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Gastrointest Endosc. 2007 Sep;66(3):620-2. Epub 2007 May 23.

EUS-guided FNA facilitates the diagnosis of retroperitoneal endometriosis.

Artifon EL, Franzini TA, Kumar A, Matsura PF, Furuya CK Jr, Ishioka S, Sakai P.

Gastrointestinal Endoscopy Unit, University of São Paulo, São Paulo, SP, Brazil.

J Clin Endocrinol Metab. 2007 Aug;92(8):3261-7. Epub 2007 May 22.

Transcriptional activation of steroidogenic factor-1 by hypomethylation of the 5′ CpG island in endometriosis.

Xue Q, Lin Z, Yin P, Milad MP, Cheng YH, Confino E, Reierstad S, Bulun SE.

Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois 60611, USA.

CONTEXT: Endometriosis is an estrogen-dependent disease. Steroidogenic factor-1 (SF-1), a transcriptional factor essential for activation of multiple steroidogenic genes for estrogen biosynthesis, is undetectable in normal endometrial stromal cells and aberrantly expressed in endometriotic stromal cells. OBJECTIVE: The objective of the study was to unravel the mechanism for differential SF-1 expression in endometrial and endometriotic stromal cells. DESIGN: We identified a CpG island flanking the SF-1 promoter and exon I region and determined its methylation patterns in endometrial and endometriotic cells. SETTING: The study was conducted at Northwestern University. PATIENTS OR OTHER PARTICIPANTS: Eutopic endometrium from disease-free subjects (n = 8) and the walls of cystic endometriosis lesions of the ovaries (n = 8) were investigated. INTERVENTION(S): Stromal cells were isolated from these two types of tissues. MAIN OUTCOME MEASURE(S): Measures are mentioned in Results. RESULTS: SF-1 mRNA and protein levels in endometriotic stromal cells were significantly higher than those in endometrial stromal cells (P < 0.001). Bisulfite sequencing showed strikingly increased methylation in endometrial cells, compared with endometriotic cells (P < 0.001). Demethylation by 5-aza-2′-deoxycytidine increased SF-1 mRNA levels by up to 55.48-fold in endometrial cell (P < 0.05). Luciferase assays showed that the -85/+239 region bearing the CpG island regulated its activity (P < 0.01). Natural or in vitro methylation of this region strikingly reduced SF-1 promoter activity in both cell types (P < 0.01). Chromatin immunoprecipitation assay showed that methyl-CpG-binding domain protein 2 binds to the SF-1 promoter in endometrial but not endometriotic cells. CONCLUSIONS: This is the first demonstration of methylation-dependent regulation of SF-1 in any mammalian tissue. These findings point to a new mechanism for targeting local estrogen biosynthesis in endometriosis.

J Dairy Sci. 2007 Jun;90(6):2804-14.

Rectal temperature, calving-related factors, and the incidence of puerperal metritis in postpartum dairy cows.

Benzaquen ME, Risco CA, Archbald LF, Melendez P, Thatcher MJ, Thatcher WW.

Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610, USA.

The objectives of this study were as follows: 1) to evaluate the association among abnormal calving, parity, and season on the incidence of puerperal metritis (PM) and clinical endometritis (CE) during d 3 to 13 and 20 to 30 postpartum, respectively; 2) to describe the rectal temperature (RT) of cows with PM before diagnosis; and 3) to document associations among PM, CE, and reproductive performance in lactating dairy cows. This study followed a prospective observational study design. Cows were classified as having an abnormal calving status (AC), i.e., cows calving with dystocia, twins, retained fetal membranes, or some combination of these conditions, and having a normal calving status (NC). Daily RT was recorded from d 3 to 13 postpartum for all cows, and health examinations were performed on cows that appeared not well. A total of 450 calvings were evaluated. Cows with an AC had greater odds of PM than cows with NC [adjusted odds ratio (AOR) = 4.8; 95% confidence interval (CI) = 2.9 to 8.0). A season by parity interaction showed that primiparous cows that calved during the warm season had lower AOR of PM than during the cool season (0.24; 95% CI = 0.09 to 0.62), whereas multiparous cows did not have seasonal effects on PM (1.43; 95% CI = 0.65 to 3.18). Cows with AC have greater AOR for CE than cows with NC (2.8; 95% CI = 1.7 to 4.9), and greater AOR of CE were detected in cows diagnosed with PM than in cows without PM (2.2; 95% CI = 1.1 to 3.9). Rectal temperature in cows with PM increased significantly 24 h before diagnosis of PM, reaching 39.2 +/- 0.05 degrees C on the day of diagnosis. In cows with PM and fever at diagnosis, the RT began to increase from 72 to 48 h before the diagnosis of PM and continued to increase to 39.7 +/- 0.09 degrees C on d 0 (day of diagnosis). Nonetheless, cows with PM without fever at diagnosis had no daily increases in RT before diagnosis of PM. Still, the RT on d 0 was different from cows without PM. Cows without PM had a stable RT (38.6 +/- 0.01 degrees C). There were no detected differences in first-service conception risk or cumulative pregnancy risk by 150 d postpartum between cows with or without PM. Still, a season effect on first-service conception AOR (warm vs. cool = 0.98; 95% CI = 0.18 to 0.72) and accumulated pregnancy AOR by 150 d postpartum was detected (warm vs. cool = 0.18; 95% CI = 0.10 to 0.33).

Ultraschall Med. 2007 Apr;28(2):195-200.

Clinical value of transrectal ultrasound in the diagnosis of suspected neoplasia in the small pelvis.

Rinnab L, Gottfried HW, Schnöller T, Hautmann RE, Kuefer R.

Department Urology, University Hospital, Ulm. Ludwig.Rinnab@medizin.uni-ulm.de

PURPOSE: In daily clinical practice, it is challenging to accurately diagnose suspected neoplasias in the small pelvis by minimal invasive means, and CT-guided biopsy is often limited in its feasibility. The aim of our study was to evaluate whether transrectal ultrasound (TRUS)-guided biopsy can verify suspected neoplasias in the small pelvis histologically. MATERIAL AND METHODS: The study population consisted of 12 patients who underwent biopsy of suspected malignancy in the pelvis by TRUS. All patients had clinical signs of an advanced tumour stage and in all cases, biopsy utilising computerised tomography (CT scan) had been unsuccessful despite of a documented lesion on CT scan or magnetic resonance imaging. For the TRUS guided biopsy, a commercially available 3-dimensional 7.5-MHz-probe was used (Combison 530 D, GENERAL ELECTRIC, Milwaukee, USA). The probe was armed with an 18 G biopsy gun. RESULTS: In all patients, the suspected lesion was easily detectable by TRUS, and tissue for verification of the malignant origin of the lesions could be collected under real-time TRUS with only 2 patients needing anaesthesia. The biopsy cores were of excellent quality and adequate for conclusive pathological diagnosis. 6 cases of lymph node metastases of a transitional cell carcinoma were detected. 1 case of extended node metastasis in prostate cancer, 1 paravesical manifestation of recurrent cervical cancer, 1 metastasis of a paravesically infiltrating colon cancer and 2 cases of paravesical metastases of a gastric cancer were also diagnosed. In one case, extragenital endometriosis could be diagnosed. CONCLUSION: Based on our experience it can be stated that TRUS-guided biopsy is a reliable diagnostic tool for verification of the neoplastic origin of suspected masses in the small pelvis. In all cases with a history of unsuccessful CT guided biopsy, sufficient tissue cores for conclusive histology could be collected with our technique, and surgical exploration could be avoided. This technique is minimally invasive, without radiation exposure, well tolerated under analgesia, time efficient and cheap.

