Rev Med Chir Soc Med Nat Iasi. 2007 Jan-Mar;111(1):200-9.

[Morphogenesis and differentiation of the female genital tract. Genetic determinism and epithelium-stromal interactions]

[Article in Romanian]

Amălinei C.

Disciplina de Histologie, Facultatea de Medicină, Universitatea de Medicină si Farmacie “Gr. T. Popa”, Iaşi.

The epithelium-stromal interaction is important in the process of morphogenesis, differentiation, and hormone response, in female genital tract. This review is organized in four sections: i) female genital tract morphogenesis, based on genetic determinism; ii) hormonal control of endometrial proliferation; iii) TGF-beta key-role in epithelium-stromal communication; iv) endometrial apoptosis. Female genital tract derives from the Müllerian ducts, a number of genes being involved in its regulation, like Lim1, Lhx9, Emx, Pax-2, Hox-A9, Hox-A10, Hox-A11, Hox-A13, Wnt-4, Wnt-7, WT1, SF-1, and GATA-4. TGF-beta, whose expression is modulated by ovarian steroids, regulates cell growth, differentiation, apoptosis, inflammatory and immune responses, extracellular matrix deposition, adhesion molecules, proteases, and protease inhibitor expression. In the endometrium, TGF-beta regulates its own expression, and that of extracellular matrix, adhesion molecules and proteases implicated in trophoblast invasion, angiogenesis, and tumor metastasis during embryo implantation, endometriosis, irregular bleeding, and endometrial cancer. Cellular response elicited by TGF-beta, mediated through a serine/threonine kinase receptor, induces the recruitment of multiple intracellular signals, specifically Smads, whose activation and subsequent translocation into the nucleus results in gene expression. Ubiquitin is involved in the degradation of short lived, regulatory or misfolded proteins, by tagging them to be taken to the proteasome. In the endometrium, ubiquitin may allow cells of stromal origin to grow, survive and evade T-cell mediated disposal, showing a functional duality. A complete understanding of the complex regulatory endometrial epithelium-stromal mechanism, concertating genes, hormones, and cytokines, may provide new therapeutic targets in female reproductive tract pathology.

 

Hum Reprod. 2007 Sep;22(9):2389-97. Epub 2007 Jun 26.

Genetic variation in tumour necrosis factor and lymphotoxin is not associated with endometriosis in an Australian sample.

Zhao ZZ, Nyholt DR, Le L, Thomas S, Engwerda C, Randall L, Treloar SA, Montgomery GW.

Molecular Epidemiology, Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane, Queensland 4029, Australia. zhen.zhao@qimr.edu.au

BACKGROUND: Tumour necrosis factor (TNF) is a pleiotropic cytokine with a wide range of immunoregulatory effects. Variation in the promoter region of TNF and the neighbouring lymphotoxin alpha (LTA) gene might be associated with endometriosis. METHODS: We examined the association between endometriosis and common single-nucleotide polymorphisms (SNPs) or haplotypes in the TNF/LTA region in an Australian sample by analysing 26 SNPs in 958 endometriosis cases and 959 unrelated controls. We selected functional SNPs in the coding and the promoter region of the TNF gene and HapMap tagging SNPs and typed them on a Sequenom MassARRAY platform. A key SNP (rs1800630) in the promoter region typed in previous studies did not give reliable results. Therefore, we also examined a statistically identical (r(2) = 1) SNP (siSNP) (rs2844482), identified using the web based program ssSNPer. RESULTS: Genotype completion rate was 99.5% for SNPs spanning a region of 15.5 kb across the TNF/LTA locus. There was no evidence for association between endometriosis and TNF/LTA SNPs or SNP haplotypes in our case-control study. CONCLUSIONS: Our data suggest both TNF and LTA genes are not major susceptibility genes for endometriosis.

 

Radiologia. 2007 Jul-Aug;49(4):263-7.

[Imaging findings in catamenial pneumothorax]

[Article in Spanish]

Ciudad MJ, Santamaría N, Bustos A, Ferreirós J, Cabeza B, Gómez A.

Servicio de Radiodiagnóstico, Hospital Clínico San Carlos, Madrid, Spain. mariajcf@yahoo.es

OBJECTIVE: To show the presentation and imaging findings of catamenial pneumothorax. MATERIAL AND METHODS: We reviewed the imaging tests (plain-film radiography, computed tomography [CT], magnetic resonance [MR]) performed in six women aged between 28 and 44 years with recurrent pneumothorax associated to menstruation. All patients underwent videothoracoscopic surgery and thoracotomy was necessary in three due to the recurrence of the pneumothorax. RESULTS: CT was performed in three cases and found pleural nodules in two; one of these was confirmed at MR. Pleural endometriosis was only demonstrated at histological examination in one case. Diaphragmatic blebs and bullae were found in five of the six patients. DISCUSSION: The most common symptoms of catamenial pneumothorax are chest pain, dyspnea, and hemoptysis. The right side is affected in 90% of cases. The radiological findings are pneumothorax, hemothorax, or hydropneumothorax. CT and MR can help to identify the pleural lesions that are not visible on plain-film radiographs and are a very common finding at surgery. CONCLUSION: The diagnosis of catamenial pneumothorax should be suspected in fertile-aged women with a history of recurrent pneumothorax coinciding with menstruation. CT and MR can help to identify lesions suspicious of endometriosis.

Am J Surg Pathol. 2007 Jul;31(7):999-1006.

Clear cell adenocarcinoma associated with clear cell adenofibromatous components: a subgroup of ovarian clear cell adenocarcinoma with distinct clinicopathologic characteristics.

Yamamoto S, Tsuda H, Yoshikawa T, Kudoh K, Kita T, Furuya K, Tamai S, Matsubara O.

Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

We occasionally encountered clear cell adenofibromatous (CCAF) components coexisting in the ovarian clear cell adenocarcinoma (CCA). To reveal the clinicopathologic significance of CCAF components in CCA, we classified 67 cases of surgically resected CCA into CCA with and without CCAF components [CCAF(+) and (-) groups], and compared clinicopathologic parameters, that is, patient age, clinical stage, the degree of optimal cytoreduction, patient outcome, histologic grade and Ki-67 labeling index of the CCA, and the presence of endometriosis, between these 2 groups. Fourteen cases (21%) and 53 cases were classified as CCAF(+) and CCAF(-) groups, respectively. Of these 14 CCAF(+) cases, the CCAF components with atypia were observed adjacent to the CCAF components without atypia in 10, and adjacent to the obvious CCAs in 13 cases. In comparison with the CCAF(-) group, the CCAF(+) group showed a higher frequency of histologically low-grade tumors [93% (13 of 14) vs. 43% (23 of 53), P=0.0027], a lower Ki-67 labeling index (mean 35.9% vs. 44.0%, P=0.0492), and better patient prognosis (5-year survival 78.8% vs. 49.3%, P=0.0277). Endometriosis was much less frequent in the CCAF(+) group than in the CCAF(-) group [14.7% (2 of 14) vs. 67.9% (36 of 53), P=0.00096]. Multivariate analysis identified only optimal cytoreduction as independent favorable prognostic factor. These results suggest that CCAF besides endometriosis is associated with the development of CCA, and that the CCAF(+) group may be a distinct subgroup of CCA with less aggressive biologic behavior.

