Fertil Steril. 2009 Sep;92(3):1107-9. Epub 2009 May 6.

Estradiol modulation of hepatocyte growth factor by stromal fibroblasts in the female reproductive tract.

Coleman KD, Wright JA, Ghosh M, Wira CR, Fahey JV.

Department of Physiology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA. Kimberly.Coleman@dartmouth.edu

Primary human uterine, cervical, and ectocervical stromal fibroblasts constitutively secrete hepatocyte growth factor (HGF), yet only uterine stromal fibroblasts increase HGF secretion in response to estradiol. Estradiol-induced HGF secretion by uterine stromal fibroblasts may have a significant effect on uterine cancer and endometriosis.

Publication Types:

Fertil Steril. 2009 May 5. [Epub ahead of print]

Interleukin-8 serum levels do not correlate with pelvic pain in patients with ovarian endometriomas.

Manero MG, Alcazar JL.

Department of Obstetrics and Gynecology, Clínica Universitaria de Navarra, University of Navarra, Pamplona, Spain.

OBJETIVE: To determine whether interleukin-8 (IL-8) serum levels are correlated with pelvic pain in patients with ovarian endometriomas. DESIGN: Prospective study. SETTING: Tertiary-care university hospital. PATIENT(S): Interleukin-8 serum levels were prospectively analyzed in 51 patients (group A, asymptomatic patients or patients with mild dysmenorrhea; group B, severe dysmenorrhea and/or chronic pelvic pain and/or dyspareunia) who underwent surgery for cystic ovarian endometriosis to asses whether a correlation exists between IL-8 serum levels and pelvic pain. INTERVENTION(S): Interleukin-8 serum levels determination. MAIN OUTCOME MEASURE(S): Interleukin-8 serum levels and pelvic pain. RESULT(S): From 56 patients, five cases were ultimateley excluded because the histologic diagnosis was not cystic ovarian endometriosis (2 teratomas and 3 haemorragic cysts). The mean (+/-SD) IL-8 serum levels in group A were 6.41 +/- 12.17 pg/mL and in group B were 6.52 +/- 8.73 pg/mL. CONCLUSION(S): Pain symptoms in ovarian endometriosis is not correlated with IL-8 serum levels.

J Minim Invasive Gynecol. 2009 May-Jun;16(3):377; author reply 377-8.

Comment on:

Laparoscopic revealed no evidence of pelvic endometriosis.

Batt RE, Yeh J.

Publication Types:

J Minim Invasive Gynecol. 2009 May-Jun;16(3):340-3.

Comparative study of the neuropeptide-Y sympathetic nerves in endometriotic involved and noninvolved sacrouterine ligaments in women with pelvic endometriosis.

Possover M, Tersiev P, Angelov DN.

Department of Advanced Surgical Gynaecology & Neuropelveology, Hirslanden Clinic, Zurich, Switzerland. Marc.Possover@hirslanden.ch

STUDY OBJECTIVE: To show the relationship between the neuropeptide-Y pelvic sympathetic nerves and neoangiogenesis in the development of endometriosis DESIGN: Prospective study. SETTING: Academic community teaching hospital. PATIENTS: Fifteen consecutive women with unilateral endometriotic infiltration of the sacrouterine ligaments. INTERVENTIONS: A laparoscopic excision/biopsy of involved and noninvolved parts of the sacrouterine ligaments were taken. The sections were incubated with the neuronal marker rabbit polyclonal anti-protein gene product 9.5 and rabbit polyclonal anti-neuropeptide-Y. We made a comparative study on the distribution of nerve fibers and their relationship to the vessels on intact and endometriotic involved tissue. MEASUREMENTS AND MAIN RESULTS: The results show that a large amount of nerves are present around the blood vessels in the endometriosis samples, and a large number of these nerves are neuropeptide-Y sympathetic nerves. Adrenergic fibers are also present in the intact control subjects, however, in significantly smaller amounts. CONCLUSION: This finding shows a strong relationship between the neuropeptide-Y sympathetic pelvic nerves and the neoangiogenesis required for the development of endometriosis.

J Minim Invasive Gynecol. 2009 May-Jun;16(3):326-32.

Laparoscopic posthysterectomy vaginal vault excision for chronic pelvic pain and deep dyspareunia.

Trehan AK, Sanaullah F.

Dewsbury and District Hospital, Dewsbury, United Kingdom. ashwini.trehan@midyorks.nhs.uk

STUDY OBJECTIVE: To evaluate the outcome of posthysterectomy laparoscopic vaginal vault excision and its long-term effects on chronic pelvic pain, dyspareunia, quality of life, and patient satisfaction. MATERIALS AND METHODS: This is a retrospective cohort study (Canadian task force classification II-3) incorporating case note review and a postal questionnaire. It describes 22 consecutive patients who underwent laparoscopic vaginal vault excision for posthysterectomy dyspareunia and chronic pelvic pain. At laparoscopy, full thickness vaginal vault was excised along with scar tissue or any cyst. The vaginal cuff was closed laparoscopically. The patients were sent a validated questionnaire to assess their pain scores, general health, quality of life, and satisfaction with the surgery. The mean interval from vaginal vault excision and to questionnaire distribution was 1.8 years. The statistical analysis was performed with SPSS 15. RESULTS: The mean age of the women was 40 years. All women had vaginal vault tenderness on examination and underwent laparoscopic vaginal vault excision. The only intraoperative complication was 1 puncture injury of the bladder, which was produced by 10-Veres needle during manipulation. A single or a combination of additional procedures was performed at the same time. The patient satisfaction questionnaires were received from 16 (72.7%) women. Of the 16 (72.7%) respondents, 13 (81.25%) confirmed improvement in dyspareunia. The mean pain scores decreased, and quality of life and general health improved significantly after vaginal vault excision (p <.05, t test). CONCLUSION: Laparoscopic vaginal apex excision is a safe and effective management option after carefully excluding other causes of deep dyspareunia and chronic pelvic pain. It also provides an opportunity to detect and surgically excise previously undiagnosed endometriosis and other disease.

