Fertil Steril. 2010 Feb;93(3):e11; author reply e12. Epub 2010 Jan 8.

Endometriosis: is laparoscopy justified without previous ultrasonogram and magnetic resonance imaging (MRI)?

Belaisch J.

Comment on:

Fertil Steril. 2010 Jan 5. [Epub ahead of print]

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model.

Machado DE, Berardo PT, Landgraf RG, Fernandes PD, Palmero C, Alves LM, Abrao MS, Nasciutti LE.

Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária-Ilha do Fundão, Rio de Janeiro, Brazil.

OBJECTIVE: To analyze the antiangiogenic effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib on the growth of endometrial implants in a rat model of peritoneal endometriosis. DESIGN: Pharmacologic interventions in an experimental model of peritoneal endometriosis. SETTING: Research laboratory in the Federal University of Rio de Janeiro. ANIMAL(S): Twenty female Sprague-Dawley rats with experimentally induced endometriosis. INTERVENTION(S): After implantation and establishment of autologous endometrium onto the peritoneum abdominal wall, rats were randomized into groups and treated with parecoxib or the vehicle by IM injection for 30 days. MAIN OUTCOME MEASURE(S): Vascular density, the expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1, the distribution of activated macrophages, the expression of COX-2, and the prostaglandin concentration in the endometriotic lesions treated with parecoxib were analyzed. RESULT(S): The treatment significantly decreased the implant size, and histologic examination indicated mostly atrophy and regression. A reduction in microvessel density and in the number of macrophages, associated with decreased expression of VEGF and Flk-1, also were observed. The treatment group showed a low concentration of prostaglandin E(2). CONCLUSION(S): These results suggest that the use of COX-2 selective inhibitors could be effective to suppress the establishment and growth of endometriosis, partially through their antiangiogenic activity. Copyright © 2009 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Jan 5. [Epub ahead of print]

Mechanisms regulating invasiveness and growth of endometriosis lesions in rat experimental model and in humans.

Sotnikova NY, Antsiferova YS, Posiseeva LV, Shishkov DN, Posiseev DV, Filippova ES.

Department of Clinical Immunology, Research State Institute of Maternity and Childhood, Ivanovo, Russia.

OBJECTIVE: To compare the expression of MMP-2, TIMP-2, and TGFbeta2 mRNA in experimental and human endometriotic lesions and to assess the possibility of its cytokine regulation. DESIGN: Experimental laboratory study. SETTING: Medical center. ANIMALS AND PATIENT(S): Thirty female Wistar rats, 17 women with endometriosis, 11 healthy women. INTERVENTION(S): Uterine transplants were attached to rat peritoneum via the surgical autotransplantation technique. The collection of endometriotic implants at 7, 14, and 21 days postsurgery and laparoscopic collection of peritoneal fluid, ectopic, and matched eutopic endometrium from women with endometriosis were performed. MAIN OUTCOME MEASURE(S): MMP-2, TIMP-2, TGFbeta2 mRNA expression in endometrium was assessed by real-time reverse-transcription polymerase chain reaction. RESULT(S): In rats, the increase of MMP-2 and decrease of TIMP-2 mRNA expression was noted at the 7th day, and an increase of TGFbeta2 mRNA expression was seen at the 14th day postsurgery. In humans, elevation of TIMP-2 mRNA expression in eutopic endometrium and of MMP-2, TGFbeta2 mRNA expression in ectopic endometrium was observed. Autologous peritoneal fluid stimulated MMP-2 mRNA expression in eutopic endometrium of women with endometriosis. Cytokines derived from ectopic lesions mononuclear cells increased TGFbeta2 mRNA expression in endometrium of healthy women. CONCLUSION(S): Supposedly MMP-TIMP balance is important in promoting endometriotic tissue invasion and TGFbeta2 in regulating ectopic endometrium growth. Copyright © 2009 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Gynecol Obstet Invest. 2009 Dec 24;69(3):203-211. [Epub ahead of print]

Treatment of Endometriosis with Transvaginal Ultrasound-Guided Drainage and Recombinant Interleukin-2 Left in the Cysts: A Third Clinical Trial.

Acién P, Velasco I, Acién M, Quereda F.

Service of Obstetrics and Gynecology, San Juan University Hospital, and Department/Division of Gynecology, School of Medicine, Miguel Hernandez University, Campus of San Juan, Alicante, Spain.

Background: To analyze the therapeutic results of recombinant interleukin-2 (rIL-2) left in the cysts after transvaginal ultrasound (US)-guided drainage of endometriomas as an alternative to surgery. Methods: Prospective and randomized clinical trial. A total of 25 consecutive patients were included. Two transvaginal US-guided punctures were performed, and 3 million IU of rIL-2 were left in the aspirated cysts once (group I) or both (group II) times according to randomization. Main Outcome Measures: Clinical results, prevented surgeries, and recurrences. Results: Results were moderate or good in only 16% of subjects at 3 months and in 33% of subjects at 6 months after treatment in group I; these numbers were 66 and 33%, respectively, in group II. Differences were not statistically significant. However, the evolution of symptoms, endometriomas, and CA-125 revealed the low efficacy of rIL-2 left intracyst as well as a poor control of the clinical manifestations. After 1 year, 20% (group I) and 73% (group II) of patients had to be operated; after 2 years, these numbers were 55 and 82%, respectively. Conclusions: Treatment of endometriomas with transvaginal US-guided drainage and rIL-2 left in the cysts, without using endometrial suppressive therapy with GnRH analogues as done in previous studies, has low efficacy. Recurrences are even more frequent after the use of two rIL-2 doses. Copyright © 2009 S. Karger AG, Basel.

Am J Orthop (Belle Mead NJ). 2009 Nov;38(11):E175-8.

Calf endometriosis: a case report and review of musculoskeletal involvement.

Saberi S, Farhoud AR, Radmehr A.

Department of Orthopedic Surgery, Tehran University of Medical Sciences, Imam Khomeini Hospital, Tehran, Iran.

Fertil Steril. 2010 Jan 2. [Epub ahead of print]

Depression: an emotional obstacle to seeking medical advice for infertility.

Herbert DL, Lucke JC, Dobson AJ.

School of Population Health, University of Queensland, Brisbane, Australia.

OBJECTIVE: To investigate the mental and general health of infertile women who had not sought medical advice for their recognized infertility and were therefore not represented in clinical populations. DESIGN: Longitudinal cohort study. SETTING: Population based. PATIENT(S): Participants in the Australian Longitudinal Study on Women’s Health aged 28-33 years in 2006 who had ever tried to conceive or had been pregnant (n = 5,936). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Infertility, not seeking medical advice. RESULT(S): Compared with fertile women (n = 4,905), infertile women (n = 1,031) had higher odds of self-reported depression (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01-1.43), endometriosis (5.43, 4.01-7.36), polycystic ovary syndrome (9.52, 7.30-12.41), irregular periods (1.99, 1.68-2.36), type II diabetes (4.70, 1.79-12.37), or gestational diabetes (1.66, 1.12-2.46). Compared with infertile women who sought medical advice (n = 728), those who had not sought medical advice (n = 303) had higher odds of self-reported depression (1.67, 1.18-2.37), other mental health problems (3.14, 1.14-8.64), urinary tract infections (1.67, 1.12-2.49), heavy periods (1.63, 1.16-2.29), or a cancer diagnosis (11.33, 2.57-49.89). Infertile women who had or had not sought medical advice had similar odds of reporting an anxiety disorder or anxiety-related symptoms. CONCLUSION(S): Women with self-reported depression were unlikely to have sought medical advice for infertility. Depression and depressive symptoms may be barriers to seeking medical advice for infertility. Copyright © 2009 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Am J Reprod Immunol. 2010 Mar 1;63(3):214-21. Epub 2009 Dec 29.