Clin Obstet Gynecol. 2007 Jun;50(2):412-24.

Erratum in:

Clin Obstet Gynecol. 2007 Sep;50(3):xii.

Chronic pelvic pain: how many surgeries are enough?

Butrick CW.

Urogynecology Center, Overland Park and Kansas University Medical Center, Kansas City, KS 66215, USA. cbutrick@aol.com

The key to treatment of chronic pelvic pain is to treat it as the complex disease it is. Evidence is reviewed showing that identifying one aspect of the disease such as endometriosis or adhesions then treating only that component is not likely to be successful. Given our understanding of the neuropathology of chronic pelvic pain this failure of traditional therapy is to be expected. This evidence is reviewed and supports that an integrated treatment approach holds the most promise for a successful outcome. The goal of chronic pelvic pain management is for the clinician to identify every pain generator and treat each one.

Hum Reprod. 2007 Jul;22(7):1866-70. Epub 2007 May 18.

Association between susceptibility to advanced stage endometriosis and the genetic polymorphisms of aryl hydrocarbon receptor repressor and glutathione-S-transferase T1 genes.

Kim SH, Choi YM, Lee GH, Hong MA, Lee KS, Lee BS, Kim JG, Moon SY.

Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center, and Youngdong Severance Hospital, Republic of Korea.

BACKGROUND: This study was performed to determine whether genetic polymorphisms of aryl hydrocarbon receptor repressor (AhRR), glutathione-S-transferase M1 (GSTM1) and glutathione-S-transferase T1 (GSTT1) are associated with susceptibility to advanced stage endometriosis in a Korean population. METHODS: This study comprised 316 women with advanced stage endometriosis and 256 control women without endometriosis. Genotyping of the AhRR codon 185 was performed by real-time polymerase chain reaction (PCR) analysis. GSTM1 and GSTT1 genotyping for gene deletions were carried out by multiplex PCR analysis. RESULTS: G allele frequency at codon 185 of AhRR was increased in patients with endometriosis (P=0.047), and there was a trend for an association of C/G+G/G genotypes with risk of endometriosis (P=0.06). The proportion of null mutation at GSTT1 also tended to increase (P=0.06) in patients with endometriosis, whereas there was no difference in the genotype distribution of GSTM1 genes. Analyzing AhRR and GSTT1 together, we found that patients with high-risk genotypes at both loci have increased risk of endometriosis, compared with patients without high-risk genotypes (P=0.015). CONCLUSIONS: These findings suggest that the AhRR codon 185 and GSTT1 polymorphisms are associated with the risk of advanced stage endometriosis.

Endocrinology. 2007 Aug;148(8):3814-26. Epub 2007 May 17.  

Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

Burney RO, Talbi S, Hamilton AE, Vo KC, Nyegaard M, Nezhat CR, Lessey BA, Giudice LC.

Department of Obstetrics and Gynecology, Stanford University, Stanford, California 94305, USA.

The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

Reprod Biomed Online. 2007 May;14(5):620-5.

Effect of ovarian involvement on peritoneal fluid cytokine concentrations in endometriosis patients.

Bedaiwy MA, El-Nashar SA, Sharma RK, Falcone T.

Reproductive Research Center, Cleveland Clinic, Cleveland, OH 44195, USA.

Peritoneal fluid cytokines are important for initiation and progression of endometriosis. The objective of this study was to compare a group of five cytokines (interleukins IL-1 beta, IL-6, IL-8, IL-13 and tumour necrosis factor alpha; TNFalpha) in peritoneal fluid of endometriosis patients with ovarian involvement (Group I, n = 17) to those in patients without ovarian involvement (Group II, n = 33) and to a reference group without endometriosis (Group III, n = 25). All three groups were comparable regarding age, parity and body mass index. IL-8 concentrations were significantly higher in groups I and II compared with the reference group (P = 0.01 and 0.02, respectively). Similarly, TNFalpha concentrations were significantly higher in groups I and II compared with the reference group (P < 0.0001 and 0.0004, respectively). All other cytokines were comparable in the three groups. No significant differences were found between groups I and II with respect to the cytokines measured. In conclusion, peritoneal fluid IL-8 and TNFalpha concentrations are significantly higher in endometriosis. Ovarian involvement does not alter the pattern of cytokines. It appears that the inflammatory mediators of endometriosis are similar with and without ovarian involvement.

Reprod Biol Endocrinol. 2007 May 17;5:18.

Laser capture microdissection and cDNA array analysis of endometrium identify CCL16 and CCL21 as epithelial-derived inflammatory mediators associated with endometriosis.

Chand AL, Murray AS, Jones RL, Hannan NJ, Salamonsen LA, Rombauts L.

Prince Henry’s Institute of Medical Research, Clayton, Victoria, Australia. ashwini.chand@princehenrys.org

BACKGROUND: Understanding the pathophysiology of chemokine secretion in endometriosis may offer a novel area of therapeutic intervention. This study aimed to identify chemokines differentially expressed in epithelial glands in eutopic endometrium from normal women and those with endometriosis, and to establish the expression profiles of key chemokines in endometriotic lesions. METHODS: Laser capture microdissection isolated epithelial glands from endometrial eutopic tissue from women with and without endometriosis in the mid-secretory phase of their menstrual cycles. Gene profiling of the excised glands used a human chemokine and receptor cDNA array. Selected chemokines were further examined using real-time PCR and immunohistochemistry. RESULTS: 22 chemokine/receptor genes were upregulated and two downregulated in pooled endometrial epithelium of women with endometriosis compared with controls. CCL16 and CCL21 mRNA was confirmed as elevated in some women with endometriosis compared to controls on individual samples. Immunoreactive CCL16 and CCL21 were predominantly confined to glands in eutopic and ectopic endometrium: leukocytes also stained. Immunoreactive CCL16 was overall higher in glands in ectopic vs. eutopic endometrium from the same woman (P < 0.05). Staining for CCL16 and CCL21 was highly correlated in individual tissues. CONCLUSION: This study provides novel candidate molecules and suggests a potential local role for CCL16 and CCL21 as mediators contributing to the inflammatory events associated with endometriosis.

BJU Int. 2007 Aug;100(2):382-5. Epub 2007 May 17.

Comment in:

BJU Int. 2007 Dec;100(6):1412.

Laparoscopic partial cystectomy for various bladder pathologies.

Tai HC, Chung SD, Wang SM, Chueh SC, Yu HJ.

Department of Urology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.

