Pag. 20

 

Rev Assoc Med Bras. 2012 Jan-Feb;58(1):26-32.

Evaluation of CA-125 and soluble CD-23 in patients with pelvic endometriosis: a case-control study.

Ramos IM, Podgaec S, Abrão MS, de Oliveira R, Baracat EC.

Source

Endometriosis Division, Obstetrics and Gynecology Department, Universidade de São Paulo, São Paulo, SP, Brazil.

Abstract

OBJECTIVE:

To evaluate serum concentrations of CA-125 and soluble CD-23 and to correlate them with clinical symptoms, localization and stage of pelvic endometriosis and histological classification of the disease.

METHODS:

Blood samples were collected from 44 women with endometriosis and 58 without endometriosis, during the first three days (1st sample) and during the 7th, 8th and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain evaluations (visual analog scale) and biomarkers concentrations.

RESULTS:

Serum levels of CA125 were higher in endometriosis patients when compared to the control group during both periods of the menstrual cycle evaluated in the study. This marker was also elevated in women with chronic pelvic pain, deep dyspareunia (2nd sample), dysmenorrhea (both samples) and painful defecation during the menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages of the disease in both samples and also in women with ovarian endometrioma. Concerning CD-23, no statistically significant differences were observed between groups.

CONCLUSION:

The concentrations of CA-125 were higher in patients with endometriosis than in patients without the disease. No significantly differences were observed for soluble CD-23 levels between groups.

Rev Bras Ginecol Obstet. 2012 Jan;34(1):11-5.

Importance of quality of life assessment in patients with endometriosis.

[Article in Portuguese]

Minson FP, Abrão MS, Sardá Júnior J, Kraychete DC, Podgaec S, Assis FD.

Source

Programo de Dor do Hospital Israelita Albert Einstein, São Paulo, SP, Brasil.

Abstract

PURPOSE:

The present study examined the relationship between some clinical variables and quality of life in a group of patients with endometriosis.

METHODS:

A total of 130 women seen at a multidisciplinary center specializing in gynecology endometriosis in 2008 participated in the study. This was a cross-sectional study conducted with a convenience sample. The diagnosis of endometriosis was performed by biopsy according to the criteria of the American Society for Reproductive Medicine. The clinical and demographic data were collected from the patients’ records. Pain intensity was assessed by a visual numerical scale (0-10), and data on the quality of life were collected using the SF-36. Data analysis consisted of descriptive and inferential statistical tests, Spearman correlation coefficient and Kruskal-Wallis test to compare scores between groups. Nonparametric tests were used for analysis because data were not normally distributed.

RESULTS:

The patients were 21 to 54 years of age or 34, standard diversion (SD)=6.56], 87% had a university degree, and 75% were married. Seventeen percent reported cases of endometriosis in the family. The average time of onset of symptoms was 4.5 years (SD=6.6), 63% of patients were in stage 3 or 4 of endometriosis 36% of patients had severe or disabling dysmenorrhea and the average intensity of pain according to a visual numerical scale was of 5.6 (SD=3.5). Results suggest that the staging of the disease did not determine the intensity of pain. The time of onset of symptoms also showed no relationship to pain intensity and SF-36 scores. On the other hand, the intensity of pain was associated with lower scores on some scales of the SF-36.

CONCLUSION:

Patients with endometriosis had lower scores of quality of life than the general population and lower than those of some other diseases.

Rofo. 2012 Jan;184(1):48-52. Epub 2011 Dec 9.

Change in health-related quality of life and change in clinical symptoms after uterine artery embolization in patients with symptomatic adenomyosis uteri – evaluation using a standardized questionnaire.

[Article in German]

Froeling V, Scheurig-Muenkler C, Steffen IG, Schreiter NF, Kröncke TJ.

Source

Universitätsmedizin Charité Berlin, Radiologie, Berlin. vera.froeling@charite.de

Abstract

AIM:

To evaluate the clinical response of uterine artery embolization (UAE) in women with symptomatic uterine adenomyosis by comparing health-related quality of life and symptom severity before and after UAE using a standardized questionnaire.

MATERIAL AND METHODS:

This longitudinal study at two time points included 17 patients with a median age of 47.1 years with symptomatic uterine adenomyosis (n = 7 pure adenomyosis; n = 10 with concomitant fibroids). The diagnosis was based on clinical symptoms and magnetic resonance imaging (MRI) criteria. Data on health-related quality of life and severity of symptoms before and after UAE were obtained by the standardized “Uterine Fibroid Symptom and Quality of Life” (UFS-QOL) questionnaire and correlated in the following. Treatment failure was defined as the need for a second invasive procedure because of recurrent symptoms or persistent symptoms after UAE.

RESULTS:

The median interval between the evaluation of the UFS-QOL questionnaire before and after UAE was 46.0 months. 70.6 % (12/17; 95 % confidence interval 44.0 %  - 88.6 %) of the patients had therapy response with a significant improvement of health-related quality of life and clinical symptoms (p-value = 0.002). The therapy failure rate was 29.4 % (5/17; 95 % confidence interval 11.4 %  – 56.0 %). One patient underwent dilatation and curettage and four patients underwent hysterectomy because of therapy failure.

CONCLUSION:

UAE to treat symptomatic adenomyosis uteri can significantly improve the health-related quality of life and clinical symptoms. However, therapy failure is possible in up to one-third of patients.

Rom J Morphol Embryol. 2012;53(2):433-7.

Ureteral stenosis due to endometriosis.

Traşcă ET, Traşcă E, Tiţu A, Riza ML, Busuioc I.

Source

Department of Surgery, University of Medicine and Pharmacy of Craiova, Romania; etrasca@yahoo.com.