J Minim Invasive Gynecol. 2009 May-Jun;16(3):269-81.

Laparoscopic management of endometriosis: comprehensive review of best evidence.

Yeung PP Jr, Shwayder J, Pasic RP.

Department of Obstetrics and Gynecology, Division of Minimally Invasive Gynecologic Surgery, Duke University, Durham, North Carolina 27704, USA. patrick.yeung@duke.edu

STUDY OBJECTIVE: To provide a comprehensive review of the best evidence available in the laparoscopic management of endometriosis for pain and/or fertility and to provide practical recommendations based on this information. DESIGN: Review article of randomized controlled trials. PATIENTS: Women with endometriosis. METHODS: A systematic search was performed of the Cochrane Library and MEDLINE database for randomized controlled trials relating only to laparoscopic management of endometriosis. The information from 7 Cochrane review articles and 35 original randomized trials is presented in a clinically relevant question-and-answer format. CONCLUSIONS: Awareness of endometriosis as a disease with substantial morbidity is vitally important. Laparoscopic treatment of endometriosis is beneficial for reducing pain and improving fertility. Laparoscopic presacral neurectomy, but not laparoscopic uterosacral nerve ablation, is a useful adjunct to conservative surgery for endometriosis in patients with a midline component of pain. Preoperative hormonal suppression with gonadotropin-receptor hormone analogue may be helpful in decreasing endometriosis disease scores. Postoperative hormonal suppression with either a gonadotropin-receptor hormone analogue or progestin (including the levonorgestrel intrauterine system) may be helpful in reducing pain and increasing time to recurrence of symptoms. Excisional cystectomy is the preferred method to treat endometrial cysts for both pain and fertility and may be aided by the use of mesna and initial circular excision. An absorbable adhesion barrier (Interceed), 4% icodextrin solution (Adept), and a viscoelastic gel (Oxiplex/AP, FzioMed, Inc., San Luis Obispd, CA; not available in the United States) are safe and effective products to help prevent adhesions in laparoscopic surgery to treat endometriosis.

Publication Types:

J Radiol. 2009 Mar;90(3 Pt 1):277-86.

Pelvic MRI at 3.0 Tesla

[Article in French]

Léautaud A, Marcus C, Ben Salem D, Bouché O, Graesslin O, Hoeffel C.

Service de Radiologie, Pôle d’imagerie, CHU Reims, Hôpital Robert Debré, Reims, France. alexandre.leautaud@yahoo.fr

High resolution MR imaging is ideal for pelvic imaging. To achieve good image quality at 3.0 Tesla MR, one may not simply import protocols used at 1.5 Tesla MR. Issues specific to 3.0 Tesla MR imaging must be considered including chemical shift, magnetic susceptibility, dielectric effect, specific absorption rates (SAR), motion artifacts and optimal echo time (TE) and repetition tome (TR) to achieve the desired tissue contrast. High quality pelvic MRI (prostate, rectum, and female pelvis) at 3.0 Tesla is possible. In addition, it offers potential advantages due to its ability to provide excellent vascular imaging and advances with functional imaging (diffusion, spectroscopy). This article discusses the parameters required to achieve quality pelvic imaging at 3.0 Tesla, the specifics of high-field MR imaging, and illustrates achievable clinical results.

Publication Types:

G Chir. 2009 Apr;30(4):141-3.

Laparoscopic treatment of incarcerated hernia through right broad ligament in patients with bilateral parametrium defects.

Leone V, Misuri D, Faggi U, Giovane A, Fazio C, Cardini S.

Santa Maria Nuova Hospital, Department of General Surgery, Firenze, Italy.

We present the first case reported in the literature of small bowel obstruction due to internal incarcerated hernia through a diagnosed bilateral broad ligament defect, and treated by laparoscopy. A 36-year-old white woman, gravida 0, para 0, was admitted to our hospital with intestinal obstruction symptoms. A laparoscopic approach was performed with 3 trocars and internal incarcerated hernia due to a defect in the right broad ligament was found. There was a similar defect in the left broad ligament. The small bowel, once reduced, appeared viable. Closure of both defects was carried out by laparoscopy with 2-0 monofilament absorbable running suture. The patient’s postoperative course was unremarkable and she was discharged from the hospital 4 days after the surgical procedure. The classification of defect was a bilateral fenestrae type I defect. Congenital ethiology is plausible because of the presence of bilateral defects and the absence of surgical trauma, pregnancy, pelvic inflammatory disease, endometriosis in the clinical history.

Minerva Urol Nefrol. 2009 Mar;61(1):68-70.

Management of urological problems in endometriosis.

Pastor-Navarro H, Carrión-López P, Martínez-Ruiz J, Martínez-Sánchiz C, Giménez-Bachs JM, Pastor-Gúzmán JM, Virseda Rodríguez JA, Salinas Sánchez AS.

Publication Types:

Ann N Y Acad Sci. 2009 Apr;1160:138-9.

Relaxin in endometriosis.

Morelli SS, Petraglia F, Weiss G, Luisi S, Florio P, Goldsmith LT.

Department of Obstetrics, Gynecology and Women’s Health, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, USA. morellsa@umdnj.edu

Endometriosis is an important contributing factor to chronic pelvic pain and infertility. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) have each been implicated in the establishment of endometriotic lesions. Since relaxin regulates the expression of MMPs and VEGF in the endometrium, we tested the hypothesis that relaxin plays a role in endometriosis by comparing the expression of relaxin mRNA and its LGR7 (RXFP1) receptor mRNA in normal human endometrium to those in samples from patients with endometriosis.