OBJECTIVE: To present our initial experience with laparoscopic partial cystectomy (LPC) in selected patients with various bladder pathologies. PATIENTS AND METHODS: Between December 2004 and April 2006, four patients had LPC at our centre (mean age 52 years, range 35-70); the transperitoneal approach was used for three and a pre-peritoneal approach for one. The surgical procedures used sequentially included transurethral incision around the lesion, laparoscopic excision of the lesion (partial cystectomy) and intracorporeal suturing. Laparoscopic pelvic lymphadenectomy was also used for the two patients with malignancy. RESULTS: All operations proceeded smoothly; the bladder pathologies included one bladder endometriosis, one bladder leiomyoma, one urothelial carcinoma within the bladder diverticulum and one urachal adenocarcinoma. The mean (range) operative duration was 197.5 (120-300) min, the estimated blood loss 70 (50-100) mL, the hospital stay 6.75 (5-9) days, and duration of Foley catheterization 7.25 (6-9) days. No open conversion was required and no patient had peri-operative complications. The surgical margins were free of cancer and the dissected lymph nodes were negative in those two patients with bladder malignancy. CONCLUSIONS: LPC is safe and feasible in selected patients with various bladder pathologies.

J Clin Lab Anal. 2007;21(3):193-6.

Elevation of CA 19-9 and chromogranin A, in addition to CA 125, are detectable in benign tumors in leiomyomas and endometriosis.

Tsao KC, Hong JH, Wu TL, Chang PY, Sun CF, Wu JT.

Department of Pathology, Chang Gung Memorial Hospital, Taipei, Taiwan.

As the best-known tumor marker for ovarian carcinoma, CA 125 has also been commonly used to monitor patients with common benign gynecologic diseases such as endometriosis and leiomyoma. Both of these benign tumors are known to be at risk of developing into cancer. During the screening of an asymptomatic population with multiple tumor markers, including alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), CA 125, CA 19-9, CA 15-3, chromogranin A (CgA), and squamous cell carcinoma antigen (SCC), we have detected elevated tumor markers in 142 individuals; 19 of them were diagnosed with endometriosis or leiomyoma or both. In addition to the detection of elevation of CA 125 in these benign tumors, elevated CA 19-9 or CgA was also found in these patients with endometriosis or leiomyoma. Many patients only had elevated CA 19-9 or CgA; the elevation of CA 125 was not detected. It appears that instead of monitoring only CA 125, as is traditionally done, multiple tumor markers, including CA 19-9, CgA, and CA 125, should be measured simultaneously in women with clinical disorders associated with the ovary or uterus in order to detect gynecologic benign tumors and in order to prevent further development of cancer. (c) 2007 Wiley-Liss, Inc.

J Reprod Med. 2007 Apr;52(4):306-12.

Local activation of TGF-beta1 at endometriosis sites.

Komiyama S, Aoki D, Komiyama M, Nozawa S.

Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan. komiyama@fujita-hu.ac.jp

OBJECTIVE: To investigate the factors related to activation of transforming growth factor-beta 1 (TGF-beta1) at sites of endometriosis. STUDY DESIGN: TGF-beta1 is activated by plasmin, which is formed when plasminogen is activated by urokinase-type plasminogen activator (uPA). We studied these factors by immunohistochemistry or immunoassay. RESULTS: TGF-beta1 protein was localized mainly in the cytoplasm of glandular epithelial cells in both endometriotic cysts and normal endometrium, but strongly positive immunostaining was significantly more common in cysts. The levels of TGF-beta1, uPA and plasmin/alpha2-plasmin inhibitor complex were all higher in cyst fluid than in peritoneal fluid. There was little uPA protein expression in the glandular epithelium of normal endometrium, but it was prominent in the cytoplasm of glandular epithelial cells from endometriotic cysts, and strongly positive immunostaining was significantly more common in cysts. CONCLUSION: These results suggest that TGF-beta1 activity is increased at sites of endometriosis due to enhanced production of both uPA and TGF-beta1 by glandular epithelium and because plasmin activates TGF-beta1 after being converted from plasminogen by uPA.

Gynecol Endocrinol. 2007 Apr;23(4):188-92.

Expression of 17beta-hydroxysteroid dehydrogenase type 2 in pelvic endometriosis.

Carneiro MM, Morsch DM, Camargos AF, Spritzer PM, Reis FM.

Department of Obstetrics and Gynecology, University of Minas Gerais, Belo Horizonte, Brazil.

Lack of expression or a deficiency of 17beta-hydroxysteroid dehydrogenase type 2 (17beta-HSD2), a key enzyme in estradiol inactivation, could be involved in the pathophysiology of endometriosis. The aim of the present study was to evaluate expression of the gene (17beta-Hsd2) encoding 17beta-HSD2 in eutopic and ectopic endometrial tissues of women with endometriosis. Thirty-four infertile women were divided into a control group, without any clinical or laparoscopic evidence of endometriosis (n = 19), and a group with pelvic endometriosis (n = 15). Diagnosis was confirmed by histological examination of the endometriotic lesions. 17beta-Hsd2 mRNA expression was detected by reverse transcription-polymerase chain reaction in the control group (54% of the samples), in the eutopic endometrium of patients with endometriosis (83% of the specimens analyzed) and in all endometriotic lesions. The semi-quantitative analysis of 17beta-Hsd2 mRNA showed a significantly higher gene expression in the endometriotic implants compared with the intrauterine endometrium of the control group (p < 0.05). 17beta-HSD2 protein was localized to the glandular epithelium of both eutopic endometrium and endometriotic implants. The present results refute the hypothesis of lower or absent 17beta-HSD2 expression in pelvic endometriosis; therefore further studies are needed to assess other potential mechanisms leading to increased estrogenic activity within endometriotic implants.

Acta Cir Bras. 2007 Mar-Apr;22 Suppl 1:8-11.

Evaluation of the macroscopic growth degree of experimental endometriosis in rats.

Nogueira Neto J, Torres OJ, Coelho TM, Nunes JN Jr, Aguiar GC, Costa LK.

Federal University of Maranhão, Mirage of the Sun Street 19, 1001 Renaissance II, 65075-760 São Luís, Maranhão, Brazil. j.nogueira.n@uol.com.br

PURPOSE: To evaluate macroscopically the growth degree of self-transplantation of endometriosis in rats. METHODS: Forty female rats, after a 7-day period for adpating and evaluating of the estrous cycle regularity, underwent tail abdominal midline laparotomy with 3-cm cuts. The average third of the left uterine horn was removed, 4mm x 4mm patches in liquid environment were made, and self-transplanted in the rat mesenterium with a single stitch, and the endometrial surface of the endometriotic implant facing the lumen of the peritoneal cavity. The rats were programmed to die after three weeks. The abdominal cavity displaying was held and self-transplants were identified and classified. RESULTS: The results achieved were: one case for degree 0 (2,5%), three cases for degree 1 (7,5%), eleven cases for degree II (27,5%) and twenty-five cases for degree III (62,5%). CONCLUSION: The experimental endometriosis development, through the self-transplantation technique, showed to be most common in degrees 3 and 2 of development.

Minerva Ginecol. 2007 Apr;59(2):175-81.

[Diagnostic and operative fertiloscopy]

[Article in Italian]

Pellicano M, Catena U, Di Iorio P, Simonelli V, Sorrentino F, Stella N, Bonifacio M, Cirillo D, Nappi C.