Abstract

Endometriosis is characterized by the presence of endometrial tissue outside the uterine cavity, with potential to undergo malignant transformation. We report the case of a 36-year-old patient with a clinical and imagistic diagnosis of left vaginal pouch and left parametrium tumor. The patient presented lumbar and pelvic pain, dysuria and polakyuria. Ultrasound revealed changes in the left kidney confirmed by the CT scan, which also revealed the presence of a tumor in the left parametrium infiltrating the bladder, juxtavesical ureter, uterus and cervix. Laboratory tests were within normal limits. Surgery consisted of interadnexal hysterectomy, proximal colpectomy, left distal ureterectomy with ureterocystoneostomy. Pathological examination established the final diagnosis of infiltrative deep endometriosis involving the urinary tract. In the case of a young fertile patient with gynecological symptoms and morphofunctional changes of the urinary system, urinary tract endometriosis should always be a diagnostic option.

Semin Reprod Med. 2012 Jan;30(1):39-45. Epub 2012 Jan 23.

Role of estrogen receptor-β in endometriosis.

Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, Tokunaga H, Su EJ.

Source

Division of Reproductive Biology Research, Department Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. s-bulun@northwestern.edu

Abstract

Endometriosis is an estrogen-dependent disease. The biologically active estrogen, estradiol, aggravates the pathological processes (e.g., inflammation and growth) and the symptoms (e.g., pain) associated with endometriosis. Abundant quantities of estradiol are available for endometriotic tissue via several mechanisms including local aromatase expression. The question remains, then, what mediates estradiol action. Because estrogen receptor (ER)β levels in endometriosis are >100 times higher than those in endometrial tissue, this review focuses on this nuclear receptor. Deficient methylation of the ERβ promoter results in pathological overexpression of ERβ in endometriotic stromal cells. High levels of ERβ suppress ERα expression. A severely high ERβ-to-ERα ratio in endometriotic stromal cells is associated with suppressed progesterone receptor and increased cyclo-oxygenase-2 levels contributing to progesterone resistance and inflammation. ERβ-selective estradiol antagonists may serve as novel therapeutics of endometriosis in the future.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Semin Reprod Med. 2012 Jan;30(1):3-4. Epub 2012 Jan 23.

The important role of estrogen receptor-β in women’s health.

Su EJ.

 

Steroids. 2012 Jan;77(1-2):27-35. Epub 2011 Nov 13.

Tissue physiology and pathology of aromatase.

Stocco C.

Source

Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, United States. costocco@uic.edu

Abstract

Aromatase is expressed in multiple tissues, indicating a crucial role for locally produced oestrogens in the differentiation, regulation and normal function of several organs and processes. This review is an overview of the role of aromatase in different tissues under normal physiological conditions and its contribution to the development of some oestrogen-related pathologies.

Tohoku J Exp Med. 2012;226(2):95-9.

Primate model research for endometriosis.

Yamanaka A, Kimura F, Takebayashi A, Kita N, Takahashi K, Murakami T.

Source

Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Japan. ykiyoshi@belle.shiga-med.ac.jp

Abstract

Endometriosis is defined as the existence of endometrial tissue outside the uterine cavity, and it includes a chronic, inflammatory reaction associated with female infertility and pelvic pain. Endometriosis occurs in 7 to 10% of women. Although it has been studied for more than 50 years, the pathogenesis and development of endometriosis are still poorly understood. There is no curative therapy for endometriosis, which often recurs after surgical or medical treatment. There is a consensus that the adverse current of menstrual blood plays a crucial role in the development of endometriosis. This places a major limitation on research using rodent models of endometriosis, although these are still widely employed, because rodents do not menstruate and endometriosis does not occur spontaneously in these animals. In fact, menstruation and spontaneous endometriosis only occur in women and some non-human primates, making models that employ non-human primates the best animal models for research into the pathogenesis, pathophysiology, spontaneous onset, and treatment of endometriosis. This review assesses the effectiveness and potential of the non-human primate models of endometriosis. It also describes the current findings and theories on the pathogenesis of endometriosis that have been obtained by research using non-human primates.

Ultrasound Obstet Gynecol. 2012 Jan;39(1):106-9. doi: 10.1002/uog.9062. Epub 2011 Dec 5.

Endometrial cancer and ultrasound: why measuring endometrial thickness is sometimes not enough.

Naftalin J, Nunes N, Hoo W, Arora R, Jurkovic D.

Source

University College Hospital, London, UK.

Abstract

Endometrial cancer is the commonest cancer of the female genital tract in the developed world. Ultrasound measurement of endometrial thickness is commonly used to triage patients with postmenopausal bleeding for histological sampling. The sensitivity of ultrasound in diagnosing endometrial cancer is high, but it has a small, well-defined false-negative rate. In this report we describe two cases, with histological confirmation, of postmenopausal women without any vaginal bleeding, who were subsequently diagnosed with advanced endometrial cancer. They were found to have a thin, normal endometrium on ultrasound. In both cases, histological examination was suggestive of endometrial cancer originating from foci of adenomyosis. These findings suggest that a proportion of the false-negative diagnoses of endometrial cancer on ultrasound could be caused by the disease being confined to the myometrium rather than as a result of suboptimal performance of ultrasound examination.

Urol Ann. 2012 Jan;4(1):6-12.

Urinary tract endometriosis: Review of 19 cases.

Kumar S, Tiwari P, Sharma P, Goel A, Singh JP, Vijay MK, Gupta S, Bera MK, Kundu AK.

Source

Department of Urology, IPGME and R, SSKM Hospital, Kolkata, India.

Abstract

AIM:

The aim of our study was to evaluate the treatment outcomes of medical and surgical management of urinary tract endometriosis.

