Nephron Clin Pract. 2010;114(2):c89-c94. Epub 2009 Nov 3.

Ureteral Endometriosis: A Rare and Underdiagnosed Cause of Kidney Dysfunction.

Ponticelli C, Graziani G, Montanari E.

Division of Nephrology IRCCS Humanitas, Ospedale San Paolo, Milan, Italy.

Little attention has been paid by the renal literature to ureteral endometriosis, a rare and silent disorder that can eventually lead to renal failure. In endometriosis, the ureteral involvement can be limited to a single ureter, more often the left one, or both ureters with consequent urine tract obstruction and ureterohydronephrosis. In most cases, the ureteral obstruction is caused by endometrial tissue surrounding the ureter (extrinsic ureteral endometriosis). In the remaining cases, endometrial cells are located within the ureter (intrinsic ureteral endometriosis). Progressive ureteral obstruction can be insidious in onset and can ultimately lead to renal failure if a correct diagnosis is missed. The true incidence of renal failure caused by endometriosis is completely unknown, although cases have been reported in the literature. The diagnosis of ureteral endometriosis is difficult since the disease may be clinically silent or associated with non-specific symptoms. Only a high index of suspicion and radiological support may help to obtain an early diagnosis. However, while renal imaging is useful in the cases of extrinsic endometriosis, the diagnosis of intrinsic endometriosis often requires ureteroscopy or laparoscopy. The prognosis of ureteral endometriosis depends on the time of diagnosis. In too many cases of bilateral obstruction, the patient is referred to the nephrologist because of an advanced, irreversible renal failure. Although some patients may benefit from progestin or anti-arotamase therapy, in most cases of ureteral endometriosis surgery is needed, laparoscopy surgery being preferred today to laparatomy. Copyright © 2009 S. Karger AG, Basel.

Yonsei Med J. 2009 Oct 31;50(5):732-5. Epub 2009 Oct 21.

Intestinal endometriosis mimicking carcinoma of rectum and sigmoid colon: a report of five cases.

Kim JS, Hur H, Min BS, Kim H, Sohn SK, Cho CH, Kim NK.

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Among women with intestinal endometriosis, the sigmoid colon and rectum are the most commonly involved areas. Sometimes, the differential diagnosis of colorectal endometriosis from carcinoma of the colon and rectum is difficult due to similar colonoscopic and radiologic findings. From October 2002 to September 2007, we performed five operations with curative intent for rectal and sigmoid colon cancer that revealed intestinal endometriosis. Colonoscopic and radiologic findings were suggestive of carcinoma of rectum and sigmoid colon, such as rectal cancer, sigmoid colon cancer and gastrointestinal stromal tumor (GIST). Anterior resection was performed in two patients, low anterior resection was performed in one patient and laparoscopic low anterior resection was done in two patients. We suggest to consider also intestinal endometriosis in reproductive women presenting with gastrointestinal symptoms and an intestinal mass of unknown origin.

Fertil Steril. 2009 Dec;92(6):e63; author reply e64. Epub 2009 Oct 29.

Management of endometrioma in women embarking on IVF: paucity of good quality evidence.

Nama V, Kalu E.

Comment on:

Reprod Biol Endocrinol. 2009 Oct 30;7:123.

Quantity and quality of retrograde menstruation: a case control study.

Bokor A, Debrock S, Drijkoningen M, Goossens W, Fülöp V, D’Hooghe T.

Leuven University Fertility Center, UZ Gasthuisberg, KULeuven, Belgium.

BACKGROUND: The purpose of this study was to test the hypothesis that menstruation is associated with a higher concentration of endometrial cells in peritoneal fluid(PF) and with increased white and red blood cell concentration in PF when compared to nonmenstrual phases of the cycle. METHODS: PF was obtained at laparoscopy from 107 women with endometriosis (n = 59) and controls with a normal pelvis (n = 48) during the luteal (n = 46), follicular (n = 38) or menstrual (n = 23) phase of the cycle. Endometriosis was classified according to the classification of the American Society for Reproductive Medicine (rAFS into minimal (n = 25), mild(n = 20), moderate(n = 6) and severe(n = 8) disease. Cell counts (leucocytes, erythrocytes, thrombocytes) were determined on a cell counter. In a subset of 32 patients (13 controls and 19 women with endometriosis), PF was fixed, processed and thinlayers were prepared and stained with Papanicolaou method and with immunocytochemistry using monoclonal antibodies against cytokeratin 7(CK 7), CK 8/18, Ber-Ep4, vimentin, calretinin and CD68. Ber-Ep4 is a marker for cells with epithelial origin (in some cases for mesothelial cells as well). CD68 is specific for cells from monocyte/macrophage lineage; CK7 and CK8/18 are markers for both endometrial epithelial and mesothelial cells, whereas calretinin and vimentin are markers for both endometrial stromal and mesothelial cells. RESULTS: In comparison with the nonmenstrual phase of the cycle, analysis of PF during menstruation showed an increased concentration of leucocytes (3.3 x 109/L vs 0.8 x 109/L, P = 0.03), erythrocytes (0.3 x 1012/L vs 0.02 x 1012/L, P = 0.006), hematocrit (0.03 L/L vs 0.003 L/L, P = 0.01) and hemoglobin (0.8 g/dL vs 0.1 g/dL, P = 0.01). Mesothelial cells stained positively with CK7, CK8/18, vimentin, and calretinin. Cells positive for Ber-Ep4 were not observed, except in 2 patients with endometriosis investigated during menses. In all patients 50-98% of single cells were strongly positive for both vimentin and CD68. CONCLUSION: When compared to nonmenstrual phases of the cycle, menstruation is associated with an increased concentration of red and white blood cells in PF. However, the presence of EM cells that are detectable by immunohistochemistry in PF is low during all phases of the cycle, including menstruation.

Acta Obstet Gynecol Scand. 2009;88(12):1397-401.

+1730 G/A polymorphism of the estrogen receptor beta gene (ERbeta) may be an important genetic factor predisposing to endometriosis.

Bianco B, Christofolini DM, Mafra FA, Brandes A, Zulli K, Barbosa CP.

Division of Genetics and Human Reproduction – Department of Gynecology and Obstetrics, ABC Faculty of Medicine, Santo André, São Paulo, Brazil. bianca.bianco@hotmail.com

OBJECTIVE: To determine the frequency of the estrogen receptor gene (ERbeta) +1730 G/A polymorphism in Brazilian women with endometriosis. DESIGN: Case-control study. SETTING: Endometriosis Outpatient Clinic and Family Planning Outpatient Clinic of ABC Faculty of Medicine. POPULATION: A total of 108 patients with endometriosis and a control group consisting of 210 fertile women. METHODS: The ERbeta gene +1730 G/A polymorphism was identified by restriction fragment length polymorphism-polymerase chain reaction. MAIN OUTCOME MEASURE(S): Genotype distribution and allele frequency of the +1730 G/A polymorphism in the ERbeta gene. RESULTS: Genotypes GG, GA and AA of the ERbeta gene presented frequencies of 50.9%, 47.2% and 1.9%, respectively, in the women with endometriosis. Among the patients with stage I/II endometriosis, 47% presented the normal homozygous genotype GG; 51% had a GA heterozygous genotype and 2% had a homozygous mutated genotype AA. Among the patients with stage III/IV endometriosis, genotypes GG, GA and AA were present in 54.3%, 44% and 1.7%, respectively. In the control group, 74.3% presented the normal homozygous genotype GG, 24.3% the heterozygous genotype GA and 1.4% the homozygous mutated genotype AA. CONCLUSION: The data suggest that the ERbeta gene +1730 G/A polymorphism can be associated with the risk of endometriosis development, regardless of the stage of the disease.

