Hum Reprod. 2010 May 26. [Epub ahead of print]

Association between genetic polymorphisms in fibroblast growth factor (FGF)1 and FGF2 and risk of endometriosis and adenomyosis in Chinese women.

Kang S, Li SZ, Wang N, Zhou RM, Wang T, Wang DJ, Li XF, Bui J, Li Y.

Department of Obstetrics and Gynaecology, Hebei Cancer Institute, Hebei Medical University, Fourth Hospital, Jiankanglu 12, Shijiazhuang 050011, China.

BACKGROUND Angiogenesis appears to be an important event in the pathophysiology of endometriosis (EM) and adenomyosis. Two angiogenic factors, fibroblast growth factor (FGF) 1 and 2, play a central role in the initiation of angiogenesis. We investigated whether FGF1 -1385A/G and FGF2 754C/G polymorphisms are associated with a risk of developing EM and adenomyosis. METHODS Genotypes were analyzed by the PCR-restriction fragment length polymorphism method in two groups of women, of Han ethnicity in north China, aged 16-55 years: (1) 421 EM patients and 421 controls; (2) 269 adenomyosis patients and 269 controls. RESULTS There was no difference in genotype distribution of the FGF1 -1385A/G polymorphism between adenomyosis cases and controls (P > 0.05), but the frequency of the A allele in EM patients was lower than that in controls (P = 0.013). Genotype and allele frequencies of the FGF2 754C/C polymorphism were significantly different in both EM and adenomyosis cases versus control groups. Compared with C/C homozygotes, the G allele (C/G + G/G) was associated with a decreased susceptibility to developing EM [odds ratio (OR) = 0.575, 95% confidence interval (CI) = 0.387-0.854] and adenomyosis (OR = 0.577, 95% CI = 0.367-0.906). Combined genotype analysis of both polymorphisms also showed differences between cases versus controls (all P < 0.001). CONCLUSIONS Our study shows for the first time that the FGF2 754C/G polymorphism may be associated with a risk of developing EM and adenomyosis in north Chinese women. Carriers of the G allele in the FGF2 gene appear to be protected from these gynecological diseases. Further studies in other populations, and of other candidate genes, are now warranted.

Gynecol Endocrinol. 2010 May 26. [Epub ahead of print]

Association between GSTM1 gene polymorphism in Iranian patients with endometriosis.

Hosseinzadeh Z, Mashayekhi F, Sorouri ZZ.

Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.

Endometriosis is defined as a condition in which tissue histologically similar to the endometrium is found outside the uterine cavity. It develops mostly in women of reproductive age. Endometriosis shows a drastically elevated frequency in industrial areas. GSTM1 gene encodes a major detoxification phase enzyme that helps detoxify various xenobiotics. Deficiency in GSTM1 activity is caused by homozygous deletion of GSTM1 and leads to various biological consequences. There are significant interethnic differences in GSTM1 allele frequencies. In this study, the relationship between GSTM1 genotypes and endometriosis in an Iranian population was investigated. The study included 120 patients and 200 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using polymerase chain reaction (PCR). The GSTM1 null genotype was significantly associated with the increased risk of endometriosis (OR = 3.75, 95% confidence interval (CI) = 2.42-6.45, P < 0.0001). The prevalence of GSTM1-null genotype in the patient group was 72.5%, compared to 40% in the control group. The proportion of GSTM1A/B genotype was higher in controls as compared to cases (20% vs. 2.5%). This study suggests that GSTM1 null genotype is associated with higher risk of endometriosis; these observations, however, requiring further confirmation in a larger multi-ethnic study.

Gynecol Endocrinol. 2010 May 26. [Epub ahead of print]

Peritoneal fluid leptin levels are increased but adiponectin levels are not changed in infertile patients with pelvic endometriosis.

Pandey N, Kriplani A, Yadav RK, Lyngdoh BT, Mahapatra SC.

Department of Physiology.

Objective. Endometriosis is a leading cause of infertility, and recent studies suggest that leptin and adiponectin may have a role in its causation and progression. This study assessed levels of leptin and adiponectin in serum and peritoneal fluid (PF) in patients with endometriosis and infertility. Design and setting. This cross-sectional study included women undergoing diagnostic and/or therapeutic laparoscopy for endometriosis with chief complaint of infertility. Following laparoscopy, patients diagnosed with endometriosis served as cases while patients with no endometriosis served as controls. Patients with polycystic ovarian syndrome, diabetes, thyroiditis and patients on prior therapy with danazol or leuprolide were excluded from the study. Leptin and adiponectin levels were analysed in blood and PF using commercially available ELISA kits. Results. Of the 50 patients (aged 22-41 years), 15 had endometriosis (cases) while 35 had no endometriosis (controls). The median PF leptin level was significantly higher in cases as compared to controls (27.7 vs. 15.6 ng/ml, p = 0.019), and this remained significant even when PF leptin was BMI-normalised (p = 0.004). However, median serum leptin and adiponectin levels remained comparable between the two groups. Conclusions. This study confirmed the role of PF leptin in causation and progression of endometriosis. However, this would have been definitive if healthy fertile females were included in this study.

Acta Obstet Gynecol Scand. 2010 Jun;89(6):782-8.

Adiponectin isoform distribution in serum and in follicular fluid of women undergoing treatment by ICSI.

Bersinger NA, Wunder DM.