MATERIALS AND METHODS:

Urinary tract endometriosis patients enrolled between Jan 2006 and May 2010 were retrospectively reviewed. Preoperative datas (mode of presentation, diagnosis, imaging), intraoperative findings (location and size of lesion), postoperative histopathology and follow-up were recorded and results were analyzed and the success rate of different modalities of treatment was calculated.

RESULTS:

In our study, of nineteen patients, nine had vesical involvement and ten had ureteric involvement. Among the vesical group, the success rate of transurethral resection followed by injection leuproide was 60% (3/5), while among the partial cystectomy group, the success rate was 100%. Among patients with ureteric involvement, success rate of distal ureterectomy and reimplantation was 100%, laparoscopic ureterolysis with Double J stenting followed by injection leuprolide was 75% while that of Gonadotropin- releasing hormone (GnRh) analogue alone was 67%.

CONCLUSION:

One should have a high index of suspicion with irritative voiding symptoms with or without hematuria, with negative urine culture, in all premenopausal women to diagnose urinary tract endometriosis. Partial cystectomy is a better alternative to transurethral resection followed by GnRh analogue in vesical endometriosis. Approach to the ureter must be individualised depending upon the severity of disease and dilatation of the upper tract to maximise the preservation of renal function.

Virchows Arch. 2012 Jan;460(1):77-87. Epub 2011 Nov 26.

PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma.

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

Source

Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan. dr21001@ndmc.ac.jp

Abstract

Somatic mutations of PIK3CA and ARID1A are the most common genetic alterations observed in ovarian clear cell adenocarcinomas (CCA). In a previous report, we showed that PIK3CA gene mutations and loss of ARID1A expression occur early during the development of CCA. In the present study, using direct genomic DNA sequencing for exons 9 and 20 of PIK3CA and immunohistochemistry for ARID1A protein expression, we analyzed the association of these molecular alterations with various clinicopathological parameters in a total of 90 cases of primary ovarian CCA, including 42 previously examined cases. The presence of PIK3CA mutations, identified in 34 (39%) of the 88 informative cases, was significantly associated with a grossly cystic tumor, the presence of adjacent endometriosis, prominent papillary architecture of tumor growth, the presence of hyalinized and mucoid stroma, and the absence of clear cell adenofibroma components (P < 0.05, each). There was no significant association of PIK3CA mutations with other clinical variables, such as age, clinical stage, or clinical outcome of the patients. The intensity of immunoreactivity for ARID1A was assigned as negative, weakly positive, and strongly positive in 44%, 22%, and 33% of tumors, respectively. Compared to tumors immunoreactive for ARID1A, ARID1A-negative tumors were significantly associated with the presence of adjacent endometriosis (P = 0.025), but there was no statistically supported association with other examined clinicopathological parameters. Compared with CCAs strongly positive for ARID1A, CCAs negative for ARID1A more frequently harbor PIK3CA mutations (P = 0.013). PIK3CA gene mutations and ARID1A immunohistochemistry lacked prognostic significance. These data further support the idea that these molecular alterations occur as very early events during tumor development of ovarian CCA.

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2012 Jan;28(1):72-3.

Effect of GnRHa on apoptosis and release of VEGF in endometrial cell cultures from patients with adenomyosis.

Xiao-xia W, Jia-li K, Xue-fei S, Jia Y, Ling-hong D.

Source

Department of Gynecology and Obstetrics, The First Municipal People’s Hospital Affiliated to Guangzhou Medical College, Guangzhou, China. wxx605@sohu.com

Abstract

AIM:

To investigate the effect of Gonadotropin-realeasing hormone agonist (GnRHa) on apoptosis and the release of vascular endothelial growth factor (VEGF) in the in vitro eutopic endometrial cell of adenomyosis.

METHODS:

Biopsy specimens of eutopic endometrium obtained from 32 women with adenomyosis and 20 normal womenwere studied. Cells were cultured with GnRHa for 24 h, 48 h and 72 h in the concentration of 10-7 mol/L and 105 mol/L. Apoptotic ratio was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and flow cytometry before and after using GnRHa. VEGF concentrations in culture supernatant were detected by commercial enzyme-linked immunosorbent assay (ELISA).

RESULTS:

(1)Cells in two groups showed cell shrinkage, floating, nucleus concentration, nuclear fragmentation and typical apoptotic bodies. (2) The apoptotic ratio of cultured AM endometrial cell without GnRHa was lower than that in control group and the apoptotic ratio increased with the prolongation of time in two groups(P<0.01). (3)After GnRHa addition, each group showed higher apoptotic ratio and a trend towards higher apoptotic ratio linked to advanced concentration. Furthermore, apoptotic ratio in study group was significantly higher than that in control group at the same time point and same concentration ( P < 0. 01 ). ( 4 ) The concentrations of VEGF in the eutopic endometrial cells of adenomyosis were significantly higher than those in the normal endometrimn. The concentrations of VEGF in the both groups were downregulated by GnRHa in a dose-dependent manner.

CONCLUSION:

(1) The abnormality of apoptotic ratio of AM endometrial cells may be associated with the AM pathogenesis. GnRHa nmy increase the apoptotic ratio of cultured AM endometrial cells by autocrine or paracrine. (2) VEGF may play an impotant role in the pathogenesis of adenomyosim. GnRHa can directly suppress the survival and growth of ectopic endometrial by decreasing the release of VEGF which was related to the adenomyosis angiogenesis.

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2012 Jan;37(1):94-9.

Expression of DNMT1, DNMT3a, and DNMT3b in eutopic endometrium.

[Article in Chinese]

Yang J, Fang X.

Source

Department of Gynecologic Oncology, Tumor Hospital of Hunan Province, Changsha, China.

Abstract

OBJECTIVE:

To examine the expression of DNMT1, DNMT3a, and DNMT3b in the eutopic and ectopic endometrium in women with endometriosis.