Adv Anat Pathol. 2007 Jul;14(4):241-60.

The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects.

Clement PB.

Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada. Phil.clement@vch.ca

Although the histologic diagnosis of endometriosis is usually straightforward, many diagnostic problems can arise as a result of alterations or absence of its glandular or stromal components. The diagnostic difficulty in such cases can be compounded by tissue that is limited to a small biopsy specimen. The appearance of the glandular component can be altered by hormonal and metaplastic changes, as well as cytologic atypia and hyperplasia. Although the last 2 findings are often referred to collectively as “atypical endometriosis,” they should be separately recognized as their premalignant potential likely differs. In some cases, the endometriotic glands are sparse or even absent (stromal endometriosis). The stromal component can be obscured or effaced by infiltrates of foamy and pigmented histiocytes, fibrosis, elastosis, smooth muscle metaplasia, myxoid change, and decidual change. Occasional findings in endometriosis that may raise concern for a neoplasm include necrotic pseudoxanthomatous nodules, polypoid growth (polypoid endometriosis), bulky disease, and venous, lymphatic, or perineural invasion. Inflammatory and reactive changes within, adjacent to, or at a distance from foci of endometriosis can complicate the histologic findings and include infection within endometriotic cysts, pseudoxanthomatous salpingitis, florid mesothelial hyperplasia, peritoneal inclusion cysts, and Liesegang rings. The histologic diagnosis of endometriosis can also be challenging when it involves an unusual or unexpected site. Five such site-specific problematic areas considered are endometriosis on or near the ovarian surface, superficial cervical endometriosis, vaginal endometriosis, tubal endometriosis, and intestinal endometriosis, including the important distinction of an endometrioid carcinoma arising from colonic endometriosis from a primary colonic adenocarcinoma. Finally, endometriotic foci can occasionally be intimately admixed with another process, such as peritoneal leiomyomatosis or gliomatosis, resulting in a potentially confusing histologic appearance.

J Ultrasound Med. 2007 Jul;26(7):899-908.

In vitro uterine strain imaging: preliminary results.

Hobson MA, Kiss MZ, Varghese T, Sommer AM, Kliewer MA, Zagzebski JA, Hall TJ, Harter J, Hartenbach EM, Madsen EL.

Department of Medical Physics, University of Wisconsin-Madison, 1300 University Ave, 1530 MSC, Madison, WI 53706, USA. mahobson@gmail.com

OBJECTIVE: Uterine abnormalities, such as leiomyomas, endometrial polyps, and adenomyosis, are often clinically associated with irregular uterine bleeding. These abnormalities can have similar B-mode characteristics but require different treatment. The objective of this study was to develop diagnostic techniques based on ultrasound strain imaging that would allow in vivo visualization and characterization of endometrial and myometrial uterine abnormalities, enabling physicians to improve diagnosis and treatment. METHODS: Ultrasound strain imaging was performed on 29 uteri removed via elective hysterectomy. An ultrasound system with a linear array transducer was used to obtain radio frequency echo data during manual freehand compressions of the tissue. Radio frequency data were post-processed with a 2-dimensional block-matching algorithm to generate strain images. RESULTS: In the uteri involved in this study, there were 19 leiomyomas, 1 case of adenomyosis, and 3 endometrial polyps observed on strain imaging. Leiomyomas appeared stiffer than the surrounding normal myometrium in strain images and were characterized by a slipping artifact at their boundary. Endometrial polyps appeared softer than the normal surrounding myometrium. The average strain contrast in small leiomyomas (<1.5 cm) compared to the myometrium was 1.75 +/- 1.14; the strain contrast was 2.50 +/- 1.15 in large leiomyomas and 0.40 +/- 0.05 in endometrial polyps. Leiomyoma strain contrast results were consistent with modulus contrast values from mechanical testing results. CONCLUSIONS: Ultrasound strain imaging can differentiate between endometrial polyps and leiomyomas. More data are necessary to validate these results and to ascertain whether other uterine abnormalities can also be differentiated.

PLoS Genet. 2007 Jun;3(6):e102.

Erratum in:

PLoS Genet. 2007 Aug;3(8):e149.

COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity.

Kurihara I, Lee DK, Petit FG, Jeong J, Lee K, Lydon JP, DeMayo FJ, Tsai MJ, Tsai SY.

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, United States of America.

Progesterone and estrogen are critical regulators of uterine receptivity. To facilitate uterine remodeling for embryo attachment, estrogen activity in the uterine epithelia is attenuated by progesterone; however, the molecular mechanism by which this occurs is poorly defined. COUP-TFII (chicken ovalbumin upstream promoter transcription factor II; also known as NR2F2), a member of the nuclear receptor superfamily, is highly expressed in the uterine stroma and its expression is regulated by the progesterone-Indian hedgehog-Patched signaling axis that emanates from the epithelium. To further assess COUP-TFII uterine function, a conditional COUP-TFII knockout mouse was generated. This mutant mouse is infertile due to implantation failure, in which both embryo attachment and uterine decidualization are impaired. Using this animal model, we have identified a novel genetic pathway in which BMP2 lies downstream of COUP-TFII. Epithelial progesterone-induced Indian hedgehog regulates stromal COUP-TFII, which in turn controls BMP2 to allow decidualization to manifest in vivo. Interestingly, enhanced epithelial estrogen activity, which impedes maturation of the receptive uterus, was clearly observed in the absence of stromal-derived COUP-TFII. This finding is consistent with the notion that progesterone exerts its control of implantation through uterine epithelial-stromal cross-talk and reveals that stromal-derived COUP-TFII is an essential mediator of this complex cross-communication pathway. This finding also provides a new signaling paradigm for steroid hormone regulation in female reproductive biology, with attendant implications for furthering our understanding of the molecular mechanisms that underlie dysregulation of hormonal signaling in such human reproductive disorders as endometriosis and endometrial cancer.

Fertil Steril. 2007 Dec;88(6):1534-40. Epub 2007 Jun 27.

Characterization of WNT7A expression in human endometrium and endometriotic lesions.

Gaetje R, Holtrich U, Karn T, Cikrit E, Engels K, Rody A, Kaufmann M.