Department of Obstetrics and Gynaecology, Endometriosis and Human Reproduction, University of Berne, DKF Murtenstrasse 35, Berne, Switzerland. nick.bersinger@dkf.unibe.ch

OBJECTIVE: Adiponectin is an adipokine, present in the circulation in comparatively high concentrations and different molecular weight isoforms. For the first time, the distribution of these isoforms in serum and follicular fluid (FF) and their usefulness as biological markers for infertility investigations was studied. DESIGN: In vitro study. SETTING: University based hospital. POPULATION AND SAMPLE: Fifty-four women undergoing intracytoplasmic sperm injection (ICSI). METHODS: Oocytes were retrieved, fertilized in vitro using ICSI, and the resulting embryos transferred. Serum was collected immediately prior to oocyte retrieval. Adiponectin isoforms (high molecular weight (HMW), medium and low molecular weight) were determined in serum and FF. Total adiponectin and the different isoform levels were compared with leptin and ovarian steroid concentrations. MAIN OUTCOME MEASURES: Adiponectin isoforms in serum and FF. RESULTS: Adiponectin isoform distribution differed between serum and FF; the HMW fraction made up half of all adiponectin in the serum but only 23.3% in the FF. Total and HMW adiponectin in both serum and FF correlated negatively with the body mass index and the concentration of leptin. No correlations were observed for total adiponectin or its isoforms with estradiol, progesterone, anti-Mullerian hormone, inhibin B, or the total follicle stimulating hormone (FSH) dose administered during the ovarian stimulation phase. CONCLUSIONS: This study shows for the first time that adiponectin isoform distribution varies between the serum and FF compartments in gonadotropin stimulated patients. A trend towards higher HMW adiponectin serum levels in successful ICSI cycles compared to implantation failures was observed; studies with larger patient groups are required to confirm this observation.

AJR Am J Roentgenol. 2010 Jun;194(6 Suppl):WS34-46.

Unusual manifestations and complications of endometriosis–spectrum of imaging findings: pictorial review.

Bennett GL, Slywotzky CM, Cantera M, Hecht EM.

Department of Radiology, Women’s Imaging Division, New York University Langone Medical Center, 560 First Ave., Rm. HW202, New York, NY 10016, USA. genevieve.bennett@med.nyu.edu

AJR Am J Roentgenol. 2010 Jun;194(6 Suppl):S89-92.

Imaging of endometriosis: self-assessment module.

Choudhary S, Fasih N.

Department of Radiology, UTHSCSA, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA. choudhary@uthscsa.edu

The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the imaging features of endometriosis and the role of imaging and various radiologic techniques in the clinical management of patients.

AJR Am J Roentgenol. 2010 Jun;194(6 Suppl):S84-8.

Unusual manifestations and complications of endometriosis–spectrum of imaging findings: self-assessment module.

Bennett GL, Slywotzky CM, Cantera M, Hecht EM.

Department of Radiology, Women’s Imaging Division, New York University Medical Center, 560 First Ave., Rm. HW202, New York, NY 10016, USA. genevieve.bennett@med.nyu.edu

The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the imaging spectrum of endometriosis.

Ultrasound Obstet Gynecol. 2010 Aug;36(2):241-8.

Value of transvaginal ultrasound in assessing severity of pelvic endometriosis.

Holland TK, Yazbek J, Cutner A, Saridogan E, Hoo WL, Jurkovic D.

Early Pregnancy and Gynaecology Assessment Unit, King’s College Hospital, London, UK.

OBJECTIVE: The objective of this study was to examine the ability of preoperative transvaginal ultrasound (TVS) scanning to assess the severity of pelvic endometriosis. METHODS: Consecutive women with clinically suspected or proven pelvic endometriosis, who were booked for laparoscopy, were invited to join the study. The severity of endometriosis was assessed preoperatively using TVS and the findings were compared with the results obtained by laparoscopy using the American Society for Reproductive Medicine (ASRM) classification. RESULTS: In total, 201 women had preoperative TVS and laparoscopies. Of these, no endometriosis was found at laparoscopy for 62/201 (30.8%; 95% CI, 24.8-37.5), whereas 33/201 (16.4%; 95% CI, 11.9-22.2) had minimal endometriosis, 31/201 (15.4%; 95% CI, 11.1-21.1) had mild endometriosis, 27/201 (13.4%; 95% CI, 9.4-18.8) had moderate endometriosis and 48/201 (23.9%; 95% CI, 18.5-30.2) had severe endometriosis. The sensitivity and specificity of the TVS diagnosis of severe pelvic endometriosis were 0.85 (95% CI, 0.716-0.934) and 0.98 (95% CI, 0.939-0.994), respectively, and the positive and negative likelihood ratios were 43.5 (95% CI, 14.1-134) and 0.15 (95% CI, 0.075-0.295), respectively. Overall, there was a good level of agreement between ultrasound and laparoscopy in identifying absent, minimal, mild, moderate and severe disease (quadratic weighted kappa = 0.786). The mean ASRM score difference between TVS and laparoscopy in assessing severity of endometriosis was – 2.398 (95% CI, – 4.685 to – 0.1112) and the limits of agreement were – 34.62 (95% CI, – 38.54 to – 30.709) to 29.83 (95% CI, 25.91-33.74). CONCLUSIONS: TVS is a good test for assessing the severity of pelvic endometriosis. TVS is particularly accurate in detecting severe disease, which could facilitate more effective triaging of women for appropriate surgical care. Copyright (c) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

J Obstet Gynaecol Can. 2010 May;32(5):421, 422.

The hockey stick sign in appendiceal endometriosis.

[Article in English, French]

Parr G, Leyland N.

St. Joseph’s Health Centre, University of Toronto, Toronto ON, Canada.

Curr Opin Obstet Gynecol. 2010 Aug;22(4):283-8.

Gonadotropin-releasing hormone agonist and add-back therapy: what do the data show?

Surrey ES.