METHODS:

RT-PCR and real-time RT-PCR were used to examine the expression of DNMT1, DNMT3a, and DNMT3b in the eutopic and ectopic endometrium in 20 women with endometriosis and the endometrium in 20 women without endometriosis. Immunofluorescene staining was used to detect the expression of DNMT1 in these tissues.

RESULTS:

The expression levels of DNMT1, DNMT3a, and DNMT3b were significantly lower in the ectopic endometrium and eutopic endometrium than those of the control endometium (P<0.05). The changes in the ectopic endometium compared with the control endometium were 0.44, 0.12, and 0.27 folds for DNMT1, DNMT3a, and DNMT3b, respectively, and these in the eutopic endometrium were 0.27, 0.13, and 0.15 folds for DNMT1,DNMT3a, and DNMT3b, respectively. The expression level of DNMT1, DNMT3a, and DNMT3b between the ectopic endometrium and eutopic endometrium was not significantly different (P>0.05 ). Immunofluorescence staining that DNMT1 protein level significantly decreased in the ectopic endometrium and eutopic endometrium of endometriosis patients.

CONCLUSION:

Decreased expression levels of DNMT1, DNMT3a, and DNMT3b in the ectopic endometrium and eutopic endometrium may play a role in patients with abnormal epigenetics which may lead to endometriosis.

Ann Ital Chir. 2011 Dec 21. pii: S0003469X11018100. [Epub ahead of print]

Intestinal occlusion caused by endometriosis of the sigmoid colon A case report and review of the literature.

Conzo G, Docimo G, Candela G, Palazzo A, Della Pietra C, Mauriello C, Santini L.

Abstract

Endometriosis (E), an estrogen-dependent inflammatory disorder in which endometrial tissue develops outside uterus, is found in approximately 10% of women in childbearing age and in 15-20% of cases is associated with sterility. There is intestinal involvement, especially of the sigmoid colon and rectum, in about 5% of patients 1. The differential diagnosis of rectosigmoid E can be complex since it includes conditions like diverticulitis, Crohn’s disease,actinic colitis and cancer, all of which can cause similar signs &symptoms 2. The authors report a case of intestinal endometriosis in which the clinical picture and imaging suggested a diagnosis of intestinal occlusion due to sigmoid colon cancer, with indication to emergency colorectal resection.

AAPS J. 2011 Dec;13(4):665-73. Epub 2011 Oct 25.

Population pharmacokinetics of telapristone (CDB-4124) and its active monodemethylated metabolite CDB-4453, with a mixture model for total clearance.

Morris D, Podolski J, Kirsch A, Wiehle R, Fleckenstein L.

Source

College of Pharmacy, University of Iowa, Iowa City, 52242, USA.

Abstract

Telapristone is a selective progesterone antagonist that is being developed for the long-term treatment of symptoms associated with endometriosis and uterine fibroids. The population pharmacokinetics of telapristone (CDB-4124) and CDB-4453 was investigated using nonlinear mixed-effects modeling. Data from two clinical studies (n = 32) were included in the analysis. A two-compartment (parent) one compartment (metabolite) mixture model (with two populations for apparent clearance) with first-order absorption and elimination adequately described the pharmacokinetics of telapristone and CDB-4453. Telapristone was rapidly absorbed with an absorption rate constant (Ka) of 1.26 h(-1). Moderate renal impairment resulted in a 74% decrease in Ka. The population estimates for oral clearance (CL/F) for the two populations were 11.6 and 3.34 L/h, respectively, with 25% of the subjects being allocated to the high-clearance group. Apparent volume of distribution for the central compartment (V2/F) was 37.4 L, apparent inter-compartmental clearance (Q/F) was 21.9 L/h, and apparent peripheral volume of distribution for the parent (V4/F) was 120 L. The ratio of the fraction of telapristone converted to CDB-4453 to the distribution volume of CDB-4453 (Fmet(est)) was 0.20/L. Apparent volume of distribution of the metabolite compartment (V3/F) was fixed to 1 L and apparent clearance of the metabolite (CLM/F) was 2.43 L/h. A two-compartment parent-metabolite model adequately described the pharmacokinetics of telapristone and CDB-4453. The clearance of telapristone was separated into two populations and could be the result of metabolism via polymorphic CYP3A5.

Am J Surg Pathol. 2011 Dec;35(12):1837-47.

PAX2 and PAX8 expression in primary and metastatic müllerian epithelial tumors: a comprehensive comparison.

Ozcan A, Liles N, Coffey D, Shen SS, Truong LD.

Source

Department of Pathology, Gulhane Military Medical Academy, Etlik, Ankara, Turkey. aozcan06018@gmail.com

Abstract

PAX2 and PAX8 are transcription factors that are essential in embryonic development of müllerian organs. They may also play a role in tumor development in these organs. The diagnostic utility of PAX2 and PAX8 relative to one another has not been comprehensively studied. Archival tissue samples for normal or non-neoplastic tissue (251), primary epithelial neoplasms (316 for PAX2 and 357 for PAX8), and metastatic epithelial neoplasms (16), all of müllerian origin, were subjected to PAX2 and PAX8 immunostaining. The staining frequency, extent, and intensity for these markers were compared. Virtually identical PAX2 and PAX8 expressions were noted in non-neoplastic tissue. They were constantly seen in most epithelial cells (but not in stromal cells) of the endocervix, endometrium, fallopian tube, paratubal cyst, endosalpingiosis, endometriosis, and endometrial polyp. Within the primary epithelial neoplasms, PAX2 and PAX8 expression was noted in 55% and 98% of serous tumors, 25% and 94% of endometrioid tumors, 19% and 100% of clear cell tumors, 11% and 67% of transitional/undifferentiated tumors, and 10% and 22% of mucinous tumors, respectively. Regardless of histologic subtypes, PAX2 staining was noted in fewer cells and with less staining intensity compared with PAX8. No tumor showed only PAX2 staining. Within the metastatic carcinomas, PAX2 and PAX8 expression was noted in 38% and 98% of cases, respectively, with a diffuse and strong staining for PAX8, contrasting with a patchy and weak PAX2 expression. PAX2 and PAX8 are constantly expressed in normal or non-neoplastic tissue of müllerian origin. For primary and metastatic müllerian epithelial tumors, PAX8 shows strong and diffuse staining in most cases of all histologic subtypes, except in mucinous tumors. In contrast, PAX2 expression is always less than PAX8, and exclusive staining for PAX2 is not seen. PAX8 supersedes PAX2 as probably the best epithelial marker hitherto for primary or metastatic müllerian epithelial tumors.