Arch Pathol Lab Med. 2009 May;133(5):739-42.

Challenges in the interpretation of peritoneal cytologic specimens.

Lin O.

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. lino@mskcc.org

CONTEXT: The presence of malignant cells in peritoneal washings leads to classification as International Federation of Gynecology and Obstetrics stage IC or higher in ovarian carcinomas and at least International Federation of Gynecology and Obstetrics stage IIIA in endometrial carcinomas. Unfortunately, the morphologic examination of cytologic specimens has not proven to be a sensitive or specific diagnostic tool. Malignant cells might be few in number and might be unrecognized among a large population of mesothelial cells and/or macrophages, or reactive mesothelial cells might be misinterpreted as neoplastic cells leading to unnecessary chemotherapy. OBJECTIVE: To evaluate the main pitfalls in the evaluation of peritoneal washings in patients with gynecologic malignancies and analyze the ancillary studies that might be helpful to achieve the correct diagnosis with an emphasis on immunocytochemistry. DATA SOURCES: A comprehensive review of the literature was performed. CONCLUSIONS: Peritoneal effusions may represent major challenges to the pathologist and can have important clinical implications. Immunostains for epithelial markers such as B72.3, MOC-31, and Ber-EP4 represent the best available markers to identify epithelial cells. Caution is advised to not overdiagnose endometriosis or endosalpingiosis as adenocarcinoma.

Publication Types:

Minerva Ginecol. 2009 Jun;61(3):215-26.

Gynecological endoscopy for symptomatic endometriosis.

Vercellini P, Abbiati A, Aimi G, Amicarelli F, De Giorgi O, Uglietti A.

Department of Obstetrics and Gynecology University of Milan, Milan 20122, Italy. paolo.vercellini@unimi.it

The best available evidence on surgery for endometriosis-associated pain has been reviewed in order to define the benefit of various interventions in the most frequently encountered clinical conditions, and discuss the robustness of the reported data in light of the quality of the relevant study design. Methodological drawbacks limit the validity of observational, non-comparative studies on the effect of laparoscopy for stage I to IV disease. The results of three randomized, controlled trials, indicate that the absolute benefit increase of destruction of lesions compared with sham operation in terms of proportion of women reporting pain relief was between 30% and 40% after short follow-up periods. The effect size decreased with time and the reoperation 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 about 70-80% of the subjects who continued the study. However, at one-year follow-up approximately 50% of the women needed medical treatments. Major complications were observed in 3-10% of the patients. Medium-term recurrence of lesions was observed in about 20% of the cases, and around 25% of the women underwent repetitive surgery. Routine complementary performance of denervating procedures cannot be recommended based on the quality of the available information, as only a few symptomatic patients complain of exclusively midline, hypogastric pain. Pain recurrence and reoperation 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 and, especially in complex conditions, acceptable results can be assured in referral centers.

Publication Types:

Clin Radiol. 2009 Jun;64(6):645-8. Epub 2009 Apr 2.

Case report: Imaging of Mullerian adenosarcoma arising in adenomyosis.

Jha P, Ansari C, Coakley FV, Wang ZJ, Yeh BM, Rabban J, Poder L.

Department of Radiology, University of California San Francisco, San Francisco, CA 94143-0628, USA.

Publication Types:

Mol Cell Endocrinol. 2009 Aug 13;307(1-2):196-204. Epub 2009 May 3.

TAK1 activation for cytokine synthesis and proliferation of endometriotic cells.

Taniguchi F, Harada T, Miyakoda H, Iwabe T, Deura I, Tagashira Y, Miyamoto A, Watanabe A, Suou K, Uegaki T, Terakawa N.

Department of Obstetrics and Gynecology, Tottori University Faculty of Medicine, Yonago, Japan. tani4327@med.tottori-u.ac.jp

Endometriosis causes pelvic pain and infertility in women of reproductive age. We explored TNFalpha-induced specific signaling pathways and gene expressions in endometriotic stromal cells (ESCs). Based on the data of the pathway specific cDNA array, we analyzed the role of TAK1, which is believed to work as a common mediator for NF-kappaB and MAPK pathways. Using the NF-kappaB pathway array, we found that TNFalpha upregulated ICAM-3, IL-6, IL-8, TAK1, JNK2, RelA, and TLR4 expressions. TNFalpha augmented the phosphorylation of TAK1. By transfection of TAK1 siRNA, TNFalpha-induced phosphorylation of IkappaBalpha, JNK1/2, and p38MAPK, as well as IL-6 or IL-8 expression, were repressed. TAK1 silencing in TNFalpha-pretreated ESCs caused a decrease in the proportion of cells in S-phase, and reduced TNFalpha-promoted BrdU incorporation. We provide the first evidence that TNFalpha and its downstream TAK1, which are key mediators for NF-kappaB and MAPK pathways, may be involved in the pathogenesis of endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2009 Jun;144(2):105-9. Epub 2009 May 5.

Differentiating interstitial cystitis from similar conditions commonly seen in gynecologic practice.

Dell JR, Mokrzycki ML, Jayne CJ.

Generations OB/GYN, 9430 Park West, Boulevard #320 Parkwest Tower, Knoxville, TN 37923, USA. Delli12@comcast.net

Interstitial cystitis is a syndrome characterized by pelvic pain, urinary urgency/frequency, nocturia, and dyspareunia, with no other identifiable etiology. The clinical presentation of interstitial cystitis is similar to that of many other conditions commonly seen in female patients, including recurrent urinary tract infections, endometriosis, chronic pelvic pain, vulvodynia, and overactive bladder. In addition, interstitial cystitis may exist concurrently with these conditions. Correct diagnosis is necessary for appropriate treatment and improved outcomes. Tools to assist in the diagnosis of interstitial cystitis, as well as effective therapies for this condition, are available. A diagnosis of interstitial cystitis should be considered in patients with irritative voiding symptoms and/or pelvic pain complaints.