Department of Obstetrics and Gynecology, Johann Wolfgang Goethe-University, Frankfurt, Germany. gaetje@em.uni-frankfurt.de

OBJECTIVE: To characterize the expression of WNT7A in human eutopic and ectopic endometrium. DESIGN: Experimental study using real-time polymerase chain reaction, laser microdissection, in situ hybridization, and immunofluorescence. SETTING: University-based laboratory. PATIENT(S): Patients with and without endometriosis undergoing surgery for benign indications. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relative expression values compared with housekeeping genes using real-time polymerase chain reaction. Detection of positive cells by immunofluorescence and in situ hybridization. RESULT(S): In endometriosis, statistically significant higher WNT7A mRNA expression was observed compared with eutopic endometrium. Expression of WNT7A was found in the luminal and glandular epithelial cells as well as stroma cells in endometrium and endometriosis by immunofluorescence, in situ hybridization, and polymerase chain reaction of laser microdissected tissue. CONCLUSION(S): The results of the present study suggest that WNT7A plays a role in the pathophysiology of endometriosis.

Gynecol Obstet Fertil. 2007 Jul-Aug;35(7-8):705; author reply 705-6. Epub 2007 Jun 22.

Comment on:

Gynecol Obstet Fertil. 2006 Jan;34(1):1-2.

[Surgeons: Pity patients who suffer from endometriosis! Gynecol Obstet Fertil 2006; 34:1-2]

[Article in French]

Belaisch J.

Rinsho Shinkeigaku. 2007 May;47(5):234-6.

[Ischemic stroke associated with LH-RH analogue (leuprorelin) administration in a young woman]

[Article in Japanese]

Fujiki F, Tsuboi Y, Yamada T.

Neurology, Hara-Sanshin Hospital.

A 33-year-old woman suffering from endometriosis was admitted to our hospital because of acute-onset diplopia and gait instability. She had a low-grade fever and cough 7 days before admission. On admission, she had left eye deviation downward on the inside, bilateral upper gaze impairment, and left Barrés sign with myoclonic-like movement of the left hand. MRI with diffusion-weighted images (DWI) showed high signal intensity in the right thalamus. The lesion had low signal intensity on an apparent diffusion coefficient (ADC) map, indicating cytotoxic edema. Although the presence of antecedent infection and moderate inflammatory changes shown by blood analysis prevented exclusion of inflammatory disorders such as cerebral angitis or acute disseminating encephalomyelitis, cerebral infarction was strongly suspected. The patient was treated with the free radical scavenger edaravone and high-dose dexamethasone; antiplatelet treatment was not used because of menstrual bleeding. Activation of coagulo-fibrinolytic system such as the elevated plasma level of D-dimer was present, and a luteinizing hormone-releasing hormone (LH-RH) analogue (leuprorelin) had been administered 4 days before hospitalization. This circumstance suggests the possibility that treatment with an LH-RH analogue may cause ischemic stroke in young women.

 

Hum Reprod Update. 2007 Jul-Aug;13(4):395-404.

Endometriosis: cost estimates and methodological perspective.

Simoens S, Hummelshoj L, D’Hooghe T.

Research Centre for Pharmaceutical Care and Pharmaco-Economics, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Onderwijs en Navorsing 2, PO Box 521, Herestraat 49, 3000 Leuven, Belgium. steven.simoens@pharm.kuleuven.be

This article aims to provide a systematic review of estimates and methodology of studies quantifying the costs of endometriosis. Included studies were cost-of-illness analyses quantifying the economic impact of endometriosis and cost analyses calculating diagnostic and treatment costs of endometriosis. Annual healthcare costs and costs of productivity loss associated with endometriosis have been estimated at $2801 and $1023 per patient, respectively. Extrapolating these findings to the US population, this study calculated that annual costs of endometriosis attained $22 billion in 2002 assuming a 10% prevalence rate among women of reproductive age. These costs are considerably higher than those related to Crohn’s disease or to migraine. To date, it is not possible to determine whether a medical approach is less expensive than a surgical approach to treating endometriosis in patients presenting with chronic pelvic pain. Evidence of endometriosis costs in infertile patients is largely lacking. Cost estimates were biased due to the absence of a control group of patients without endometriosis, inadequate consideration of endometriosis recurrence and restricted scope of costs. There is a need for more and better-designed studies that carry out longitudinal analyses of patients until the cessation of their symptoms or that model the chronic nature of endometriosis.

J Reprod Med. 2007 May;52(5):439-40.

Vaginal cuff endometriosis resulting in a fistula between the vagina and abdominal cavity and presenting as peritonitis: a case report.

Chong KM, Chuang J, Tsai YL, Hwang JL, Chu CC.

Department of Obstetrics and Gynecology, Shin-Kong Wu Ho Su Memorial Hospital, No. 95, Wen Chang Road, Shih Lin District, Taipei, Taiwan.

BACKGROUND: The specimen from a vaginal cuff fistula between the vagina and abdominal cavity revealed endometriosis. Culture of the fluid revealed Streptococcus viridans. CASE: A 44-year-old woman presented with lower abdominal pain for 1 week. She also had cyclic vaginal spotting that had started 1 month after she underwent laparoscopically assisted vaginal hysterectomy for a myoma 2 years earlier. One year prior to this admission, she was noted to have a right endometrioma on a sonographic examination; monthly follow-up revealed that the cyst was enlarging. The patient was admitted for surgery. On laparotomy, severe adhesions were noted. After adhesiolysis, a right adnexal cyst with chocolatelike contents mixed with malodorous, yellowish, mucoid fluid was noted. A vaginal cuff fistula between the vagina and abdominal cavity was also noted. The specimen from this area revealed endometriosis. Culture of the fluid showed Streptococcus viridans. CONCLUSION: Various laparoscopic complications are cited in the literature. Although rare, the risk of infection after laparoscopy can occur. In our case the infection may have been caused by the presence of vaginal cuff fistula in the presence of endometriosis.

J Reprod Med. 2007 May;52(5):422-4.

Leiomyomatosis peritonealis disseminata presenting with intravascular extension and coexisting with endometriosis: a case report.

Haberal A, Kayikcioglu F, Caglar GS, Cavusoglu D.

Department of Obstetrics and Gynecology, SSK Ankara Maternity and Women’s Health Teaching Hospital, Ankara, Turkey.

BACKGROUND: Leiomyomatosis peritonealis disseminata is a benign disease of women of reproductive age. Female gonadal steroids play the major role in pathogenesis, but reported cases in postmenopausal women suggests other factors. A few cases in the literature with coexisting endometriosis confirm the hypothesis that both originate in submesothelial multipotential mesenchymal cells. The clinical behavior can be life threatening due to extension through the pelvic veins. CASE: A 46-year-old woman with endometriosis diagnosed at laparotomy 3 years earlier presented with a huge pelvic mass. Postoperative histologic examination of the peritoneal nodules confirmed the diagnosis. Magnetic resonance angiography performed postoperatively revealed intravenous leiomyomatosis. Surgical castration was satisfactory after 2 years of follow-up. CONCLUSION: Although malignant transformation of the disease is known, intravascular extension of the tumor increases the risk of mortality. Close follow-up by clinical examination and radiologic evaluations is required.