BJOG. 2010 Jan;117(2):185-92.

The menstrual disorder of teenagers (MDOT) study: determining typical menstrual patterns and menstrual disturbance in a large population-based study of Australian teenagers.

Parker MA, Sneddon AE, Arbon P.

Australian National University Medical School, Garran, Canberra, Australia. melissa.parker@act.gov.au

OBJECTIVE: The aim of this study was to: (1) establish the typical experience of menstruation for senior high school girls and (2) determine how many experience considerable menstrual disturbance that could require further investigation and management of underlying pathology. DESIGN: Cross-sectional study. SETTING: Senior High Schools in the Australian Capital Territory (ACT), Australia. POPULATION: A total of 1051 girls aged between 15 and 19 years. METHODS: Data based on a quantitative survey. MAIN OUTCOME MEASURES: Self-reports of menstrual bleeding patterns, typical and atypical symptoms and morbidities. RESULTS: Typical menstruation in adolescence includes pain (93%), cramping (71%), premenstrual symptoms (96%) and mood disturbance (73%). Highly significant associations were found between increasing severity of menstrual pain, number of menstrual-related symptoms, interference with life activities and school absence. These associations indicate that approximately 25% of the sample had marked menstrual disturbance: 21% experienced severe pain; 26% school absence; 26% suffering five or more symptoms; > or =24% reporting moderate to high interference with four out of nine life activities. Approximately 10% reported atypical symptoms associated with menstruation. Diagnosis of menstrual pathology in the sample was low, even though 33% had seen a GP and 9% had been referred to a specialist. CONCLUSIONS: Menstrual pain and symptoms are common in teenagers. Girls indicating moderate to severe pain in association with a high number of menstrual symptoms, school absence and interference with life activities should be effectively managed to minimise menstrual morbidity. Those girls who do not respond to medical management should be considered for further investigation for possible underlying pathology, such as endometriosis.

Clin Nephrol. 2009 Nov;72(5):418-9.

Hydroureteronephrosis caused by endometriosis around the ureter.

Lee TH, Kim W, Lee S, Kang KP, Kim YK, Kim MK, Jeong YB, Park HS, Lee NH, Park SK.

J Ethnopharmacol. 2010 Feb 3;127(2):561-4. Epub 2009 Oct 24.

Fertility inducing effect of aerial parts of Coccinia cordifolia L. in female rats.

Jha U, Asad M, Asdaq SM, Das AK, Prasad VS.

Department of Pharmacology, Krupanidhi College of Pharmacy, 5 Sarjapur Road, Koramangala, Bangalore 560 034, India.

ETHNOPHARMACOLOGICAL RELEVANCE: The aerial parts of Coccinia cordifolia L. are used to treat female infertility in West Bengal state of India. AIM OF THE STUDY: The present study was undertaken to evaluate the fertility inducing effect of aerial parts of Coccinia cordifolia L. in female rats. MATERIALS AND METHODS: The effect of aqueous extract of Coccinia cordifolia L. on hyperprolactinemia induced infertility, endometriosis induced infertility and androgen-induced infertility was studied. The effect on serum estrogen level, serum progesterone level and reproductive tract was also evaluated in normal healthy female rats. The extract was administered orally at two different doses of 500 mg/kg and 1000 mg/kg. RESULTS: In hyperprolactinemia induced infertility model, the numbers of uterine implants were almost 10 times more in the extract treated groups as compared to control. The high dose of extract also produced a significant increase in serum estrogen levels (p<0.01) and number of corpus luteum (p<0.05) in healthy female rats. The extract at both doses was effective in reducing the weight of endometrial implants by 70-80%, but failed to induce fertility in rats with endometriosis. The extract was ineffective in inducing fertility in androgen-induced infertility model. CONCLUSIONS: The aqueous extract of Coccinia cordifolia L. induces fertility in hyperprolactinemia induced infertility model in female rats. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Ned Tijdschr Geneeskd. 2009;153:B430.

Loss of renal function due to deep infiltrating endometriosis; a complicated consideration in women who wish to have children.

[Article in Dutch]

de Graaff AA, Beets-Tan RG, Beets GL, van de Beek CK, Dunselman GA.

Maastricht Universitair Medisch Centrum, Afd. Obstetrie en Gynaecologie, Maastricht, The Netherlands. aa.de.graaff@mumc.nl

Three nulliparous women, aged 39, 34 and 26 years, who were treated for fertility problems and who were affected by endometriosis, presented with ureteral obstruction caused by deep infiltrating endometriosis. The first two patients had complete unilateral loss of kidney function at the time of diagnosis. They chose to have fertility treatment first and both became pregnant. The third patient still had 24% renal function in the affected left kidney. She was treated by complete surgical resection of the endometriosis and reimplantation of the ureter. Ureteral obstruction is a rare, but serious, complication of deep infiltrating endometriosis. Timely recognition is important, since delay results in unnoticed loss of renal function. Clinical investigation for endometriosis of the posterior vaginal fornix is recommended for all patients with chronic abdominal pain, severe dysmenorrhoea or deep dyspareunia. On diagnosis of deep infiltrating endometriosis, further examination is necessary to detect possible ureteral obstruction and consequent hydronephrosis, which can be demonstrated by ultrasound. MRI is of value to map the extent of disease, which is usually multi-focal. Surgery to relieve ureteral obstruction and remove all endometriotic lesions is the treatment of choice if the kidney is still functional.

Int J Clin Oncol. 2009 Oct;14(5):383-91. Epub 2009 Oct 25.

Ovarian cancer in endometriosis: molecular biology, pathology, and clinical management.

Mandai M, Yamaguchi K, Matsumura N, Baba T, Konishi I.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. mandai@kuhp.kyoto-u.ac

Recent molecular and pathological evidence suggests that endometriosis is a monoclonal, neoplastic disease. Moreover, endometriosis serves as a precursor of ovarian cancer (endometriosis-associated ovarian cancer; EAOC), especially of the endometrioid and clear cell subtypes. Although a variety of molecular events, such as p53 alteration, PTEN silencing, K-ras mutations, and HNF-1 activation, have been identified in EAOC, its precise carcinogenic mechanism remains poorly understood. Our recent data indicate that microenvironmental factors, including oxidative stress and inflammation, play an important role in the carcinogenesis and phenotype of EAOC. The management of endometriosis from the standpoint of EAOC is not standardized yet. To this end, clarification of the precise natural course and the risk factors that contribute to malignant transformation remain important goals. Among the phenotypes of EAOC, clear cell carcinoma, seems to require a specific treatment strategy, including molecular targeting.

Int J Clin Oncol. 2009 Oct;14(5):378-82. Epub 2009 Oct 25.

Ovarian cancer in endometriosis: epidemiology, natural history, and clinical diagnosis.

Kobayashi H.