Colorado Center for Reproductive Medicine, Lone Tree, Colorado, USA. esurrey@colocrm.com

PURPOSE OF REVIEW: Endometriosis is a gynecologic disorder that can lead to debilitating chronic pelvic pain and infertility. Gonadotropin-releasing hormone agonists (GnRHa) have emerged as a primary medical therapy for patients with symptomatic disease, but secondary hypoestrogenic side effects may limit compliance. Add-back therapy is a means of surmounting this problem. RECENT FINDINGS: Progestins such as norethindrone acetate may be administered with or without addition of low doses of estrogens to safely and effectively extend GnRHa therapy while minimizing side effects. Recent studies have demonstrated that the use of add-back enhances compliance and duration of therapy. The initiation of an add-back should not be deferred given evidence demonstrating an increase in vasomotor symptoms and bone loss if not administered concomitantly. The subset of adolescents with endometriosis who require GnRHa therapy should be administered an add-back, but require careful monitoring of bone mineral density. SUMMARY: Implementation of an appropriately selected add-back will significantly reduce hypoestrogenic side effects, enhance compliance, and allow for prolongation of therapy without interfering with the efficacy of GnRHa in treating symptomatic endometriosis.

J Comput Assist Tomogr. 2010 May-Jun;34(3):338-42.

Deep infiltrating endometriosis: CT imaging evaluation.

Jung SI, Kim YJ, Jeon HJ, Jeong KA.

Department of Radiology, Research Institute of Medical Science, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea.

OBJECTIVE: To retrospectively evaluate the feasibility of computed tomography (CT) in depicting deep-infiltrating endometriosis. MATERIALS: The study population included 54 patients (age: mean, 35.5 years; range, 23-48 years) with histologically confirmed ovarian endometriomas between January 2007 and July 2009. All the patients underwent preoperative CT imaging before laparotomy or laparoscopy. The CT images were evaluated for the presence of a tethered appearance of the rectum in the direction of the uterus, stranding of periuterine pelvic fat, thickening of the uterosacral ligament, and retroflexed uterus. Two radiologists performed a blinded and independent review for each CT finding. The sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy of each CT finding and kappa statistics were determined. RESULTS: Deep-infiltrating endometriosis was confirmed after surgery and pathologic examination in 34 patients (63.0%). The most specific finding for the diagnosis of deep-infiltrating endometriosis was tethered appearance of rectum in the direction of the uterus (90.0%). The mean sensitivity, specificity, positive predictive value, negative predictive value, and accuracy values of all the CT findings except that of retroflexed uterus were 56.9%, 70.0%, 78.1%, 60.4%, and 61.7%, respectively. The mean kappa value was 0.82 (range, 0.67-0.96). CONCLUSIONS: Computed tomographic imaging may constitute another potential option as a complementary imaging modality for the evaluation of deep-infiltrating endometriosis.

Rom J Morphol Embryol. 2010;51(2):215-28.

Matrix metalloproteinases involvement in pathologic conditions.

Amălinei C, Căruntu ID, Giuşcă SE, Bălan RA.

Department of Normal and Pathological Morphology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, Iassy, Romania. cornelia_amalinei@yahoo.com.

Matrix metalloproteinases (MMPs) have a great variability that provides a complex intervention in pathophysiological conditions. MMPs roles in pathology may be grouped into the following main types: (1) tissue destruction, as in cancer invasion and metastasis, rheumatoid arthritis, osteoarthritis, different types of ulcers, periodontal disease, brain injury and neuroinflammatory diseases; (2) fibrosis, as in liver cirrhosis, fibrotic lung disease, otosclerosis, atherosclerosis, and multiple sclerosis; (3) weakening of matrix, as in dilated cardiomyopathy, epidermolysis bullosa, aortic aneurysm and restenotic lesions. Recent data also adds new MMPs functions in angiogenesis and apoptosis. Interesting opposite intervention in escaping mechanisms vs. antitumor defensive mechanisms had been also reported. As MMP-7 is expressed by tumor cells of epithelial and mesenchymal origin, it may be used as a biological marker of an aggressive phenotype and as a target of therapeutic intervention. MMPs play a pivotal role in the pathogenesis of arthritis, atherosclerosis, pulmonary emphysema, and endometriosis. Although MMP involvement in pathology is more than simple excessive matrix degradation, or an imbalance between them and their specific tissular inhibitors (TIMPs), MMP inhibition may be of therapeutic benefit, so synthetic MMPs inhibitors had been developed and are currently under clinical testing.

Eur J Obstet Gynecol Reprod Biol. 2010 May 19. [Epub ahead of print]

Absence of activating somatic mutations of PI3KCA and AKT1 genes in South Indian women with endometriosis.

Rai P, Deenadayal M, Shivaji S.

Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, Andhra Pradesh, India.

OBJECTIVE: To investigate whether the PI3KCA and AKT1 gene influences the risk of developing endometriosis in South Indian women. STUDY DESIGN: Mutations in exon 9 and 20 of PI3KCA gene and E17K mutation in exon 4 of AKT1 gene were tested for association in a case-control study between eutopic and ectopic endometrium tissue from 30 endometriosis cases and eutopic endometrium tissue from 30 controls. The genotype frequencies of these mutations were compared using polymerase chain reaction and direct sequencing analysis of tissue DNA. RESULTS: The analysis did not reveal any activating somatic mutations in either PI3KCA or AKT1 gene in the cases. CONCLUSION: In the present study we could not observe any mutation in PI3KCA and AKT1 gene, indicating that these mutations are rarely associated with endometriosis in South Indian women. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Fertil Steril. 2010 May 19. [Epub ahead of print]

Increased viability of endometrial cells by in vitro treatment with di-(2-ethylhexyl) phthalate.

Kim YH, Kim SH, Lee HW, Chae HD, Kim CH, Kang BM.

Department of Pharmacology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.

Based on the findings of several reports that have shown an increased plasma level of di-(2-ethylhexyl) phthalate (DEHP) in women with endometriosis, the present study was designed to evaluate whether in vitro treatment with DEHP can increase viability of endometrial cells. Utilizing 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide assay, fluorescent activated cell sorter analysis, and microscopic evaluation after Hoechst staining, we revealed that in vitro treatment with DEHP leads to increased viability of Ishikawa cells as well as endometrial stromal cells in serum-free condition and following exposure to hydrogen peroxide, which suggests that exposure to phthalate might play a role in the establishment of endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Dermatol Online J. 2010 May 15;16(5):9.