Publication Types:

Fertil Steril. 2009 Jul;92(1):61-7. Epub 2009 May 5.

 

The impact of peritoneal fluid from healthy women and from women with endometriosis on sperm DNA and its relationship to the sperm deformity index.

Mansour G, Aziz N, Sharma R, Falcone T, Goldberg J, Agarwal A.

Obstetrics and Gynecology and Women’s Health Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

OBJECTIVE: To study the effect of peritoneal fluid (PF) from healthy women and from women with endometriosis on sperm DNA and its relationship to sperm morphology as assessed by the sperm deformity index (SDI). DESIGN: Experimental study. SETTING: Research laboratory at an academic hospital. PATIENT(S): Healthy women undergoing laparoscopic tubal ligation and women with endometriosis. INTERVENTION(S): Aliquots of prepared sperm from 10 healthy donors were incubated with PF from healthy women undergoing laparoscopic tubal ligation (treatment 1, n = 10), with PF from patients with endometriosis (treatment 2, n = 10), and with human tubal fluid media with 10% bovine serum albumin (control, n = 10). MAIN OUTCOME MEASURE(S): Sperm DNA fragmentation was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay and SDI. RESULT(S): There was a significant increase in sperm DNA damage at 24 hours compared with at 1.5 and 3 hours. The SDI scores significantly correlated with sperm DNA damage after 1.5 and 24 hours of incubation in all aliquots. Percentage normal morphology did not correlate with DNA damage. CONCLUSION(S): In vitro exposure of sperm to PF from patients with endometriosis is associated with significantly increased DNA damage. There is evidence of interdependence between the sperm morphology as assessed by SDI scores and DNA damage. The significant increase in sperm DNA damage observed after 24 hours of incubation may be clinically relevant.

Publication Types:

Fertil Steril. 2009 Oct;92(4):1250-2. Epub 2009 May 5.

Histopathologic features of endometriotic rectal nodules and the implications for management by rectal nodule excision.

Roman H, Opris I, Resch B, Tuech JJ, Sabourin JC, Marpeau L.

Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen, France. horace.roman@gmail.com

Using data from 27 women with deep rectal endometriosis, managed by segmental resection, we observed that in 89% of cases active glandular endometrial foci were responsible for a deeper infiltration of rectal layers than that of fibrosis and smooth fibers by 5 mm on average. These data might be useful for surgeons performing rectal nodule excision, suggesting the benefits of administrating postoperative medical treatment to reduce the risk of rectal recurrences caused by remaining active endometriotic foci.

Int J Gynecol Cancer. 2009 Apr;19(3):471-9.

The role of hepatocyte nuclear factor-1beta in the pathogenesis of clear cell carcinoma of the ovary.

Kobayashi H, Yamada Y, Kanayama S, Furukawa N, Noguchi T, Haruta S, Yoshida S, Sakata M, Sado T, Oi H.

 

Department of Obstetrics and Gynecology, Nara Medical University, Japan. hirokoba@naramed-u.ac.jp

PROBLEM: Clear cell carcinoma (CCC) of the ovary has a number of features distinguishing it from other epithelial ovarian carcinomas (EOC) because of its characteristic histology and biology, frequent concurrence with endometriotic lesion, and highly chemoresistant nature resulting in an extremely poor prognosis. The incidence of CCC has been steadily increasing in Japan. They comprise approximately 20% of all EOC. Understanding the mechanisms of CCC development and elucidating pathogenesis and pathophysiology are intrinsic to prevention and effective therapies for CCC. METHOD OF STUDY: This article reviews the English language literature for biology, pathogenesis, and pathophysiological studies on endometriosis-associated EOC. Several data are discussed in the context of endometriosis and CCC biology. RESULTS: Recent studies based on genome-wide expression analysis technology have noted specific expression of hepatocyte nuclear factor-1beta (HNF-1beta) in endometriosis and CCC, suggesting that early differentiation into the clear cell lineage takes place in the endometriosis. The HNF-1beta-dependent pathway of CCC will be discussed, which are providing new insights into regulation of apoptosis and glycogen synthesis and resistance of CCC to anticancer agents. CONCLUSIONS: This review summarizes recent advances in the HNF-1beta and its target genes; the potential challenges to the understanding of carcinogenesis, pathogenesis, and pathophysiology of CCC; and a possible novel model is proposed.

Publication Types:

Mol Endocrinol. 2009 Aug;23(8):1291-305. Epub 2009 Apr 30.

Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms.

Banu SK, Lee J, Speights VO Jr, Starzinski-Powitz A, Arosh JA.

Reproductive Endocrinology and Cell Signaling Laboratory, Department of Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, Texas 77843, USA.

