilone arm. In the latter, 4/115 women reported recurrence of pain in the treatment group compared with 0/57 patients in the no-treatment arm. Neither finding was statistically different.Confirmed recurrence or exacerbation of endometriosis This outcome was not reported in the first trial. The second found that 2/115 of the treatment group developed recurrence of endometriosis with no recurrence reported in the no-treatment group. This was not statistically significant. No woman was re-operated on in the no-treatment group compared with 2/115 in the treatment group. AUTHORS’ CONCLUSIONS: Hormone replacement therapy for women with endometriosis in post-surgical menopause could result in pain and disease recurrence. However, the evidence in the literature is not strong enough to suggest depriving severely symptomatic patients from this treatment. There is a need for more randomised controlled studies.
Eur J Obstet Gynecol Reprod Biol. 2009 Mar;143(1):55-60. Epub 2009 Jan 20.
Ectopic, autologous eutopic and normal endometrial stromal cells have altered expression and chemotactic activity of RANTES.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, 99 Ding Huai Men Street, 210036 Nanjing, China.
OBJECTIVE: To evaluate if the expression and chemotactic activity of RANTES are different in IL-1beta treated autologous eutopic endometrial stromal cells compared to ectopic and normal endometrium. STUDY DESIGN: Conditioned media from IL-1beta-treated ectopic, autologous eutopic and normal endometrial stromal cells were analyzed with a specific sandwich ELISA to quantify RANTES. The monocyte chemotactic activity of RANTES was assayed in a Boyden Chamber. RESULTS: RANTES expression in IL-1beta-treated autologous eutopic and normal endometrial stromal cells was significantly lower than ectopic endometrium. Autologous eutopic endometrial stromal cells showed a significant increase in RANTES expression compared to normal endometrium after IL-1beta stimulation for 60 h. The monocyte chemotactic activities of these conditioned media were highly correlated with the immunoreactive RANTES concentration. We observed significantly increased monocyte chemotactic activity in conditioned media of ectopic stromal cells compared to autologous eutopic and normal endometrium. The different chemotactic activity of RANTES between the autologous eutopic and normal endometrial stromal cells was also statistically significant. RANTES accounts for the majority (62%) of the monocyte chemotactic activity in ectopic endometrial stromal cells conditioned media and 55% of that activity in autologous eutopic endometrium. CONCLUSIONS: Although the eutopic endometric of women with and without endometriosis are histologically similar, our findings confirm that different expression and chemotactic activity of RANTES exist between autologous eutopic and normal endometrium. The altered expression of RANTES and monocyte chemotactic activity observed in ectopic, autologous eutopic and normal endometrium suggest the autologous eutopic endometrium may contribute to the pathogenesis of endometriosis.
Obstet Gynecol. 2009 Feb;113(2 Pt 2):563-6.
Inguinal hernia containing functioning, rudimentary uterine horn and endometriosis.
Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, Kagoshima, Japan.
BACKGROUND: Inguinal hernia containing uterus and endometriosis is exceedingly rare. Most inguinal endometriosis is located at an extrapelvic site near the round ligament. We report a case of a patient with inguinal hernia containing rudimentary uterine horn and endometriosis. CASE: A young, nulliparous, regularly menstruating woman manifested right inguinal mass and pain in the mass during menstruation. At 20 years old, she underwent a surgical procedure for right inguinal mass. Postoperative pathology findings demonstrated inguinal endometriosis. Based on the findings of magnetic resonance imaging, a history of inguinal endometriosis, and the occurrence of inguinal pain during menstruation, she was diagnosed as having incarcerated inguinal hernia containing anomalous uterus and endometriosis. A functioning, noncommunicating, rudimentary uterine horn and endometriosis were surgically removed from the hernia sac. Laparoscopy demonstrated intraabdominal unicornuate uterus, but no pelvic endometriosis. CONCLUSION: Functioning, incarcerated hernia uterus inguinale may be associated with müllerian abnormality and concomitant occurrence of inguinal endometriosis.
Dig Surg. 2009;26(1):50-5. Epub 2009 Jan 21.
Surgical outcome and long-term follow-up after segmental colorectal resection in women with a complete obstruction of the rectosigmoid due to endometriosis.
Department of Gastrointestinal Surgery, Endometriosis Center VUMC, VU University Medical Center, de Boelelaan 1117, Amsterdam, The Netherlands.