Ned Tijdschr Geneeskd. 2007 Jun 2;151(22):1239-43.

Comment in:

Ned Tijdschr Geneeskd. 2007 Jun 2;151(22):1214-6.

[Defecation complaints after hysterectomy because of a benign condition are rare; a prospective study]

[Article in Dutch]

Roovers JP, Weenen M, van der Bom JG, van der Vaart CH.

Universitair Medisch Centrum Utrecht, afd. Obstetrie en Gynaecologie, Utrecht. j.p.roovers@amc.uva.nl

OBJECTIVE: To determine the frequency of defecation symptoms after hysterectomy. DESIGN: Prospective multicentre study, 3 year follow-up. METHODS: 404 patients from 13 teaching or non-teaching hospitals in The Netherlands, who underwent hysterectomy for benign disease other than symptomatic uterine prolapse or known endometriosis, were asked to complete the defecation distress inventory before and 3 years after surgery. The defecation distress inventory is a validated disease specific quality of life questionnaire for assessment of the presence and experienced inconvenience of defecation symptoms. RESULTS: A response rate of 328/372 (88%) of 404 patients whose address could be recovered after 3 years was found. De novo constipation occurred in 2% of the patients following hysterectomy. Sensation of anal blockage and incomplete defecation occurred in more than 15% of the patients. Defecation symptoms reported before surgery had persisted in about half of the patients at 3 years after hysterectomy. A feeling of incomplete defecation at 3 years after hysterectomy was more common after subtotal hysterectomy than after total or vaginal hysterectomy (adjusted odds ratio: 2.1 (95% CI: 1.1-3.8) and 1.4 (95% CI: 0.7-2.7), respectively). CONCLUSION: Defecation symptoms seldom developed after hysterectomy for benign disease. The type of operation did not play a role.

Int J Gynecol Pathol. 2007 Jul;26(3):345-51.

The role of p53 mutation in the carcinomas arising from endometriosis.

Akahane T, Sekizawa A, Purwosunu Y, Nagatsuka M, Okai T.

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

To probe the mechanism of the development of ovarian cancer from endometriosis, which is a multistep process that involves the activation of oncogenes and inactivation of tumor suppressor genes, we evaluated p53 mutations in solitary endometriosis and endometriosis coexisting with ovarian clear cell carcinoma (OCCA) and ovarian endometrioid carcinoma (OEC). We examined 7 cases of solitary ovarian endometriosis, 13 cases of OCCA, and 9 cases of OEC. Cancer tissue specimens that also contained endometriosis without atypia were chosen. Using a laser microdissection system, epithelial cells from the areas of endometriosis were isolated, and DNA was extracted. We amplified exons 5, 6, 7, and 8 of the p53 gene, and direct sequencing was performed. p53 mutation was observed in 4 (30.8%) of 13 specimens of endometriosis coexisting with OCCA, whereas no mutations were detected in solitary endometriosis or endometriosis coexisting with OEC. We thought that some genetic alterations, which induce p53 mutations in endometriosis, may affect malignant transformation of endometriosis into OCCA.

 

Int J Gynecol Pathol. 2007 Jul;26(3):278-83.

Adenomyosis is associated with myometrial invasion by FIGO 1 endometrial adenocarcinoma.

Ismiil ND, Rasty G, Ghorab Z, Nofech-Mozes S, Bernardini M, Thomas G, Ackerman I, Covens A, Khalifa MA.

Department of Pathology, Sunnybrook and Women’s College Health Sciences Center, Toronto, Ontario, Canada. Nadia.Ismiil@sunnybrook.ca

Adenomyosis is commonly seen in hysterectomy specimens for endometrial adenocarcinoma where it could be involved with the tumor. When adenocarcinoma involves adenomyosis, the tumor may remain limited to the adenomyosis or proceeds to invade the adjacent myometrium. The purpose of this study was to investigate whether the risk of myometrial invasion by grade 1 endometrioid adenocarcinoma in cases with cancer-positive adenomyosis is different from that of cases where cancer occurs in the absence of adenomyosis. Forty-six consecutive hysterectomy specimens with International Federation of Gynecology and Obstetrics (FIGO) grade 1 endometrial endometrioid adenocarcinoma involving adenomyosis and 49 consecutive specimens with the same tumor occurring in the absence of adenomyosis were retrospectively studied by 4 experienced gynecologic pathologists. In cases with adenomyosis, myometrial invasion was confirmed by CD10-negative staining around glands with irregular outline surrounded by inflamed desmoplastic stroma. Myometrial invasion was found in significantly more adenomyosis cases (n = 42, 91.3%) than in cases without adenomyosis (n = 38, 77.5%) (chi = 4.79, P = 0.03). In 16 cases of the former group, the invasion only occurred from the foci of adenomyosis. Although myometrial invasion in the outer half was more common in the adenomyosis group (n = 16, 34.8%) than in cases without adenomyosis (n = 9, 18.4%), the difference was not statistically significant (chi = 3.29, P = 0.07). By involving coexistent adenomyosis, FIGO grade 1 endometrial endometrioid adenocarcinoma is associated with myometrial invasion, probably through increasing the surface area of its interface with the adjacent myometrium. When compared with their counterparts that occur in the absence of adenomyosis, these tumors are significantly more likely to invade the myometrium.

 

J Obstet Gynaecol Res. 2007 Jun;33(3):294-8.

Ovarian endometriosis associated with ovarian cancer and endometrial-endocervical polyps.

Kontoravdis A, Augoulea A, Lambrinoudaki I, Christodoulakos G, Tzortziotis D, Grammatikakis I, Kontoravdis N, Creatsas G.

Second Department of Obstetrics and Gynecology, University of Athens, Aretaieion Hospital, Athens, Greece.

AIM: To determine the prevalence of ovarian cancer and endometrial polyps in women with moderate and severe ovarian endometriosis. METHODS: A retrospective analysis of 667 cases of moderate and severe endometriosis laparoscopically and histologically confirmed during the period 1997-2004. RESULTS: One hundred and ninety-three (29%) of cases were American Fertility Society (AFS) stage III (moderate endometriosis) and 473 (71%) were AFS stage IV (severe endometriosis). Ovarian cancer was diagnosed in 13 cases (2.0%), while an endometrial or endocervical polyp was identified in 35 cases (5.3%). The incidence of endometrial polyps in the group with moderate endometriosis tended to be higher (15/193, 7.8%) than in the group with severe endometriosis (20/473, 4.2%), and the same results were obtained in the ovarian cancer group (moderate: 6/193, 3.1%; severe: 7/473, 1.5%). However, neither of the two differences was statistically significant. CONCLUSIONS: Ovarian endometriosis may be associated with an increased incidence of both ovarian cancer and endometrial polyps. Careful evaluation for coexistent pathology should be undertaken in women with symptomatic endometriosis.