Dipartimento di Ginecologia, Ostetricia e Fisiopatologia della Riproduzione Umana Università degli Studi Federico II, Via Sergio Pansini 5, 80131 Naples, Italy. pellican@unina.it

In the last decade, ”fertiloscopy”, a new mini-invasive diagnostic technique, is becoming more and more popular: it is a good alternative to the diagnostic laparoscopy, a standard procedure but surely not harmless, very often capable to discover pathologies in asymptomatic patients. Fertiloscopy allows the visualization of the posterior pelvis (posterior face of the uterus, ovaries, tubes and intestinal ansae with the rectum), with a technique of introducing an optical device in the pouch of Douglas, through the posterior vaginal fornix, under previous general or local anesthesia. When fertiloscopy is performed under local anesthesia, it can comfortably be carried out in out-patient departments and it is generally well tolerated by patients, who follow the whole procedure on the monitor. Moreover, it is possible to perform small interventions, such as adhesiolysis, ovarian drilling, coagulation of endometriosis spots and to perform chromosalpingoscopy and salpingoscopy, important investigations in the diagnostic iter of unexplained female infertility. With fertiloscopy, the patient, therefore, can avoid a real surgical intervention, such as diagnostic laparoscopy, and also uncomfortable examinations, such as hysterosalpingography.

J Clin Endocrinol Metab. 2007 Aug;92(8):3213-8. Epub 2007 May 15.

Metformin suppresses interleukin (IL)-1beta-induced IL-8 production, aromatase activation, and proliferation of endometriotic stromal cells.

Takemura Y, Osuga Y, Yoshino O, Hasegawa A, Hirata T, Hirota Y, Nose E, Morimoto C, Harada M, Koga K, Tajima T, Yano T, Taketani Y.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

CONTEXT: Metformin, a widely used treatment for diabetes that improves insulin sensitivity, also has both antiinflammatory properties and a modulatory effect on ovarian steroid production, two actions that have been suggested to be efficacious in therapy for endometriosis. OBJECTIVE: To determine whether metformin may be effective for the treatment of endometriosis, we evaluated the effects of this agent on inflammatory response, estradiol production, and proliferation of endometriotic stromal cells (ESCs). DESIGN: ESCs derived from ovarian endometriomas were cultured with various concentrations of metformin. MAIN OUTCOME MEASURES: IL-8 production, mRNA expression and aromatase activity, and 5-bromo-2′-deoxyuridine incorporation in ESCs were measured. RESULTS: Metformin dose-dependently suppressed IL-1beta-induced IL-8 production, cAMP-induced mRNA expression and aromatase activity, and 5-bromo-2′-deoxyuridine incorporation in ESCs. CONCLUSION: These results suggest that further investigation into the unique therapeutic potential of metformin as an antiendometriotic drug is warranted.

Skeletal Radiol. 2007 Sep;36(9):879-83. Epub 2007 May 15.

Endometriosis of the superior gluteal nerve.

Reddy S, Porter D, Patton JT, Al-Nafussi A, Beggs I.

Department of Orthopaedics, Royal Infirmary, Edinburgh, EH16 4SA, UK.

Endometriosis that involves nerves is rare and usually occurs in the pelvis. We describe a case of extra-pelvic endometriosis that involved the superior gluteal nerve. The patient presented with ill-defined buttock and thigh pain and a Trendelenberg gait. MRI demonstrated atrophic changes in the gluteus minimus, gluteus medius and tensor fascia lata muscles indicating involvement of the superior gluteal nerve. MRI showed a mass in the line of the superior gluteal nerve. The mass was hyperintense on STIR and T1-weighted images and did not enhance after intravenous contrast although surrounding edema did enhance. Histological examination of material obtained at open biopsy showed endometriosis. The patient was commenced on hormonal treatment to suppress ovarian activity.

BJOG. 2007 Jul;114(7):889-95. Epub 2007 May 15.

Comment in:

BJOG. 2008 Feb;115(3):414; author reply 414-5.

Surgical outcome and long-term follow up after laparoscopic rectosigmoid resection in women with deep infiltrating endometriosis.

Seracchioli R, Poggioli G, Pierangeli F, Manuzzi L, Gualerzi B, Savelli L, Remorgida V, Mabrouk M, Venturoli S.

Center of Reconstructive Pelvic Endo-surgery, Reproductive Medicine Unit, S.Orsola Hospital, University of Bologna, Bologna, Italy. seracchioli@orsola-malpighi.med.unibo.it

The aim of this study was to assess the long-term outcome of treating severely symptomatic women with deep infiltrating intestinal endometriosis by laparoscopic segmental rectosigmoid resection. Detailed intraoperative and postoperative records and questionnaires (preoperatively, 1 month postoperatively and every 6 months for 3 years) were collected from 22 women. The estimated blood loss during surgery was 290 +/- 162 ml (range 180-600), and average hospital stay was 8 days (range 6-19). One woman required blood transfusion after surgery. Two cases were converted to laparotomy. One woman had early dehiscence of the anastomosis. Six months after surgery, there was a significant reduction of symptom scores (greater than 50% for most types of pain) related to intestinal localisation of endometriosis (P < 0.05). Score improvements were maintained during the whole period of follow up. Noncyclic pelvic pain scores showed significant reductions (P < 0.05) after 6 and 12 months, but there was a high recurrence rate later. Dysmenorrhoea and dyspareunia improved in 18/21 and 14/18 women with preoperative symptoms, respectively. Constipation, diarrhoea and rectal bleeding improved in all affected women for the whole period of follow up. Laparoscopic segmental rectosigmoid resection seems safe and effective in women with deep infiltrating colorectal endometriosis resulting in significant reductions in painful and dysfunctional symptoms associated with deep bowel involvement.

Fertil Steril. 2007 Oct;88(4 Suppl):1108-19. Epub 2007 May 11.

PPAR-gamma receptor ligand induces regression of endometrial explants in baboons: a prospective, randomized, placebo- and drug-controlled study.

Lebovic DI, Mwenda JM, Chai DC, Mueller MD, Santi A, Fisseha S, D’Hooghe T.

Reproductive Endocrinology Division, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan 48109, USA. lebovic@umich.edu

OBJECTIVE: To determine the effects of a thiazolidinedione (TZD) agonist of peroxisome proliferator-activated receptor (PPAR)-gamma, rosiglitazone, in a baboon model of established endometriosis. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: Experimental surgery laboratory at the Institute of Primate Research in Nairobi, Kenya. ANIMAL(S): Endometriosis was induced using intrapelvic injection of eutopic menstrual endometrium in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. INTERVENTION(S): Induction of endometriosis by laparoscopy was performed in 12 baboons with a normal pelvis. Endometrial tissue was extracted from each baboon by curettage, and a standard amount of endometrium was then seeded onto several peritoneal sites. About 34-68 days after the induction of laparoscopy, a pretreatment laparoscopy (baseline disease assessment) was performed in the baboons to record the extent of endometriotic lesions. The 12 baboons were randomized into three groups and treated from the day after the staging laparoscopy for a total duration of 30 days. They received phosphate-buffered saline tablets (n = 4, placebo control; placebo tablets once a day by mouth for 30 days), GnRH-antagonists (n = 4, active control; ganirelix acetate 125 microg/day for 30 days), or rosiglitazone (n = 4, test drug, 2 mg by mouth each day for 30 days). A third and final laparoscopy on day 30 after the start of treatment was performed to record the extent of endometriosis. The type of lesion (typical, red, white, or suspicious) was recorded. Biopsies were obtained to confirm the histological presence of endometriosis. MAIN OUTCOME MEASURE(S): A videolaparoscopy was performed 30 days after treatment to document the number and surface area of endometriotic lesions as well as to calculate the revised American Society for Reproductive Medicine score and stage. RESULT(S): The surface area of endometriotic lesions was statistically significantly lower in rosiglitazone-treated baboons when compared with the placebo group. Baboons treated with rosiglitazone or ganirelix had a greater negative relative change in surface area of peritoneal endometriotic lesions than controls. The overall weighted appearance of the lesion types suggests that rosiglitazone may deter the development of newer endometriotic lesions. CONCLUSION(S): A PPAR-gamma ligand, rosiglitazone, effectively diminishes the burden of endometriosis disease in a baboon endometriosis model. This animal model holds promise that a TZD drug may be helpful in women with endometriosis.