INTRODUCTION: Intestinal involvement is reported in up to 12% of women with endometriosis. Complete large bowel obstruction is a rare complication of intestinal endometriosis. It is estimated to occur in less than 1% of the cases. OBJECTIVE: The aim of this study is to evaluate the surgical outcome and long-term follow-up after segmental colorectal resection in women with a complete obstruction of the rectosigmoid due to endometriosis. In addition, the diagnostic work-up is described and discussed in view of the current literature. PATIENTS AND METHODS: We present a case series of 5 patients with a complete obstruction of the rectosigmoid due to endometriosis who were finally treated in our hospital within a multidisciplinary endometriosis team. We retrospectively analyzed all patients with this condition who were referred in the period January 2000 to December 2006. RESULTS: All patients (mean age 31.8 years, range 25-43 years) underwent emergency surgery resulting in a diverting colostomy before referral to our hospital. The principal diagnostic tool used was magnetic resonance imaging which demonstrated in all patients multiorgan endometriosis with complete obstruction of the rectosigmoid. Thereafter, all patients underwent a segmental colorectal resection by re-laparotomy. The diagnosis intestinal endometriosis was histologically confirmed in all cases. After surgery no major complications occurred. During a follow-up of 18-36 months, residual symptoms such as chronic constipation, deep dyspareunia and chronic pelvic pain were reported in 2 patients. No recurrences of intestinal endometriosis occurred. CONCLUSION: In our case series, segmental colorectal resection showed a favorable surgical outcome with no major complications. In the long-term follow-up, a limited number of residual symptoms were reported and no recurrences occurred. Intestinal endometriosis as a cause of bowel obstruction is often a diagnostic challenge mimicking a broad spectrum of diseases. It should be included in the differential diagnosis in women of reproductive age presenting with any symptoms of bowel obstruction. Magnetic resonance imaging is recommended as the primary imaging technique in such cases. In our opinion, these patients should be treated in a multidisciplinary setting. Copyright (c) 2009 S. Karger AG, Basel.
J Clin Pathol. 2009 Jun;62(6):530-3. Epub 2009 Jan 20.
Peritoneal stromal endometriosis: a detailed morphological analysis of a large series of cases of a common and under-recognised form of endometriosis.
Department of Pathology, Royal Group of Hospitals Trust, Belfast, Northern Ireland, UK.
AIMS: It is generally considered that an unequivocal histological diagnosis of endometriosis requires the presence of endometrioid-type glands and endometrioid-type stroma. However, small nodules or plaques of endometrioid-type stroma without glands have been noticed by the authors in repeated peritoneal biopsies performed for suspected endometriosis. These are often, but not always, accompanied by typical endometriosis with glands. This form of endometriosis has been previously referred to as stromal or micronodular stromal endometriosis. However, there has been little reference to this condition in the literature. METHODS: In this study, there was a review of a large series (n = 274) of peritoneal biopsies with a diagnosis of endometriosis with a view to ascertaining the frequency of stromal endometriosis. RESULTS: Stromal endometriosis, characterised histologically by small microscopic nodules or plaques of endometrioid-type stroma, sometimes with a whorled pattern and prominent vascularity and erythrocyte extravasation, was identified in 44.9% of the biopsies. In 6.6% of the biopsies, stromal endometriosis occurred without typical endometriosis. The foci of stromal endometriosis usually had a superficial location just beneath the mesothelial surface or protruding above this. Associated histological features present in some cases included reactive mesothelial proliferation, inflammation, giant cell or granuloma formation, haemosiderin pigment deposition, microcalcification and decidualisation and myxoid change. CONCLUSIONS: Stromal endometriosis, usually in the form of superficial nodules or plaques, is a relatively common form of endometriosis which typically occurs in association with typical endometriosis but occasionally on its own. Pathologists should be aware of the existence of this form of endometriosis, the morphological features of which may be subtle. The typical location, intimately associated with surface mesothelium, may suggest that stromal endometriosis derives from mesothelial or submesothelial cells via a metaplastic process.
Fertil Steril. 2009 Apr;91(4):1294.e13-5. Epub 2009 Jan 18.
Endometriosis of the soleus and gastrocnemius muscles.