In Process Citation.

[Article in Portuguese]

Esteves T, Cabrita J, Coelho R, Vale E.

Hospital Central do Funchal, Madeira, Portugal.

CASE REPORT: A 26-year-old woman presented with a history of a dark red, asymptomatic, firm, dome-shaped tumor, approximately 2.5 cm in diameter. The nodule had been developing for one year near a scar in the lower abdominal wall. Her past medical history was significant for a caesarean section five years prior to presentation. Histopathological examination revealed numerous glands of various sizes exhibiting small to large lumina, surrounded by a cellular, edematous stroma composed of spindle-shaped cells or round large cells admixed with lymphocytes, plasma cells, and few eosinophils. COMMENT: Cutaneous endometriosis is a well recognized but uncommon entity, representing approximately 1 percent of all cases of ectopic endometrial tissue. It may arise spontaneously within the umbilicus or inguinal region, but the majority of lesions develop on surgical excisions of the abdominal and genital regions (cesarean sections, hysterectomy, laparotomy, laparoscopy, and episiotomy) in women of reproductive age. The pathogenesis of cutaneous endometriosis is still not clear and several theories have been put forward to explain its development. Despite its clinical rarity, cutaneous endometriosis is a well-known condition to dermatopathologists. Nevertheless, they should be aware of those unusual metaplastic changes that may represent a diagnostic pitfall.

J Obstet Gynaecol Res. 2010 Apr;36(2):344-51.

Expression of macrophage migration inhibitory factor in human endometriosis: relation to disease stage, menstrual cycle and infertility.

Lin W, Chen S, Li M, Wang B, Qu X, Zhang Y.

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Ji’nan, China.

AIM: The aim of the present study was to compare the expression of macrophage migration inhibitory factor (MIF) in eutopic and ectopic endometria of women with endometriosis and eutopic endometria of women without endometriosis, and to investigate whether such an expression varies according to disease stage, menstrual cycle and infertility status. METHODS: Forty patients with endometriosis and 15 control women were recruited for the study. Following isolation of total RNA from endometria and reverse transcription, cDNA samples were amplified to quantify the level of MIF expression by real-time fluorescent quantitative polymerase chain reaction. All of the endometriosis tissue and normal endometrium specimens were analyzed using immunohistochemistry. RESULTS: The levels of MIF in eutopic and ectopic endometria in endometriosis patients were significantly higher than in normal eutopic endometria (P < 0.01). Further, when comparing MIF in eutopic endometria (separated by phases) between the endometriosis and control groups, MIF was higher in the former group, both in the proliferative and secretory phases (P < 0.05). In addition, the MIF mRNA level was cycle phase-dependent and increased in the proliferative phase, both in women with endometriosis and the control women, compared with the level in the secretory phase (P < 0.05). There was no significant association between MIF expression and American Fertility Society staging of endometriosis (P > 0.05). However, MIF levels were obviously elevated in sterile women in the endometriosis group compared with women in the endometriosis group who were not sterile (P < 0.05). CONCLUSION: The expression of MIF was increased significantly in the eutopic and ectopic endometrial tissue of women with endometriosis, and this factor may play a possible role in endometriosis-associated infertility.

J Womens Health (Larchmt). 2010 Jun;19(6):1185-93.

Diagnosis and treatment of interstitial cystitis/painful bladder syndrome: a review.

Butrick CW, Howard FM, Sand PK.

Department of Obstetrics & Gynecology, The Urogynecology Center, Overland Park, Kansas 66215, USA. cwbutrick@gmail.com

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder characterized by pelvic pain and irritative voiding symptoms. The symptoms of IC/PBS can overlap with such conditions as endometriosis, recurrent urinary tract infection, chronic pelvic pain, overactive bladder, and vulvodynia. The etiology of IC/PBS is likely multifactorial and may involve a defective urothelium, neurogenic upregulation, and mast cell activation. A thorough patient history and physical examination are critical in the differential diagnosis of IC/PBS. Frequent follow-up and patient education are important components of treatment once a condition is diagnosed. A multimodal approach to therapy can provide optimal relief for patients with IC/PBS.

Gynecol Endocrinol. 2010 May 21. [Epub ahead of print]

Endometriosis-associated infertility: a decade’s trend study of women from the Estrie Region of Quebec, Canada.

Paris K, Aris A.

Department of Obstetrics-Gynecology.

Endometriosis (ENDO) has been believed to increase during the last years, but recent data supporting this trend are lacking. The aim of this study was to verify whether the incidence of ENDO, infertility (INF) and the both increased during the last 10 years among women living in the Estrie region of Quebec. This retrospective cross-sectional study was realised using data from the CIRESS (Centre Informatisé de Recherche Evaluative en Services et Soins de Santé) system, the database of the CHUS (Centre Hospitalier Universitaire de Sherbrooke), Sherbrooke, Canada. Among the 6845 studied patients, 2564 had ENDO, 4537 were infertile and 256 suffered from both. According to the last 10 years, a significant increase in the number of cases with ENDO (r(2) = 0.717, p = 0.001) and endometriosis-associated infertility (r(2) = 0.601, p = 0.003) was noted, while INF remained stable (r(2) = 2813 e-005, p = 0.987). We showed a prevalence of ENDO of 10.91%. Women with ENDO were at increased risk for being infertile (OR = 2.30; 95% CI = 2.014-2.626, p <0.0001). An increase of ENDO in women 18-24 years of age has been shown (r(2) = 0.418, p = 0.023), suggesting an earlier onset of the disease.

Ann Surg. 2010 Jun;251(6):1018-23.

Randomized trial of laparoscopically assisted versus open colorectal resection for endometriosis: morbidity, symptoms, quality of life, and fertility.