Cir Esp. 2007 May;81(5):289-90.

[Extragenital endometriosis as a cause of acute inguinal pain in a woman of reproductive age]

[Article in Spanish]

Moreno-Egea A, Girela E, Aguayo JL.

Arch Gynecol Obstet. 2007 Nov;276(5):559-61. Epub 2007 May 12.

High levels of CA125 (over 1,000 IU/ml) in patients with gynecologic disease and no malignant conditions: three cases and literature review.

Ghaemmaghami F, Karimi Zarchi M, Hamedi B.

Gynecologic Oncology Department, Vali-e-Asr Hospital, Tehran University of Medical Sciences, Imam Khomeini Hospital Complex, Tehran 14194, Iran.

OBJECTIVE: To report the very high serum levels of CA125 in patients with benign gynecologic disease which manifests as pelvic mass. METHODS: Clinical data of three cases with high levels of CA125 over 1,000 IU/ml and benign gynecologic conditions were gathered. in Vali-Asr hospital. RESULTS: Three patients were scheduled for laparatomy as ovarian cancer and leiomyosarcoma. Histologic results after laparatomy showed uterine myoma in two patients and endometrioma in a third patient. CONCLUSION: High levels of CA125 over 1,000 IU/ml, may be showed in other gynecologic conditions with no malignancy. So, other clinical and imaging data could be helpful for differential diagnosis of these patients.

Curr Opin Obstet Gynecol. 2007 Jun;19(3):284-8.

Long-term use of gonadotropin-releasing hormone analogues before IVF in women with endometriosis.

Tavmergen E, Ulukus M, Goker EN.

Family Planning-Infertility Research and Treatment Center, Ege University School of Medicine, Bornova-Izmir, Turkey. eroltavmergen@ttnet.net.tr

PURPOSE OF REVIEW: To discuss the relationship between endometriosis and infertility, the impact of endometriosis on assisted reproductive techniques and also the benefits of prolonged use of gonadotropin-releasing hormone analogue before IVF in women with endometriosis. RECENT FINDINGS: The available evidence suggests that endometriosis is strongly associated with infertility. Many studies indicate lower pregnancy and implantation rates even in assisted reproductive cycles in women with endometriosis. It is well known that medical suppression of endometriosis does not appear to be warranted for endometriosis-associated infertility. Prolonged pretreatment with gonadotropin-releasing hormone analogue before IVF has been reported to improve clinical pregnancy rates in infertile women with endometriosis. SUMMARY: Based on the recently published data, infertile women with endometriosis may benefit from long-term pretreatment of gonadotropin-releasing hormone analogue prior to IVF.

Curr Opin Obstet Gynecol. 2007 Jun;19(3):229-37.

Reproductive performance of women with müllerian anomalies.

Rackow BW, Arici A.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA. beth.rackow@yale.edu

PURPOSE OF REVIEW: This review discusses current diagnostic techniques for müllerian anomalies, reproductive outcome data, and management options in reproductive-age women. RECENT FINDINGS: Multiple retrospective studies have investigated reproductive outcomes with müllerian anomalies, but few current prospective studies exist. Uterine anomalies are associated with normal and adverse reproductive outcomes such as recurrent pregnancy loss and preterm delivery, but not infertility. Furthermore, unicornuate, didelphic, bicornuate, septate, arcuate, and diethylstilbestrol-exposed uteri have their own reproductive implications and associated abnormalities. Common presentations of müllerian anomalies and current diagnostic techniques are reviewed. Surgical intervention for müllerian anomalies is indicated in women with pelvic pain, endometriosis, obstructive anomalies, recurrent pregnancy loss, and preterm delivery. Although surgery for most uterine anomalies is a major intervention, the uterine septum is preferentially managed with a hysteroscopic procedure. Several recent studies and review articles discuss management of the septate uterus in asymptomatic women, infertile women, and women with a history of poor reproductive outcomes. Current assessment of reproductive outcomes with uterine anomalies and management techniques is warranted. SUMMARY: Müllerian anomalies, especially uterine anomalies, are associated with both normal and adverse reproductive outcomes, and management in infertile women remains controversial.

Fertil Steril. 2007 Oct;88(4):969.e7-9. Epub 2007 May 10.

Intestinal endometriosis complicated by ileal perforation after initiation of gonadotropin-releasing hormone agonist therapy.

Saito S, Murakami T, Suzuki K, Terada Y, Fukushima K, Moriya T.

Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan.

OBJECTIVE: To report a rare complication of GnRH agonist therapy for intestinal endometriosis. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 45-year-old nulliparous Japanese woman with catamenial digestive symptoms. INTERVENTION(S): GnRH agonist therapy. MAIN OUTCOME MEASURE(S): Acute abdomenal crisis with free air in the abdominal X-ray. RESULT(S): An emergency laparotomy showed both an ileal constriction and perforation. An ileocecal enterectomy with an end-to-end anastomosis was performed. A pathological examination of the ileum revealed ileal endometriosis. CONCLUSION(S): Flare-up of intestinal endometriosis induced by GnRH agonist has the potential to lead to intestinal perforation. Careful diagnosis and treatment are necessary for cyclic and periodic gastrointestinal manifestation.

Gastroenterol Hepatol. 2007 May;30(5):274-6.

[Ileal perforation secondary to intestinal endometriosis]

[Article in Spanish]

Vanrell Garau M, Ginard Vicens D, Mariño Méndez Z, Bosque López MJ, Reyes Moreno J, Escarda Gelabert A, Corteza A, Gayá Cantallops J.

Servicio de Aparato Digestivo, Hospital Universitario Son Dureta, Andrea Doria 55, 07014 Palma de Mallorca, Mallorca, Spain.

Endometriosis is defined as the presence of endometrial tissue outside the uterus. The bowel is not often affected. There are no specific clinical findings for intestinal endometriosis. It is typically asymptomatic, but sometimes can present with abdominal pain, diarrhoea, constipation or intestinal obstruction. Ileal perforation is a rare complication of intestinal endometriosis and only a few cases have been reported in the literature. Intestinal endometriosis can mimic many gastrointestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, infections and neoplasms. The diagnosis is made by laparoscopy or laparotomy. We present a case of a woman with intermittent abdominal pain and ileal perforation secondary to intestinal endometriosis.

Int J Mol Med. 2007 Jun;19(6):909-13.

Expression of vascular endothelial growth factor receptor-3 in the endometrium in menorrhagia.

Mints M, Blomgren B, Palmblad J.