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

We review whether endometriosis-associated ovarian cancer is a specific entity compared with ovarian cancer not associated with endometriosis, with respect to epidemiology, natural history, and clinical diagnosis; we present a review of the English-language literature for ovarian cancer in endometriosis with respect to these three features. A recent prospective study in Japan directly showed that, during a follow-up of up to 17 years of an ovarian endometrioma cohort (n = 6398), 46 incident ovarian cancers were identified, showing that the ovarian cancer risk was significantly elevated in patients with ovarian endometrioma (standardized incidence ratio [SIR], 8.95; 95% confidence interval [CI], 4.12 to 15.3). Advancing age (>40 years) and the size of the endometriomas (>9 cm) were independent predictors of the development of ovarian cancer among the women with ovarian endometrioma. Although some endometriosis lesions may predispose to clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) of the ovary, both of these cancers differ from the other histological types with respect to their clinical characteristics and carcinogenesis. In patients with endometriosis-associated ovarian cancer, benign-appearing ovarian masses are typically present several years before the diagnosis of the cancer. A slightly elevated carbohydrate antigen [CA] 125 level is also typically present many years before the diagnosis in these patients. However, serous-type ovarian cancer may exhibit a rapid progression possibly through de-novo carcinogenesis. Ovarian endometrioma could be viewed as a neoplastic process, particularly in perimenopausal women. Understanding the mechanisms of the development of endometriosis and elucidating its pathogenesis and pathophysiology are intrinsic to the prevention of endometriosis-associated ovarian cancer and the search for effective therapies.

Int J Clin Oncol. 2009 Oct;14(5):377. Epub 2009 Oct 25.

Ovarian cancer in endometriosis.

Konishi I.

Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. konishi@kuhp.kyoto-u.ac.jp

Virchows Arch. 2009 Nov;455(5):413-22. Epub 2009 Oct 24.

Aberrant expression of p27(Kip1)-interacting cell-cycle regulatory proteins in ovarian clear cell carcinomas and their precursors with special consideration of two distinct multistage clear cell carcinogenetic pathways.

Yamamoto S, Tsuda H, Miyai K, Takano M, Tamai S, Matsubara O.

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

We have previously reported that alterations of p27(Kip1)-interacting cell-cycle proteins frequently occur during the development of endometriosis-associated ovarian clear cell adenocarcinoma (CCA; Yamamoto et al., Histopathology in press, 20). However, CCA also occurs in association with clear cell adenofibroma (CCAF). In this study, the expressions of p27(Kip1)-interacting proteins, i.e., p27(Kip1), Skp2, Cks1, cyclin A, cyclin E, and the Ki-67 labeling index (LI), were analyzed in 25 CCAFs (11 benign and 14 borderline) and 15 CCAF-associated CCAs, and compared with the expression status of each protein in the 23 previously studied endometriosis-associated CCAs. Although aberrant expression of all p27(Kip1)-interacting proteins was more frequent in the CCAF-associated CCAs than in the benign CCAFs, statistical significance was found only for Cks1 overexpression. The frequencies of p27(Kip1) downregulation and overexpression of Skp2 and cyclin A were significantly lower in CCAF-associated than in endometriosis-associated CCAs (P < 0.05, respectively). The frequencies of p27(Kip1) downregulation and Skp2 overexpression in borderline CCAFs were significantly lower than those in atypical endometriosis components in endometriosis-associated CCAs (P < 0.05, respectively). Mean Ki-67 LI increased significantly through benign (4.9%) to borderline (11.1%) CCAF and to CCAF-associated CCA (30.6%), but the latter two values were significantly lower than those in atypical endometriosis (21.4%) and endometriosis-associated CCA (46.9%; P < 0.05, respectively). These data suggest that accumulated alterations of p27(Kip1)-interacting proteins may accelerate the development of CCAs regardless of their carcinogenetic pathways, but that tumor cells in the CCAF-associated pathway appear to show slower cell-cycle progression than those in the endometriosis-associated pathway, possibly accounting for the distinct clinicopathological features of the two CCA subtypes.

Hum Reprod. 2010 Jan;25(1):118-26. Epub 2009 Oct 24.

The relative contribution of IVF to the total ongoing pregnancy rate in a subfertile cohort.

Brandes M, Hamilton CJ, de Bruin JP, Nelen WL, Kremer JA.

Department of Obstetrics and Gynaecology, Jeroen Bosch Ziekenhuis, PO Box 90153, 5200 ME ‘s-Hertogenbosch, The Netherlands. m.brandes@jbz.nl

BACKGROUND: Although in vitro fertilization (IVF) was introduced more than 30 years ago, its exact role in the spectrum of fertility treatments has never been studied in an unselected population. The aim of this study was to visualize the contribution of IVF to the ongoing pregnancy rates in a cohort of newly referred subfertile couples. MATERIALS: All new subfertile couples (n = 1391) that were referred to our fertility clinic by their general practitioner between January 2002 and December 2006 were included. Fertility care was provided according to the national Dutch fertility guidelines. Data on diagnosis, treatment, mode of conception and pregnancy outcome were documented. If follow-up data were missing, couples were contacted. Cumulative pregnancy curves were constructed for the whole cohort and per diagnostic group. RESULTS: As per December 2008 the overall ongoing pregnancy rate was 72.0% (n = 1001). Almost half of the pregnancies were conceived spontaneously (45.6%), 19.2% after ovulation induction (OI), 14.0% after intrauterine insemination (IUI) and 21.2% after IVF. A quarter (n = 349) of couples received IVF treatment, which was successful in 60% of cases. IVF had the largest contribution to ongoing pregnancies in patients with ‘tubal factor’, ‘endometriosis’ and ‘male factor’ (45, 45 and 37%, respectively) while in couples with ‘unexplained subfertility’ and ‘ovulation disorders’ the contribution to ongoing pregnancies of IVF was limited (13 and 4.5%, respectively). CONCLUSIONS: In a cohort of subfertile couples, most pregnancies were conceived spontaneously. The contribution of IVF to ongoing pregnancy rates was comparable to those of OI and IUI. Compared with the pre-IVF era, couples with ‘endometriosis’, ‘tubal factor’ and ‘male subfertility’ have benefited most from its introduction.

Acta Obstet Gynecol Scand. 2009;88(12):1418-9.

Laparoscopic treatment of diaphragmatic endometriosis causing chronic shoulder and arm pain.

Cucinella G, Granese R, Calagna G, Candiani M, Perino A.

Int J Gynecol Pathol. 2009 Nov;28(6):584-8.

Ovarian clear cell carcinoma arising in a mucinous cystadenoma.

Wani Y, Notohara K.

Department of Pathology, Kurashiki Central Hospital, Miwa, Kurashiki 710-8602, Japan. yw7144@kchnet.or.jp

Here we report a rare case of ovarian clear cell carcinoma (CC) arising in a mucinous cystadenoma. A 59-year-old woman presented with a dull pain at the left inguinal area. She was found to have a left ovarian cyst measuring 4.7 cm and underwent a salpingo-oophorectomy. The unilocular cyst contained thick mucin, lacking any solid components. Histopathologically, most of the cyst wall was lined with a single layer of tall columnar cells with basophilic mucin. Within limited areas, small glands consisting of clear cytoplasm aggregated and intermingled with or partially transitioned to the mucinous glands. The clear cell components had adenofibroma-like features devoid of significant nuclear atypia or stromal invasion, including distinctive foci of CC with a hobnail appearance and hyperchromatic nuclei surrounded by desmoplastic or hyalinized stroma. Immunohistochemically, both mucinous and clear cells were positive for estrogen receptor. Hepatocyte nuclear factor-1beta and laminin were positive in all of the clear cell components, in contrast to a consistent lack of staining in the mucinous epithelium. An eleven-month follow-up revealed no recurrence or metastasis. This case was considered as an early manifestation of ovarian CC arising in a mucinous cystadenoma in the absence of demonstrable endometriosis.