Department of Surgery and Anatomy, Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
OBJECTIVE: To document a rare case of endometriosis in the soleus and gastrocnemius muscles. DESIGN: Case report. SETTING: Tertiary care center. PATIENT(S): A 30-year-old fertile woman presented with moderate dysmenorrhea associated with calf pain and bulging that had been gradually worsening over the last years, particularly during menses. A mass in the soleus and gastrocnemius muscles was identified in ultrasonography and magnetic resonance imaging. INTERVENTION(S): Endometriosis was diagnosed by incisional biopsy on the basis of histopathology, and wide excisional biopsy was performed. MAIN OUTCOME MEASURE(S): Unusual clinical presentation of endometriosis. RESULT(S): The patient was disease free for 2 months. Recurrence of the lesion was then diagnosed, and a new surgical approach was planned. CONCLUSION(S): Endometriosis in muscles is a rare event, and existing theories are not totally sufficient in explaining it.
Hum Reprod. 2009 Apr;24(4):827-34. Epub 2009 Jan 16.
Rich innervation of deep infiltrating endometriosis.
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China.
BACKGROUND: Deep infiltrating endometriosis (DIE) is a specific type of endometriosis, which can be associated with more severe pelvic pain than other forms of endometriotic lesions. However, the mechanisms by which pain is generated are not well understood. METHODS: DIE (n = 31) and peritoneal endometriotic (n = 40) lesions were sectioned and stained immunohistochemically with antibodies against protein gene product 9.5, neurofilament, nerve growth factor (NGF), NGF receptors tyrosine kinase receptor-A (Trk-A) and p75, substance P, calcitonin gene-related peptide, vesicular acetylcholine transporter, neuropeptide Y, vasoactive intestinal peptide and tyrosine hydroxylase to demonstrate myelinated, unmyelinated, sensory and autonomic nerve fibres. RESULTS: There were significantly more nerve fibres in DIE (67.6 +/- 65.1/mm(2)) than in peritoneal endometriotic lesions (16.3 +/- 10.0/mm(2)) (P < 0.01). DIE was innervated abundantly by sensory Adelta, sensory C, cholinergic and adrenergic nerve fibres; NGF, Trk-A and p75 were strongly expressed in endometriotic glands and stroma of DIE. CONCLUSIONS: The rich innervation of DIE may help to explain why patients with this type of lesion have severe pelvic pain.
Mol Cell Endocrinol. 2009 Mar 5;300(1-2):104-8. Epub 2008 Dec 25.
Steroidogenic factor-1 and endometriosis.
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, 333 E. Superior Street, Suite 484, Chicago, IL 60611, United States. firstname.lastname@example.org
Endometriosis is a common and chronic disease characterized by persistent pelvic pain and infertility. Estradiol is essential for growth and inflammation in endometriotic tissue. The complete cascade of steroidogenic proteins/enzymes including aromatase is present in endometriosis leading to de novo estradiol synthesis. PGE(2) induces the expression of the genes that encode these enzymes. Upon PGE(2) treatment, coordinate recruitment of the nuclear receptor SF-1 to the promoters of these steroidogenic genes is the key event for estradiol synthesis. SF-1 is the key factor determining that an endometriotic cell will respond to PGE(2) by increased estradiol formation. The presence of SF-1 in endometriosis and its absence in endometrium is determined primarily by the methylation of its promoter. The key steroidogenic enzyme in endometriosis is aromatase encoded by a single gene because its inhibition blocks all estradiol biosynthesis. Aromatase inhibitors diminish endometriotic implants and associated pain refractory to existing treatments in affected women.
Arch Gynecol Obstet. 2009 Sep;280(3):369-73. Epub 2009 Jan 16.
The influence of peritoneal endometriotic lesions on the generation of endometriosis-related pain and pain reduction after surgical excision.
Department of Gynaecology, Endometriosis Research Centre Charité, Charité, Campus Benjamin Franklin, Berlin, Germany.
PURPOSE: To investigate the influence of different kinds of endometriotic lesions, especially peritoneal endometriotic implants in pain generation and the pain reduction after surgical excision in a prospective study. METHODS: Fifty-one pre-menopausal patients underwent surgical laparoscopy due to chronic pelvic pain, dysmenorrhoea and/or for ovarian cysts. In 44 patients, endometriosis was diagnosed. The pre- and post-operative pain score was determined using a standardized questionnaire with a visual analogue scale. Patients with peritoneal endometriosis were divided into two different groups depending on their pre-operative pain score: group A had a pain score of 3 or more, while group B a pain score of 2 or less. Patients without peritoneal endometriosis were classified as group C, and patients without endometriosis were classified as group D. The pre- and post-operative pelvic pain and/or dysmenorrhoea was analysed according to the different types of endometriotic lesions. RESULTS: In groups A and C, the post-operative pain score decreased by at least 2 grades or more (p < 0.0). In group D, the post-operative pain score showed no significant reduction. CONCLUSION: The present study suggests that the surgical excision of endometriotic lesions — including peritoneal implants — is an effective treatment of endometriosis-associated pelvic pain and/or dysmenorrhoea.