Leptin on peritoneal macrophages of patients with endometriosis.

Wu MH, Huang MF, Chang FM, Tsai SJ.

Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan, Taiwan.

PROBLEM: The expression of cyclooxygenase (COX)-2 is considered as a marker of macrophage activation and has been implicated in the development of endometriosis. Leptin is an immunomodulator, which may also affect the development of endometriosis. However, how leptin contributes to these pathological processes has not been completely understood. The aim of this study was to investigate the effects of leptin on peritoneal macrophages and its relationship with endometriosis. METHODS OF STUDY: Peritoneal fluid from 60 women of reproductive age was obtained while they underwent laparoscopy. Forty patients had endometriosis and 20 patients did not have endometriosis. The concentration of leptin in the peritoneal fluid and prostaglandin F(2alpha) levels was measured by ELISA, and the other protein expression using Western blot when peritoneal macrophages were stimulated with leptin. RESULTS: Concentration of leptin in peritoneal fluid was increased in patients with endometriosis compared with disease-free normal control. Functional leptin receptor was present in peritoneal macrophages. Treatment of peritoneal macrophages with leptin induced COX-2 expression. Production of prostaglandin F(2alpha) by peritoneal macrophages was increased after leptin stimulation in women with endometriosis. CONCLUSION: Elevated concentration of leptin in peritoneal fluid may contribute to the pathological process of endometriosis through activation of peritoneal macrophages.

Am J Reprod Immunol. 2010 Mar 1;63(3):222-6. Epub 2009 Dec 29.

No association between the GSTP1 exon 5 polymorphism and susceptibility to advanced stage endometriosis in the Korean population.

Jeon MJ, Choi YM, Hong MA, Lee GH, Ku SY, Kim SH, Kim JG, Moon SY.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yungun-dong, Chongno-ku, Seoul, South Korea.

PROBLEM: To investigate whether the glutathione-S-transferase P1 (GSTP1) exon 5 polymorphism is associated with susceptibility to advanced stage endometriosis in Korean women. METHOD OF STUDY: Case-control study in a collective of 260 patients and 164 controls. Genotyping of the GSTP1 exon 5 polymorphism was performed by using real-time TaqMan PCR assay. RESULTS: The genotype distribution of the GSTP1 exon 5 polymorphism in the endometriosis group was not significantly different from that of the control group (AA/AG/GG rates were 64.2%/32.7%/3.1% and 65.2%/31.7%/3.0% for the endometriosis and control groups, respectively, P = 0.977). Further subgroup analysis according to either stage or bilaterality of ovarian endometrioma also found no significant difference in the genotype distribution between any of the endometriosis subgroups and the control group. CONCLUSION: These findings suggest that the GSTP1 exon 5 polymorphism is not a major determinant of the development of advanced stage endometriosis in the Korean population.

Fertil Steril. 2009 Dec 31. [Epub ahead of print]

Attenuated oocyte fertilization and embryo development associated with altered growth factor/signal transduction induced by endometriotic peritoneal fluid.

Ding GL, Chen XJ, Luo Q, Dong MY, Wang N, Huang HF.

Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China.

OBJECTIVE: To investigate whether the embryotoxic effect of peritoneal fluid (PF) from infertile women with mild endometriosis on mouse oocytes and embryos is associated with changes in embryonic epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and their receptors. DESIGN: Experimental animal study. SETTING: University-based research laboratory. ANIMAL(S): Adult ICR mice. INTERVENTION(S): Peritoneal fluid was obtained from fertile women with no endometriosis (PF-NE) and infertile women with mild endometriosis (PF-E). In vitro fertilization was performed, and mouse two-cell stage embryos were cultured in human tubal fluid medium with or without PF. MAIN OUTCOME MEASURE(S): Rates of fertilization, cleavage, and blastulation. The embryonic EGF and IGF-I levels in culture medium were analyzed by enzyme-linked immunosorbent assay, and EGF receptor, IGF-I receptor, and phosphorylated extracellular signal-regulated protein kinases (p-ERK) expression was determined by immunofluorescence and confocal microscopy. RESULT(S): When oocytes and embryos were cultured in media with PF-E, the fertilization capability of oocytes and the development potential of embryos were decreased. The levels of embryonic EGF, IGF-I, and their receptors were increased. However, p-ERK of the postreceptor signal transduction pathway was down-regulated. CONCLUSION(S): Endometriotic PF may attenuate oocyte and embryo development by impairing embryonic growth factor/receptor/signal transduction, resulting in endometriotic infertility. Copyright © 2009 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2009 Dec 31. [Epub ahead of print]

Phosphatase of regenerating liver-3: a novel and promising marker in human endometriosis.

Ruan F, Lin J, Wu RJ, Xu KH, Zhang XM, Zhou CY, Huang XF.

Department of Obstetrics and Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China.

OBJECTIVE: To investigate the expression of phosphatase of regenerating liver-3 (PRL-3) in ectopic, eutopic, and normal endometria and explore its relationship with endometriosis. DESIGN: A clinical retrospective and molecular study. SETTING: Department of obstetrics, gynecology, and reproductive medicine. PATIENT(S): One hundred and five women with histopathologically confirmed endometriosis, and 50 women with histopathologically assessed normal endometria. INTERVENTION(S): Immunohistochemical staining and Western blot analysis. MAIN OUTCOME MEASURE(S): Expression of PRL-3 protein. RESULT(S): As shown by the immunohistochemical analysis, PRL-3 was mainly located in the cytoplasm and membrane. The cells that tested positive for PRL-3 were detected in endometriotic tissues that did not occur in eutopic and normal endometria. Statistical analysis indicated that the expression of PRL-3 was closely associated with the clinical stages and recurrence of endometriosis. CONCLUSION(S): Expression of PRL-3 is related to the clinical stages and recurrence of endometriosis, which provides use with a novel marker and promising target in the treatment of human endometriosis. Copyright © 2009 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2009 Dec 31. [Epub ahead of print]

Identification biomarkers of eutopic endometrium in endometriosis using artificial neural networks and protein fingerprinting.

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

The 2nd Affiliated Hospital, Department of Gynecology, and Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China.

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) protein chip array technology was used to detect biomarkers of eutopic endometrium in endometriosis patients. Five potential biomarkers (6,898 m/z, 5,891 m/z, 5,385 m/z, 6,448 m/z, and 5,425 m/z) were found. Copyright © 2009 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2009 Dec 31. [Epub ahead of print]

Antiproliferative effects of anastrozole, methotrexate, and 5-fluorouracil on endometriosis in vitro and in vivo.

Ngô C, Nicco C, Leconte M, Chéreau C, Weill B, Batteux F, Chapron C.

Université Paris Descartes, Faculté de Médecine, EA 1833, ERTi, AP-HP Hôpital Cochin, Paris; Université Paris Descartes, Faculté de Médecine, AP-HP Hôpital Cochin, Service de gynécologie obstétrique II et Médecine de la Reproduction, Paris.

OBJECTIVE: To investigate the effects of antiproliferative drugs (anastrozole, methotrexate, and 5-fluorouracil [5-FU]) on the proliferation of endometriotic cells in vitro and in vivo. DESIGN: Ex vivo study on human endometrial and endometriotic cells in culture; establishment of a murine model using mice implanted with human endometriosis. SETTING: University research center. PATIENT(S): Ten patients with ovarian endometrioma, 10 patients with deep infiltrating endometriosis, and 10 patients without endometriosis. INTERVENTION(S): Stromal and epithelial cells were extracted from endometrial and endometriotic biopsies from patients with endometriosis and from patients without endometriosis. Cells were treated in vitro with anastrozole, methotrexate, progesterone, or 5-FU. Human endometriotic lesions were implanted in nude mice. Mice were treated with 5-FU or phosphate-buffered saline during 4 weeks before sacrifice and extraction of the endometriotic implants. MAIN OUTCOME MEASURE(S): Stromal and epithelial cell proliferation and pathology score of endometriotic implants. RESULT(S): Although anastrozole, methotrexate, and progesterone were ineffective, 5-FU significantly decreased the proliferation of endometriotic cells in vitro and controlled the growth of both cells from ovarian endometrioma and deep infiltrating endometriosis. CONCLUSION(S): Considering common features between endometriotic cells and tumor cells, the use of 5-FU could be an option in the management of severe endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2009 Dec 31. [Epub ahead of print]

Exclusive nodal recurrence after treatment of degenerated parietal endometriosis: report of a case and review of the literature.