Department of Clinical Science, Division of Obstetrics and Gynaecology, Karolinska Institutet at Karolinska University Hospital Huddinge, S-14186 Stockholm, Sweden. miriam.mints@telia.com

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common gynecological disorders, including menorrhagia and endometriosis. We have recently shown that expression of vascular endothelial growth factor (VEGF)-A and its two main receptors, VEGFR-1 and -2, is increased in idiopathic menorrhagia (IM). The aim of this study was to determine the expression of VEGFR-3 in normal and IM endometrium. Endometrial biopsies from 24 patients with IM and 18 healthy and fertile women were used for immunohistochemistry assessments and image analyses of VEGFR-3 and CD34-stained endothelial structures. We found that weak to moderate expression of VEGFR-3 was present in stroma and glands throughout the menstrual cycle without differences between patients and controls. Capillaries expressed VEGFR-3 markedly, whereas arterioles and venules stained moderately to markedly. However, we observed that vascular expression of VEGFR-3 in capillaries was 1.6-fold higher in the IM group than in controls, when assessed as the number of stained capillaries per mm(2). There was also a 2.0-fold higher number of arterioles, which were VEGFR-3 positive in the IM group. There was no difference with regard to the menstrual cycle between patients and controls. Thus, human endometrium expresses VEGFR-3, and expression of this receptor is increased in idiopathic menorrhagia. These results indicate that VEGFR-3 may play a role in the abnormal endometrial angiogenesis of IM.

Oncol Rep. 2007 Jun;17(6):1333-9.

Increased synthesis of indoleamine-2,3-dioxygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer.

Takao M, Okamoto A, Nikaido T, Urashima M, Takakura S, Saito M, Saito M, Okamoto S, Takikawa O, Sasaki H, Yasuda M, Ochiai K, Tanaka T.

Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.

We previously reported that indoleamine-2,3-dioxygenase (IDO) is associated with paclitaxel resistance and that IDO serves as a marker of poor prognosis in ovarian serous adenocarcinomas (SA). In this study, to explore the role of IDO in the development of various histological types of ovarian cancer, we further examined IDO expression not only in SA but also in other types of ovarian cancers. Expression of IDO protein was analyzed by immunohistochemistry for a total of 122 ovarian cancers including 40 SA, 67 clear cell adenocarcinomas (CCA), and 15 endometrioid adenocarcinomas (EA) with informed consent. Among these cases, there were 11 CCA accompanied with endometriosis and 60 cases with lymph node metastasis. We classified the samples into four categories by IDO staining pattern. IDO staining was positive in 57.5% of SA, 49.2% of CCA, and 73.3% of EA, respectively. The Kaplan-Meier survival curve showed a clear relationship between staining score and overall survival for patients with advanced (stages III and IV) SA (n=33) who underwent optimal surgery and paclitaxel-carboplatin (TC) chemotherapy as a first-line regimen. There was no association between IDO staining score and overall survival in the CCA cases. Eight of 11 cases (72.7%) of CCA accompanied by endometriosis presented identical staining patterns of IDO between CCA and endometriosis. In 43 of 60 cases (71.6%) with lymph node metastasis, the staining patterns of IDO showed a correspondence between the primary lesion and metastatic site. These results suggested that the increased synthesis of IDO protein was positively associated with impaired survival only in the serous type of ovarian cancer.

Asian J Androl. 2007 May;9(3):388-93.

Gossypol inhibits proliferation of endometrioma cells in culture.

Badawy SZ, Souid AK, Cuenca V, Montalto N, Shue F.

Department of Obstetrics and Gynecology, SUNY Upstate Medical University, Syracuse, New York 13210, USA. badawys@upstate.edu

AIM: To evaluate the anti-proliferative activity and mitochondrial toxicity of gossypol in endometrioma cells maintained in short-term cultures. METHODS: (A) Three endometrioma cell lines from patients were treated with 25 or 50 nmol/L gossypol for up to 12 days. The effect of gossypol on the cell growth was recorded. (B) A phosphorescence oxygen analyzer was used to determine the effects of gossypol on mitochondrial oxygen consumption of six endometrioma cell lines from patients. (C) Cellular gossypol accumulations in three endometrioma cell lines from patients were measured by high-pressure liquid chromatography. RESULTS: Proliferation of the endometrioma cells was inhibited by 25 and 50 nmol/L gossypol. Respiration of the endometrioma cells was inhibited by 10 micromol/L gossypol. Cellular gossypol was detected in the endometrioma cell lines that were treated for 24 h with 10 and 0.3 micromol/L gossypol. CONCLUSION: Gossypol invokes a potent toxicity on cultured endometrioma cells.

Front Biosci. 2007 May 1;12:3247-55.

Genetics of endometriosis: current status and prospects.

Vigano P, Somigliana E, Vignali M, Busacca M, Blasio AM.

Molecular Biology Laboratory, Istituto Auxologico Italiano, Milano, Italy. paola.vigano@unimi.it

Family and twin studies have shown that heritability accounts for endometriosis development to an extent similar to other complex genetic diseases. Both linkage analysis and association studies have been performed to identify genetic determinants for the disease. Results from the linkage scan of 1,176 families collected thanks to a joint effort between an Australian and a UK group supported significant linkage to a novel susceptibility locus on chromosome 10q26. Although gene variants with effects on the disease predisposition have been proposed to exist and several candidates have been put forward, their effects have not been or are yet to be confirmed. The main categories of candidate genes studied have been those involved in detoxification processes, sex steroid biosynthesis and action, immune system regulation. Genetic studies on endometriosis face numerous challenges as the disease has several manifestations and different forms. Moreover, strong gene-environmental interactions might definitively influence approaches to identify genetic variants involved. Genome-wide association studies that survey most of the genome for causal genetic variants provide the potential for future progress.

Front Biosci. 2007 May 1;12:3140-51.

Apoptosis and endometriosis.

Harada T, Taniguchi F, Izawa M, Ohama Y, Takenaka Y, Tagashira Y, Ikeda A, Watanabe A, Iwabe T, Terakawa N.

Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago, Japan. tasuku@grape.med.tottori-u.ac.jp

Apoptosis plays a critical role in maintaining tissue homeostasis and represents a normal function to eliminate excess or dysfunctional cells. Accumulated evidence suggest that apoptosis helps to maintain cellular homeostasis during the menstrual cycle by eliminating senescent cells from the functional layer of the uterine endometrium during the late secretory and menstrual phase of the cycle. BCL-2 family and Fas/FasL system have been extensively studied in human endometrium and endometriotic tissues. Eutopic endometrium from women with endometriosis reportedly has some fundamental differences compared with normal endometrium of women without endometriosis. The differences could contribute to the survival of regurgitating endometrial cells into the peritoneal cavity and the development of endometriosis. One mechanism that recently gained a lot of interest is the finding that apoptosis appeared in eutopic and ectopic endometrium of patients with endometriosis. This study is a current review of the literature focused on the physiological role of apoptosis in normal endometrium and the alterations in regulation of apoptosis in eutopic and ectopic endometrium from women with endometriosis. Finally, role of apoptosis in the treatment of endometriosis is reviewed to link the basic research findings into clinical applications.

Gynecol Endocrinol. 2007 Jan;23(1):29-33.

Genetic polymorphisms of cytochrome P450cl7alpha (CYP17) and progesterone receptor genes (PROGINS) in the assessment of endometriosis risk.