Daraï E, Dubernard G, Coutant C, Frey C, Rouzier R, Ballester M.

Department of Gynecology and Obstetrics, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, CancerEst, Université Pierre et Marie Curie Paris 6, France. emile.darai@tnn.aphp.fr

OBJECTIVE: We report the first randomized trial of laparoscopically assisted versus open colorectal resection for endometriosis focusing on perioperative complications, improvement in symptoms, quality of life, and fertility. SUMMARY OF BACKGROUND DATA: Bowel endometriosis is one of the most severe forms of endometriosis. Although laparoscopically assisted surgery is a validated technique for colorectal cancer, there are serious concerns about its appropriateness for endometriosis in young women wishing to conceive because it is almost invariably a traumatic procedure. METHODS: We conducted a noninferiority trial and randomly assigned 52 patients with colorectal endometriosis to undergo laparoscopically assisted or open colorectal resection. The median follow-up was 19 months. The primary end point was improvement in dyschesia. RESULTS: Overall, a significant improvement in digestive symptoms (dyschesia P < 0.0001, diarrhea P < 0.01, and bowel pain and cramping P < 0.0001), gynecologic symptoms (dysmenorrhea P < 0.0001 and dyspareunia P < 0.0001), and general symptoms (back pain P = 0.001 and asthenia P = 0.0001) was observed. No difference in the symptom delta values and quality of life was noted between the groups. Median blood loss was lower in the laparoscopic group (P < 0.05). Total number of complications was higher in the open surgery group (P = 0.04), especially grade 3 (P = 0.03). Pregnancy rate was higher in the laparoscopic group (P = 0.006), and the cumulative pregnancy rate was 60%. CONCLUSION: Our findings support that laparoscopy is a safe option for women requiring colorectal resection for endometriosis. Moreover, laparoscopy offers a higher pregnancy rate than open surgery with similar improvements in symptoms and in quality of life.

Rev Recent Clin Trials. 2010 Sep 1;5(3):143-6.

Mirena Intra-Uterine System: Does it Improve Long Term Symptoms in Women with Chronic Pelvic Pain and/or Endometriosis after Laparoscopy? A Multicentre Randomized Controlled Trial.

Alhamdan D, Bignardi T, Hardas G, Merkur H, Condous G.

Early Pregnancy and Advanced Endosurgery Unit, Nepean Clinical School, Penrith NSW 2750, Sydney, Australia. doctord972@yahoo.com.

Background: Chronic pelvic pain (CPP) is a complex clinical scenario, which affects 15% of women. The published literature lacks a consistent definition of CPP. However according to Vercillini et al., CPP is defined by the duration and type of pelvic pain [1]. CPP is present if the pelvic pain persists for more than 3 months duration and is constant or intermittent, cyclical or noncyclical in nature. Four types of pelvic pain have also been described and these include: cyclical pain during menstruation (dysmenorrhoea), deep dyspareunia, dyschezia and noncyclical pelvic pain. Therefore for the purposes of this study, CPP will be defined by these aforementioned types of pelvic pain and duration. Methods: Multi-centre randomised controlled trial comparing Mirena IUS versus expectant management in women with CPP and/or dysmenorrhoea who undergo laparoscopic surgery. All women aged 18 – 45 years with CPP scheduled for laparoscopy will be eligible for inclusion. Women with a non-gynecological cause of pelvic pain, contraindications to the use of Mirena IUS, previous hysterectomy, contraindications to laparoscopy and/or general anesthesia, use of hormonal treatment in the preceding three months, underlying gynaecological malignancies or known ovarian cysts other than endometriomata will be excluded. Importantly, all randomised women with endometriosis noted at the time of surgery will have the disease excised laparoscopically. Routine excision of endometriosis at laparoscopy will be performed according to the anatomical location and type (superficial or deep infiltrating endometriosis (DIE)). Women will be followed for up to 24 months after laparoscopic surgery. Results: The primary outcome measure is improvement of pelvic pain and/or of dysmenorrhoea post-laparoscopic surgery for women. Assuming a 30% reduction in pain for the expectantly managed group in order to detect a reduction in pain in the study group of 50% with an alpha of 0.05 and a beta of 0.20, the sample size was estimated at a minimum of 103 women per trial arm. Discussion: This trial will provide evidence to validate the effectiveness or otherwise of progestogen-releasing IUS in treating women with CPP who undergo laparoscopy surgery. The pros and cons of both trial arms will offer guidance to clinicians in making the right treatment choice.

Virchows Arch. 2010 Jun;456(6):703-10. Epub 2010 May 16.

Proangiogenetic molecules, hypoxia-inducible factor-1alpha and nitric oxide synthase isoforms in ovarian endometriotic cysts.

Goteri G, Lucarini G, Zizzi A, Rubini C, Di Primio R, Tranquilli AL, Ciavattini A.

Section of Anatomic Pathology, Department of Neurosciences, Polytechnic University of Marche Region, Via Conca, 71, 60020, Torrette di Ancona, Italy. g.goteri@univpm.it

Endometriosis is a common disease characterised by ectopic growth of endometrial tissue outside the uterine cavity. Angiogenesis has been implicated in the pathogenesis of the disease; some molecules, like hypoxia-inducible factor-1alpha (HIF-1alpha) and neuronal, endothelial and inducible nitric oxide synthase isoforms (nNOS, eNOS and iNOS), are known as proangiogenetic factors. We evaluated expression of these molecules by immunohistochemistry in 32 cases of ovarian endometriomas, formalin-fixed and paraffin-embedded. Analysis was focused on the cells composing the inner layer of the cyst, constituted by the ectopic endometrial glands, stromal cells and vessels, and the outer one, constituted by a fibrous layer of fibroblasts and vessels. We found that epithelial glands and capsular vessel endothelial cells showed a correlated expression of NOS isoforms; that expression of nNOS, iNOS and HIF-1alpha was correlated in epithelial glands and capsular fibroblasts; that vessel endothelial cells showed a higher mean expression for all the proangiogenetic molecules in the outer layer than in the inner one; and that capsular fibroblasts showed a higher mean expression for HIF-1alpha, iNOS and eNOS compared to the specialised stromal cells of the inner layer. Our data seem to indicate that angiogenesis is stimulated more in the outer capsule than in the inner layer of ovarian endometriotic cysts. The knowledge of the complex mechanisms associated to angiogenesis might be useful in a therapeutic approach of ovarian endometriosis based on anti-angiogenetic drugs. The therapeutic target would be mainly the capsular vasculature, more than the vasculature of ectopic endometrial tissues.