Bourdel N, Durand M, Gimbergues P, Dauplat J, Canis M.

Department of Obstetrics and Gynecology, La Polyclinique, Hôtel-Dieu, CHU Clermont-Ferrand, France; Univ Clermont 1, UFR Médecine, Clermont-Ferrand, F-63001 France.

OBJECTIVE: To report a case of endometriosis degenerated into clear cell carcinoma with positron-emission tomography (PET) scan staging. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 43-year-old woman diagnosed with endometriosis degenerated into clear cell carcinoma with nodal metastasis at the initial diagnosis and exclusive nodal recurrence 6 months after surgery. INTERVENTION(S): Resection of the mass with partial resection of the pubic symphysis and bilateral external iliac lymphadenectomy. Forty-five days later, hysterectomy with bilateral adnexectomy and then adjuvant chemotherapy and abdominal-pelvic radiotherapy. MAIN OUTCOME MEASURE(S): The PET scan showed positive lymph nodes in the cervical, supraclavicular, bilateral axillary, bilateral inguinal, and lumbar-aortic regions. RESULT(S): The patient experienced a tumor recurrence after 6 months. After surgical management, she was scheduled to receive six cycles of rescue chemotherapy. She died 22 months after the initial diagnosis. CONCLUSION(S): The use of PET scan could allow better staging at the initial diagnosis and improve follow-up in such patients. The treatment of this entity is based on radical surgery associated with adjuvant chemotherapy and radiotherapy, but the results are not satisfactory. Copyright © 2009 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Am J Pathol. 2010 Feb;176(2):585-93. Epub 2009 Dec 30.

High-resolution ultrasound imaging: a novel technique for the noninvasive in vivo analysis of endometriotic lesion and cyst formation in small animal models.

Laschke MW, Körbel C, Rudzitis-Auth J, Gashaw I, Reinhardt M, Hauff P, Zollner TM, Menger MD.

Institute for Clinical and Experimental Surgery, University of Saarland, D-66421 Homburg/Saar, Berlin, Germany. matthias.laschke@uniklinik-saarland.de

Endometriosis, the presence of endometrial tissue at ectopic sites, is a highly prevalent gynecological disease severely affecting a patient’s quality of life. To analyze the mechanisms involved in the disease and to identify new molecular targets for effective therapies, small animal models are an important approach. Herein, we report the first use of high-resolution ultrasound imaging for the in vivo analysis of intraperitoneal endometriotic lesions in mice. This noninvasive technology allows for the repetitive quantitative analysis of growth, cyst development, and adhesion formation of endometriotic lesions with a low intra- and interobserver variability. Moreover, it enables one to easily differentiate between endometrial cysts and stroma. Accordingly, volume measurements of both endometrial cysts and stroma indicated that the initial establishment of endometriotic lesions is associated with enhanced cellular proliferation, followed by a phase of increased secretory activity of endometrial glands. Results of ultrasound analysis correlated well with measurements of lesion volumes by caliper and histology. Importantly, ultrasound imaging could be performed repetitively and noninvasively and reflected best the in vivo situation. The technique could further be demonstrated to successfully monitor the significant inhibition of growth of endometriotic lesions after specific estrogen receptor destabilizator treatment. Thus, high-resolution ultrasound imaging represents an important tool for future preclinical small animal studies, which address the pathophysiology of endometriosis and the development of new treatment strategies.

Am J Pathol. 2010 Feb;176(2):1050-6. Epub 2009 Dec 30.

The immunoconjugate “icon” targets aberrantly expressed endothelial tissue factor causing regression of endometriosis.

Krikun G, Hu Z, Osteen K, Bruner-Tran KL, Schatz F, Taylor HS, Toti P, Arcuri F, Konigsberg W, Garen A, Booth CJ, Lockwood CJ.

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University, School of Medicine, New Haven, CT 06520-8063, USA. graciela.krikun@yale.edu

Endometriosis is a major cause of chronic pain, infertility, medical and surgical interventions, and health care expenditures. Tissue factor (TF), the primary initiator of coagulation and a modulator of angiogenesis, is not normally expressed by the endothelium; however, prior studies have demonstrated that both blood vessels in solid tumors and choroidal tissue in macular degeneration express endothelial TF. The present study describes the anomalous expression of TF by endothelial cells in endometriotic lesions. The immunoconjugate molecule (Icon), which binds with high affinity and specificity to this aberrant endothelial TF, has been shown to induce a cytolytic immune response that eradicates tumor and choroidal blood vessels. Using an athymic mouse model of endometriosis, we now report that Icon largely destroys endometriotic implants by vascular disruption without apparent toxicity, reduced fertility, or subsequent teratogenic effects. Unlike antiangiogenic treatments that can only target developing angiogenesis, Icon eliminates pre-existing pathological vessels. Thus, Icon could serve as a novel, nontoxic, fertility-preserving, and effective treatment for endometriosis.

J Ultrasound Med. 2010 Jan;29(1):105-10.

Sonographic findings of inguinal endometriosis.

Yang DM, Kim HC, Ryu JK, Lim JW, Kim GY.

Department of Radiology, Kyung Hee University East-West Neo Medical Center, Gangdong-Gu, Seoul 134-090, Korea. dmy2988@yahoo.co.kr

OBJECTIVE: The purpose of this series was to describe the sonographic findings of inguinal endometriosis. METHODS: This was a retrospective analysis of 3 cases of inguinal endometriosis. The following gray scale and color Doppler sonographic features were analyzed: size, shape, echogenicity, and blood flow within inguinal endometriosis. RESULTS: The size of inguinal endometriosis ranged from 3.1 to 4.2 cm (mean, 3.7 cm). All 3 cases were cystic lesions. Two of 3 cases were lesions with internal septa. On color Doppler sonography, 1 of the 3 cases showed a few flow signals within the lesion, whereas in 2 of the 3 lesions, no blood flow could be identified within the lesions. CONCLUSIONS: Although the sonographic features of inguinal endometriosis may be variable, endometriosis should be included in the differential diagnosis when unilocular and multilocular cystic masses are seen on sonography.

Fertil Steril. 2010 Feb;93(3):e10; author reply e12. Epub 2009 Dec 29.

High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners.

Ilangavan K, Kalu E.

Comment on:

Am J Pathol. 2010 Feb;176(2):850-60. Epub 2009 Dec 24.

Inhibition of CD36-dependent phagocytosis by prostaglandin E2 contributes to the development of endometriosis.

Chuang PC, Lin YJ, Wu MH, Wing LY, Shoji Y, Tsai SJ.

Department of Physiology, National Cheng Kung University Medical College, Tainan 701, Taiwan, Republic of China.

Dysfunction in macrophage-mediated phagocytosis of aberrant cells that undergo retrograde transport to the peritoneal cavity is considered an important factor in the development of endometriosis. However, the mechanisms responsible for the loss of function of macrophages remain largely unknown. Herein, we report that prostaglandin (PG) E(2), via the EP2 receptor-dependent signaling pathway, inhibits the expression of CD36 in peritoneal macrophages, resulting in reduced phagocytic ability. PGE(2)-mediated inhibition of macrophage phagocytic capability was restored by ectopic expression of CD36. Treatment with PGE(2) inhibited CD36-dependent phagocytosis of peritoneal macrophages and increased the number and size of endometriotic lesions in mice. In contrast, blockade of PGE(2) production by cyclooxygenase inhibitors enhanced the phagocytic ability of peritoneal macrophages and reduced endometriotic lesion formation. Taken together, our findings reveal a potential mechanism of immune dysfunction during endometriosis development and may contribute to the design of an effective prevention/treatment regimen.