World J Gastroenterol. 2009 Oct 21;15(39):4974-5.

Forgotten node: a case report.

Fratellone PM, Holowecki MA.

Fratellone Medical Associates, 47 West 57th Street 5th Floor New York, NY 10019, United States. fratmd@aol.com

Sister Mary Joseph nodule or node refers to a palpable nodule bulging into the umbilicus and is usually a result of a malignant cancer in the pelvis or abdomen. Traditionally it has been considered a sign of ominous prognosis. Gastrointestinal malignancies, most commonly gastric, colon and pancreatic cancer account for about 52% of the underlying sources. Gynecological cancers, most commonly ovarian and uterine cancers account for about 28% of the sources.

Dis Model Mech. 2009 Nov-Dec;2(11-12):593-603. Epub 2009 Oct 19.

A conditional mouse model for human MUC1-positive endometriosis shows the presence of anti-MUC1 antibodies and Foxp3+ regulatory T cells.

Budiu RA, Diaconu I, Chrissluis R, Dricu A, Edwards RP, Vlad AM.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine and Magee Womens Research Institute, Pittsburgh, PA 15213, USA.

Endometriosis is defined by the presence of tissue implants resembling endometrial glands outside of the uterus, at ectopic sites, frequently on the ovarian surface. The ectopic lesions are often invasive, resistant to therapy, and may predispose to endometrioid and clear cell ovarian tumors. The complex mechanisms leading to chronic endometriosis are mediated partly by impaired immune surveillance in the host. Although innate immunity has been addressed previously, the response of adaptive immune effectors to specific antigens has not been characterized, mostly because very few endometriosis antigens have been defined to date. We postulated that the mucin 1 (MUC1) glycoprotein, which is normally present on eutopic human endometrial glands and overexpressed in endometrioid and clear cell ovarian tumors, is also present in ectopic lesions of ovarian endometriosis. Furthermore, changes in MUC1 expression in endometriosis could promote adaptive anti-MUC1 immunity that might play a role in the malignant progression. To test our hypothesis, we crossed MUC1 transgenic mice, which express human MUC1 under the endogenous promoter, with the loxP-Stop-loxP-Kras(G12D/+) (Kras) mice, in which endometriosis can be induced through Cre-loxP recombination. The double transgenic MUC1Kras mice develop benign, MUC1-positive ovarian lesions, closely resembling human endometriosis. Subsequent to disease induction, the mice generate high titers of IgM and IgG antibodies that are specific for MUC1. Antibodies appear early in disease and the predominance of the IgG1 subclass suggests Th2-driven immunity. Immune phenotyping revealed an accumulation of Foxp3+ CD4 regulatory T cells (Tregs) in the draining lymph nodes at late-stage disease. Furthermore, our observations in human endometriosis showed a similar recruitment of FOXP3+ CD4 T cells. Overall, our results reveal a Th2/Treg-dominant natural immunity in endometriosis with potential implications for cancer progression.

Rev Bras Ginecol Obstet. 2009 Jul;31(7):349-52.

Evaluation of basal FSH serum levels in infertile patients with deep ovarian endometriosis who underwent surgery.

[Article in Portuguese]

Frankfurt S, Nunes AL, Reis AD, Christofolini DM, Bianco B, Barbosa CP.

Médica Residente da Disciplina de Ginecologia Patológica e Reprodução Humana–FMABC-Santo André (SP), Brasil.

PURPOSE: to evaluate the ovarian reserve of infertile patients with severe ovarian endrometriosis, submitted to excisional surgery of endometriomas and attended from February to November, 2008. METHODS: prospective study, including 30 patients with endometriosis grades III and IV, with severe ovarian impairment, submitted to excisional surgery of the endometriomas, and 30 patients with endometriosis grades I and II, allocated as a Control Group. The ovarian reserve was indirectly assessed, through the basal (U/L) follicle stimulating hormone (FSH), between the third and fifth days of the cycle, 12 months after the surgery. The body mass index (BMI) was calculated according to Quetelet’s formula [weight (kg)/height(cm(2))]. The Mann-Whitney non-parametric U test was used to compare the variables ‘age’, ‘BMI’ and ‘basal SFH’ between the groups. RESULTS: there was no significant difference between the groups about age and BMI. Concerning basal FSH, in the group of patients with severe endometriosis, the average value was 7.0 U/L, while in the Control Group, it was 5.6 U/L (p=0.3), what demonstrates that the difference between the two groups was not significant. CONCLUSIONS: the surgery did not affect the ovarian reserve of patients with severe ovarian endometriosis.

Trends Endocrinol Metab. 2010 Jan;21(1):17-24.

Lysophosphatidic acid (LPA) signaling in vertebrate reproduction.

Ye X, Chun J.

Department of Physiology and Pharmacology, College of Veterinary Medicine, and Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA.

Lysophosphatidic acid (LPA) is a cell membrane phospholipid metabolite that can act as an extracellular signal. Its effects are mediated through at least five G protein-coupled receptors, LPA(1-5), and probably others as well. Studies in multiple species including LPAR-deficient mice and humans have identified or implicated important roles for receptor-mediated LPA signaling in multiple aspects of vertebrate reproduction. These include ovarian function, spermatogenesis, fertilization, early embryo development, embryo implantation, embryo spacing, decidualization, pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and ovarian cancer. Here we review recent progress in LPA signaling research relevant to female and male reproduction.

Fertil Steril. 2009 Dec;92(6):2038.e9-12.

Lower limb compartment syndrome as a complication of laparoscopic laser surgery for severe endometriosis.

Tomassetti C, Meuleman C, Vanacker B, D’Hooghe T.

Department of Obstetrics and Gynaecology, Leuven University Fertility Centre, University Hospitals Leuven, Leuven, Belgium.

OBJECTIVE: To report a case of lower limb compartment syndrome (LLCS) during long duration laparoscopic interventions for resection of extensive endometriosis, and evaluate the efficiency of a novel patient positioning method to reduce its prevalence. DESIGN: Case report and observational study. SETTING: University Hospitals, Belgium. PATIENT(S): Thirty-year-old woman undergoing a long duration laparoscopic intervention for resection of stage IV pelvic endometriosis. INTERVENTION(S): Laparoscopic intervention for resection of stage IV pelvic endometriosis. MAIN OUTCOME MEASURE(S): The occurrence of LLCS after laparoscopic surgery for extensive endometriosis, in this case, and the prevention of subsequent LLCS after the application of a novel patient positioning method including the following steps: maximal avoidance of the lithotomy position, patient positioning in a modified supine position, mobilization of the legs of the patient in between different surgical phases, and application of intermittent compression stockings. RESULT(S): The prevalence of lower limb compartment syndrome has been reduced to 0 since the application of the new patient positioning method. CONCLUSION(S): Lower limb compartment syndrome can be prevented in patients undergoing long duration multidisciplinary laparoscopic resection of extensive endometriosis by a novel sequential positioning method of patients before and during surgery.

J Obstet Gynaecol. 2009 Nov;29(8):729-31.

Can high histological confirmation rates be achieved for pelvic endometriosis?

Stavroulis AI, Saridogan E, Benjamin E, Cutner AS.

Elizabeth Garrett Anderson and Obstetric Hospital, The University College London Hospitals NHS Foundation Trust, London, UK. stavroulis@btinternet.com

This paper aims to determine the correlation between the diagnosis of endometriosis on the basis of the visualisation at laparoscopy and the histological diagnosis. Histological confirmation rates vary in the current literature. We retrospectively reviewed 160 patients over 2 years, who had laparoscopy for pelvic pain or suspected endometriosis. Our results showed higher histological confirmation rate compared with other studies. In addition, the use of CD10 IHC may increase detection rates further when the diagnosis is suspected but not confirmed by routine histology. Diagnosis of endometriosis is essential as it can influence patients’ management.