J Obstet Gynaecol Res. 2007 Jun;33(3):242-7.

Expression of epidermal growth factor, fibroblast growth factor-2, and platelet-derived growth factor-A in the eutopic endometrium of women with endometriosis.

Lee SR, Kim SH, Lee YJ, Hong SH, Chae HD, Kim CH, Kang BM, Choi YM.

Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Korea.

AIM: The objective of the present study was to compare the levels of expression of epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), and platelet-derived growth factor-A (PDGF-A) mRNA in the eutopic endometrium of women with and without endometriosis. METHODS: Thirty-five women with advanced stage endometriosis and 31 control women were recruited. Following isolation of total RNA from endometrial tissue and reverse transcription, cDNA samples were amplified to quantify the level of expression of EGF, FGF-2, PDGF-A. RESULTS: While the levels of mRNA of EGF and FGF-2 were not different between the two groups, the PDGF-A mRNA level was significantly lower in the endometriosis group than in the control group during the secretory phase (6.12 +/- 0.51 vs 12.50 +/- 0.99, mean +/- SEM, P < 0.05). CONCLUSION: The expression level of PDGF-A, but not EGF and FGF-2, might be decreased during the secretory phase in the eutopic endometrium of women with advanced stage endometriosis.

Vnitr Lek. 2007 Apr;53(4):386-90.

[How corticoids, growth hormone and oestrogens influence lipids and atherosclerosis]

[Article in Czech]

Marek J, Hána V, Krsek M.

III. interní klinika 1. lékarské fakulty UK a VFN Praha. jmarek@lf1.cuni.cz

The hormones with a strong influence on the lipid spectrum and the development of atherosclerosis include cortisol, growth hormone and oestrogens. Cortisol accelerates atherosclerosis both through dyslipidemia and through an increase in visceral fat, hypertension, increased insulin resistance and the development of reduced glucose tolerance which may result in diabetes mellitus. Even when a cortisol excess disappears, as is the case of patients cured of Cushing syndrome, arterial walls remain permanently vulnerable to the atherosclerotic process. In conditions involving a lack of growth hormone, dyslipidemia develops and increases the burden on the cardiovascular system if not treated in a timely manner by the substitution of growth hormone. Oestrogens have a double effect: they have an anti-atherogenic effect on artery walls that are not yet damaged by an atherosclerotic process, but where atherosclerosis has already developed they have a prothrombotic effect and destabilise the atheromatous plaques. If oestrogen is to be used as protection against the onset of atherogenesis, it is necessary to start in a period when the atherosclerotic process has not yet begun to damage the woman’s arterial walls and it is best to use natural hormones (estradiol) and to prevent endometriosis it should be combined with crystalline progesterone applied locally–inravaginally. Oestrogens should be given in small doses, preferably parenterally. Even this will not prevent genetic oestrogen effects though.

 

Hum Reprod Update. 2007 Sep-Oct;13(5):487-99. Epub 2007 Jun 16.

Evolution of medical treatment for endometriosis: back to the roots?

Wieser F, Cohen M, Gaeddert A, Yu J, Burks-Wicks C, Berga SL, Taylor RN.

Division of Gynecological Endocrinology and Reproductive Medicine, University of Vienna, 1090 Vienna, Austria. fwieser@emory.edu

Experimental evidence is accumulating to suggest that medicinal botanicals have anti-inflammatory and pain-alleviating properties and hold promise for treatment of endometriosis. Herein, we present a systematic review of clinical and experimental data on the use of medicinal herbs in the treatment of endometriosis. Although there is a general lack of evidence from clinical studies on the potential efficacy of medicinal herbs for the treatment of endometriosis-associated symptoms, our review highlights the anti-inflammatory and pain-alleviating mechanisms of action of herbal remedies. Medicinal herbs and their active components exhibit cytokine-suppressive, COX-2-inhibiting, antioxidant, sedative and pain-alleviating properties. Each of these mechanisms of action would be predicted to have salutary effects in endometriosis. Better understanding of the mechanisms of action, toxicity and herb-herb and herb-drug interactions permits the optimization of design and execution of complementary alternative medicine trials for endometriosis-associated pain. A potential benefit of herbal therapy is the likelihood of synergistic interactions within individual or combinations of plants. In this sense, phytotherapies may be analogous to nutraceuticals or whole food nutrition. We encourage the development of herbal analogues and establishment of special, simplified registration procedures for certain medicinal products, particularly herbal derivates with a long tradition of safe use.

 

Microvasc Res. 2007 Sep-Nov;74(2-3):121-30. Epub 2007 May 6.

Angiogenesis and antiangiogenic therapy in endometriosis.

Becker CM, D’Amato RJ.

Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, University of Oxford, UK.

Endometriosis, the presence of endometrium-like tissue outside of the uterine cavity, is a common disease among women of reproductive age. Typical symptoms include abdominal pain and painful menstruation. In addition, endometriosis is associated with reduced fertility. Current treatment modalities, the surgical removal of endometriotic lesions and the hormonal suppression of estrogen are associated with significant morbidity, side-effects and recurrence rates. Despite uncertainties about the pathophysiology of the disease it has recently become apparent that angiogenesis plays a pivotal role in endometriosis. This review focuses on a multitude of factors involved in the angiogenic phenotype of endometriosis demonstrating that many biological systems such as the immune system and steroid hormones are closely connected to angiogenic pathways in this disease. In addition, experimental and clinical data are discussed that concentrate on the inhibition of angiogenesis as a novel therapeutic approach for endometriosis.

Obstet Gynecol Surv. 2007 Jul;62(7):461-70.

Bowel endometriosis: presentation, diagnosis, and treatment.

Remorgida V, Ferrero S, Fulcheri E, Ragni N, Martin DC.

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

Bowel endometriosis opens a new frontier for the gynecologist, as it forces the understanding of a new anatomy, a new physiology, and a new pathology. Although some women with bowel endometriosis may be asymptomatic, the majority of them develop a variety of gastrointestinal complains. No clear guideline exists for the evaluation of patients with suspected bowel endometriosis. Given the fact that, besides rectal nodules, bowel endometriosis can not be diagnosed by physical examination, imaging techniques should be used. Several techniques have been proposed for the diagnosis of bowel endometriosis including double-contrast barium enema, transvaginal ultrasonography, rectal endoscopic ultrasonography, magnetic resonance imaging, and multislice computed tomography enteroclysis. Medical management of bowel endometriosis is currently speculative; expectant management should be carefully balanced with the severity of symptoms and the feasibility of prolonged follow-up. Several studies demonstrated an improvement in quality of life after extensive surgical excision of the disease. Bowel endometriotic nodules can be removed by various techniques: mucosal skinning, nodulectomy, full thickness disc resection, and segmental resection. Although the indications for colorectal resection are controversial, recent data suggest that aggressive surgery improves symptoms and quality of life. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to describe the varied appearance of bowel endometriosis, recall that it is difficult to diagnose preoperatively, and explain that surgical treatment offers the best treatment in symptomatic patients through a variety of surgical techniques which is best accomplished with a team approach.