AJR Am J Roentgenol. 2010 Jan;194(1):W119; author reply W120.

Scar endometrioma: too unusual to be remembered?

Francica G.

Comment on:

Obstet Gynecol. 2010 Jan;115(1):206-18.

ACOG Practice Bulletin No. 110: noncontraceptive uses of hormonal contraceptives.

[No authors listed]

Pathology. 2010 Jan;42(1):95-7.

Endometriosis with myxoid change mimicking pseudomyxoma peritonei.

Tang K, Lyons S, Valmadre S, Russell P.

Hum Reprod. 2010 Mar;25(3):734-41. Epub 2009 Dec 19.

Expression of eicosanoid biosynthetic and catabolic enzymes in peritoneal endometriosis.

Lousse JC, Defrère S, Colette S, Van Langendonckt A, Donnez J.

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

BACKGROUND: Increased peritoneal eicosanoid concentrations have been reported in endometriosis patients and might be important in disease-associated pain and inflammation. Here, we evaluated the expression of key biosynthetic and catabolic enzymes involved in this abnormal eicosanoid production in peritoneal macrophages and endometriotic lesions. METHODS: Peritoneal macrophages, endometriotic lesions and matched eutopic endometrium were collected from endometriosis patients (n = 40). Peritoneal macrophages and eutopic endometrium samples were also collected from disease-free women (n = 25). Expression of type IIA secretory phospholipase A(2) (sPLA(2)-IIA), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 5-lipoxygenase (5-LO) was quantified by real-time PCR, and these five key enzymes were localized by immunohistochemistry. RESULTS: sPLA(2)-IIA, COX-2 and mPGES-1 mRNA was significantly increased in peritoneal macrophages of endometriosis patients compared with controls (P = 0.006, P = 0.016 and P = 0.025, respectively). In endometriosis patients, sPLA(2)-IIA, mPGES-1 and 15-PGDH mRNA was significantly enhanced in peritoneal lesions compared with matched eutopic endometrium (P < 0.001, P < 0.001 and P = 0.005, respectively). In eutopic endometrium, a significant decrease in 15-PGDH mRNA was found in the endometriosis group compared with controls (P = 0.023). Finally, sPLA(2)-IIA, COX-2, mPGES-1 and 15-PGDH immunostaining was found mainly in endometrial glands, whereas 5-LO was distributed throughout the glands and stroma. CONCLUSIONS: Our study highlights an imbalance between eicosanoid biosynthesis and degradation in endometriosis patients. Both peritoneal macrophages and endometriotic lesions may be involved. Research into new molecules inhibiting biosynthetic enzymes (such as sPLA(2)-IIA and mPGES-1) and/or activating catabolic enzymes (such as 15-PGDH) may prove to be a major field of investigation in the development of targeted medical therapies.

Hum Reprod. 2010 Mar;25(3):665-71. Epub 2009 Dec 19.

Transvaginal ultrasonography with bowel preparation is able to predict the number of lesions and rectosigmoid layers affected in cases of deep endometriosis, defining surgical strategy.

Goncalves MO, Podgaec S, Dias JA Jr, Gonzalez M, Abrao MS.

Digimagem, 04534-010 São Paulo, Brazil.

BACKGROUND: Successful surgical treatment of deep bowel endometriosis depends on obtaining detailed information about the lesions, prior to the procedure. The objective of this study was to determine the capability of transvaginal ultrasonography with bowel preparation (TVUS-BP) to predict the presence of one or more rectosigmoid nodules and the deepest bowel layer affected by the disease. METHODS: A prospective study of 194 patients with clinical and TVUS-BP suspected deep endometriosis submitted to videolaparoscopy. Image data were compared with surgical and histological results. RESULTS: With respect to bowel nodule detection and presence of at least two rectosigmoid lesions, TVUS-BP had a sensitivity of 97 and 81%, specificity 100 and 99%, positive predictive value (PPV) 100 and 93% and negative predictive value (NPV) 98 and 96%, respectively. Regarding diagnosis of infiltration of the submucosal/mucosal layer, TVUS-BP had a sensitivity of 83%, specificity 94%, PPV 77%, NPV 96%. CONCLUSIONS: These findings show that TVUS-BP is an adequate exam for evaluating the presence of one or more rectosigmoid nodules and the deepest layer affected in deep infiltrating bowel endometriosis, confirming the importance of this technique for defining the most appropriate surgical strategy to be implemented.

Gynecol Obstet Fertil. 2010 Feb;38(2):142-146.

Endometriosis of the ischio-rectal excavation at the contact of the sciatic nerve: A case report of neurolysis by pararectal incision.

[Article in French]

Chauvin C, Azria E, Mahieu-Caputo D, Madelenat P.

Service de gynécologie-obstétrique, maternité Aline-de-Crépy, hôpital Bichat, AP-HP, 46, rue Henri-Huchard, 75018 Paris, France.

Localisation of endometriosis on the sciatic nerve is exceptional. We report the case of a patient presenting an endometriotic nodule of the left ischio-rectal excavation, with an extension contiguous to the sciatic nerve, responsible of invalidating sciatalgia. Two laparoscopies did not allow to localise the lesion. Finally the endometriotic nodule was treated by a direct access of the left ischio-rectal excavation through a pararectal incision. In this article we discuss the means to localise such lesion and the surgical approach to propose. Copyright © 2009 Elsevier Masson SAS. All rights reserved.

Acta Obstet Gynecol Scand. 2010;89(1):71-7.

Radical excision of rectovaginal endometriosis results in high rate of pain relief – results of a long-term follow-up study.

Tarjanne S, Sjöberg J, Heikinheimo O.

Department of Obstetrics and Gynecology, University of Helsinki, Finland.

OBJECTIVE: To evaluate the long-term results of radical excision for rectovaginal endometriosis (RVE) with special emphasis on current symptoms and risk factors as regards recurrence. METHODS: A total of 116 patients operated upon because of RVE were offered a clinical follow-up evaluation visit; 60 (52%) consented. The time (mean +/- SD) from the index surgery to the follow-up visit was 4.0 +/- 0.5 years. MAIN OUTCOME MEASURES: Daily symptoms using a visual analogue scale for 30 consecutive days prior to clinical assessment; the amount of uterine bleeding was also assessed. Endometriosis recurrence was evaluated via clinical and ultrasonographic examination. RESULTS: The symptom sum scores (maximum 300) were low with median scores (range) of 3 (0-32) for dysmenorrhea and 9 (0-72) for pelvic pain. Evidence of RVE recurrence was found or suspected in 29 (48%) of the 60 women assessed. Clinical recurrence was not associated with pain symptoms. In univariable analysis, amenorrhea at the time of clinical assessment was associated with a lower risk of recurrence (odds ratio; OR 0.13; 95% CI (confidence interval) 0.02-0.65, p = 0.01); the effect of bowel resection was not significant (OR 0.37: 95% CI 0.13-1.07, p = 0.07). In multivariable analysis, the protective effect of bowel resection on recurrence was significant (OR 0.23; 95% CI 0.06-0.89, p = 0.03). CONCLUSIONS: Radical surgery may result in long-term pain relief in cases of RVE. Bowel resection is associated with a lower risk of RVE recurrence. Therapy that induces amenorrhea may be effective in preventing recurrence following surgical treatment of RVE.

Acta Cytol. 2009 Nov-Dec;53(6):625-9.