Int J Mol Med. 2009 Feb;23(2):237-43.
Danazol enhances Fas-mediated apoptosis in human endometrial epithelial cells within normal physiology.
Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-0012, Japan. email@example.com
Local danazol therapy reduces the signs and symptoms of endometriosis without inhibition of regular ovulation and menstruation and without atrophic changes to the endometrium or vaginal wall. It has been suggested that danazol has possible non-cytotoxic direct actions on eutopic endometrial cells and endometriotic cells. We have investigated the direct effects of danazol on a human endometrial epithelial cell line, HHUA, which is believed to retain many normal intracellular signaling pathways. A thoroughly dissolved solution of danazol enhanced Fas-mediated apoptosis in HHUA cells without inhibiting cell proliferation. Semi-quantitative flow cytometric analysis revealed that danazol did not enhance cell surface expression of Fas antigens. The enhancement of Fas-mediated apoptosis by endometrial cytokines such as EGF, IL-1beta and interferon-gamma was not additively enhanced by danazol; nor did danazol enhance growth suppression by anticancer drugs such as paclitaxel, carboplatin and 5-fluorouracil. Moreover, danazol did not enhance the irradiation-induced cell growth suppression of radiation-sensitive human cervical squamous cancer ME180 cells. These results indicate that danazol may regulate endometrial epithelial cell proliferation and apoptosis within normal physiology.
Hum Reprod. 2009 Feb;24(2):253.
Fertil Steril. 2009 Jan 13. [Epub ahead of print]
Effect of pentoxifylline on vascular endothelial growth factor C and flk-1 expression on endometrial implants in the rat endometriosis model.
Second Department of Obstetrics and Gynecology, University of Athens Medical School, Aretaieion Hospital, Athens, Greece; Department of Gynecology and Obstetrics, The Johns Hopkins Hospital School of Medicine, Baltimore, Maryland.
OBJECTIVE: To investigate the effects of pentoxifylline, on vascular endothelial growth factor (VEGF)-C and flk-1 expression in the rat endometriosis model. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Academic institution. ANIMAL(S): Twenty Wistar rats with surgically induced endometriosis. INTERVENTION(S): Animals were evaluated after surgical induction of endometriosis and random allocation to a group that received pentoxifylline and a control group that received NaCl 0.9%, for 3 weeks. At the end of the treatment period the animals were killed and the implants evaluated macroscopically as well as by immunohistochemistry. MAIN OUTCOME MEASURE(S): Morphologic changes of the endometriotic implants; and evaluation of VEGF-C and flk-1 expression by a semiquantitative analysis (HSCORE) for the intensity of immunohistochemical reactivity. RESULT(S): A significant reduction was observed in the mean volume of the endometriotic implants per animal in the treatment group as compared with the control group. There was a significant reduction not only in the mean volume of implants per animal but also in the mean number of implants per animal after treatment. By immunohistochemical evaluation (HSCORE), there was a significant reduction in VEGF-C expression after treatment in all areas examined. A significant reduction of flk-1 expression was also noted in the glandular compartment after treatment but not in the epithelial surface or stroma. CONCLUSION(S): Pentoxifylline may cause suppression of endometriotic lesions by suppressing angiogenesis through VEGF-C and flk-1 expression.
Nippon Yakurigaku Zasshi. 2009 Jan;133(1):32-40.
Pharmacological and clinical profile of dienogest (DINAGEST Tab. 1 mg)
[Article in Japanese]
N Engl J Med. 2009 Jan 15;360(3):268-79.
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. firstname.lastname@example.org
South Med J. 2009 Feb;102(2):206-7.
Inguinal endometriosis: three cases and literature review.
First Propedeutic Surgical Department, A.H.E.P.A University Hospital, Aristotle’s University of Thessaloniki, Thessaloniki, Greece.