Anticancer Res. 2011 Dec;31(12):4301-6.

Association of p53 and CDKN1A genotypes with endometriosis.

Ying TH, Tseng CJ, Tsai SJ, Hsieh SC, Lee HZ, Hsieh YH, Bau DT.

Source

Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

Abstract

BACKGROUND:

The tumor suppressor p53 protein plays a critical role in different cellular processes in response to DNA damage and it is responsible for transcriptional induction of the p21 (CDKN1A/WAF1/CIP1) gene. Both p53 and p21 are thought to play major roles in the development of human malignancy. Polymorphic variants of p53 at codon 72, and CDKN1A at codon 31, have been found to be associated with cancer susceptibility, but few studies have investigated their effect on endometriosis risk.

MATERIALS AND METHODS:

In this hospital-based case-control study, we investigated the association of p53 codon 72 and CDKN1A codon 31 polymorphisms with endometriosis susceptibility in a Taiwanese population. In total, 180 patients with endometriosis, and 330 age-matched controls in Central Taiwan were recruited and genotyped.

RESULTS:

We found a significant difference in the distribution of the p53 genotype, but not the CDKN1A genotype, between the endometriosis and control groups. Individuals with the C (Pro) allele at p53 codon 72 had a 1.6-fold increased odds ratio of endometriosis, and those with Arg/Pro and Pro/Pro genotypes for p53 codon 72 had a 1.84- and 2.74-fold (95% confidence interval=1.17-2.92 and 1.58-4.74) increased risk of endometriosis compared to those with Arg/Arg, respectively. The distribution of haplotype combinations of p53 codon 72 and CDKN1A codon 31 was statistically different in the endometriosis and control groups. The percentages of the three subgroups with p53 CC homozygote were all higher in the endometriosis group than in the control group.

CONCLUSION:

Our findings suggest that the C (Pro) allele of p53 codon 72 may be associated with the development of endometriosis, and could serve as a potential biomarker for early prediction of this disease.

Arch Gynecol Obstet. 2011 Dec;284(6):1423-9. Epub 2011 Sep 20.

Endometriosis: the consequence of uterine denervation-reinnervation.

Quinn MJ.

Source

Womens Hospital, University of Zhejiang, Hangzhou, China. mjquinn001@btinternet.com

Abstract

Difficult intrapartum episodes and persistent straining during defecation cause injuries to uterine nerves and uterosacral ligaments. Injuries to uterine nerves (denervation) result in loss of fundocervical polarity, uterotubal dysmotility and retrograde menstruation. Ectopic endometrium, delivered by retrograde menstruation, adheres to injuries to uterosacral ligaments and peritoneal surfaces. Difficult vaginal deliveries result in laparoscopic appearances of asymmetry of uterosacral ligaments with, or without, ectopic endometrium. Straining during defaecation causes the “classic” appearances of nulliparous endometriosis including hypertrophy of the uterosacral ligaments often with large volumes of ectopic endometrium. Laparoscopic appearances depend on the site, nature, extent, and timing of tissue injury, as well as the presence of available endometrium. Tissue repair, including reinnervation in the uterine isthmus, cervix, vagina and uterosacral ligaments, contributes to chronic pelvic pain, dysmenorrhea, dyspareunia and subfertility some time after the primary injuries.

Arch Gynecol Obstet. 2011 Dec;284(6):1473-9. Epub 2011 Aug 12.

Relationship between endometriosis and cancer from current perspective.

Kokcu A.

Source

Department of Obstetrics and Gynecology, School of Medicine, University of Ondokuz Mayis, Samsun, Turkey. arifkokcu@yahoo.com

Abstract

PURPOSE:

To examine the current mechanisms of the increased incidence of cancer in women with endometriosis.

METHODS:

The synthesis and review of the relevant current literature in English language.

RESULTS:

Compared with general population, women with endometriosis have two times higher risk for developing ovarian cancer, 30% higher risk for developing breast cancer, and 40% higher risk for developing hematopoietic malignancies, mainly non-Hodgkin lymphoma.

CONCLUSIONS:

Endometriosis comprises many predisposing factors including genetic, epigenetic, local environmental, hormonal, inflammatory and immunologic changes, for the development of some cancers.

Arch Gynecol Obstet. 2011 Dec;284(6):1567-72. Epub 2011 Jul 20.

Expression and localization of CXCL16 and CXCR6 in ovarian endometriotic tissues.

Manabe S, Iwase A, Goto M, Kobayashi H, Takikawa S, Nagatomo Y, Nakahara T, Bayasula, Nakamura T, Hirokawa W, Kikkawa F.

Source

Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

Abstract

PURPOSE:

Inflammatory mediators, including chemokines, may play crucial roles in the development of endometriosis. Therefore, we investigated the expression and localization of CXCL16 and its receptor, CXCR6, in ovarian endometriotic tissues. We also examined whether CXCL16 induces IL-8 production in endometriotic stromal cells.