Endometriosis is a benign chronic gynecological disease of reproductive-age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, and the reproductive health of women and fail to prevent reoccurrence of disease. There is a critical need to identify new specific signaling modules for non-estrogen-targeted therapies for endometriosis. In our previous study, we reported that selective inhibition of cyclooxygenase-2 prevented survival, migration, and invasion of human endometriotic epithelial and stromal cells, which was due to decreased prostaglandin E(2) (PGE(2)) production. In this study, we determined mechanisms through which PGE(2) promoted survival of human endometriotic cells. Results of the present study indicate that 1) PGE(2) promotes survival of human endometriotic cells through EP2 and EP4 receptors by activating ERK1/2, AKT, nuclear factor-kappaB, and beta-catenin signaling pathways; 2) selective inhibition of EP2 and EP4 suppresses these cell survival pathways and augments interactions between proapoptotic proteins (Bax and Bad) and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome c, and thus activates caspase-3/poly (ADP-ribose) polymerase-mediated intrinsic apoptotic pathways; and 3) these PGE(2) signaling components are more abundantly expressed in ectopic endometriosis tissues compared with eutopic endometrial tissues during the menstrual cycle in women. These novel findings may provide an important molecular framework for further evaluation of selective inhibition of EP2 and EP4 as potential therapy, including nonestrogen target, to expand the spectrum of currently available treatment options for endometriosis in women.

Publication Types:

Drugs. 2009;69(6):649-75. doi: 10.2165/00003495-200969060-00002.

 

Endometriosis: current therapies and new pharmacological developments.

Vercellini P, Somigliana E, Viganò P, Abbiati A, Barbara G, Crosignani PG.

Clinica Ostetrica e Ginecologica I, University of Milan, Milan, Italy. paolo.vercellini@unimi.it

Endometriosis is a chronic inflammatory condition that is responsive to management with steroids. The establishment of a steady hormonal environment and inhibition of ovulation can temporarily suppress ectopic implants and reduce inflammation as well as associated pain symptoms. In terms of pharmacological management, the currently available agents are not curative, and treatment often needs to be continued for years or until pregnancy is desired. Similar efficacy has been observed from the various therapies that have been investigated for endometriosis. Accordingly, combined oral contraceptives and progestins, based on their favourable safety profile, tolerability and cost, should be considered as first-line options, as an alternative to surgery and for post-operative adjuvant use. In situations where progestins and oral contraceptives prove ineffective, are poorly tolerated or are contraindicated, gonadotrophin-releasing hormone analogues, danazol or gestrinone may be used. Future therapeutic options for managing endometriosis must compare favourably against existing agents before they can be considered for inclusion into current practice. Finally, as reproductive prognosis is not ameliorated by medical treatment, it is not indicated for women seeking conception.

Publication Types:

Biol Reprod. 2009 Aug;81(2):371-7. Epub 2009 Apr 29.

A botanical extract from channel flow inhibits cell proliferation, induces apoptosis, and suppresses CCL5 in human endometriotic stromal cells.

Wieser F, Yu J, Park J, Gaeddert A, Cohen M, Vigne JL, Taylor RN.

Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA. fwieser@emory.edu

Growing evidence suggests that medicinal herbs have direct actions on endometrial cells. By screening multiple herbs using an in vitro model of endometriosis, we found that a commonly used herbal formula exerted considerable antiproliferative effects. Our purpose was to investigate the effects of this antiendometriosis herbal mixture on cell proliferation, apoptosis, and CCL5 expression and secretion in endometriotic stromal cells in vitro. Isolated normal endometrial, eutopic, and ectopic endometriotic stromal cells were cultured under established conditions. Cell proliferation, apoptosis, and CCL5 gene expression protein secretion was evaluated after incubation with different concentrations of an antiendometriosis herbal mixture extract. Cell proliferation was assessed by cell counting, (3)H-thymidine incorporation, and MTS assays. Apoptosis was determined by blotting using anti-cleaved caspase 3 antibodies and by a TUNEL assay. CCL5 gene expression and protein secretion were determined by transient transfection of gene promoter reporters and ELISAs in cell supernatants. Extracts of a traditional herbal mixture dose-dependently decreased cell proliferation in normal, eutopic, and ectopic endometriotic stromal cells. (3)H-Thymidine uptake and MTS confirmed these findings. The herbal extracts induced apoptosis, as evidenced by activation of caspase 3 and the presence of TUNEL-positive cells after treatment. The herbal extracts also suppressed CCL5 gene transcription and protein secretion in endometriotic stromal cells, even when corrected for cell number. Extracts from a medicinal herbal mixture have direct effects on cell proliferation, apoptosis, and CCL5 production in endometriotic stromal cells. Our findings support the further investigation of novel, potentially safe and well-tolerated botanical products as future endometriosis treatments.

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N Engl J Med. 2009 Apr 30;360(18):1911-2; author reply 1912.

 

Comment on:

Endometriosis.

Colette S, Donnez J.

Publication Types:

Nan Fang Yi Ke Da Xue Xue Bao. 2009 Apr;29(4):757-9.

Small interference RNA targeting nuclear factor-kappaB inhibits endometriotic angiogenesis in chick embryo chorioallantocic membrane.

[Article in Chinese]

Liu MB, He YL, Zhong J.

Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China. liumb1972@126.com

OBJECTIVE: To investigate the effect of small interference RNA (siRNA) targeting nuclear factor-kappaB (NF-kappaB) on endometriosis. METHOD: The eutopic endometrium of women with endometriosis were transplanted into the nonvascular region of 8-day-old chicken embryo chorioallantocic membrane (CAM), and the effects of NF-kappaB p65 siRNA on the vascularization and endometriotic lesion formation were tested with proper controls. RESULTS: Transplantation of the endometrium onto the CAM resulted in a strong angiogenic response in the chicken tissue. The angiogenesis was significantly reduced and endometriotic lesion formation significantly suppressed with siRNA targeting NF-kappaB in comparison with the control group. CONCLUSIONS: The NF-kappaB pathway is involved in the development of endometriotic lesions in vitro, and NF-kappaB gene silencing reduces endometriotic angiogenesis and promotes cell apoptosis in the endometriotic lesions, suggesting that NF-kappaB might be a good target for endometriosis treatment.

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Ultrasound Obstet Gynecol. 2009 May;33(5):497-501.