De Carvalho CV, Nogueira-De-Souza NC, Costa AM, Baracat EC, Girão MJ, D’Amora P, Schor E, da Silva ID.

Molecular Gynecology Laboratory, Federal University of São Paulo, São Paulo, Brazil.

We designed the present study in order to evaluate the eventual role of polymorphisms in the genes encoding cytochrome P450c17alpha (CYP17) and the progesterone receptor (PROGINS) as risk factors for endometriosis development. Eligible cases consisted of 121 women with surgically confirmed endometriosis who underwent treatment in a hospital in São Paulo, Brazil during the period from September 2003 to September 2005. The 281 controls were participants with normal gynecological as well as pelvic ultrasound evaluation, who did not have any gynecological conditions during their reproductive lives such as pelvic pain and/or dyspareunia nor infertility history. Genomic DNA was obtained from buccal cells and processed for DNA extraction using the GFX DNA extraction kit (GE Healthcare). The CYP17 (-34T–>C) polymerase chain reaction-restriction fragment length polymorphism assay has been described previously, as has the progesterone receptor polymorphism (PROGINS) detection assay. PROGINS heterozygosis genotype frequencies were shown to be statistically higher in endometriosis cases compared with controls. On the other hand, differences in the CYP17 polymorphism (-34T–>C) frequencies were not even close to significance (p = 0.278) according to our findings.

Gynecol Endocrinol. 2007 Jan;23(1):5-12.

Endometriosis: the way forward.

Hompes PG, Mijatovic V.

Division of Reproductive Medicine, Department of Obstetrics & Gynecology, Vrije Universiteit Medical Centre, Amsterdam, The Netherlands. p.hompes@vumc.nl

Endometriosis, a common cause of morbidity, affects 10% of women of reproductive age. In this review we focus on the new developments in pathogenesis, diagnosis and treatment options, reviewing the literature published about this enigmatic disorder over the past three years. More specifically, new theories of the pathogenesis of the syndrome of Sampson and Cullen are discussed. The new era of genomics may characterize endometriosis and transform clinical management of the disease. Literature suggesting that endometriosis may have an environmental origin is reviewed. New approaches to medical therapy of endometriosis have been developed, including the levonorgestrel-releasing intrauterine device, aromatase inhibitors, immunomodulatory drugs, angiogenesis inhibitors, selective estrogen and progesterone receptor modulators, and statins. Subfertility is another well-known result of endometriosis and often complex decisions must be made regarding management of the endometriosis patient who wishes to conceive. Laparoscopic surgery and assisted reproduction–with or without gonadotropin-releasing hormone-agonist treatment–are reviewed. Finally we speculate about new developments in the field of endometriosis in the coming three years.

Mol Hum Reprod. 2007 Jul;13(7):503-9. Epub 2007 May 5.

Nuclear factor-kappa B is constitutively activated in peritoneal endometriosis.

González-Ramos R, Donnez J, Defrère S, Leclercq I, Squifflet J, Lousse JC, Van Langendonckt A.

Department of Gynecology, Université Catholique de Louvain, Cliniques Universitaires St Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium.

Red (active), black and white endometriotic lesions are characteristic of peritoneal endometriosis. The transcription factor nuclear factor-kappa B (NF-kappaB) activates proinflammatory, proliferative and antiapoptotic genes in many cell types. To determine whether NF-kappaB is activated in peritoneal endometriosis in women, and further ascertain the differential inflammatory status of endometriotic implants, NF-kappaB activation and intercellular adhesion molecule (ICAM)-1 expression were investigated in peritoneal endometriotic lesions according to their type. Furthermore, p65 and p50 subunits of active NF-kappaB dimers were evaluated in endometriotic lesions to gain some insight into NF-kappaB-implicated pathways. Thirty-six biopsies of peritoneal endometriotic lesions were analyzed. Constitutive NF-kappaB activation, involving p65- and p50-containing dimers, was demonstrated in peritoneal endometriotic lesions by electrophoretic mobility shift assays and supershift analyses, as well as NF-kappaB (p65) DNA-binding activity immunodetection assays. NF-kappaB activation and ICAM-1 expression (evaluated by immunoblotting) were significantly higher in red lesions than black lesions, whereas IkappaBalpha (NF-kappaB inhibitory protein) expression was constant, as shown by western blot analysis. This is the first study to demonstrate constitutive NF-kappaB activation in peritoneal endometriosis in women. NF-kappaB activation and ICAM-1 expression in red lesions confirm the more extensive inflammatory pattern of these lesions compared with black lesions. The involvement of p50/p65 dimers in NF-kappaB activation suggests implication of the classic NF-kappaB activation pathway, making it an attractive therapeutic target in endometriosis.

Thromb Res. 2007;120 Suppl 1:S17-20. Epub 2007 May 7.

More than menorrhagia: a review of the obstetric and gynaecological manifestations of von Willebrand disease.

James AH.

Women’s Hemostasis and Thrombosis Clinic, Duke University Medical Center, Durham, NC 27710, USA. andra.james@duke.edu

Menorrhagia is the most common symptom experienced by women with von Willebrand’s disease (VWD), but several other gynaecological disorders also occur more frequently in these women; primarily ovarian cysts and endometriosis. Women with VWD are most likely to experience an increased incidence of gynaecological disorders and obstetric complications that manifest with bleeding. The incidence of these disorders and the complications of pregnancy are discussed with particular reference to a case-control study conducted by the U.S. Centers for Disease Control and Prevention.

Fertil Steril. 2007 Dec;88(6):1700-2. Epub 2007 May 7.

Artificial neural networks combined with surface-enhanced laser desorption/ionization mass spectra distinguish endometriosis from healthy population.

Wang L, Zheng W, Yu JK, Jiang WZ, Mu L, Zhang SZ.

Department of Gynecology, Second Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, China.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein chip array technology was used to detect the serum proteomic patterns in patients with endometriosis. Four potential biomarkers (8,141 m/z, 6,096 m/z, 5,894 m/z, and 3,269 m/z) were found. This method showed great potential in screening better biomarkers for endometriosis.

Fertil Steril. 2007 Oct;88(4 Suppl):1207-11. Epub 2007 May 4.

Immunohistochemical study of osteopontin and L-selectin in a rat endometriosis model and in human endometriosis.

Odagiri K, Konno R, Fujiwara H, Netsu S, Ohwada M, Shibahara H, Suzuki M.

Department of Gynecology, Omiya Medical Center, Jichi Medical School, Saitama, Japan.

OBJECTIVE: To investigate the localization of the proteins osteopontin (OPN) and L-selectin (SELL). DESIGN: Retrospective nonrandomized immunohistochemical study in a surgically induced rat model of peritoneal endometriosis and in samples of human endometriotic lesions of ovaries. SETTING: Department of gynecology in a university hospital. PATIENT(S): A rat endometriosis model was induced in 10 8-week-old SLC-Sprague-Dawley rats by surgical autotransplantation of uterus. Fourteen premenopausal women with histologically diagnosed endometriosis were selected (mean age, 39 y; range, 25-53 y). Twenty endometriotic specimens were obtained from 14 patients who underwent laparoscopic surgery for enlarged endometriotic cysts. INTERVENTION(S): Histopathological examination of endometriotic ovarian specimens for OPN and SELL expression by immunohistochemistry. MAIN OUTCOME MEASURE(S): Demonstration of the immunoreactive staining of OPN and SELL expressions in tissues of a rat endometriosis model and of human endometriosis. RESULT(S): In both tissues from a rat endometriosis model and from human endometriosis, OPN was stained more prominently in glandular epithelium than in interstitial space, whereas SELL stained more prominently in interstitial space (macrophages and lymphocytes) than in epithelium. The staining pattern of OPN in ectopic endometriotic lesions was very similar to that in eutopic normal human endometrium in the secretory phase. CONCLUSION(S): These results suggested important roles for OPN and SELL in the pathogenesis of endometriosis.