Cochrane Database Syst Rev. 2009 Oct 7;(4):CD001300.

Laparoscopic surgery for pelvic pain associated with endometriosis.

Jacobson TZ, Duffy JM, Barlow D, Koninckx PR, Garry R.

Department of Obstetrics and Gynaecology, South Auckland Clinical School, Middlemore Hospital, Private Bag 93311, Auckland, New Zealand.

Update of:

BACKGROUND: Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity. It is variable in both its surgical appearance and clinical manifestation often with poor correlation between the two. Surgical treatment of endometriosis aims to remove visible areas of endometriosis and restore anatomy by division of adhesions and relieve painful symptoms. OBJECTIVES: To assess the efficacy of laparoscopic surgery in the treatment of pelvic pain associated with endometriosis. SEARCH STRATEGY: For the update in July 2009 we searched the Cochrane Menstrual Disorders and Subfertility Group’s specialised register of trials (searched July 2009), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2009), MEDLINE (1966 July 2009), EMBASE (1980 July 2009), and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials were selected comparing the effectiveness of laparoscopic surgery used to treat pelvic pain associated with endometriosis, with other treatment modalities or diagnostic laparoscopy only. DATA COLLECTION AND ANALYSIS: Assessment of trial quality and extraction of relevant data was performed independently by two reviewers. MAIN RESULTS: Five studies were included in the meta-analysis, including three full papers and two conference reports. All the randomised controlled trials with the exception of Lalchandani 2003 compared different laparoscopic surgical techniques with diagnotic laparoscopy only. Lalchandani 2003 compared laparoscopic coagulation therapy with diagnostic laparoscopy and medical treatment. Three studies (Abbott 2004; Sutton 1994; Tutunaru 2006) reported the pain scores six months post operatively. Meta-analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only (OR of 5.72 95%Cl 3.09 to 10.60 ; 171 participants, three trials, Analysis 1.1). A single study (Tutunaru 2006) reported pain scores twelve months after the procedure. Analysis demonstrated an advantage of laparoscopic surgery when compared to diagnostic laparoscopy only (OR of 7.72 95%Cl 2.97 to 20.06 ; 33 participants, one trial, Analysis 1.1). AUTHORS’ CONCLUSIONS: Laparoscopic surgery results in improved pain outcomes when compared to diagnostic laparoscopy alone. There were few women diagnosed with severe endometriosis included in the meta-analysis and therefore any conclusions from this meta-analysis regarding treatment of severe endometriosis should be made with caution. It is not possible to draw conclusions from the meta-analysis which specific laparoscopic surgical intervention is most effective.

Hum Reprod. 2010 Jan;25(1):94-100. Epub 2009 Oct 10.

Norethisterone acetate in the treatment of colorectal endometriosis: a pilot study.

Ferrero S, Camerini G, Ragni N, Venturini PL, Biscaldi E, Remorgida V.

Department of Obstetrics and Gynaecology, San Martino Hospital and University of Genoa, Largo R. Benzi 1, 16132 Genoa, Italy. dr@simoneferrero.com

BACKGROUND: This pilot study evaluates the efficacy of norethisterone acetate in treating pain and gastrointestinal symptoms of women with colorectal endometriosis. METHODS: This prospective study included 40 women with colorectal endometriosis, who had pain and gastrointestinal symptoms. Patients received norethisterone acetate (2.5 mg/day) for 12 months; in case of breakthrough bleeding, the dose of norethisterone acetate was increased by 2.5 mg/day. The degree of patient satisfaction with treatment (primary end-point) and the changes in symptoms (secondary end-point) were evaluated. Side effects of treatment were recorded. RESULTS: Norethisterone acetate determined a significant improvement in the intensity of chronic pelvic pain, deep dyspareunia, dyschezia. Treatment determined the disappearance of symptoms related to the menstrual cycle (dysmenorrhea, constipation during the menstrual cycle, diarrhoea during the menstrual cycle and cyclical rectal bleeding). The severity of diarrhoea, intestinal cramping and passage of mucus significantly improved during treatment. On the contrary, the administration of norethisterone acetate did not determine a significant effect on constipation, abdominal bloating and feeling of incomplete evacuation after bowel movements. At the completion of treatment, 57% of the patients with diarrhoea or diarrhoea during the menstrual cycle continued the treatment with norethisterone acetate compared with 17% of the patients with constipation or constipation during the menstrual cycle. CONCLUSIONS: In some patients with bowel endometriosis, the administration of norethisterone acetate may determine a relief of pain and gastrointestinal symptoms. This therapy has greater benefits in patients with gastrointestinal symptoms related to the menstrual cycle, diarrhoea and intestinal cramping.

Pain. 2009 Dec 15;147(1-3):255-64. Epub 2009 Oct 12.

Endometriosis-induced vaginal hyperalgesia in the rat: role of the ectopic growths and their innervation.

McAllister SL, McGinty KA, Resuehr D, Berkley KJ.

Program in Neuroscience, Florida State University, Tallahassee, FL 32306-4301, USA.

Endometriosis is a painful disorder defined by extrauteral endometrial growths whose contribution to pain symptoms is poorly understood. Endometriosis is created in rats by autotransplanting on abdominal arteries pieces of either uterus (ENDO), which form cysts, or fat (shamENDO), which do not form cysts. ENDO, but not shamENDO induces vaginal hyperalgesia. We tested the hypothesis that the cysts are necessary to maintain vaginal hyperalgesia by assessing the effect of surgically removing them. Complete-cyst-removal eliminated ENDO-induced vaginal hyperalgesia up to 4 months post-operatively. Sham-cyst-removal in ENDO rats, in which cysts were not removed, or partial cyst-removal increased the ENDO-induced hyperalgesia. The decreases and increases both took 3-6 weeks to develop. Changes in ENDO-induced hyperalgesia did not occur in a control group of ENDO rats who had no surgery after ENDO. In a double-surgery control group, neither shamENDO surgery nor a subsequent sham surgery that mimicked “removal” of non-existent cysts influenced vaginal nociception. In a no-surgery control group, vaginal nociception remained stable for >6 months. The increases in ENDO-induced hyperalgesia produced by the sham-cyst-removal surgery were smaller in proestrus than in other estrous stages. During the other stages (but not during proestrus), sympathetic innervation of the cysts increased. These results suggest that maintenance of ENDO-induced vaginal hyperalgesia requires continued presence of at least some ectopic endometrial tissue, and that surgical treatment that fails to remove ectopic endometrial tissue can exacerbate the hyperalgesia, possibly due in part to an increase in the cysts’ sympathetic innervation.

Int J Gynaecol Obstet. 2010 Jan;108(1):21-5.

A dose-ranging study to determine the efficacy and safety of 1, 2, and 4mg of dienogest daily for endometriosis.

Köhler G, Faustmann TA, Gerlinger C, Seitz C, Mueck AO.