Curr Opin Pulm Med. 2010 Jul;16(4):381-6.

Catamenial pneumothorax.

Alifano M.

Department of Thoracic Surgery, Hôtel-Dieu Hospital, AP-HP, Paris V University, Paris, France. marcoalifano@yahoo.com

PURPOSE OF REVIEW: Although known for several decades, catamenial pneumothorax has been considered until recently as an extremely rare entity. The condition is now more easily recognized and several studies have been published, with somewhat relevant discrepancies with respect to etiologic, epidemiologic, and management features. In the present review, I will provide a synthesis of available knowledge on the subject. RECENT FINDINGS: Catamenial pneumothorax accounts for approximately one third of cases of spontaneous pneumothoraces in women referred for surgery. At video-assisted thoracic surgery, diaphragmatic defects and nodules are the most frequent findings. Pathology shows endometriosis in most instances. Endometrial implants in visceral pleura are also found, although less frequently. Findings of surgical explorations support the theory of transabdominal-transdiaphragmatic passage of air to explain the pathogenesis of catamenial pneumothorax. SUMMARY: Management of patients with catamenial pneumothorax implies surgery, if possible by video-assisted technology, to obtain samples for pathologic confirmation of endometriosis and to treat the main pathogenic mechanisms of pneumothorax. Partial diaphragmatic resection and/or exeresis of visceral pleural implants, as well as talc pleurodesis, are nowadays frequently carried out. Medical therapy to achieve ovarian rest is mandatory in the postoperative period, the multimodality management being the key to treatment success in this condition.

J Minim Invasive Gynecol. 2010 Jul;17(4):480-486. Epub 2010 May 14.

Incidence of Complications during Gynecologic Laparoscopic Surgery in Patients after Previous Laparotomy.

Kumakiri J, Kikuchi I, Kitade M, Kuroda K, Matsuoka S, Tokita S, Takeda S.

Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan.

STUDY OBJECTIVE: To estimate the incidence of complications arising during gynecologic laparoscopic surgery in patients who have undergone previous abdominal surgeries and to assess predictable factors associated with complications based on the characteristics of the previous laparotomy. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University-affiliated hospital. PATIENTS: We enrolled 307 patients with a history of laparotomy who underwent laparoscopic surgery at our hospital between January 2002 and June 2009. INTERVENTIONS: The closed primary approach via either the ninth intercostal space or the posterior vaginal fornix was used to avert bowel injury. Complications were defined as organ injury that required repair during surgery and immediate conversion to laparotomy because of technical difficulties. Factors influencing complications during laparoscopic surgery were analyzed using logistic regression. MEASUREMENTS AND MAIN RESULTS: No complications developed during primary entry. Adhesiolysis was required in 195 areas of adhesion in 146 patients before laparoscopic surgery could proceed. These areas comprised 45 (14.7%) and 31 (10.1%) abdominal wall adhesions without and within the umbilicus, respectively, and 119 (38.8%) with intrapelvic adhesions. Complications in 41 patients (13.4%) included bowel damage (n = 35), urinary system damage (n = 4), and conversion to laparotomy because of technical difficulties (n = 2). Overall, 38 complications were laparoscopically repaired, and 1 complication was repaired at minilaparotomy. Intrapelvic adhesions were found in all patients with complications, and bowel adherent to the intrapelvis was identified in 38 of these (92.7%). The most significant predictive factors positively associated with development of complications according to logistic regression analysis were a history of abdominal myomectomy (odds ratio, 6.27; 95% confidence interval, 2.95-13.38; p <.001) and excisional endometriosis surgery (odds ratio, 5.80; 95% confidence interval, 2.08-16.13; p = .001). No patients developed severe delayed complications after surgery. CONCLUSION: Our findings suggest that potential predictive factors of complications are a history of abdominal myomectomy and excisional endometriosis surgery performed because of intrapelvic adhesions. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.

Reprod Biomed Online. 2010 Jul;21(1):142-147. Epub 2010 Apr 4.

New evidence of the presence of endometriosis in the human fetus.

Signorile PG, Baldi F, Bussani R, D’Armiento M, De Falco M, Boccellino M, Quagliuolo L, Baldi A.

Fondazione Italiana Endometriosi, via E Longoni 81, 00155 Rome, Italy.

The aetiology of endometriosis, a gynaecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity, is still open to debate. Research has recently found evidence for endometriosis in human female fetuses at different gestational ages. This paper reports a new case of fetal endometriosis in a 25-week female fetus, deceased due to placental pathology, from a series of 13 female fetuses analysed at autopsy. The exact anatomical localization of this misplaced endometrium, as well as its histopathological and immunohistochemical characteristics are illustrated. The case suggests that endometriosis can be caused by dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis. Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Cutan Ocul Toxicol. 2010 Sep;29(3):221-4.

Hypersensitivity vasculitis associated with leuprolide (Lupron).

Gnanaraj J, Saif MW.

Internal Medicine Residency Program, Assistant Program Director, Griffin Hospital, Derby, CT, Affiliated to Yale University School of Medicine, New Haven.