Three cases of endometriosis infiltrating the round ligament are presented. The initial diagnosis was irreducible hernia, since this rare nosologic entity often causes unusual preoperative symptoms and diagnostic problems. Diagnosis is frequently made by histologic examination. The rarity of inguinal endometriosis should not exclude it from a possible diagnosis in cases with a painful mass in the inguinal region in a fertile woman, especially if the groin mass is associated in size and tenderness with menstrual variability. Surgery is the treatment of choice and is curative; laparoscopy is suggested during the same operation to evaluate the intraperitoneal conditions.
J Minim Invasive Gynecol. 2009 Mar-Apr;16(2):153-6. Epub 2009 Jan 9.
Feasibility of the use of novel matrix hemostatic sealant (FloSeal) to achieve hemostasis during laparoscopic excision of endometrioma.
Department of Obstetrics and Gynecology at Campus Bio Medico, University of Rome, Italy. email@example.com
STUDY OBJECTIVE: To evaluate the use of FloSeal, a 2-component (collagen granules and thrombin) topical hemostatic agent for the control of minor bleeding of the ovarian wall at the end of the laparoscopic stripping procedure for endometriomas. DESIGN: Pilot study. SETTING: Tertiary care university hospital. PATIENTS: Twenty consecutive patients who underwent laparoscopic excision of endometriomas were included in the study. INTERVENTIONS: Eight patients was allocated to FloSeal group, whereas the remaining 12 patients were allocated to the control group. MEASUREMENTS AND MAIN RESULTS: At the end of the laparoscopic stripping procedure for ovarian cyst (diameter between 3 and 6 cm), the ovarian cortex was carefully everted and thoroughly rinsed to identify the precise localization of bleeding spots. In the FloSeal group the sites of bleeding were covered with FloSeal under direct vision with a laparoscopic applicator. Gentle pressure on the ovary was applied for 5 minutes and subsequently bleeding sites were reexamined. In the control group hemostasis was obtained with conventional methods. Hemostasis was obtained in all cases by 3 minutes from FloSeal application in both study arms. The time of hemostasis was similar in control and FloSeal groups with a median time of 172 and 182 seconds, respectively. CONCLUSION: This preliminary series suggests that FloSeal may be used instead of bipolar electric coagulation after excision of ovarian endometriomas. Because the latter was identified by some authors as a possible cause of follicular damage, the use of FloSeal for bleeding control should be investigated in patients undergoing laparoscopic stripping of endometriomas.
Mod Pathol. 2009 Mar;22(3):450-9. Epub 2009 Jan 9.
Endometrial changes from short-term therapy with CDB-4124, a selective progesterone receptor modulator.
Department of Pathology, University of Maryland, Baltimore, MD, USA.
Selective progesterone receptor modulators are a class of drugs with progesterone antagonist activity that may confer therapeutic benefit for reproductive disorders in premenopausal women. Endometrial structure, which is dynamically controlled by circulating sex hormones, is likely to be perturbed by progesterone receptor modulators through their progesterone antagonist properties. We examined endometrial histology in 58 premenopausal women treated with the progesterone receptor modulator CDB-4124 (also known as Proellex) for endometriosis or uterine leiomyomata in two clinical trials. Endometrial biopsies obtained after 3 or 6 months with doses of 12.5, 25, or 50 mg daily oral CDB-4124 were reviewed independently by three pathologists. Consensus diagnoses using the World Health Organization hyperplasia scoring system, comments on specific histologic features, and clinical annotation were collected and analyzed. The majority of the endometrial biopsies (103 of 174 biopsies) contained histologic changes that are not seen during normal menstrual cycles. The histology of CDB-4124-treated patients was generally inactive or atrophic, and less frequently, proliferative or secretory, superimposed upon which were novel changes including formation of cystically dilated glands, and secretory changes coexisting with mitoses and apoptotic bodies. With increasing treatment dose and duration, the cysts became predominant and their lining inactive or atrophic. Cystic glands in the CDB-4124-treated subjects correlated with increased endometrial thickness by ultrasound. None of the CDB-4124-treated patients developed endometrial carcinoma or hyperplasia while on therapy. CDB-4124 therapy for 3-6 months produces histologic changes that are sufficiently novel that they might easily be misinterpreted by pathologists, particularly as disordered proliferative or hyperplastic endometrium. Knowledge of the constellation of endometrial changes associated with this agent and other progesterone receptor modulators, including cystic architecture and mixed non-physiologic epithelial changes will prevent misdiagnosis.
Hum Reprod. 2009 Apr;24(4):835-41. Epub 2009 Jan 9.