The adjunctive value of CD10 immunostaining on cell block preparations in pelvic endometriosis.

Dharan M.

Bruce Rappaport Faculty of Medicine, Institute of Technology, Haifa, Israel. dharan_m@clalit.org.il

OBJECTIVE: To evaluate the utility of CD10 immunostaining on cell block preparations from pelvic washing cytology material obtained during laparoscopy in cases of pelvic endometriosis (PE). STUDY DESIGN: Six premenopausal women presenting with ovarian masses underwent a laparoscopic procedure. In addition to routine cytospin preparations, cell blocks were prepared using the formalin-fixed, paraffin-embedded method from the pelvic washings in each case. Immunocytochemistry using monoclonal antibodies for cytokeratin (CK) 7, CK20, CD10, estrogen receptor (ER), progesterone receptor (PR) and CA125 was performed on sections from cell blocks using the streptavidin-biotin peroxidase complex. RESULTS: Clusters of epithelial cells (3 cases) and stromal cells (2 cases) were seen in a background rich in hemosiderin-laden macrophages and poorly preserved mesothelial cells on cytospin smears. CD10 and CK7 were consistently positive in the stromal and epithelial components, respectively, in all cases on cell block sections. Variable staining reactions were noted for ER, PR and CA125. CONCLUSION: CD10 immunostaining is a useful ancillary method in the diagnosis of endometriosis. Its routine use on cell block preparations from pelvic washings in women undergoing a laparoscopic procedure is recommended.

Hum Reprod. 2010 Mar;25(3):642-53. Epub 2009 Dec 15.

Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy.

Khan KN, Kitajima M, Hiraki K, Fujishita A, Sekine I, Ishimaru T, Masuzaki H.

Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. nemokhan@nagasaki-u.ac.jp

BACKGROUND: Information is limited regarding the multifunctional role of GnRH agonist (GnRHa) therapy in reproductive diseases. We investigated the pattern of changes in inflammatory reaction, micro-vessel density and apoptosis in the tissues collected from women with endometriosis, adenomyosis and uterine myoma who were treated with or without GnRHa therapy. METHODS: Biopsy specimens were collected from lesions, myometria and corresponding endometria of 45 women with ovarian endometrioma, 35 women with adenomyosis and 56 women with uterine myoma. A fraction of these women were treated with GnRHa therapy for a variable period of 3-6 months before surgery. We performed immunohistochemical analysis of CD68, a macrophage (Mvarphi) marker and von Willebrand factor (VWF), a vessel marker, using respective antibodies. Changes in apoptosis were examined using TdT-mediated dUTP-biotin nick end-labeling assay and by the immunoexpression of activated caspase-3 in tissues after GnRHa therapy. RESULTS: The infiltration of CD68-positive Mvarphi and VWF-positive micro-vessel density were significantly decreased in the endometria of women with endometriosis, adenomyosis and uterine myoma in the GnRHa-treated group when compared with that in the non-treated group. Marked decreases in inflammatory and angiogenic responses were observed in lesions and myometria of these diseases. When compared with the non-treated group, a significant increase in apoptotic index (apoptotic cells per 10 mm(2) area) and quantitative-histogram scores of activated caspase-3 after GnRHa therapy were observed in the eutopic endometria, lesions and myometria of these diseases. CONCLUSIONS: GnRHa was able to markedly reduce the inflammatory reaction and angiogenesis and to significantly induce apoptosis in tissues derived from women with endometriosis, adenomyosis and uterine myoma. These multiple biological effects at the tissue level may be involved in the regression of these reproductive diseases.

Hum Reprod. 2010 Mar;25(3):742-50. Epub 2009 Dec 10.

Analysis of matrix metalloproteinase-7 expression in eutopic and ectopic endometrium samples from patients with different forms of endometriosis.

Matsuzaki S, Maleysson E, Darcha C.

CHU Clermont-Ferrand, Polyclinique-Hôtel-Dieu, Gynécologie Obstétrique et Médecine de la Reproduction, Boulevard Léon Malfreyt, 63058 Clermont-Ferrand, France. sachikoma@aol.com

BACKGROUND: The objective of the present study was to expand our understanding of the role of matrix metalloproteinase-7 (MMP-7) in the pathophysiology of endometriosis. METHODS: Expression levels of MMP-7 mRNA and protein in the eutopic endometrium and ectopic endometrium of patients with different forms of endometriosis were measured with immunohistochemistry and real-time RT-PCR. Endometrial tissues from patients with uterine myomas and those with macroscopically normal pelvic cavities were included as comparison groups. The real-time RT-PCR utilized endometrial cells isolated by laser capture microdissection. MMP-7 immunostained cells were quantified using a computerized image analysis system. RESULTS: MMP-7 expression levels were significantly higher in the endometrial epithelial cells from patients with deep infiltrating endometriosis compared with those isolated from the endometria of patients with only superficial peritoneal endometriosis, uterine myomas or normal endometrium, in the proliferative, late secretory and menstrual phases. MMP-7 protein expression was detected in the ectopic endometrial epithelial cells of 13 samples of deep infiltrating endometriosis (24.5%), 11 samples of ovarian endometriosis (28.6%), 23 samples of black peritoneal lesions (76.7%) and 24 samples of red peritoneal lesions (100%). MMP-7 protein expression in epithelial cells was significantly higher in red peritoneal lesions compared with that of deep infiltrating endometriosis, ovarian endometriosis and black peritoneal lesions, in all phases of the menstrual cycle. CONCLUSION: These findings suggest that MMP-7 expression levels vary significantly among the different forms of endometriosis.

Hum Reprod. 2010 Mar;25(3):654-64. Epub 2009 Dec 9.

Non-invasive diagnosis of endometriosis based on a combined analysis of six plasma biomarkers.

Mihalyi A, Gevaert O, Kyama CM, Simsa P, Pochet N, De Smet F, De Moor B, Meuleman C, Billen J, Blanckaert N, Vodolazkaia A, Fulop V, D’Hooghe TM.

Department of Obstetrics and Gynaecology, University Hospital Gasthuisberg, Leuven University Fertility Centre, Herestraat 49, B-3000 Leuven, Belgium.

BACKGROUND: Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis. The aim of this study was to evaluate the combined performance of six potential plasma biomarkers in the diagnosis of endometriosis. METHODS: This case-control study was conducted in 294 infertile women, consisting of 93 women with a normal pelvis and 201 women with endometriosis. We measured plasma concentrations of interleukin (IL)-6, IL-8, tumour necrosis factor-alpha, high-sensitivity C-reactive protein (hsCRP), and cancer antigens CA-125 and CA-19-9. Analyses were done using the Kruskal-Wallis test, Mann-Whitney test, receiver operator characteristic, stepwise logistic regression and least squares support vector machines (LSSVM). RESULTS: Plasma levels of IL-6, IL-8 and CA-125 were increased in all women with endometriosis and in those with minimal-mild endometriosis, compared with controls. In women with moderate-severe endometriosis, plasma levels of IL-6, IL-8 and CA-125, but also of hsCRP, were significantly higher than in controls. Using stepwise logistic regression, moderate-severe endometriosis was diagnosed with a sensitivity of 100% (specificity 84%) and minimal-mild endometriosis was detected with a sensitivity of 87% (specificity 71%) during the secretory phase. Using LSSVM analysis, minimal-mild endometriosis was diagnosed with a sensitivity of 94% (specificity 61%) during the secretory phase and with a sensitivity of 92% (specificity 63%) during the menstrual phase. CONCLUSIONS: Advanced statistical analysis of a panel of six selected plasma biomarkers on samples obtained during the secretory phase or during menstruation allows the diagnosis of both minimal-mild and moderate-severe endometriosis with high sensitivity and clinically acceptable specificity.