Leuprolide (Lupron) is a synthetic analog of naturally occurring gonadotropin-releasing hormone (GnRH). Leuprolide is used as a hormonal antagonist in the treatment of advanced prostatic cancer, and as hormonal therapy in the treatment of endometriosis. Off-label, it is also used in premenopausal or perimenopausal women with hormone-responsive breast cancer for the purpose of ovarian ablation. Ever since its FDA approval in 1985, many adverse reactions have been reported in association with leuprolide ranging from local skin irritation to severe anaphylactoid reactions. In this case report, we present a case of hypersensitivity vasculitis (serum sickness) in a patient who received leuprolide for his prostate cancer. Serum sickness has never been reported as a side-effect of leuprolide. Our case is the first case of serum sickness associated with leuprolide. We emphasize that physicians using leuprolide should be wary of signs and symptoms of hypersensitivity vasculitis or serum sickness.

Hum Reprod Update. 2010 May 12. [Epub ahead of print]

Peripheral biomarkers of endometriosis: a systematic review.

May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM.

Nuffield Department of Obstetrics & Gynaecology, University of Oxford, Women’s Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.

BACKGROUND Endometriosis is estimated to affect 1 in 10 women during the reproductive years. There is often delay in making the diagnosis, mainly due to the non-specific nature of the associated symptoms and the need to verify the disease surgically. A biomarker that is simple to measure could help clinicians to diagnose (or at least exclude) endometriosis; it might also allow the effects of treatment to be monitored. If effective, such a marker or panel of markers could prevent unnecessary diagnostic procedures and/or recognize treatment failure at an early stage. METHODS We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature over the last 25 years to assess critically the clinical value of all proposed biomarkers for endometriosis in serum, plasma and urine. RESULTS We identified over 100 putative biomarkers in publications that met the selection criteria. We were unable to identify a single biomarker or panel of biomarkers that have unequivocally been shown to be clinically useful. CONCLUSIONS Peripheral biomarkers show promise as diagnostic aids, but further research is necessary before they can be recommended in routine clinical care. Panels of markers may allow increased sensitivity and specificity of any diagnostic test.

Genes Chromosomes Cancer. 2010 Jul;49(7):630-4.

HMGA1 and HMGA2 rearrangements in mass-forming endometriosis.

Medeiros F, Araujo AR, Erickson-Johnson MR, Kashyap PC, Dal Cin P, Nucci M, Wang X, Bell DA, Oliveira AM.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.

Endometriosis is a common gynecologic disorder characterized by ectopic endometrium associated with pelvic pain and infertility. The pathogenesis of endometriosis is unclear, and several genetic, endocrine, immune, and environmental agents have been studied as putative causative factors. However, consistent somatic genetic alterations have not been identified. Rarely, endometriosis presents as a mass lesion with an infiltrative pattern reminiscent of malignancy. We describe cytogenetic and molecular cytogenetic findings of mass-forming endometriosis. The index case of pulmonary endometriosis underwent conventional and molecular cytogenetics analysis. In addition, 16 cases of mass-forming endometriosis, 11 cases of usual endometriosis, and six endometriomas were investigated by fluorescence in situ hybridization (FISH) for HMGA1 and HMGA2 loci, performed on paraffin-embedded thin tissue sections with custom-designed probes. The index patient had an endometriotic lung nodule, with a 46,XX, t(5;6)(q13;p21) karyotype and HMGA1 rearrangement by FISH. A second patient had decidualized endometriosis forming a large abdominal mass and HMGA1 rearrangement by FISH. Of the 15 other cases of mass-forming endometriosis, one had HMGA1 rearrangement and two had HMGA2 rearrangement. The rearrangements were found in the stromal component exclusively. None of the usual endometriosis cases or endometriomas had HMGA1 or HMGA2 rearrangements. In conclusion, mass-forming endometriosis is an uncommon subset of endometriosis that harbors HMGA1 or HMGA2 rearrangements in up to 29% of cases. The present findings support the concept that endometriosis is clonal and that rearrangement of HMGA genes likely contributes to its pathogenesis. (c) 2010 Wiley-Liss, Inc.

Int J Surg Pathol. 2010 Jun;18(3):214-6.

Loose mesothelial cysts in the peritoneal cavity.

Ramirez Y, Rosai J, Segura JJ.

Department of Pathology, Pontificia Universidad Javeriana, Bogotá, Colombia. yuly.ramirez@javeriana.edu.co

J Biomol Screen. 2010 Jun;15(5):508-17. Epub 2010 May 10.

A high-throughput small-molecule ligand screen targeted to agonists and antagonists of the G-protein-coupled receptor GPR54.

Kuohung W, Burnett M, Mukhtyar D, Schuman E, Ni J, Crowley WF, Glicksman MA, Kaiser UB.

Department of Obstetrics and Gynecology, Boston University School of Medicine, USA.

Recent data have shown that the G-protein-coupled receptor GPR54 (also known as KiSS-1 receptor) regulates GnRH release from the hypothalamus. This essential role of GPR54 in controlling the hypothalamic-pituitary-gonadal axis makes it an attractive target for therapeutic intervention in reproductive and cancer medicine. Currently, there are no small-molecule modulators of GPR54 function for experimental or clinical use. To identify small-molecule compounds that modify GPR54 signal transduction, the authors have adapted a cell-based functional assay for high-throughput screening (HTS) using a commercially available homogeneous time-resolved fluorescence assay for inositol phosphate accumulation. They generated stable Chinese hamster ovary cell transfectants that express human GPR54 for use in this assay. After optimization in an automated HTS environment, they screened a library of 110,000 small-molecule compounds using 2 protocols, one to identify agonists and one to identify antagonists. Hits obtained in the primary screen were confirmed to be active in secondary in vitro assays. Compounds identified as agonists or antagonists from HTS and secondary screening will be characterized to identify agents with the potential to be developed as novel orally active agents to treat hormone-dependent disorders such as abnormal puberty, infertility, endometriosis, and sex steroid-dependent tumors.