Department of Gynecology and Obstetrics, University of Greifswald, Greifswald, Germany. koehlerg@uni-greifswald.de

OBJECTIVES: To compare the efficacy and safety of dienogest at doses of 1, 2, and 4mg/day orally in the treatment of endometriosis. METHODS: An open-label, randomized, multicenter, 24-week comparative trial in women with histologically confirmed endometriosis. Efficacy was assessed by second-look laparoscopy and patient-reported symptoms. Statistical tests included chi(2) and Wilcoxon signed rank tests. RESULTS: Dienogest reduced mean revised American Fertility Society scores from 11.4 to 3.6 (n=29; P<0.001) in the 2-mg group and from 9.7 to 3.9 (n=35; P<0.001) in the 4-mg group. Dienogest at 2 and 4mg/day was associated with symptom improvements in substantial proportions of women. Both dienogest doses were generally well tolerated, with low rates of treatment discontinuation due to adverse events. The 1-mg dose arm was discontinued owing to insufficient bleeding control. CONCLUSION: Dienogest at 2mg once a day is recommended as the optimal dose in future studies of endometriosis.

Reprod Biol Endocrinol. 2009 Oct 12;7:109.

Laparoscopic conservative management of ureteral endometriosis: a survey of eighty patients submitted to ureterolysis.

Camanni M, Bonino L, Delpiano EM, Berchialla P, Migliaretti G, Revelli A, Deltetto F.

1GINTEAM Unit of Minimally Invasive Gynaecology, Corso Marconi 35, 10125 Turin, Italy. marcocamanni@tiscali.it

BACKGROUND: this study aims to evaluate the effectiveness and safety of laparoscopic conservative management of ureteral endometriosis. METHODS: Eighty cases of histologically confirmed endometriosis affecting the ureter, 10 of which with bladder involvement were prospectively studied. In detail, patients were 13 women with ureteral stenosis (7 with hydronephrosis), 32 with circular lesions totally encasing the ureter, and 35 with endometriotic foci on the ureteral wall, but not completely encasing it. They were submitted to laparoscopic ureterolysis with or without partial cystectomy, ureteroneocistostomy. The rate of surgical complications, the recurrence rate, the patients’ satisfaction rate was assessed during 22 months (median) follow-up. RESULTS: Laparoscopic ureterolysis was employed for all patients and set free the ureter from the disease in 95% of cases, whereas ureteroneocystostomy was necessary for 4 patients showing severe stenosis with hydronephrosis, among which 2 had intrinsic endometriosis of the ureteral muscularis. Three post-surgery ureteral fistulae occurred in cases with ureteral involvement longer than 4 cm: two cases were successfully treated placing double J catheter, the third needed ureteroneocistostomy. During follow-up, ureteral endometriosis recurred in 2 patients who consequently underwent ureteroneocystostomy. Most patients expressed high satisfaction rate throughout the whole follow-up period. CONCLUSION: laparoscopic ureterolysis is effective and well tolerated in most cases of ureteral endometriosis. Ureteroneocystostomy is a better strategy for patients with extended (more than 4 cm) ureteral involvement or with severe stenosis with or without hydronephrosis.

Sci Total Environ. 2009 Dec 15;408(1):37-42. Epub 2009 Oct 6.

Urinary phthalate monoesters and endometriosis in infertile Japanese women.

Itoh H, Iwasaki M, Hanaoka T, Sasaki H, Tanaka T, Tsugane S.

Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Phthalates may act as an estrogen and are a potential risk factor for estrogen-related diseases such as endometriosis. We assessed the association between phthalate exposure and endometriosis in 166 consecutive women who presented at a university hospital for consultation regarding infertility. The subjects were interviewed and provided a urine specimen prior to a laparoscopic diagnosis of endometriosis. They were then categorized by the severity of endometriosis as controls (stages 0-I) and cases (stages II-IV). Urinary concentrations of the phthalate metabolites monoethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-oxohexyl) phthalate, and mono(2-ethyl-5-hydroxyhexyl) phthalate were measured in 57 cases and 80 controls using high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Adjusted odds ratios for endometriosis in relation to dichotomized individual phthalate metabolites (standardized for creatinine) were calculated. No significant association between endometriosis and any urinary creatinine-adjusted phthalate monoester was seen. Adjusted odds ratio (95% confidence interval) for higher dichotomized MEHP by endometriosis was 1.57 (0.74-3.30). No monotonic trend was seen in urinary creatinine-adjusted concentration of phthalate metabolites by endometriosis stage (p=0.23-0.90). Our results do not support the hypothesis that higher urinary concentrations of phthalate metabolites are associated with the risk of endometriosis in infertile Japanese women.

Reprod Sci. 2010 Jan;17(1):47-55. Epub 2009 Oct 2.

Haptoglobin expression in endometrioid adenocarcinoma of the uterus.

Nabli H, Tuller E, Sharpe-Timms KL.

Division of Reproductive and Perinatal Research, The Department of Obstetrics and Gynecology and Women’s Health, The University of Missouri-Columbia, Columbia, Missouri 65212, USA.

OBJECTIVE: Elevated serum haptoglobin (Hp) concentrations have been reported in patients with malignant diseases. We have shown that Hp is produced by and localizes only in the stroma and not the epithelium of endometriotic lesions, which share many characteristics of carcinoma. Furthermore, Hp mRNA and protein are found exclusively in the stroma of eutopic endometrium from women with endometriosis and not those without endometriosis. We hypothesized that characteristic patterns of Hp gene expression and protein localization in endometrioid adenocarcinoma of the uterus may provide insight into the clinical utility of Hp as a tumor marker or alternative therapeutic approach. METHODS: Biopsies of endometrioid adenocarcinoma tumors of the uterus and their adjacent nonaffected endometrium were collected. Normal endometrium was collected from healthy women. Haptoglobin messenger RNA (mRNA) levels were quantified by quantitative polymerase chain reaction (Q-PCR). Haptoglobin protein cell-specific localization was identified by immunohistochemistry. RESULTS: Haptoglobin mRNA levels were significantly greater (P < .005) in endometrioid adenocarcinoma and adjacent nonaffected endometrial tissues than normal endometrium. No correlation was found between Hp levels and cancer stage (P = .673) or grade (P = .739). Haptoglobin protein localized in both stromal and glandular epithelial cells of endometrioid adenocarcinoma and their adjacent nonaffected tissue but not in control endometrium. CONCLUSIONS: Our results have identified, for the first time, unique patterns of Hp mRNA expression and protein localization in the stromal and glandular epithelial cells of endometrioid adenocarcinoma of the uterus. We propose that this unique pattern of endometrioid adenocarcinoma Hp expression may be developed as a novel diagnostic marker. Modulation of Hp, with its immunomodulatory and angiogenic properties, may generate novel methods of prevention or treatment for endometrial cancer.

Urology. 2009 Dec;74(6):1191-4. Epub 2009 Oct 2.

A 45-year-old woman with an asymptomatic, extensive bladder mass.

Potepalov S, Bilello S, Gomelsky A.

Department of Urology, Louisiana State University, Health Sciences Center, Shreveport, Louisiana 71130, USA.

Eur J Obstet Gynecol Reprod Biol. 2010 Jan;148(1):49-52.

The impact of IVF procedures on endometriosis recurrence.

Benaglia L, Somigliana E, Vercellini P, Benedetti F, Iemmello R, Vighi V, Santi G, Ragni G.