Macrophages and nerve fibres in peritoneal endometriosis.
Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, University of Sydney, Sydney, NSW 2006, Australia. firstname.lastname@example.org
BACKGROUND: Endometriosis is considered to be an inflammatory disease, and macrophages are the most numerous immune cells in endometriotic lesions. However, the mechanisms underlying the elevation of macrophages and their role in the pathogenesis and manifestations of endometriosis still remain unclear. METHODS: The number of macrophages stained for CD68 in endometriotic lesions (n = 24) and in peritoneum distant from the lesions (n = 14) from women with endometriosis was compared with the number of macrophages in normal peritoneum from women without endometriosis (n = 18). Peritoneal lesions were also double-stained for CD68 and protein gene product 9.5 to study the relationship between macrophages and nerve fibres. RESULTS: The densities of macrophages in peritoneal endometriotic lesions and unaffected peritoneum from women with endometriosis were both significantly higher than that in normal peritoneum from women without endometriosis (P < 0.001). More nerve fibres were also found in the areas where increased numbers of macrophages were identified. CONCLUSIONS: There was a significant elevation of macrophages in both normal peritoneum and peritoneal lesions from women with endometriosis compared with normal peritoneum from women without endometriosis. These cells may well play roles in the growth and development of endometriotic lesions and in the generation of pain through interaction with nerve fibres.
Hum Reprod Update. 2009 Mar-Apr;15(2):177-88. Epub 2009 Jan 9.
The effect of surgery for symptomatic endometriosis: the other side of the story.
Department of Obstetrics and Gynecology, University of Milan, Italy. email@example.com
BACKGROUND: Surgery is often considered the best treatment option in women with symptomatic endometriosis. However, extent and duration of the therapeutic benefit are still poorly defined. METHODS: The best available evidence on surgery for endometriosis-associated pain has been reviewed to estimate the effect size of interventions in the most frequently encountered clinical conditions. RESULTS: Methodological drawbacks limit considerably the validity of observational, non-comparative studies on the effect of laparoscopy for stage I-IV disease. As indicated by the results of three RCTs, the absolute benefit increase of destruction of lesions compared with diagnostic only operation in terms of proportion of women reporting pain relief was between 30% and 40% after short follow-up periods. The effect size tended to decrease with time and the re-operation rate, based on long-term follow-up studies, was as high as 50%. In most case series on excisional surgery for rectovaginal endometriosis, substantial short-term pain relief was experienced by approximately 70-80% of the subjects who continued the study. However, at 1 year follow-up, approximately 50% of the women needed analgesics or hormonal treatments. Major complications were observed in 3-10% of the patients. Medium-term recurrence of lesions was observed in approximately 20% of the cases, and around 25% of the women underwent repetitive surgery. CONCLUSIONS: Pain recurrence and re-operation rates after conservative surgery for symptomatic endometriosis are high and probably underestimated. Clinicians and patients should be aware that the expected benefit is operator-dependent.
Am J Obstet Gynecol. 2009 Jun;200(6):615.e1-6. Epub 2009 Jan 10.
A role for menstruation in preconditioning the uterus for successful pregnancy.
Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom. firstname.lastname@example.org
Menstruation is widely viewed as serving no purpose other than to reinitiate the endometrial cycle in the absence of pregnancy. Yet, it is striking that cyclic endometrial decidualization followed by menstrual shedding is confined to the few species, including human beings, where placenta formation entails deep trophoblast invasion of maternal tissues and its vasculature. Both menstruation and pregnancy are inflammatory conditions that cause a degree of physiological ischemia-reperfusion tissue injury, albeit much more so in pregnancy. Thus, the emergence of cyclic menstruation may not have been an evolutionary coincidence but serves to protect uterine tissues from the profound hyperinflammation and oxidative stress associated with deep placentation, a process known as preconditioning. The concept of menstrual preconditioning provides a novel paradigm for understanding how reproductive disorders impact on pregnancy outcome. For example, endometriosis could be viewed as a disorder of exaggerated menstrual preconditioning that confers protection against placentation-related disorders, such as preeclampsia.
Fertil Steril. 2009 Jan 8. [Epub ahead of print]
Up-regulation of endocrine gland-derived vascular endothelial growth factor but not vascular endothelial growth factor in human ectopic endometriotic tissue.