Histopathology. 2010 Apr;56(5):654-6.

Functioning extraovarian stromal luteinization of the peritoneum.

Aneiros-Fernández J, Carballo P, Molina S, Muñoz E, Nogales FF.

Arch Gynecol Obstet. 2010 May 11. [Epub ahead of print]

94 months follow-up after laparoscopic assisted vaginal resection of septum rectovaginale and rectosigmoid in women with deep infiltrating endometriosis.

Kavallaris A, Chalvatzas N, Hornemann A, Banz C, Diedrich K, Agic A.

Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Campus Luebeck, Ratzeburgerallee 160, 23538, Lübeck, Germany, andreas.kavallaris@uk-sh.de.

BACKGROUND: Endometriosis with bowel involvement is the most invasive form and can cause infertility, chronic pelvic pain and bowel symptoms. Effective surgical treatment of endometriosis requires complete excision of endometriosis and in same case may require segmental rectosigmoid resection. METHODS: Between December 1997 and October 2003, 55 patients with rectovaginal endometriosis underwent a combined laparoscopic vaginal technique. 30 patients were found at a follow-up and underwent a telephone interview. The questionnaire covered questions about symptoms related to recurrences of intestinal endometriosis, dyspareunia, dysmenorrhea and pregnancy. RESULTS: Twenty-seven of 30 (90%) women have no clinical symptoms of reported recurrence of endometriosis. Two patients (6.6%) had evidence of recurrence of bowel endometriosis. Dysmenorrhoea disappeared in 28 (93.3%), dyspareunia in 26 (86.7%) and pelvic pain in 27 (90%) patients. 17 patients (31%) tried to become pregnant and 11 of these patients (65%) became pregnant: 9 patients delivered healthy newborns, 18 pregnancies occurred and 19 healthy children were born. CONCLUSIONS: Despite the small number of follow-up patients, our 94-month follow-up data demonstrated that endometriosis with bowel involvement and radical resection was associated with significant reductions in painful and dysfunctional symptoms, a low recurrence rate (6.6%) and high pregnancy rate (36.6%).

Hum Reprod. 2010 May 10. [Epub ahead of print]

Activin A regulates trophoblast cell adhesive properties: implications for implantation failure in women with endometriosis-associated infertility.

Stoikos CJ, Salamonsen LA, Hannan NJ, O’Connor AE, Rombauts L, Dimitriadis E.

Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC 3800, Australia.

BACKGROUND During implantation, the embryo adheres to the endometrium via cell adhesion molecules (CAMs) present on blastocyst trophectoderm and endometrial epithelial cells. CAMs, including integrins and extracellular matrix (ECM) ligands, are most likely regulated by hormones, cytokines and growth factors. We hypothesized first that activin A affects the adhesive properties of trophoblast cells and second that alterations in dimeric activin A levels in the uterine cavity could disrupt adhesion, thereby causing implantation failure. METHODS This study examined effects of activin A on trophoblast cell adhesion and measured activin A levels in secretory phase uterine washings from women with and without endometriosis (EOS). Activin receptor expression on trophoblast (HTR8) cells was examined by RT-PCR, and adhesive molecules measured by integrin antibody and cell-matrix adhesion assays. Dimeric activin A was measured (enzyme-linked immunosorbent assay) in uterine washings (14 controls and 23 EOS), and betaA-subunit localization was verified in endometrial tissues. RESULTS Activin receptors are expressed by HTR8 cells. Activin A activated Smad2 in a concentration-dependent manner which was blocked by an activin receptor inhibitor (SB431542). Following activin A treatment (50 ng/ml for 24 h), trophoblast cell surface integrins alpha1 alpha2 alpha3 alpha5, beta1, beta2, beta4 and alphavbeta5 were decreased, as was cell binding to the ECM ligands, fibronectin, collagen IV and collagen I (P < 0.05). Activin A was detected in 56.5% of EOS and 21.4% of control washings, with measured levels from 42 to 8481 pg/ml (not significantly different). CONCLUSIONS Decreased trophoblast CAM production and adhesion could be caused by dysregulated local activin A levels and may contribute to implantation failure. This could explain, in part, the infertility observed in women with EOS.

Reproduction. 2010 Jul;140(1):11-22. Epub 2010 May 10.

Human uterine stem/progenitor cells: their possible role in uterine physiology and pathology.

Maruyama T, Masuda H, Ono M, Kajitani T, Yoshimura Y.

Department of Obstetrics and Gynaecology, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan. tetsuo@sc.itc.keio.ac.jp

The human uterus mainly consists of the endometrium and the outer smooth muscle layer termed the myometrium. The uterus harbours the exceptional and remarkable regenerative ability responsible for cyclical regeneration and remodelling throughout the reproductive life. The uterus must swiftly and cooperatively enlarge to hold the growing foetus during pregnancy. Furthermore, the endometrium, in particular the functionalis layer, must also regenerate, differentiate and regress with each menstrual cycle under hormonal control. Endometrial regeneration from the basal layer is thought to contribute to replacement of the functionalis layer followed by its slough off during menses and parturition. These morphological and functional features of human endometrium can be reproduced in murine models in which severely immunodeficient mice are xenotransplanted with dispersed human endometrial cells under the kidney capsule. The uterine myometrium possesses the similar plasticity of the endometrium. This is demonstrated by multiple cycles of pregnancy-induced enlargement and regression after parturition. It is likely that regeneration and remodelling in the female reproductive tract are achieved presumably through endometrial and myometrial stem cell systems. Recent evidence now supports the existence of these stem cell systems in humans. Here, we will review our current understanding of uterine stem/progenitor cells. We also propose a novel hypothetical model in which stem cell activities explain the physiological remodelling and regeneration of the human uterus and the pathogenesis of gynaecological diseases such as endometriosis.

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