Transvaginal sonography for the assessment of ovarian and pelvic endometriosis: how deep is our understanding?

Savelli L.

 

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Gynecol Obstet Invest. 2009;68(2):73-81. Epub 2009 Apr 28.

Gonadotropin-releasing hormone agonist reduces aromatase cytochrome P450 and cyclooxygenase-2 in ovarian endometrioma and eutopic endometrium of patients with endometriosis.

Kim YA, Kim MR, Lee JH, Kim JY, Hwang KJ, Kim HS, Lee ES.

Department of Obstetrics and Gynecology, Ilsan Paik Hospital, Inje University, Ilsan, Korea.

AIMS: To investigate whether the GnRH agonist may reduce aromatase P450 and COX-2 in the eutopic endometrium of patients with endometriosis and ovarian endometrioma. MATERIALS AND METHODS: Endometrial specimens and ovarian endometrioma were obtained from 15 women with endometriosis undergoing laparoscopic surgery. The stromal cells of the eutopic endometrium and ovarian endometroma were cultured in the presence of the GnRH agonist (leuprolide acetate 0, 1, 5 and 10 microM) for 24 h. To investigate the effects of the GnRH agonist on the eutopic endometrium in vivo, biopsy samples of the endometrium (n = 5) among the patients who underwent laparoscopy were obtained after GnRH agonist therapy. The protein production of aromatase cytochrome P450 and COX-2 was examined by Western blot. RESULTS: Proteins of aromatase P450 and COX-2 were reduced in the eutopic endometrium of patients with endometriosis treated with the GnRH agonist for 3 months. The stromal cells in the culture of endometrial explants and ovarian endometrioma which were treated with the GnRH agonist reduced the aromatase P450 and COX-2. CONCLUSION: The GnRH agonist reduced aromatase P450 and COX-2 by direct action on the eutopic endometrium of patients with endometriosis and ovarian endometrioma. Copyright 2009 S. Karger AG, Basel.

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Hum Reprod. 2009 Aug;24(8):1900-8. Epub 2009 Apr 28.

Doxycycline causes regression of endometriotic implants: a rat model.

Akkaya P, Onalan G, Haberal N, Bayraktar N, Mülayim B, Zeyneloglu HB.

Obstetrics and Gynecology, Baskent University School of Medicine, Kubilay Sok no. 36 Maltepe, 06570 Ankara, Turkey.

BACKGROUND: Doxycycline (Dox) has a number of non-antibiotic properties. One of them is the inhibition of matrix metalloproteinase (MMP) activity. The aim of this study was to assess the effects of Dox in a rat endometriosis model. METHODS: Endometriosis was surgically induced in 40 rats by transplanting of endometrial tissue. After 3 weeks, repeat laparotomies were performed to check the implants and the animals were randomized into four groups: Group I, low-dose Dox (5 mg/kg/day); Group II, high-dose Dox (40 mg/kg/day); Group III, leuprolide acetate 1 mg/kg single dose, s.c.; and Group VI (controls), no medication. The treatment, initiated on the day of surgery and continuing for 3 weeks, was administered to the study groups. Three weeks later, the rats were euthanized and the implants were evaluated morphologically and histologically for immunoreactivity of MMP-2 and -9, and interleukin-6 (IL-6) concentration in the peritoneal fluid was assayed. RESULTS: Treatment with leuprolide acetate, or high-dose or low-dose Dox caused significant decreases in the implant areas compared with the controls (P = 0.03, P = 0.006, and P = 0.001, respectively). IL-6 levels in peritoneal fluid decreased in Group I (P = 0.02) and Group III (P < 0.05). MMP H scores were significantly lower in the group that received low-dose Dox in both epithelial and stromal MMP-2 and -9 immunostaining when compared with the control group [P = 0.048, P = 0.002, P = 0.007 and P = 0.002, respectively, MMP-2 (epithelia), MMP-2 (stroma), MMP-9 (epithelia) and MMP-9 (stroma)]. CONCLUSIONS: Low-dose Dox caused regression of endometriosis in this experimental rat model.

Publication Types:

Reprod Biomed Online. 2009 Apr;18(4):582-8.

IVF outcome in women with endometriosis in relation to tumour necrosis factor and anti-Müllerian hormone.

Falconer H, Sundqvist J, Gemzell-Danielsson K, von Schoultz B, D’Hooghe TM, Fried G.

Department of Woman and Child Health, Division of Obstetrics and Gynecology, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden. henrik.falconer@karolinska.se

This study reports on anti-Müllerian hormone (AMH) in serum and follicular fluid (FF) in relation to inflammatory parameters in women with and without endometriosis undergoing IVF. Serum and FF samples were obtained from 72 women, with (n = 34) and without (n = 38) endometriosis, undergoing IVF. The concentrations of AMH, FSH, tumour necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF) and several interleukins were analysed. Women with endometriosis had significantly lower AMH in serum and FF (serum: 6.38 versus 12.8 pM; P < 0.01, FF: 14.0 versus 19.6 pM; P < 0.05). TNF was increased in FF (40.0 versus 30.8 pg/ml, P < 0.05) from women with endometriosis and significantly higher concentrations of IL-15 and GM-CSF were detected in FF (both P < 0.05). During IVF, women with endometriosis responded well to FSH but had lower fertilization rates. Women with endometriosis have elevated concentrations of several cytokines in FF. They respond adequately to exogenous FSH but may have impaired oocyte quality, reflected in lower fertilization rates, presumably resulting from an inflammatory process in the ovaries. Further studies are needed to elucidate the role of AMH in predicting ovarian reserve in women with endometriosis.

Publication Types:

Clin Exp Obstet Gynecol. 2009;36(1):49-52.

Near lethal endometriosis and a massive (64 kg) endometrioma: case report and review of the literature.