Department of Obstetrics and Gynaecology, Development and Growth, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China; Center for Reproduction, Development and Growth, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
OBJECTIVE: To study the expression of vascular endothelial growth factor (VEGF), endocrine gland-derived VEGF (EG-VEGF/PK1), and its receptors (PKR1 and PKR2) in eutopic and ectopic endometrial tissues. DESIGN: A case-control study. SETTING: University reproduction unit. PATIENT(S): Infertile women undergoing diagnostic laparoscopy for tubal patency. INTERVENTION(S): Endometrial and endometriotic tissue sampling from women with and without endometriosis. MAIN OUTCOME MEASURE(S): Quantitative polymerase chain reaction (PCR) analysis of genes in eutopic and ectopic endometrial tissues. The EG-VEGF protein was studied by immunohistochemistry. RESULT(S): In normal endometrium, EG-VEGF messenger RNA (mRNA) expression was 50-fold higher in the secretory than in the proliferative phase, but that of PKR1 was 6-fold higher in the latter than in the former. The PKR2 transcript was detected in the proliferative but not the secretory endometrium. In patients with endometriosis, eutopic endometrial PKR2 transcript level was 4-fold higher in the proliferative than in the secretory phase. No differences in EG-VEGF or PKR1 were found in proliferative versus secretory endometrium in these patients. There were no significant differences in the expression of EG-VEGF in eutopic endometrium of normal women and in those with endometriosis. In the paired laser-captured microdissected eutopic endometrial and ectopic endometriotic samples, a significantly higher EG-VEGF, but not VEGF, transcript level was detected in the ectopic when compared with eutopic samples; whereas the expressions of PKR1 and PKR2 were barely detectable. The H-scoring confirmed that the stroma of endometriotic samples had a significantly higher EG-VEGF protein expression than that in the paired eutopic endometrium. CONCLUSION(S): High levels of EG-VEGF expression may play an important role in angiogenesis in endometriotic tissues.
Zhong Xi Yi Jie He Xue Bao. 2009 Jan;7(1):41-7.
Regulatory mechanism of malignant behavior of endometriosis mediated by puerarin[Article in Chinese]
Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. email@example.com
OBJECTIVE: To observe the inhibitory effects of puerarin on angiopoiesis of endometriotic tissue, and to explore the regulatory effects of puerarin on tumor-related gene expression of endometriosis. METHODS: The regulatory effects of puerarin on endometriotic angiopoiesis and tumor-related gene expression were observed by using a chicken chorioallantoic membrane model and gene array method. RESULTS: Chicken chorioallantoic membrane experiment indicated that puerarin obviously inhibited endometriotic vasiculation and angiopoiesis. The area of blood vessels was significantly reduced as compared with the untreated group (P<0.05). The expressions of oncogenes and genes related to adhesion, invasion, and apoptosis, including ERBB2, ETS2, FOS, S100A4, TEK, TERT, NFKBIA, CDH1, CD44, ITGA6, NCAM1, MMP1, FLT1, AKT1, BCL2L and BIRC5 genes, were obviously higher, while the expressions of the anti-oncogenes, anti-apoptosis genes and anti-invasion genes, including KAI1, KISS1, SERPINB5, TNFRSF25, TNFRSF1A, TNFRSF6 and SERPINB2, were significantly lower in eutopic endometrial tissue from patients with endometriosis than those from endometriosis-free women. The expressions of oncogenes (ERBB2, ETS2, FOS), apoptosis gene (BCL2L1), cyclin-dependent kinases (CDK4, CDC25A), and growth factor and receptors (HGF, FGFR2, TGFBR) were significantly enhanced, while the expressions of the anti-oncogenes (KAI1, SERPINB5), apoptosis genes (BAD and TNF) and cyclin-dependent kinase inhibiting factor (CDKN2A) were obviously reduced in ectopic tissue as compared with those in eutopic tissue from patients with endometriosis. Puerarin significantly enhanced the gene expressions in endometriotic stromal cells, including BAD, BAX, CASP8, CASP9, TNFRSF6, CDKN1B, CDKN2A, IFNA1 and IFNB1, and reduced the gene expressions of FOS, CHEK2, SRC, ITGB5, MMP9, PDGFA and NFKBIA. CONCLUSIONS: The tumor-related gene expression has significant differences in eutopic endometrial tissue between patients with endometriosis and endometriosis-free women, and between ectopic and eutopic tissues from patients with endometriosis. Puerarin can reduce angiopoiesis, regulate tumor-related gene expression and facilitate apoptosis in endometriotic tissue.