Clin Orthop Relat Res. 2007 Oct;463:221-4.

Case report: Endometrioma of the abdominal wall.

Huff TN, Geiger XJ, Duffy GP, O’Connor MI.

Medical College of Georgia School of Medicine, Augusta, GA, USA.

We present the case of a 39-year-old woman with a 2- to 3-month history of a soft tissue mass involving the abdominal wall and increasing symptoms that fluctuated relative to her menses. Magnetic resonance imaging showed a hemorrhagic multiloculated mass within the rectus abdominus muscle. Correlation of the clinical history and imaging finding suggested a preoperative diagnosis of endometrioma of the abdominal wall. This was confirmed on histologic analysis of the resected specimen.

Int J Gynaecol Obstet. 2007 Aug;98(2):164-7. Epub 2007 Jun 18.

Appendiceal endometriosis presenting as acute appendicitis during pregnancy.

Perez CM, Minimo C, Margolin G, Orris J.

Department of Obstetrics and Gynecology, The Lankenau Hospital, MLHS, Thomas Jefferson University Health System, 100 Lancaster Avenue, Wynnewood, PA 19096, USA. perezc@mlhs.org

 

J Am Acad Dermatol. 2007 Jul;57(1):134-46.

Morphological variations of scar-related and spontaneous endometriosis of the skin and superficial soft tissue: a study of 71 cases with emphasis on atypical features and types of müllerian differentiations.

Kazakov DV, Ondic O, Zamecnik M, Shelekhova KV, Mukensnabl P, Hes O, Dvorak V, Michal M.

Sikl’s Department of Pathology, Charles University Medical Faculty Hospital, Pilsen, Czech Republic. kazakov@medima.cz

BACKGROUND: Seventy-one cases of scar-related and spontaneous endometriosis of the skin and superficial soft tissue were studied, with a focus on atypical features and types of müllerian differentiation. All patients were women, whose ages ranged from 22 to 65 years (median, 32 years). METHODS: Histological, immunohistochemical, and electronmicroscopic studies were performed. Clinical information was ascertained via a questionnaire solicited by the referring physicians. RESULTS: All types of metaplastic changes of müllerian epithelium were found, including tubal (61%), oxyphilic (15%), hobnail (10%), mucinous (4%), and papillary syncytial (3%) metaplasia. Atypical features included reactive atypia (23%) and atypical mitoses in glandular epithelium (6%). Stromal changes included smooth muscle metaplasia (31%), decidualization (<1%), stromal endometriosis (<1%), and elastosis (<1%). Other features recognized included lipoblast-like cells (15%), some with intranuclear inclusions; atypical/degenerative myocytes (10%); spiral arteries (4%); and perineurial invasion (<1%). CD56 staining identified large granular lymphocytes in 15 of 20 studied specimens. Ultrastructurally, these cells showed cytoplasmic granules, some with a delimiting membrane. LIMITATIONS: This study utilizes tissue specimens that mainly were received as consultations; therefore some inherent selection bias exists. Specimens were randomly selected for CD56 immunostaining, leading also to potential sampling error. CONCLUSIONS: All types of müllerian metaplasia can be encountered in cutaneous endometriosis. In addition, so-called atypical features described in endometriosis affecting other anatomic sites may be seen in the skin. Some features may represent a diagnostic pitfall.

 

Urology. 2007 Jun;69(6):1208.e9-11.

Müllerianosis of ureter: a rare cause of hydronephrosis.

Li WM, Yang SF, Lin HC, Juan HC, Wu WJ, Huang CH, Wang CJ, Li CC.

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Müllerianosis of the urinary tract is a very rare and morphologically complex tumor-like lesion. It is composed of several types of müllerian-type lesions, including endometriosis, endocervicosis, and endosalpingiosis. We present a case of ureteral müllerianosis in woman with a history of a cesarean section about 20 years previously but with silent clinical symptoms. She was treated with segmental ureteral resection, followed by ureteroureteral anastomosis. The pathogenesis and treatment of this lesion are discussed.

J Clin Invest. 2007 Jul;117(7):1824-34.

FKBP52 deficiency-conferred uterine progesterone resistance is genetic background and pregnancy stage specific.

Tranguch S, Wang H, Daikoku T, Xie H, Smith DF, Dey SK.

Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232-2678, USA.

Immunophilin FKBP52 serves as a cochaperone to govern normal progesterone (P(4)) receptor (PR) function. Using Fkbp52(-/-) mice, we show intriguing aspects of uterine P(4)/PR signaling during pregnancy. Implantation failure is the major phenotype found in these null females, which is conserved on both C57BL6/129 and CD1 backgrounds. However, P(4) supplementation rescued implantation and subsequent decidualization in CD1, but not C57BL6/129, null females. Surprisingly, experimentally induced decidualization in the absence of blastocysts failed in Fkbp52(-/-) mice on either background even with P(4) supplementation, suggesting that embryonic signals complement uterine signaling for this event. Another interesting finding was that while P(4) at higher than normal pregnancy levels conferred PR signaling sufficient for implantation in CD1 null females, these levels were inefficient in maintaining pregnancy to full term. However, elevating P(4) levels further restored PR signaling to a level optimal for successful term pregnancy with normal litter size. Collectively, the results show that the indispensability of FKBP52 in uterine P(4)/PR signaling is a function of genetic disparity and is pregnancy stage specific. Since there is evidence for a correlation between P(4) supplementation and reduced risks of P(4)-resistant recurrent miscarriages and remission of endometriosis, these findings have clinical implications for genetically diverse populations of women.

Med Clin (Barc). 2007 May 19;128(19):759.

[Nuck’s duct endometriosis]

[Article in Spanish]

Bianchi A, Espin F, Pulido L, Fantova MJ.

 

 

Am J Reprod Immunol. 2007 Jul;58(1):65-74.

The impact of leukemia inhibitory factor in uterine flushing on the reproductive potential of infertile women–a prospective study.

Mikolajczyk M, Wirstlein P, Skrzypczak J.

Division of Reproduction, Department of Obstetrics and Gynecology, University of Medical Sciences, Poznan, Poland.