METHODS:

We performed immunohistochemical and Western blotting analyses of in vivo and in vitro samples. IL-8 production was assayed using an ELISA.

RESULTS:

Both CXCL16 and CXCR6 were expressed by endometriotic epithelial cells and stromal cells, but not normal ovarian stroma. A Western blotting analysis using primary cultured endometriotic stromal cells showed a constant expression of CXCL16 and CXCR6 in the proliferative phase, secretory phase and during gonadotropin-releasing hormone agonist therapy. CXCL16 induced IL-8 production in several endometriotic stromal cells in vitro.

CONCLUSIONS:

CXCL16 and CXCR6 might be involved in the pathophysiology of endometriosis through regulation of the inflammatory response.

Arq Neuropsiquiatr. 2011 Dec;69(6):995-6.

Endometriosis of the sciatic nerve.

Teixeira AB, Martins WA, d’Ávila R, Stochero L, Alberton L, Bezerra S, Romero AC, Freitas PE, Silva CE.

Atherosclerosis. 2011 Dec;219(2):784-8. Epub 2011 Aug 10.

Increased asymmetric dimethylarginine and enhanced inflammation are associated with impaired vascular reactivity in women with endometriosis.

Kinugasa S, Shinohara K, Wakatsuki A.

Source

Department of Obstetrics and Gynecology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.

Abstract

OBJECTIVE:

Enhanced inflammatory responses which may inhibit vascular reactivity, are associated with endometriosis development. Asymmetric dimethylarginine (ADMA), an inhibitor of endogenous nitric oxide synthase, is also implicated in endothelial dysfunction. We aimed to determine whether plasma ADMA and systemic inflammation are associated with endothelial function in women with endometriosis.

METHODS:

We evaluated 41 women with and 28 women without endometriosis. Plasma levels of lipids and inflammatory markers such as high sensitive-C reactive protein (hs-CRP), serum amyloid protein A (SAA), and interleukin-6 (IL-6) were measured in the two groups. We also measured levels of ADMA and symmetric dimethylarginine (SDMA). High-resolution ultrasonography measured flow-mediated vasodilation (FMD) to assess vasodilatory responses.

RESULTS:

FMD was significantly lower in women with endometriosis compared to those without endometriosis (8.39 ± 0.43% vs 10.79 ± 0.54%, P = 0.001). While plasma lipid levels did not differ significantly between groups, levels of AMDA, but not SDMA, were significantly higher in women with endometriosis (409.7 ± 10.1 pmol/L vs 383.0 ± 48.3 pmol/L, P = 0.04). Inflammatory markers were also significantly higher in these women (hs-CRP: 1053.3 ± 252.0 ng/mL vs 272.0 ± 83.3 ng/mL, P = 0.02; SAA: 8.00 ± 1.53 μg/mL vs 3.82 ± 0.42 μg/mL, P = 0.04; IL-6: 2.73 ± 0.75 pg/mL vs 1.05 ± 0.60 pg/mL, P = 0.04). FMD was negatively correlated with plasma levels of ADMA (r = -0.37, P=0.01) and log hs-CRP (r = -0.34, P = 0.01).

CONCLUSION:

Increased plasma ADMA levels and enhanced inflammation are associated with inhibited endothelial function in women with endometriosis.

Br J Neurosurg. 2011 Dec;25(6):775-7. Epub 2011 Jun 27.

Abdominal wall endometrioma in a patient with lumbo-peritoneal shunt: case report.

Shoakazemi A, Brady A, Cooke RS.

Source

Department of Neurosurgery, Regional Neuroscience Unit, Royal Victoria Hospital, Belfast BT12 6BA, UK. ashoakazemi@yahoo.com

Abstract

Lumbo-peritoneal shunt as one of the modalities for management of benign intracranial hypertension is prone to complications. We are reporting a rare complication of lumbo-peritoneal shunt insertion in which our patient had developed a painful swelling on the scar site. Surgical exploration confirmed diagnosis of abdominal wall endometriosis. Abdominal wall swelling with variation in size and tenderness during menstrual cycle in female patients with shunt, especially lumbo-peritoneal shunt, should raise the suspicion of endometriosis.

Cancer Epidemiol Biomarkers Prev. 2011 Dec;20(12):2496-506. Epub 2011 Oct 25.

Serum human epididymis protein 4 and risk for ovarian malignancy algorithm as new diagnostic and prognostic tools for epithelial ovarian cancer management.

Bandiera E, Romani C, Specchia C, Zanotti L, Galli C, Ruggeri G, Tognon G, Bignotti E, Tassi RA, Odicino F, Caimi L, Sartori E, Santin AD, Pecorelli S, Ravaggi A.

Source

Angelo Nocivelli, Institute of Molecular Medicine, Division of Gynecologic Oncology, University of Brescia, Brescia, Italy. bandieraelisabetta@libero.it

Abstract

BACKGROUND:

The aim of this work was to analyze the diagnostic and prognostic value of serum human epididymis protein 4 (HE4) and Risk for Ovarian Malignancy Algorithm (ROMA) in epithelial ovarian cancer (EOC).

METHODS:

Preoperative serum samples of 419 women (140 healthy controls, 131 ovarian benign cysts, 34 endometriosis, and 114 EOC) were tested for CA125 and HE4 using fully automated methods (Abbott ARCHITECT) and validated cutoff values.