Infertility Unit, Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy. laurabenaglia@hotmail.it

OBJECTIVE: In infertile women with endometriosis requiring an in vitro fertilization (IVF) procedure, the potential risk of an IVF-related progression of the disease remains a matter of debate. Thus, since available data on this issue are scanty and controversial, an observational study has been herein conducted in order to clarify this issue. STUDY DESIGN: We recruited 233 women with endometriosis who underwent IVF cycles in our unit. Patients were contacted to assess whether they experienced recurrences of the disease after IVF. The main outcome was to evaluate the impact of the number of IVF cycles and the responsiveness to ovarian hyperstimulation on the likelihood of recurrence. Clinical characteristics of women who did and did not have a recurrence were compared. RESULTS: One hundred and eighty-nine women were included, 41 of whom (22%) had a diagnosis of endometriosis recurrence. The 36 months cumulative recurrence rate was 20%. The number of IVF cycles and the responsiveness to ovarian hyperstimulation were not associated with the risk of disease recurrence. The adjusted OR for recurrences according to the number of started cycles was 0.92 (95% CI: 0.77-1.10) per cycle (p=0.35). The adjusted OR for recurrences in women with intact versus compromised ovarian reserve was 0.80 (95% CI: 0.40-1.58) (p=0.52). CONCLUSIONS: IVF procedures do not seem to influence the likelihood of endometriosis recurrence.

Fertil Steril. 2009 Dec;92(6):2037.e19-21. Epub 2009 Oct 1.

Malignant transformation of residual endometriosis after hysterectomy: a case series.

Karanjgaokar VC, Murphy DJ, Samra JS, Mann CH.

Department of Gynaeoncology, New Cross Hospital, Wolverhampton, West Midlands, Wolverhampton, United Kingdom. vrnkar@aol.com

OBJECTIVE: To explore the role of long-standing hormone replacement therapy (HRT) in the malignant transformation of endometriosis. DESIGN: Short case series. Three cases of women with pelvic clearance receiving long-standing HRT studied in detail. SETTING: Teaching hospital in the United Kingdom (Gynaecological Cancer Centre) (Institutional Review Board approval was not obtained as it was not deemed necessary, this being a case series). PATIENT(S): Women with a history of pelvic clearance for endometriosis and longstanding HRT. INTERVENTION(S): HRT. MAIN OUTCOME MEASURE(S): Malignant transformation of endometriosis. RESULT(S): Long-standing HRT in all three women with pelvic clearance for endometriosis resulted in malignant transformation of residual endometriosis many years after the initial surgery. All cases presented with a new pelvic lesion. CONCLUSION(S): The diagnosis of malignant transformation needs to be considered in women with a history of endometriosis and with long-term HRT use in whom a new pelvic lesion is detected. The risk of malignant transformation in women with endometriosis after pelvic clearance receiving HRT needs to be explored further. Surveillance with CA-125 and imaging in such cases to predict recurrence or malignant transformation needs to be studied further in a research setting.

Hum Reprod Update. 2010 Mar-Apr;16(2):131-41. Epub 2009 Sep 30.

Should the ovaries be removed or retained at the time of hysterectomy for benign disease?

Hickey M, Ambekar M, Hammond I.

School of Women’s and Infants’ Health, University of Western Australia, King Edward Memorial Hospital, Subiaco, WA, Australia. mhickey@meddent.uwa.edu.au

BACKGROUND: Bilateral oophorectomy is commonly performed at the time of hysterectomy for benign disease. Indications for oophorectomy vary, but in most cases relatively little high-quality information is available to inform the surgeon or patient regarding the relative risks and benefits of ovarian conservation or removal. This review will address the common clinical situations when oophorectomy may be performed and will evaluate the evidence for risk and benefit in each of these circumstances. The aim of this review is to bring together the evidence regarding oophorectomy in pre- and post-menopausal women and to highlight the areas needing further study. METHODS: We searched the published literature for studies related to outcomes following surgical menopause, risk-reducing surgery for ovarian cancer, surgical treatment for endometriosis, bilateral oophorectomy for benign disease and treatment for premenstrual syndrome/premenstrual dysphoric disorder. RESULTS: Rates of oophorectomy at the time of hysterectomy for benign disease appear to be increasing. There is good evidence to support bilateral salpingoophorectomy (BSO) as a risk-reducing surgery for women at high risk of ovarian cancer, but relatively little evidence to support oophorectomy or BSO in other circumstances. There is growing evidence from observational studies that surgical menopause may impact negatively on future cardiovascular, psychosexual, cognitive and mental health. CONCLUSION: Clinicians and patients should fully consider the relative risks and benefits of oophorectomy on an individual basis prior to surgery.

Expert Opin Ther Pat. 2009 Nov;19(11):1521-34.

Recent patent trends in the field of progesterone receptor agonists and modulators.

Schmees N, Weinmann H.

Bayer Schering Pharma, Medicinal Chemistry, Muellerstrasse 178, 13353 Berlin, Germany. norbert.schmees@bayerhealthcare.com

BACKGROUND: Progesterone receptor agonists are used in female contraception, hormone replacement therapy or some gynecological conditions like endometriosis. The interest for antagonists or selective progesterone receptor modulators (SPRMs) is growing. Recent reports on this class of compounds indicate that they could become the next generation of therapeutics in gynecological treatments. OBJECTIVE: This overview summarizes the work on progesterone receptor agonists, SPRMs and antagonists reported in the patent literature in the past 4 years. METHODS: The focus of the article is the examination of patents, primarily published as WO, EU or US patents since 2005. In some cases, additional data from the public literature is included into the discussion. These data are of substantial interest as the available biological data disclosed in patents are usually limited for new compound classes. RESULTS/CONCLUSION: Some highly active clusters of compounds have been disclosed in the past 4 years. The current research seems to focus on SPRMs and progesterone receptor antagonists.

Int J Gynaecol Obstet. 2010 Jan;108(1):16-20.

Primary squamous cell carcinoma of the ovary associated with endometriosis.

Acién P, Abad M, Mayol MJ, Garcia S, Garde J.

Department of Obstetrics and Gynecology, San Juan University Hospital, Alicante, Spain. acien@umh.es

OBJECTIVE: To analyze the clinical, therapeutic, and pathologic features of published cases presenting primary squamous cell carcinoma (SCC) of the ovary associated with endometriosis. METHODS: A case report, 15 cases of infiltrating SCC of the ovary associated with or arising from endometriosis, and 1 case of synchronous carcinoma in situ in the cervix and ovary from a review of the literature were studied. RESULTS: Young age, advanced stage of the disease, and hypogastric pain were frequent at the time of diagnosis. There was no ascites, but infiltration of neighboring organs was common. The tumor was associated with 80% patient mortality in the first few months. Adjuvant chemotherapy with paclitaxel and carboplatin or cisplatin appeared to improve the results. CONCLUSION: Primary SCC of the ovary associated with endometriosis is extremely rare and has a poor prognosis. The best therapeutic results are obtained with paclitaxel and carboplatin or cisplatin after radical surgery.

Chin Med J (Engl). 2009 Sep 5;122(17):2079-80.

A gastric duplication cyst at the splenic hilum mimicking endometriosis clinically in a female adult.

Hsu HT, Hsing MT, Chen ML, Chen CJ.

Department of Surgical Pathology, Changhua Christian Hospital, Changhua, 500 Taiwan, China.

Aust N Z J Obstet Gynaecol. 2009 Oct;49(5):554-7.

The obstructed hemivagina, ipsilateral renal anomaly, uterus didelphys triad.

Kimble RM, Khoo SK, Baartz D, Kimble RM.