PROBLEM: To determine the value of leukemia inhibitory factor (LIF) assessment for predicting the reproductive outcome. METHOD OF STUDY: Two phase study. Phase I: assessment of LIF in uterine flushing. Phase II: 1,5 years after examining the last patient, a questionnaire was sent to all participants of the phase I. Phase I: Uterine flushing and endometrial samples were collected during implantation window from infertile patients with stage I/II endometriosis (n = 14), patients with idiopathic infertility (n = 27), luteal phase deficiency (n = 13), and fertile control (n = 21). LIF was assessed in uterine flushings in all patients by ELISA. In endometrium, semiquantitative RT-PCR was performed for LIF mRNA expression. Phase II: questionnaire has been sent to all infertile women taking part in the first phase of the experiment, regarding their reproductive outcome. RESULTS: 65.4% patients who had returned the questionnaire did get pregnant. LIF concentration at a cut-off point of 2.31 pg/ml had a 95.7% sensitivity and 81.8% specificity in predicting the reproductive outcome. CONCLUSION: This prospective study for the first time in literature indicates that the LIF assessment can be used as a predictor of reproductive success.

 

Mol Hum Reprod. 2007 Aug;13(8):587-94. Epub 2007 Jun 11.

Variants in EMX2 and PTEN do not contribute to risk of endometriosis.

Treloar SA, Zhao ZZ, Le L, Zondervan KT, Martin NG, Kennedy S, Nyholt DR, Montgomery GW.

Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia, and Nuffield Department of Obstetrics and Gynaecology, University of Oxford, UK. susan.treloar@qimr.edu.au

Endometriosis has a genetic component, and significant linkage has been found to a region on chromosome 10q. Two candidate genes, EMX2 and PTEN, implicated in both endometriosis and endometrial cancer, lie on chromosome 10q. We hypothesized that variation in EMX2 and/or PTEN could contribute to the risk of endometriosis and may account for some of the linkage signal on 10q. We genotyped single nucleotide polymorphisms (SNPs) in a case-control design to evaluate association between endometriosis and common variations in these two genes. The genotyping and statistical analysis were based on samples collected from Australian volunteers. The cases were 768 unrelated women with surgically confirmed endometriosis selected from affected sister pair (ASP) families participating in the Australian Genes behind Endometriosis Study. The controls were 768 female participants in twin studies who, based on screening questions, did not have a diagnosis of endometriosis. Genotypes of 22 SNPs in the EMX2 gene and 15 SNPs in the PTEN gene were the main outcome measures. Statistical analysis provided measures of linkage disequilibrium and association. Permutation testing showed no globally significant association between any SNPs or haplotypes and endometriosis for either gene. It is unlikely that the EMX2 or PTEN gene variants investigated contribute to risk for initiation and/or development of endometriosis.

Hum Reprod Update. 2007 Sep-Oct;13(5):477-85. Epub 2007 Jun 11.

The position of diagnostic laparoscopy in current fertility practice.

Bosteels J, Van Herendael B, Weyers S, D’Hooghe T.

Department of Obstetrics and Gynaecology, Imeldahospitaal, Imeldalaan 9, 2820 Bonheiden, Belgium. jan.bosteels@imelda.be

In everyday clinical practice, it is not always clear if and when exactly in the fertility work-up a diagnostic laparoscopy should be offered. The aim of this review is to analyse the available evidence with respect to alternative diagnostic methods for detecting tuboperitoneal infertility and with respect to the position of diagnostic laparoscopy in women with infertility. A literature search of the National Library of Medicine and the National Institutes of Health (PubMed) was performed using the key words ‘diagnostic laparoscopy and infertility’. The study methodology was carefully considered in an effort to present conclusions preferably based on randomized controlled trials (RCTs). The routine use of diagnostic laparoscopy for the evaluation of all cases of female infertility is currently under debate. According to data published in retrospective non-controlled studies, diagnostic laparoscopy after several failed cycles of ovulation induction enables the detection of a significant proportion of pelvic pathology amenable to treatment. A Cochrane review has shown that laparoscopic ovarian diathermy in clomiphene-resistant polycystic ovarian syndrome is at least as effective as gonadotrophin treatment, and results in a lower multiple pregnancy rate. The role of laparoscopy before the start of treatment with intrauterine insemination is controversial, according to one RCT. In women with bilateral ultrasonically visible hydrosalpinges, two RCTs have demonstrated increased implantation and pregnancy rates in IVF cycles after salpingectomy. Although RCTs which have studied the benefit of laparoscopic surgery in moderate or severe endometriosis are still lacking, its value has generally been accepted. In conclusion, some specific clinical settings, solid evidence is available to recommend the use of diagnostic laparoscopy in current fertility practice. There is however a need for more RCTs to answer remaining questions regarding its value in the diagnosis and treatment of some patients with infertility.

Hum Reprod. 2007 Aug;22(8):2084-7. Epub 2007 Jun 11.

Comment in:

Hum Reprod. 2008 May;23(5):1237-8.

Unexplained infertility: does it really exist? Does it matter?

Siristatidis C, Bhattacharya S.

Assisted Reproduction Unit, Department of Obstetrics and Gynaecology, Aberdeen Maternity Hospital, Foresterhill, Aberdeen, UK. harrysiri@hotmail.com

Unexplained infertility (UI) refers to a diagnosis made in couples in whom standard investigations including semen analysis, tests of ovulation and tubal patency are normal. It has been suggested that the term UI is unsustainable, as conditions such as endometriosis, tubal infertility, premature ovarian ageing and immunological infertility tend to be misdiagnosed as UI. In this debate, we present the view that, although scientifically unsatisfying, the diagnosis of UI is sustainable from a clinical and practical perspective. Given our present treatment options, further investigations leading to a more ‘accurate’ diagnosis is unlikely to change our management in these cases. Scientific curiosity must take second place to a more pragmatic approach, which takes into account the clinical and financial costs of making a more ‘accurate’ diagnosis.

Hum Reprod. 2007 Aug;22(8):2093-102. Epub 2007 Jun 11.

A system-wide analysis of differentially expressed genes in ectopic and eutopic endometrium.

Wren JD, Wu Y, Guo SW.

Arthritis and Immunology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th Street, Oklahoma City, OK 73104-5005, USA. jdwren@gmail.com

BACKGROUND: Decades of research suggest that endometriosis is a complex disorder, with varying severity, onset and progression. Many genes have been associated with endometriosis through a number of studies and now microarray analyses have added to the list of perturbed or differentially regulated genes. Thus, it is difficult to see ‘the big picture’ without first integrating these multiple, heterogeneous sources of high-quality information for analysis. METHODS: The goal of this study was to infer correlative and/or causal trends by combining empirical microarray analysis with a historical knowledge base of genetic relationships in endometriosis via a program called IRIDESCENT. RESULTS: Importantly, we found a number of genes, which may have a central role in endometriosis, despite the fact that few or no past studies have reported these associations. CONCLUSIONS: Several genes listed as non-responders on the microarray were found to be regulated post-transcriptionally, illustrating the importance of integrating multiple data sources.

Fertil Steril. 2007 Dec;88(6):1674-5. Epub 2007 Jun 11.

Primary umbilical adenomyotic lesion presenting as cyclical periumbilical swelling.

Ploteau S, Malvaux V, Draguet AP.