RESULTS:

For the discrimination of benign masses from EOC, in premenopausal women, the sensitivity and specificity were 92.3% and 59.4% for CA125, 84.6% and 94.2% for HE4, and 84.6% and 81.2% for ROMA, whereas in postmenopausal women, the sensitivity and specificity were 94.3% and 82.3% for CA125, 78.2% and 99.0% for HE4, and 93.1% and 84.4% for ROMA. In patients with EOC, elevated CA125, HE4, and ROMA levels were associated with advanced Federation of Gynaecologists and Obstetricians (FIGO) stage, suboptimally debulking, ascites, positive cytology, lymph node involvement, and advanced age (all P ≤ 0.05). Elevated HE4 and ROMA (both P ≤ 0.01), but not CA125 (P = 0.0579), were associated with undifferentiated tumors. In multivariable analysis, elevated HE4 and ROMA (all P ≤ 0.05) were independent prognostic factors for shorter overall, disease-free, and progression-free survival. CONCLUSIONS AND IMPACT: This study underlines the high specificity of HE4 in discriminating endometriosis and ovarian benign cysts from EOC and the high sensitivity of CA125 in detecting EOC. We showed HE4 and ROMA as independent prognostic factors. Multicenter studies are needed to draw firm conclusions about the applicability of HE4 and ROMA in clinical practice.

Cardiovasc Intervent Radiol. 2011 Dec;34(6):1143-50. Epub 2011 Feb 18.

Pre-uterine artery embolization MRI: beyond fibroids.

Williams PL, Coote JM, Watkinson AF.

Source

Department of Clinical Imaging, Derriford Hospital, Plymouth PL6 8DH, UK. Petra.Williams@phnt.swest.nhs.uk

Abstract

Uterine leiomyomata, or fibroids, although benign, cause debilitating symptoms in many women. Symptoms are often nonspecific and may be the presenting complaint in a number of other conditions. Furthermore, because the presence of fibroids may be coincident with other symptomatic conditions that result in similar complaints, there may be diagnostic difficulty and consequent difficulty in planning therapeutic strategy. Uterine artery embolization (UAE) is a safe and effective treatment for symptomatic fibroids and is increasingly being performed. Magnetic resonance imaging (MRI) evaluation before and after treatment is routine practice with the potential to significantly alter management in up to a fifth of patients. It is well recognized that significant incidental findings may be demonstrated during imaging investigations, and in particular that abnormalities that are not directly related to the clinical question may be overlooked. Radiologists evaluating pre-UAE MRI studies must be aware of the MRI appearances of gynecological pathologies that may cause similar symptoms or that may affect the success or complication rates of UAE, and they must also be wary of “satisfaction of search,” reviewing imaging thoroughly so that relevant other pathologies are not missed. We demonstrate the appearances of coincidental pathologies found on pre-UAE MRI, with the potential to change patient management.

Clin Cancer Res. 2011 Dec 1;17(23):7359-72. Epub 2011 Sep 8.

Preclinical testing of PI3K/AKT/mTOR signaling inhibitors in a mouse model of ovarian endometrioid adenocarcinoma.

Wu R, Hu TC, Rehemtulla A, Fearon ER, Cho KR.

Source

Department of Pathology, The University of Michigan Medical School, Ann Arbor, USA.

Abstract

PURPOSE:

Genetically engineered mouse (GEM) models of ovarian cancer that closely recapitulate their human tumor counterparts may be invaluable tools for preclinical testing of novel therapeutics. We studied murine ovarian endometrioid adenocarcinomas (OEA) arising from conditional dysregulation of canonical WNT and PI3K/AKT/mTOR pathway signaling to investigate their response to conventional chemotherapeutic drugs and mTOR or AKT inhibitors.

EXPERIMENTAL DESIGN:

OEAs were induced by injection of adenovirus expressing Cre recombinase (AdCre) into the ovarian bursae of Apc(flox/flox); Pten(flox/flox) mice. Tumor-bearing mice or murine OEA-derived cell lines were treated with cisplatin and paclitaxel, mTOR inhibitor rapamycin, or AKT inhibitors API-2 or perifosine. Treatment effects were monitored in vivo by tumor volume and bioluminescence imaging, in vitro by WST-1 proliferation assays, and in OEA tissues and cells by immunoblotting and immunostaining for levels and phosphorylation status of PI3K/AKT/mTOR signaling pathway components.

RESULTS:

Murine OEAs developed within 3 weeks of AdCre injection and were not preceded by endometriosis. OEAs responded to cisplatin + paclitaxel, rapamycin, and AKT inhibitors in vivo. In vitro studies showed that response to mTOR and AKT inhibitors, but not conventional cytotoxic drugs, was dependent on the status of PI3K/AKT/mTOR signaling. AKT inhibition in APC(-)/Pten(-) tumor cells resulted in compensatory upregulation of ERK signaling.

CONCLUSIONS:

The studies show the utility of this GEM model of ovarian cancer for preclinical testing of novel PI3K/AKT/mTOR signaling inhibitors and provide evidence for compensatory signaling, suggesting that multiple rather than single agent targeted therapy will be more efficacious for treating ovarian cancers with activated PI3K/AKT/mTOR signaling.

Clin Exp Reprod Med. 2011 Dec;38(4):222-7. Epub 2011 Dec 31.

Serum anti-Müllerian hormone is a better predictor of ovarian response than FSH and age in IVF patients with endometriosis.

Yoo JH, Cha SH, Park CW, Kim JY, Yang KM, Song IO, Koong MK, Kang IS, Kim HO.

Source

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Cheil General Hospital and Women’s Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.

Abstract

OBJECTIVE:

To evaluate the ability of serum anti-Müllerian hormone (AMH), FSH, and age to clinically predict ovarian response to controlled ovarian hyperstimulation (COH) in IVF patients with endometriosis.