Fertil Steril. 2007 Nov;88(5):1298-303. Epub 2007 May 4.

Levels of complement components iC3b, C3c, C4, and SC5b-9 in peritoneal fluid and serum of infertile women with endometriosis.

Kabut J, Kondera-Anasz Z, Sikora J, Mielczarek-Palacz A.

Department of Immunology and Serology, Medical University of Silesia, Katowice, Poland.

OBJECTIVE: To assess whether complement components iC3b, C3c, C4, and SC5b-9 may be involved in the pathogenesis of endometriosis. DESIGN: Prospective, experimental trial. SETTING: Medical university. PATIENT(S): 112 women infertile women undergoing laparoscopy. INTERVENTION(S): Venipuncture and laparoscopic peritoneal fluid collection. MAIN OUTCOME MEASURE(S): Peritoneal fluid and serum iC3b, C3c, C4, and SC5b-9 levels were measured by the enzyme-linked immunosorbent assay (ELISA) method. RESULT(S): Higher levels of C3c, C4, and SC5b-9 complement components were found in the serum compared with the peritoneal fluid, but the levels of iC3b were higher in the peritoneal fluid. We observed higher concentrations of C3c, C4, and SC5b-9 in the peritoneal fluid and serum of women with endometriosis compared with healthy women. However, the levels of iC3b in both peritoneal fluid and serum were statistically significantly lower than in the control group. CONCLUSION(S): The impairment of the mechanisms involved in the regulation of activation of complement system may be an important factor in the pathogenesis of endometriosis and endometriosis-associated infertility.

J Steroid Biochem Mol Biol. 2007 May;104(3-5):246-51. Epub 2007 Mar 20.

A sensitive HPLC method for the assessment of metabolic conversion of estrogens.

Delvoux B, Husen B, Aldenhoff Y, Koole L, Dunselman G, Thole H, Groothuis P.

Research Institute GROW, University Hospital Maastricht, University of Maastricht, The Netherlands.

Disorders of estrogen-responsive tissues are frequently associated with aberrations in steroid metabolism due to altered expression of synthesizing and metabolizing enzymes. For instance, overexposure to unopposed 17beta-estradiol has been associated with the pathogenesis of endometrial proliferative disorders, such as endometriosis. Investigations into the metabolic conversion in tissues and cells have been rather limited. This is mostly due to fact that such studies have to make use of radioactive steroid hormones and expensive equipment to obtain sufficient sensitivity. We adapted a sensitive non-radioactive HPLC method to study estrogen metabolism in more detail. This HPLC method is based on the solid phase extraction of estrogens and the derivatization of the steroids with 2-(4-carboxy-phenyl)-5,6-dimethylbenzimidazole. The technique is sensitive, robust and is useful for the detection of aromatase, 17beta-HSD types 1 and 2 and sulfatase activities in lysates of placenta and endometrium.

Fertil Steril. 2007 Nov;88(5):1304-10. Epub 2007 May 4.

Immunohistochemical detection of heparanase-1 expression in eutopic and ectopic endometrium from women with endometriosis.

Xu X, Ding J, Ding H, Shen J, Gattuso P, Prinz RA, Rana N, Dmowski WP.

Department of General Surgery, Rush University Medical Center, Chicago, IL 60612, USA. xxu@rush.edu

OBJECTIVE: To investigate the expression of heparanase-1, an endoglycosidase that degrades heparan sulfate proteoglycans, in eutopic and ectopic endometrial tissues from women with endometriosis. DESIGN: An immunohistochemical study. SETTING: Academic research laboratory and a private infertility clinic affiliated with a university medical center. PATIENT(S): Premenopausal women undergoing laparoscopy for endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Expression of heparanase-1 analyzed by immunohistochemical staining in 91 eutopic and 14 ectopic endometrial specimens. RESULT(S): We found that 17% (4/24) of the eutopic endometrial specimens in the early proliferative phase and 32% (9/28) of the samples in the midproliferative phase were heparanase-1 positive. However, >or=80% of eutopic endometrial specimens at late proliferate phase and at luteal phase were heparanase-1 positive. Twelve of 14 ectopic endometriotic specimens stained heparanase-1 positive. Comparison of heparanase-1 expression in paired eutopic and ectopic endometrial tissues revealed that 5 of 6 ectopic specimens in the early proliferative phase were heparanase-1 positive, whereas only 1 eutopic specimen was heparanase-1 positive. In comparison with our recent study of heparanase-1 expression in normal endometrium, we found that there was no significant difference in heparanase-1 expression in the eutopic endometrium from women with or without endometriosis. CONCLUSION(S): Heparanase-1 was differentially expressed in the eutopic endometrium in the different menstrual phases. Heparanase-1 was highly expressed in the ectopic endometriotic lesions regardless of their menstrual phases, suggesting that the local environment is responsible for increased heparanase-1 expression.

Eur J Gynaecol Oncol. 2007;28(2):77-82.

Robotic surgery in gynecology.

Magrina JF.

Director Division of Gynecologic Oncology Department of Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Scottsdale, AZ 85259, USA.

Robotic technology is nothing more than an enhancement along the continuum of laparoscopic technological advances and represents only the beginning of numerous more forthcoming advances. It constitutes a major improvement in the efficiency, accuracy, ease, and comfort associated with the performance of laparoscopic operations. Instrument articulation, downscaling of movements, absence of tremor, 3-D image, and comfort for the surgeon, assistant and scrub nurse are all new to the practice of laparoscopy. In our hands, robotic operative times for simple and radical hysterectomy are shorter than those obtained by conventional laparoscopy. Robotic technology is preferable to conventional laparoscopic instrumentation for the surgical treatment of gynecologic malignancies and most operations for benign disease of certain complexity such as hysterectomy myomectomy, and invasive pelvic endometriosis.

Qual Health Res. 2007 May;17(5):571-85.

Relational patterns of couples living with chronic pelvic pain from endometriosis.

Strzempko Butt F, Chesla C.

San Francisco, California, USA.

Chronic pelvic pain (CPP) is a disabling condition affecting 15 to 20% of U.S. women of reproductive age. Endometriosis, one of the most common causes of CPP, is associated with symptoms of pelvic pain, painful sexual intercourse, and infertility. In this qualitative study, the authors examined the relational impact of CPP from endometriosis on 13 couples through narrative interviews conducted individually and jointly. They describe five relational patterns that vary on degree of closeness, how care responsibilities are enacted, the degree to which couples are conjoined in their experiences, and how much their lives are overtaken with the disease. These patterns articulate couples’ relational concerns as well as daily management of illness.

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