Department of Gynecology and Obstetrics and Reproductive Medicine, Centre Hospitalier Universitaire, Nantes, France. stephane.ploteau@chu-nantes.fr

A 5-cm umbilical endometriotic lesion associated with a nodule of the posterior aspect of the cervix was discovered in a 32-year-old woman who was consulting for primary infertility. Histological examination of these lesions confirmed smooth muscle hyperplasia that was infiltrated by numerous endometrial glands (adenomyosis).

J Assist Reprod Genet. 2007 Jul;24(7):271-7. Epub 2007 Jun 12.

Single nucleotide polymorphisms and haplotypes of the genes encoding the CYP1B1 in Korean women: no association with advanced endometriosis.

Cho YJ, Hur SE, Lee JY, Song IO, Moon HS, Koong MK, Chung HW.

Department of Obstetrics and Gynecology, Kwandong University School of Medicine, Cheil General Hospital and Women’s Healthcare Center, Seoul, Korea.

OBJECTIVE: To investigate whether single nucleotide polymorphisms and its haplotypes of gene encoding CYP1B1 are associated with the risk of advanced endometriosis in Korean women. METHODS: We investigated 221 patients with histopathologically confirmed endometriosis rAFS stage III/IV and 188 control group women who were surgically proven to have no endometriosis. The genetic distribution of four different CYP1B1 polymorphisms at Ala119Ser, Leu432Val, Asp(449)(C>T), Asn453Ser were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism of PCR products. Haplotype analysis was also performed. RESULTS: We found no overall association between each individual CYP1B1 genotype or haplotype and the risk of endometriosis. Also, the odds ratio of each haplotypes of CYP1B1 showed no association with the risk of endometriosis. CONCLUSIONS: These results suggest that CYP1B1 genetic polymorphism may not be associated with development of advanced endometriosis in Korean women.

Fertil Steril. 2007 Oct;88(4 Suppl):1232-9. Epub 2007 Jun 11.

Effect of highly purified human chorionic gonadotropin preparations on the gene expression signature of stromal cells derived from endometriotic lesions: potential mechanisms for the therapeutic effect of human chorionic gonadotropin in vivo.

Huber A, Hudelist G, Knöfler M, Saleh L, Huber JC, Singer CF.

Division of Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.

OBJECTIVE: To investigate alterations in the overall gene expression profile of endometriosis-derived stroma with increasing concentrations of hCG by using the Affymetrix GeneChip U133 Set. DESIGN: In vitro study. SETTING: Academic research institution. PATIENT(S): Women undergoing diagnostic laparoscopic surgery for endometriosis. INTERVENTION(S): Increasing concentrations of hCG, added to fibroblast monocultures from endometriotic lesions. RESULT(S): We have found that hCG concentrations of 0.1 U/mL and higher lead to a dose-dependent increase in the expression of 68 genes. Most of the up-regulated genes encoded proteins that are involved in cell adhesion, intercellular communication, extracellular matrix (ECM) remodeling, apoptosis, and inflammation. We then incubated stromal monocultures from nine patients treated with and without 50 U/mL of hCG and performed reverse transcriptase-polymerase chain reaction (RT-PCR) for selected, highly up-regulated genes to validate our DNA array findings and to confirm that the alterations in the gene expression signature are exemplary of patients with endometriosis. CONCLUSION(S): We have shown that hCG induces dose-dependent alterations in the gene expression profile of stromal cells obtained from endometriotic lesions and have, for the first time, identified potential mechanisms by which hCG might exert its therapeutic effect on endometriotic lesions.

Fertil Steril. 2007 Oct;88(4 Suppl):1129-34. Epub 2007 Jun 7.

Genistein causes regression of endometriotic implants in the rat model.

Yavuz E, Oktem M, Esinler I, Toru SA, Zeyneloglu HB.

Department of Obstetrics and Gynecology, Baskent University Faculty of Medicine, Ankara, Turkey.

OBJECTIVE: To determine the effects of raloxifene and genistein on experimentally induced endometriosis in a rat model. DESIGN: Prospective, randomized animal study. SETTING: Animal surgery laboratory in a university hospital. ANIMAL(S): Thirty-three adult, mature female Wistar-Albino rats in which endometriotic implants were induced by transplanting autologous uterine tissue to ectopic sites on the peritoneum. INTERVENTION(S): After the endometriotic implants were formed surgically, the 33 rats were randomly divided into three groups. Group 1 (genistein group, 10 rats) were given 500 mg/kg per day of oral genistein. Group 2 (raloxifene group, 10 rats) were given 10 mg/kg per day of oral raloxifene. Group 3 were given no medication and served as controls (13 rats). All the rats continued to receive treatment for 21 days, and then were killed to assess the implants’ size and for histologic examination. MAIN OUTCOME MEASURE(S): The surface area of the endometriotic implants and the score of histologic analysis. RESULT(S): At the beginning of the medical treatment, the mean surface areas of the endometriotic implants were comparable in all three groups. At the end of the medical treatment, the mean surface area of implants in groups 1 and 2 was smaller than that of implants in the control group. The decrease in the surface area of the endometriotic implants was greater in group 1 and group 2 than found in the control group. The histologic assessment revealed that the mean of the histopathologic score of the implants at the end of the treatment was lower in groups 1 and 2 when compared with the control group. CONCLUSION(S): Genistein caused a statistically significant regression of endometriotic implants.

Cytopathology. 2007 Aug;18(4):255-9, 210. Epub 2007 Jun 8.

Endoscopic ultrasonography-guided fine needle aspiration of a nodule in the rectovaginal septum.

Dagher C, Palazzo L, Guillermand-Gérard H, Lalloue C, Fabre M.

Department of Pathology, Bicêtre University Hospital, AP-HP, Paris, France.

Surg Innov. 2007 Jun;14(2):102-6.

Individual physician experience with laparoscopic supracervical hysterectomy in a single outpatient setting.

McClellan SN, Hamilton B, Rettenmaier MA, Lopez K, John CR, Hu JC, Goldstein BH.

Newport Beach, California 92663, USA.

The authors report the surgical experience of a single physician operating at 1 outpatient surgery center using laparoscopic supracervical hysterectomy for the treatment of 100 patients with benign gynecologic disease. Operative status was evaluated in terms of patient morbidity, length of surgery, blood loss, and duration of hospital stay. The mean operative time was 2.6 hours, and the mean anesthesia time was 3.2 hours. The mean estimated blood loss was 116.6 mL, and the mean patient hospital stay was 16.5 hours. There were no reported intraoperative or postoperative complications. Laparoscopic supracervical hysterectomy was not feasible and was converted to laparotomy and total abdominal hysterectomy in 4 patients. The authors present one of the first individual physician experiences at a single outpatient surgery center using laparoscopic supracervical hysterectomy for benign gynecologic conditions. Optimal patient postoperative stay and a minimal complication rate suggest that this procedure performed at a single outpatient surgery center is feasible.

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