METHODS:

We evaluated 91 COH cycles, including 43 cycles with endometriosis (group I) and 48 cycles with male factor infertility (group II) from January to December, 2010. Patients were classified into study groups based on their surgical history of endometriosis-group Ia (without surgical history, n=16), group Ib (with a surgical history, n=27).

RESULTS:

The mean age was not significantly different between group I and group II. However, AMH and FSH were significantly different between group I and group II (1.9±1.9 ng/mL vs. 4.1±2.9 ng/mL, p<0.01; 13.1±7.2 mIU/mL vs. 8.6±3.3 mIU/mL, p<0.01). Furthermore, the number of retrieved oocytes and the number of matured oocytes were significantly lower in group I than in group II. In group II, AMH and FSH as well as age were significant predictors of retrieved oocytes on univariate analysis. Only the serum AMH level was a significant predictor of poor ovarian response in women with endometriosis.

CONCLUSION:

Serum AMH may be a better predictor of the ovarian response of COH in patients with endometriosis than basal FSH or age. AMH level can be considered a useful clinical predictor of poor ovarian response in endometriosis patients.

Clin Obstet Gynecol. 2011 Dec;54(4):720-6.

Managing endometriosis-associated infertility.

Senapati S, Barnhart K.

Source

Reproductive Endocrinology and Infertility, Reproductive Research Unit, Women’s Heath Clinical Research Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Suneeta.Senapati@uphs.upenn.edu

Abstract

Endometriosis is associated with infertility; however, the etiology of this association is unclear, thus complicating management. Several mechanisms of pathogenesis have been proposed; however, no one theory has been implicated. Medical therapy can be helpful in managing symptoms, but does not improve pregnancy rates. The role of surgical treatment remains controversial. There is little data regarding ovulation induction treatments for endometriosis only, whereas superovulation with intrauterine insemination has shown modest improvement in pregnancy rates in women who may have endometriosis. The most effective treatment for endometriosis-associated infertility is in vitro fertilization. Recent focus on proteomics and genetics of the disease may aid in optimizing treatment options.

Clin Obstet Gynecol. 2011 Dec;54(4):710-9.

The modern role of reproductive surgery.

Adamson GD.

Source

Fertility Physicians of Northern California, Palo Alto, California, USA. gdadamson@arcfertility.com

Abstract

The modern role of reproductive surgery has changed because of improved capabilities of endoscopic surgery resulting from innovation, instrumentation and experience, the development and increasing applicability of assisted reproductive technologies, and improved knowledge of the optimal application of these and other technologies. Rather than these technologies being competitive, the challenge for the reproductive specialist is to know and utilize reproductive surgery appropriately and effectively in the management of unexplained infertility, endometriosis, myomas, hydrosalpinges, proximal tubal occlusion, adhesions, ectopic pregnancy, tubal reversal, laparoscopic ovarian drilling for polycystic ovarian disease, as an adjunct to assisted reproductive technologies and in other clinical reproductive conditions.

Clin Obstet Gynecol. 2011 Dec;54(4):696-709.

Clinical management of the uterine factor in infertility.

Hatasaka H.

Source

Reproductive Care Center, Sandy, Utah, USA. hatasakah@fertilitydr.com

Abstract

This review on uterine factor infertility focuses on the most common congenital and acquired conditions affecting the uterus. Clinical approaches based upon the current literature are assessed. Recommendations are provided for which conditions and in which circumstances surgical interventions are appropriate to enhance reproductive outcomes.

Epigenomics. 2011 Dec;3(6):690-1.

Endometriosis as an epigenetic disease.

Peltomäki P, Bützow R.

Source

Departments of Obstetrics, Gynecology & Pathology, Helsinki University Central Hospital, Helsinki, Finland. paivi.peltomaki@helsinki.fi

Comment on

Epigenomics. 2011 Dec;3(6):689-90.

Pathogenesis of endometriosis and its relationship to gynecological cancers.

Peltomäki P, Bützow R.

Source

Departments of Obstetrics, Gynecology & Pathology, Helsinki University Central Hospital, Helsinki, Finland. paivi.peltomaki@helsinki.fi

Comment on

 

Eur J Obstet Gynecol Reprod Biol. 2011 Dec;159(2):439-42. Epub 2011 Oct 21.

The effect of the levonorgestrel-releasing intrauterine system, Mirena® on mast cell numbers in women with endometriosis undergoing symptomatic treatment.

Engemise SL, Willets JM, Emembolu JO, Konje JC.

Source

Reproductive Science Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, United Kingdom.

Abstract

OBJECTIVES:

Mirena® has been shown to improve symptoms in women with minimal to moderate endometriosis. The precise mechanisms for this have not been thoroughly investigated. We investigate here one possible mechanism-alteration in the number of mast cells in the endometriotic tissue.

STUDY DESIGN:

Tissues (endometrial, endometriotic and normal peritoneal biopsies) prospectively collected from twenty-eight women with laparoscopically confirmed minimal to moderate endometriosis before and 6 months after treatment with Mirena® were processed for immunohistochemistry for ER and PR expression followed by toluidine blue staining for mast cells. Photographs were obtained and the receptors and mast cells identified and quantified.

RESULTS:

The mean (± SEM) age of the twenty-eight women was 31 (±7.2) (range 18-42) years. Eight of the endometrial biopsies were in the proliferative phase and twenty in the secretory phase. Six months after Mirena®, the number of mast cell expressed in the tissues decreased significantly in the eutopic (P=0.0358) and ectopic endometrium (P=0.0220) but not in the normal peritoneum (P>0.05). There were no ERs or PRs found in mast cells.

CONCLUSION:

Mirena® causes a reduction in mast cell numbers in ectopic and eutopic endometrium in women undergoing symptomatic treatment of minimal to moderate endometriosis. This reduction could partly explain the efficacy of Mirena® in modulating pain in these women.

 

 

 

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