Fertil Steril. 2010 Jan;93(1):e3-4; author reply e5. Epub 2009 Dec 11.

Patient’s fertility desire should be taken into consideration in the surgical treatment algorithm of infiltrating endometriosis.

Calcagno M, Bellati F, Pastore M, Plotti F, Palaia I, Panici PB.

Womens Health (Lond Engl). 2010 Jan;6(1):27-35.

Dienogest: a new therapeutic agent for the treatment of endometriosis.

Harada T, Taniguchi F.

Department of Obstetrics & Gynecology, Tottori University Faculty of Medicine, Yonago, 683-8504, Japan. tasuku@med.tottori-u.ac.jp

Dienogest (DNG), a progestin of 19-nortestosterone derivative, has good oral bioavailability and is highly selective for progesterone receptors. Owing to its antiovulatory, antiproliferative activities in endometrial cells, and its inhibitory effects on the secretion of cytokines, DNG is expected to be an effective treatment for endometriosis. Progesterone receptor-binding affinity is higher for DNG than for progesterone. Several pilot studies demonstrated that after 24 weeks of DNG treatment, there was a significant decrease in terms of dysmenorrhea, premenstrual pain, dyspareunia and diffuse pelvic pain. Most of the cases of genital bleeding occurring in the DNG treatment were spotting or breakthrough bleeding, which decreased with continued treatment and resolved either during treatment or after the end of treatment. The therapeutic effects of DNG 2 mg/day and norethisterone acetate 10 mg/day for endometriotic symptoms during a period of 24 weeks were almost similar. The only disadvantage of DNG seems to be the irregular bleeding. Good efficacy and tolerability of DNG in patients with endometriosis have been demonstrated in an open, randomized European clinical trial as compared with norethisterone acetate. In Japan, a Phase III, randomized, double-blind, multicenter, controlled trial was conducted to compare the efficacy and safety of DNG with intranasal buserelin acetate in patients with endometriosis. The study demonstrated that DNG is as effective as intranasal buserelin acetate in alleviating endometriosis symptoms, and causes less bone mineral density loss, resulting in the use on a commercial basis for endometriosis patients in Japan from 2008. This paper provides summarized data on this new promising drug for endometriosis.

Am Fam Physician. 2009 Dec 15;80(12):1483.

Cutaneous abdominal nodule after cesarean delivery.

Hawayek LH, Abdulla FR.

University of Cincinnati, Cincinnati, OH, USA. lanahawayek@gmail.com

Klin Lab Diagn. 2009 Oct;(10):16-9.

Various acute phase reactants in different types of proliferative diseases of the uterine appendages.

[Article in Russian]

Zorina VN, Kozlov IG, Tret’iakova TV, Promzeleva NV, Bazhenova LG, Zorina RM, Riabicheva TG, Zorin NA.

The authors examined serum in patients with ovarian cancer (OC; a disseminated process), ovarian cystadenoma (OCA), or external endometriosis (EM) before treatment and in apparently healthy females (a control) for the content of some acute-phase proteins and cytokines to clarify the specific features of changes in their concentrations in relation to the type of the proliferative process. It was shown that in OC, there were significant reductions in the levels of alpha2-macroglobulin (MG), plasmin (PL), alpha1-antitrypsin (AT) and statistically significantly increases in the content of lactoferrin (LF), interleukin (IL)-6, IL-8, Ig, and the regulatory transport complex of P–M. In M, the concentrations of AT were lower and those of IL-6, IL-8, and PL-MG were higher (to a lesser degree than those in OC). In OCA, the levels of MG and IgA were increased; those of IL-8 and PL-MG were decreased. The concentrations of interferon and IgM were unchanged in all groups. The findings suggest that difefrent proliferative processes initially provoke a number of changes of varying magnitude and even directions in the serum levels of inflammation reactants, which should be borne in mind when conducting clinical tests in the intraoperative and, probably, postoperative periods.

Adv Nurse Pract. 2009 Feb;17(2):47-8, 50, 52.

Beyond birth control. The health benefits of hormonal contraception.

Geraghty P.

Muir Obstetric and Gynecologic Medical Group in Walnut Creek, CA, USA.

Rev Med Univ Navarra. 2009 Jul-Sep;53(3):15-6.

Treatment to conserve fertility in a patient diagnosed with deep pelvic endometriosis

[Article in Spanish]

García Manero M.

Departamento de Ginecología y Obstetricia, Clínica Universidad de Navarra, 31008 Navarra. mgmanero@unav.es

Rev Med Univ Navarra. 2009 Jul-Sep;53(3):12-4.

Treatment for endometriosis.

[Article in Spanish]

Olartecoechea B, García Manero M, Royo P, Aubà M.

Departamento de Ginecología y Obstetricia, Clínica Universidad de Navarra, 31008 Navarra.

Endometriosis is defined as the presence of endometrial-like tissue outside the uterus, which induced a chronic inflammatory reaction. Endometriosis is associated with severe dysmenorrhea, deep dyspareunia, chronic pelvic pain, ovulation pain, cyclical, or perimenstrual symptoms, with or without abnormal bleeding, infertility, and chronic fatigue. Therapies can be useful to relieve and sometimes solve the symptoms, encourage fertility, eliminate endometrial lesions, and restore the anatomy of the pelvis. For medical therapy, several different preparations (oral contraceptives, progestogenics, gestrinone, danazol, and GnRHa) and new options (GnRH antagonists, aromatase inhibitors, estrogen receptor beta agoinist, progesterone receptor modulators, angiogenesis inhibitors, and COX-2 selective inhibitors) are available.

Rev Med Univ Navarra. 2009 Jul-Sep;53(3):10-1.

Basic research into endometriosis. Are we going in the right direction?

[Article in Spanish]

García Manero M.

Departamento de Ginecología y Obstetricia, Clínica Universidad de Navarra, 31008 Navarra. mgmanero@unav.es

Endometriosis is a common gynaecological syndrome of unknown aetiology. The most widely accepted hypothesis for the development of endometriosis is retrograde menstruation. However, some other factor renders certain women susceptible to the implantation and growth of ectopic endometrium. Angiogenesis appears to be one of the process involved in the pathogenesis of endometriosis. Angiogenic factors are increased in the peritoneal fluid of patients with endometriosis in peritoneal implants and in ovarian endometriomas. We believe that the optimal serum marker should be used to monitor the response of new antiangiogenic agents in endometriosis treatment.

Rev Med Univ Navarra. 2009 Jul-Sep;53(3):6-9.

Diagnosis of endometriosis.

[Article in Spanish]

García Manero M, Olartecoechea B, Royo Manero P, Aubá M, Alcázar JL.

Departamento de Ginecología y Obstetricia, Clínica Universidad de Navarra, 31008 Navarra. mgmanero@unav.es

There are no sufficiently sensitive and specific signs and symptoms or diagnostic tests for the clinical diagnosis of endometriosis, and no diagnostic strategy is supported by evidence of effectiveness. Pelvic and rectal examinations should be performed, although the yield of the physical examination is low. Laboratory tests and radiological examinations are usually not warranted. Measurement of CA 125 levels may be useful for monitoring disease progress, and MRI has a high sensitivity in detecting endometrial cysts but poor diagnostic accuracy for endometriosis in general. Patients with persistent symptoms after empirical treatment should be referred for laparoscopy, the preferred method for diagnosis of endometriosis.

Rev Med Univ Navarra. 2009 Jul-Sep;53(3):3-5.

Ultrasound study of the myoendometrial border.

Tocci A, Royo P, Alcázar JL, García-Manero M.