Department of Obstetrics and Gynaecology, 5th Floor Ned Hanlon Building, Royal Brisbane and Women’s Hospital, Herston, Qld 4029, Australia. rebecca_kimble@health.qld.gov.au

The triad of obstructed hemivagina, renal anomaly and uterus didelphys is an uncommon cause of abdominal pain and menstrual discomfort in adolescent girls. Accurate diagnosis and surgical treatment can be delayed for several months or even years. Adolescent girls presenting with these symptoms should have a baseline pelvic ultrasound scan to establish uterine anatomy. In those with ultrasound findings of Müllerian anomalies appropriate follow up would include a magnetic resonance imaging, preferably at a tertiary centre with expertise in interpretation of Müllerian anatomy, as well as early consultation and referral to a centre with experience in the management of these rare conditions. Appropriate surgery would be a single stage procedure to either excise or completely divide the obstructing septum. There is currently no consensus on concurrent laparoscopy. We present a case series of four patients with the triad of uterus didelphys, obstructed hemivagina and ipsilateral renal agenesis managed between 2005-2009 at a tertiary centre for paediatric and adolescent gynaecology.

Urologe A. 2009 Oct;48(10):1193-4,1196-8.

Chronic pelvic pain in women from a gynecologic viewpoint.

[Article in German]

Siedentopf F.

Frauenklinik, DRK-Kliniken Westend, Berlin. f.siedentopf@drk-kliniken-berlin.de

Chronic pelvic pain in women is a difficult subject that challenges the gynecologist in practice. Possible gynecological causes are endometriosis, adhesions/PID, pelvic varicosis and ovarian retention syndrome/ovarian remnant syndrome. Other somatic causes are irritable bowel syndrome, bladder pain syndrome and fibromyalgia.Confirmed psychosocial factors contributing to chronic pelvic pain are comorbidity with anxiety disorders, substance abuse or depression, but the influence of social factors is less certain. The connection to physical and sexual abuse also remains unclear. Important diagnostic steps are studying the patient’s history, a gynecological examination and laparoscopy. Multidisciplinary therapeutic approaches are helpful. Basic psychosomatic care and psychotherapy should be integrated into the therapeutic concept at an early stage of the disease.

J Clin Lab Anal. 2009;23(5):331-5.

The utility of serum human epididymis protein 4 (HE4) in patients with a pelvic mass.

Montagnana M, Lippi G, Ruzzenente O, Bresciani V, Danese E, Scevarolli S, Salvagno GL, Giudici S, Franchi M, Guidi GC.

Sezione di Chimica Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università degli Studi di Verona, Verona, Italy. martina.montagnana@med.lu.se

AIM: Although CA125 is the most widely used cancer marker in the diagnostic approach of pelvic masses in women, its clinical usefulness is limited because it lacks expression of the antigen in the early stages of disease. The human epididymis protein 4 (HE4) is frequently over-expressed in ovarian cancer, whereas its expression in normal tissues, including the ovary, is low. The aim of this study was to assess the concentration of both HE4 and CA125 in patients with different forms of benign and malign pelvic masses. METHODS: The study population included 99 patients with gynecological cancer (46 ovarian, 39 endometrial, 14 cervical) and 40 affected by benign disease (22 endometriosis and 18 benign ovarian mass). Twelve control subjects were also included in the study. In all the patients, serum samples were collected on the day before scheduled surgery. RESULTS: The median CA125 and HE4 serum levels were significantly higher among ovarian cancer patients as compared with healthy subjects and with those with benign mass, cervical, and endometrial tumors. The receiver operating characteristics curve analysis on healthy controls and patients with ovarian cancers revealed that HE4 had a significantly higher area under the curve when compared with CA125 (0.99 vs. 0.91), with a sensibility and specificity of 98 and 100%, respectively. CONCLUSIONS: HE4 seems to be a promising ovarian cancer marker, and its measurement might improve the diagnostic approach to patients with pelvic masses.

Hum Reprod Update. 2010 Mar-Apr;16(2):142-65. Epub 2009 Sep 22.

The role of microRNAs in endometriosis and associated reproductive conditions.

Teague EM, Print CG, Hull ML.

School of Paediatrics and Reproductive Health, Research Centre for Reproductive Health, Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA 5005, Australia. maria.teague@adelaide.edu.au

BACKGROUND: microRNAs (miRNAs) are short, single-stranded RNAs that regulate gene expression at the post-transcriptional level. Recent research has shown that miRNAs and their target mRNAs are differentially expressed in endometriosis and other disorders of the female reproductive system. Since miRNAs control a broad spectrum of normal and pathological cellular functions, they may play pivotal roles in the pathogenesis of these disorders. METHODS: A systematic review was undertaken of the published literature on; (i) the expression and functions of miRNAs in mammalian female reproductive tissues with a focus on endometriosis and the malignancies and fertility disorders related to this disease; and (ii) the potential roles played by validated mRNA targets of endometriosis-associated miRNAs. The current understanding of the biology of miRNAs is overviewed and the potential diagnostic and therapeutic potential of miRNAs in endometriosis is highlighted. RESULTS: The differential expression of miRNAs in endometriosis, and the putative molecular pathways constituted by their targets, suggests that miRNAs may play an important role in endometriotic lesion development. Models for miRNA regulatory functions in endometriosis are presented, including those associated with hypoxia, inflammation, tissue repair, TGFbeta-regulated pathways, cell growth, cell proliferation, apoptosis, extracellular matrix remodelling and angiogenesis. In addition, specific miRNAs which may be associated with malignant progression and subfertility in endometriosis are discussed. CONCLUSIONS: miRNAs appear to be potent regulators of gene expression in endometriosis and its associated reproductive disorders, raising the prospect of using miRNAs as biomarkers and therapeutic tools in endometriosis.

Methods Mol Biol. 2009;590:295-306.

Use of laser capture microdissection in studying hormone-dependent diseases: endometriosis.

Matsuzaki S, Canis M, Mage G.

CHU Clermont-Ferrand, Polyclinique-Hôtel-Dieu, Gynécologie Obstétrique et Médecine de la Reproduction, Clermont-Ferrand Cédex, France.

Endometriosis, a common gynecological disorder responsible for infertility and pelvic pain, is defined as the presence of endometrial glands and stroma within extra-uterine sites. Gene expression studies performed on endometriotic tissue homogenates have yielded results reflecting mRNA abundance in a mixture of cell types (including epithelial cells, stromal cells, fibrotic tissue, and muscle tissue). Therefore, a method for quantifying gene expression separately in individual cell populations is essential for identifying genetic markers. Laser capture microdissection is a technique for obtaining pure populations of cells from heterogeneous tissues. This chapter provides methods to obtain high-quality RNA suitable for a variety of different down stream applications from frozen endometrial and endometriotic tissues for laser capture microdissection, using the Arcturus PixCell II system.

Trop Doct. 2009 Oct;39(4):250-1.

Adenomyosis and uterine rupture during labour in a primigravida: an unusual obstetric emergency in Nigeria.

Dim CC, Agu PU, Dim NR, Ikeme AC.

Department of Obstetrics, University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria. dyme72@yahoo.com

The primigravid uterus is believed to be immune to rupture during labour. This may not be true for those who have had prior adenomyomectomy, hence this report. The patient was a 28-year-old nullipara who became pregnant 11 months after an adenomyomectomy. Twelve hours after vaginal delivery at term, she developed haemoperitoneum of unclear cause. Emergency laparotomy and subsequent histology showed a fundal complete uterine rupture through the adenomyomectomy site, which was repaired. It is concluded that adenomyomectomy predisposes a pregnant uterus to rupture during labour. Therefore, such women should be offered elective caesarean delivery at term.

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