Sakpal SV, Patel C, Chamberlain RS.

 

Department of Surgery, Saint Barnabas Medical Center, Livingston, New Jersey 07039, USA.

A 51-year-old morbidly obese, hypertensive, anemic, and amenorrheic female presented with anuria and respiratory symptoms. The patient had a distinctly massive abdomen with necrotic anterior abdominal wall, and laboratory findings revealed a leukocytosis, profound anemia, coagulopathy and renal failure. An abdominal sonogram showed a large, complex intra-abdominopelvic mass and ascites. At surgery, a massive, cystic left ovarian mass, 37 1 of ascitic/cyst fluid, and several peritoneal nodules were removed–a total of 64 kg of tumorous tissue. Histopathological evaluation of the mass revealed an endometrioma. We present this rare case of severe endometriosis in a morbidly obese patient who presented with an exceptionally large endometrioma (64 kg), multifactorial respiratory and renal failure, coagulopathy, and profound anemia.

Publication Types:

Clin Exp Obstet Gynecol. 2009;36(1):46-8.

Complete remission of OC-resistant catamenial shoulder joint pain and inguinal pain associated with extraperitoneal endometriosis following personalized GnRH agonist therapy.

Tanaka T, Umesaki N.

Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama, Japan. tetanaka@wakayama-med.ac.jp

BACKGROUND: Patients with severe extraperitoneal endometriosis require rapid remission and cannot wait for the effects of oral contraceptive hormones (OCs) to appear. CASE: We successfully achieved personalized gonadotropin-releasing hormone agonist (GnRHa) therapy for a patient with catamenial right shoulder joint pain and right inguinal pain associated with extraperitoneal endometriosis, which was completely unable to be suppressed by OCs. A total of 15 subcutaneous GnRHa depot injections over a period of 19 months was performed according to the serum estradiol and LH levels, in order to maintain long-term amenorrhea without any estrogen-deprivation effects. No recurrence of the catamenial symptoms has been observed for more than 35 months after the final GnRHa depot injection. CONCLUSION: Personalized GnRHa therapy should become the first-choice therapy for OC-resistant inoperable extraperitoneal endometriosis.

Publication Types:

Clin Exp Obstet Gynecol. 2009;36(1):23-5.

Serological testing for celiac disease in women with endometriosis. A pilot study.

Aguiar FM, Melo SB, Galvão LC, Rosa-e-Silva JC, dos Reis RM, Ferriani RA.

Sector of Human Reproduction, Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, SP, Brazil.

PURPOSE OF INVESTIGATION: Celiac disease (CD) involves immunologically mediated intestinal damage with consequent micronutrient malabsorption and varied clinical manifestations, and there is a controversial association with infertility. The objective of the present study was to determine the presence of CD in a population of infertile women with endometriosis. METHODS: A total of 120 women with a diagnosis of endometriosis confirmed by laparoscopy (study group) and 1,500 healthy female donors aged 18 to 45 years were tested for CD by the determination of IgA-transglutaminase antibody against human tissue transglutaminase (t-TGA) and anti-endomysium (anti-EMA) antibodies. RESULTS: Nine of the 120 women in the study group were anti-tTGA positive and five of them were also anti-EMA positive. Four of these five patients were submitted to intestinal biopsy which revealed CD in three cases (2.5% prevalence). The overall CD prevalence among the population control group was 1:136 women (0.66%). CONCLUSION: This is the first study reporting the prevalence of CD among women with endometriosis, showing that CD is common in this population group (2.5%) and may be clinically relevant.

Am J Obstet Gynecol. 2009 Jul;201(1):107.e1-6. Epub 2009 Apr 26.

Diagnostic accuracy of transvaginal sonography for the diagnosis of adenomyosis: systematic review and metaanalysis.

Meredith SM, Sanchez-Ramos L, Kaunitz AM.

Department of Obstetrics and Gynecology, University of Florida College of Medicine, Jacksonville, FL, USA.

OBJECTIVE: The purpose of this study was to critically appraise the diagnostic accuracy of transvaginal sonography for diagnosing adenomyosis. STUDY DESIGN: Computerized databases were used to identify relevant reports published between 1966 and 2007 reporting data on the accuracy of transvaginal sonography for diagnosing adenomyosis in women having hysterectomy. The presence or absence of adenomyosis was confirmed by histopathologic analysis of hysterectomy specimens. The total analysis included 14 trials with 1895 aggregate participants. Two authors independently assessed methodological quality and constructed tables for the assessment of diagnostic measures. RESULTS: Transvaginal ultrasound predicted adenomyosis with a likelihood ratio of 4.67 (95% confidence interval [CI], 3.13-6.17). The overall prevalence of adenomyosis was 27.9% (95% CI, 25.5-30.3). The probability of adenomyosis with an abnormal transvaginal ultrasound was 66.2% (95% CI, 61.6- 70.6). The probability of adenomyosis with a normal transvaginal ultrasound was 9.1% (95% CI, 7.3-11.1). CONCLUSION: Transvaginal sonography appears to be an accurate diagnostic test for adenomyosis.

Publication Types:

Med Sci Monit. 2009 May;15(5):RA116-23.

What have the ‘omics done for endometriosis?

Siristatidis CS.

Gynecological Clinic, General Air Force Hospital, Athens, Greece.