Reproductive Medicine, Nuova Villa Claudia Clinic, Via Flaminia Nuova 280, Rome, Italy. info@donnamed.it

Abnormal thickening of the Endometrial Subendometrial Myometrium Unit (ESEMy Unit, including basal endometrium and inner myometrium) has been detected on imaging and referred to as “diffuse adenomyosis” in infertile patients with proven endometriosis. However, no robust relationship exists between enlargement of the ESEMy Unit and adenomyosis proven on hysterectomy specimen examination; moreover, if any correlation exists, it lacks histological validation in women wishing to preserve fertility. While adenomyosis effects on fertility, if any, remain elusive, thickening of the ESEMy Unit have been consistently linked to fertility impairment in both experimental and clinical models. The hypothesis tested herein is that a novel condition exists, called “ESEMy Unit disruption disease”; it is epidemiologically different from adenomyosis, diagnosable on imaging and bears a clear impact on human fertility through various mechanisms. A new wave of good quality studies may be elicited by a clear distinction between adenomyosis and the “ESEMy Unit disruption disease”.

Rev Med Univ Navarra. 2009 Apr-Jun;53(2):14-9.

Proposal for a new microsurgical model for the study of induced endometriosis in Wistar rats. Preliminary results.

[Article in Spanish]

González Ramos P, Royo Manero P, Pastor Oliver C, Calleja Aguayo E, De Martino A, Godino J, Bejarano Lasunción P, Manero FJ, Pecondón A, Vicente B, Gracia Romero J, Ortega J, García Manero M, Alcázar Zambrano JL, González de Agüero R, Fabre González E, López García G.

Universidad de Zaragoza.

The current knowledge status on the patogenesis of endometriosis as well as devastating consequences of disease evolution in women’s reproductive health, have promoted researchers advances in a great manner during last years. The immunologic and neangiogenesis systems implication have opened new ways of knowledge over classic theories from the beginning of the xx century. The experimental resesearch, using animal induction models. Below we explain the first steps a new induction model (“PGR1-HotDog”), based on Wistar rats using a new disease autogeneration system, created for te study of the early stages of the endometriosis.

Rev Med Univ Navarra. 2009 Apr-Jun;53(2):8-13.

Angiogenesis and endometriosis.

[Article in Spanish]

García Manero M, Olartecoechea B, Aubá M, Alcázar JL, López G.

Departamento de Ginecología y Obstetricia, Clínica Universidad de Navarra. mgmanero@unav.es

Endometriosis is a common gynaecological disease of unknown aetiology. Angiogenesis appears to be one of the processes involved in its pathogenesis. Angiogenic factors are increased in the peritoneal fluid of patients with endometriosis (McLaren 1996 et al; Taylor et al, 2002), in peritoneal implants (Ferriani et al, 1993) and in ovarian endometriomas. On the other hand, some researchers have found that angiogenesis is related to pelvic pain. We speculated that ovarian endometriomas in patients presenting with pelvic pain would be more angiogenic than those in asymptomatic women and that their vascular features would therefore be different.

Rev Med Univ Navarra. 2009 Apr-Jun;53(2):4-7.


[Article in Spanish]

García Manero M, Olartecoechea B, Royo Manero P, Aubá M, López G.

Departamento de Ginecología y Obstetricia, Clínica Universidad de Navarra. mgmanero@unav.es

Endometriosis is a common gynaecological disease of unknown aetiology which affects an estimated 10% to 15% of all premenopausal women. It is defined as the presence of endometrial tissue, consisting of both glandular epithelium and stroma, outside the uterine cavity. Three different clinical entities of endometriosis can be distinguished: peritoneal endometriosis, ovarian endometriosis and deep invasive endometriosis. There are several theories to explain their pathogenesis: metaplasia of the mesothelium, in situ development of Müllerian remnants in the rectovaginal area (deep-invasive lesions) or retrograde transplantation of shed menstrual effluent (peritoneal implants). The most widely accepted hypothesis for the development of endometriosis is retrograde menstruation. However, some other factor renders certain women susceptible to the implantation and growth of this ectopic endometrium.

Rev Med Univ Navarra. 2009 Apr-Jun;53(2):3.


[Article in Spanish]

García Manero M.

Int J Mol Med. 2010 Jan;25(1):17-23.

Immunohistochemical localization of inhibin and activin subunits, activin receptors and Smads in ovarian endometriosis.

Mabuchi Y, Yamoto M, Minami S, Umesaki N.

Department of Obstetrics and Gynecology, Wakayama Medical University, School of Medicine, 811-1 Kimiidera Wakayama 641-0012, Japan. booyan@wakayama-med.ac.jp

We previously reported that activin A, not inhibin, was localized to endometrial tissues, and that the endometrium might be a major source of activin A during the menstrual cycle, using an immunohistochemical method. However, there are few detailed reports concerning the expression of inhibin subunits, activin receptors and Smad proteins in the ectopic endometrial tissues of endometriosis. In this study, our purpose was to evaluate the immunohistochemical localization of inhibin alpha-, betaA-subunits, activin A, activin receptor, and Smad proteins in ovarian endometriosis. Tissue samples from ovarian endometriosis were obtained from 13 women. Normal endometrial tissues were obtained during the proliferative phase from 5 premenopausal women without endometriosis who were undergoing a hysterectomy for the treatment of uterine cervical intraepithelial neoplasia 3. We examined the immunohistochemical localization of inhibin/activin alpha-, betaA-subunit, activin A, activin receptors types IA, IB, IIA, IIB, Smad2, Smad3 and Smad4 using an avidin-biotin-peroxidase complex technique. No immunostaining for the alpha-subunit of inhibin was observed in ovarian endometriosis and the normal endometrium. Positive immunostaining for the betaA-subunit of inhibin, activin A, activin receptors types IA, IB, IIA, IIB, Smad2, Smad3 and Smad4 was observed in ovarian endometriosis and the normal endometrium. In conclusion, these results suggest that activin A, but not inhibins, is produced by ovarian endometriosis and the normal endometrium, and that the activin signal transduction system exists in both ovarian endometriosis and the normal endometrium.

Am J Surg Pathol. 2010 Jan;34(1):10-7.

Endometriosis-associated skeletal muscle regeneration: a hitherto undescribed entity and a potential diagnostic pitfall.

Colella R, Mameli MG, Bellezza G, Sordo RD, Cavaliere A, Sidoni A.

Institute of Pathological Anatomy and Histology, University of Perugia, Medical School, Perugia, Italy. renato.colella@tin.it

Skeletal muscle undergoes regeneration generally after an injury and in some cases it may mimic a malignant process. We observed these aspects in association with abdominal wall endometriosis and as no similar conditions were found in the literature this prompted us to study the main clinicopathologic and immunohistochemical profile of this phenomenon. Thirteen cases of abdominal wall endometriosis were retrieved from the files of our Institute. All original slides were reviewed to reveal the presence of skeletal muscle and 8 cases were enrolled for morphologic and immunohistochemical studies as follows: vimentin, desmin, myoglobin, myogenin, myoD1, CD56, S100, and p21. Histologically, in 4 of the 8 cases in the skeletal muscle adjacent to the endometriotic foci there was a proliferation of round cells with the typical appearance of maturing myoblasts. More peripherally, myotubes and early myocytes were present. This proliferation was florid in 1 case and focal in 3 cases. At immunohistochemical investigation, the less differentiated cells reacted with vimentin, desmin, S100, CD56, myoD1, and myogenin but not with myoglobin or p21. On the contrary, intermediately differentiated cells showed a progressive loss of vimentin, CD56, and myoD1 whereas they were positive for desmin, S100, myogenin, myoglobin, and p21. Terminally differentiated cells reacted only with desmin and myoglobin. This peculiar immunohistochemical profile was consistent with the immunophenotype of maturing myoblasts, confirmed the regenerative nature of the phenomenon and allowed differential diagnosis with other proliferations sharing a similar morphology. The expression of early differentiation markers was greatest in the islands of cells nearest to endometriosis, whereas in the more distant areas the markers of late differentiation prevailed. This gradient of expression suggests that muscle cells are stimulated by growth factors or other signals produced by the cycling endometrioid foci. In conclusion, we report a hitherto undescribed entity that may mimic a malignant process, especially when the reaction is florid or when endometriotic glands and stroma are not clearly evident, as during the examination of small biopsies, frozen sections, or cytology samples. Therefore, although the histologic diagnosis of endometriosis is usually straightforward, pathologists should be aware of the concomitant regenerative effects on skeletal muscle, which may represent a possible diagnostic pitfall.