A review of the current literature was attempted in order to determine to what degree new technological features, such as the use of proteomics, genomics, and gene microarrays, have contributed to the elucidation of the specific pathways to the formation of endometriosis as well as to the discovery of potential biomarkers and new treatment strategies. Endometriosis is well described as a condition in which multiple genetic components and still foggy environmental risk factors are important determinants of the disease’s origin, maintenance, persistence, and clinical outcome. The concept is that because of the special features and complexity of the disease, endometriosis is ideally suited as a target for genome- and proteome-wide scanning. Reviewing the current literature we found that, apart from the better understanding of the pathophysiology and the metabolic pathways which lead to potential biomarkers for endometriosis, there are still issues to be clarified and applications to be achieved. The evolving genomic and proteomic technologies remain poised to revolutionize the diagnosis and treatment of endometriosis but have not yet lead to a single new therapy or tested biomarker. The reasons have mainly to do with the complex and multifactorial character of the disease itself.

Publication Types:

Fertil Steril. 2009 Apr 24. [Epub ahead of print]

Tumor necrosis factor alpha -C850T polymorphism is significantly associated with endometriosis in Asian Indian women.

Vijaya Lakshmi K, Shetty P, Vottam K, Govindhan S, Ahmad SN, Hasan Q.

Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre, Khairatabad, Hyderabad, India.

OBJECTIVE: To establish the association of tumor necrosis factor alpha (TNFA) promoter C850T polymorphism in Asian Indian women with endometriosis. DESIGN: Case control study, from multiple gynecological centers from Hyderabad, a cosmopolitan city in southern India. The study included 245 women who comprised 110 surgically confirmed cases of endometriosis, 50 ultrasonographically confirmed cases of fibroid tumors, and 85 healthy female volunteers. SETTING: Academic hospital. PATIENT(S): The cases were 245 women, 160 patients and 85 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Tumor necrosis factor alpha -C850T polymorphism may be used as a molecular marker for endometriosis in our population. RESULT(S): In this study we have demonstrated an association between TNFA -C850T polymorphism and endometriosis. The T allele is significantly associated with endometriosis when compared to women with fibroids as well as healthy controls. Our data imply that the T allele is associated with endometriosis (OR = 1.9594: 95% CI, 1.3833-2.7753; in our population. The TT genotype increases the risk of endometriosis by fourfold (4.5542: 95% CI, 2.0388-10.1701. CONCLUSION(S): This study suggests that -C850T TNFA gene polymorphism could be used as a relevant molecular marker to identify women with risk of developing endometriosis in our population.

Fertil Steril. 2009 Apr 24. [Epub ahead of print]

A prospective, randomized, double-blind, placebo-controlled trial of multimodal intraoperative analgesia for laparoscopic excision of endometriosis.

Costello MF, Abbott J, Katz S, Vancaillie T, Wilson S.

School of Women’s and Children’s Health, Division of Obstetrics and Gynaecology, University of New South Wales, Royal Hospital for Women, Randwick, Sydney, New South Wales, Australia; Department of Reproductive Medicine and IVF Australia, Royal Hospital for Women, Randwick, Sydney, NSW, Australia, 2031.

OBJECTIVE: To assess the efficacy of multimodal intraoperative analgesia in reducing postoperative pain and/or opioid requirements in women undergoing laparoscopic excision of endometriosis. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Endogynecologic department of a university teaching hospital. PATIENT(S): Women booked for laparoscopic excision of endometriosis. INTERVENTION(S): Intraoperative multimodal analgesia versus placebo. Analgesia consisted of Diclofenac sodium 100 mg suppository per rectum and 0.75% Ropivacaine to portal sites, subperitoneally under excision sites and topically to each subdiaphragmatic area. MAIN OUTCOME MEASURE(S): Postoperative total hospital opioid analgesic requirements and postoperative pain intensity. RESULT(S): The study was terminated prematurely, after a planned interim analysis (which included 66 randomized patients or 43% of the planned number of patients) found significantly less total hospital opioid requirements in the analgesic group compared with the placebo group (19.0 mg vs. 34.5 mg; difference -14.0 mg [95% confidence interval -26.0 to -2.0 mg]). There was no difference in postoperative pain intensity between the two groups. CONCLUSION(S): The use of multimodal intraoperative analgesia at laparoscopic excision of endometriosis reduces postoperative opioid requirements.

Fertil Steril. 2009 Apr 24. [Epub ahead of print]

Discoid or segmental rectosigmoid resection for deep infiltrating endometriosis: a case-control study.

Fanfani F, Fagotti A, Gagliardi ML, Ruffo G, Ceccaroni M, Scambia G, Minelli L.

Division of Gynecologic Oncology, Catholic University of the Sacred Heart, Rome.

OBJECTIVE: To evaluate the efficacy of discoid resection for the treatment of deep infiltrating endometriosis and whether it could be considered to be a valid alternative to the rectosigmoid segmental resection. DESIGN: Case-control study. SETTING: Departments of Obstetrics and Gynecology, Ospedale Sacro Cuore of Negrar, Verona, and Catholic University of the Sacred Heart, Rome, Italy. PATIENT(S): Women with deep infiltrating and intestinal endometriosis divided into study group (48 patients) and control group (88 patients). INTERVENTION(S): All patients underwent laparoscopic endometriosis excision plus discoid rectosigmoid resection (study group) or segmental resection (control group). MAIN OUTCOME MEASURE(S): Short- and long-term outcomes. RESULT(S): In the study group, median operating time was 200 minutes, with a median estimated blood loss of 203 mL. Median ileus was 3 days with a median postoperative hospitalization of 7 days. Early complications were observed in six patients (12.5%), and in two of them (4.16%) a surgical management was necessary. Median follow-up period was 33 months, and five recurrences (10.4%) were registered. In the control group, no significant differences were noticed except for longer operative time, more temporary ileostomy, postoperative fever, and long-term bladder dysfunctions. CONCLUSION(S): Laparoscopic mechanical discoid resection is feasible, markedly improved endometriosis related symptoms, and could be considered as a worthy alternative to classic segmental resection in selected patients. 

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