Hum Reprod. 2010 Feb;25(2):392-7. Epub 2009 Dec 1.

Nerve fibres in ovarian endometriotic lesions in women with ovarian endometriosis.

Zhang X, Yao H, Huang X, Lu B, Xu H, Zhou C.

Department of Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China. zhangxinmei20071116@yahoo.cn

BACKGROUND: Although nerve fibres are present in eutopic and ectopic endometrium, it is unclear whether they appear in ovarian endometriotic lesions. We investigated the presence of nerve fibres in ovarian endometriotic lesions and its correlation with clinical parameters in women with ovarian endometriosis. METHODS: Histological sections of ovarian endometriotic lesions from 61 women with ovarian endometriosis (Stages II-IV) who underwent laparoscopic endometrioma cystectomy were stained immunohistochemically using a specific polyclonal rabbit anti-protein gene product 9.5 (PGP9.5) antibody to demonstrate myelinated and unmyelinated nerve fibres. RESULTS: Nerve fibres stained with PGP9.5 were detected in ovarian endometriotic lesions in 31.1% of women, and most appeared in fibrotic interstitium of ovarian endometriotic lesions. The density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions in women with pain symptoms (n = 35) was higher than in women with no pain symptoms (n = 26, P = 0.039), although the percentage (positive cases/total) of PGP9.5-positive fibres did not differ. In women with pain symptoms, PGP9.5-positive fibres appeared in 40.0% of cases and the density of PGP9.5-immunoactive fibres in ovarian endometriotic lesions was correlated with severity of pain symptoms (r = 0.466, P = 0.005). In women with no pain, PGP9.5-positive fibres were detected in only 5 (19.2%) women. Both the percentage and the density of PGP9.5-positive fibres in ovarian endometriotic lesions were associated with pelvic adhesions (chi2 = 6.833, P = 0.009; Z = 2.442, P = 0.015, respectively) but not with disease severity. CONCLUSIONS: PGP9.5-immunoactive nerve fibres in ovarian endometriotic lesions may be involved in the pathophysiology of pain generation and pelvic adhesion formation in women with ovarian endometriosis.

Rev Med Suisse. 2009 Oct 21;5(222):2085-6, 2088-90.

Endometriosis: review of the literature and clinical management.

[Article in French]

Wenger JM, Loubeyre P, Marci R, Dubuisson JB.

Département de gynécologie et d’obstétrique, HUG, Geneva. jmwenger@bluewin.ch

Despite numerous studies, endometriosis remains unclear concerning the etiopathogenesis, the natural history and optimal treatment. It occurs preferentially in young women and may be associated with a series of painful symptoms very disabling, together with infertility and significant psychological problems. Because of the multiple consultations, operations and disability it can cause, endometriosis takes an increasing part in health costs. Delays between onset and diagnosis are still long, and it is important to diagnose as early as possible to stop this disease so as to maintain or restore fertility and quality of life for patients. That is why a careful listening and clinical examination with appropriate investigations will improve our global care.

Hum Reprod. 2010 Feb;25(2):398-405. Epub 2009 Nov 26.

Influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with endometriosis.

Cosín R, Gilabert-Estellés J, Ramón LA, Gómez-Lechón MJ, Gilabert J, Chirivella M, Braza-Boïls A, España F, Estellés A.

Research Center, Hospital Universitario La Fe, Valencia, Spain.

BACKGROUND: Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent benign gynaecological diseases. It has been suggested that both endometrial and peritoneal factors, related to angiogenesis and proteolysis, can be implicated in this disease. The aim of this study was to evaluate the influence of peritoneal fluid on the expression of angiogenic and proteolytic factors in cultures of endometrial cells from women with and without endometriosis. METHODS: Endometrial cells were isolated, cultured and treated with endometriotic or normal peritoneal fluid. Vascular endothelial growth factor-A (VEGF-A), urokinase plasminogen activator (uPA), matrix metalloproteinase-3 (MMP-3) and their inhibitors including thrombospondin-1, plasminogen activator inhibitor-1 and MMP inhibitor type 1 (TIMP-1) mRNA levels were evaluated by quantitative RT-PCR, and protein levels were quantified by ELISA. RESULTS: Peritoneal fluid from women with endometriosis induced an increase in VEGF-A and uPA protein and VEGF-A mRNA and uPA mRNA levels in endometrial cell culture from women with (P < 0.01) and without endometriosis (P < 0.05). The highest levels of VEGF-A and uPA were observed in endometrial cell cultures from patients with endometriosis and treated with peritoneal fluid from women with endometriosis. CONCLUSIONS: Peritoneal fluid from women with endometriosis induced more VEGF and uPA expression in endometrial cell culture from women with endometriosis than did normal peritoneal fluid. Endometrial-peritoneal interactions increased angiogenic and proteolytic factors in endometrial cells, which could contribute to the development of endometriotic lesions.

Int J Gynaecol Obstet. 2010 Mar;108(3):250-1. Epub 2009 Nov 26.

Triptorelin improves intestinal symptoms among patients with colorectal endometriosis.

Ferrero S, Camerini G, Ragni N, Menada MV, Venturini PL, Remorgida V.

Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Italy.

Sangyo Eiseigaku Zasshi. 2010 Feb 5;52(1):21-7. Epub 2009 Nov 27.

Regional differences in prevalence of anemia found by periodic health checkups at workplaces in Japan.

[Article in Japanese]

Shimomura T, Wakabayashi I.

Department of Environmental and Preventive Medicine, Hyogo College of Medicine, Hyogo, Japan.

Anemia-related blood examinations are included in examinations for periodic health checkups at workplaces designated by the Industrial Safety and Health Law in Japan. The aim of this study was to determine whether there were regional differences in the prevalence of anemia in workers and, if so, to investigate possible reasons for the differences. Relationships between prevalence of anemia found by periodic health checkups and some common factors related to anemia in each prefecture of Japan were investigated by ecological regression analysis using Spearman’s rank correlation coefficient. There were regional differences in the prevalence of anemia in the prefectures of Japan (5.2-11.7%), and high prevalence was observed in prefectures in the northeastern district, such as Iwate, Akita and Yamagata Prefectures, and in Fukui, Shimane and Nagasaki Prefectures. Prevalence of anemia in each prefecture was significantly correlated with the prevalence of hypertension, dyslipidemia, liver dysfunction, abnormality in ECG, hyperglycemia or glucosuria at health checkups in each prefecture. Prevalence of anemia in each prefecture was significantly correlated with the percentage of patients receiving therapy for anemia in each prefecture but not with the prevalence of myoma uteri, endometriosis uteri or mortality of uterus cancer in each prefecture. There was also no significant correlation of the prevalence of anemia with the prevalence of iron-deficiency anemia or dietary iron intake in each prefecture. The prevalence of anemia in each prefecture showed significant positive correlations with the ratio of female population to total population and the ratio of female workers to total workers in each prefecture; it also showed a significant negative correlation with the ratio of the number of large-sized workplaces (300 or more workers) to the number of workplaces with 50 or more workers in each prefecture. A considerable regional difference in the prevalence of anemia was found by periodic health checkups at workplaces, and we consider that this difference is not due to regional differences in the incidence of diseases causing genital bleeding in women but to regional differences in the ratio of female workers to total workers and the status of health control at the workplace, which depends on size of the workplace.

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